Effect of the ß-tricalcium phosphate particle on dental enamel associated with 10% carbamide peroxide bleaching.

Background: Since bleaching gels can cause adverse effects on tooth enamel, it is important to evaluate new remineralizing agents on the market and their effects. Material and Methods: Seventy-five bovine enamel/dentin blocks (4x4x3mm) were randomly divided into six groups (n=10): Negative Control (NC) with no bleaching treatment or brushing; 10 CP (Carbamide Peroxide) (no brushing - Whiteness Perfect FGM); CT12 + 10 CP (Colgate Total® 12); ES + 10 CP (Elmex® Sensitive); BPC + 10 CP (Bianco® ProClinical); CMP + 10 CP (Colgate® Máxima Proteção Anticáries). The color was evaluated by reflectance spectrophotometry (∆E*ab, ∆E00, and ∆WID) at times T1 (baseline), T2 (24 hours after brushing), and T3 (24 hours after bleaching). Knoop microhardness (KHN) analysis were performed at T3. The enamel surface was qualitatively analyzed by Scanning Electron Microscopy (SEM). The data were analyzed using generalized linear models through descriptive and exploratory analyses, and a significance level of 5% was considered. Results: Significant differences were observed when the bleached groups were compared to the NC group for ∆E*ab, ∆E00, and ∆WID at time T3 (p= <0.0001). However, the bleached groups presented no significant differences regarding studied times (p> 0.05). KHN did not differ significantly among the six groups (p=0.7585). Conclusions: Toothpastes with tricalcium phosphate (ß-TCP) do not intervene with the efficacy of bleaching treatment with 10% carbamide peroxide. Although a slight mineral deposition on enamel surface can be observed on SEM images, KHN was not significantly altered, and the polishing of the samples were maintained. Key words:Dental Bleaching, Carbamide Peroxide, Hydrogen Peroxide, Dental Enamel, Tricalcium Phosphate.

Overexpression of α-Klotho isoforms promotes distinct Effects on BDNF-Induced Alterations in Dendritic Morphology.

α-Klotho (α-Kl) is a modulator of aging, neuroprotection, and cognition. Transcription of the Klotho gene produces two splice variants-a membrane protein (mKl), which can be cleaved and released into the extracellular milieu, and a truncated secreted form (sKl). Despite mounting evidence supporting a role for α-Kl in brain function, the specific roles of α-Kl isoforms in neuronal development remain elusive. Here, we examined α-Kl protein levels in rat brain and observed region-specific expression in the adult that differs between isoforms. In the developing hippocampus, levels of isoforms decrease after the third postnatal week, marking the end of the critical period for development. We overexpressed α-Kl isoforms in primary cultures of rat cortical neurons and evaluated effects on brain-derived neurotrophic factor (BDNF) signaling. Overexpression of either isoform attenuated BDNF-mediated signaling and reduced intracellular Ca2+ levels, with mKl promoting a greater effect. mKl or sKl overexpression in hippocampal neurons resulted in a partially overlapping reduction in secondary dendrite branching. Moreover, mKl overexpression increased primary dendrite number. BDNF treatment of neurons overexpressing sKl resulted in a dendrite branching phenotype similar to control neurons. In neurons overexpressing mKl, BDNF treatment restored branching of secondary and higher order dendrites close, but not distal, to the soma. Taken together, the data presented support the idea that sKl and mKl play distinct roles in neuronal development, and specifically, in dendrite morphogenesis.

Stretch-Induced Injury Affects Cortical Neuronal Networks in a Time- and Severity-Dependent Manner.

