Perda gestacional de repetição e o papel dos progestagênios: evidências atuais / Recurrent pregnancy loss and the role of progestagens: current evidence

Objetivo: Discutir o uso dos progestagênios em mulheres com perda gestacional de repetição (PGR) sem causa aparente, abordando tipos de progestagênios e resultados de ensaios clínicos, revisões sistemáticas e metanálises. Métodos: Trata-se de uma revisão não sistemática de artigos publicados nas bases eletrônicas PubMed, Cochrane e SciELO nos últimos cinco anos, utilizando-se os seguintes descritores: "progesterone", "dydrogesterone", "recurrent pregnancy loss" e "recurrent abortion". Resultados: Duas grandes metanálises encontraram uma redução da taxa de abortamento e aumento da taxa de nascidos vivos com o uso do progestágeno sintético em pacientes com PGR inexplicada, porém essa conclusão foi contestada em uma metanálise mais recente. Entretanto, a progesterona vaginal micronizada poderia aumentar a taxa de nascidos vivos em mulheres com ameaça de aborto e com história de um ou mais abortos anteriores (risco relativo [RR]: 1,08, intervalo de confiança [IC] de 95%: 1,02-1,15). O benefício foi maior no subgrupo de mulheres com três ou mais perdas anteriores. Conclusão: Ainda restam dúvidas sobre o uso de "progesterona" nas pacientes com PGR inexplicada. Sua administração deve ser discutida individualmente com cada mulher, levando-se em conta especialmente a idade materna, o número de abortos prévios e a história de sangramento na gestação em curso, evitando-se tratamentos que trazem custos e não são isentos de efeitos colaterais.(AU)

Objective: To discuss the use of progestins in women with recurrent pregnancy loss (RPL) with no apparent cause, addressing types of progestins, and results of clinical trials, systematic reviews, and meta-analyses. Methods: This is a non-systematic review of articles published in the PubMed, Cochrane, SciELO electronic databases in the last five years, using the following descriptors: "progesterone", "dydrogesterone", "recurrent pregnancy loss", and "recurrent abortion". Results: Two large meta-analyses found a reduction in the rate of miscarriage, and an increase in the rate of live births with the use of synthetic progestin in patients with unexplained RPL, but this conclusion was challenged in a more recent meta-analysis. However, micronized vaginal progesterone could increase the rate of live births in women with a threatened miscarriage and a history of one or more previous miscarriages (RR: 1.08, 95% CI: 1.02-1.15). The benefit was greatest in the subgroup of women with three or more previous losses. Conclusion: There are still doubts about the use of "progesterone" in patients with unexplained RPL. Its administration should be discussed individually with each woman, taking into account especially the maternal age, number of previous abor tions, and history of bleeding during pregnancy, avoiding treatments that bring costs and are not free from side effects.(AU)

Revisión sistemática de la exactitud diagnóstica de la gota gruesa en comparación con la reacción en cadena de la polimerasa para malaria asociada al embarazo, 2010-2022 / Systematic review of the diagnostic accuracy of thick smear compared to polymerase chain reaction for pregnancy-associated malaria, 2010-2022

RESUMEN Objetivos. Evaluar la exactitud de gota gruesa (GG) frente a la reacción en cadena de la polimerasa (PCR) cuantitativa para la malaria asociada al embarazo (MAE). Materiales y métodos. Se realizó una revisión sistemática de pruebas diagnósticas en nueve bases de datos. Se evaluó la calidad metodológica con QUADAS. Se estimó sensibilidad, especificidad, cociente de probabilidad positivo (CPP) y negativo (CPN), razón de odds diagnóstica (ORD) y área bajo la curva ROC. Se determinó la heterogeneidad con el estadístico Q de Der Simonian-Laird y la incertidumbre con el porcentaje de peso de cada estudio sobre el resultado global. Resultados. Se incluyeron diez estudios con 5691 gestantes, 1415 placentas y 84 neonatos. En los estudios con nPCR (PCR anidada) y qPCR (PCR cuantitativa) como estándar, los resultados de exactitud diagnóstica fueron estadísticamente similares, con sensibilidad muy baja (50 y 54%, respectivamente), alta especificidad (99% en ambos casos), alto CPP y deficiente CPN. Usando nPCR la OR diagnóstica fue 162 (IC95%=66-401) y el área bajo la curva ROC fue 95%, mientras que con qPCR fueron 231 (IC95%=27-1951) y 78%, respectivamente. Conclusiones. Mediante un protocolo exhaustivo se demostró el bajo desarrollo de investigaciones sobre la exactitud diagnóstica de la GG en MAE. Se demostró que la microscopía tiene un desempeño deficiente para el diagnóstico de infecciones asintomáticas o de baja parasitemia, lo que afianza la importancia de implementar otro tipo de técnicas en el seguimiento y control de las infecciones por malaria en las gestantes, con el fin de lograr el control y posible eliminación de la MAE.

