ABSTRACT This study aims to evaluate the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on inflammation, cardiac autonomic modulation, and clinical evolution of patients with COVID-19. This is a clinical, sham-controlled, randomized, and blind trial, in which 52 hospitalized individuals diagnosed with COVID-19 will participate. They will be randomized into: experimental group (usual medical treatment associated with active taVNS) and control group (usual medical treatment associated with sham taVNS). The taVNS will be performed by a neuromuscular electric stimulator (Dualpex model 071 of Quark Medical Products), with the stimulation electrode positioned on the left tragus, with alternating current, at a 30Hz frequency with 50% variation. Intensity will be adjusted to the patient’s sensory threshold, with 90-minutes-long stimulation sessions, happening twice per day for seven consecutive days, totaling 14 sessions. Interleukin-6 (IL-6) and interleukin-10 (IL-10), cortisol and C-reactive protein (CRP), blood pressure, heart rate variability (HRV) by low frequency (LF), high frequency (HF) and low and high frequency ratio (LF/HF) parameters will be evaluated before and after the intervention, as well as patients’ clinical evolution-including anxiety and depression levels-whose data will be obtained through medical records and questionnaires. A follow-up will also be performed seven and 14 days after the end of the interventions to verify the clinical evolution, including anxiety and depression levels. Memory and attention levels will be evaluated for six months.

RESUMEN El objetivo de este estudio es evaluar el efecto de la estimulación eléctrica transcutánea del nervio vago (EETNV) sobre la inflamación, la modulación autonómica cardíaca y la evolución clínica de pacientes con COVID-19. Se trata de un ensayo clínico, controlado por simulado, aleatorizado y ciego, en el que participarán 52 individuos hospitalizados diagnosticados de COVID-19, que serán aleatorizados en dos grupos de tratamiento: grupo experimental (tratamiento médico habitual asociado a la EETNV activa) o grupo control (tratamiento médico habitual asociado a la EETNV simulada). La EETNV se realizará mediante un estimulador eléctrico neuromuscular (modelo Dualpex 071 de Quark Medical Products), con el electrodo de estimulación colocado en el trago izquierdo, con corriente alterna, frecuencia de 30Hz y 50% de variación, intensidad ajustada al umbral sensorial del paciente, con una duración de 90 minutos cada sesión de estimulación, dos veces al día, durante siete días consecutivos, lo que totaliza 14 sesiones. Se evaluarán antes y después de la intervención la interleucina-6 (IL-6) y la interleucina-10 (IL-10), el cortisol y la proteína C reactiva (PCR), la presión arterial, la variabilidad de la frecuencia cardíaca por los parámetros de baja frecuencia (BF), alta frecuencia (AF) y razón de baja y alta frecuencia (BF/AF), así como la evolución clínica de los pacientes, incluidos los parámetros de ansiedad y depresión cuyos datos se obtendrán de historias clínicas y cuestionarios. También se realizará un seguimiento de 7 y 14 días tras finalizadas las intervenciones para verificar la evolución clínica, incluidos el nivel de ansiedad y de depresión, y durante seis meses se evaluará la memoria y la atención.

RESUMO O objetivo deste estudo é avaliar o efeito da estimulação elétrica transcutânea do nervo vago (EETNV) na inflamação, modulação autonômica cardíaca e evolução clínica dos pacientes com COVID-19. Trata-se de um ensaio clínico, controlado por sham, randomizado e cego, no qual participarão 52 indivíduos hospitalizados com diagnóstico de COVID-19, que serão randomizados em dois grupos de tratamento: grupo experimental (tratamento médico usual associado à EETNV ativa) ou grupo-controle (tratamento médico usual associado à EETNV sham). A EETNV será realizada por meio de um estimulador elétrico neuromuscular (modelo Dualpex 071 da Quark Medical Products), com o eletrodo de estimulação posicionado sobre o tragus esquerdo, com corrente alternada, frequência de 30Hz e variação de 50%, intensidade ajustada para o limiar sensorial do paciente, com duração de 90 minutos cada sessão de estimulação, duas vezes ao dia, durante sete dias consecutivos, totalizando 14 sessões. Serão avaliados pré e pós-intervenção o nível de interleucina-6 (IL-6) e interleucina-10 (IL-10), cortisol e proteína C reativa (PCR), pressão arterial, variabilidade da frequência cardíaca pelos parâmetros de baixa frequência (BF), alta frequência (AF) e pela razão da baixa e alta frequência (BF/AF), além de evolução clínica dos pacientes, incluindo o nível de ansiedade e depressão, cujos dados serão obtidos por meio de prontuários e questionários. Será realizado também um acompanhamento 7 e 14 dias após o término das intervenções para verificar a evolução clínica, incluindo nível de ansiedade e depressão, e durante seis meses serão avaliadas memória e atenção.