Traumatic brain injury (TBI) is the leading cause of accident-related death and disability in the world and can lead to long-term neuropsychiatric symptoms, such as a decline in cognitive function and neurodegeneration. TBI includes primary and secondary injury, with head trauma and deformation of the brain caused by the physical force of the impact as primary injury, and cellular and molecular cascades that lead to cell death as secondary injury. Currently, there is no treatment for TBI-induced cell damage and neural circuit dysfunction in the brain, and thus, it is important to understand the underlying cellular mechanisms that lead to cell damage. In the current study, we use stretchable microelectrode arrays (sMEAs) to model the primary injury of TBI to study the electrophysiological effects of physically injuring cortical cells. We recorded electrophysiological activity before injury and then stretched the flexible membrane of the sMEAs to injure the cells to varying degrees. At 1, 24, and 72 h post-stretch, we recorded activity to analyze differences in spike rate, Fano factor, burstlet rate, burstlet width, synchrony of firing, local network efficiency, and Q statistic. Our results demonstrate that mechanical injury changes the firing properties of cortical neuron networks in culture in a time- and severity-dependent manner. Our results suggest that changes to electrophysiological properties after stretch are dependent on the strength of synchronization between neurons prior to injury.

Malondialdehyde Analysis in Biological Samples by Capillary Electrophoresis: The State of Art.

Lipid peroxidation occurs when substances, such as reactive oxygen species, attack lipids. Polyunsaturated fatty acids are the main targets. Several products are formed, including primary products such as lipid hydroperoxides and secondary products such as malondialdehyde (MDA), the most used lipid peroxidation biomarker. As MDA levels are elevated in several diseases, MDA is an essential indicator for assessing pathological states. The thiobarbituric acid reactive substances assay is the most widely used method for MDA determination. However, it lacks specificity. Capillary Electrophoresis (CE) is a separation technique that has been used to quantify MDA in biological samples. This technique has advantages such as the low amount of biological sample required, absence or low volume of organic solvent, short analysis time, separation of interferents, sample preparation step with only protein precipitation, and the possibility of direct detection of the MDA, without derivatization. To our knowledge, this review article is the first to show the CE background for analyzing MDA in biological samples. Therefore, given the potential of MDA in evaluating pathological states, this article demonstrates the potential of CE to become a reference method for MDA determination in clinical analysis laboratories, which will play a significant role in diagnosing and monitoring diseases.

Modification of pectin/starch-based beads with additives to improve Bacillus subtilis encapsulation for agricultural applications.

The use of Bacillus as biofertilizer is a sustainable strategy to increase agricultural productivity, but it still requires the development of formulations to protect cells from stressful conditions. Ionotropic gelation using a pectin/starch matrix is a promising encapsulation strategy to achieve this goal. By incorporating additives such as montmorillonite (MMT), attapulgite (ATP), polyethylene glycol (PEG), and carboxymethyl cellulose (CMC), the properties of these encapsulated products could be further improved. In this study, we investigated the influence of these additives on the properties of pectin/starch-based beads for the encapsulation of Bacillus subtilis. FTIR analysis indicated pectin and Ca2+ ions interactions, while the XRD showed good dispersion of clays in the materials. SEM and X-ray microtomography revealed differences in the morphology of the beads due to the use of the additives. The viabilities at the encapsulation were higher than 1010 CFU g-1 for all formulations, with differences in the release profiles. In terms of cell protection, the pectin/starch, pectin/starch-MMT and pectin/starch-CMC formulations showed the highest cell viability after exposure to fungicide, while the pectin/starch-ATP beads showed the best performance after UV exposure. Moreover, all formulations maintained more than 109 CFU g-1 after six months of storage, which meets values required for microbial inoculants.

