Evidence-Based Guidelines and Secondary Meta-Analysis for the Use of Transcranial Direct Current Stimulation in Neurological and Psychiatric Disorders.

BACKGROUND: Transcranial direct current stimulation has shown promising clinical results, leading to increased demand for an evidence-based review on its clinical effects. OBJECTIVE: We convened a team of transcranial direct current stimulation experts to conduct a systematic review of clinical trials with more than 1 session of stimulation testing: pain, Parkinson's disease motor function and cognition, stroke motor function and language, epilepsy, major depressive disorder, obsessive compulsive disorder, Tourette syndrome, schizophrenia, and drug addiction. METHODS: Experts were asked to conduct this systematic review according to the search methodology from PRISMA guidelines. Recommendations on efficacy were categorized into Levels A (definitely effective), B (probably effective), C (possibly effective), or no recommendation. We assessed risk of bias for all included studies to confirm whether results were driven by potentially biased studies. RESULTS: Although most of the clinical trials have been designed as proof-of-concept trials, some of the indications analyzed in this review can be considered as definitely effective (Level A), such as depression, and probably effective (Level B), such as neuropathic pain, fibromyalgia, migraine, post-operative patient-controlled analgesia and pain, Parkinson's disease (motor and cognition), stroke (motor), epilepsy, schizophrenia, and alcohol addiction. Assessment of bias showed that most of the studies had low risk of biases, and sensitivity analysis for bias did not change these results. Effect sizes vary from 0.01 to 0.70 and were significant in about 8 conditions, with the largest effect size being in postoperative acute pain and smaller in stroke motor recovery (nonsignificant when combined with robotic therapy). CONCLUSION: All recommendations listed here are based on current published PubMed-indexed data. Despite high levels of evidence in some conditions, it must be underscored that effect sizes and duration of effects are often limited; thus, real clinical impact needs to be further determined with different study designs.

Neurofeedback impacts cognition and quality of life in pediatric focal epilepsy: An exploratory randomized double-blinded sham-controlled trial.

OBJECTIVE: Children with epilepsy experience cognitive deficits and well-being issues that have detrimental effects on their development. Pharmacotherapy is the standard of care in epilepsy; however, few interventions exist to promote cognitive development and to mitigate disease burden. We aimed to examine the impact of two different modalities of neurofeedback (NFB) on cognitive functioning and quality-of-life (QOL) measurements in children and adolescents with controlled focal epilepsy. The study also explored the effects of NFB on clinical outcomes and electroencephalography (EEG) quantitative analysis. METHODS: Participants (n = 44) with controlled focal epilepsy were randomized to one of three arms: sensorimotor rhythm (SMR) NFB (n = 15), slow cortical potentials (SCP) NFB (n = 16), or sham NFB (n = 13). All participants received 25 sessions of intervention. The attention switching task (AST), Liverpool Seizure Severity Scale (LSSS), seizure frequency (SF), EEG power spectrum, and coherence were measured at baseline, postintervention, and at 3-month follow-up. RESULTS: In children and adolescents with controlled focal epilepsy, SMR training significantly reduced reaction time in the AST (p = 0.006), and this was correlated with the difference of change for theta power on EEG (p = 0.03); only the SMR group showed a significant decrease in beta coherence (p = 0.03). All groups exhibited improvement in QOL (p = <0.05). CONCLUSIONS: This study provides the first data on two NFB modalities (SMR and SCP) including cognitive, neurophysiological, and clinical outcomes in pediatric epilepsy. Sensorimotor rhythm NFB improved cognitive functioning, while all the interventions showed improvements in QOL, demonstrating a powerful placebo effect in the sham group.

Impact of Therapeutic Interventions on Pain Intensity and Endogenous Pain Modulation in Knee Osteoarthritis: A Systematic Review and Meta-analysis.

