Eficácia da ivermectina e atazanavir no tempo de recuperação dos sintomas de covid-19: uma coorte prospectiva / Effectiveness of ivermectin and atazanavir on time to resolution from covid-19 symptoms: a prospective cohort / Eficacia de ivermectina y atazanavir en el tiempo hasta lá resolución de los síntomas de covid-19: una cohorte prospectiva

Objetivo: avaliar a eficácia da Ivermectina e do Atazanavir em comparação com placebo no tempo de resolução dos sintomas e no tempo de duração da doença por COVID-19. Método: estudo observacional, de coorte prospectivo, longitudinal, descritivo e analítico com pacientes sintomáticos ambulatoriais, acompanhados por 06 meses em duas Unidades Básicas de Saúde para atendimento de COVID-19 em Teresina- Piauí, Brasil, no período de novembro a abril de 2021 identificados por amostragem aleatória 1:1:1. Foram realizados exames Reverse transcription polymerase chain reaction (RT-PCR) para confirmação laboratorial da suspeita de infecção pelo novo coronavírus e avaliação sociodemográfica e clínica. Resultados: dos 87 pacientes randomizados, 62,1% (n=54) eram do sexo masculino, com média de idade de 35,1 anos, possuíam companheira (53,9%), baixa renda (50,6%), eutróficos (40,7%) e sem comorbidades de saúde (78,2%). Não houve diferença entre o tempo médio para resolução dos sintomas, que foi de 21 dias (IQR, 8-30) no grupo atazanavir, 30 dias (IQR, 5-90) no grupo ivermectina em comparação com 14 dias (IQR, 9-21) no grupo controle. No dia 180, houve resolução dos sintomas em 100% no grupo placebo, 93,9% no grupo atazanavir e 95% no grupo ivermectina. A duração mediana da doença foi de 08 dias em todos os braços do estudo. Conclusão: o tratamento com atazanavir (6 dias) e ivermectina (3 dias) não reduziu o tempo de resolução dos sintomas e nem o tempo de duração da doença entre os pacientes ambulatoriais com COVID-19 leve em comparação com o grupo placebo. Os resultados não suportam o uso de ivermectina e atazanavir para tratamento de COVID-19 leve a moderado.

Objective: to evaluate the effectiveness of Ivermectin and Atazanavir compared to placebo in the time to resolution of symptoms and duration of illness due to COVID-19. Method: observational, prospective, longitudinal, descriptive and analytical cohort study with symptomatic outpatients, followed for 06 months in two Basic Health Units for COVID-19 care in Teresina-Piauí, Brazil, from November to April 2021 identified by 1:1:1 random sampling. Reverse transcription polymerase chain reaction (RT-PCR) tests were performed for laboratory confirmation of suspected infection with the new coronavirus and sociodemographic and clinical evaluation. Results: of the 87 randomized patients, 62.1% (n=54) were male, with a mean age of 35.1 years, had a partner (53.9%), low income (50.6%), eutrophic (40.7%) and without health comorbidities (78.2%). There was no difference between the median time to resolution of symptoms, which was 21 days (IQR, 8-30) in the atazanavir group, 30 days (IQR, 5- 90) in the ivermectin group compared with 14 days (IQR, 9- 21) in the control group. At day 180, there was resolution of symptoms in 100% in the placebo group, 93.9% in the atazanavir group, and 95% in the ivermectin group. The median duration of illness was 8 days in all study arms. Conclusion: Treatment with atazanavir (6 days) and ivermectin (3 days) did not reduce the time to symptom resolution or the duration of illness among outpatients with mild COVID-19 compared to the placebo group. The results do not support the use of ivermectin and atazanavir for the treatment of mild to moderate COVID-19.

Objetivo: evaluar la efectividad de Ivermectina y Atazanavir en comparación con placebo en el tiempo de resolución de los síntomas y duración de la enfermedad por COVID-19. Método: estudio de cohorte observacional, prospectivo, longitudinal, descriptivo y analítico con pacientes ambulatorios sintomáticos, seguidos durante 06 meses en dos Unidades Básicas de Salud para atención de COVID-19 en Teresina-Piauí, Brasil, de noviembre a abril de 2021 identificados por 1:1:1 muestreo aleatorio. Se realizaron pruebas de reacción en cadena de la polimerasa con transcriptasa inversa (RT-PCR) para confirmación de laboratorio de sospecha de infección por el nuevo coronavirus y evaluación sociodemográfica y clínica. Resultados: de los 87 pacientes aleatorizados, 62,1% (n=54) eran del sexo masculino, con una edad media de 35,1 años, tenían pareja (53,9%), bajos ingresos (50,6%), eutróficos (40,7%) y sin comorbilidades de salud (78,2%). No hubo diferencia entre la mediana de tiempo hasta la resolución de los síntomas, que fue de 21 días (RIC, 8-30) en el grupo de atazanavir, 30 días (RIC, 5- 90) en el grupo de ivermectina en comparación con 14 días (RIC, 9 - 21) en el grupo control. En el día 180, hubo una resolución de los síntomas del 100 % en el grupo de placebo, del 93,9 % en el grupo de atazanavir y del 95 % en el grupo de ivermectina. La mediana de duración de la enfermedad fue de 8 días en todos los brazos del estudio. Conclusión: El tratamiento con atazanavir (6 días) e ivermectina (3 días) no redujo el tiempo de resolución de los síntomas ni la duración de la enfermedad entre los pacientes ambulatorios con COVID-19 leve en comparación con el grupo placebo. Los resultados no respaldan el uso de ivermectina y atazanavir para el tratamiento de la COVID-19 de leve a moderada.