Effect of clinical treatments for metabolic syndrome on albuminuria: a systematic review protocol

Introduction:Metabolic syndrome (MetS) predicts cardiovascular disease, and patients with this condition and type 2 diabetes have increased albuminuria, significantly impacting cardiovascular mortality and kidney disease progression. A considerable number of interventions to control MetS exist and are considered efficient, including the use of medication and changes in lifestyle. However, which approaches are effective in controlling albuminuria remains unclear. This systematic review protocol aims to map in the available literature whether lifestyle, medication, and surgical intervention for MetS have an impact on reducing albuminuria in adult patients. Methods: The Joanna Briggs Institute methodology for systematic reviews will be followed. Cochrane Database of Systematic Reviews, Scopus, Embase, and MEDLINE/PubMed databases will be used. For the Gray Literature, the DART-Europe E-theses Portal. There will be no language restriction. Studies written after 2009 will be included due to the consensus and definition of metabolic syndrome. This review will include studies considering pharmacological and non-pharmacological treatments for controlling albuminuria in patients with MetS. Studies where MetS is described in children and adolescents, animals, pregnant women, and patients with type 1 diabetes will be excluded. First, the selection will be based on reading the title and summary of the texts retrieved in the search strategy, followed by reading the relevant texts in full by two reviewers. After the selection of the studies, the extraction of the data, analysis, and synthesis will be conducted according to the JBI methodology

Exploring the roles of starch for microbial encapsulation through a systematic mapping review.

Microorganism encapsulation protects them from stressful conditions and assists in maintaining their viability, being especially beneficial when the carrier material is a renewable and biodegradable biopolymer, such as starch. Here, a systematic mapping was performed to provide a current overview on the use of starch-based systems for microbial encapsulation. Following well-established guidelines, a systematic mapping was conducted and the following could be drawn: 1) there was a significant increase in publications on microbial encapsulation using starch over the past decade, showing interest from the scientific community, 2) ionotropic gelation, emulsification and spray drying are the most commonly used techniques for starch-based microbial encapsulation, and 3) starch play important functions in the encapsulation matrix such as assisting in the survival of the microorganisms. The information gathered in this systematic mapping can be useful to guide researchers and industrial sectors on the development of innovative starch-based systems for microbial encapsulation.

Self-management strategies and multicomponent training to mitigate the effects of the interruption of physical exercise programmes in the pandemic context on functionality, sedentary behaviour, physical capacity, mental health, body composition and quality of life in older adults: a blinded randomized controlled study protocol.

BACKGROUND: Considering the confinement recommended by the World Health Organization due to the pandemic caused by COVID-19, many community physical exercise programmes for older adults have had their activities cancelled. In this context, proposing strategies to recover the possible adverse effects of the confinement period is pertinent. The use of self-management strategies associated with regular physical activity reduces sedentary behaviour and improves physical capacity in older adults. Thus, the purpose of this study was to describe a multicomponent training programme combined with a self-management strategy protocol to mitigate the effects of interruptions in physical exercise programmes on functionality, physical capacity, mental health, body composition and quality of life in older adults. METHODS: This will be a blinded, randomized and controlled clinical trial performed in São Carlos, SP, Brazil. Eighty older adults will be divided into two groups: multicomponent training (Multi) and multicomponent training + self-management strategies (Multi+SM). The intervention will be performed over 16 weeks on three alternate days of every week, with 50-min sessions. The assessment of physical capacity will be performed before the interruption of physical exercise programmes (T0: initial assessment, March 2020), preintervention (T1: immediately after the return of the exercise programme) and postintervention (T2). The assessments of physical activity level, quality of life, mental health, functionality and body composition will be performed at T1 and T2. DISCUSSION: The results from this MC+SM protocol will allow us to contribute clinical support to evaluate the variables analysed and to guide future public health policies with the aim of minimizing the possible deleterious effects arising from the physical exercise interruption periods caused by epidemics and pandemics. TRIAL REGISTRATION: RBR-10zs97gk . Prospectively registered in Brazilian Registry of Clinical Trials (ReBEC) on 17 June 2021. Registry name: Use of self-management strategies combined with multicomponent training to mitigate the effects of social distancing due to COVID-19 on capacity, physical capacity, mental health and quality of life in older adults - A blind, randomized and controlled clinical trial.