OBJECTIVE: To study the impact of therapeutic interventions on pain analgesia and endogenous pain modulation in knee osteoarthritis (KOA). DESIGN: Systematic review and meta-analysis. METHODS: We searched for KOA randomized clinical trials and observational studies with data on therapeutic interventions comparing pain intensity, temporal summation (TS), and conditioned pain modulation (CPM) scores relative to control. These data were pooled as Hedge's g. To study the relationship between pain intensity and TS/CPM, we performed metaregression with 10,000 Monte-Carlo permutations. RESULTS: We reviewed 11 studies (559 participants). On studying all the interventions together, we found no significant changes in pain modulation, TS, or CPM. Our findings show that this lack of difference is likely because surgical and nonsurgical interventions resulted in contrary effects. Metaregression significantly correlated pain reduction with normalization of TS and CPM. CONCLUSIONS: We demonstrate an association between pain reduction and TS/CPM normalization. Though we cannot directly compare these interventions, the results allow us to draw hypotheses on potential practice schemas. Recovering defective endogenous pain modulation mechanisms may help establish long-term analgesia. However, to validate these paradigms as robust clinical biomarkers, further investigation into their mechanisms would be necessary. The registration number for this review is CRD42017072066.

Challenges and potential solutions for physician suicide risk factors in the COVID-19 era: psychiatric comorbidities, judicialization of medicine, and burnout.

INTRODUCTION: Suicide among physicians constitutes a public health problem that deserves more consideration. A recently performed meta-analysis and systematic review evaluated suicide mortality in physicians by gender and investigated several related risk factors. It showed that the post-1980 suicide mortality was 46% higher in female physicians than among women in the general population, while the risk in male physicians was 33% lower than among men in general, despite an overall contraction in physician mortality rates in both genders. METHODS: This narrative review was conducted by searching and analyzing articles/databases that were relevant to addressing questions raised by a prior meta-analysis and how they might be affected by COVID-19. This process included unstructured searches on Pubmed for physician suicide, burnout, judicialization of medicine, healthcare organizations, and COVID-19, and Google searches for relevant databases and medical society, expert, and media commentaries on these topics. We focus on three factors critical to addressing physician suicides: epidemiological data limitations, psychiatric comorbidities, and professional overload. RESULTS: We found relevant articles on suicide reporting, physician mental health, the effects of healthcare judicialization, and organizational involvement on physician and patient health, and how COVID-19 may impact such factors. This review addresses information sources, underreporting/misreporting of physician suicide rates, inadequate diagnosis and management of psychiatric comorbidities and the chronic effects on physicians' work capacity, and, finally, judicialization of medicine and organizational failures increasing physician burnout. We discuss these factors in general and in relation to the COVID-19 pandemic. CONCLUSIONS: We present an overview of the above factors, discuss possible solutions, and specifically address how COVID-19 may impact such factors.

Physician suicide demographics and the COVID-19 pandemic.

OBJECTIVE: To identify suicide rates and how they relate to demographic factors (sex, race and ethnicity, age, location) among physicians compared to the general population when aggravated by the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We searched U.S. databases to report global suicide rates and proportionate mortality ratios (PMRs) among U.S. physicians (and non-physicians in health occupations) using National Occupational Mortality Surveillance (NOMS) data and using Wide-ranging Online Data for Epidemiologic Research (WONDER) in the general population. We also reviewed the effects of age, suicide methods and locations, COVID-19 considerations, and potential solutions to current challenges. RESULTS: Between NOMS1 (1985-1998) and NOMS2 (1999-2013), the PMRs for suicide increased in White male physicians (1.77 to 2.03) and Black male physicians (2.50 to 4.24) but decreased in White female physicians (2.66 to 2.42). CONCLUSIONS: The interaction of non-modifiable risk factors, such as sex, race and ethnicity, age, education level/healthcare career, and location, require further investigation. Addressing systemic and organizational problems and personal resilience training are highly recommended, particularly during the additional strain from the COVID-19 pandemic.

Cost-Effectiveness Analysis to Inform Randomized Controlled Trial Design in Chronic Pain Research: Methods for Guiding Decisions on the Addition of a Run-In Period.

