Comparación potencial de las actividades antiinflamatorias de las formulaciones de enjuague bucal de quercetina y diclofenaco / Potential Comparison of Anti-inflammatory Activities of Quercetin and Diclofenac Mouthwash Formulations

Introduction: Periodontitis is a pandemic, with about 14 percent of people worldwide already suffering from severe periodontitis. Early intervention in the disease could probably reduce its progression and eliminate the need for the extraction of affected teeth. Quercetin is a probable candidate as it has exemplary anti-inflammatory properties. The presence of phenolic hydroxyl groups in them greatly contributes to their antioxidant and anti-inflammatory activities. Objectives: The study introduces the formulation of Quercetin mouthwash and assesses its anti-inflammatory properties in comparison to Diclofenac sodium. Methods: Quercetin mouthwash was prepared using a commercially procured bioactive agent. One standard nonsteroidal anti-inflammatory drug, Diclofenac was used as a reference drug. The percentage inhibition of protein denaturation was calculated and its anti-inflammatory properties were evaluated through Bovine Serum Albumin Assay and Egg Albumin Assay. Results: Quercetin mouthwash showed parallel anti-inflammatory properties and showed a proportionate increase in anti-inflammatory properties with the increase in the concentration of the mouthwash. Comparable inhibition of protein denaturation at 10µl and 50µl concentrations with a proportionate variation of 1 percent (p>0.05) to the control in Egg Albumin Assay and 47 percent and 83 percent denaturation at 10µl and 50µl of Bovine Serum Albumin Assay were observed. Conclusion: Quercetin mouthwash has shown significant anti-inflammatory activity and hence is considered a potent anti-inflammatory agent comparable to Diclofenac sodium. It is found to be a suitable agent as an oral formulation for reducing the progression of inflammatory conditions(AU)

Introducción: La periodontitis es una pandemia, ya que alrededor del 14 por ciento de las personas en todo el mundo padecen periodontitis grave. Una intervención precoz en la enfermedad podría, probablemente, reducir su progresión y eliminar la necesidad de extraer los dientes afectados. La quercetina es un candidato probable, ya que tiene propiedades antiinflamatorias ejemplares. Su presencia de grupos hidroxilos fenólicos contribuye en gran medida a sus actividades antioxidantes y antiinflamatorias. Objetivos: El estudio presenta la formulación del colutorio de quercetina y evalúa sus propiedades antiinflamatorias en comparación con el diclofenaco sódico. Métodos: Se preparó un colutorio de quercetina, utilizando un agente bioactivo obtenido comercialmente. Se utilizó como fármaco de referencia un antiinflamatorio no esteroideo estándar, el diclofenaco. Se calculó el porcentaje de inhibición de la desnaturalización de proteínas y se evaluaron sus propiedades antiinflamatorias mediante ensayo con albúmina de suero bovino y con albúmina de huevo. Resultados: El colutorio de quercetina mostró propiedades antiinflamatorias paralelas y mostró un aumento proporcional de las propiedades antiinflamatorias con el aumento de la concentración del colutorio. Se observó una inhibición comparable de la desnaturalización de proteínas a concentraciones de 10µl y 50µl con una variación proporcional del 1 por ciento (p > 0,05), respecto al control en el ensayo de albúmina de huevo y una desnaturalización del 47 por ciento y 83 por ciento a 10µl y 50µl del ensayo de albúmina de suero bovino. Conclusiones: El enjuague bucal de quercetina ha mostrado una actividad antiinflamatoria significativa, por lo que se considera un potente agente antiinflamatorio comparable al diclofenaco sódico. Se considera un agente adecuado como formulación oral para reducir la progresión de las afecciones inflamatorias(AU)

Cambios en el pH salival de pacientes con ortodoncia fija, tras la aplicación de dos tipos de enjuagues bucales / Changes in salivary pH in patients with fixed orthodontics following the use of two types of mouthwashes

Introducción: Los enjuagues bucales contribuyen a la inhibición de la formación de la placa bacteriana y, por tanto, pueden ayudar a mantener el pH salival cercano a neutro. Objetivo: Identificar cambios en el pH salival de pacientes portadores de aparatología ortodóncica fija, después del enjuague con una solución de Stevia rebaudiana Bertoni y un enjuague comercial de aceites esenciales. Métodos: Se realizó un experimento clínico con un diseño factorial mixto en pacientes portadores de aparatología ortodóncica fija. Una vez firmado el consentimiento informado, treinta y dos pacientes fueron asignados aleatoriamente a uno de 2 grupos: la solución de S. rebaudiana B. al 2 por ciento o un enjuague comercial de aceites esenciales. Se utilizaron 15 ml de enjuague durante 60 s en todos los pacientes. El pH salival fue medido por dos observadores independientes calibrados, utilizando papel medidor de pH antes del enjuague (medición basal) y después del enjuague, a los 5 y 20 min. Los datos fueron analizados mediante el ANOVA mixto. Resultados: Se encontró una interacción estadísticamente significativa entre el tipo de tratamiento y el momento de medición del pH. Los pH medio de los grupos S. rebaudiana y aceites esenciales fueron respectivamente en la medición basal: 6,61 y 6,52 (p = 0,72); a los 5 min: 7,61 y 7,77 (p = 0,40); y a los 20 min: 7,72 y 6,82 (p < 0,001). Conclusiones: Ambos enjuagues tenían el efecto de aumentar el pH salival a niveles alcalinos a los 5 min, pero solo el enjuague de S. rebaudiana B. al 2 por ciento mantuvo el pH básico a los 20 min(AU)