Association between Cardiovascular Risk in Adolescents and Daily Consumption of Soft Drinks: a Brazilian National Study

Abstract Background: Cardiovascular risk in adolescence is a public health problem that has grown along with the increase in soft drink consumption. Objective: To investigate the association between cardiovascular risk factors and daily consumption of soft drinks in Brazilian adolescents. Methods: We conducted a cross-sectional, national, school-based study of 36,956 Brazilian adolescents aged 12 to 17 years. Daily soft drink consumption was estimated using a 24-hour dietary recall. Cardiovascular risk was categorized as overweight, obesity, hypertension, hyperglycemia, and dyslipidemia. The survey command of Stata 14.0® was used to analyze data from a complex sample. The chi-square test was used to assess differences in soft drink consumption and other variables in the descriptive analysis. The odds ratio of cardiovascular risk factors and their respective 95% confidence intervals were estimated, considering sociodemographic and behavioral variables in the Mantel-Haenszel model. Statistical significance was set at p < 0.05. Results: Daily consumption of soft drinks was common among adolescents. A daily serving ≥ 450 mL was significantly associated with overweight and hypertension. Results associated with the consumption of regular soft drinks show the possibility of reverse causality. Consumption of diet soft drinks in adolescence should be considered a cardiovascular risk factor. Conclusion: Daily consumption of soft drinks can be understood as a relevant risk factor in the epidemiological scenario. Improper eating habits are multifactorial in nature and need to be better understood in the context of adolescent health and further explored in national surveys.

Sales of "COVID kit" drugs and adverse drug reactions reported by the Brazilian Health Regulatory Agency.

Off-label use of azithromycin, hydroxychloroquine, and ivermectin (the "COVID kit") has been suggested for COVID-19 treatment in Brazil without clinical or scientific evidence of efficacy. These drugs have known adverse drug reactions (ADR). This study aimed to analyze if the sales of drugs in the "COVID kit" are correlated to the reported number of ADR after the COVID-19 pandemic began. Data was obtained from the Brazilian Health Regulatory Agency (Anvisa) website on reported sales and ADRs for azithromycin, hydroxychloroquine, and ivermectin for all Brazilian states. The period from March 2019 to February 2020 (before the pandemic) was compared to that from March 2020 to February 2021 (during the pandemic). Trend adjustment was performed for time series data and cross-correlation analysis to investigate correlation between sales and ADR within the same month (lag 0) and in the following months (lag 1 and lag 2). Spearman's correlation coefficient was used to assess the magnitude of the correlations. After the pandemic onset, sales of all investigated drugs increased significantly (69.75% for azithromycin, 10,856,481.39% for hydroxychloroquine, and 12,291,129.32% for ivermectin). ADR levels of all medications but azithromycin were zero before the pandemic, but increased after its onset. Cross-correlation analysis was significant in lag 1 for all drugs nationwide. Spearman's correlation was moderate for azithromycin and hydroxychloroquine but absent for ivermectin. Data must be interpreted cautiously since no active search for ADR was performed. Our results show that the increased and indiscriminate use of "COVID kit" during the pandemic correlates to an increased occurrence of ADRs.

Förster resonance energy transfer efficiency of the vinculin tension sensor in cultured primary cortical neuronal growth cones.

