Effects of Melatonin on Glycemic Variability in Type 2 Diabetes Mellitus: Protocol for a Crossover, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Glycemic variability is recognized as a significant factor contributing to the development of micro- and macrovascular complications in individuals with type 2 diabetes mellitus (T2DM). Numerous studies have shown that melatonin, a hormone involved in regulating various biological rhythms, including those related to glucose regulation, such as hunger, satiety, sleep, and circadian hormone secretion (ie, cortisol, growth hormone, catecholamines, and insulin), is deficient in individuals with T2DM. This raises an important question: Could melatonin replacement potentially reduce glycemic variability in these patients? This warrants investigation as a novel approach to improving glycemic control and reducing the risk of complications associated with T2DM. OBJECTIVE: We aimed to investigate whether melatonin replacement in individuals with T2DM who supposedly have melatonin deficiency can positively impact the regulation of insulin secretion rhythms and improve insulin sensitivity, ultimately resulting in a reduction in glycemic variability. METHODS: This study will use a crossover, randomized, double-blind, placebo-controlled trial design. Patients with T2DM in group 1 will receive 3 mg of melatonin at 9:00 PM in the first week, undergo a washout period in the second week, and receive a placebo in the third week (melatonin-washout-placebo). Group 2 will be randomized to receive a placebo-washout-melatonin sequence (3 mg). Capillary blood glucose levels will be measured at 6 different times before and after meals during the last 3 days of the first and third weeks. The study aims to compare the mean differences in blood glucose levels and the coefficient of glycemic variability in patients receiving melatonin and placebo during the first and third weeks. After analyzing the initial results, the number of needed patients will be recalculated. If the recalculated number is higher than 30, new participants will be recruited. Thirty patients with T2DM will be randomized into the 2 groups: melatonin-washout-placebo or placebo-washout-melatonin. RESULTS: Participant recruitment took place between March 2023 to April 2023. In all, 30 participants were eligible and completed the study. We expect that patients will show different glycemic variability on the days they receive placebo or melatonin. Studies on melatonin and glycemic control have shown both positive and negative results. We hope that there will be a positive outcome regarding glycemic variability (ie, a reduction in glycemic variability), as melatonin has a well-described chronobiotic effect in the literature. CONCLUSIONS: This study aims to determine whether melatonin supplementation can effectively reduce glycemic variability in patients with T2DM. The crossover design is necessary due to the multiple variables involved in the circadian variations of glucose, including diet, physical activity, sleep parameters, and pharmacological treatments. The relatively low cost of melatonin and its potential role in reducing the severe complications associated with T2DM have motivated this research effort. Furthermore, the indiscriminate use of melatonin in current times makes conducting this study essential to evaluate the effect of this substance in patients with T2DM. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials RBR-6wg54rb; https://ensaiosclinicos.gov.br/rg/RBR-6wg54rb. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47887.

Do ball-type attachment systems for overdenture result in better patient-satisfaction? A systematic review of randomized crossover clinical trial.

OBJECTIVE: This review is to compare patient-satisfaction with ball-type overdenture attachment systems with others attachment systems. MATERIAL AND METHODS: This study was registered in PROSPERO (CRD42018097234) and adheres the PRISMA guidelines. Electronic searches on PubMed/MEDLINE, Scopus, Cochrane, and Web of Science databases for published articles were performed before October 2020. The PICO question was: "Do patients with a ball-type overdenture retention system have greater satisfaction, when compared to other attachment systems?" The evaluation of risk of bias was performed using the Cochrane risk of bias tool. RESULTS: After searching the databases, seven articles were selected out of a total of 2583. A total of 312 implants were placed in 139 patients, with a mean age of 65.9 years. The risk of bias in the included studies varied according to the different domains in a risk of uncertain bias or low bias risk. No difference was found between the ball attachment systems and the others systems, with respect to patient-satisfaction. The meta-analysis revealed no statistically significant difference between the ball systems and another systems (P = 0.11; MD: 10.90; 95% CI: -2.55 to 24.35). CONCLUSIONS: Regarding patient general satisfaction, it was not possible to determine differences between the ball system and another types of attachment system for overdenture. The ball-type system was statistically superior only to the magnet system.