ABSTRACT Objective. To evaluate the accuracy of thick smear (TS) versus quantitative polymerase chain reaction (PCR) for pregnancy-associated malaria (PAM). Materials and methods. We carried out a systematic review of diagnostic tests in nine databases. Methodological quality was evaluated with QUADAS. Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the ROC curve were estimated. Heterogeneity was determined with the Der Simonian-Laird Q method and uncertainty with the weighted percentage of each study on the overall result. Results. We included 10 studies with 5691 pregnant women, 1415 placentas and 84 neonates. In the studies with nested PCR (nPCR) and quantitative PCR (qPCR) as the standard, the diagnostic accuracy results were statistically similar, with very low sensitivity (50 and 54%, respectively), high specificity (99% in both cases), high PLR and poor NLR. When nPCR was used, the DOR was 162 (95%CI=66-401) and the area under the ROC curve was 95%, while with qPCR it was 231 (95%CI=27-1951) and 78%, respectively. Conclusions. We demonstrated that research on the diagnostic accuracy of TS in PAM is limited. Microscopy showed poor performance in the diagnosis of asymptomatic or low parasitemia infections, which reinforces the importance of implementing other types of techniques for the follow-up and control of malaria infections in pregnant women, in order to achieve the control and possible elimination of PAM.

Eficacia terapéutica y seguridad del tocilizumab en COVID-19 / Therapeutic efficacy of tocilizumab in COVID-19

A la fecha, excepto los glucocorticoides, ningún otro tratamiento farmacológico ha demostrado disminución de la mortalidad en pacientes con COVID-19 grave-crítico. Con el objetivo de discutir su utilidad en la terapéutica, se realizó una revisión y lectura crítica de los estudios publicados más significativos sobre el uso de tocilizumab.Se llevó adelante una búsqueda en las principales bases de datos bibliográficas priorizando la inclusión de revisiones sistemáticas y ensayos clínicos aleatorizados controlados (ERC) que analizaran el efecto del tocilizumab en COVID-19 en diferentes puntos de valoración.Se incluyeron 5 ERC y 4 metaanálisis en la evaluación, todos ellos incluyeron pacientes con COVID-19 confirmado y mayoritariamente graves-críticos. El punto de valoración principal (PVP) fue la mortalidad a los 28 días y como resultado secundario de relevancia, la progresión a ventilación mecánica invasiva (VMI). Se analizó, además, la seguridad de la intervención, fundamentalmente a nivel de la ocurrencia de infecciones secundarias.Del análisis surge que la mayor posibilidad de beneficio parece estar circunscripta a pacientes con enfermedad grave-crítica, que reciben corticoides, con marcadores de inflamación elevados (PCR >10 mg/dL) y enfermedad rápidamente progresiva. Existe alto grado de certeza respecto del impacto del tocilizumab en evitar la progresión a VMI, con una pequeña magnitud del efecto y moderado grado de certeza respecto de su impacto en la mortalidad; además de que resultó una medicación segura

Up until now, other than corticosteroids, no other pharmacological treatment has shown a decrease in mortality rate in patients with severe-critical COVID-19. In order to discuss its place in therapy, a review and critical reading of the most significant published studies on the use of tocilizumab was carried out.Search was done in the main bibliographic databases, prioritizing the inclusion of systematic reviews and randomized controlled clinical trials (RCTs); that analyzed the effect of tocilizumab on COVID-19 at different endpoints.5 RCTs and 4 meta-analysis were considered in the evaluation, all of them including patients with confirmed COVID-19 and predominantly severe-critical illness. The primary endpoint was 28-day all-cause mortality and, as a secondary outcome of relevance, progression to invasive mechanical ventilation. The safety of the intervention was also analyzed, mainly the occurrence of secondary infections.From our analysis it appears that the greatest possibility of benefit seems to be limited to patients with severe-critical illness, who receive corticosteroids, with high markers of inflammation values (CRP> 10 mg/dL) and rapidly progressive disease. There is high certainty regarding the impact of tocilizumab in preventing progression to IMV, with a small effect size and moderate certainty regarding its impact on mortality. Moreover, it was a well-tolerated and safe medication