Introduction: Run-In (RI) periods can be used to improve the validity of randomized controlled trials (RCTs), but their utility in Chronic Pain (CP) RCTs is debated. Cost-effectiveness analysis (CEA) methods are commonly used in evaluating the results of RCTs, but they are seldom used for designing RCTs. We present a step-by-step overview to objectively design RCTs via CEA methods and specifically determine the cost effectiveness of a RI period in a CP RCT. Methods: We applied the CEA methodology to data obtained from several noninvasive brain stimulation CP RCTs, specifically focusing on (1) defining the CEA research question, (2) identifying RCT phases and cost ingredients, (3) discounting, (4) modeling the stochastic nature of the RCT, and (5) performing sensitivity analyses. We assessed the average cost-effectiveness ratios and incremental cost effectiveness ratios of varied RCT designs and the impact on cost-effectiveness by the inclusion of a RI period vs. No-Run-In (NRI) period. Results: We demonstrated the potential impact of varying the number of institutions, number of patients that could be accommodated per institution, cost and effectiveness discounts, RCT component costs, and patient adherence characteristics on varied RI and NRI RCT designs. In the specific CP RCT designs that we analyzed, we demonstrated that lower patient adherence, lower baseline assessment costs, and higher treatment costs all necessitated the inclusion of an RI period to be cost-effective compared to NRI RCT designs. Conclusions: Clinical trialists can optimize CP RCT study designs and make informed decisions regarding RI period inclusion/exclusion via CEA methods.

Male and Female Physician Suicidality: A Systematic Review and Meta-analysis.

Importance: Population-based findings on physician suicide are of great relevance because this is an important and understudied topic. Objective: To evaluate male and female physician suicide risks compared with the general population from 1980 to date and test whether there is a reduction of SMR in cohorts after 1980 compared with before 1980 via a meta-analysis, modeling studies, and a systematic review emphasizing physician suicide risk factors. Data Sources: This study uses studies retrieved from PubMed, Scielo, PsycINFO, and Lilacs for human studies published by October 3, 2019, using the search term "(((suicide) OR (self-harm) OR (suicidality)) AND ((physicians) OR (doctors)))." Databases were also searched from countries listed in articles selected for review. Data were also extracted from an existing article by other authors to facilitate comparisons of the pre-1980 suicide rate with the post-1980 changes. Study Selection: Original articles assessing male and/or female physician suicide were included; for the meta-analysis, only cohorts from 1980 to the present were included. Data Extraction and Synthesis: The preregistered systematic review and meta-analysis followed Cochrane, PRISMA, and MOOSE guidelines. Data were extracted into standardized tables per a prespecified structured checklist, and quality scores were added. Heterogeneity was tested via Q test, I2, and τ2. For pooled effect estimates, we used random-effects models. The Begg and Egger tests, sensitivity analyses, and meta-regression were performed. Proportional mortality ratios were presented when SMR data could not be extracted. Main Outcomes and Measures: Suicide SMRs for male and female physicians from 1980 to the present and changes over time (before and after 1980). Results: Of 7877 search results, 32 articles were included in the systematic review and 9 articles and data sets in the meta-analysis. Meta-analysis showed a significantly higher suicide SMR in female physicians compared with women in general (1.46 [95% CI, 1.02-1.91]) and a significantly lower suicide SMR in male physicians compared with men in general (0.67 [95% CI, 0.55-0.79]). Male and female physician SMRs significantly decreased after 1980 vs before 1980 (male physicians: SMR, -0.84 [95% CI, -1.26 to -0.42]; P < .001; female physicians: SMR, -1.96 [95% CI, -3.09 to -0.84]; P = .002). No evidence of publication bias was found. Conclusions and Relevance: In this study, suicide SMR was found to be high in female physicians and low in male physicians since 1980 but also to have decreased over time in both groups. Physician suicides are multifactorial, and further research into these factors is critical.

Transcranial direct current stimulation effects on hand sensibility as measured by an objective quantitative analysis device: a randomized single-blind sham-control crossover clinical trial.