Significance: Interaction of neurons with their extracellular environment and the mechanical forces at focal adhesions and synaptic junctions play important roles in neuronal development. Aim: To advance studies of mechanotransduction, we demonstrate the use of the vinculin tension sensor (VinTS) in primary cultures of cortical neurons. VinTS consists of TS module (TSMod), a Förster resonance energy transfer (FRET)-based tension sensor, inserted between vinculin's head and tail. FRET efficiency decreases with increased tension across vinculin. Approach: Primary cortical neurons cultured on glass coverslips coated with poly-d-lysine and laminin were transfected with plasmids encoding untargeted TSMod, VinTS, or tail-less vinculinTS (VinTL) lacking the actin-binding domain. The neurons were imaged between day in vitro (DIV) 5 to 8. We detail the image processing steps for calculation of FRET efficiency and use this system to investigate the expression and FRET efficiency of VinTS in growth cones. Results: The distribution of fluorescent constructs was similar within growth cones at DIV 5 to 8. The mean FRET efficiency of TSMod ( 28.5 ± 3.6 % ) in growth cones was higher than the mean FRET efficiency of VinTS ( 24.6 ± 2 % ) and VinTL ( 25.8 ± 1.8 % ) ( p < 10 - 6 ). While small, the difference between the FRET efficiency of VinTS and VinTL was statistically significant ( p < 10 - 3 ), suggesting that vinculin is under low tension in growth cones. Two-hour treatment with the Rho-associated kinase inhibitor Y-27632 did not affect the mean FRET efficiency. Growth cones exhibited dynamic changes in morphology as observed by time-lapse imaging. VinTS FRET efficiency showed greater variance than TSMod FRET efficiency as a function of time, suggesting a greater dependence of VinTS FRET efficiency on growth cone dynamics compared with TSMod. Conclusions: The results demonstrate the feasibility of using VinTS to probe the function of vinculin in neuronal growth cones and provide a foundation for studies of mechanotransduction in neurons using this tension probe.

Exposure to Sodium Hypochlorite or Cigarette Smoke Induces Lung Injury and Mechanical Impairment in Wistar Rats.

Pulmonary irritants, such as cigarette smoke (CS) and sodium hypochlorite (NaClO), are associated to pulmonary diseases in cleaning workers. We examined whether their association affects lung mechanics and inflammation in Wistar rats. Exposure to these irritants alone induced alterations in the lung mechanics, inflammation, and remodeling. The CS increased airway cell infiltration, acid mucus production, MMP-12 expression, and alveolar enlargement. NaClO increased the number of eosinophils and macrophages in the bronchoalveolar lavage fluid, with cells expressing IL-13, MMP-12, MMP-9, TIMP-1, and iNOS in addition to increased IL-1ß and TNF-α levels. Co-exposure to both irritants increased epithelial and smooth muscle cell area, acid mucus production, and IL-13 expression in the airways, while it reduced the lung inflammation. In conclusion, the co-exposure of CS with NaClO reduced the pulmonary inflammation, but increased the acidity of mucus, which may protect lungs from more injury. A cross-resistance in people exposed to multiple lung irritants should also be considered.

Paraprobiotic Enterococcus faecalis EC-12 prevents the development of irinotecan-induced intestinal mucositis in mice.

AIMS: This study tested the protective effect of purified paraprobiotic Enterococcus faecalis (EC-12) and an E. faecalis-based formulation (Med LanS) on irinotecan-induced intestinal mucositis murine model. MAIN METHODS: C57BL/6 male mice received saline, irinotecan (75 mg/Kg, i.p.), EC-12 (0.3, 1, or 3 × 107 CFU/Kg, p.o.) + irinotecan or Med Lan-S (3 × 107 CFU/Kg, p.o.) + irinotecan. Body mass variation was assessed daily, and blood samples were collected for evaluating bacteremia and leukocyte count. The ileum was harvested for myeloperoxidase assay, histopathology, quantitative PCR, and immunofluorescence for macrophages (F4/80), TLR4, and IL-18 binding protein (IL-18BP). KEY FINDINGS: The best therapeutic strategy was EC-12 administration at 3 × 107 CFU/Kg, starting 1 week before irinotecan. EC-12 and Med Lan-S did not prevent the irinotecan-induced body mass loss or leukopenia but attenuated the neutrophil infiltration in the intestine and increased the villus/crypt ratio (P < 0.05). Additionally, EC-12 and Med Lan-S reduced the mRNA expression of Cldn-2, Ocln, and Tlr4 versus the irinotecan group (P < 0.05). Irinotecan also augmented the expression of Il-18, IL-18BP, the immunofluorescence of F4/80, and TLR4, while only EC-12 prevented the expression of all these markers. Remarkably, EC-12 and Med Lan inhibited the irinotecan-induced bacterial translocation to the blood. SIGNIFICANCE: Paraprobiotic E. faecalis EC-12 prevents the development of intestinal mucositis by downregulating the inflammatory response. Med Lan-S also protects from mucositis. Possibly, the complexity of the formulation accounts for an innate immune-driven protective mechanism.