Introduction: Mouthwashes contribute to the inhibition of bacterial plaque formation and, therefore, may help to maintain salivary pH close to neutral. Objective: To identify changes in salivary pH in patients with fixed orthodontics after using a Stevia rebaudiana Bertoni solution and a commercial essential oil mouthwash. Methods: A clinical experiment with a mixed factorial design was carried out in patients with fixed orthodontic appliances. Once informed consent was signed, thirty-two patients were randomly assigned to one of 2 groups: 2 % S. rebaudiana B. solution or a commercial essential oil mouthwash. Fifteen ml of mouthwash was used for 60 s in all patients. Salivary pH was measured by two independent calibrated observers using pH-measuring paper before rinsing (basal measurement) and after rinsing, after 5 and 20 min. The data were analyzed by mixed ANOVA. Results: A statistically significant interaction was found between the type of treatment and the time of pH measurement. The medium pH of the S. rebaudiana and essential oil groups were respectively as per basal measurement: 6.61 and 6.52 (p = 0.72); after 5 min: 7.61 and 7.77 (p = 0.40); and after 20 min: 7.72 and 6.82 (p < 0.001). Conclusions: Both mouthwashes had the effect of increasing salivary pH to alkaline levels after 5 min, but only the 2 percent S. rebaudiana B. mouthwash maintained the basic pH after 20 min(AU)

Safety and efficacy of Oro-T oral rinse in oral mucositis during cancer radiotherapy and/or chemotherapy: Cumulative analysis of two studies.

INTRODUCTION: Oral mucositis is inflammation of the mucosa of the mouth which ranges from redness to severe ulceration. It results from the local effects of radiation to the oral mucosa. OBJECTIVES: The study is cumulative analysis of two studies (one comparative and the other open labeled) evaluated in individuals with oral mucositis during cancer radiotherapy and/or chemotherapy for the safety and efficacy of Oro-T mouthwash in a comparative design with normal saline. METHODOLOGY: Both the studies were similar with respect to clinical and laboratory parameters for analysis. The participants were advised to use 10 ml of Oro-T for 1 min 4 times daily for 6 weeks starting from day 1 of standard care. Patients were followed up, and the results were assessed from baseline on visit days: At entry and at the end of every week for 6 weeks. Clinical assessment of oral condition was done objectively (by the investigator) and also subjectively. Clinical symptoms such as sore throat, number of ulcer, burning sensation, pain, difficulty in chewing, difficulty in drinking, and mucositis grading along with Patient Reported Outcome Measures Scale were evaluated at each interval. Data was available for 40 subjects in Oro-T and 15 subjects in NS groups respectively. RESULTS AND CONCLUSION: The significant positive outcome was reported both subjectively and objectively in Oro-T group as compared to NS group with the delay in the onset of symptoms and less severe manifestation of oral mucositis with an improvement in quality of life. No adverse effects were reported that prompted discontinuation of study medication. Overall compliance to study medication was good.

Eficacia de Enjuagues Naso-oro-faríngeos como prevención y tratamiento de COVID-19: (diciembre de 2021) / Efficacy of Naso-oro-pharyngeal Remedies as a Prevention and Treatment of COVID-19: (December 2021)

