Efficacy and safety of nitazoxanide in treating SARS-CoV-2 infection: a systematic review and meta-analysis of blinded, placebo-controlled, randomized clinical trials.

PURPOSE: Nitazoxanide is a broad-spectrum antiparasitic that has been tested for COVID-19 due to its anti-inflammatory effects and in vitro antiviral activity. This study synthesized the best evidence on the efficacy and safety of nitazoxanide in COVID-19. METHODS: Searches for studies were performed in peer-reviewed and grey-literature from January 1, 2020 to May 23, 2022. The following elements were used to define eligibility criteria: (1) Population: individuals with COVID-19; (2) Intervention: nitazoxanide; (3) Comparison: placebo; (4) Outcomes: primary outcome was death, and secondary outcomes were viral load, positive RT-PCR status, serum biomarkers of inflammation, composite measure of disease progression (ICU admission or invasive mechanical ventilation), and any adverse events; (5) Study type: blinded, placebo-controlled, randomized clinical trials (RCTs). Treatment effects were reported as relative risk (RR) for dichotomous variables and standardized mean difference (SMD) for continuous variables with 95% confidence intervals (CI). RESULTS: Five blinded, placebo-controlled RCTs were included and enrolled individuals with mild or moderate SARS-CoV-2 infection. We found no difference between nitazoxanide and placebo in reducing viral load (SMD = - 0.16; 95% CI - 0.38 to 0.05) and the frequency of positive RTP-PCR results (RR = 0.92; 95% CI 0.81 to 1.06). In addition, there was no decreased risk for disease progression (RR = 0.63; 95% CI 0.38 to 1.04) and death (RR = 0.81; 95% CI 0.36 to 1.78) among patients receiving nitazoxanide. Patients with COVID-19 treated with nitazoxanide had decreased levels of white blood cells (SMD = - 0.15; 95% - 0.29 to - 0.02), lactate dehydrogenase (LDH) (SMD - 0.32; 95% - 0.52 to - 0.13), and D-dimer (SMD - 0.49; 95% CI - 0.68 to - 0.31) compared to placebo, but the magnitude of effect was considered small to moderate. CONCLUSION: This systematic review showed no evidence of clinical benefits of the use of nitazoxanide to treat patients with mild or moderate COVID-19. In addition, we found a reduction in WBC, LDH, and D-dimer levels among nitazoxanide-treated patients, but the effect size was considered small to moderate.

Lições da pandemia de Covid-19: um estudo quali-quantitativo com estudantes de Medicina e médicos recém-formados / Lessons from the Covid-19 pandemic: a quali-quantitative study with newly graduated doctors and medical students

Resumo: Introdução: A pandemia de Covid-19 impactou negativamente a saúde mental de médicos e estudantes de Medicina. Muito tem sido discutido sobre as lições aprendidas, no que se refere a aspectos clínicos, de diagnóstico, tratamento e prevenção. Entretanto, os médicos são treinados para o cuidado dos pacientes, o que envolve técnica e humanidade. Objetivo: Este estudo apresenta e discute as lições e reflexões aprendidas por internos de Medicina e médicos recém-formados durante a pandemia de Covid-19. Método: Trata-se de um estudo quali-quantitativo realizado durante a segunda quinzena de setembro de 2020 (seis meses após o início da pandemia) por meio de formulário em plataforma digital. Todos os alunos do internato e todos os médicos formados desde 2018 nas três faculdades de Medicina de Sergipe foram convidados a participar da pesquisa. Resultado: Obtiveram-se 148 questionários respondidos, dos quais quatro não continham respostas nos campos abertos. Quanto ao estágio de formação universitária, 36,5% eram recém-formados (n = 54), dos quais 90,7% trabalharam na linha de frente do atendimento aos pacientes com Covid-19. Ao serem questionados sobre os principais aprendizados que a pandemia havia trazido, 41 respostas estiveram voltadas para a paciência, a imprevisibilidade do futuro e a resiliência no enfrentamento das adversidades. Aproximadamente 42% (n = 62) dos participantes conheciam ao menos uma pessoa que faleceu por Covid-19, e isso se associou à necessidade de aproveitar o tempo, a vida e as pessoas (p = 0,009). Um total de 34 respostas (23%) demonstrou uma atitude positiva de reaprendizado e esperança quando os participantes foram perguntados sobre como imaginavam o trabalho e o ensino médico após pandemia. A necessidade de um retorno cauteloso foi citada em 34 (23%) respostas. Conclusão: Os estudantes de Medicina e os médicos recém-formados relataram aprendizados relacionados à paciência e resiliência. A perda de familiares e amigos por Covid-19 esteve relacionada à necessidade de aproveitar o momento presente.