Studies show that transcranial direct current stimulation (tDCS) can modulate somatosensory processing, but optimum parameters for tDCS effects on hand sensibility remain in question. We aimed to test the effects of anodal tDCS (atDCS) and cathodal tDCS (ctDCS) compared with sham tDCS (stDCS) of primary motor (M1) and sensory (S1) cortices on healthy subjects' hand sensibility. In this single-blind clinical trial, 30 randomized healthy volunteers received six tDCS sessions over 6 weeks: one session each of atDCS, ctDCS and stDCS over M1, and one session each of atDCS, ctDCS and stDCS over S1. Current perception threshold (CPT) was assessed using an objective quantitative analysis device (PainVision) at baseline, immediately (T0) and 30 min (T30) after each intervention. Our results showed that both atDCS and ctDCS of S1 and M1 significantly increased CPT. M1 ctDCS at T30 had the greatest effect of all M1 and S1 stimulation conditions (mean difference: 32.94%, Z: 3.12, effect size: 1.82, P < 0.001 The largest effect at S1 was for atDCS at T30 (mean difference: 29.87%, Z: 2.53, effect size: 1.72, P < 0.001. Our results are consistent with tDCS' modulatory effects on hand sensation, especially M1 ctDCS and S1 atDCS.

Transcranial Direct Current Stimulation Optimization - From Physics-Based Computer Simulations to High-Fidelity Head Phantom Fabrication and Measurements.

BACKGROUND: Transcranial direct current stimulation (tDCS) modulates neural networks. Computer simulations, while used to identify how currents behave within tissues of different conductivity properties, still need to be complemented by physical models. OBJECTIVE/HYPOTHESIS: To better understand tDCS effects on biology-mimicking tissues by developing and testing the feasibility of a high-fidelity 3D head phantom model that has sensing capabilities at different compartmental levels. METHODS: Models obtained from MRI images generated 3D printed molds. Agar phantoms were fabricated, and 18 monitoring electrodes were placed on specific phantom brain areas. RESULTS: When using rectangular electrodes, the measured and simulated voltages at the monitoring electrodes agreed reasonably well, except at excitation locations. The electric field distribution in different phantom layers appeared better confined with circular electrodes compared to rectangular electrodes. CONCLUSION: The high-fidelity 3D head model was found to be feasible and comparable with computer-based electrical simulations, with high correlation between simulated and measured brain voltages. This feasibility study supports testing to further assess the reliability of this model.

Transcranial direct current stimulation (tDCS) effects on traumatic brain injury (TBI) recovery: A systematic review.

Traumatic brain injury (TBI) is a major cause of chronic disability. Less than a quarter of moderate and severe TBI patients improved in their cognition within 5 years. Non-invasive brain stimulation, including transcranial direct current stimulation (tDCS), may help neurorehabilitation by boosting adaptive neuroplasticity and reducing pathological sequelae following TBI. METHODS: we searched MEDLINE/PubMed and Web of Science databases. We used Jadad scale to assess methodological assumptions. RESULTS: the 14 papers included reported different study designs; 2 studies were open-label, 9 were crossover randomized clinical trials (RCTs), and 3 were parallel group RCTs. Most studies used anodal tDCS of the left dorsolateral prefrontal cortex, but montages and stimulation parameters varied. Multiple studies showed improved coma recovery scales in disorders of consciousness, and improved cognition on neuropsychological assessments. Some studies showed changes in neurophysiologic measures (electroencephalography (EEG) and transcranial magnetic stimulation (TMS), correlating with clinical findings. The main methodological biases were lack of blinding and randomization reports. CONCLUSION: tDCS is a safe, non-invasive neuromodulatory technique that can be given as monotherapy but may be best combined with other therapeutic strategies (such as cognitive rehabilitation and physical therapy) to further improve clinical cognitive and motor outcomes. EEG and TMS may help guide research due to their roles as biomarkers for neuroplasticity.