INTRODUCCIÓN: El virus SARS-CoV-2, sigue presentando múltiples variantes, las cuales en muchos casos han tomado el nombre de la ciudad o país donde fueron detectados, la Organización Mundial de la Salud (OMS) ha estandarizado dichas variantes según el interés y preocupación que ocasionan, a continuación se detalla (2). El espectro de la enfermedad es amplio e incluye desde cuadros leves y autolimitados hasta neumonía atípica severa y progresiva, falla multiorgánica y muerte (3,4). El SARS-CoV-2, se detecta en la saliva de pacientes con enfermedad por coronavirus (COVID-19) ha sido que este fluido biológico fuera relevante en términos del diagnóstico y transmisión de la infección (5). Se cree que el virus se replica en la nariz y la garganta, como se evidencia por la alta carga viral en la etapa temprana de infección en estas áreas (6). Dada la patogenia de la enfermedad, hacer gárgaras o enjuagues bucales con un antiséptico que tiene actividad viricida contra el SARS-CoV-2 podría ayudar en el tratamiento y prevención de COVID-19, o suprimir la carga viral y reducir la propagación del virus (7,8). Existen vacunas eficaces para prevenir COVID-19, y algunos medicamentos muestran resultados promisorios; su disponibilidad en países en desarrollo aún es baja; por lo que es necesario evaluar alternativas que sean de bajo costo y alta disponibilidad. Esta revisión fue hecha para actualizar la evidencia científica disponible sobre la eficacia de los enjuagues naso-oro-faríngeos reduciendo la carga viral de SARS-CoV-2, mejorando los desenlaces de los pacientes, y/o previniendo la enfermedad COVID-19. OBJETIVO: El objetivo de esta revisión es actualizar la evidencia disponible sobre la eficacia de los enjuagues orales y/o lavados naso-oro-faríngeos reduciendo la carga viral, mejorando los desenlaces de los pacientes, y/o previniendo la enfermedad COVID-19 causada por el virus SARS-CoV-2. METODOLOGÍA: En la SRR N° 02-2021, se realizó una búsqueda sistemática hasta el 26 de abril de 2021 en las bases de datos MEDLINE (a través de PubMed), EMBASE/Ovid, LILACS/Biblioteca virtual en salud (BVS), y Cochrane Library, incluyendo términos en lenguaje natural y lenguaje estructurado (Tesauros, MeSH terms, DeCS terms) según cada base de datos para los términos de la pregunta PICO. Se revisaron también las referencias de los estudios incluidos y estudios sugeridos por los solicitantes de esta revisión. No se hizo búsqueda en la literatura gris. RESULTADOS: En la SRR N° 02-2021, se identificaron 15 estudios in vitro, 3 ensayos no controlados, 6 ensayos clínicos aleatorizados abiertos, y 2 revisiones sistemáticas relacionada a alguna de las 3 preguntas PICO. Los estudios hallados evaluaron diferentes enjuagues bucales, gárgaras faríngeas, lavados nasales, y espráis nasales/orales. Los componentes incluyeron Iodo-povidona (PVP-I), Clorhexidina (CHX), Peróxido de hidrogeno (H2O2), Dióxido de Cloro, los amonios cuaternarios Cetilpiridinio (CPC) y Decualinio, Iota y Kappa-carragenina, Xylitol, Octenidina, Polihexanida, Xylometazolina, Tramazolina, Oxymetazolina, Metilcelulosa, Delmopinol, Timol, Mentol, Eucaliptol, y combinaciones comerciales que además pueden incluir Etanol, Bicarbonato, y Cloruro de Sodio. Además de ellas, los estudios encontrados evaluaron otras 16 sustancias; así como preparados comerciales combinando dichas sustancias con Etanol, Bicarbonato, y/o Cloruro de Sodio. La PVP-I parece ser eficaz eliminando partículas virales en cultivos celulares; mientras que la evidencia para CHX y H2O2 es variable. No hubo suficiente evidencia para otras sustancias. Un solo estudio mostró que los Enjuagues de CHX son eficaces reduciendo el porcentaje de pacientes con virus detectable en la orofaringe. La evidencia para PVP-I, dióxido de cloro, y peróxido de hidrogeno fue insuficiente; y no se encontraron estudios para las otras sustancias. Según un solo estudio, el número de hospitalizaciones fue igual entre los que usaron o no enjuagues naso-oro-faríngeos de PVP-I; aunque su uso se asoció a supresión tiroidea. No hubo estudios para las otras sustancias, ni tampoco estudios evaluando ingreso a UCI o mortalidad. Para esta actualización de esta Nota Técnica, se identificaron 6 estudios de los cuales 2 revisiones sistemáticas, 1 estudio piloto clínico y 3 ensayos clínicos aleatorizados, entre las fechas 27 de abril hasta el 3 de diciembre de 2021. Los estudios hallados evaluaron diferentes enjuagues bucales, gárgaras faríngeas, lavados nasales, y espráis nasales/orales. Las sustancias más comúnmente estudiadas fueron Iodo-povidona (PVP-I), Clorhexidina (CHX), y Peróxido de hidrogeno (H2O2). CONCLUSIONES: De la SRR N° 02-2021, se identificaron 15 estudios in vitro, 3 ensayos no controlados, 6 ensayos clínicos aleatorizados (ECA) abiertos, y 2 revisiones sistemáticas relacionadas a alguna de las tres preguntas PICO. Para la actualización de esta Nota Técnica, se seleccionó estudios desde el 27 de abril hasta el 3 de diciembre de 2021 y se identificó 6 estudios de los cuales 2 revisiones sistemáticas, 2 estudios piloto clínico y 2 ensayos clínicos aleatorizados. Los estudios evaluaron diferentes preparaciones acuosas de enjuagues bucales, gárgaras faríngeas, lavados nasales, y espráis nasales/orales. Los componentes incluyeron Iodo-povidona (PVP-I), Clorhexidina (CHX), Peróxido de hidrogeno (H2O2), Dióxido de Cloro, los amonios cuaternarios, Cloruro de cetilpiridinio (CPC) y Decualinio, Iota y Kappa-carragenina, Octenidina, Polihexanida, Xylometazolina, Tramazolina, Oxymetazolina, Metilcelulosa, Xylitol, Delmopinol, Timol, Mentol, Eucaliptol, Dexpantenol, Zinc y combinaciones comerciales que además pueden incluir Etanol, Bicarbonato, y Cloruro de Sodio. En el estudio de Matthias Schürmann, et al., demostró que la solución de enjuague bucal (dexpantenol y zinc) puede reducir la carga viral tras la ejecución del procedimiento de enjuague bucal, pero está disminución de carga viral solo persiste hasta 6 horas. El enjuague bucal (dexpantenol y zinc), in vitro, disminuyeron la expresión de las citoquinas inflamatorias, mientras que en la muestra antiviral no se vio alterada de manera significativa. El gluconato de clorhexidina al 0,12%, dan como resultado una disminución de su carga viral del SARS-CoV-2 hasta 60 min en comparación con los que usaron placebo. Una limitación es que el ensayo semicuantitativo de RT-PCR mide las diferencias relativas de ARNm y no en la infectividad o viabilidad viral. De los estudios encontrados muestran resultados relacionados a la reducción de la carga viral en cultivos In vitro y en orofaringe de pacientes conCOVID-19, sin embargo, no hay evidencia que muestren la eficacia de estas sustancias en la prevención del COVID-19. De acuerdo a los estudios de las revisiones sistemáticas, concluye que no hay pruebas relacionadas con los beneficios y los riesgos del uso de antimicrobianos por parte del personal sanitario para protegerse cuando tratan a personas con COVID-19 o por parte de los pacientes. Además, advierten que es importante que los futuros estudios recojan y analicen la información sobre los efectos adversos y que se tenga en cuenta que los antisépticos también pueden eliminar los microorganismos de la boca o la nariz que son útiles para proteger el organismo contra las infecciones.

Treatment of periodontal diseases by the local drug delivery system using 1% chlorhexidine gel: A randomized clinical trial.

The idea of the local drug delivery system is getting popular nowadays to treat gingivitis and periodontitis. The method of delivering the drug locally is quite easy and requires minimal intervention. This delivery system not only treats the periodontal diseases effectively but also prevents the side effects linked with the use of the drugs which are used orally for longer periods to cure these diseases. Chlorhexidine (CHX) is being widely used to treat these conditions because of its broad spectrum anti-bacterial effect and is found to be more effective in lowering plaque formation. The aim of this study was to appraise the effect of the local drug delivery system by using 1% CHX gel in patients with periodontal diseases. 1% CHX gel was prepared and its physicochemical characteristics were then assessed. Clinical parameters and inflammatory salivary biomarkers were evaluated in two groups of patients. Group I: standard treatment group. Group II: gel treatment group. These parameters were evaluated before treatment and after 4 weeks of treatment. 1% CHX gel was highly effective in reducing gingivitis and periodontitis by using the local drug delivery system which allowed the drug to retain into the periodontal pocket for prolong period of time.