Challenges faced and lessons learned A multi-component prospective memory training program for Malaysian older adults.

The surrounding circumstances and environments of Malaysian older adults could make conducting interventions (mainly in terms of clinical or randomized controlled trials) a challenge. Working with older adults and facing cultural issues could be challenging. OBJECTIVE: This paper illustrates a significant perspective of some of the challenges faced while conducting a randomized controlled trial exploring the impact of a multi-component intervention that included strategy- and process-based prospective memory (PM) training among Malaysian older adults. METHODS: The current study was a randomized controlled trial (RCT) and therefore the challenges were presented in accordance with the CONSORT statement style. RESULTS: A discussion on how these issues were addressed is provided. CONCLUSION: Some suggestions were presented to help researchers plan and create interventions for similar studies and to support a practical method of addressing all related challenges.

As circunstâncias e ambientes circundantes de adultos idosos da Malásia poderiam tornar a condução da intervenção (principalmente em termos de ensaios clínicos ou randomizados controlados) um desafio. Trabalhar com adultos mais velhos e enfrentar problemas culturais pode ser instigante. OBJETIVO: Este artigo ilustra uma perspectiva significativa de alguns dos desafios enfrentados durante a realização de um estudo controlado randomizado que explora o impacto de uma intervenção de múltiplos componentes, incluindo treinamento de memória prospectiva baseado em estratégia e processo (PM) entre idosos da Malásia. MÉTODOS: Como o estudo atual foi um ensaio clínico randomizado (ECR), os desafios foram apresentados de acordo com o estilo de declaração CONSORT. RESULTADOS: Uma discussão sobre como essas questões foram abordadas é fornecida. CONCLUSÃO: Algumas sugestões foram apresentadas para ajudar os pesquisadores a planejar e criar intervenções para estudos semelhantes e capacitar um método prático para abordar todos os desafios relacionados.

Challenges faced and lessons learned: a multi-component prospective memory training program for Malaysian older adults / Desafios enfrentados e lições aprendidas: um programa de treinamento de memória prospectiva de vários componentes para adultos idosos da Malásia

Abstract The surrounding circumstances and environments of Malaysian older adults could make conducting interventions (mainly in terms of clinical or randomized controlled trials) a challenge. Working with older adults and facing cultural issues could be challenging. Objective: This paper illustrates a significant perspective of some of the challenges faced while conducting a randomized controlled trial exploring the impact of a multi-component intervention that included strategy- and process-based prospective memory (PM) training among Malaysian older adults. Methods: The current study was a randomized controlled trial (RCT) and therefore the challenges were presented in accordance with the CONSORT statement style. Results: A discussion on how these issues were addressed is provided. Conclusion: Some suggestions were presented to help researchers plan and create interventions for similar studies and to support a practical method of addressing all related challenges.

Resumo As circunstâncias e ambientes circundantes de adultos idosos da Malásia poderiam tornar a condução da intervenção (principalmente em termos de ensaios clínicos ou randomizados controlados) um desafio. Trabalhar com adultos mais velhos e enfrentar problemas culturais pode ser instigante. Objetivo: Este artigo ilustra uma perspectiva significativa de alguns dos desafios enfrentados durante a realização de um estudo controlado randomizado que explora o impacto de uma intervenção de múltiplos componentes, incluindo treinamento de memória prospectiva baseado em estratégia e processo (PM) entre idosos da Malásia. Métodos: Como o estudo atual foi um ensaio clínico randomizado (ECR), os desafios foram apresentados de acordo com o estilo de declaração CONSORT. Resultados: Uma discussão sobre como essas questões foram abordadas é fornecida. Conclusão: Algumas sugestões foram apresentadas para ajudar os pesquisadores a planejar e criar intervenções para estudos semelhantes e capacitar um método prático para abordar todos os desafios relacionados.