Do Bulk-Fill Resin Composites Present More Susceptibility to Marginal Degradation in Different Clinical Scenarios? A Systematic Review and Meta-Analysis

Abstract Objective: To compare the marginal degradation (susceptibility to marginal adaptation and marginal discoloration) of composite restorations placed in class II and V cavities using conventional and bulk-fill resin composites. Material and Methods: This study was approved by PROSPERO database (#42020201596). PubMed, Scopus, Embase, Web of Science, Lilacs, Cochrane, Open Grey, Clinical Trials, and Rebec databases were searched by three independent investigators using MeSH terms, supplementary concepts, synonyms, and free keywords, based on the PICOS strategy (P, population: restoration in permanent teeth; I, intervention: bulk-fill resin composite; C, comparison: conventional resin composite; O, outcome: marginal discoloration and adaptation; and S, study design: randomized and non-randomized clinical trials). The risk of bias was evaluated according to the Cochrane Collaboration's tool, the meta-analyses by RevMan software, the certainty of evidence by the Grading of Recommendations Assessment, Development, and Evaluation, and the leave-one-out sensitivity test. The prevalence of successful events and the total number of restorations were used to calculate the risk difference at a confidence interval of 95%, according to a fixed-effect model. The heterogeneity was evaluated using the I2 index. Results: 16 from 10,780 studies were selected and included for qualitative and quantitative analysis. Two studies were considered as high risk of bias, one showing some concerns, and 13 as low risk of bias. Four meta-analyses evaluated the marginal adaptation and marginal discoloration in class II and V cavities, with a nonsignificant heterogeneity (I2 = 0%, p>0.05). The certainty of evidence was considered high, except for two subgroups of each outcome. Conclusion: There is evidence that composite restorations using conventional and bulk-fill resin composites present similar clinical performance related to marginal degradation (AU).

Traditional Chinese medicine treatment for COVID-19: An overview of systematic reviews and meta-analyses / 中西医结合学报

BACKGROUND@#Coronavirus disease 2019 (COVID-19) is a rapidly spreading disease that has caused an extensive burden to the world. Consequently, a large number of clinical trials have examined the efficacy of traditional Chinese medicine (TCM) for treating and preventing COVID-19, with coinciding proliferation of reviews summarizing these studies.@*OBJECTIVE@#This study aimed to evaluate the methodological quality and evidence quality of systematic reviews and meta-analyses on the efficacy of TCM.@*SEARCH STRATEGY@#Seven electronic databases, including PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chongqing VIP, Wanfang Data and SinoMed, were searched for systematic reviews and meta-analyses in October 2021. Search terms such as "Chinese medicine," "Lianhua Qingwen" and "COVID-19" were used.@*INCLUSION CRITERIA@#Systematic reviews and meta-analyses of randomized controlled trials that evaluated the efficacy of TCM treatment of COVID-19 were included.@*DATA EXTRACTION AND ANALYSIS@#A Measurement Tool to Assess Systematic Reviews Version 2.0 (AMSTAR 2) was used to evaluate the methodological quality. The quality of evidence was graded using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Data extraction and analysis were performed by two reviewers independently.@*RESULTS@#There were 17 meta-analyses included in our overview. The intervention group was defined as TCM combined with Western medicine, while the control group was Western medicine alone. The methodological quality of all the included studies was moderate to poor. A total of 89 outcome indicators were evaluated, of which, 8 were rated as moderate quality, 39 as low quality, and 41 as very low quality. Only one outcome measure was graded as being of high quality. The moderate quality of evidence indicated that, for the treatment of COVID-19, the clinical efficacy of TCM in combination with Western medicine was better, in terms of lung recovery, rate of conversion to severe/critical cases, symptom scores, duration of symptoms, mortality, and length of hospital stay.@*CONCLUSION@#Evidence from the included studies shows that, compared with conventional Western medical therapy alone, the addition of TCM to COVID-19 treatment may improve clinical outcomes. Overall, the quality of evidence of TCM for COVID-19 was moderate to poor. Meta-analyses of the use of TCM in the treatment of COVID-19 can be used for clinical decision making by accounting for the experiences of clinical experts, medical policies, and other factors.