Eficacia de Enjuagues Naso-oro-faríngeos como prevención y tratamiento de COVID-19 / Efficacy of Naso-oro-pharyngeal Remedies as a Prevention and Treatment of COVID-19

ANTECEDENTES: La enfermedad por coronavirus 2019 (COVID-19), causada por el virus SARS-CoV-2 fue inicialmente reportada en Wuhan, China en diciembre de 2019, produciendo millones de casos y muertes a nivel global hasta la fecha. Si bien ya existen vacunas eficaces para prevenir dicha enfermedad, y algunos medicamentos han mostrado tener un rol terapéutico; su disponibilidad en países en desarrollo aún es baja; por lo que es necesario estar al tanto de alternativas que sean de bajo costo y alta disponibilidad. Entre ellas, se ha propuesto el uso de gárgaras faríngeas, enjuagues orales, y/o lavados nasales. Por esta razón, se elaboró la presente Revisión Rápida con el fin de identificar y evaluar la evidencia disponible sobre este tema. OBJETIVO: El objetivo de esta revisión es identificar y sistematizar la evidencia disponible sobre la eficacia de los enjuagues orales y/o lavados naso-oro-faríngeos reduciendo la carga viral, mejorando los desenlaces de los pacientes, y/o previniendo la enfermedad COVID-19 causada por el virus SARS-CoV-2. METODOLOGÍA: Se realizó una revisión rápida basada en tres preguntas: i) En cultivos virales ¿el uso de enjuagues naso-oro-faríngeos, comparado con no uso o sustancia control, es eficaz reduciendo la carga viral/títulos virales? ii) En pacientes con infección confirmada por SARS-CoV-2 ¿el uso de enjuagues naso-oro-faríngeos comparado con no uso o placebo, es eficaz mejorando los desenlaces clínicos y laboratoriales? iii) En personas en riesgo de exposición al SARS-CoV-2, ¿el uso de enjuagues naso-oro-faríngeos comparado con no uso o placebo, es eficaz reduciendo el desarrollo de COVID-19? Se incluyeron revisiones sistemáticas, ensayos clínicos, estudios observacionales, y estudios pre-clínicos. Para ello, se realizó una búsqueda sistemática en las bases de datos MEDLINE/PubMed, EMBASE/Ovid, LILACS, y la Biblioteca Cochrane. Luego de eliminar duplicados, los autores seleccionaron los ítems que cumplieran con alguna de las tres preguntas establecidas. No se evaluó riesgo de sesgo ni la calidad de la evidencia identificada. RESULTADOS: Se identificaron 15 estudios in vitro, 3 ensayos no controlados, 6 ensayos clínicos aleatorizados (ECA) abiertos, y 2 revisiones sistemáticas relacionadas a alguna de las tres preguntas PICO. Los estudios evaluaron diferentes preparaciones acuosas de enjuagues bucales, gárgaras faríngeas, lavados nasales, y espray nasales/orales. Los componentes incluyeron Iodo-povidona (PVP-I), Clorhexidina (CHX), Peróxido de hidrogeno (H2O2), Dióxido de Cloro, los amonios cuaternarios Cetilpiridinio (CPC) y Decualinio, Iota y Kappa-carragenina, Xylitol, Octenidina, Polihexanida, Xylometazolina, Tramazolina, Oxymetazolina, Metilcelulosa, Delmopinol, Timol, Mentol, Eucaliptol, y combinaciones comerciales que además pueden incluir Etanol, Bicarbonato, y Cloruro de Sodio. PVP-I mostró gran actividad en todos los estudios in vitro en que fue probada. La eficacia de CHX y H2O2 in vitro fue variable. Para las otras sustancias, hubo dos o menos estudios in vitro. Hubo 7 estudios clínicos que evaluaron reducción de títulos virales en pacientes COVID-19. El ECA más grande encontró que recibir 4 días de enjuagues bucales, o enjuagues más espray orofaríngeo de CHX, se asoció significativamente a un menor porcentaje de PCR positivo en orofaringe. Los otros estudios no encontraron diferencias significativas, tuvieron pocos pacientes, o no tuvieron controles. Dos ECAs, hechos en pocos pacientes, encontraron una duración menor pero no significativa, de síntomas por coronavirus en usuarios de irrigación nasal más gárgaras de salino hipertónico. Un ECA no observó hospitalizaciones en usuarios de PVP-I, pero tampoco en los controles. En cambio, hubo aumento de TSH en todos los usuarios de PVP-I. No se encontraron publicaciones que evaluaran el efecto de algún enjuague sobre admisiones a UCI o fallecimientos. Una serie pequeña de 15 trabajadores de salud que usaron enjuagues bucales y espray oro-faríngeo de CHX a diario durante 7 meses, no presentaron casos de COVID-19, pero no tuvieron controles. Las dos revisiones sistemáticas que evaluaron efectos sobre desenlaces en pacientes con COVID-19, y efectos previniendo la infección por SARS-CoV-2 en los trabajadores de salud que los atienden, no encontraron estudios concluidos a la fecha de su búsqueda (junio 1, 2020). CONCLUSIONES: El PVP-I parece ser eficaz reduciendo los títulos virales en cultivos; mientras que la evidencia para CHX y H2O2 es variable. No hubo suficiente evidencia para otras sustancias. Según un único ECA, cuatro días de enjuagues de CHX son eficaces reduciendo el porcentaje de pacientes con PCR positivo en orofaringe. La evidencia para PVP-I, dióxido de cloro, peróxido de hidrogeno fue insuficiente; y no se encontraron estudios para las otras sustancias. El único ECA que evaluó hospitalizaciones no observó diferencias ente los controles y los usuarios de enjuagues naso-oro-faríngeos de PVP-I. No hubo estudios para las otras sustancias, ni tampoco estudios evaluando ingreso a UCI o mortalidad. No hubo evidencia sobre eficacia de los enjuagues naso-oro-faríngeos previniendo COVID-19 en personas aún no infectadas, excepto por una serie pequeña de casos que no se infectaron durante los meses que usaron enjuague bucal más espray orofaríngeo de CHX.