Potentially carcinogenic effects of hydrogen peroxide for tooth bleaching on the oral mucosa: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: Little is known about the extent to which hydrogen peroxide as used for tooth bleaching could be carcinogenic to the oral mucosa. PURPOSE: The purpose of this systematic review and meta-analysis was to evaluate whether hydrogen peroxide as used for tooth bleaching has carcinogenic effects on the oral mucosa. MATERIAL AND METHODS: PubMed, Web of Science, Scopus, and Embase electronic databases were searched. Studies evaluating different outcomes potentially related to the carcinogenic effects of hydrogen peroxide for tooth bleaching on the oral mucosa were included. Risk of bias was assessed by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE), Risk Of Bias in Non-randomized Studies of Interventions (ROBINS-I), or Risk of Bias 2 (RoB 2) tools. The strength of the evidence was assessed by using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) protocol. The quantitative analysis was performed with means, standard deviations, and 95% confidence intervals (CIs). Heterogeneity was analyzed by using I-squared statistics. RESULTS: Thirteen articles comprising 5 animal and 8 clinical studies met the inclusion criteria. Three of the 5 animal studies associated the bleaching agents with a carcinogen and demonstrated an enhancement of the carcinogenic effect, but probably with the bleaching agent acting only as a promoter. Five clinical studies concluded that the bleaching agents did not cause mutagenic stress on the oral mucosa by using the micronucleus test. The meta-analysis demonstrated that the frequency of micronuclei did not differ significantly between baseline and 30 days after bleaching (mean difference: 0.48; 95% CI, -1.49, 2.46; P=.63). CONCLUSIONS: This systematic review indicated that hydrogen peroxide does not appear to have carcinogenic effects on the oral mucosa.

Medicinal plant use in primary health care: an integrative review. / O uso de plantas medicinais na atenção primária à saúde: revisão integrativa.

Medicinal plant (MP) use supports comprehensiveness of care in Primary Health Care (PHC), enabling appreciation of popular knowledge and self-care. This integrative literature review aims to analyze researches that approach the insertion of using MP in PHC. PICO strategy was used as a guideline in search of evidence, reuniting 18 articles published between January 2015 and August 2020, in the Virtual Health Library and PubMed databases. The variables of analysis were knowledge of PHC healthcare professionals about MP and associated policies, MP use by its users, highlighting their profile, the reasons that lead to the use and lack of security in MP use. The results show insufficient knowledge of healthcare professionals about Integrative and Complementary Practices policies and the medicinal uses of plants. The main users are women, elderly, with low income and education, either in Brazil or other countries. Regarding safety in MP use, frequently there is no correct identification of species, its origin, its preparation and the appropriate dose for each case. Finally, failure to approach these contents during training of healthcare professionals generates less knowledge, less research and more prejudice due to lack of information, impairing incentive and dissemination to the community.

O uso de plantas medicinais (PM) favorece a integralidade do cuidado na atenção primária à saúde (APS), valorizando o saber popular e o autocuidado. Esta revisão integrativa de literatura objetiva analisar estudos sobre a inserção do uso de PM na APS. A estratégia PICO norteou a busca de evidências, reunindo 18 artigos publicados de janeiro de 2015 a agosto de 2020 nos bancos de dados Biblioteca Virtual de Saúde e PubMed. As variáveis de análise foram o conhecimento dos profissionais da saúde da APS sobre PM e políticas associadas, o uso de PM pelos usuários, destacando seu perfil, fatores que favorecem o uso e a falta de segurança no uso de PM. A literatura aponta insuficiência de conhecimento dos profissionais de saúde sobre as políticas de práticas integrativas e complementares e o uso de plantas para fins medicinais. Os principais usuários são mulheres, idosas, com baixa renda e escolaridade, tanto no Brasil quanto em outros países. Sobre a segurança no uso de PM, frequentemente não há correta identificação de espécie, origem, preparo e dose adequada para cada caso. Por fim, a não abordagem desses conteúdos durante a formação de profissionais da saúde gera menos conhecimento, menos pesquisas e mais preconceito por falta de informação, prejudicando o incentivo e divulgação à comunidade.