Bone effects of epidural and intra-articular glucocorticoids: a systematic literature review / Efectos óseos de los glucocorticoides epidurales e intraarticulares: revisión sistemática de la literatura

Osteoporosis and vertebral and non-vertebral fractures are common in glucocorticoids (GC) treated patients. Oral GC treatment leads to bone loss, particularly of trabecular bone. The benefits of GC used in rheumatological and traumatological disorders are known but they would have possible negative effects on bone. This systematic review aimed to evaluate the effects of epidural steroid injections (ESI), and intra-articular and intramuscular GC administration on bone mineral density (BMD) and fragility fractures. A systematic review of Medline/PubMed, Cochrane, and LILACS up to November 2020 was conducted. Meta-analyses, systematic reviews, randomized and non-randomized controlled trials, and prospective and retrospective studies comparing the effect of ESI, intra-articular or intramuscular GC used compared to a control group or baseline measurements were included. Results: A total of 8272 individuals were included among the 13 selected articles (10 about ESI and 3 about intra-articular GC; no article was found evaluating intramuscular GC). Only a few studies showed a negative effect of ESI on bone in the qualitative analysis considering osteopenia and osteoporosis in lumbar spine, femoral neck and total hip and BMD as surrogate outcomes. On the other hand, the qualitative analysis showed that most studies found an increased risk of fragility fracture. However, only two studies could be included in the quantitative analysis, in which there were no differences between patients exposed to ESI versus controls in all evaluated regions. In conclusion, there was insufficient evidence to suggest that ESI and intra-articular GC, unlike oral GC, negatively affect bone mass. Longitudinal studies are needed to obtain more knowledge regarding the effect of ESI or intra-articular GC on BMD and fragility fractures. (AU)

La osteoporosis y las fracturas vertebrales y no vertebrales son comunes en pacientes tratados con glucocorticoides (GC). El tratamiento oral con GC conduce a la pérdida ósea, particularmente del hueso trabecular. Los beneficios de los GC utilizados en patologías reumatológicas y traumatológicas son conocidos, pero tendrían posibles efectos negativos sobre el hueso. Esta revisión sistemática tuvo como objetivo evaluar los efectos de las inyecciones epidurales de esteroides (ESI), GC intraarticulares e intramusculares sobre la densidad mineral ósea (DMO) y las fracturas por fragilidad. Se realizó una revisión sistemática de Medline/PubMed, Cochrane y LILACS hasta noviembre de 2020. Se incluyeron metanálisis, revisiones sistemáticas, ensayos controlados aleatorizados y no aleatorizados, estudios prospectivos y retrospectivos que compararon el efecto de ESI, GC intraarticular o intramuscular utilizado en comparación con un grupo de control o mediciones iniciales. Resultados: Se incluyeron un total de 8272 individuos entre los 13 artículos seleccionados (10 sobre ESI y 3 sobre GC intraarticular; no se encontró ningún artículo que evaluara GC intramuscular). Solo unos pocos estudios mostraron un efecto negativo del ESI sobre el hueso en el análisis cualitativo considerando la osteopenia y la osteoporosis en la columna lumbar, el cuello femoral y la cadera total y la DMO como un resultado indirecto. Por otro lado, el análisis cualitativo mostró que la mayoría de los estudios encontraron un mayor riesgo de fractura por fragilidad. Sin embargo, solo dos estudios pudieron incluirse en el análisis cuantitativo, en los que no hubo diferencias entre los pacientes expuestos a ESI versus los controles en todas las regiones evaluadas. En conclusión, no hallamos datos suficientes para sugerir que la ESI y los GC intraarticulares, a diferencia de los GC orales, afectan negativamente a la pérdida ósea. Se necesitan estudios longitudinales para obtener más conocimiento sobre el efecto de ESI o GC intraarticular en la DMO y las fracturas por fragilidad. (AU)

Intervenções para TDAH: o que dizem as revisões sistemáticas Cochrane? / Interventions for ADHD: what do the Cochrane systematic reviews say?

Contextualização: O transtorno de déficit de atenção e hiperatividade (TDAH) é um transtorno do neurodesenvolvimento bastante prevalente e caracterizado por alterações nos níveis de atenção, presença de hiperatividade e impulsividade, cuja efetividade das abordagens terapêuticas é discutível atualmente. Objetivos: Sumarizar as evidências de revisões sistemáticas da Cochrane, referentes à efetividade das intervenções para tratamento de TDAH. Métodos: Trata-se de overview de revisões sistemáticas Cochrane. Procedeu-se à busca na Cochrane Library (2023), sendo utilizado o descritor MeSH "Attention Deficit Disorder with Hiperactivity". Todas as revisões sistemáticas de ensaios clínicos foram incluídas. O desfecho primário de análise foi a melhora clínica (redução dos sintomas). Resultados: Treze estudos foram incluídos, totalizando 317 ensaios clínicos (n = 25.946 participantes). Foram avaliadas intervenções com anfetaminas, antidepressivos, ácidos graxos poli-insaturados tipo ômega 3 e 6, acupuntura, terapia de meditação, terapia cognitivo-comportamental e treinamento dos pais. Discussão: Nenhuma intervenção mostrou efetividade com evidência de boa qualidade. Embora a maioria das intervenções pareça trazer algum benefício na redução dos sintomas do TDAH, há riscos de efeitos adversos, em geral não graves, sobretudo nos tratamentos farmacológicos. Os estudos realizados até o momento são heterogêneos e desprovidos de análises por subgrupos, o que impacta a obtenção de melhor evidência. Sugere-se a realização de novos ensaios clínicos com padronização de relato dos resultados. Conclusão: Não há suporte com bom nível de evidência atualmente para a maioria das intervenções para tratamento do TDAH, à luz das revisões sistemáticas da Cochrane, sendo sugerida a realização de novos ensaios clínicos de qualidade.