Randomized placebo-controlled phase II trial of high-dose melatonin mucoadhesive oral gel for the prevention and treatment of oral mucositis in patients with head and neck cancer undergoing radiation therapy concurrent with systemic treatment.

PURPOSE: The objective of this trial was to evaluate the safety and efficacy of melatonin oral gel mouthwashes in the prevention and treatment of oral mucositis (OM) in patients treated with concurrent radiation and systemic treatment for head and neck cancer. METHODS: Randomized, phase II, double-blind, placebo-controlled trial (1:1 ratio) of 3% melatonin oral gel mouthwashes vs. placebo, during IMRT (total dose ≥ 66 Gy) plus concurrent Q3W cisplatin or cetuximab. Primary endpoint: grade 3-4 OM or Severe Oral Mucositis (SOM) incidence by RTOG, NCI, and a composite RTOG-NCI scales. Secondary endpoints: SOM duration and grade 2-4 OM or Ulcerative Oral Mucositis (UOM) incidence and duration. RESULTS: Eighty-four patients were included in the study. Concurrent systemic treatments were cisplatin (n = 54; 64%) or cetuximab (n = 30; 36%). Compared with the placebo arm, RTOG-defined SOM incidence was numerically lower in the 3% melatonin oral gel arm (53 vs. 64%, P = 0.36). In patients treated with cisplatin, assessed by the RTOG-NCI composite scale, both SOM incidence (44 vs. 78%; P = 0.02) and median SOM duration (0 vs. 22 days; P = 0.022) were significantly reduced in the melatonin arm. Median UOM duration assessed by the RTOG-NCI scale was also significantly shorter in the melatonin arm (49 vs. 73 days; P = 0.014). Rate of adverse events and overall response rate were similar between the two arms. CONCLUSIONS: Treatment with melatonin oral gel showed a consistent trend to lower incidence and shorter SOM duration and shorter duration of UOM. These results warrant further investigation in phase III clinical trial.

Effectiveness of mouthrinses in prevention and treatment of radiation induced mucositis: A systematic review.

Mucositis is a frequent, severe consequence of radiation therapy among patients undergoing radiotherapy for the head-and-neck cancer, often requiring hospitalization and even breaks or discontinuity in treatment. Mouth rinsing with various agents has demonstrated effectiveness in the prevention and treatment of radiation-induced mucositis (OM), but evidence for the same is lacking. This systematic review is therefore conducted with the aim of assessing the evidence for the effectiveness of mouthrinses in prevention and treatment of OM. Joanna Briggs Institute guidelines were followed to conduct this review. Six databases were searched and a total of 25 randomized clinical trials published over a period of the past 31 years were included for qualitative synthesis. Analysis of 25 studies revealed that 1299 participants, aged 46-69 years were assigned to the test groups and control groups. A total of 16 different formulations were studied among patients over a duration of 6 days to 1 year in varying dosages. The overall preventive fraction ranged from 1.9% to 77.8% for a reduction in clinical grades of mucositis, 7.6%-83.3% for a reduction in pain and 20%-50% for a reduction in bacterial counts. Adverse effects such as mouth burning, altered taste, sore throat, have been reported, especially with chlorhexidine and benzydamine hydrochloride. Evidence for the included studies is IC and ID. Studies using herbal based products and tissue regenerating agents revealed comparatively better effectiveness with lesser side effects. However, the number of studies to support such a claim is very limited.

Preventive effect and safety of Chinese herbal medicine mouthwash in chemotherapy-induced oral mucositis: A protocol for systematic review and meta analysis.

BACKGROUND: Oral mucositis (OM), one of the most common side effects for cancer patients who have undergone chemotherapy, can cause severe impairment to patients' functional ability and impact their quality of life, resulting in delayed and/or incomplete treatment. Traditional Chinese medicine offers empirical herbal decoctions to gargle for the prevention of chemotherapy-induced OM; however, evidence for its clinical efficacy and safety is lacking. Therefore, we provide a protocol to evaluate the preventive effect and safety of Chinese herbal medicine mouthwash in chemotherapy-induced OM. METHODS: We will comprehensively retrieve relevant articles published till August 15, 2020, in the following electronic databases: the Cochrane Library, PubMed, EMBASE, Chinese National Knowledge Infrastructure Database, Chinese Biomedical Literature Database, Chinese Science and Technique Journals Database, and the Wan-fang Database. Only randomized controlled trials will be included. We will use the criteria provided by the Cochrane Handbook for quality assessment and risk assessment of the included studies and use the RevMan 5.3 software for meta-analysis of the preventive effect and safety. RESULTS: This study will assess the preventive effect and safety of Chinese herbal medicine mouthwash in chemotherapy-induced OM. CONCLUSION: This systematic review will provide evidence-based medical corroboration for the clinical application of the Chinese herbal medicine mouthwash in chemotherapy-induced OM. PROSPERO REGISTRATION NUMBER: CRD42020206614.

Mouthwashes and Nasal Sprays as a Way to Prevent the Spread of SARS-CoV-2 / Enjuagues Bucales y Aerosoles Nasales como un Método de Prevenir la Propagación de SARS-CoV-2

ABSTRACT: COVID-19 pandemic has infected millions of people around the world. Due to its large accumulation in the nasopharyngeal region and transmission through respiratory fluids, its spread among people is extremely high. Considering the needed time for treatments and vaccine development, the research of preventive methods, such as the use of mouthwash and nasal spray, that could decrease the viral load in the nasopharyngeal region, and thus the spread of SARS-CoV-2, becomes fundamental. The evidence has shown that there are compounds with antiviral capacity that could be used for this purpose, among which are povidone-iodine, hydrogen peroxide, cyclodextrins, and the synthetic drug PUL-042. Currently, there is no clinical evidence that proves the effectiveness of these substances against SARS-CoV-2. Nevertheless, there are ongoing clinical trials to prove it and generate methods that could help to prevent or, at least, decrease its spread among the population and stop this pandemic.

