What is an "ongoing" clinical trial? An analysis of different sources revealed heterogeneous definitions of when a clinical trial starts and ends: a meta-research study

ABSTRACT BACKGROUND: Although the concept of an "ongoing study" seems self-explanatory, it is difficult to determine whether a trial is underway. OBJECTIVE: To analyze the definitions of "ongoing clinical trial" across different clinical trial registries, methodological guidelines, and other sources. DESIGN AND SETTING: This meta-research study was conducted at the Universidade Federal de São Paulo (UNIFESP), Brazil. METHODS: We performed a cross-sectional analysis of relevant clinical trial registry databases, methodological guidelines for conducting systematic reviews, and other sources that would define or regulate clinical trials. RESULTS: We identified various heterogeneous definitions used by eligible sources at both the start and end of a clinical trial. The starting criteria used were as follows: when the team is planning the protocol, when permission is given to conduct the study, or when the first participant is enrolled. Some sources used the time at which the last outcome data was collected as a criterion to determine the end of the trial. The International Committee of Medical Journal Editors stated that a study is still "ongoing" during the analysis process. Several sources use a vague definition or present no clear criteria for defining the start or end of a study. CONCLUSION: The concept of "ongoing clinical trials" lacks a transparent and homogeneous definition across relevant sources. A consensus on this concept is important to facilitate the evaluation of available evidence and conduct research synthesis. Further efforts are necessary to determine the best definition for the start and end of a clinical trial.

Application of Quality Evaluation of Blind Method in Clinical Trials of Traditional Chinese Medicine / 中国实验方剂学杂志

The quality evaluation of the blind method is to evaluate the clinical blind data obtained from clinical trials adopting the blind method and judge the effectiveness of the blind method by investigating the blind effect of different blind objects. A successful blind method can avoid the influence of subjective factors on the test results of subjects and researchers to a certain extent. The quality evaluation of the blind method can reflect not only the effectiveness of the blind method but also the accuracy and credibility of clinical trial results. In recent years， randomized controlled trials have been widely used in the evaluation of the clinical efficacy of traditional Chinese medicine （TCM）， but the quality of the implementation of blind methods is uneven， and the evaluation criteria have not yet been formed. In this paper， the data collection methods， calculation principles， advantages， and disadvantages of two quantitative quality evaluation methods of blind methods， namely James Blinding Index （JBI） and Bang Blinding Index （BBI）， were introduced. The two indexes were analyzed in a randomized controlled trial of acupuncture and moxibustion to relieve postoperative oral pain. The calculation process of the results was demonstrated by R software and visualized by forest map. At the same time， a tool table was designed to facilitate the collection of evaluation data of blind methods in TCM clinical trials at different stages. Finally， the necessity and feasibility of quality evaluation of blind method in TCM research were discussed to provide a basis for evaluating and improving the quality of blind method implementation in TCM clinical trials.

COVID-19 en sujetos de riesgo participantes en ensayos clínicos durante la pandemia en Argentina / COVID-19 in subjects at risk participating in clinical trials during the pandemic in Argentina

Resumen Introducción : Existe poca información sobre la pre sencia de COVID-19 en participantes de ensayos clínicos. El objetivo del estudio fue evaluar la tasa de infección acumulada por SARS-CoV-2 en esta población. Además, investigamos el riesgo, letalidad y mortalidad por CO VID-19. Métodos : Diseño observacional retrospectivo que incluyó adultos participantes en ensayos clínicos de intervención aprobados por nuestro comité de ética du rante los dos primeros años de la pandemia (31/3/2020 a 31/3/2022). Se excluyeron protocolos pediátricos, obser vacionales, de corta duración y con sujetos internados. Resultados : Se incluyeron 513 sujetos adultos que participaron en ensayos clínicos durante ese período de la pandemia por COVID-19. Los pacientes con CO VID-19 se caracterizaron por tener una edad de 59.7 ± 13.7 años (50% sexo femenino) y el 92% presentó riesgo incrementado de letalidad por COVID-19. La tasa acu mulada de COVID-19 fue de 9.74% (IC 95%: 7.32-12.64%) que se situó por debajo del 17% de la población de 60 a 69 años de la Argentina (p<0.0001). La tasa de letalidad por COVID-19 fue de 14% (IC 95%: 5.8-26.7), que se situó por encima del 2.45% de la población de 50 a 69 años de la Argentina (p<0.0001). Conclusión : La tasa de COVID-19 en los sujetos adultos participantes de ensayos clínicos estuvo por debajo de las cifras de la población argentina de simi lar edad. La tasa de letalidad estuvo por encima de las cifras poblacionales y se explica por el alto riesgo de esa población.