A lesão cerebral traumática (TCE) é uma das principais causas de incapacidade crônica. Menos de um quarto dos pacientes com TCE moderada e grave melhoraram sua cognição dentro de cinco anos. A estimulação cerebral não invasiva, incluindo a estimulação transcraniana por corrente contínua (ETCC), pode ajudar na reabilitação neurológica, aumentando a neuroplasticidade adaptativa e reduzindo as sequelas patológicas após o TCE. MÉTODOS: pesquisamos os bancos de dados MEDLINE / PubMed e Web of Science. Usamos a escala de Jadad para avaliar os métodos utilizados nos ensaios clínicos. RESULTADOS: os 14 artigos incluídos relataram diferentes desenhos de estudo; 2 estudos foram abertos, 9 foram ensaios clínicos randomizados (ECRs) cruzados e 3 foram ECR de grupos paralelos. A maioria dos estudos utilizou a ETCC anódica do córtex pré-frontal dorsolateral esquerdo, mas os parâmetros de montagem e estimulação variaram. Múltiplos estudos mostraram melhoras nas escalas de recuperação de coma em pacientes com distúrbios da consciência e melhora da cognição. Alguns estudos mostraram alterações nas medidas neurofisiológicas (eletroencefalografia (EEG) e estimulação magnética transcraniana (EMT)), correlacionando com os achados clínicos. Os principais vieses metodológicos foram a falta de relatos de cegamento e randomização. CONCLUSÃO: a ETCC é uma técnica neuromodulatória segura e não invasiva que pode ser administrada em monoterapia, mas a utilização da ETCC parece impulsionar os resultados clínicos quando combinada com outras estratégias terapêuticas (como reabilitação cognitiva e fisioterapia). O EEG e o EMT podem ajudar a orientar a pesquisa e tambem mensurar os ganhos clínicos por serem potenciais biomarcadores da neuroplasticidade.

Optimised transcranial direct current stimulation (tDCS) for fibromyalgia-targeting the endogenous pain control system: a randomised, double-blind, factorial clinical trial protocol.

INTRODUCTION: Fibromyalgia (FM) is a common debilitating condition with limited therapeutic options. Medications have low efficacy and are often associated with adverse effects. Given that FM is associated with a defective endogenous pain control system and central sensitisation, combining interventions such as transcranial direct current stimulation (tDCS) and aerobic exercise (AE) to modulate pain-processing circuits may enhance pain control. METHODS AND ANALYSIS: A prospective, randomised (1:1:1:1), placebo-controlled, double-blind, factorial clinical trial will test the hypothesis that optimised tDCS (16 anodal tDCS sessions combined with AE) can restore of the pain endogenous control system. Participants with FM (n=148) will undergo a conditioning exercise period and be randomly allocated to one of four groups: (1) active tDCS and AE, (2) sham tDCS and AE, (3) active tDCS and non-aerobic exercise (nAE) or (4) sham tDCS and nAE. Pain inhibitory activity will be assessed using conditioned pain modulation (CPM) and temporal slow pain summation (TSPS)-primary outcomes. Secondary outcomes will include the following assessments: Transcranial magnetic stimulation and electroencephalography as cortical markers of pain inhibitory control and thalamocortical circuits; secondary clinical outcomes on pain, FM, quality of life, sleep and depression. Finally, the relationship between the two main mechanistic targets in this study-CPM and TSPS-and changes in secondary clinical outcomes will be tested. The change in the primary efficacy endpoint, CPM and TSPS, from baseline to week 4 of stimulation will be tested with a mixed linear model and adjusted for important demographic variables. ETHICS AND DISSEMINATION: This study obeys the Declaration of Helsinki and was approved by the Institutional Review Board (IRB) of Partners Healthcare under the protocol number 2017P002524. Informed consent will be obtained from participants. Study findings will be reported in conferences and peer-reviewed journal publications. TRIAL REGISTRATION NUMBER: NCT03371225.

Combining Fluoxetine and rTMS in Poststroke Motor Recovery: A Placebo-Controlled Double-Blind Randomized Phase 2 Clinical Trial.

Background. Although recent evidence has shown a new role of fluoxetine in motor rehabilitation, results are mixed. We conducted a randomized clinical trial to evaluate whether combining repetitive transcranial magnetic stimulation (rTMS) with fluoxetine increases upper limb motor function in stroke. Methods. Twenty-seven hemiparetic patients within 2 years of ischemic stroke were randomized into 3 groups: Combined (active rTMS + fluoxetine), Fluoxetine (sham rTMS + fluoxetine), or Placebo (sham rTMS + placebo fluoxetine). Participants received 18 sessions of 1-Hz rTMS in the unaffected primary motor cortex and 90 days of fluoxetine (20 mg/d). Motor function was assessed using Jebsen-Taylor Hand Function (JTHF) and Fugl-Meyer Assessment (FMA) scales. Corticospinal excitability was assessed with TMS. Results. After adjusting for time since stroke, there was significantly greater improvement in JTHF in the combined rTMS + fluoxetine group (mean improvement: -214.33 seconds) than in the placebo (-177.98 seconds, P = 0.005) and fluoxetine (-50.16 seconds, P < 0.001) groups. The fluoxetine group had less improvement than placebo on both scales (respectively, JTHF: -50.16 vs -117.98 seconds, P = 0.038; and FMA: 6.72 vs 15.55 points, P = 0.039), suggesting that fluoxetine possibly had detrimental effects. The unaffected hemisphere showed decreased intracortical inhibition in the combined and fluoxetine groups, and increased intracortical facilitation in the fluoxetine group. This facilitation was negatively correlated with motor function improvement (FMA, r2 = -0.398, P = 0.0395). Conclusion. Combined fluoxetine and rTMS treatment leads to better motor function in stroke than fluoxetine alone and placebo. Moreover, fluoxetine leads to smaller improvements than placebo, and fluoxetine's effects on intracortical facilitation suggest a potential diffuse mechanism that may hinder beneficial plasticity on motor recovery.