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)

Placenta prévia: um estudo baseado nas teorias de enfermagem / Placenta previa: a study based on nursing theories / Placenta previa: un estudio basado en las teorías de enfermería

Introdução: A gestação, apesar de ser um processo fisiológico na saúde da mulher, é uma etapa complexa que exige atenção diferenciada na assistência à saúde. Outrossim, existem algumas condições que provocam danos durante essa fase, como a placenta prévia. Objetivo: Este estudo tem como escopo evidenciar o processo de enfermagem frente à assistência à gestante com tal diagnóstico. Metodologia: A pesquisa tem caráter qualitativo, teórico com subsídio na bibliografia científica, envolvendo a compreensão holística e integral da paciente para a implementação de estratégia para o processo de enfermagem. A partir do estudo das teorias e da fisiopatologia e impactos clínicos, empregou-se as taxonomias do NANDA-I para traçar os diagnósticos de enfermagens mais condizentes. Resultados: Foram identificados 15 diagnósticos que contemplaram os dez domínios encontrados no NANDA. Considerações Finais: Os dados eleitos e o confronto com a literatura enfatizam a relevância positiva na prescrição de diagnósticos de enfermagem na escolha dos cuidados prestados e as teorias subsidiam a assistência materno-fetal.

Introduction: Pregnancy, despite being a physiological process in women's health, is a complex stage that requires special attention in health care. Also, there are some conditions that cause damage during this phase, such as placenta previa. Objective: The purpose of this study is to highlight the nursing process regarding care for pregnant women with such a diagnosis. Methodology: The research is qualitative, theoretical with support in the scientific bibliography, involving the patients holistic and integral understanding for the implementation of a strategy for the nursing process. Based on the study of theories and pathophysiology and clinical impacts, the NANDA-I taxonomies were used to outline the most consistent nursing diagnoses. Results: 15 diagnoses were identified that included the ten domains found in NANDA. Final Considerations: The chosen data and the confrontation with the literature emphasize the positive relevance in the prescription of nursing diagnoses in the choice of care provided and the theories subsidize maternal-fetal assistance.

Introducción: El embarazo, a pesar de ser un proceso fisiológico en la salud de la mujer, es una etapa compleja que requiere especial atención en el cuidado de la salud. Además, existen algunas condiciones que causan daños durante esta fase, como la placenta previa. Objetivo: El propósito de este estudio es resaltar el proceso de enfermería en relación con la atención a las gestantes con dicho diagnóstico. Metodología: La investigación es cualitativa, teórica con apoyo en la bibliografía científica, involucrando la comprensión holística e integral de las pacientes para la implementación de una estrategia para el proceso de enfermería. Con base en el estudio de teorías y fisiopatología e impactos clínicos, se utilizaron las taxonomías NANDA-I para delinear los diagnósticos de enfermería más consistentes. Resultados: Se identificaron 15 diagnósticos que incluían los diez dominios encontrados en la NANDA. Consideraciones finales: Los datos escogidos y la confrontación con la literatura enfatizan la relevancia positiva en la prescripción de los diagnósticos de enfermería en la elección de los cuidados prestados y las teorías subsidian la asistencia materno-fetal.

Microencapsulação de enterocina e oleo de oregano em leitelho / Microencapsulation of the enterocin and essential oil oregano in buttermilk / Microencapsulación de enterocina y aceite esencial de orégano en suero de leche

A pesquisa busca técnicas alternativas para expansão da vida de prateleira dos alimentos, isto tem impulsionado estudos sobre a utilização de conservantes naturais, tais como as bacteriocinas e óleos essenciais, que são considerados agentes antimicrobianos naturais. No entanto estes antimicrobianos naturais, não são adicionados diretamente em produtos alimentícios, devido a alterações sensoriais e em suas características físico e química. Com avanço tecnológico da microencapsulação, tem sido um potencial em fornecer sistemas que garantem estabilidade para os antimicrobianos naturais desta forma podendo compor a matriz de alimentos. Portanto, o objetivo desse trabalho foi microencapsular a enterocina produzida por Enterococcus durans MF5 e óleo de orégano usando leitelho. Para a microencapsulação, foram realizados três tratamentos: T1 controle leitelho, T2 leitelho/enterocina (LE), e T3 leitelho/enterocina/óleo (LEO). O material foi submetido ao processo de spray dryer e foram realizados ensaios para determinar a atividade antimicrobiana do material encapsulado contra as bactérias Listeria monocytogenes, Listeria innocua e Listeria ivanovi. O rendimento da microencapsulação foi de 13,01% e 11,63% para LE e LEO, respectivamente. Os resultados apresentados nos microencapsulados LE e LEO mostraram inibição contra todas as bactérias teste, foi constatado que a microencapsulação de enterocina e óleo de orégano mantiveram seu poder antimicrobiano. A efetividade da microencapsulação foi realizada por (FTIR), onde picos de intensidade entre as amostras na região 1000 a 930 cm-¹ e 1800 a 1500 cm-¹ foram observadas. Os resultados apontam para mudança no perfil químico das amostras encapsuladas, corroborando com a hipótese que o leitelho apresentou papel encapsulante da bactericiona e óleo de orégano.Portanto a microencapsulação aumenta a eficácia antimicrobiana dos antimicrobianos.

The research seeks alternative techniques for expanding the shelf life of foods, this has driven studies on the use of natural preservatives, such as bacteriocins and essential oils, which are considered natural antimicrobial agents. However, these natural antimicrobials are not directly added to food products due to sensory changes and their physical and chemical characteristics. With technological advancement of microencap- sulation, it has been a potential to provide systems that ensure stability for natural anti- microbials in this way can compose the food matrix. Therefore, this study has an objective microencapsulated the interocin and essencial oil, used buttermilk as a encapsulating ma- terial where, T1 Buttermilk Control, T2 buttermilk/enterocin (LE), e T3 Buttermilk/en- terocin/oil (LEO). The product has been submitted to spray drier process, were conducted trials to determine antimicrobial activity. Was observed with mass yield 13,01% e 11,63% para LE e LEO. These results the microencapsulate indicate then LE e LEO there was inihibiton against bacteria tests. Was observed that the microencapsulated between enter- ocin and essential oil oregano maintained antimicrobial power. The effectiveness of the microencapsulated was performed by Fourier transform infrared (FTIR) analysis, where a sample in the region 1000 to 930 cm-¹ and 1800 to 1500 cm-¹ was observed. Therefore microencapsulation increases antimicrobial efficacy of antimicrobials.