Abstract: Introduction: The COVID-19 pandemic has affected the mental health of doctors and medical students. There has been plenty of discussion about the lessons learned, in relation to clinical aspects, diagnosis, treatment and prevention. However, doctors are trained in patient care, which involves technique and humanity. Objective: Presentation and discussion of lessons learned from the COVID-19 pandemic for medical interns and newly graduated doctors. Method: This is a quali-quantitative study performed in the second half of September 2020 (six months after the start of the pandemic) using a digital platform. All medical internship students and all physicians graduated since 2018 from the three medical schools in Sergipe-NE-Brazil were invited to participate. Result: 148 forms were obtained, and four of them did not contain answers in the open fields. As regards the university training internship, 36.5% were newly graduated physicians (n=54), of which 90.7% worked on the front line of care for patients with COVID-19. When asked about the main lessons that the pandemic brought, 41 responses referred to patience, unpredictability of the future and resilience in facing the adversities of the pandemic. About 42% (n=62) of the participants knew at least one person who died of COVID-19, and this was associated with the need to enjoy time, life and people (p=0.09). A total of 34 participants (23%) responded with a positive attitude of relearning and hope when asked about how they imagined work and medical education after the pandemic. The need for a cautious return was cited in 34 (23%) responses. Conclusion: Newly qualified doctors and medical students reported learnings related to patience and resilience. The loss of family and friends by COVID-19 was associated with the need to seize the moment.

Recommendations by the Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and the Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) on vaccination in general and specifically against SARS-CoV-2 for patients with demyelinating diseases of the central nervous system.

The Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) provide recommendations in this document for vaccination of the population with demyelinating diseases of the central nervous system (CNS) against infections in general and against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. We emphasize the seriousness of the current situation in view of the spread of COVID-19 in our country. Therefore, reference guides on vaccination for clinicians, patients, and public health authorities are particularly important to prevent some infectious diseases. The DCNI/ABN and BCTRIMS recommend that patients with CNS demyelinating diseases (e.g., MS and NMOSD) be continually monitored for updates to their vaccination schedule, especially at the beginning or before a change in treatment with a disease modifying drug (DMD). It is also important to note that vaccines are safe, and physicians should encourage their use in all patients. Clearly, special care should be taken when live attenuated viruses are involved. Finally, it is important for physicians to verify which DMD the patient is receiving and when the last dose was taken, as each drug may affect the induction of immune response differently.

Recommendations by the Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and the Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) on vaccination in general and specifically against SARS-CoV-2 for patients with demyelinating diseases of the central nervous system / Recomendações do Departamento Científico de Neuroimunologia da Academia Brasileira de Neurologia (DCNI/ABN) e do Comitê Brasileiro de Tratamento e Pesquisa em Esclerose Múltipla e Doenças Neuroimunológicas (BCTRIMS) sobre vacinação em geral e contra a SARS-CoV-2 para pacientes com doenças desmielinizantes do sistema nervoso central

ABSTRACT The Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) provide recommendations in this document for vaccination of the population with demyelinating diseases of the central nervous system (CNS) against infections in general and against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. We emphasize the seriousness of the current situation in view of the spread of COVID-19 in our country. Therefore, reference guides on vaccination for clinicians, patients, and public health authorities are particularly important to prevent some infectious diseases. The DCNI/ABN and BCTRIMS recommend that patients with CNS demyelinating diseases (e.g., MS and NMOSD) be continually monitored for updates to their vaccination schedule, especially at the beginning or before a change in treatment with a disease modifying drug (DMD). It is also important to note that vaccines are safe, and physicians should encourage their use in all patients. Clearly, special care should be taken when live attenuated viruses are involved. Finally, it is important for physicians to verify which DMD the patient is receiving and when the last dose was taken, as each drug may affect the induction of immune response differently.

