Chronic Mercury Exposure and GSTP1 Polymorphism in Munduruku Indigenous from Brazilian Amazon.

Genetic polymorphisms may be involved with mercury levels and signs and symptoms of intoxication from this exposure. Therefore, the aims were to describe the frequency of the GSTP1 polymorphism and to evaluate its effects on mercury levels and neurological signs in three Munduruku indigenous villages in the Brazilian Amazon. One-hundred-and-seven indigenous (over 12 years old) were included and genotyped (rs1695) using a TaqMan validated assay. Then, associations were evaluated by binary logistic regression, using odds ratios (OR) and 95% confidence intervals (CI). Mean age was 27.4 ± 13.9 years old, 52.3% were male, mean hair mercury concentration was 8.5 ± 4.3, exceeding the reference limit (≥6.0 µg/g), and were different among the three villages: 13.5 ± 4.6 µg/g in Sawré Aboy, 7.4 ± 2.3 µg/g in Poxo Muybu and 6.9 ± 3.5 µg/g in Sawré Muybu. The minor allele frequency of GSTP1 G was significantly different among the villages: 57% Sawré Muybu, 21% Poxo Muybu and 15% Sawré Aboy. Finally, after adjustment, GSTP1 GG and GA genotypes were associated with lower levels of Hg (OR = 0.13; CI95% = 0.03-0.49) and abnormal somatosensory signs (OR = 3.7; 95%IC = 1.5-9.3), respectively. In conclusion, monitoring this population is imperative to identify individuals at higher risk of developing signs of chronic mercury exposure based on the genetic profile.

Jornada do paciente com lombalgia crônica no Brasil: uma revisão semi-sistemática sobre a melhor abordagem / Patient journey for those with chronic low back pain in Brazil: a semi-systematic review on the best approach

Histórico -O tratamento de pacientes com lombalgia crônica (LC) em muitos países, incluindo o Brasil, é um grande desafio no nível de atendimento primário e especializado. Além disso, as informações sobre epidemiologia e tratamento de pacientes com LC são escassas. O objetivo principal desta revisão semi-sistemática foi a construção de evidências locais sobre a prevalência e o padrão de tratamento da LC. Métodos: Esta revisão semi-sistemática utilizou Medline, Embase e Biosis via plataforma Ovid e recursos adicionais (Google, Google Scholar, Banco de dados de incidência e prevalência, Organização Mundial da Saúde, Ministério da Saúde do Brasil e informações anedóticas de especialistas locais) para identificar literatura relevante entre 2002 e 2020 para mapear a jornada do paciente. Artigos de texto completos e originais do Brasil em inglês contendo dados sobre pontos de contato predefinidos na jornada do paciente (conscientização, triagem, diagnóstico, tratamento, adesão e controle) foram selecionados. Os dados foram obtidos usando uma média simples ou ponderada, conforme aplicável para os componentes da jornada do paciente. Resultados: De 297 registros, incluindo os fornecidos por especialistas locais, oito estudos foram incluídos para análise. A conscientização da LC e da LC-NeP foi de 30,4% e 12%, respetivamente. De acordo com estudos publicados, a adesão e o controle dos sintomas dos pacientes foram estimados com percentual semelhante de 38% e 18%, respetivamente para a LC e a LC-NeP. A prevalência de LC-NeP (3,6%) foi menor que a de LC (20,6%). Com exceção de uma porcentagem comparável da população tratada, para LC (39,1%) e LC-NeP (38%), a porcentagem de pontos de contato restantes foi maior no caso de LC do que no LC-NeP, o que implicava uma melhora no trajeto do paciente para a LC. Conclusão: O estudo destaca a necessidade de melhorar os resultados dos pacientes em nível nacional, medindo esses pontos de contato da jornada do paciente. O resultado deste estudo baseado em evidências é importante para preencher a lacuna de conhecimento do paciente com LC. Portanto, recomenda-se garantir a educação médica contínua, a conscientização do paciente e a restruturação do sistema de saúde brasileiro, ao mesmo tempo em que adota novas práticas sobre o gerenciamento da dor. [au]