Reporting and methodological quality of meta-analyses of acupuncture for patients with migraine: A methodological investigation with evidence map / 中西医结合学报

BACKGROUND@#Acupuncture has been widely used to relieve migraine-related symptoms. However, the findings of previous systematic reviews (SRs) and meta-analyses (MAs) are still not completely consistent. Their quality is also unknown, so a comprehensive study is needed.@*OBJECTIVE@#To evaluate the reporting and methodological quality of these MAs concerning acupuncture for migraine, and summarize evidence about the efficacy and safety of acupuncture for migraine.@*SEARCH STRATEGY@#PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Databases, Wanfang Data, and VIP databases were searched from inception to September 2020, with a comprehensive search strategy.@*INCLUSION CRITERIA@#The pairwise MAs of randomized controlled trials (RCTs) concerning migraine treated by acupuncture or acupuncture-based therapies, with a control group that received sham acupuncture, medication, no treatment, or acupuncture at different acupoints were included.@*DATA EXTRACTION AND ANALYSIS@#Two independent investigators screened studies, extracted relevant data, and assessed reporting and methodological quality using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 and A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), then all results were cross-checked. Spearman correlation test was used to evaluate the correlation between reporting and methodological quality scores.@*RESULTS@#A total of 20 MAs were included in this study. The included MAs indicated that acupuncture was efficacious and safe in preventing and treating migraine when compared with control intervention. There was a high correlation between reporting and methodological quality scores (rs = 0.87, P < 0.001). The quality of the included SRs needs to be improved mainly with regard to protocol and prospective registration, using a comprehensive search strategy, summarizing the strength of evidence body for key outcomes, a full list of excluded studies with reasons for exclusion, reporting of RCTs' funding sources, and assessing the potential impact of risk of bias in RCTs on MA results.@*CONCLUSION@#Acupuncture is an effective and safe intervention for preventing and treating migraine, and could be considered as a good option for patients with migraine. However, the reporting and methodological quality of MAs included in this overview is suboptimal. In the future, AMSTAR 2 and PRISMA tools should be followed when making and reporting an SR with MA.

Evaluation of immune persistence of vaccine / 中华预防医学杂志

The evaluation methods of immune persistence include direct evaluation, indirect evaluation, model prediction, and meta-analysis and so on. Direct evaluation is the gold standard for evaluating the immune persistence of vaccines by quantifying the protective effect of vaccines on the onset and (or) infection of preventable diseases. Indirect evaluation of immune persistence by immunological surrogate indicators is more widely used in practice. In addition, mathematical models and meta-analysis can also be used to evaluate the immune persistence of vaccines. It is of great significance to select the appropriate evaluation method to analyze the immune persistence of the vaccine according to the specific situation.

Polyphenols for improvement of inflammation and symptoms in rheumatic diseases: systematic review

ABSTRACT BACKGROUND: Rheumatic diseases (RDs) are a group of pathological conditions characterized by inflammation and functional disability. There is evidence suggesting that regular consumption of polyphenols has therapeutic effects capable of relieving RD symptoms. OBJECTIVE: To synthesize data from randomized controlled trials on administration of polyphenols and their effects on RD activity. DESIGN AND SETTING: Systematic review conducted at Universidade Federal de Ouro Preto, Minas Gerais, Brazil. METHODS: A systematic search was conducted in the databases PubMed (Medline), LILACS (BVS), IBECS (BVS), CUMED (BVS), BINACIS (BVS), EMBASE, Web of Science and Cochrane Library and in the grey literature. The present study followed a PRISMA-P checklist. RESULTS: In total, 646 articles were considered potentially eligible, of which 33 were then subjected to complete reading. Out of these, 17 randomized controlled trials articles were selected to form the final sample. Among these 17 articles, 64.71% assessed osteoarthritis (n = 11), 23.53% rheumatoid arthritis (n = 4), 5.88% rheumatoid arthritis and fibromyalgia (n = 1) and 5.88% osteoarthritis and rheumatoid (n = 1). Intake of polyphenol showed positive effects in most of the studies assessed (94.12%): it improved pain (64.70%) and inflammation (58.82%). CONCLUSION: Polyphenols are potential allies for treating RD activity. However, the range of polyphenol sources administered was a limitation of this review, as also was the lack of information about the methodological characteristics of the studies evaluated. Thus, further primary studies are needed in order to evaluate the effects of polyphenol consumption for reducing RD activity. SYSTEMATIC REVIEW REGISTER: PROSPERO - CRD42020145349.