RESUMEN: La pandemia de COVID-19 ha infectado a millones de personas en el mundo. Su extremadamente alta capacidad de propagación se debe a la gran acumulación en la región nasofaríngea y su transmisión vía fluidos respiratorios.Considerando el tiempo necesario para desarrollar vacunas y tratamientos, se vuelve fundamental la investigación de métodos preventivos como el uso de enjuague bucal y spray nasal, que puedan disminuir la carga viral en la zona nasofaríngea y así también la capacidad de propagación de SARS-CoV-2La evidencia presenta compuestos con capacidad antiviral como la povidona iodada, peróxido de hidrógeno, ciclodextrinas y la droga sintética PUL-042, que podrían ser usados para dicho propósito. Actualmente no existe evidencia clínica que demuestre la efectividad de estas sustancias contra SARS-Cov-2, sin embargo, se están desarrollando estudios clínicos para probarlos y generar métodos que ayuden a disminuir o prevenir su transmisión en la población, y así detener esta pandemia.

A quadruple blind, randomised controlled trial of gargling agents in reducing intraoral viral load among hospitalised COVID-19 patients: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: 1- To compare the effectiveness of 1% Hydrogen peroxide, 0.2% Povidone-Iodine, 2% hypertonic saline and a novel solution Neem extract (Azardirachta indica) in reducing intra-oral viral load in COVID-19 positive patients. 2- To determine the salivary cytokine profiles of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL- 17 among COVID-19 patients subjected to 1% Hydrogen peroxide, 0.2% Povidone-Iodine, 2% hypertonic saline or Neem extract (Azardirachta indica) based gargles. TRIAL DESIGN: This will be a parallel group, quadruple blind-randomised controlled pilot trial with an add on laboratory based study. PARTICIPANTS: A non-probability, purposive sampling technique will be followed to identify participants for this study. The clinical trial will be carried out at the Aga Khan University Hospital (AKUH), Karachi, Pakistan. The viral PCR tests will be done at main AKUH clinical laboratories whereas the immunological tests (cytokine analysis) will be done at the Juma research laboratory of AKUH. The inclusion criteria are laboratory-confirmed COVID-19 positive patients, male or female, in the age range of 18-65 years, with mild to moderate disease, already admitted to the AKUH. Subjects with low Glasgow coma score, with a history of radiotherapy or chemotherapy, who are more than 7 days past the onset of COVID- 19 symptoms, or intubated or edentulous patients will be excluded. Patients who are being treated with any form of oral or parenteral antiviral therapy will be excluded, as well as patients with known pre-existing chronic mucosal lesions such as lichen planus. INTERVENTION AND COMPARATOR: Group A (n=10) patients on 10 ml gargle and nasal lavage using 0.2% Povidone-Iodine (Betadiene® by Aviro Health Inc./ Pyodine® by Brooks Pharma Inc.) for 20-30 seconds, thrice daily for 6 days. Group B (n=10) patients will be subjected to 10 ml gargle and nasal lavage using 1% Hydrogen peroxide (HP® by Karachi Chemicals Products Inc./ ActiveOxy® by Boumatic Inc.) for 20-30 seconds, thrice daily for 6 days. Group C will comprised of (n=10) subjects on 10ml gargle and nasal lavage using Neem extract solution (Azardirachta indica) formulated by Karachi University (chemistry department laboratories) for 20-30 seconds, thrice daily for 6 days. Group D (n=10) patients will use 2% hypertonic saline (Plabottle® by Otsuka Inc.) gargle and nasal lavage for a similar time period. Group E (n=10) will serve as positive controls. These will be given simple distilled water gargles and nasal lavage for 20-30 seconds, thrice daily for six days. For nasal lavage, a special douche syringe will be provided to each participant. Its use will be thoroughly explained by the data collection officer. After each use, the patient is asked not to eat, drink, or rinse their mouth for the next 30 minutes. MAIN OUTCOMES: The primary outcome is the reduction in the intra-oral viral load confirmed with real time quantitative PCR. RANDOMISATION: The assignment to the study group/ allocation will be done using the sealed envelope method under the supervision of Clinical Trial Unit (CTU) of Aga Khan University, Karachi, Pakistan. The patients will be randomised to their respective study group (1:1:1:1:1 allocation ratio) immediately after the eligibility assessment and consent administration is done. BLINDING (MASKING): The study will be quadruple-blinded. Patients, intervention provider, outcome assessor and the data collection officer will be blinded. The groups will be labelled as A, B, C, D or E. The codes of the intervention will be kept in lock & key at the CTU and will only be revealed at the end of study or if the study is terminated prematurely. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): As there is no prior work on this research question, so no assumptions for the sample size calculation could be made. The present study will serve as a pilot trial. We intend to study 50 patients in five study groups with 10 patients in each study group. For details, please refer to Fig. 1 for details. TRIAL STATUS: Protocol version is 7.0, approved by the department and institutional ethics committees and clinical trial unit of the university hospital. Recruitment is planned to start as soon as the funding is sanctioned. The total duration of the study is expected to be 6 months i.e. August 2020-January 2021. TRIAL REGISTRATION: This study protocol was registered at www.clinicaltrials.gov on 10 April 2020 NCT04341688 . FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). Fig. 1 Flow diagram of study-participants' timeline.

Hydrogen peroxide and viral infections: A literature review with research hypothesis definition in relation to the current covid-19 pandemic.