Abstract Introduction : There is little information on the pres ence of COVID-19 in clinical trial participants. The objec tive of the study was to evaluate the cumulative infec tion rate for SARS-CoV-2 in this population. Additionally, we investigated the risk, lethality, and mortality from COVID-19. Methods : The design was observational retrospective that included adult subjects participating in clinical intervention trials approved by our ethics committee during the first two years of the pandemic (March 31, 2020 to March 31, 2022). Pediatric, observational, short-term, and inpatient protocols were excluded. Results : We included 513 adult subjects who par ticipated in clinical trials during the first two years of the COVID-19 pandemic. Patients with COVID-19 were characterized as being 59.7 ± 13.7 years old (50% fe male), and 92% had an increased risk of fatality from COVID-19. The cumulative rate of COVID-19 was 9.74% (95% CI: 7.32-12.64%) and its confidence intervals were below 17% of the population aged 60 to 69 in Argentina (p<0.0001). The case fatality rate for COVID-19 was 14% (95% CI: 5.8%-26.7%) and its confidence intervals were above 2.45% of the population aged 50 to 69 in Argentina (p< 0.0001). Conclusion : The rate of COVID-19 in adult subjects participating in clinical trials was below the figures for the Argentine population of similar age. The fatality rate was above the population figures, and it is explained by the high risk of the population.

Terapia genica: ¿Dónde estamos?, ¿A dónde vamos? / Gene therapy: Where are we? Where are we going?

Resumen La terapia génica ha logrado avances significativos en el tratamiento de enfermedades genéticas, especial mente en enfermedades raras y monogénicas. Se han desarrollado y aprobado terapias génicas para tratar en fermedades como la atrofia muscular espinal, brindando esperanza a los pacientes y demostrando la eficacia de esta terapia. Actualmente, se están realizando numerosos ensayos clínicos para evaluar la seguridad y eficacia de la terapia génica en diversas enfermedades, particularmente en el campo de la neurología pediátrica. Estos estudios están generando datos alentadores y contribuyen al conoci miento sobre cómo mejorar las técnicas de terapia génica. A pesar de los avances, la terapia génica enfrenta desafíos importantes. Es una terapia costosa y téc nicamente compleja, lo que limita su accesibilidad. Además, aspectos como la entrega eficiente de genes, la respuesta inmunológica a los vectores y la duración de la respuesta terapéutica requieren mejoras. se está investigando activamente. En cuanto al futuro de la terapia génica, se espera que los avances en tecnología de edición génica, como CRISPR-Cas9, permitan una mayor precisión y eficiencia en la modificación de genes. Se espera que la investigación en vectores de terapia génica mejore la capacidad de entrega y la seguridad de los tratamientos. Se están desarrollando nuevas ge neraciones de vectores virales y no virales que podrían superar las limitaciones actuales y permitir una admi nistración más eficiente y precisa de genes terapéuticos.

Abstract Gene therapy has achieved significant advancements in the treatment of genetic diseases, especially in rare and monogenic diseases. Gene therapies have been de veloped and approved to treat diseases such as spinal muscular atrophy, offering hope to patients and dem onstrating the effectiveness of this therapy. Currently, numerous clinical trials are being conduct ed to evaluate the safety and efficacy of gene therapy in various diseases, particularly in the field of pediatric neurology. These studies are generating encouraging data and contributing to the knowledge on how to im prove gene therapy techniques. Despite the advancements, gene therapy faces significant challenges. It is a costly and technically complex therapy, limiting its accessibility. Addition ally, aspects such as efficient gene delivery, immune response to vectors, and duration of therapeutic re sponse require improvements and are actively being investigated. Regarding the future of gene therapy, advances in gene editing technology, such as CRISPR-Cas9, are ex pected to allow for greater precision and efficiency in gene modification. Research on gene therapy vectors is expected to en hance the delivery capacity and safety of treatments. New generations of viral and non-viral vectors are be ing developed that could overcome current limitations and enable more efficient and precise administration of therapeutic genes.