Background: Managing patients with chronic low back pain (CLBP) in many countries, including Brazil, is a major challenge at the primary and specialty care level. Moreover, the information about epidemiology and patient management with CLBP is sparse. The primary objective of this semi-systematic review was to build local evidence about the prevalence and management pattern of CLBP. Methods: This semi-systematic review used Medline, Embase, and Biosis via Ovid the platform and additional resources (Google, Google Scholar, Incidence and Prevalence Database, World Health Organization, Brazilian Ministry of Health, and anecdotal information from local experts) to identify relevant literature between 2002­2020 to map the patient journey. Original full-text articles from Brazil in English containing data on pre-defined patient journey touchpoints (awareness, screening, diagnosis, treatment, adherence, and control) were screened. Data were synthesized using a simple or weighted mean, as applicable for patient journey components. Results. Of 297 records including those provided by local experts, eight studies were included for analysis. Awareness of CLBP and CLBP-NeP was 30.4% and 12%, respectively. According to published studies, adherence and symptoms control of patients was estimated with a similar percentage of 38% and 18%, respectively for CLBP and CLBP-NeP. CLBP-NeP prevalence (3.6%) was lower than that of CLBP (20.6%). Except for a comparable percentage of the treated population, for CLBP (39.1%) and CLBP-NeP (38%), the percentage of remaining touchpoints are higher in the case of CLBP than in CLBP-NeP, implying an improved patient journey for CLBP. Conclusion: The study highlights the usefulness to improve patient outcomes at the national level by measuring these mapping patient journey touchpoints. The outcome of this evidence-based study was fruitful to bridges the know-do gap in CLBP patients. Therefore, it is recommended to ensure continuing medical education, patient awareness, and health system preparedness while embracing the emerging insights on pain management. [au]

Chronic pain patients in the Brazilian private healthcare system: a claim database study with the experts' perspective / Pacientes com dor crônica no sistema de saúde suplementar brasileiro: um estudo de banco de dados com a perspectiva dos especialistas

Objective: This study aimed to describe the demands and costs from chronic pain patients over the private Brazilian healthcare system. Methods: This was a retrospective claim database study to assess the resource utilization of pain patients in the private setting. We used a four-year follow-up period to assess inpatient, outpatient, and procedures reported. Further, we promoted a forum of discussion with five pain experts and healthcare managers to address the management of chronic pain and assistance models.Results: We identified 79,689 patients with chronic pain. The orthopedist was the main medical specialist consulted with a total number of 38,879 visits performed. The ophthalmologist, cardiologist, gynecologist, and general practitioner were also frequently consulted (rheumatologist was seldom consulted). Among non-medical specialists, the physical therapist was consulted 87,574 times by 12,342 patients (15% of the entire cohort), Among chronic pain patients, 96% performed at least one exam and 86% of the patients presented at least one ER visit during the follow-up period. In 4 years, we estimate that pain patients costed more than 3 billion reais to the private health care system. According to the experts' opinions, a fragmented healthcare system and the lack of patient centered interdisciplinary approaches contributes to a high ineffective pain management leading to a high use of resources. Conclusion: There is an urgent need to change the chronic pain care model in the Brazilian private setting. Qualification in pain management, a multidisciplinary patient centered care, integrated approaches, pain centers, and patients' education may help changing this scenario.

Objetivo: O objetivo do estudo foi descrever as demandas e custos dos pacientes com dor crônica no sistema privado de saúde brasileiro. Métodos: Neste estudo retrospectivo do banco de dados administrativo, avaliamos a utilização de recursos de pacientes com dor no ambiente privado. Em um período de quatro anos, avaliamos internações, visitas ambulatoriais e procedimentos. Adicionalmente, promovemos um fórum de discussão com cinco especialistas em dor e gerentes de saúde para abordar o manejo da dor e os modelos de assistência. Resultados: Identificamos 79.689 pacientes com dor crônica. O ortopedista foi o principal especialista médico consultado, com 38.879 visitas realizadas. O oftalmologista, o cardiologista, o ginecologista e o clínico geral também foram consultados com frequência (o reumatologista foi raramente consultado). Entre os especialistas não médicos, o fisioterapeuta foi consultado 87.574 vezes por 12.342 pacientes (15% de toda a coorte). Entre os pacientes, 96% realizaram pelo menos um exame e 86% apresentaram pelo menos uma consulta de emergência durante o período. Em 4 anos, estimamos um custo de mais de 3 bilhões de reais para o sistema privado de saúde. De acordo com as opiniões dos especialistas, um sistema de saúde fragmentado e a falta de abordagens centradas no paciente contribuem para um manejo ineficaz da dor, resultando em um alto uso de recursos. Conclusão: Há necessidade de mudar o modelo de manejo da dor crônica no sistema privado brasileiro. Qualificação dos profissionais, atendimento multidisciplinar centrado no paciente, abordagens integradas, centros de dor e educação dos pacientes podem ajudar a mudar esse cenário.