Appraising the effectiveness of electrical and magnetic brain stimulation techniques in acute major depressive episodes: an umbrella review of meta-analyses of randomized controlled trials

Electrical and magnetic brain stimulation techniques present distinct mechanisms and efficacy in the acute treatment of depression. This was an umbrella review of meta-analyses of randomized controlled trials of brain stimulation techniques for managing acute major depressive episodes. A systematic review was performed in the PubMed/MEDLINE databases from inception until March 2020. We included the English language meta-analysis with the most randomized controlled trials on the effects of any brain stimulation technique vs. control in adults with an acute depressive episode. Continuous and dichotomous outcomes were assessed. A Measurement Tool to Assess Systematic Reviews-2 was applied and the credibility of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Seven meta-analyses were included (5,615 patients), providing evidence for different modalities of brain stimulation techniques. Three meta-analyses were evaluated as having high methodological quality, three as moderate, and one as low. The highest quality of evidence was found for high frequency-repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, and bilateral rTMS. There is strong clinical research evidence to guide future clinical use of some techniques. Our results confirm the heterogeneity of the effects across these techniques, indicating that different mechanisms of action lead to different efficacy profiles.

Association of the Maternal Folic Acid Supplementation with the Autism Spectrum Disorder: A Systematic Review / Associação da suplementação de ácido fólico materno com o transtorno do espectro do autismo: uma revisão sistemática

Abstract Objective To analyze the scientific production regarding maternal folic acid (FA) supplementation and its relationship with autistic spectrum disorder (ASD). Data Sources We performed unrestricted electronic searches in the BIREME virtual bank, Virtual Health Library (VHL) and Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMed) databases. Selection of Studies For sample selection, articles that met the proposed objectives were included, published in English, Spanish and Portuguese, the use of Health Sciences Descriptors (DeCS): autistic OR autism AND autism spectrum disorder AND folic acid, AND, with the use of the Medical Subject Headings (MeSH): autistic OR autism AND autistic spectrum disorder AND folic acid. Data Collection Data extraction was performed by the reviewers with a preestablished data collection formulary. Data Synthesis The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) was used based on a checklist with 27 items and a 4-step flowchart. Results A total of 384 articles was found by the search strategies, of which 17 were eligible following the pre-established criteria. The main findings of the present review point to maternal FA supplementation in the pre-conception period and beginning of pregnancy as a protective effect in relation to ASD, which should be indicated in this period as prevention to the problem. Conclusion According to the research analyzed, more studies are necessary to know its effects on pregnancy, since the consumption of excessive FA may not be innocuous.

Resumo Objetivo Analisar a produção científica a respeito da suplementação de ácido fólico (AF) materno e sua relação com o transtorno do espectro autista (TEA). Fontes de Dados Realizamos buscas eletrônicas irrestritas nas bases de dados do banco virtual BIREME, Biblioteca Virtual em Saúde (VHL) e Medical Literature Analysis and Retrieval System Online (MEDLINE / PubMed). Seleção dos Estudos Incluímos os artigos publicados em inglês, espanhol e português, com o uso dos DeCS: autistic OR autism AND autism spectrum disorder AND folic acid, e com o uso dos Medical Subject Headings (MeSH, na sigla em inglês): autistic OR autism AND Autistic Spectrum Disorder AND folic acid ". Coleta de Dados A extração de dados foi realizada pelos revisores com um formulário de coleta de dados pré-estabelecido. Síntese dos Dados Foram usados os itens de relatório preferidos para protocolos de revisão sistemática e meta-análise (PRISMA-P) com base em uma lista de verificação com 27 itens e um fluxograma de 4 etapas. Resultados Foram encontrados 384 artigos pelas estratégias de busca, dos quais 17 eram elegíveis segundo os critérios pré-estabelecidos. Os principais achados da presente revisão apontam para a suplementação de AF materno no período de preconcepção e início da gravidez como efeito protetor em relação ao TEA, que deve ser indicada neste período como prevenção do problema. Conclusão De acordo com as pesquisas analisadas, mais estudos são necessários para conhecer seus efeitos sobre a gravidez, uma vez que o consumo excessivo de AF pode não ser inócuo.