Chlorhexidine with or without alcohol against biofilm formation: efficacy, adverse events and taste preference

Abstract In recent years, different chlorhexidine formulations have been tested, including an alcohol-free alternative, but the effect of this solution on early biofilm formation is not clear. A crossover, randomized, double-blind clinical trial was conducted to evaluate the effect of two chlorhexidine solutions against supra- and subgingival biofilm formation (NCT#02656251). Thirty-five participants were randomized and asked to rinse twice daily with 15 ml of an alcohol-containing 0.12% chlorhexidine solution, an alcohol-free 0.12% chlorhexidine solution, or placebo. The study was conducted in three experimental periods of 4 days each, with a 10-day washout between the periods. All the experimental periods followed the same protocol, except that the solutions were switched. Biofilm distribution was evaluated every 24 hours by the Plaque-Free Zone Index, during 96 hours. Adverse events were self-reported and sensory evaluation was performed using a hedonic scale. Compared to the placebo, the chlorhexidine solutions resulted in a significantly higher number of surfaces free of plaque over 96 hours (p < 0.01), and were able to prevent subgingival biofilm formation (p < 0.01). The alcohol-free chlorhexidine solution was associated with a lower incidence of adverse events, compared with alcohol-containing chlorhexidine (p < 0.05); it also received better sensory evaluation and acceptance by trial participants, compared with the alcohol-containing chlorhexidine (p = 0.007), and had a similar inhibitory effect on the formation of supra- and subgingival biofilms.

Treatment of hypothyroidism with levothyroxine plus liothyronine: a randomized, double-blind, crossover study

ABSTRACT Objective To compare the effects of a unique fixed combination levothyroxine/liothyronine (LT4/LT3) therapy in patients with primary hypothyroidism. Subjects and methods This is a randomized, double-blind, crossover study. Adults with primary hypothyroidism (n = 32, age 42.6 ± 13.3, 30 females) on stable doses of LT4 for ≥ 6 months (125 or 150 μg/day) were randomized to continue LT4 treatment (G1) or to start LT4/LT3 therapy (75/15 μg/day; G2). After 8 weeks, participants switched treatments for 8 more weeks. Thyroid function, lipid profile, plasma glucose, body weight, electrocardiogram, vital signs, and quality of life (QoL) were evaluated at weeks 0, 8 and 16. Results Free T4 levels were significantly lower while on LT4/LT3 (G1: 1.07 ± 0.29 vs. 1.65 ± 0.46; G2: 0.97 ± 0.26 vs. 1.63 ± 0.43 ng/dL; P < 0.001). TSH and T3 levels were not affected by type of therapy. More patients on LT4/LT3 had T3 levels above the upper limit (15% vs. 3%). The combination therapy led to an increase in heart rate, with no significant changes in electrocardiogram or arterial blood pressure. Lipid profile, body weight and QoL remained unchanged. Conclusions The combination therapy yielded significantly lower free T4 levels, with no changes in TSH or T3 levels. More patients on LT4/T3 had elevated T3 levels, with no significant alterations in the evaluated outcomes. No clear clinical benefit of the studied formulation could be observed. Future trials need to evaluate different formulations and the impact of the combined therapy in select populations with genetic polymorphisms.