RESUMO O DC de Neuroimunologia da ABN e o BCTRIMS trazem, nesse documento, as recomendações sobre vacinação da população com doenças desmielinizantes do sistema nervoso central (SNC) contra infecções em geral e contra o coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2), causador da COVID-19. Destaca-se a gravidade do atual momento frente ao avanço da COVID-19 em nosso País, o que torna mais evidente e importante a criação de guia de referência para orientação aos médicos, pacientes e autoridades de saúde pública quanto à vacinação, meio efetivo e seguro no controle de determinadas doenças infecciosa. O DCNI/ABN e o BCTRIMS recomendam que os pacientes com doenças desmielinizantes do SNC (ex., EM e NMOSD) sejam constantemente monitorados, quanto a atualização do seu calendário vacinal, especialmente, no início ou antes da mudança do tratamento com uma droga modificadora de doença (DMD). É importante também salientar que as vacinas são seguras e os médicos devem estimular o seu uso em todos os pacientes. Evidentemente, deve ser dada especial atenção às vacinas com vírus vivos atenuados. Por fim, é importante que os médicos verifiquem qual DMD o paciente está em uso e quando foi feita a sua última dose, pois cada fármaco pode interagir de forma diferente com a indução da resposta imune.

Miller Fisher Syndrome in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Systematic Review.

BACKGROUND AND PURPOSE: Miller Fisher syndrome (MFS) is a subtype of Guillain-Barré syndrome characterized by the triad of ophthalmoparesis, areflexia, and ataxia. Although cases of MFS have been associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, no studies have synthesized the clinical characteristics of patients with this condition. METHODS: In this rapid systematic review, we searched the PubMed database to identify studies on MFS associated with SARS-CoV-2 infection. RESULTS: This review identified 11 cases, of whom 3 were hospitalized with motor and/or sensory polyneuropathy as the first sign of SARS-CoV-2 infection. SARS-CoV-2 RNA was not detected in analyses of cerebrospinal fluid, suggesting a mechanism of immune-mediated injury rather than direct viral neurotropism. However, antiganglioside antibodies were found in only two of the nine patients tested. It is possible that target antigens other than gangliosides are involved in MFS associated with SARS-CoV-2 infection. CONCLUSIONS: The present patients exhibited clinical improvement after being treated with intravenous immunoglobulin. Although rare, patients with SARS-CoV-2 infection may present neurological symptoms suggestive of MFS. Early recognition of the MFS clinical triad is essential for the timely initiation of treatment.

Efficacy and safety of hydroxychloroquine as pre-and post-exposure prophylaxis and treatment of COVID-19: A systematic review and meta-analysis of blinded, placebo-controlled, randomized clinical trials.