Consideraciones bioéticas sobre los incentivos a participantes voluntarios sanos en investigaciones Fase I

Los ensayos clínicos en Fase I se realzan con la participación de voluntarios sanos de prueban la seguridad y tolerabilidad de los productos farmacéuticos en investigación. En ellos, los participantes están expuestos a riesgos de medicamentos del estudio sin la posibilidad de un beneficio médico directo y, por lo general, deben pasar días o semanas en un centro de investigación. Los incentivos, como pagos monetarios se utilizan para incentivar la inscripción y compensar a los participantes por su tiempo. Estas características de los ensayos voluntarios sanos de fase I crean un contexto de investigación que difiere notablemente de la mayoría de las otras investigaciones clínicas, pues la mayoría de ellos son personas vulnerables económicamente. Este artículo presenta el objetivo de analizar factores bioéticos que inciden en el otorgamiento de incentivos a participantes voluntarios sanos en investigaciones Fase I.

Phase I Clinical Trials are conducted with the participation of healthy volunteers to test the safety and tolerability of pharmaceutical products. In them, participants are exposed to study drug risks without the possibility of direct medical benefit and usually must spend days or weeks at a research site. Incentives such as monetary payments are used to encourage enrollment and compensate participants for their time. These characteristics of Phase I healthy volunteer trials create a research context that differs markedly from most other clinical research, as most of them are financially vulnerable individuals. This paper aims to analyze bioethical factors that influence the granting of incentives to healthy volunteer participants in Phase I research.

La muestra en ensayos clínicos aleatorizados con análisis interino / Samples in randomized clinical trials with interim analysis

RESUMEN En este artículo se introducen los ensayos clínicos aleatorizados y conceptos básicos de la inferencia estadística. Se presenta como calcular el tamaño de muestra por tipo de desenlace e hipótesis a probar, junto con el código en el lenguaje de programación R para realizar su aplicación. Se presentan cuatro métodos para realizar el ajuste del tamaño de muestra original, cuando se planean análisis interinos. De una manera sencilla y concreta se busca realizar una introducción a estos temas, considerando las expresiones matemáticas que soportan los resultados y su implementación en programas estadísticos disponibles. Con el fin de acercar a los estudiantes de áreas de la salud a la estadística y al uso de programas estadísticos, aspectos poco considerados en su formación.

ABSTRACT This article introduces randomized clinical trials and basic concepts of statistical inference. We present methods for calculating the sample size by outcome type and the hypothesis to be tested, together with the code in the R programming language. We describe four methods for adjusting the original sample size for interim analyses. We sought to introduce these topics in a simple and concrete way, considering the mathematical expressions that support the results and their implementation in available statistical programs; therefore, bringing health students closer to statistics and the use of statistical programs, which are aspects that are rarely considered during their training.

Behavior of total alkaline phosphatase after radium-233 therapy in metastatic castration-resistant prostate cancer: a single-center, real-world retrospective study / Estudo retrospectivo de vida-real, em centro único, para avaliação do comportamento da fosfatase alcalina total após terapia com rádio-223 no câncer de próstata resistente a castração

Abstract Objective: To describe the behavior of total alkaline phosphatase (tALP) in patients with metastatic castration-resistant prostate cancer receiving radium-223 therapy, in a real-world scenario, and to describe overall survival (OS) among such patients. Materials and Methods: This was a retrospective study involving 97 patients treated between February 2017 and September 2020. Patients were stratified by the baseline tALP (normal/elevated). A tALP response was defined as a ≥ 30% reduction from baseline at week 12. For patients with elevated baseline tALP, we also evaluated treatment response as a ≥ 10% reduction in tALP after the first cycle of treatment. We defined OS as the time from the first treatment cycle to the date of death. Results: There was a significant reduction in the median tALP after each cycle of treatment (p < 0.05 for all). Data for tALP at week 12 were available for 71 of the 97 patients. Of those 71 patients, 26 (36.6%) responded. Elevated baseline tALP was observed in 47 patients, of whom 19 (40.4%) showed a response. Longer OS was observed in the patients with normal baseline tALP, in those with elevated baseline tALP that showed a response to treatment (≥ 10% reduction), and in those who received 5-6 cycles of therapy. Conclusion: The tALP may be used to predict which patients will benefit from treatment with a greater number of cycles of radium-223 therapy and will have longer OS.