Frequency of DPYD gene variants and phenotype inference in a Southern Brazilian population.

Fluoropyrimidines are chemotherapy drugs that may cause severe adverse events, and their metabolism occurs by dihydropyrimidine deydrogenase (DPD), coded by DPYD. Variants in the DPYD were associated to a greater risk of toxicity. Our aim was to determine the frequency of the most relevant DPYD alleles according to CPIC guidelines (DPYD*2A-rs3918290, DPYD*13-rs55886062, rs67376798, and HapB3-rs75017182) in a sample of 800 healthy Southern Brazilians. Frequencies for rs3918290, rs75017182, and rs67376798 were 0.25%, 1.06%, and 0.38%, respectively. No rs55886062 allele was detected. In total, 3.4% of individuals were classified as intermediate metabolizers. Frequencies for rs3918290, rs55886062, and rs67376798 were similar to those found in non-Finnish Europeans; however, rs75017182 was less frequent when compared to non-Finnish Europeans, but more frequent than in Africans and East Asians. rs3918290 and rs67376798 also presented higher frequency when compared to Africans. The Latino population was the only one that did not differ from our sample in any variant analyzed. The frequencies for all the other populations (non-Finnish European, African, South Asian, and East Asian) presented differences from our sample in at least one variant. rs115232898 was not analyzed in the present study. Cost-effective studies should be performed to evaluate the implementation of these tests in the clinical practice in the Southern Brazil.

Sales of "COVID kit" drugs and adverse drug reactions reported by the Brazilian Health Regulatory Agency / Vendas de "kit-COVID" e reações adversas a esses medicamentos relatadas pela Agência Nacional de Vigilância Sanitária / Ventas de medicamentos del "kit-COVID" y reacciones adversas a los medicamentos notificadas por la Agencia Nacional de Vigilancia Sanitaria

Off-label use of azithromycin, hydroxychloroquine, and ivermectin (the "COVID kit") has been suggested for COVID-19 treatment in Brazil without clinical or scientific evidence of efficacy. These drugs have known adverse drug reactions (ADR). This study aimed to analyze if the sales of drugs in the "COVID kit" are correlated to the reported number of ADR after the COVID-19 pandemic began. Data was obtained from the Brazilian Health Regulatory Agency (Anvisa) website on reported sales and ADRs for azithromycin, hydroxychloroquine, and ivermectin for all Brazilian states. The period from March 2019 to February 2020 (before the pandemic) was compared to that from March 2020 to February 2021 (during the pandemic). Trend adjustment was performed for time series data and cross-correlation analysis to investigate correlation between sales and ADR within the same month (lag 0) and in the following months (lag 1 and lag 2). Spearman's correlation coefficient was used to assess the magnitude of the correlations. After the pandemic onset, sales of all investigated drugs increased significantly (69.75% for azithromycin, 10,856,481.39% for hydroxychloroquine, and 12,291,129.32% for ivermectin). ADR levels of all medications but azithromycin were zero before the pandemic, but increased after its onset. Cross-correlation analysis was significant in lag 1 for all drugs nationwide. Spearman's correlation was moderate for azithromycin and hydroxychloroquine but absent for ivermectin. Data must be interpreted cautiously since no active search for ADR was performed. Our results show that the increased and indiscriminate use of "COVID kit" during the pandemic correlates to an increased occurrence of ADRs.