We reviewed the literature concerning the innate response from nasal and oral epithelial cells and their reaction to hydrogen peroxide (H2O2). Hydrogen peroxide is produced physiologically by oral bacteria and plays a significant role in the balance of oral microecology since it is an important antimicrobial agent. In the epithelial cells, the enzyme superoxide dismutase catalyzes a reaction leading from hydrogen peroxide to the ion superoxide. The induced oxidative stress stimulates a local innate response via activation of the toll-like receptors and the NF-κB. Those kinds of reactions are also activated by viral infections. Virus-induced oxidative stress plays an important role in the regulation of the host immune system and the specific oxidant-sensitive pathway is one of the effective strategies against viral infections. Therefore, nose/mouth/throat washing with hydrogen peroxide may enhance those local innate responses to viral infections and help protect against the current coronavirus pandemic. We strongly encourage the rapid development of randomized controlled trials in both SARS-CoV-2 positive and negative subjects to test the preliminary findings from the in-vitro and in-vivo observational studies that we identified.

Effectiveness of local drug delivery system using 1% metronidazole gel and mouthwash in treating periodontal diseases.

The gold standard therapy for treating the periodontal infections is the removal of bacterial plaque and deposits of calculus from tooth surfaces by scaling and root planning. In order to eliminate these bacterial reservoirs, beside conventional treatment, chemo therapeutic agents are commonly prescribed by periodontologists. To avoid the systemic side effects and development of antibiotics resistance, local drug delivery methods has gained the attention of dentists to treat periodontal infections, along with scaling and root planning. The aim of this study was to evaluate the effectiveness of local drug delivery system in combination with scaling and root planning, by using 1% metronidazole gel and mouthwash. The patients were divided into 3 groups. Group I: conventional treatment group. Group II: patients received treatment with gel. Group III: patients received treatment with mouthwash. All groups received treatment for 30 days. Clinical parameters and salivary concentration of TNF-α, PGE2 and nitric oxide were measured before and after treatment in both groups. All clinical parameters and inflammatory biomarkers significantly reduced in gel and mouthwash group patients (p≤0.001) as compared to patients received conventional treatment. The gel is found to be more efficacious than mouthwash especially in reducing clinical attachment loss (p< 0.05) and in reducing inflammatory biomarkers (p≤0.001). We strongly suggest the use of metronidazole via local drug delivery system combined with scaling and root planning to treat periodontal diseases.

Relationship of the Esophageal Microbiome and Tissue Gene Expression and Links to the Oral Microbiome: A Randomized Clinical Trial.

INTRODUCTION: Although the microbiome is altered in various esophageal diseases, there is no direct evidence for a link between the oral or esophageal microbiome and underlying esophageal tissue. Here, we aimed to address these gaps through use of an antimicrobial mouth rinse to modify the esophageal microbiome and tissue gene expression. METHODS: In this randomized controlled trial, patients scheduled to undergo endoscopy for clinical indications used chlorhexidine mouth rinse or no treatment for 2 weeks before endoscopy. Oral swabs and saliva were collected at baseline and at follow-up, and the esophagus was sampled on the day of endoscopy. The microbiome was analyzed by 16S rRNA gene sequencing, and esophageal tissue gene expression was ascertained by RNA-Seq. RESULTS: Twenty subjects were enrolled and included in the analyses. Within individuals, the oral and esophageal microbiome composition was significantly correlated. Chlorhexidine treatment associated with significant alterations to the relative abundance of several esophageal bacterial taxa, and to expression of genes in the esophagus including reductions in periostin, claudin-18, chemokines CXCL1 and CXCL13, and several members of the tumor necrosis factor receptor superfamily. A taxon in genus Haemophilus in the esophagus also associated with significant changes in tissue gene expression. DISCUSSION: The oral and esophageal microbiomes are closely related within individuals, and esophageal microbiome alterations correlate with tissue gene expression changes. The esophageal microbiome may act as an important cofactor that influences pathogenesis and outcomes of diseases such as eosinophilic esophagitis, gastroesophageal reflux, and Barrett's esophagus.

Epidemiology, patient adherence, and costs of oral mucositis in routine care in stem cell transplantation.

PURPOSE: Limited data about oral mucositis (OM) in stem cell transplant patients with underlying hematological disease is available in Germany. The purpose of this feasibility study was to determine the incidence, treatment patterns, patients' adherence, and costs of OM. METHODS: Prospective, noninterventional single-center observational study. INCLUSION CRITERIA: allogenic/autologous stem cell transplant patients ≥ 18 years, high-dose chemotherapy. OM assessment: WHO Oral Toxicity Scale. Adherence was measured in patient interviews. Preventive and therapeutic measures were extracted from patients' charts. RESULTS: Forty-five patients (25 allogenic, 20 autologous) were enrolled. Twenty-six (58%) patients developed OM (54% grade I/II, 46% grade III/IV). Age ≥ 65 (31% vs 69%, p = 0.021) was associated with a lower OM incidence. A positive history of smoking (1.77 vs 2.69, p = 0.036) was associated with a lower OM grade, patients with unrelated donors (2.63 vs 1.29, p = 0.014) were associated with higher OM grades and females (80% vs 47%, RR = 1.71, p = 0.035) with a higher incidence. OM patients were less adherent to recommended daily mouth rinses (35% vs 68%, p = 0.027). More analgesic treatment (80% vs 32%, p = 0.001) and intravenous opioids (24% vs 0%, p = 0.023) were prescribed in OM patients. Total drug treatment and nutrition costs were 824€ (p = 0.037) higher in autologous transplanted patients. CONCLUSION: Initial risk and consecutive OM assessment, determination of patients' adherence, resource consumption, and costs are prerequisites to evaluate OM care. In the best case, several centers will follow the same methodological approach and the collected data will serve as a basis for benchmarking analyses to optimize OM care where required.

Epigallocatechin-3-gallate mouthwash protects mucosa from radiation-induced mucositis in head and neck cancer patients: a prospective, non-randomised, phase 1 trial.