Avaliação de aspectos relacionados á utilização de um adesivo para próteses totais convencionas: estudo in vitro / Evaluation of aspects related to the use of an adhesive to conventional dentures: in vivo study

O objetivo do presente estudo foi avaliar a influência da utilização de um adesivo para prótese (Ultra Corega creme) na formação de biofilme sobre a superfície interna de próteses totais e na microbiota bucal, no grau de satisfação, além da estimativa de custo médio diário do produto. Trinta pacientes receberam próteses totais novas, e foram divididos em dois protocolos: protocolo 1- utilização do adesivo durante os primeiros 15 dias de teste, seguida por não utilização de nenhum tipo de adesivo durante os próximos 15 dias; protocolo 2- não utilização de adesivo durante os primeiros 15 dias de teste, seguida por utilização do adesivo durante os próximos 15 dias. Após cada período de 15 dias, o biofilme formado na superfície interna das próteses totais foi corado e quantificado por meio de um método fotográfico com o auxílio de um software (Image Tool 3.00). Amostras de material da mucosa palatina e da superfície interna das próteses superiores foram plaqueadas em meios seletivos para Candida spp. e Streptococcus mutans e em um meio não seletivo. Ainda, foi aplicado um questionário para avaliação da satisfação com as próteses e o custo médio diário do produto foi estimado por meio de fórmulas matemáticas. Todas as análises foram realizadas com α = 0,05 e foram empregados testes apropriados à distribuição dos dados. Foi observada formação de biofilme semelhante com ou sem o uso do adesivo sobre as próteses superiores (Wilcoxon, p=0,255) e inferiores (Wilcoxon, p=0,433). Contagens de colônias semelhantes foram observadas com ou sem a utilização do adesivo na mucosa e na superfície interna da prótese total superior (p>0,05). O uso de adesivo proporcionou maior satisfação aos participantes (Wilcoxon, p=0,04). Em média, cada paciente utilizou 3,9 ± 0,3 gramas de adesivo por dia...

The aim of this study was to evaluate the influence of adhesive usage (Ultra Corega cream) on biofilm formation on the internal surface of dentures and oral microbiota, degree of satisfaction, and the estimated average daily cost of product. Thirty patients received new dentures, and have been divided into two protocols: Protocol 1-use of the adhesive during the first 15 days of the test, followed by not using adhesive over the next 15 days; Protocol 2- no use of adhesive for the first 15 days of the test, followed by use of adhesive over the next 15 days. After each period of 15 days, the internal surfaces of the dentures were stained and photographed and the areas (total internal surface and surface stained with biofilm) quantified (Image Tool 3.00). Samples of material from the palatal mucosa and the internal surface of the maxillary denture were plated on selective media for Candida spp. and Streptococcus mutans and a non-selective medium. A questionnaire was applied to evaluate satisfaction with the dentures and the average daily cost of the product was estimated by mathematical formulas. All analyzes were performed with α=.05 and appropriate tests were applied to the data distribution. Similar biofilm formation was found with or without adhesive usage for maxillary (Wilcoxon, p=.255) and mandibular dentures (Wilcoxon, p=.433). Similar colony counts were observed with or without adhesive for mucosa and the internal surface of dentures, irrespective of the culture medium (p>.05). The use of adhesive provided higher satisfaction (Wilcoxon, p=.04). On average, each patient used 3.9 ± 0.3 grams of adhesive per day, equivalent to R $ 4.02 for average daily cost. It is concluded that the use of the adhesive did not affect the quantification of the biofilm and the oral microbiota, besides providing greater overall satisfaction

Avaliação de aspectos relacionados á utilização de um adesivo para próteses totais convencionas: estudo in vitro / Evalution of aspects related to the use of an adhesive to conventional dentures: in vivo study

