Desjudicialização da saúde e diálogos interinstitucionais em Minas Gerais: a análise do Acordo de Cooperação Técnica para a gestão dos medicamentos Ranibizumabe e Aflibercept / De-judicialization of health and inter-institutional dialogues in Minas Gerais: an analysis of the Technical Cooperation Agreement for the management of the drugs Ranibizumab and Aflibercept / Desjudicialización de la salud y diálogos interinstitucionales en Minas Gerais: un análisis del Acuerdo de Cooperación Técnica para la gestión de los medicamentos Ranibizumab y Aflibercept

Objetivo: compreender a judicialização da saúde no Brasil e analisar, na perspectiva da desjudicialização da saúde, o Acordo de Cooperação Técnica, firmado em 02 de dezembro de 2021, entre a Secretaria de Estado de Saúde de Minas Gerais, a Advocacia Geral do Estado de Minas Gerais e a Defensoria Pública Estadual de Minas Gerais para a gestão dos medicamentos Ranibizumabe e Aflibercept. Método: realizou-se revisão narrativa da literatura sobre a judicialização da saúde e um estudo exploratório baseado em análise documental dos antecedentes do Acordo de Cooperação Técnica. Resultados e discussões: a autocomposição e solução consensual de conflitos por parte da Administração Pública possui amplo respaldo legal e, no atual cenário jurídico e administrativo, é o meio mais eficaz e eficiente para concretizar o interesse público subjacente, notadamente o direito à saúde, promovendo sua desjudicialização. Esse cenário aponta para o potencial de novas soluções, entre elas a implementação de diálogos interinstitucionais, como é exemplo o Acordo de Cooperação Técnica estudado, o qual projeta-se poder servir de embrião para uma tendência permanente na gestão da judicialização da saúde no âmbito da Secretaria de Estado da Saúde de Minas Gerais. Considerações finais: o acordo de cooperação estudado tem grande potencial para a desjudicialização das ações com pedidos dos medicamentos oftalmológicos, além de outros cujas incorporações forem propostas em seu bojo. Ele também promove a atuação sinérgica e convergente dos atores que atuam na judicialização. A perspectiva é que, a partir desse marco, estas ações judiciais diminuam e os pacientes passem a ser atendidos pela via de fornecimento administrativo do Sistema Único de Saúde.

Objective: to understand the judicialization of health in Brazil and analyze, from the perspective of health de-judicialization, the Technical Cooperation Agreement signed on December 2, 2021, between the State Health Departmentof Minas Gerais , the State Attorney General's Office of Minas Gerais, and the State Public Defender's Office of Minas Gerais for the management of the medications Ranibizumab and Aflibercept. Method: a narrative review of the literature on the judicialization of health and an exploratory study based on documentary analysis of the antecedents of the Technical Cooperation Agreement were carried out. Results and discussions: Self-composition and consensual resolution of conflicts by the Public Administration has broad legal support and, in the current legal and administrative scenario, is the most effective and efficient means of realizing the underlying public interest, notably the right to health, promoting its dejudicialization. This scenario points to the potential for new solutions, including the implementation of interinstitutional dialogues, such as the Technical Cooperation Agreement studied, which is expected to serve as the embryo for a permanent trend in the management of the judicialization of health within the scope of State Health Departmentof Minas Gerais. Final considerations: ahe cooperation agreement studied has great potential for the dejudicialization of actions with requests for ophthalmological medicines, in addition to others whose incorporations are proposed within it. It also promotes synergistic and convergent action by actors involved in judicialization. The perspective is that, from this milestone, these legal actions will decrease and patients will begin to be served through the United Health System administrative supply route.