BACKGROUND: Hydroxychloroquine (HCQ) is an anti-malarial and immunomodulatory drug considered a potential candidate for drug repurposing in COVID-19 due to their in vitro antiviral activity against SARS-CoV-2. Despite the potential antiviral effects and anti-inflammatory profile, the results based on clinical studies are contradictory. Therefore, the quality of the decision-making process from meta-analyses summarizing the available evidence selecting studies with different designs and unblinded trials is limited. The aim of this study was to synthesize the best evidence on the efficacy and safety of HCQ as pre-and post-exposure prophylaxis and treatment of non-hospitalized and hospitalized patients with COVID-19. METHODS: Searches were performed in PubMed, Web of Science, Embase, Lilacs, the website ClinicalTrials.gov and the preprint server medRxiv from January 1, 2020 to May 17, 2021. The following elements were used to define eligibility criteria: (1) Population: individuals at high-risk of exposure to SARS-CoV-2 (pre-exposure), individuals who had close contact with a positive or probable case of COVID-19 (post-exposure), non-hospitalized patients with COVID-19 and hospitalized patients with COVID-19; (2) Intervention: HCQ; (3) Comparison: placebo; (4) Outcomes: incidence of SARS-CoV-2 infection, need for hospitalization, length of hospital stay, need for invasive mechanical ventilation (MV), death, and adverse events; and (5) Study type: blinded, placebo-controlled, randomized clinical trials (RCTs). Risk of bias was judged according to the Cochrane guidelines for RCTs. Treatment effects were reported as relative risk (RR) for dichotomous variables and mean difference (MD) for continuous variables with 95% confidence intervals (CI). We used either a fixed or random-effects model to pool the results of individual studies depending on the presence of heterogeneity. The GRADE system was used to evaluate the strength of evidence between use of HCQ and the outcomes of interest. FINDINGS: Fourteen blinded, placebo-controlled RCTs were included in this meta-analysis. Four trials (1942 patients: HCQ = 1271; placebo = 671) used HCQ as a prophylactic medication pre-exposure to COVID-19, two (1650 patients: HCQ = 821; placebo = 829) as a prophylactic medication post-exposure to COVID-19, three (1018 patients: HCQ = 497; placebo = 521) as treatment for non-hospitalized patients, and five (1138 patients: HCQ = 572; placebo = 566) as treatment for hospitalized patients with COVID-19. We found no decreased risk of SARS-CoV-2 infection among individuals receiving HCQ as pre-exposure (RR = 0.90; 95% CI 0.46 to 1.77) or post-exposure (RR = 0.96; 95% CI 0.72 to 1.29) prophylaxis to prevent COVID-19. There was no significant decreased risk of hospitalization for outpatients with SARS-CoV-2 infection (RR = 0.64; 95% CI 0.33 to 1.23) and no decreased risk of MV (RR = 0.81; 95% CI 0.49 to 1.34) and death (RR = 1.05; 95% CI 0.62 to 1.78) among hospitalized patients with COVID-19 receiving HCQ. The certainty of the results on the lack of clinical benefit for HCQ was rated as moderate. Moreover, our results demonstrated an increased risk for any adverse events and gastrointestinal symptoms among those using HCQ. INTERPRETATION: Available evidence based on the results of blinded, placebo-controlled RCTs showed no clinical benefits of HCQ as pre-and post-exposure prophylaxis and treatment of non-hospitalized and hospitalized patients with COVID-19. FUNDING: There was no funding source.

First Report of SARS-CoV-2 Detection in Cerebrospinal Fluid in a Child With Guillain-Barré Syndrome.

Underlying mechanisms on the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and neurologic complications are still poorly understood. Cases of Guillain-Barré Syndrome (GBS) have been linked to the SARS-CoV-2 infection as the result of dysregulated immune response with damage in neuronal tissues. In the current report, we present the first pediatric case of GBS with detection of SARS-CoV-2 in the cerebrospinal fluid (CFS). This unique case of COVID-19-associated GBS with detection of SARS-CoV-2 RNA in the CSF indicates direct viral involvement inducing peripheral nerve inflammation.

Mental health and illness of medical students and newly graduated doctors during the pandemic of SARS-Cov-2/COVID-19.