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

RESUMO JUSTIFICATIVA E OBJETIVOS: Para investigar métodos mais seguros e eficazes para o manejo da artrite reumatoide, avaliou-se o efeito do tratamento com dexametasona (DEX, 0,25mg/kg) combinado com estimulação transcraniana por corrente contínua (ETCC) sobre parâmetros comportamentais e bioquímicos de ratos submetidos a um modelo de artrite reumatoide. MÉTODOS: Trinta e seis ratos Wistar foram alocados em 4 grupos: controle+DEX (CTRL+DEX), artrite+DEX (AR+DEX), artrite+DEX+sham-ETCC (AR+DEX+sham-ETCC) e artrite+DEX+ETCC (AR+DEX+ETCC). O modelo de artrite foi induzido pela administração de complete Freund’s adjuvant (CFA) na pata. Edema na pata e a alodínia mecânica foram avaliadas por pletismômetro e teste de von Frey, respectivamente. 14 dias após injeção de CFA, ratos foram tratados por 8 dias (DEX e/ou ETCC). Atividade locomotora foi avaliada pelo teste do campo aberto. TNF-alfa (hipocampo e medula espinal) e BDNF (córtex e tronco) foram mensurados por ELISA. RESULTADOS: Nas medições pré-tratamento, ratos com artrite exibiram aumento de o inchaço articular e alodínia mecânica comparados ao grupo controle, confirmando o estabelecimento de modelo de dor crônica. Também se observou discreto efeito antinociceptivo da dexametasona combinada com ETCC no modelo de artrite. O modelo de dor induziu um aumento no comportamento de grooming e reduziu os níveis de TNF-alfa no hipocampo; estes efeitos foram revertidos nos grupos sham- e ETCC ativo. Entretanto, não foram observados efeitos da DEX ou ETCC nos níveis de BDNF no córtex cerebral ou no tronco encefálico. CONCLUSÃO: Apesar dos discretos efeitos observados, não se pode descartar a ETCC como uma abordagem terapêutica não farmacológica para o manejo da dor crônica inflamatória na artrite reumatoide.

ABSTRACT BACKGROUND AND OBJECTIVES: To pursue safer and more effective treatments for rheumatoid arthritis, the effect of dexamethasone treatment (DEX, 0.25mg/kg) combined with transcranial direct current stimulation (tDCS) in the behavior and neurochemical parameters of arthritic rats was evaluated. METHODS: Thirty-six Wistar rats were divided into four groups: control+DEX (CTRL+DEX), arthritis+DEX (RA+DEX), arthritis+DEX+sham-tDCS (RA+DEX+sham-tDCS) and arthritis+DEX+tDCS (RA+DEX+tDCS). The arthritic model (RA) was induced by complete Freund’s adjuvant (CFA) paw administration. Paw edema and mechanical allodynia were assessed by plethysmometer and von Frey apparatus, respectively. Fourteen days after the CFA injection, rats received the treatment for eight days (DEX and/or tDCS). Behavioral parameters were measured with the Open-Field test. ELISA was used to evaluate hippocampal and spinal cord tumor necrosis factor (TNF-α) levels, cerebral cortex and brainstem BDNF levels. RESULTS: In pre-treatment measurements, arthritic rats presented an increase in joint swelling and mechanical allodynia when compared to the control group, confirming chronic pain establishment. A slight antinociceptive effect of dexamethasone combined with tDCS in the pain model was observed. The pain model significantly induced an increase in the grooming behavior and a reduction in the spinal cord and hippocampal TNF-α levels; these effects were reverted in the sham- and active-tDCS-treated rats. However, no effects of DEX or tDCS were observed in the BDNF levels in the cerebral cortex and brainstem. CONCLUSION: Despite the small effect observed, tDCS treatment cannot be discarded as a non-pharmacological adjuvant technique for inflammatory chronic pain treatment.