Objetivo: comprender la judicialización de la salud en Brasil y analizar, desde la perspectiva de la desjudicialización de la salud, el Acuerdo de Cooperación Técnica firmado el 2 de diciembre de 2021 entre la Secretaría de Estado de Saludde Minas Gerais, la Procuraduría General del Estado de Minas Gerais (AGE-MG) y la Defensoría Pública Estatal de Minas Gerais para la gestión de los medicamentos Ranibizumab y Aflibercept. Método: Se realizó una revisión narrativa de la literatura sobre la judicialización de la salud y un estudio exploratorio basado en un análisis documental de los antecedentes del Acuerdo de Cooperación Técnica. Resultados y discusiones: La autocomposición y resolución consensuada de conflictos por parte de la Administración Pública tiene un amplio respaldo legal y, en el actual escenario jurídico y administrativo, es el medio más eficaz y eficiente para realizar el interés público subyacente, en particular el derecho a la salud. promoviendo su desjudicialización. Este escenario apunta al potencial de nuevas soluciones, incluida la implementación de diálogos interinstitucionales, como el Acuerdo de Cooperación Técnica estudiado, que se espera sirva como embrión de una tendencia permanente en la gestión de la judicialización de la salud en el ámbito de la Secretaría de Estado de Salud de Minas Gerais. Consideraciones finales: el convenio de cooperación estudiado tiene un gran potencial para la desjudicialización de acciones con solicitudes de medicamentos oftalmológicos, además de otras cuyas incorporaciones se proponen dentro del mismo. También promueve acciones sinérgicas y convergentes por parte de los actores involucrados en la judicialización. La perspectiva es que, a partir de este hito, esas acciones legales disminuyan y los pacientes comiencen a ser atendidos a través de la vía administrativa de abastecimiento del Sistema de Salud Unido.

A Judicialização da Saúde na era do Big Data / The judicialization of Health in the era of Big Data / La Judicialización de la Salud en la era del Big Data

No Brasil, a judicialização da saúde, que é o uso de ações judiciais para garantir acesso a medicamentos e serviços de saúde, atende a interesses diversos e torna mais complexa a gestão das políticas públicas de saúde. A produção de estatísticas sobre essas ações é desafiadora, pois existem grandes divergências entre fontes de dados. Em Minas Gerais há um número significativo de ações, com grandes desafios na classificação e na padronização das informações. A pesquisa realizada mostrou que, com técnicas de mineração de dados e padronização da definição de processos de saúde, é possível avançar nessa direção. Ferramentas como o JUDJe objetivam facilitar a compreensão da judicialização da saúde, utilizando tecnologia de ponta e respeitando as regras de privacidade e segurança. Conclui-se pela necessidade de incorporar amplamente essas ferramentas e padronizar os assuntos, para beneficiar a gestão do setor de saúde em todo o Brasil.

The judicialization of health in Brazil, through legal actions to guarantee access to medicines and health services, complicates health policies and serves different interests. Accurately accounting for these actions is challenging, highlighting divergences between data sources. Analysis of data from Minas Gerais reveals significant numbers, but highlights challenges in classifying and standardizing information. Research showed that, with data mining techniques and standardization of the definition of health processes, it is possible to move in this direction. Tools like JUDJe promise to improve understanding of the judicialization of health, facing technological, privacy and security challenges. It is concluded that there is a need to widely incorporate these tools and standardize matters, to benefit the management of the health sector throughout Brazil.

La judicialización de la salud en Brasil, a través de acciones legales para garantizar el acceso a medicamentos y servicios de salud, complica las políticas de salud y atiende intereses diferentes. Contabilizar con precisión estas acciones es un desafío, lo que pone de relieve las divergencias entre las fuentes de datos. El análisis de datos de Minas Gerais revela cifras significativas, pero destaca los desafíos en la clasificación y estandarización de la información. Investigaciones muestran que, con técnicas de minería de datos y estandarización de la definición de procesos de salud, es posible avanzar en esa dirección. Herramientas como JUDJe prometen mejorar la comprensión de la judicialización de la salud, enfrentando desafíos tecnológicos, de privacidad y de seguridad. Se concluye que es necesario incorporar ampliamente estas herramientas y estandarizar las materias, para beneficiar la gestión del sector salud en todo Brasil.