O objetivo do presente estudo foi avaliar a influência da utilização de um adesivo para prótese (Ultra Corega creme) na formação de biofilme sobre a superfície interna de próteses totais e na microbiota bucal, no grau de satisfação, além da estimativa de custo médio diário do produto. Trinta pacientes receberam próteses totais novas, e foram divididos em dois protocolos: protocolo 1- utilização do adesivo durante os primeiros 15 dias de teste, seguida por não utilização de nenhum tipo de adesivo durante os próximos 15 dias; protocolo 2- não utilização de adesivo durante os primeiros 15 dias de teste, seguida por utilização do adesivo durante os próximos 15 dias. Após cada período de 15 dias, o biofilme formado na superfície interna das próteses totais foi corado e quantificado por meio de um método fotográfico com o auxílio de um software (Image Tool 3.00). Amostras de material da mucosa palatina e da superfície interna das próteses superiores foram plaqueadas em meios seletivos para Candida spp. e Streptococcus mutans e em um meio não seletivo. Ainda, foi aplicado um questionário para avaliação da satisfação com as próteses e o custo médio diário do produto foi estimado por meio de fórmulas matemáticas. Todas as análises foram realizadas com α = 0,05 e foram empregados testes apropriados à distribuição dos dados. Foi observada formação de biofilme semelhante com ou sem o uso do adesivo sobre as próteses superiores (Wilcoxon, p=0,255) e inferiores (Wilcoxon, p=0,433). Contagens de colônias semelhantes foram observadas com ou sem a utilização do adesivo na mucosa e na superfície interna da prótese total superior (p>0,05). O uso de adesivo proporcionou maior satisfação aos participantes (Wilcoxon, p=0,04). Em média, cada paciente utilizou 3,9 ± 0,3 gramas de adesivo por dia, o que equivale a R$ 4,02 de custo médio diário. Conclui-se que a utilização do adesivo não influenciou na quantificação do biofilme e na microbiota bucal, além de proporcionar maior satisfação gera

The aim of this study was to evaluate the influence of adhesive usage (Ultra Corega cream) on biofilm formation on the internal surface of dentures and oral microbiota, degree of satisfaction, and the estimated average daily cost of product. Thirty patients received new dentures, and have been divided into two protocols: Protocol 1-use of the adhesive during the first 15 days of the test, followed by not using adhesive over the next 15 days; Protocol 2- no use of adhesive for the first 15 days of the test, followed by use of adhesive over the next 15 days. After each period of 15 days, the internal surfaces of the dentures were stained and photographed and the areas (total internal surface and surface stained with biofilm) quantified (Image Tool 3.00). Samples of material from the palatal mucosa and the internal surface of the maxillary denture were plated on selective media for Candida spp. and Streptococcus mutans and a non-selective medium. A questionnaire was applied to evaluate satisfaction with the dentures and the average daily cost of the product was estimated by mathematical formulas. All analyzes were performed with α=.05 and appropriate tests were applied to the data distribution. Similar biofilm formation was found with or without adhesive usage for maxillary (Wilcoxon, p=.255) and mandibular dentures (Wilcoxon, p=.433). Similar colony counts were observed with or without adhesive for mucosa and the internal surface of dentures, irrespective of the culture medium (p>.05). The use of adhesive provided higher satisfaction (Wilcoxon, p=.04). On average, each patient used 3.9 ± 0.3 grams of adhesive per day, equivalent to R $ 4.02 for average daily cost. It is concluded that the use of the adhesive did not affect the quantification of the biofilm and the oral microbiota, besides providing greater overall satisfaction

Salivary retention after application of fluoride gel using toothbrush or tray: a crossover trial

Currently, there are no studies in the literature evaluating salivary fluoride retention after small amounts of fluoride gel are applied to children's teeth. Therefore, the objective of the present study was to compare salivary retention after gel application using a toothbrush or by traditional application with trays. In this crossover study, children with active caries (n = 10) were randomized into one of the following treatment groups: a) application of fluoride gel using a tray (control), or b) application of fluoride gel with a toothbrush (treatment). After a 7-day washout period, the treatments were inverted. Unstimulated saliva samples were collected at baseline and 0.5, 5, 15, 30, 60 and 120 minutes after acidulated phosphate fluoride (APF) gel application in order to analyze fluoride retention in saliva. The area under the curve (AUC) was also calculated. There were no differences in fluoride retention after application of small amounts of APF with a toothbrush compared to traditional gel application using trays at all time points studied, and no differences in AUC were observed (Student t-test, p > 0.05). These results suggest that application of fluoride gel in children using a toothbrush can be utilized as an option rather than traditional trays, since the same salivary retention of fluoride is obtained using a lower dose.