La investigación busca técnicas alternativas para ampliar la vida útil de los alimentos, esto ha impulsado estudios sobre el uso de conservantes naturales, como las bacteriocinas y los aceites esenciales, que se consideran agentes antimicrobianos naturales. Sin embargo, estos antimicrobianos naturales no se añaden directamente a los productos alimentarios debido a los cambios sensoriales y a sus características físicas y químicas. Con el avance tecnológico de la microencapsulación, ha sido un potencial para proporcionar sistemas que garanticen la estabilidad de los antimicrobianos naturales de esta manera puede componer la matriz alimentaria. Por lo tanto, este estudio tiene como objetivo microencapsular la interocina y el aceite esencial, utilizando suero de leche como material encapsulante donde, T1 Suero de leche Control, T2 Suero de leche/enterocina (LE), e T3 Suero de leche/enterocina/aceite (LEO). El producto ha sido sometido al proceso de secado por pulverización, se realizaron ensayos para determinar la actividad antimicrobiana. Se observó con rendimiento de masa 13,01% e 11,63% para LE e LEO. Estos resultados indican que el microencapsulado LE e LEO fue inhibido contra las pruebas bacterianas. Se observó que el microencapsulado entre enterocina y aceite esencial de orégano mantuvo el poder antimicrobiano. La eficacia del microencapsulado fue realizada por análisis de infrarrojo transformado de Fourier (FTIR), donde fue observada una muestra en la región de 1000 a 930 cm-¹ y de 1800 a 1500 cm-¹. Por lo tanto, la microencapsulación aumenta la eficacia antimicrobiana de los antimicrobianos. PALABRAS CLAVE: Bacteriocina; Enterococcus durans; Suero de Leche; Origanum vulgare; Spray Dryer.

A decade's review for membrane anatomy: the setting,events in it, order formed by primary fascia and serous membrane / 中华胃肠外科杂志

The successful report of total mesorectal excision (TME)/complete mesocolic excision (CME) has encouraged people to apply this concept beyond colorectal surgery. However, the negative results of the JCOG1001 trial denied the effect of complete resection of the "mesogastrium" including the greater omentum on the oncological survival of gastric cancer patients. People even believe that the mesentery is unique in the intestine, because they have a vague understanding of the structure of the mesentery. The discovery of proximal segment of the dorsal mesogastrium (PSDM) proved that the greater omentum is not the mesogastrium, and further revised the structure (definition) of the mesentery and revealed its container characteristics, i.e. the mesentery is an envelope-like structure, which is formed by the primary fascia (and serosa) that enclose the tissue/organ/system and its feeding structures, leading to and suspended on the posterior wall of the body. Breakdown of this structure leads to the simultaneous reduction of surgical and oncological effects of surgery. People quickly realized the universality of this structure and causality which cannot be matched by the existing theories of organ anatomy and vascular anatomy, so a new theory and surgical map- membrane anatomy began to form, which led to radical surgery upgraded from histological en bloc resection to anatomic en bloc resection.

Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol / 中西医结合学报

As one of the key components of clinical trials, blinding, if successfully implemented, can help to mitigate the risks of implementation bias and measurement bias, consequently improving the validity and reliability of the trial results. However, successful blinding in clinical trials of traditional Chinese medicine (TCM) is hard to achieve, and the evaluation of blinding success through blinding assessment lacks established guidelines. Taking into account the challenges associated with blinding in the TCM field, here we present a framework for assessing blinding. Further, this study proposes a blinding assessment protocol for TCM clinical trials, building upon the framework and the existing methods. An assessment report checklist and an approach for evaluating the assessment results are presented based on the proposed protocol. It is anticipated that these improvements to blinding assessment will generate greater awareness among researchers, facilitate the standardization of blinding, and augment the blinding effectiveness. The use of this blinding assessment may further advance the quality and precision of TCM clinical trials and improve the accuracy of the trial results. The blinding assessment protocol will undergo continued optimization and refinement, drawing upon expert consensus and experience derived from clinical trials. Please cite this article as: Wang XC, Liu XY, Shi KL, Meng QG, Yu YF, Wang SY, Wang J, Qu C, Lei C, Yu XP. Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol. J Integr Med. 2023; 21(6): 528-536.

Sham acupuncture and placebo acupuncture in clinical trials / 中国针灸

The commonly used terms "sham acupuncture" and "placebo acupuncture" in clinical acupuncture research is compared and analyzed in this article. In terms of their respective characteristics, sham acupuncture has a wider scope, including various types of acupoints, needle insertion at non-acupoint or non-insertion at acupoints, while placebo acupuncture mainly focuses on non-insertion at acupoints. Sham acupuncture mainly emphasizes the appearance similarity to real acupuncture, while placebo acupuncture emphasizes both similarity in appearance and the absence of therapeutic effects. Properly distinguishing and applying sham acupuncture and placebo acupuncture can help standardize their usage in terminology. Considering the difficulty in setting up qualified placebo acupuncture, it is suggested that researchers use the term "sham acupuncture" to describe the acupuncture control methods used in clinical research.