Neurological Impacts of Chronic Methylmercury Exposure in Munduruku Indigenous Adults: Somatosensory, Motor, and Cognitive Abnormalities.

There has been increasing evidence about mercury (Hg) contamination in traditional populations from the Amazon Basin due to illegal gold mining. The most concerning health impact is neurotoxicity caused by Hg in its organic form: methylmercury (MeHg). However, the severity and extent of the neurotoxic effects resulting from chronic environmental exposure to MeHg are still unclear. We conducted a clinical-epidemiological study to evaluate the neurological impacts of chronic MeHg exposure in Munduruku indigenous people, focusing on somatosensory, motor, and cognitive abnormalities. All participants were subjected to a systemized neurological exam protocol, including Brief Cognitive Screening Battery (BCSB), verbal fluency test, and Stick Design Test. After the examination, hair samples were collected to determine MeHg levels. Data collection took place between 29 October and 9 November 2019, in three villages (Sawré Muybu, Poxo Muybu, and Sawré Aboy) from Sawré Muybu Indigenous Land, Southwest of Pará state. One hundred and ten individuals >12 years old were included, 58 of which were men (52.7%), with an average age of 27.6 years (range from 12 to 72). Participants' median MeHg level was 7.4 µg/g (average: 8.7; S.D: 4.5; range: 2.0-22.8). In Sawré Aboy village, the median MeHg level was higher (12.5 µg/g) than in the others, showing a significant statistical exposure gradient (Kruskal-Wallis test with p-value < 0.001). Cerebellar ataxia was observed in two participants with MeHg levels of 11.68 and 15.68 µg/g. Individuals with MeHg exposure level ≥10 µg/g presented around two-fold higher chances of cognitive deficits (RP: 2.2; CI 95%: 1.13-4.26) in BCSB, and in the verbal fluency test (RP: 2.0; CI 95%: 1.18-3.35). Furthermore, adolescents of 12 to 19 years presented three-fold higher chances of verbal development deficits, according to the fluency test (RP: 3.2; CI 95%: 1.06-9.42), than individuals of 20 to 24 years. The worsened motor and cognitive functions are suggestive of neurotoxicity due to chronic MeHg exposure. In conclusion, we believe monitoring and follow-up measures are necessary for chronic mercury exposed vulnerable people, and a basic care protocol should be established for contaminated people in the Brazilian Unified Health System.

Mercury Exposure in Munduruku Indigenous Communities from Brazilian Amazon: Methodological Background and an Overview of the Principal Results.