No Brasil, o uso off label de azitromicina, hidroxicloroquina e ivermectina (o "kit-COVID") foi sugerido para tratar COVID-19 sem que tivéssemos evidências clínicas ou científicas de sua eficácia. Estas drogas têm causado reações adversas (RA) em quem as tomam. Este estudo almejou analisar se a venda dos medicamentos que compõem o "kit-COVID" correlaciona-se com o número relatado de RAs após o início da pandemia da COVID-19. Os dados sobre vendas e RA associados a azitromicina, hidroxicloroquina e ivermectina foram obtidos no site da Agência Nacional de Vigilância Sanitária (Anvisa) para todos os estados brasileiros. Comparamos o período entre março de 2019 e fevereiro de 2020 (antes da pandemia) ao de março de 2020 a fevereiro de 2021 (durante a pandemia). Ajustamos tendências para os dados de séries temporais e as análises de correlação cruzada para investigar a correlação entre vendas e RA em um mesmo mês (lag 0) e nos seguintes (lag 1 e 2). O coeficiente de correlação de Spearman foi utilizado para avaliar a magnitude das correlações. Após o início da pandemia, as vendas de todos os medicamentos investigados aumentaram significativamente (69,75% para azitromicina, 10.856.481,39% para hidroxicloroquina e 12.291.129,32% para ivermectina). Os níveis de RAs de todos os medicamentos (com exceção de azitromicina) eram zero antes da pandemia mas aumentaram após seu início. A análise de correlação cruzada foi significativa no lag 1 para todas as drogas em todo o país. A correlação de Spearman foi moderada para azitromicina e hidroxicloroquina, mas ausente para ivermectina. Os dados devem ser interpretados com cautela, uma vez que não realizamos uma busca ativa por RA. Nossos resultados mostram que o uso aumentado e indiscriminado do "kit-COVID" durante a pandemia se correlaciona com uma ocorrência aumentada de RAs.

Se ha sugerido el uso fuera de lo establecido de azitromicina, hidroxicloroquina e ivermectina (el "kit-COVID") para el tratamiento de la COVID-19 en Brasil sin evidencia clínica o científica de su eficacia. Estos medicamentos tienen reacciones adversas (RAM) conocidas. Este estudio pretendía analizar si las ventas de medicamentos del "kit-COVID" están correlacionadas con el número de reacciones adversas notificadas tras el inicio de la pandemia de COVID-19. Los datos se obtuvieron del sitio web de la Agencia Nacional de Vigilancia Sanitaria (Anvisa) sobre las ventas y las RAM notificadas para la azitromicina, la hidroxicloroquina y la ivermectina para todos los estados brasileños. Se comparó el periodo de marzo de 2019 a febrero de 2020 (antes de la pandemia) con el de marzo de 2020 a febrero de 2021 (durante la pandemia). Se realizó un ajuste de tendencia para los datos de las series de tiempo y un análisis de correlación cruzada para investigar la correlación entre las ventas y la RAM dentro del mismo mes (lag 0) y en los meses siguientes (lag 1 y lag 2). Se utilizó el coeficiente de correlación de Spearman para evaluar la magnitud de las correlaciones. Tras el inicio de la pandemia, las ventas de todos los medicamentos investigados aumentaron significativamente (69,75% para la azitromicina, 10.856.481,39% para la hidroxicloroquina y 12.291.129,32% para la ivermectina). Los niveles de RAM de todos los medicamentos, excepto la azitromicina, eran nulos antes de la pandemia, pero aumentaron tras su inicio. El análisis de correlación cruzada fue significativo en el lag 1 para todos los medicamentos a nivel nacional. La correlación de Spearman fue moderada para la azitromicina y la hidroxicloroquina, pero no para la ivermectina. Los datos deben interpretarse con cautela, ya que no se realizó una búsqueda activa de RAM. Nuestros resultados muestran que el uso creciente e indiscriminado del "kit-COVID" durante la pandemia se correlaciona con una mayor aparición de las RAM.