Closing the gap: prognostic and predictive biomarker validation for personalized care in a Latin American hormone-dependent breast cancer cohort.

BACKGROUND: Several guidelines recommend the use of different classifiers to determine the risk of recurrence (ROR) and treatment decisions in patients with HR+HER2- breast cancer. However, data are still lacking for their usefulness in Latin American (LA) patients. Our aim was to evaluate the comparative prognostic and predictive performance of different ROR classifiers in a real-world LA cohort. METHODS: The Molecular Profile of Breast Cancer Study (MPBCS) is an LA case-cohort study with 5-year follow-up. Stages I and II, clinically node-negative HR+HER2- patients (n = 340) who received adjuvant hormone therapy and/or chemotherapy, were analyzed. Time-dependent receiver-operator characteristic-area under the curve, univariate and multivariate Cox proportional hazards regression (CPHR) models were used to compare the prognostic performance of several risk biomarkers. Multivariate CPHR with interaction models tested the predictive ability of selected risk classifiers. RESULTS: Within this cohort, transcriptomic-based classifiers such as the recurrence score (RS), EndoPredict (EP risk and EPClin), and PAM50-risk of recurrence scores (ROR-S and ROR-PC) presented better prognostic performances for node-negative patients (univariate C-index 0.61-0.68, adjusted C-index 0.77-0.80, adjusted hazard ratios [HR] between high and low risk: 4.06-9.97) than the traditional classifiers Ki67 and Nottingham Prognostic Index (univariate C-index 0.53-0.59, adjusted C-index 0.72-0.75, and adjusted HR 1.85-2.54). RS (and to some extent, EndoPredict) also showed predictive capacity for chemotherapy benefit in node-negative patients (interaction P = .0200 and .0510, respectively). CONCLUSION: In summary, we could prove the clinical validity of most transcriptomic-based risk classifiers and their superiority over clinical and immunohistochemical-based methods in the heterogenous, real-world node-negative HR+HER2- MPBCS cohort.

Implementing Standard Diagnosis and Treatment for Locally Advanced Breast Cancer Through Global Research in Latin America: Results From a Multicountry Pragmatic Trial.

PURPOSE: Breast cancer mortality rates in Latin America (LA) are higher than those in the United States, possibly because of advanced disease presentation, health care disparities, or unfavorable molecular subtypes. The Latin American Cancer Research Network was established to address these challenges and to promote collaborative clinical research. The Molecular Profiling of Breast Cancer Study (MPBCS) aimed to evaluate the clinical characteristics and treatment outcomes of LA participants with locally advanced breast cancer (LABC). PATIENTS AND METHODS: The MPBCS enrolled 1,449 participants from Argentina, Brazil, Chile, Mexico, and Uruguay. Through harmonized procedures and quality assurance measures, this study evaluated clinicopathologic characteristics, neoadjuvant chemotherapy response, and survival outcomes according to residual cancer burden (RCB) and the type of surgery. RESULTS: Overall, 711 and 480 participants in the primary surgery and neoadjuvant arms, respectively, completed the 5-year follow-up period. Overall survival was independently associated with RCB (worse survival for RCBIII-adjusted hazard ratio, 8.19, P < .001, and RCBII [adjusted hazard ratio, 3.69, P < .008] compared with RCB0 [pathologic complete response or pCR]) and type of surgery (worse survival in mastectomy than in breast-conserving surgery [BCS], adjusted hazard ratio, 2.97, P = .001). The hormone receptor-negative-human epidermal growth factor receptor 2-positive group had the highest proportion of pCR (48.9%). The analysis of the ASCO Quality Oncology Practice Initiative breast module revealed high compliance with pathologic standards but lower adherence to treatment administration standards. Notably, compliance with trastuzumab administration varied widely among countries (33.3%-88.7%). CONCLUSION: In LABC, we demonstrated the survival benefit of BCS and the prognostic effect of the response to available neoadjuvant treatments despite an important variability in access to key treatments. The MPBCS represents a significant step forward in understanding the real-world implementation of oncologic procedures in LA.