Antimalarials and macrolides: a review of off-label pharmacotherapies during the first wave of the SARS-CoV-2 pandemic

Abstract We critically analyzed clinical trials performed with chloroquine (CQ) and hydroxychloroquine (HCQ) with or without macrolides during the first wave of COVID-19 and discussed the design and limitations of peer-reviewed studies from January to July 2020. Seventeen studies were eligible for the discussion. CQ and HCQ did not demonstrate clinical advantages that justified their inclusion in therapeutic regimens of free prescription for treatment or prophylactic purposes, as suggested by health authorities, including in Brazil, during the first wave. Around August 2020, robust data had already indicated that pharmacological effects of CQ, HCQ and macrolides as anti-SARS-CoV-2 molecules were limited to in vitro conditions and largely based on retrospective trials with low quality and weak internal validity, which made evidence superficial for decision-making. Up to that point, most randomized and nonrandomized clinical trials did not reveal beneficial effects of CQ or HCQ with or without macrolides to reduce lethality, rate of intubation, days of hospitalization, respiratory support/mechanical ventilation requirements, duration, type and number of symptoms, and death and were unsuccessful in increasing virus elimination and/or days alive in hospitalized or ambulatory patients with COVID-19. In addition, many studies have demonstrated that side effects are more common in CQ-or HCQ-treated patients.

Meta-analysis and trial sequential analysis of Chaihuang Granules in treatment of upper respiratory tract infection in children / 中国中药杂志

This study aimed to evaluate the efficacy and safety of Chaihuang Granules in the treatment of upper respiratory tract infection in children. The databases such as CNKI, Wanfang, VIP, SinoMed, Cochrane Library, PubMed, EMbase, Web of Science, Chinese Clinical Trial Registry, and ClinicalTrials.gov were searched for randomized controlled trial(RCT) of Chaihuang Granules for the treatment of upper respiratory tract infection in children, and supplemented by manual searching of gray literature. Two investigators independently screened the literature, extracted data, and assessed the methodological quality. Meta-analysis was performed using RevMan 5.4 software, trial sequential analysis was conducted using TSA 0.9.5.10 Beta software, and evidence quality evaluation was carried out using GRADE profiler 3.6.1 software. Eighteen RCTs involving 2 459 patients(1 262 in the treatment group and 1 197 in the control group) were included. Meta-analysis showed that compared with conventional therapy alone, Chaihuang Granules significantly improved the total effective rate(RR=1.18, 95%CI[1.15, 1.22], P<0.000 01), reduced the disappearance time of symptoms/signs(MD=-1.39, 95%CI[-1.66,-1.12], P<0.000 01), improved cytokine levels(MD=-2.40, 95%CI[-3.80,-1.00], P=0.000 8), improved humoral immune levels(MD=0.75, 95%CI[0.60, 0.90], P<0.000 01), and reduced the recurrence rate(MD=-2.11, 95%CI[-2.98,-1.25], P<0.000 01). However, the incidence of adverse reactions was not increased(RR=0.94, 95%CI[0.59, 1.49], P=0.78). Subgroup analysis showed that:(1) both Chaihuang Granules used alone(RR=1.19, 95%CI[1.11, 1.27], P<0.000 01) and in combination with other therapies(RR=1.18, 95%CI[1.14, 1.22], P<0.000 01) effectively improved the total effective rate.(2) In terms of symptoms/signs disappearance time, Chaihuang Granules effectively reduced the duration of fever(MD=-1.18, 95%CI[-1.78,-0.58], P=0.000 1), cough with sputum(MD=-1.82, 95%CI[-2.38,-1.25], P<0.000 01), cough(MD=-1.31, 95%CI[-1.89,-0.74], P<0.000 01), sore throat(MD=-1.57, 95%CI[-2.25,-0.89], P<0.000 01), and lung rales(MD=-1.49, 95%CI[-2.06,-0.92], P<0.000 01).(3) Regarding cytokine levels, Chaihuang Gra-nules effectively improved the levels of interleukin(IL)-2(MD=-0.94, 95%CI[-1.16,-0.72], P<0.000 01), IL-6(MD=-4.71, 95%CI[-6.39,-3.03], P<0.000 01), and tumor necrosis factor-α(TNF-α)(MD=-2.07, 95%CI[-2.43,-1.71], P<0.000 01).(4) In terms of cellular immune levels, Chaihuang Granules effectively improved the levels of CD3~+(MD=4.11, 95%CI[1.53, 6.69], P=0.002), CD4~+(MD=4.21, 95%CI[1.69, 6.73], P=0.001), CD8~+(MD=-2.65, 95%CI[-3.93,-1.37], P<0.000 1), and CD4~+/CD8~+(MD=0.25, 95%CI[0.14, 0.37], P<0.000 1).(5) In terms of humoral immune levels, Chaihuang Granules effectively improved the levels of IgA(MD=0.44, 95%CI[0.23, 0.64], P<0.000 1), IgM(MD=0.31, 95%CI[0.15, 0.46], P=0.000 1), and IgG(MD=2.02, 95%CI[1.60, 2.43], P<0.000 01). Trial sequential analysis showed that the cumulative Z-curve of the total effective rate crossed the boundary value, further confirming its clinical efficacy. The GRADE evidence quality evaluation showed that the evidence quality of the above outcome indicators was low or very low, and the recommendation strength was weak. Compared to conventional therapy alone, Chaihuang Granules can effectively improve the total effective rate of treatment, alle-viate symptoms and signs of upper respiratory tract infection in children, improve inflammatory conditions, enhance immune function, and reduce the recurrence rate. Due to the limited quality of the included studies, high-quality RCT is still needed to provide evidence support for the above conclusions.