The Amazonian indigenous peoples depend on natural resources to live, but human activities' growing impacts threaten their health and livelihoods. Our objectives were to present the principal results of an integrated and multidisciplinary analysis of the health parameters and assess the mercury (Hg) exposure levels in indigenous populations in the Brazilian Amazon. We carried out a cross-sectional study based on a census of three Munduruku indigenous villages (Sawré Muybu, Poxo Muybu, and Sawré Aboy), located in the Sawré Muybu Indigenous Land, between 29 October and 9 November 2019. The investigation included: (i) sociodemographic characterization of the participants; (ii) health assessment; (iii) genetic polymorphism analysis; (iv) hair mercury determination; and (v) fish mercury determination. We used the logistic regression model with conditional Prevalence Ratio (PR), with the respective 95% confidence intervals (CI95%) to explore factors associated with mercury exposure levels ≥6.0 µg/g. A total of 200 participants were interviewed. Mercury levels (197 hair samples) ranged from 1.4 to 23.9 µg/g, with significant differences between the villages (Kruskal-Wallis test: 19.9; p-value < 0.001). On average, the general prevalence of Hg exposure ≥ 6.0 µg/g was 57.9%. For participants ≥12 years old, the Hg exposure ≥6.0 µg/g showed associated with no regular income (PR: 1.3; CI95%: 1.0-1.8), high blood pressure (PR: 1.6; CI95%: 1.3-2.1) and was more prominent in Sawré Aboy village (PR: 1.8; CI95%: 1.3-2.3). For women of childbearing age, the Hg exposure ≥6.0 µg/g was associated with high blood pressure (PR: 1.9; CI95%: 1.2-2.3), with pregnancy (PR: 1.5; CI95%: 1.0-2.1) and was more prominent among residents in Poxo Muybu (PR: 1.9; CI95%: 1.0-3.4) and Sawré Aboy (PR: 2.5; CI95%: 1.4-4.4) villages. Our findings suggest that chronic mercury exposure causes harmful effects to the studied indigenous communities, especially considering vulnerable groups of the population, such as women of childbearing age. Lastly, we propose to stop the illegal mining in these areas and develop a risk management plan that aims to ensure the health, livelihoods, and human rights of the indigenous people from Amazon Basin.

Cannabinoids in Neurology - Position paper from Scientific Departments from Brazilian Academy of Neurology.

Cannabinoids comprehend endocannabinoids, phytocannabinoids, and synthetic cannabinoids, with actions both in the central and peripherical nervous systems. A considerable amount of publications have been made in recent years, although cannabis has been known for over a thousand years. Scientific Departments from the Brazilian Academy of Neurology described evidence for medical use in their areas. Literature is constantly changing, and possible new evidence can emerge in the next days or months. Prescription of these substances must be discussed with patients and their families, with knowledge about adverse events and their efficacy.

Cannabinoids in Neurology - Position paper from Scientific Departments from Brazilian Academy of Neurology / Canabinoides em Neurologia - Artigo de posicionamento dos Departamentos Científicos da Academia Brasileira de Neurologia

ABSTRACT Cannabinoids comprehend endocannabinoids, phytocannabinoids, and synthetic cannabinoids, with actions both in the central and peripherical nervous systems. A considerable amount of publications have been made in recent years, although cannabis has been known for over a thousand years. Scientific Departments from the Brazilian Academy of Neurology described evidence for medical use in their areas. Literature is constantly changing, and possible new evidence can emerge in the next days or months. Prescription of these substances must be discussed with patients and their families, with knowledge about adverse events and their efficacy.

RESUMO Os canabinoides compreendem os endocanabinoides, fitocanabinoides e os canabinoides sintéticos e desempenham ações no sistema nervoso central e periférico. Uma quantidade enorme de publicações tem sido lançada nos últimos anos, embora a cannabis seja conhecida por milênios. Os Departamentos Científicos da Academia Brasileira de Neurologia descreveram as evidências do uso médico em suas áreas. A literatura está em constantes mudanças e possíveis novas evidências podem surgir nos próximos dias ou meses. A prescrição dessas substâncias deve ser discutida com os pacientes e suas famílias, com conhecimento sobre eventos adversos e sua eficácia.

Pharmacological treatment of central neuropathic pain: consensus of the Brazilian Academy of Neurology.

BACKGROUND: Central neuropathic pain (CNP) is often refractory to available therapeutic strategies and there are few evidence-based treatment options. Many patients with neuropathic pain are not diagnosed or treated properly. Thus, consensus-based recommendations, adapted to the available drugs in the country, are necessary to guide clinical decisions. OBJECTIVE: To develop recommendations for the treatment of CNP in Brazil. METHODS: Systematic review, meta-analysis, and specialists opinions considering efficacy, adverse events profile, cost, and drug availability in public health. RESULTS: Forty-four studies on CNP treatment were found, 20 were included in the qualitative analysis, and 15 in the quantitative analysis. Medications were classified as first-, second-, and third-line treatment based on systematic review, meta-analysis, and expert opinion. As first-line treatment, gabapentin, duloxetine, and tricyclic antidepressants were included. As second-line, venlafaxine, pregabalin for CND secondary to spinal cord injury, lamotrigine for CNP after stroke, and, in association with first-line drugs, weak opioids, in particular tramadol. For refractory patients, strong opioids (methadone and oxycodone), cannabidiol/delta-9-tetrahydrocannabinol, were classified as third-line of treatment, in combination with first or second-line drugs and, for central nervous system (CNS) in multiple sclerosis, dronabinol. CONCLUSIONS: Studies that address the treatment of CNS are scarce and heterogeneous, and a significant part of the recommendations is based on experts opinions. The CNP approach must be individualized, taking into account the availability of medication, the profile of adverse effects, including addiction risk, and patients' comorbidities.