RESUMO Introdução A estimulação transcraniana por corrente contínua (ETCC) é uma técnica não invasiva que permite a modulação da excitabilidade cortical e pode produzir alterações na plasticidade neuronal. A aplicação da ETCC tem sido recentemente associada à atividade física. Objetivos Verificar o efeito da Estimulação Transcraniana por Corrente Contínua (ETCC) em combinação com o exercício físico, caracterizando os aspectos metodológicos da técnica. Métodos Na busca em base de dados, excluíram-se estudos com animais e outras técnicas de neuromodulação, além de artigos de revisão e opinião. Foram selecionadas publicações até 2016 e a qualidade metodológica dos artigos foi verificada através da escala PEDRo. Resultados A maioria dos estudos (86%) utilizou a ETCC na área do córtex motor, com corrente anódica e montagem monocefálica (unipolar) (46,5%). A intensidade da corrente dominante foi 2mA (72%) com duração de 20 min (55,8%). O perfil dos participantes da pesquisa foi predominantemente de indivíduos com até 60 anos de idade (72,1%). Os desfechos foram favoráveis ao uso da ETCC anódica em combinação com o exercício físico. Conclusão A Estimulação Transcraniana por Corrente Contínua é uma técnica promissora quando utilizada em combinação com os os exercícios aeróbicos e anaeróbicos; entretanto, é necessário investigar o exercício concomitante. Nível de evidência II; Estudos terapêuticos investigando os resultados do tratamento (revisão sistemática dos estudos de nível II ou estudos de nível I com resultados inconsistentes).

ABSTRACT Introduction Transcranial direct-current stimulation (tDCS) is a noninvasive technique that allows the modulation of cortical excitability and can produce changes in neuronal plasticity. The application of tDCS has recently been associated with physical activity. Objectives To verify the effect of Transcranial Direct-Current Stimulation (tDCS) in combination with physical exercise, characterizing methodological aspects of the technique. Methods In the database search, studies with animals, other neuromodulation techniques and opinion and review articles were excluded. Publications up to 2016 were selected and the methodological quality of the articles was verified through the PEDro scale. Results The majority of studies (86%) used tDCS on the motor cortex area, with anodal current and the allocation of monocephalic electrodes (46.5%). The prevalent current intensity was 2mA (72%), with duration of 20min (55.8%). The profile of the research participants was predominantly of subjects aged up to 60 years (72.1%). The outcomes were favorable for the use of anodal tDCS in combination with physical exercise. Conclusion Transcranial Direct-Current Stimulation is a promising technique when used in combination with aerobic and anaerobic exercises; however, it is necessary to investigate concurrent exercise. Level of Evidence II; Therapeutic Studies Investigating the Results of Treatment (systematic review of Level II studies or Level I studies with inconsistent results).

RESUMEN Introducción La estimulación transcraneana por corriente continua (ETCC) es una técnica no invasiva que permite la modulación de la excitabilidad cortical y puede producir alteraciones en la plasticidad neuronal. La aplicación de la ETCC ha sido recientemente asociada a la actividad física. Objetivos Verificar el efecto de la Estimulación Transcraneana por Corriente Continua (ETCC) en combinación con el ejercicio físico, caracterizando los aspectos metodológicos de la técnica. Métodos En la búsqueda en base de datos, se excluyeron estudios con animales y otras técnicas de neuromodulación, además de artículos de revisión y opinión. Fueron seleccionadas publicaciones hasta 2016 y la calidad metodológica de los artículos fue verificada a través de la escala PEDRo. Resultados La mayoría de los estudios (86%) utilizó la ETCC en el área del córtex motor, con corriente anódica y montaje monocefálico (unipolar) (46,5%). La intensidad de la corriente dominante fue 2mA (72%) con duración de 20 min (55,8%). El perfil de los participantes de la investigación fue predominantemente de individuos con hasta 60 años de edad (72,1%). Los desenlaces fueron favorables al uso de la ETCC anódica en combinación con el ejercicio físico. Conclusión La Estimulación Transcraneana por Corriente Continua es una técnica alentadora cuando utilizada en combinación con los ejercicios aeróbicos y anaeróbicos; entretanto, es necesario investigar el ejercicio concomitante. Nivel de evidencia II; Estudios terapéuticos investigando los resultados del tratamiento (revisión sistemática de los estudios de nivel II o estudios de nivel I con resultados inconsistentes).