Resumo Objetivo: Descrever o comportamento da fosfatase alcalina total (tALP) em pacientes com carcinoma de próstata metastático resistente a castração, submetidos a terapia com rádio-223 em um cenário do mundo real, e a sobrevida global (SG) desses pacientes. Materiais e Métodos: Estudo retrospectivo envolvento 97 pacientes, no período de fevereiro/2017 a setembro/2020. Os pacientes foram estratificados de acordo com a tALP basal (normal/elevada). A resposta à tALP foi definida como uma redução em relação à linha de base de ≥ 30% na semana-12. Para pacientes com tALP basal elevada, também foi avaliada a resposta ao tratamento como uma redução de ≥ 10% de tALP após o primeiro ciclo. A SG foi definida como o tempo entre o primeiro ciclo e a data do óbito. Resultados: A redução da tALP média após cada ciclo foi significativa (p < 0,05). A tALP na semana 12 estava disponível para 71 dos 97 pacientes. Desses 71 pacientes, 26 (36,6%) responderam. Dezenove (40,4%) dos 47 pacientes com tALP elevada apresentaram resposta. Foi observada uma SG mais longa nos pacientes com tALP basal normal, nos pacientes com tALP basal elevada que apresentaram resposta ao tratamento (redução de ≥ 10%) e nos pacientes que receberam 5-6 ciclos. Conclusão: A tALP pode ser usada para prever parte dos pacientes que se beneficiarão do tratamento com um maior número de ciclos e uma SG mais longa.

THE POTENTIAL OF TELECOMMUNICATIONS IN CANCER CLINICAL TRIALS: AN OVERVIEW

This review article explores the potential bene?ts and challenges of using telecommunications technology, including telemedicine and mobile health apps, in cancer clinical trials. The author conducted a search of four electronic databases for studies published in English between 2010 and 2021 that evaluated the use of telecommunications technology in adult cancer patients and reported patient outcomes. The studies were grouped based on the type of telecommunications technology used, and the outcomes were synthesized to provide an overview of the potential impact of telecommunications technology on cancer clinical trials. Telecommunications technologies were found to improve patient access and recruitment, data collection, management, and analysis, and enable real-time monitoring of patients' health and adherence to treatment. Telecommunications technologies can also reduce trial costs by minimizing the need for in- person visits and other expenses. However, the implementation of telecommunications technologies in clinical trials is not without challenges, including technical issues, patient acceptance and adherence, regulatory and legal approvals, and variability in healthcare systems. The author suggests that addressing these challenges could lead to improved patient outcomes and better overall health outcomes for cancer patients

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)

To explore the application status and prospect of sham acupuncture in clinical trials of acupuncture based on 5G+VR technology / 国际中医中药杂志

Acupuncture has been proved to be safe and effective by large-scale and authoritative clinical observation at home and abroad. However, in recent years, the results of some randomized controlled trials of acupuncture in JAMA showed no significant difference between acupuncture effect and sham acupuncture effect. Acupuncture and moxibustion in clinical practice is a summary of academic and clinical rules. Different from chemical drugs, the amount of stimulation, methods of operation and techniques vary. At present, sham acupuncture in clinical trials at home and abroad has been questioned by many scholars, who believe that sham acupuncture is not fake, and call for "fake targeted research" to be stopped. In order to improve the sham acupuncture control design, 5G + VR technology and the principle elements of sham acupuncture should be combined. We also discussed and analyzed advantages and prospects of modern intelligent medical technology of 5G + VR technology in the sham acupuncture RCT. We hope to promote standardization of acupuncture clinical trials, and the development, innovation and application of acupuncture research at home and abroad.