Efficacy and safety of Botulinum toxin A for improving esthetics in facial complex: A systematic review

Abstract Aim: To evaluate efficacy and safety of Botulinum toxinA for improving esthetics in the facial complex and correlating them to the dosage and side effects through a systematic review. Methods: A literature search was performed using PubMed, Medline, Web of Sciences, and Scopus databases. Quality of studies was appraised through the GRADE system. This review follows the 'Preferred reporting items for systematic review and meta-analysis protocols' (PRISMA-P) 2015 statement. Efficacy was analyzed through improvement rate and effect sizes. Graphical comparison of efficacy and ocular adverse effects (adverse effects around the eye) at various anatomical locations was made by calculating the average improvement rate and adverse events. Results: Twenty-five studies were included in this systematic review after application of the inclusion criteria. Moderate to severe cases in glabellar, lateral canthal, and forehead regions showed higher improvement rates between 20U to 50U, with an effect lasting up to 120 days. Gender and age seemed to have a direct effect on efficacy. Headaches were the most common adverse effect, followed by injection site bruising; all adverse effects resolved within 3-4 days. Conclusions: Treatment with Botulinum toxinA to enhance esthetics of facial complex is efficient and safe at all recommended dosages. Presence of complexing proteins influenced the efficacy of BoNT-A. undesirable muscular adverse effects around the eyes were more predominant when treating the glabellar region. There was no correlation found between the BoNT-A dosage and side effects, however, an increase in dosage did not always lead to an increase in efficacy.

Resumo Objetivo: Avaliar a eficácia e segurança da toxina botulínica-A para melhorar a estética no complexo facial e correlacioná-la com a dosagem e os efeitos secundários através de uma revisão sistemática. Métodos: Foi realizada uma pesquisa bibliográfica utilizando bases de dados PubMed, Medline, Web of Sciences, e Scopus. A qualidade dos estudos foi avaliada através do sistema GRADE. Esta revisão segue a declaração "Preferred reporting items for systematic review and meta-analysis protocols" (PRISMA-P) 2015. A eficácia foi analisada através da taxa de melhoria e da dimensão dos efeitos.A comparação gráfica da eficácia e dos efeitos adversos oftalmológicos (efeitos adversos em torno do olho) em vários locais anatômicos foi feita através do cálculo da taxa média de melhoria e dos eventos adversos. Resultados: Vinte e cinco estudos foram incluídos nesta revisão sistemática após a aplicação dos critérios de inclusão. Casos moderados a graves em regiões glabelares, canais laterais e testa mostraram taxas de melhoria mais elevadas entre 20U a 50U, com um efeito que durou até 120 dias. O sexo e a idade mostraram ter efeito direto na eficácia. As dores de cabeça foram o efeito adverso mais comum, seguido de hematomas no local da injecção; todos os efeitos adversos foram resolvidos em 3-4 dias. Conclusões: O tratamento com toxina botulínica-A para melhorar a estética do complexo facial é eficiente e seguro em todas as dosagens recomendadas. A presença de proteínas complexas influenciou a eficácia do BoNT-A. Os efeitos adversos musculares indesejáveis à volta dos olhos foram mais predominantes no tratamento da região glabelar. Não foi encontrada qualquer correlação entre a dosagem de BoNT-A e os efeitos secundários, contudo, um aumento da dosagem nem sempre levou a um aumento da eficácia.

Pulmonary rehabilitation for COVID-19: a living systematic review protocol

Objective This living systematic review aims to provide a timely, rigorous and continuously updated summary of the evidence available on the role of pulmonary rehabilitation in the treatment of patients with COVID-19. Design This is the protocol of a living systematic review. Data sources We will conduct searches in the L·OVE (Living OVerview of Evidence) platform for COVID-19, a system that maps PICO questions to a repository maintained through regular searches in electronic databases, preprint servers, trial registries and other resources relevant to COVID-19. No date or language restrictions will be applied. Eligibility criteria for selecting studies and methods We adapted an already published common protocol for multiple parallel systematic reviews to the specificities of this question. We will include randomized trials evaluating the effect of pulmonary rehabilitation as monotherapy or in combination with other interventions-versus sham or no treatment in patients with COVID-19. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will pool the results using meta-analysis and will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to assess the certainty of the evidence for each outcome. Ethics and dissemination No ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media.