Tratamientos y bioterapias para COVID-19 / Therapeutics and biotherapies for covid-19

INTRODUCCIÓN: Un nuevo brote de coronavirus surgió en 2019 en Wuhan, China, causando conmoción en el sistema sanitario de todo el mundo; el Comité Internacional de Taxonomía de Virus lo denominó SARS-CoV-2, agente causante de la enfermedad COVID-19.El espectro de gravedad de la enfermedad es muy amplio: la mayoría de los pacientes no presentan gravedad, pero otros pueden desarrollar neumonías, y la insuficiencia respiratoria aguda es la causa más frecuente de mortalidad. Objetivo: analizar y desarrollar las distintas alternativas terapéuticas aportadas por la Biotecnología para tratar los síntomas de aquellos pacientes con COVID-19. Metodología: se realizó una revisión de la bibliografía disponible, a partir de enero de 2020 en PubMed, acerca de los tratamientos que se encuentran aún en ensayos clínicos y aquellos que cuentan con aprobación bajo uso de emergencia para la enfermedad COVID-19. También se realizaron búsquedas a través de Google y Google Académico para publicaciones de organismos de Salud en referencia a políticas de salud establecidas para la terapéutica durante dicha pandemia. Resultados: este trabajo aborda las nuevas alternativas terapéuticas para COVID-19 derivadas de la Biotecnología, que se encuentran tanto en uso como en etapas de ensayos clínicos comprendidos dentro del segmento de los biofármacos y las bioterapias. Se incluye un breve resumen del estatus regulatorio de entidades de salud, el mecanismo de acción de dichas terapias y características generales de cada uno. Se incluyen novedosas bioterapias que se empezaron a implementar para afrontar la pandemia. Conclusiones: la pandemia de coronavirus está poniendo a prueba el sistema sanitario internacional, para brindar soluciones tanto desde el diagnóstico y prevención como para el tratamiento de la población a fin de disminuir la mortalidad. Esto incluyó, obviamente también, al área de la Biotecnología aplicada a la salud, que ha aportado en los tres aspectos mencionados; el presente trabajo se centra en las respuestas de tipo terapéutico que ha brindado y que están comercializadas o en fases clínicas. (AU)

INTRODUCTION: A new coronavirus outbreak emerged in 2019 in Wuhan, China, causing a shock to the healthcare system around the world; the International Committee on Taxonomy of Viruses named it SARS-CoV- 2, the infectious agent of the COVID-19 disease. The spectrum of severity of the disease is very wide, most patients are not serious, but others can develop pneumonia, with acute respiratory failure being the most frequent cause of mortality. Objective: to analyze and develop the different therapeutic alternatives provided by Biotechnology dedicated to Health, to treat the symptoms of those COVID-19 patients who require it, and thus reduce mortality.Methodology: a review of the available literature from January 2020 in PubMed of the treatments that are still in clinical trials and those that have been approved under emergency use for the disease COVID-19 was performed. Searches were also carried out through Google and Google Scholar for publications of Health organizations in reference to health policies established for therapeutics during the mentioned pandemic. Results: this work addresses the new therapeutic alternatives derived from Biotechnology, which are both in use and in stages of clinical trials, to treat patients who developed COVID-19 included within the segment of biopharmaceuticals and biotherapies. A brief summary of the regulatory status of health entities, the mechanism of action of said therapies and general characteristics of each one is included. Innovative biotherapies that began to be implemented to face the pandemic are included. Conclusions: The coronavirus pandemic has driven the international health system to the test, to provide solutions both from the diagnosis, prevention and treatment of the population to reduce the mortality of patients. This obviously also included the area of Biotechnology applied to health, which has contributed in the three aspects mentioned. The present work focuses on the therapeutic responses that it has provided and that are commercialized or in clinical phases. (AU)

Perfil dos casos de câncer de mama entre acometidos no acre período de 2015 a 2019 ­ um estudo transversal / Profile of breast cancer cases between affected in acre period from 2015 to 2019 - a cross-sectional study / Perfil de los casos de cáncer de mama entre las personas afectadas en el período acre de 2015 a 2019 - un estudio transversal

Este estudo teve como objetivo analisar o perfil dos casos de câncer de mama no estado do Acre no período de 2015 a 2019. Trata-se de um estudo quantitativo com delineamento transversal. A amostra foi constituída por todos os casos de câncer de mama registrados no Acre e inseridos no Departamento de Informática do Sistema Único de Saúde (DATASUS) no período de 2015 a 2019. Foram identificados no período 293 casos da doença, com maior número de casos registrados no ano de 2019 (25,0%), sendo a maioria do sexo feminino (98,0%), na faixa etária de 40 a 49 anos (29,0%). O tempo decorrido desde o diagnóstico até o início do tratamento foi de mais de 60 dias (51,0%). A modalidade terapêutica mais utilizada foi a quimioterapia (55,0%). O local da realização do tratamento ocorreu capital do estado Rio Branco (80,0%). A maior parte dos acometidos, ainda encontra-se em tratamento (56,0%), no entanto (44,0%) evoluiu para óbito. O aumento da doença com o passar dos anos é notável no Acre. É importante destacar que ações voltadas para a prevenção e controle do câncer de mama continuam sendo fundamentais para auxiliar na diminuição do número de casos, como o rastreamento e diagnóstico precoce.

This study aimed to analyze the profile of breast cancer cases in the state of Acre in the period from 2015 to 2019. This is a quantitative study with a cross-sectional design. The sample consisted of all breast cancer cases registered in Acre and inserted in the Informatics Department of the Unified Health System (DATASUS) in the period from 2015 to 2019. In the period 293 cases of the disease were identified, with a greater number of cases registered in 2019 (25.0%), with the majority being female (98.0%), aged 40 to 49 years (29.0%). The time elapsed from diagnosis to the start of treatment was more than 60 days (51.0%). The most used therapeutic modality was chemotherapy (55.0%). The place where the treatment was performed took place in the state of Rio Branco (80.0%). Most of the people affected are still under treatment (56.0%), however (44.0%) died. The increase in the disease over the years is notable in Acre. It is important to highlight that actions aimed at the prevention and control of breast cancer continue to be fundamental to assist in reducing the number of cases, such as screening and early diagnosis.