Abstract Halitosis is defined as a foul odor emanated from the oral cavity, with great impact in quality of life and social restraints. Recently, the use of Breath Alert™ in research increased significantly. Halimeter™, another portable device, is often used in clinical practice. Nevertheless, not many studies have verified the accuracy and compared the results of both devices simultaneously. Objective: To verify the accuracy of Breath Alert™ and Halimeter™ in patients without chief complaint of halitosis, using the organoleptic test (OT) as "gold standard." The second aim was to verify whether their concomitant use could enhance the diagnostic accuracy of halitosis. Material and Methods: A cross-sectional analytical study was performed. The quality of expired air of 34 subjects without chief complaint of halitosis was assessed. Two experienced examiners carried out the OT. Afterward, a third blinded examiner performed Halimeter™ (HT) and Breath Alert™ (BA) tests. Results: The OT identified halitosis in 21 subjects (62%). The area under the ROC curve (95% confidence interval) was 0.67 (0.48-0.85) and 0.54 (0.34-0.75) for HT and BA, respectively. The accuracy for HT and BA was 59% and 47%, respectively. The combined usage of HT and BA provided 11 positive results, being 9 subjects (43%) out of the total of 21 positive cases. Conclusions: Halimeter™ and Breath Alert™ were not able to diagnose halitosis in non-complainer subjects at the same level as the organoleptic examination, since their accuracy were low. Our results suggest that such portable devices are not reliable tools to assess halitosis and may neglect or misdiagnose a considerable number of patients in clinical practice.

ABSTRACT CONTEXT AND OBJECTIVE: Patients undergoing the same neuromodulation protocol may present different responses. Computational models may help in understanding such differences. The aims of this study were, firstly, to compare the performance of aphasic patients in naming tasks before and after one session of transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS) and sham, and analyze the results between these neuromodulation techniques; and secondly, through computational model on the cortex and surrounding tissues, to assess current flow distribution and responses among patients who received tDCS and presented different levels of results from naming tasks. DESIGN AND SETTING: Prospective, descriptive, qualitative and quantitative, double blind, randomized and placebo-controlled study conducted at Faculdade de Ciências Médicas da Santa Casa de São Paulo. METHODS: Patients with aphasia received one session of tDCS, TMS or sham stimulation. The time taken to name pictures and the response time were evaluated before and after neuromodulation. Selected patients from the first intervention underwent a computational model stimulation procedure that simulated tDCS. RESULTS: The results did not indicate any statistically significant differences from before to after the stimulation.The computational models showed different current flow distributions. CONCLUSIONS: The present study did not show any statistically significant difference between tDCS, TMS and sham stimulation regarding naming tasks. The patients’responses to the computational model showed different patterns of current distribution.

Background: Transcranial direct-current stimulation (tDCS) has been widely studied with the aim of enhancing local synaptic efficacy and modulating the electrical activity of the cortex in patients with neurological disorders. Objective: The purpose of the present study was to determine the effect of a single session of tDCS regarding immediate changes in spatiotemporal gait and oscillations of the center of pressure (30 seconds) in children with cerebral palsy (CP). Method: A randomized controlled trial with a blinded evaluator was conducted involving 20 children with CP between six and ten years of age. Gait and balance were evaluated three times: Evaluation 1 (before the stimulation), Evaluation 2 (immediately after stimulation), and Evaluation 3 (20 minutes after the stimulation). The protocol consisted of a 20-minute session of tDCS applied to the primary motor cortex at an intensity of 1 mA. The participants were randomly allocated to two groups: experimental group - anodal stimulation of the primary motor cortex; and control group - placebo transcranial stimulation. Results: Significant reductions were found in the experimental group regarding oscillations during standing in the anteroposterior and mediolateral directions with eyes open and eyes closed in comparison with the control group (p<0.05). In the intra-group analysis, the experimental group exhibited significant improvements in gait velocity, cadence, and oscillation in the center of pressure during standing (p<0.05). No significant differences were found in the control group among the different evaluations. Conclusion: A single session of tDCS applied to the primary motor cortex promotes positive changes in static balance and gait velocity in children with cerebral palsy.