Desafios e possibilidades da jurimetria na judicialização em saúde: uma investigação em Minas Gerais do período 2014 a 2020 / Challenges and possibilities of jurimetry in health judicialization: an investigation in Minas Gerais state from 2014 2020 / Desafíos y posibilidades de la jurimetría en la judicialización de la salud: una investigación en Minas Gerais de 2014 a 2020

Objetivo: analisar os processos de saúde, de medicamentos e de medicamentos antineoplásicos em Minas Gerais, em 2014 a 2020, a partir da comparação de diferentes bases de dados. Metodologia: foram utilizadas técnicas de pareamento de bases de dados entre os processos existentes no Tribunal de Justiça do Estado de Minas Gerais e os processos recebidos pela Secretaria Estadual de Saúde de Minas Gerais, descreveram-se as dificuldades encontradas na identificação e quantificação desses processos, e os resultados encontrados foram comparados com informações provenientes de outras fontes. Resultados: nas bases do Tribunal de Justiça de Minas Gerais foram identificados 564.763 processos de saúde. Houve um aumento significativo do número de processos até 2017 e uma estabilização, em patamares altos, a partir de 2017. Ao comparar com os resultados obtidos pelo Instituto Superior de Ensino e Pesquisa e pelo Laboratório de Inovação, Inteligência e Objetivos de Desenvolvimento Sustentável, houve uma importante divergência nos números de processos. Tomando como exemplo a judicialização de saúde contra o estado de Minas Gerais, não foi possível encontrar de forma direta todos os processos recebidos pela Secretaria Estadual de Saúde de Minas Gerais nas diversas bases fornecidas pelo Tribunal de Justiça de Minas Gerais, tendo sido necessária uma integração entre as diferentes bases de dados e uma busca adicional para identificar todos os processos. Conclusão: recomendam-se a padronização e organização dos dados dos processos judiciais em saúde, já na entrada de dados, para facilitar a realização de estudos quantitativos sobre a judicialização da saúde.

Objective: to analyze the health, drug, and antineoplastic drug lawsuits in Minas Gerais, in 2014 to 2020, from the comparison of different databases. Methodology: database pairing techniques were used to link lawsuits from the Minas Gerais State Court of Justice with the processes received by the Minas Gerais Health State Department, the difficulties encountered in identifying and quantifying these processes were described, and the results found were compared with information from other sources. Results: in the Minas Gerais State Court of Justice databases, 564,763 health lawsuits were identified in the studied period. There was a significant increase in the number of processes until 2017 and a stabilization, at high levels, from 2017 onwards. In comparison with the results obtained by the Institute of Higher Education and Research and the Laboratory of Innovation, Intelligence and Sustainable Development Goals there was a great divergence in the number of processes found. Conclusion: taking the health judicialization against Minas Gerais state as an example, it was not possible to directly find all the processes received by Minas Gerais Health State Department in the various databases provided by the Minas Gerais State Court of Justice, requiring integration between the different databases and an additional search to identify all processes.

Objetivo: analizar los juicios de salud, drogas y medicamentos antineoplásicos en Minas Gerais, en 2014 a 2020, a partir de la comparación de diferentes bases de datos. Metodología: técnicas de emparejamiento de bases de datos fueron utilizadas para vincular los juicios existentes en el Tribunal de Justicia del Estado de Minas Gerais con los procesos recibidos por la Secretaría de Estado de Salud de Minas Gerais, las dificultades encontradas en la identificación y cuantificación de esos procesos fueron descritas, y los resultados encontrados fueron comparados con informaciones de otras fuentes. Resultados: en las bases del Tribunal de Justicia del Estado de Minas Gerais se identificaron 564.763 procesos de salud. Hubo un aumento significativo en el número de procesos hasta 2017 y una estabilización, en niveles altos, a partir de 2017. Sin embargo, al comparar con los resultados obtenidos por el Instituto Superior de Educación e Investigación y por el Laboratorio de Innovación, Inteligencia y Objetivos de Desarrollo Sostenible hubo una divergencia importante en el número de procesos. Conclusión: tomando como ejemplo la judicialización de la salud contra el estado de Minas Gerais, no era posible encontrar directamente todos los procesos recibidos por la Secretaría de Estado de Salud de Minas Gerais en las diversas bases de datos proporcionadas por el Tribunal de Justicia del Estado de Minas Gerais, lo que requería una integración entre las diferentes bases de datos y una búsqueda adicional a identificar todos los procesos.