Este estudio tuvo como objetivo analizar el perfil de los casos de cáncer de mama en el estado de Acre en el período de 2015 a 2019. Se trata de un estudio cuantitativo con diseño transversal. La muestra consistió en todos los casos de cáncer de mama registrados en Acre e ingresados en el Departamento de Informática del Sistema Único de Salud (DATASUS) en el período de 2015 a 2019. En el periodo se identificaron 293 casos de la enfermedad, siendo el mayor número de casos registrados en 2019 (25,0%), siendo la mayoría mujeres (98,0%), en el grupo de edad de 40 a 49 años (29,0%). El tiempo transcurrido desde el diagnóstico hasta el inicio del tratamiento fue superior a 60 días (51,0%). La modalidad terapéutica más utilizada fue la quimioterapia (55,0%). El lugar donde se realizó el tratamiento fue Rio Branco, la capital del estado (80,0%). La mayoría de los pacientes afectados siguen en tratamiento (56,0%), sin embargo, (44,0%) fallecieron. El aumento de la enfermedad a lo largo de los años es notable en Acre. Es importante destacar que las acciones dirigidas a la prevención y control del cáncer de mama siguen siendo fundamentales para ayudar a reducir el número de casos, como el cribado y el diagnóstico precoz.

Sesgos en investigación quirúrgica / Biases in surgical research

Resumen Los resultados de diversos hallazgos de investigación han sido objeto de crítica, en especial en los últimos años, debido a presencia de errores sistemáticos (sesgos), los que ponen en duda la validez interna de los resultados obtenidos. Estos sesgos pueden ocurrir en cualquier etapa del curso de una investigación, es decir, desde la planificación del estudio hasta la presentación y publicación de sus resultados. Los sesgos se han clasificado de diferentes formas, intentado agruparlos bajo dimensiones conceptuales, objeto de organizar de mejor forma la información existente, que además es considerable. Los sesgos pueden ocurrir por diversos motivos, pero en general, los más frecuentes son aquellos originados por el observador (él o los que miden), por lo que es observado (sujeto en estudio); y aquello con lo que se observa (instrumento de medición). Por otra parte, varios de los múltiples sesgos existentes, se pueden agrupar en: sesgos de selección, de medición o información, y de confusión. El objetivo de este manuscrito fue comentar la importancia de los sesgos más comunes en la investigación quirúrgica, y su relación con algunos diseños de investigación; así como, conocer las estrategias existentes para minimizar su ocurrencia.

The results of many research findings have come under scrutiny in recent years due to the introduction of systematic errors (biases), which can occur at any stage during an investigation, from planning to presentation of results and their presentation and further publication. Biases have been classified in different ways, trying to group them under conceptual dimensions to better organize the existing information, which is considerable. Biases can occur for various reasons, but in general, the most frequent are those originated by the observer, what is observed; and what is observed with. I.e., the subject that is measured, who measures it and with what it measures it. On the other hand, several of the multiple biases can be grouped into selection, measurement or information, and confounding biases. The aim of this manuscript was to comment on the importance of the most common biases in surgical research, and their relationship with some research designs; as well as know the existing strategies to reduce its occurrence.

Implementación de ensayos clínicos y acceso posensayo a vacunas para la COVID-19 en Latinoamérica / Implementation of clinical trials and post-trial access to COVID-19 vaccines in Latin America

Latinoamérica fue durante noviembre de 2020 una de las regiones más afectada por la pandemia de COVID-19 en cuanto a prevalencia y muertes atribuidas al virus. Por ello, el inicio de testeo de vacunas en ciudadanos de la región fue recibido con altas expectativas sobre su efectividad. Frente a lo cual es esencial tener en cuenta ciertos principios fundamentales que deben guiar este proceso asegurando su correcta implementación. El objetivo de este artículo es ofrecer consideraciones sobre el proceso de implementación de ensayos clínicos y acceso posensayo a vacunas para COVID-19 en Latinoamérica. En particular los relacionados con el respeto a la dignidad de los participantes, las tensiones históricas globales y regionales en materia de economía política de ensayos clínicos, algunos aspectos de la gobernanza global y el rol de la Organización Mundial de la Salud en la pandemia, y la necesidad de asegurar el acceso posensayo a la vacuna. Se concluye que la pandemia es una oportunidad para estrechar lazos de cooperación y solidaridad entre países latinoamericanos. Los ensayos clínicos son una instancia clave para reforzar la gobernanza local y regional con miras a fortalecer la transparencia y la vigilancia de la correcta realización de alianzas público-privadas en el desarrollo de terapias, en los que la Organización Mundial de la Salud y la Organización Panamericana de la Salud, tienen un rol importante para la implementación de estrategias de integración y acceso a vacunas(AU)

Latin America was during November 2020 one of the most affected regions by the COVID-19 pandemic in terms of prevalence and deaths attributed to the virus. Therefore, the start of vaccine testing in citizens of the region was received with high expectations about its effectiveness. Therefore, it is essential to take into account certain fundamental principles that should guide this process ensuring its correct implementation. The objective of this article is to provide considerations on the process of implementing clinical trials and post-trial access to COVID-19 vaccines in Latin America, in particular those related to respect for the dignity of participants, the historical global and regional tensions regarding the political economy of clinical trials, some aspects of global governance and the role of the World Health Organization in the pandemic, and the need to ensure post-trial access to the vaccine. It is concluded that the pandemic is an opportunity to strengthen bonds of cooperation and solidarity between Latin American countries. Clinical trials are a key instance to strengthen local and regional governance with a view to consolidate transparency and monitoring of the correct implementation of public-private partnerships in the development of therapies, in which the World Health Organization and the Pan American Health Organization have an important role for the implementation of integration strategies and access to vaccines(AU)

Are we ready for pig-to-human clinical xenotransplantation trials? / Estamos prontos para ensaios clínicos de xenotransplante porco-para-humanos? / ¿Estamos listos para ensayos clínicos de xenotrasplante del cerdo al humano?