Rare tumors: a blue ocean of investigation / 医学前沿

Advances in novel drugs, therapies, and genetic techniques have revolutionized the diagnosis and treatment of cancers, substantially improving cancer patients' prognosis. Although rare tumors account for a non-negligible number, the practice of precision medicine and development of novel therapies are largely hampered by many obstacles. Their low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and subtyping. Sample exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines, insufficient biomarkers for prognosis/efficacy, and inability to identify potential novel therapies in clinical trials. Herein, by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas, we proposed a definition of rare tumor in China, including 515 tumor types with incidences of less than 2.5/100 000 per year. We also summarized the current diagnosis process, treatment recommendations, and global developmental progress of targeted drugs and immunotherapy agents on the status quo. Lastly, we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by NCCN. With this informative report, we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients.

Rehabilitation programs of executive functions in young and middle adulthood based on computational systems: a scoping review

Introduction: The use of computational systems has ventured into different healthcare areas, such as rehabilitation and stimulation of cognitive processes. To this date, it is possible to identify some reviews collecting studies on the efficacy and effects of those programs in groups such as older adults, children, and teenagers; there is a lack of academic literature giving an account of young and middle-aged adults. Objective: To identify empirical studies that measured the feasibility and effect of computer-based stimulation and rehabilitation programs for cognitive functions in young and middle-aged adults. Materials and methods: The PRISMA ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) extension was used as a base for a scoping review, as suggested by Cochrane Collaboration. Five databases -Science Direct, Scopus, Springer, PubMed, and Taylor & Francis- were used to trace information. The data registry and synthesis of the results was carried out independently by two reviewers. Results: 896 registries were found between 2015 and 2022, of which 91 met the eligibility principles, which evaluated the effects of programs based on computational systems on executive functions on young and middle-aged adults. Conclusion: Most of the interventions based on computational systems showed to be feasible and had moderate to significant effects on executive functions in young and middle-aged adults.

Introducción: El uso de los sistemas computacionales ha incursionado de forma notable en diferentes áreas de la salud, como la rehabilitación y estimulación de los procesos cognitivos. Si bien a la fecha se pueden identificar algunas revisiones que recopilan estudios sobre la eficacia y efectos de estos programas en grupos como adultos mayores, niños y adolescentes, existe poca literatura orientada a la adultez joven y la adultez media. Objetivo: Identificar estudios empíricos que midieron la viabilidad y el efecto de los programas de estimulación y rehabilitación de las funciones ejecutivas basados en computadora en la población adulta joven y media. Materiales y métodos: Se realizó revisión de alcance basado en la extensión PRISMA ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extensión for Scoping Reviews) sugerido por Cochrane Collaboration. Para el rastreo de información se seleccionaron cinco bases de datos: Science Direct, Scopus, Springer, PubMed y Taylor & Francis. El proceso de registro de datos y la síntesis de los resultados fue realizada por dos revisores de forma independiente. Resultados: Se encontraron 896 registros desde el 2015 al 2022, de los cuales 91 cumplieron los principios de elegibilidad, en los que se evaluaron los efectos de programas basados en sistemas computacionales sobre las funciones ejecutivas en adultos jóvenes y adultos medios. Conclusión: La mayoría de las intervenciones basadas en sistemas computacionales mostraron ser viables y tener efectos favorables de moderados a significativos sobre las funciones ejecutivas de adultos jóvenes y medios.

Different kinesio taping tensions present similar benefits for postural control, dynamic balance, agility and instability sensation in individuals with chronic ankle instability: randomized clinical trial / Diferentes tensões de kinesio taping apresentam benefícios semelhantes para controle postural, equilíbrio dinâmico, agilidade e sensação de instabilidade em indivíduos com instabilidade crônica do tornozelo: ensaio clínico randomizado