Positive Effect of Green Photo-Selective Filter on Graft Union Formation in Tomatoes.

This study investigated the effects of green and red photo-selective filters (shade nets) on the process of graft union formation (healing and acclimation) in grafted tomato plants. The research evaluated oxidative stress, physiological characteristics, and anatomical development of graft unions. Plants were subjected to green-netting, red-netting, and no-netting treatments for 28 days, starting 4 days after grafting. Markers of oxidative stress, including reactive oxygen species (ROS), superoxide dismutase (SOD), peroxidase (POD), and malondialdehyde (MDA), as well as protein concentration of SOD/POD enzyme-enriched extracts, were quantified. The anatomical development of the graft unions was examined using microscopy. The results demonstrated that the red and green photo-selective filters increased ROS production by 5% and 4% after 3 days of exposure, by 58% and 14% after 7 days, and by 30% and 13% after 14 days in comparison to the control treatment. The increase in ROS activates the defense mechanism, enhancing the activity of SOD and POD enzymes. In terms of anatomy, the green netting resulted in enhanced cell proliferation and early differentiation of vascular tissue cells. Notably, at the 28-day mark, when the plants were ready for transplanting, the green-net treatment showed a reduction in lipid peroxidation damage and increases of 20% and 54% in dry weight compared with the control and red-net treatments, respectively. Finally, our results suggest that the use of a green photo-selective filter has a positive effect on oxidative stress, anatomical development, and overall growth of grafted tomato plants during the process of graft union formation.

Health litigation and cancer survival in patients treated in the public health system in a large Brazilian city, 2014-2019.

BACKGROUND: Litigation for health care, also known as health judicialization, is frequent in Brazil. It involves recourse to the court system to access health services. The study aimed to evaluate whether cancer patients in Belo Horizonte, Minas Gerais, Brazil, increased their overall survival by increasing access to certain drugs or treatments through litigation, controlling for the effect of demographic and disease-related variables. METHODS: A retrospective cohort study was conducted. Patients with breast, prostate, brain, lung, or colon cancers from 2014 to 2019 were included. Survival analysis was performed using the Cox proportional hazards model. RESULTS: In the multivariate analysis, litigation was significantly associated with increased survival in cancers of breast (HR = 0.51, 95%CI 0.33-0.80), prostate (HR = 0.50, 95%CI 0.30-0.85), colon (HR = 0.59, 95%CI 0.38-0.93), and lung (HR = 0.36, 95%CI 0.22-0.60). Five-year survival rates of patients who sued for treatment were 97.8%, 88.7%, 59.3%, and 26.0%, compared to median survival of 95.7%, 78.7%, 41.2%, and 2.4%, respectively, among patient that did not resort to court action. The study suggests that litigation for access to cancer treatment may represent a step forward in obtaining more effective treatment. This study´s main limitations are the lack of patients´ clinical information for use as control variables and the lack of variables to assess patients´ quality of life. The study also found that many cases involved claims that could have been solved by administrative rather than legal action. Some claims thus reflect the lack of adequate administrative procedures. CONCLUSION: When based on scientific evidence, access to new therapies, combined with other technologies already available, can favor patient survival. Access to new therapies through litigation may increase health inequalities since low-income patients have limited access to legal recourse against the State to meet their needs. The timely approval of new effective therapies can mitigate the judicialization of cancer treatment.