Pharmacological treatment of central neuropathic pain: consensus of the Brazilian Academy of Neurology / Tratamento farmacológico da dor neuropática central: consenso da Academia Brasileira de Neurologia

ABSTRACT Background: Central neuropathic pain (CNP) is often refractory to available therapeutic strategies and there are few evidence-based treatment options. Many patients with neuropathic pain are not diagnosed or treated properly. Thus, consensus-based recommendations, adapted to the available drugs in the country, are necessary to guide clinical decisions. Objective: To develop recommendations for the treatment of CNP in Brazil. Methods: Systematic review, meta-analysis, and specialists opinions considering efficacy, adverse events profile, cost, and drug availability in public health. Results: Forty-four studies on CNP treatment were found, 20 were included in the qualitative analysis, and 15 in the quantitative analysis. Medications were classified as first-, second-, and third-line treatment based on systematic review, meta-analysis, and expert opinion. As first-line treatment, gabapentin, duloxetine, and tricyclic antidepressants were included. As second-line, venlafaxine, pregabalin for CND secondary to spinal cord injury, lamotrigine for CNP after stroke, and, in association with first-line drugs, weak opioids, in particular tramadol. For refractory patients, strong opioids (methadone and oxycodone), cannabidiol/delta-9-tetrahydrocannabinol, were classified as third-line of treatment, in combination with first or second-line drugs and, for central nervous system (CNS) in multiple sclerosis, dronabinol. Conclusions: Studies that address the treatment of CNS are scarce and heterogeneous, and a significant part of the recommendations is based on experts opinions. The CNP approach must be individualized, taking into account the availability of medication, the profile of adverse effects, including addiction risk, and patients' comorbidities.

RESUMO Introdução: A dor neuropática central (DNC) é frequentemente refratária às estratégias terapêuticas disponíveis e há poucas opções de tratamento baseado em evidência. Muitos pacientes com dor neuropática não são diagnosticados ou tratados adequadamente. Desse modo, recomendações baseadas em consenso, adaptadas à disponibilidade de medicamentos no país, são necessárias para guiar decisões clínicas. Objetivo: Desenvolver recomendações para o tratamento da DNC no Brasil. Métodos: Revisão sistemática, metanálise e discussão dos resultados entre especialistas e pesquisadores da área, considerando eficácia, perfil de eventos adversos, custo e disponibilidade do fármaco na saúde pública. Resultados: Foram encontrados 44 estudos sobre tratamento da DNC, dos quais 20 foram incluídos na análise qualitativa e 15, na quantitativa. Classificaram-se as medicações em primeira, segunda e terceira linhas de tratamento, baseando-se em revisão sistemática, meta-análise e opinião de especialistas. Como primeira linha, foram incluídos gabapentina, duloxetina e antidepressivos tricíclicos. Como segunda, venlafaxina, pregabalina para DNC secundária à lesão medular, lamotrigina para DNC pós-acidente vascular cerebral e, em associação aos fármacos de primeira linha, opioides fracos, em particular tramadol. Para os pacientes refratários, opioides fortes (metadona e oxicodona) e canabidiol/delta-9-tetrahidrocanabinol foram classificados como terceira linha de tratamento, em associação com drogas de primeira ou segunda linha, e, para DNC na esclerose múltipla, dronabinol. Conclusões: Os estudos que abordam o tratamento da DNC são escassos e heterogêneos, e parte significativa das recomendações é baseada em opiniões de especialistas. A abordagem da DNC deve ser individualizada, levando em conta a disponibilidade de medicação, o perfil de efeitos adversos, incluindo risco de dependência e as comorbidades do paciente.