Abstract Ankle sprain is the most common injury in the lower limbs of physically active individuals, and one of its complications is chronic ankle instability (CAI), for which Kinesio Taping (KT) can be an alternative treatment. The aim of this study was to compare two treatment protocols with KT at different tensions on postural control, dynamic balance, agility and instability in individuals with chronic ankle instability. This is a randomized clinical trial in which postural control was evaluated through the force platform, agility by the side Hop Test, dynamic balance by the modified Star Excursion balance Test, and application of the Cumberland Ankle Tool Instability and Foot and Ankle Outcome Score to assess self-reported instability and functional instability. An initial assessment was conducted, followed by 5 weeks of intervention with weekly applications of KT, and one week after the completion of the intervention, a reassessment was performed. 21 participants were distributed to the group KT with tension (KTT: n=11) and the group KT without tension (KTWT: n=10). KT improves postural control (anteroposterior velocity: p=0.006 and mediolateral: p<0.001; anteroposterior frequency: p<0.001 and mediolateral: p=0.043 of the area of the center of pressure), dynamic balance (p< 0.001), agility (p=0.001) and feeling of instability in individuals with ICT (p=0.001) for both groups. Only one variable, sports category of the FAOS-FOOT questionnaire showed significant change (p=0.008). KT, with or without tension, is able to improve postural control, balanced balance, postural control, and feelings of instability in young adults with ICT.

Resumo A entorse de tornozelo, uma lesão comum em indivíduos fisicamente ativos, frequentemente resulta em uma complicação chamada instabilidade crônica do tornozelo (ICT). A Kinesio Taping (KT) pode ser uma alternativa de tratamento para essa condição. O objetivo deste estudo foi comparar dois protocolos de tratamento com KT em diferentes tensões no controle postural, equilíbrio dinâmico, agilidade e instabilidade em indivíduos com instabilidade crônica do tornozelo. Trata-se de um ensaio clínico randomizado no qual o controle postural foi avaliado por meio da plataforma de força, a agilidade pelo side Hop Test, o equilíbrio dinâmico pelo Star Excursion balance Test modificado e para avaliar instabilidade funcional e autorrelatada aplicou-se o Foot and Ankle Outcome Score e o Cumberland Ankle Tool Instability. Foi realizada uma avaliação inicial, seguida de 5 semanas de intervenção com aplicações semanais de KT, e uma semana após o término da intervenção, foi realizada uma reavaliação. 21 participantes foram distribuídos para o grupo KT com tensão (KTT: n=11) e o grupo KT sem tensão (KTWT: n=10). KT melhora o controle postural (velocidade ântero-posterior: p=0,006 e médio-lateral: p<0,001; frequência anteroposterior: p<0,001 e médio-lateral: p=0,043 da área do centro de pressão), equilíbrio dinâmico (p<0,001), agilidade (p=0,001) e sensação de instabilidade em indivíduos com ICT (p=0,001) para ambos os grupos. Apenas uma variável, categoria esportiva, do questionário FAOS-FOOT apresentou alteração significativa (p=0,008). O KT, com ou sem tensão, é capaz de melhorar o controle postural, o equilíbrio equilibrado, o controle postural e a sensação de instabilidade em adultos jovens com ICT.

Longitudinal analyses of composite resin restoration on erosive lesions: effect of dentin treatment with a chitosan nanoformulation containing green tea

Aim To evaluate the influence of the biomodification of erosive lesions with a chitosan nanoformulation containing green tea (NanoCsQ) on the clinical performance of a composite resin. Methods The study was performed in a split-mouth, randomized and double-blinded model with 20 patients with 40 erosive lesions. The patient's teeth were randomized into two groups (n=20) according to the surface treatment: 1) Without biomodification (control), and 2) Biomodification with NanoCsQ solution (experimental). The lesions were restored with adhesive (Tetric N-bond, Ivoclar) and composite resin (IPS Empress Direct, Ivoclar). The restorations were polished and 7 days (baseline), 6 months, and 12 months later were evaluated according to the United States Public Health Service (USPHS) modified criteria, using clinical exam and photographics. Data were analyzed by Friedman's and Wilcoxon signed-rank tests. Results No significant differences were found between the control and experimental groups (p=0.423), and also among the follow-up periods (baseline, six months, and 12 months) (p=0.50). Regarding the retention criteria, 90% of the restoration had an alpha score in the control group. Only 10% of the restorations without biomodification (control) had a score charlie at the 12-month follow-up. None of the patients reported post-operatory sensitivity. Conclusion The NanoCsQ solution did not negatively affect the performance of the composite resin restorations after 12 months.