Argentine consensus recommendations for lung cancer screening programmes: a RAND/UCLA-modified Delphi study.

BACKGROUND: Lung cancer (LC) screening improves LC survival; the best screening method in terms of improving survival is low-dose CT (LDCT), outpacing chest X-ray and sputum cytology. METHODS: A consensus of experts in Argentina was carried out to review the literature and generate recommendations for LC screening programmes. A mixed-method study was used with three phases: (1) review of the literature; (2) modified Delphi consensus panel; and (3) development of the recommendations. The Evidence to Decision (EtD) framework was used to generate 13 evaluation criteria. Nineteen experts participated in four voting rounds. Consensus among participants was defined using the RAND/UCLA method. RESULTS: A total of 16 recommendations scored ≥7 points with no disagreement on any criteria. Screening for LC should be performed with LDCT annually in the population at high-risk, aged between 55 and 74 years, regardless of sex, without comorbidities with a risk of death higher than the risk of death from LC, smoking ≥30 pack-years or former smokers who quit smoking within 15 years. Screening will be considered positive when finding a solid nodule ≥6 mm in diameter (or ≥113 mm3) on baseline LDCT and 4 mm in diameter if a new nodule is identified on annual screening. A smoking cessation programme should be offered, and cardiovascular risk assessment should be performed. Institutions should have a multidisciplinary committee, have protocols for the management of symptomatic patients not included in the programme and distribute educational material. CONCLUSION: The recommendations provide a basis for minimum requirements from which local institutions can develop their own protocols adapted to their needs and resources.

Influence of socioeconomic inequality on the distribution of COVID-19 hospitalizations and deaths in Brazilian municipalities, 2020: an ecological study. / Influência da desigualdade socioeconômica na distribuição das internações e dos óbitos por covid-19 em municípios brasileiros, 2020: um estudo ecológico.

OBJECTIVE: to analyze the influence of socioeconomic inequality on COVID-19 distribution in larger Brazilian municipalities, controlling for effect of hospital infrastructure, comorbidities and other variables. METHODS: this was an ecological study of COVID-19 hospitalizations and deaths in 2020; outcome data were obtained from the Ministry of Health; incidence ratios were estimated using a generalized linear model. RESULTS: we identified 291,073 hospitalizations and 139,953 deaths; we found higher mortality rates in municipalities with a higher proportion of non-White people (95%CI 1.01;1.16) and with more households with more than two people per room (95%CI 1.01;1.13); presence of sewerage systems was protective for both outcomes (hospitalizations: 95%CI 0.87;0.99 - deaths: 95%CI 0.90;0.99), while a higher proportion of the population in subnormal housing clusters was a risk factor (hospitalizations: 95%CI 1.01;1.16 - deaths: 95%CI 1.09;1.21), with this variable interacting with the proportion of people receiving Emergency Aid (hospitalizations: 95%CI 0.88;1.00 - deaths: 95%CI 0.89;0.98). CONCLUSION: socioeconomic conditions affected illness and death due to COVID-19 in Brazil.

Influência da desigualdade socioeconômica na distribuição das internações e dos óbitos por covid-19 em municípios brasileiros, 2020: um estudo ecológico / Influencia de la desigualdad socioeconómica en la distribución de hospitalizaciones y muertes por COVID-19 en municipios brasileños, 2020: un estudio ecológico / Influence of socioeconomic inequality on the distribution of COVID-19 hospitalizations and deaths in Brazilian municipalities, 2020: an ecological study