Abstract: The invention and widely use of organ allotransplantation provides effective treatment of some originally fetal diseases such as liver/kidney failure and has saved million of lives around the globe. However, the scarcity of human organs has caused many patients, who could have been treated, to die while waiting for suitable organs around the world. Pig-to human xenotransplantation provides a potential solution to solve this tough problem. Pig organs have been considered as major sources of xenotransplantation because of the sufficient number of donors, the sizes of organs, and physiologically structural similarities. However, xenotransplantation also has some problems, such as the possibility of spreading animal diseases to human, the interspecies immunological barrier, organs of animal origin challenging human nature, and potential informed consent issues. This article will discuss these potential issues and to see whether it is the suitable time to conduct clinical xenotransplantation trials in humans.

Resumen: La invención y el amplio uso de trasplantes alógenos proporciona tratamiento efectivo de algunas enfermedades de origen fetal, como la insuficiencia renal y hepática, y ha salvado a millones de pacientes en el mundo. Sin embargo, la escasez de órganos humanos ha causado que muchos pacientes en el mundo, que podrían haber sido tratados, murieran por esperar un órgano adecuado. El xenotrasplante del cerdo al humano proporciona una solución potencial para resolver este difícil problema. Los órganos de cerdo han sido considerados como fuentes mayores para xenotrasplantes debido al suficiente número de donantes, el tamaño de los órganos y estructuras fisiológicas similares. No obstante, el xenotrasplante también tiene algunos problemas, como la posibilidad de expandir enfermedades animales a humanos, la barrera inmunológica entre especies, el desafío para la naturaleza humana de tener órganos de origen animal y problemas potenciales de consentimiento informado. Este artículo discute estos temas potenciales y plantea si estamos en un momento apropiado para realizar ensayos clínicos de xenotrasplantes en humanos.

Resumo: A invenção e amplo uso de alotransplante de órgãos propicia tratamento efetivo para algumas doenças originalmente fetais tais como falência hepática/renal e tem salvo milhões de vidas em todo o globo. Entretanto, a escassez de órgãos humanos tem causado a morte de muitos pacientes que poderiam ter sido tratados - aguardando por órgãos apropriados em todo o globo. Xenotransplante porco-para-humanos propicia uma solução potencial para resolver este difícil problema. Órgãos de porco tem sido considerados como as principais fontes de xenotransplante por causa do número suficiente de doadores, do tamanho dos órgãos e de similaridades estruturais fisiológicas. Entretanto, xenotransplante também tem alguns problemas, tais como a possibilidade de disseminar doenças animais aos humanos, a barreira imunológica entre espécies, órgão de origem animal desafiando a natureza humana e aspectos potenciais de consentimento informado. Esse artigo discutirá esses aspectos potenciais e verificará se é o momento adequado para conduzir ensaios clínicos de xenotransplante em humanos.

JCOG lung cancer surgery trial series: review and interpretation / 中华肿瘤杂志

Surgery is so far the most effective treatment for early-stage non-small cell lung cancer (NSCLC). Since the 1990s, the pathology spectrum of early-stage lung cancer has gradually changed because of the increased detection of ground-glass opacity (GGO). The findings from preoperative thin-section computed tomography are strong predictors for the invasiveness and lymph node involvement of GGO, and limited surgery is believed to be implemented safely for radiological less invasive lesions, which calls into question the dominance of lobectomy. After the JCOG0201 trial establishing the radiologic criteria of pathological noninvasiveness for lung adenocarcinoma, the Japan Clinical Oncology Group (JCOG) and the West Japan Oncology Group (WJOG) have successively carried out a series of prospective imaging-guided trials to investigate the optimal surgical procedure for early-stage lung cancer. JCOG0804, was a single-arm, non-randomized, confirmatory trial to evaluate the efficacy and safety of sublobar resection (wedge resection and segmentectomy) for GGO dominant peripheral lung cancer. The primary end point was 5-year relapse-free survival. JCOG0802/WJOG4607L, was a multicentre, open-label, phase 3, randomized, controlled, non-inferiority trial to investigate if segmentectomy was non-inferior to lobectomy in patients with small-sized peripheral NSCLC. The primary endpoint was 5-year overall survival. JCOG1211 was also a non-randomized confirmatory trial to confirm the efficacy of a segmentectomy for clinical T1N0 lung cancer with dominant GGO. The primary endpoint was 5-year relapse-free survival. The findings of JCOG0804 and JCOG0802, and the primary analysis results of JCOG1211 have been officially published. This article systematically reviewed and interpreted the results of the JCOG lung cancer surgery trial series.

Rethinking the marketing strategy of anti-tumor drugs by single-arm trials supported / 中华肿瘤杂志

Single-arm trial refers to a clinical trial design that does not set up parallel control group, adopts open design, and does not involve randomization and blind method. These features, on the one hand, speed up the process of clinical trials, significantly shorten the time to market and meet the needs of patients with advanced malignancies, but also lead to the uncertainty of single-arm clinical trials themselves. Recently, the US Food and Drug Administration held a meeting of the oncologic drug advisory committee to discuss six tumor indications that have been accelerated approved, which once again triggered the discussion of single-arm trials. The basis of accelerated approval by single-arm trial is actually a compromise on the level of evidence-based medical evidence requirements after assessing the benefit risk. Therefore, the sponsor should strictly grasp the applicable conditions of single-arm trial in anti-tumor drugs and conduct single-arm trial scientifically. Post-marketing clinical trial should be implement as early as possible to ensure the benefit of patients. Based on the characteristics of single-arm trial, combined with two guidance relevant to single-arm trial issued by National Medical Products Administration recently, this article is supposed to propose and summarize the strategy of single-arm trial supporting the marketing of anti-tumor drugs.