Conserved multiepitope vaccine constructs: A potent HIV-1 therapeutic vaccine in clinical trials

Abstract Despite the success of Antiretroviral Therapy (ART) in preventing HIV-1-associated clinical progression to AIDS, it is unable to eliminate the viral reservoirs and eradicate the HIV-1 infection. Therapeutic vaccination is an alternative approach to alter the HIV-1 infection course. It can induce effective HIV-1-specific immunity to control viremia and eliminate the need for lifelong ART. Immunological data from spontaneous HIV-1 controllers have shown that cross-reactive T-cell responses are the key immune mechanism in HIV-1 control. Directing these responses toward preferred HIV-1 epitopes is a promising strategy in therapeutic vaccine settings. Designing novel immunogens based on the HIV-1 conserved regions containing a wide range of critical T- and B-cell epitopes of the main viral antigens (conserved multiepitope approaches) supplies broad coverage of global diversity in HIV-1 strains and Human Leukocyte Antigen (HLA) alleles. It can also prevent immune induction to undesirable decoy epitopes theoretically. The efficacy of different novel HIV-1 immunogens based on the conserved and/or functional protective site of HIV-1 proteome has been evaluated in multiple clinical trials. Most of these immunogens were generally safe and able to induce potent HIV-1-specific immunity. However, despite these findings, several candidates have demonstrated limited efficacy in viral replication control. In this study, we used the PubMed and ClinicalTrial.gov databases to review the rationale of designing curative HIV-1 vaccine immunogens based on the conserved favorable site of the virus. Most of these studies evaluate the efficacy of vaccine candidates in combination with other therapeutics and/or with new formulations and immunization protocols. This review briefly describes the design of conserved multiepitope constructs and outlines the results of these vaccine candidates in the recent clinical pipeline.

Diagnostic criteria and outcome measures in randomized clinical trials on carpal tunnel syndrome: a systematic review

ABSTRACT BACKGROUND: The diagnostic criteria for carpal tunnel syndrome (CTS) lack uniformity. Moreover, because CTS is a syndrome, there is no consensus as to which signs, symptoms, clinical and complementary tests are more reproducible and accurate for use in clinical research. This heterogeneity is reflected in clinical practice. Thus, establishing effective and comparable care protocols is difficult. OBJECTIVE: To identify the diagnostic criteria and outcome measures used in randomized clinical trials (RCTs) on CTS. DESING AND SETTING: Systematic review of randomized clinical trials carried out at the Federal University of São Paulo, São Paulo, Brazil. METHODS: We searched the Cochrane Library, PubMed, and Embase databases for RCTs with surgical intervention for CTS published between 2006 and 2019. Two investigators independently extracted relevant data on diagnosis and outcomes used in these studies. RESULTS: We identified 582 studies and 35 were systematically reviewed. The symptoms, paresthesia in the median nerve territory, nocturnal paresthesia, and special tests were the most widely used clinical diagnostic criteria. The most frequently assessed outcomes were symptoms of paresthesia in the median nerve territory and nocturnal paresthesia. CONCLUSION: The diagnostic criteria and outcome measures used in RCTs about CTS are heterogeneous, rendering comparison of studies difficult. Most studies use unstructured clinical criteria associated with ENMG for diagnosis. The Boston Questionnaire is the most frequently used main instrument to measure outcomes. REGISTRATION: PROSPERO (CRD42020150965- https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=150965).

Da imaginação à neuroimagem: uma análise antropológica sobre a racionalidade do efeito placebo em ensaios clínicos / From imagination to neuroimage: An anthropological analysis on the rationality of the placebo effect in clinical trials

Resumo O efeito placebo é um ponto de passagem obrigatório para a compreensão da racionalidade envolvida nos ensaios clínicos randomizados. A partir da antropologia da ciência e da tecnologia, este artigo analisa como a noção de efeito placebo tem sido utilizada pela ciência na produção de fronteiras biossociais. Assim, enfoca fenômenos que inicialmente eram atribuídos à imaginação e analisa as consequências de novas metodologias científicas que têm reconhecido outras potencialidades desse efeito, mas tendem a privilegiar marcadores biológicos. O argumento central é que a disputa epistemológica oculta a existência múltipla do efeito placebo que pode ser reconhecida em função das diferentes práticas às quais ele confere racionalidade.