Objetivo analisar a influência da desigualdade socioeconômica na distribuição da covid-19 nos maiores municípios brasileiros (> 100 mil habitantes), controlando, pelo efeito da infraestrutura hospitalar, comorbidades e outras variáveis. Métodos estudo ecológico sobre internações e óbitos por covid-19 em 2020; dados de desfecho obtidos do Ministério da Saúde; a razão de incidência foi estimada via modelo linear generalizado. Resultados identificados 291.073 internações e 139.953 óbitos; encontrou-se maior taxa de mortalidade nos municípios com maior população não branca (IC95% 1,01;1,16) e nos domicílios com mais de duas pessoas por cômodo (IC95% 1,01;1,13); para ambos os desfechos, esgotamento sanitário foi protetivo (internações: IC95% 0,87;0,99 - óbitos: IC95% 0,90;0,99), e população em aglomerados subnormais revelou-se fator de risco (internações: IC95% 1,01;1,16 - óbitos: IC95% 1,09;1,21) com interação, com a proporção de pessoas a receber auxílio emergencial (internações: IC95% 0,88;1,00 - óbitos: IC95% 0,89;0,98). Conclusão condições socioeconômicas afetaram o adoecimento e morte por covid-19 no Brasil.

Objetivo: analizar la influencia de la desigualdad socioeconómica en la distribución de COVID-19 en los mayores municipios brasileños (> 100 mil habitantes), controlando, por la infraestructura hospitalaria, comorbilidades y otras variables. Métodos: estudio ecológico sobre hospitalizaciones y muertes por COVID-19 en 2020; datos del resultado fueran obtenidos del Ministerio de Salud; razón de incidencia estimada a través del modelo lineal generalizado. Resultados: 291.073 hospitalizaciones y 139.953 muertes; mayor tasa de mortalidad en municipios con mayor proporción de población no blanca (IC95% 1,01;1,16) y con más hogares con más de dos personas por habitación (IC95% 1,01;1,13); el alcantarillado sanitario resultó protector (hospitalizaciones: IC95% 0,87;0,99 - muertes: IC95% 0,90;0,99) y la mayor proporción de población en aglomeraciones subnormales fue un factor de riesgo (hospitalizaciones: IC95% 1,01;1,16 - muertes: IC95% 1,09;1,21), interactuando con proporción de personas con asistencia de emergencia (hospitalizaciones IC95% 0,88;1,00, defunciones IC95% 0,89;0,98). Conclusión: las condiciones socioeconómicas afectaron la enfermedad y la muerte por COVID-19.

Objective: to analyze the influence of socioeconomic inequality on COVID-19 istribution in larger Brazilian municipalities, controlling for effect of hospital infrastructure, comorbidities and other variables. Methods: this was an ecological study of COVID-19 hospitalizations and deaths in 2020; outcome data were obtained from the Ministry of Health; incidence ratios were estimated using a generalized linear model. Results: we identified 291,073 hospitalizations and 139,953 deaths; we found higher mortality rates in municipalities with a higher proportion of non-White people (95%CI 1.01;1.16) and with more households with more than two people per room (95%CI 1.01;1.13); presence of sewerage systems was protective for both outcomes (hospitalizations: 95%CI 0.87;0.99 - deaths: 95%CI 0.90;0.99), while a higher proportion of the population in subnormal housing clusters was a risk factor (hospitalizations: 95%CI 1.01;1.16 - deaths: 95%CI 1.09;1.21), with this variable interacting with the proportion of people receiving Emergency Aid (hospitalizations: 95%CI 0.88;1.00 - deaths: 95%CI 0.89;0.98). Conclusion: socioeconomic conditions affected illness and death due to COVID-19 in Brazil.

Effects of LED Light Spectra on the Development, Phytochemical Profile, and Antioxidant Activity of Curcuma longa from Easter Island.