Principles of designing a clinical trial: optimizing chances of trial success.

PURPOSE OF REVIEW: Clinical trials are essential to advance health care and develop new therapies. In this review we discuss the underlying principles of clinical trial design with an emphasis on assessing design risks that lead to trial failure as well as negative trials. While of general interest, this is perhaps particularly timely for the neuromodulation community, given the paucity of well-designed trials in the field. We give some examples from the phantom limb pain (PLP) literature. RECENT FINDINGS: It is critical to gather as much preliminary data as possible and to know how to interpret it in order to choose an appropriate trial design. Therefore, the investigator needs to effectively assess the likely trial design risk/benefit ratio with a view to maximizing the chance of a meaningful outcome, whether this outcome rejects or fails to reject the null hypothesis. This analysis is especially important in a complex and heterogeneous disorder such as PLP, which has had many negative trials. SUMMARY: We discuss the factors pertaining to a strong trial design benefit/risk assessment, how late trial phases require greater support from preliminary data, how to design trials to minimize risks, maximize benefits, and optimize internal validity as well as the chances of a positive outcome. We highlight the need for investigators to incorporate best practice in trial design to increase the chances of success, to always anticipate unexpected challenges during the trial.

Challenges and potential solutions for physician suicide risk factors in the COVID-19 era: psychiatric comorbidities, judicialization of medicine, and burnout

Abstract Introduction Suicide among physicians constitutes a public health problem that deserves more consideration. A recently performed meta-analysis and systematic review evaluated suicide mortality in physicians by gender and investigated several related risk factors. It showed that the post-1980 suicide mortality was 46% higher in female physicians than among women in the general population, while the risk in male physicians was 33% lower than among men in general, despite an overall contraction in physician mortality rates in both genders. Methods This narrative review was conducted by searching and analyzing articles/databases that were relevant to addressing questions raised by a prior meta-analysis and how they might be affected by COVID-19. This process included unstructured searches on Pubmed for physician suicide, burnout, judicialization of medicine, healthcare organizations, and COVID-19, and Google searches for relevant databases and medical society, expert, and media commentaries on these topics. We focus on three factors critical to addressing physician suicides: epidemiological data limitations, psychiatric comorbidities, and professional overload. Results We found relevant articles on suicide reporting, physician mental health, the effects of healthcare judicialization, and organizational involvement on physician and patient health, and how COVID-19 may impact such factors. This review addresses information sources, underreporting/misreporting of physician suicide rates, inadequate diagnosis and management of psychiatric comorbidities and the chronic effects on physicians' work capacity, and, finally, judicialization of medicine and organizational failures increasing physician burnout. We discuss these factors in general and in relation to the COVID-19 pandemic. Conclusions We present an overview of the above factors, discuss possible solutions, and specifically address how COVID-19 may impact such factors.