O uso de estimulação de nervos cranianos de maneira transcutânea tem sido uma estratégia em desenvolvimento recente. Diferentes estudos apontam para resultados clínicos favoráveis no tratamento de diferentes quadros neuropsiquiátricos. Método: Revisão sistemática da literatura com base nas bibliotecas eletrônicas Medline e Embase, sem restrição de data inicial, até agosto de 2013. Os termos de busca utilizados foram [(1) trigeminal nerve stimulation OR (2) cranial nerve OR (3) trigemin* OR (4) transcutaneous VNS OR (5) transcutaneous cranial nerve stimulation] and (6) mental disorders. Resultados: Incluímos quatro estudos pré-clinicos e cinco estudos clínicos abordando estimulação do nervo trigêmeo. Todos os estudos foram abertos, com pequenas amostras, o que reduz a validade externa dos dados, refletindo a ainda incipiente atuação da técnica, apesar de promissora. Considerando-se a estimulação do nervo vago, três artigos avaliaram aspectos fisiológicos em voluntários saudáveis e um artigo estudou pacientes com epilepsia. Conclusão: As estratégias de estimulação transcutânea de nervos cranianos, apesar de incipiente, tem demonstrado resultados clínicos favoráveis no tratamento de distúrbios neuropsiquiátricos.

We reviewed trigeminal nerve stimulation (TNS) and transcutaneous vagus nerve stimulation (tVNS). All techniques have shown preliminary promising results, although the results are mixed. Method: We performed a systematic review of the Medline and Embase databases, with no constraint to dates, through June 2013. The keywords were [(1) trigeminal nerve stimulation OR (2) cranial nerve OR (3) trigemin* OR (4) transcutaneous VNS OR (5) transcutaneous cranial nerve stimulation] and (6) mental disorders. Results: We included four preclinical and clinical five studies on TNS. All clinical data were based on open-label studies with small samples, which diminished the external validity of the results, thus reflecting the modest impact of TNS in current clinical practice. Of the tVNS clinical trials, three assessed physiological features in healthy volunteers, and one examined patients with epilepsy. Conclusion: TNS and tVNS improve treatment of particular neuropsychiatric disorders such as depression.

Solid organ transplantation has greatly improved survival in children with end-stage disease, becoming one of the main treatment options in this population. Nonetheless, there are significant challenges associated with validating and optimizing the effects of these interventions in clinical trials. Therefore, we reviewed the main issues related to conducting clinical transplantation research in children. We divided these challenges into three different categories: (i) challenges related to surgical techniques and anesthetic procedures, (ii) challenges related to post-transplant care and (iii) challenges specific to a particular population group and disease type. Some of the observed burdens for clinical research in this field are related to the limitations of conducting studies with a placebo or sham procedure, determining the standard of care for a control group, low prevalence of cases, ethical concerns related to use of a placebo control group and lack of generalizability from animal studies and clinical trials conducted in adult populations. To overcome some of these barriers, it is necessary to utilize alternative clinical trial designs, such as observational studies or non-inferiority trials, and to develop multicenter collaborations to increase the recruitment rate. In conclusion, the lack of robust data related to pediatric transplantation remains problematic, and further clinical trials are needed to develop more efficacious and safer treatments.

CONTEXTO E OBJETIVO: Estudos prévios em animais e humanos mostram que a estimulação transcraniana por corrente contínua pode induzir neuroplasticidade significante e duradoura e pode melhorar a recuperação de linguagem na afasia. O objetivo do estudo foi descrever uma coorte de pacientes com afasia após acidente vascular cerebral que foi tratada com estimulação transcraniana por corrente contínua. TIPO DO ESTUDO E LOCAL: Estudo de coorte único prospectivo realizado em um hospital público universitário. MÉTODO: Dezenove pacientes com afasia crônica receberam 10 sessões de estimulação transcraniana por corrente contínua com duração de 20 minutos de cada, corrente de 2 mA em dias consecutivos (anodo posicionado em área supraorbital e catodo no cortes motor contraleral). Foram analisadas as seguintes variáveis antes e depois de 10 sessões de neuromodulação: compreensão de linguagem oral, cópia, ditado, leitura, escrita, nomeação e fluência verbal. RESULTADOS: Não houve efeitos adversos no estudo. Encontramos diferença estatisticamente significante pré e pós-estimulação para compreensão de frases simples (P = 0.034), nomeação (P = 0.041) e fluência verbal para nomes de animais (P = 0.038). Houve melhora no desempenho em três tarefas após estimulação. CONCLUSÃO: Observamos que a excitabilidade no córtex motor primário através de estimulação transcraniana por corrente contínua está associada a efeitos em diferentes aspectos da linguagem, além de contribuir para futuras testagens em estudos randomizados.