Abstract The placebo effect is an obligatory passage point to understand rationality in randomized clinical trials. From the perspective of science and technology studies, this paper analyzes how the notion of the placebo effect has been used by science in the production of biosocial borders. Thus, it will pay attention to the phenomena considered caused by imagination, and we will analyze the consequences of new methodologies that have recognized other potentialities of this effect but tend to favor biological markers. The central argument is that the epistemological dispute hides the multiple existences of the placebo effect to be recognized due to the different scientific practices to which it confers rationality.

Clinical Evaluation of a Vancomycin Dosage Strategy Based on a Serum Trough Concentration Model in Elderly Patients with Severe Pneumonia / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to evaluate the clinical benefits of a vancomycin dosage strategy based on a serum trough concentration model in elderly patients.@*METHODS@#This prospective single-center, open-label, randomized controlled trial categorized 66 elderly patients with severe pneumonia into study and control groups. The control group received vancomycin using a regimen decided by the attending physician. Meanwhile, the study group received individualized vancomycin therapy with a dosing strategy based on a serum trough concentration model. The primary endpoint was the proportion of patients with serum trough concentrations reaching the target values. The secondary endpoints were clinical response, vancomycin treatment duration, and vancomycin-associated acute kidney injury (VA-AKI) occurrence.@*RESULTS@#All patients were at least 60 years old (median age = 81 years). The proportion of patients with target trough concentration achievement (≥ 15 mg/L) with the initial vancomycin regimen was significantly higher in the study group compared to the control group (75.8% vs. 42.4%, P = 0.006). Forty-five patients (68.2%) achieved clinical success, the median duration of vancomycin therapy was 10.0 days, and VA-AKI occurred in eight patients (12.1%). However, there were no significant differences in these parameters between the two groups. The model for predicting vancomycin trough concentrations was upgraded to: serum trough concentration (mg/L) = 17.194 - 0.104 × creatinine clearance rate (mL/min) + 0.313 × vancomycin daily dose [(mg/(kg∙d)].@*CONCLUSION@#A vancomycin dosage strategy based on a serum trough concentration model can improve the proportion of patients achieving target trough concentrations in elderly patients with severe pneumonia.

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.

Analysis of the progress of clinical trials for ophthalmic drug in China, 2022 / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the progress of clinical trials for ophthalmic drugs in China in 2022 and discuss its changes with 2014 to 2021, thus providing the latest data reference for the development of new drug and the implementation of clinical trials, and a basis for decision-making.METHODS: In this cross-sectional study, we retrieved the drug clinical trials registration and information disclosure platform of National Medical Products Administration database. Drug clinical trials for eye diseases registered from January 1 to December 31, 2022 were included. Number(proportion)was used to describe the characteristics of clinical trials for ophthalmic drug, the indication, the trial phase, the efficacy and the geographical distribution.RESULTS:A total of 55 clinical trials for ophthalmic drug were included, which accounted for 1.66% of all clinical trials, showing a steady growth trend. Main drug type was chemical drugs with the highest proportion of 58.18%. The top three indications with the most clinical trials were age-related macular degeneration, myopia and dry eye. Two gene drugs emerged in 2022, and 7 drugs carried out ≥2 trials, of which atropine sulfate and recombinant anti-vascular endothelial growth factor(VEGF)humanized monoclonal antibody were the most(7 and 5 respectively). Most trials were in phase I and phase III stages, accounting for 36.36% and 27.27% respectively. The median start-up time of phase I trials in 2022 was 2.72(0.77, 3.47)mo, which was significantly shorter than 3.87(3.00, 6.30)mo of 2014～2021(Z=-2.630, P=0.009), and there were no significant differences between BE, phase II, III, IV comparing with 2014～2021(P&#x003E;0.05).CONCLUSIONS: In 2022, the number and implementation efficiency of clinical trials for ophthalmic drugs in China increased steadily. The indications are mainly fundus disease, myopia and dry eye. Most new drugs are in the early stage of research and development or close to market. Gene therapy drugs began to emerge.