INTRODUCTION: SARS-Cov-2 virus pandemic causes serious emotional consequences. It has occurred widespread medical courses suspension, and graduations were anticipated. Field hospitals, set up to treat patients with mild to moderate COVID-19, were the main workplaces of newly graduated doctors. OBJECTIVE: To assess the impact of SARS-Cov-2/COVID-19 pandemic on mental health of medical interns and newly graduated doctors. METHOD: This is a cross-sectional study performed using a digital platform. Links to forms were sent in two moments: moment 1 (M1), at the beginning of the pandemic, in the first half of April/2020 and moment 2 (M2), after six months of pandemic, in the second half of September/2020. All students from the medical internship and all doctors graduated since 2018 from the three medical schools in Sergipe-NE-Brazil were invited. RESULTS: 335 forms were answered in April and 148 in September. In M1 88.9% considered themselves exposed to excess of information about COVID-19, which was associated with anxiety symptoms (p = 0.04). Long family physical distance was also associated with these symptoms, as increased appetite (p = 0.01), feeling shortness of breath (p = 0.003) and sweating (p = 0.007). Fear of acquire COVID-19 was reported as intense by almost half of participants, and of transmitting by 85.7% in M1. In M2 41.2% reported the death of friends or relatives. Psychiatric illness was described by 38.5% and psychotropic drugs use by 30.1% in M1, especially those who lived alone (p = 0.03) and the single ones (p = 0.01). Alcohol intake was reported by 54.3%, and among doctors graduated in 2020 it increased from 50% in M1 to 85% in M2 (p = 0.04). CONCLUSION: The pandemic had a negative impact on the mental health of medical students and newly graduated doctors. Exposure to excessive COVID-19 information and family physical distance were associated to anxiety symptoms. Among doctors graduated in 2020, alcohol intake increased during pandemic evolution.

Restless legs syndrome in Parkinson's disease: clinical characteristics and biochemical correlations / Síndrome das pernas inquietas na doença de Parkinson: características clínicas e correlações bioquímicas

Restless legs syndrome (RLS) is a neurological disorder that responds to dopaminergic drugs, indicating a common pathophysiology with Parkinson's disease (PD). The prevalence of RLS was estimated in a group of PD patients and its clinical and biochemical characteristics were analysed. Forty-eight patients with PD were evaluated into two groups, with and without RLS. Clinical characteristics assessed in both groups were age, gender, duration of PD, Hoehn and Yahr, and Schwab and England scales. Laboratory variables such as hemoglobin, s-iron, s-ferritin and creatinine were obtained. The prevalence of RLS was 18.75 percent. No significant differences regarding clinical variables and biochemical parameters were observed. The high prevalence of RLS found in PD patients suggests the concept of a common etiological link and it seems that secondary causes did not play a central role in the pathophysiology of RLS in this group of parkinsonian patients.

A síndrome das pernas inquietas (SPI) é um distúrbio sensitivo-motor que responde aos agentes dopaminérgicos, demonstrando uma possível semelhança fisiopatológica com a doença de Parkinson (DP). Foi avaliada a prevalência da SPI em um grupo de pacientes com DP e suas características clínicas e laboratoriais. Quarenta e oito pacientes diagnosticados com DP foram divididos em dois grupos: com e sem SPI. Características clínicas como idade, sexo, duração da DP, escalas de Hoehn e Yahr, e Schwab e England e achados bioquímicos como hemoglobina, ferro sérico, ferritina sérica e creatinina foram obtidos. A freqüência da SPI foi de 18,75 por cento. Não se observaram diferenças estatisticamente significativas quanto às características clínicas e aos achados bioquímicos. A alta prevalência de SPI encontrada em pacientes com DP sugere associação entre essas duas doenças. É provável que causas secundárias não exerçam papel central na fisiopatologia da SPI nesse grupo de pacientes parkinsonianos.

Restless legs syndrome in Parkinson's disease: clinical characteristics and biochemical correlations.

Restless legs syndrome (RLS) is a neurological disorder that responds to dopaminergic drugs, indicating a common pathophysiology with Parkinson's disease (PD). The prevalence of RLS was estimated in a group of PD patients and its clinical and biochemical characteristics were analysed. Forty-eight patients with PD were evaluated into two groups, with and without RLS. Clinical characteristics assessed in both groups were age, gender, duration of PD, Hoehn and Yahr, and Schwab and England scales. Laboratory variables such as hemoglobin, s-iron, s-ferritin and creatinine were obtained. The prevalence of RLS was 18.75%. No significant differences regarding clinical variables and biochemical parameters were observed. The high prevalence of RLS found in PD patients suggests the concept of a common etiological link and it seems that secondary causes did not play a central role in the pathophysiology of RLS in this group of parkinsonian patients.