CONTEXT AND OBJECTIVE: Previous animal and human studies have shown that transcranial direct current stimulation can induce significant and lasting neuroplasticity and may improve language recovery in patients with aphasia. The objective of the study was to describe a cohort of patients with aphasia after stroke who were treated with transcranial direct current stimulation. DESIGN AND SETTING: Prospective cohort study developed in a public university hospital. METHODS: Nineteen patients with chronic aphasia received 10 transcranial direct current stimulation sessions lasting 20 minutes each on consecutive days, using a current of 2 mA. The anode was positioned over the supraorbital area and the cathode over the contralateral motor cortex. The following variables were analyzed before and after the 10 neuromodulation sessions: oral language comprehension, copying, dictation, reading, writing, naming and verbal fluency. RESULTS: There were no adverse effects in the study. We found statistically significant differences from before to after stimulation in relation to simple sentence comprehension (P = 0.034), naming (P = 0.041) and verbal fluency for names of animals (P = 0.038). Improved scores for performing these three tasks were seen after stimulation. CONCLUSIONS: We observed that excitability of the primary motor cortex through transcranial direct current stimulation was associated with effects on different aspects of language. This can contribute towards future testing in randomized controlled trials.

Os ensaios clínicos controlados e randomizados (ECCR) são considerados o padrão ouro da medicina baseada em evidências na atualidade, sendo importantes para direcionar a conduta médica através de observações científicas consistentes. Passos como seleção dos pacientes, randomização e cegamento são fundamentais na realização de um ECCR e apresentam algumas dificuldades extras nos ensaios que envolvem procedimentos cirúrgicos, como é comum na Ortopedia. O objetivo deste artigo é destacar e discutir algumas dificuldades e eventuais limitações dos ECCR na área cirúrgica.

Randomized controlled clinical trials (RCTs) are considered to be the gold standard for evidence-based medicine nowadays, and are important for directing medical practice through consistent scientific observations. Steps such as patient selection, randomization and blinding are fundamental for conducting an RCT, but some additional difficulties are presented in trials that involve surgical procedures, as in common in orthopedics. The aim of this article was to highlight and discuss some difficulties and possible limitations on RCTs within the field of surgery.

Randomized clinical trials are considered to be the gold standard of evidence-based medicine nowadays. However, it is important that we point out some limitations of randomized clinical trials relating to surgical interventions. There are limitations that affect the external and internal validity of many surgical study designs. Some limitations can be bypassed, but can make it more difficult for the study to be carried out. Other limitations cannot be bypassed. When it is intended to extrapolate the result of a randomized clinical trial, the premise is that the performed or to be performed intervention will be similar wherever applied and/or for every doctor using it. However, no matter how standardized the technique may be, the results are not similar for all surgeons, which implies a significant limitation to surgical randomized clinical trials concerning external validity. When considering the various limitations presented for performing surgical trials capable of generating scientific evidence within the patterns currently proposed in the evidence level classifications of medical publications, it is necessary to rethink whether those scientific evidence levels are similarly applicable to surgical works and to nonsurgical trials. We currently live in a time of supposed ''inferiority'' of surgical scientific works under the optics of the current quality criteria for a ''suitable'' clinical trial

Motor impairment following stroke is a leading cause of disability in adults. Despite advances in motor rehabilitation techniques, many adult stroke survivors never approach full functional recovery. Intriguingly, children exhibit better rehabilitation outcomes when compared to adults suffering from comparable brain injuries, yet the reasons for this remain unclear. A common explanation is that neuroplasticity in adults is substantially limited following stroke, thus constraining the brain's ability to reorganize in response to neurological insult. This explanation, however, does not suffice for there is much evidence suggesting that neuroplasticity in adults is not limited following stroke. We hypothesize that diminished functional recovery in adults is in part due to inhibitory neuronal interactions, such as transcallosal inhibition, that serve to optimize motor performance as the brain matures. Following stroke, these inhibitory interactions pose rigid barriers to recovery by inhibiting activity in the affected regions and hindering recruitment of compensatory pathways. In contrast, children exhibit better rehabilitation outcomes in part because they have not fully developed the inhibitory interactions that impede functional recovery in adults. We suggest that noninvasive brain stimulation can be used in the context of motor rehabilitation following stroke to reduce the effects of existing inhibitory connections, effectively returning the brain to a state that is more amenable to rehabilitation. We conclude by discussing further research to explore this hypothesis and its implications.