Radiation-induced oral mucositis has a dismal outcome with limited treatment options. We conducted a phase I study to evaluate the safety and preliminary efficacy of epigallocatechin-3-gallate (EGCG) mouthwash when given along with radiation in head and neck cancer. Patients with pathologically confirmed head and neck cancer were eligible for this study. EGCG mouthwash was administered at the assigned dosage level (starting at 440 µmol/L, three times a day) in a standard 3 + 3 dose escalation design. Mucosal toxicity, patient satisfaction, and mucositis-related pain (MTP) were assessed weekly. The primary endpoint was safety of EGCG, and the secondary endpoint was to determine the relief of the mucositis symptom. The pre- and post-treatment parameters were compared using the paired t-test. 20 patients were enrolled. The maximum tolerated dose of the EGCG mouthwash was 2200 µmol/L. Burning (n = 1/20) and nausea (n = 3/20) were the most common toxicities. No patients experienced WHO Grade 3 or higher mucositis. MTP scores significantly decreased after EGCG administration over time (p < 0.05). Adding EGCG mouthwash to radiotherapy is feasible without increasing toxicities. The recommended dose for phase II study is determined to be 1760 µmol/L, and EGCG administration reduces radiation-induced oral mucosal injury in patients.

Protocol for a multi-centered, stepped wedge, cluster randomized controlled trial of the de-adoption of oral chlorhexidine prophylaxis and implementation of an oral care bundle for mechanically ventilated critically ill patients: the CHORAL study.

BACKGROUND: Routine application of chlorhexidine oral rinse is recommended to reduce risk of ventilator-associated pneumonia (VAP) in mechanically ventilated patients. Recent reappraisal of the evidence from two meta-analyses suggests chlorhexidine may cause excess mortality in non-cardiac surgery patients and does not reduce VAP. Mechanisms for possible excess mortality are unclear. The CHORAL study will evaluate the impact of de-adopting chlorhexidine and implementing an oral care bundle (excluding chlorhexidine) on mortality, infection-related ventilator-associated complications (IVACs), and oral health status. METHODS: The CHORAL study is a stepped wedge, cluster randomized controlled trial in six academic intensive care units (ICUs) in Toronto, Canada. Clusters (ICU) will be randomly allocated to six sequential steps over a 14-month period to de-adopt oral chlorhexidine and implement a standardized oral care bundle (oral assessment, tooth brushing, moisturization, and secretion removal). On study commencement, all clusters begin with a control period in which the standard of care is oral chlorhexidine. Clusters then begin crossover from control to intervention every 2 months according to the randomization schedule. Participants include all mechanically ventilated adults eligible to receive the standardized oral care bundle. The primary outcome is ICU mortality; secondary outcomes are IVACs and oral health status. We will determine demographics, antibiotic usage, mortality, and IVAC rates from a validated local ICU clinical registry. With six clusters and 50 ventilated patients on average each month per cluster, we estimate that 4200 patients provide 80% power after accounting for intracluster correlation to detect an absolute reduction in mortality of 5.5%. We will analyze our primary outcome of mortality using a generalized linear mixed model adjusting for time to account for secular trends. We will conduct a process evaluation to determine intervention fidelity and to inform interpretation of the trial results. DISCUSSION: The CHORAL study will inform understanding of the effectiveness of de-adoption of oral chlorhexidine and implementation of a standardized oral care bundle for decreasing ICU mortality and IVAC rates while improving oral health status. Our process evaluation will inform clinicians and decision makers about intervention delivery to support future de-adoption if justified by trial results. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03382730 . Registered on December 26, 2017.

[Study of the quantity of interleukin-6 by SDS-PAAG electrophoresis and immuno-enzyme analysis in mixed saliva after rinsing the oral cavity with oligonucleotide specific.]

The selective properties of a solution of oligonucleotide specific to IL-6 on the concentration of IL-6 in mixed saliva of patients with oral inflammatory processes were studied using SDS-PAGE by electrophoresis and enzyme immunoassay. The application of these methods showed that in the mixed saliva of patients after rinsing with a solution of an oligonucleotide specific for IL-6, the amount of IL-6 decreases. The ELISA Kit and 20% SDS-PAGE showed the highest sensitivity to determine the concentration of IL-6 in saliva, which should be considered in clinical laboratory practice.

The ergogenic potency of carbohydrate mouth rinse on endurance running performance of dehydrated athletes.

PURPOSE: To examine the effect of carbohydrate (CHO) mouth rinsing on endurance running responses and performance in dehydrated individuals. METHODS: In a double blind, randomised crossover design, 12 well-trained male runners completed 4 running time to exhaustion (TTE) trials at a speed equivalent to 70% of VO2peak in a thermoneutral condition. Throughout each run, participants mouth rinsed and expectorated every 15 min either 25 mL of 6% CHO or a placebo (PLA) solution for 10 s. The four TTEs consisted of two trials in the euhydrated (EU-CHO and EU-PLA) and two trials in the dehydrated (DY-CHO and DY-PLA) state. Prior to each TTE run, participants were dehydrated via exercise and allowed a passive rest period during which they were fed and either rehydrated equivalent to their body mass deficit (i.e., EU trials) or ingested only 50 mL of water (DY trials). RESULTS: CHO mouth rinsing significantly improved TTE performance in the DY compared to the EU trials (78.2 ± 4.3 vs. 76.9 ± 3.8 min, P = 0.02). The arousal level of the runners was significantly higher in the DY compared to the EU trials (P = 0.02). There was no significant difference among trials in heart rate, plasma glucose and lactate, and psychological measures. CONCLUSIONS: CHO mouth rinsing enhanced running performance significantly more when participants were dehydrated vs. euhydrated due to the greater sensitivity of oral receptors related to thirst and central mediated activation. These results show that level of dehydration alters the effect of brain perception with presence of CHO.