Physician suicide demographics and the COVID-19 pandemic

Objective: To identify suicide rates and how they relate to demographic factors (sex, race and ethnicity, age, location) among physicians compared to the general population when aggravated by the coronavirus disease 2019 (COVID-19) pandemic. Methods: We searched U.S. databases to report global suicide rates and proportionate mortality ratios (PMRs) among U.S. physicians (and non-physicians in health occupations) using National Occupational Mortality Surveillance (NOMS) data and using Wide-ranging Online Data for Epidemiologic Research (WONDER) in the general population. We also reviewed the effects of age, suicide methods and locations, COVID-19 considerations, and potential solutions to current challenges. Results: Between NOMS1 (1985-1998) and NOMS2 (1999-2013), the PMRs for suicide increased in White male physicians (1.77 to 2.03) and Black male physicians (2.50 to 4.24) but decreased in White female physicians (2.66 to 2.42). Conclusions: The interaction of non-modifiable risk factors, such as sex, race and ethnicity, age, education level/healthcare career, and location, require further investigation. Addressing systemic and organizational problems and personal resilience training are highly recommended, particularly during the additional strain from the COVID-19 pandemic.

Transcranial direct current stimulation (tDCS) effects on traumatic brain injury (TBI) recovery: A systematic review / Efeitos da estimulação transcraniana por corrente contínua (ETCC) na recuperação do traumatismo cranioencefálico (TCE): uma revisão sistemática

ABSTRACT. Traumatic brain injury (TBI) is a major cause of chronic disability. Less than a quarter of moderate and severe TBI patients improved in their cognition within 5 years. Non-invasive brain stimulation, including transcranial direct current stimulation (tDCS), may help neurorehabilitation by boosting adaptive neuroplasticity and reducing pathological sequelae following TBI. Methods: we searched MEDLINE/PubMed and Web of Science databases. We used Jadad scale to assess methodological assumptions. Results: the 14 papers included reported different study designs; 2 studies were open-label, 9 were crossover randomized clinical trials (RCTs), and 3 were parallel group RCTs. Most studies used anodal tDCS of the left dorsolateral prefrontal cortex, but montages and stimulation parameters varied. Multiple studies showed improved coma recovery scales in disorders of consciousness, and improved cognition on neuropsychological assessments. Some studies showed changes in neurophysiologic measures (electroencephalography (EEG) and transcranial magnetic stimulation (TMS), correlating with clinical findings. The main methodological biases were lack of blinding and randomization reports. Conclusion: tDCS is a safe, non-invasive neuromodulatory technique that can be given as monotherapy but may be best combined with other therapeutic strategies (such as cognitive rehabilitation and physical therapy) to further improve clinical cognitive and motor outcomes. EEG and TMS may help guide research due to their roles as biomarkers for neuroplasticity.

RESUMO. A lesão cerebral traumática (TCE) é uma das principais causas de incapacidade crônica. Menos de um quarto dos pacientes com TCE moderada e grave melhoraram sua cognição dentro de cinco anos. A estimulação cerebral não invasiva, incluindo a estimulação transcraniana por corrente contínua (ETCC), pode ajudar na reabilitação neurológica, aumentando a neuroplasticidade adaptativa e reduzindo as sequelas patológicas após o TCE. Métodos: pesquisamos os bancos de dados MEDLINE / PubMed e Web of Science. Usamos a escala de Jadad para avaliar os métodos utilizados nos ensaios clínicos. Resultados: os 14 artigos incluídos relataram diferentes desenhos de estudo; 2 estudos foram abertos, 9 foram ensaios clínicos randomizados (ECRs) cruzados e 3 foram ECR de grupos paralelos. A maioria dos estudos utilizou a ETCC anódica do córtex pré-frontal dorsolateral esquerdo, mas os parâmetros de montagem e estimulação variaram. Múltiplos estudos mostraram melhoras nas escalas de recuperação de coma em pacientes com distúrbios da consciência e melhora da cognição. Alguns estudos mostraram alterações nas medidas neurofisiológicas (eletroencefalografia (EEG) e estimulação magnética transcraniana (EMT)), correlacionando com os achados clínicos. Os principais vieses metodológicos foram a falta de relatos de cegamento e randomização. Conclusão: a ETCC é uma técnica neuromodulatória segura e não invasiva que pode ser administrada em monoterapia, mas a utilização da ETCC parece impulsionar os resultados clínicos quando combinada com outras estratégias terapêuticas (como reabilitação cognitiva e fisioterapia). O EEG e o EMT podem ajudar a orientar a pesquisa e tambem mensurar os ganhos clínicos por serem potenciais biomarcadores da neuroplasticidade.