Curcuma longa (C. longa), an herbaceous plant used for medicinal purposes by the indigenous people of Easter Island, has been overexploited in its natural habitat, leading to its conservation status being designated as a vulnerable species. We have recently reported on the use of light-emitting diodes (LEDs) to improve the productivity of C. longa in vitro cultures under a temporary immersion system (TIS), but the effects of light quality on plant growth, phytochemical composition, and antioxidant capacity remained unexplored. Here, we set out to study these three aspects as observed at the end of TIS culture (day 0) and after 30 days of greenhouse acclimation (day 30). Thus, we evaluated plant morphological characteristics, phytochemical profile (polyphenols, tannins, flavonoids, reducing sugars, and curcumin), and radical scavenging activity by DPPH, ORAC, and FRAP assays. The results showed that, during in vitro cultivation under TIS, the red:blue (RB) LED light spectrum promoted C. longa shoot proliferation, with the resulting seedlings exhibiting greater fresh weight and no signs of etiolation. In the acclimation phase, the RB spectrum increased phytochemicals, such as polyphenols, flavonoids, and reducing sugars, and boosted curcumin synthesis. Nevertheless, the antioxidant activity of the plants under the RB light spectrum did not intensify. We surmise that this may be due to the premature intraplant allocation of metabolites to alternative pathways (e.g., curcumin synthesis) under RB light.

Risk factors for hospitalization and death due to COVID-19 among frail community-dwelling elderly people: a retrospective cohort study

ABSTRACT BACKGROUND: Advanced age, multiple chronic diseases and frailty have been correlated with worse prognosis among coronavirus disease 2019 (COVID-19) inpatients. OBJECTIVE: To investigate potential risk factors for hospitalization and death due to COVID-19 among frail community-dwelling elderly people. DESIGN AND SETTING: Retrospective cohort study of patients followed up at a geriatric outpatient clinic in Belo Horizonte, Minas Gerais, Brazil. METHODS: The associations of demographic characteristics (age and sex) and clinical characteristics (frailty, multimorbidity, number of medications with long-term use, obesity, smoking, diabetes mellitus, pulmonary diseases, cardiovascular diseases, cerebrovascular disease, and chronic kidney disease) with the risk of hospitalization and death due to COVID-19 were explored using a multivariable logistic regression model. RESULTS: 5,295 patients (mean age 78.6 ± 9.4 years; 72.6% females) were included. After adjustments, the number of medications with long-term use was found to increase the odds of hospitalization due to COVID-19 (odds ratio, OR: 1.13; 95% confidence interval, CI: 1.06-1.22). Frailty, multimorbidity and diabetes mellitus also increased the odds of hospitalization (OR: 1.06, 95% CI: 1.02-1.09; OR: 1.17, 95% CI: 1.09-1.26; and OR: 2.27, 95% CI: 1.45-3.54, respectively) and the odds of death due to COVID-19 (OR: 1.07, 95% CI: 1.00-1.14; OR: 1.16, 95% CI: 1.03-1.32; and OR: 2.69, 95% CI: 1.79-6.14, respectively). CONCLUSIONS: Multimorbidity, frailty and diabetes mellitus increased the odds of hospitalization and death due to COVID-19 and the number of medications with long-term use increased the odds of hospitalization due to COVID-19 among frail community-dwelling elderly people.

Micropropagation of Citronella mucronata D. Don, a Vulnerable Chilean Endemic Tree Species.

Citronella mucronata (C. mucronata), a tree species endemic to Chile, has become threatened in its natural habitat and is currently listed as vulnerable. Tree population parameters have deteriorated due to indiscriminate logging and other anthropogenic activities, warranting research on mass propagation as a means of recovery. This study, unprecedented for this native species, has developed a successful method for its micropropagation. The objective was to establish a protocol for in vitro propagation of C. mucronata to produce large quantities of high-quality seedlings in an accelerated plant acquisition process. The best results were achieved by growing explants on Murashige and Skoog (MS) basal culture medium supplemented with 4.44 µM 6-benzylaminopurine (BAP) and 14.76 µM indole-3-butyric acid (IBA). Explant survival rate was 78 %, the average shoot length reached 3.2 cm, the number of lateral shoots was 3.9, and rooting rate was 60%. Furthermore, stimulation with red and blue light in a 1:2 ratio, supplemented with 14.76 µM IBA, improved the rooting rate to 93%. The survival rate of rooted explants reached 100% in the acclimatization stage when using peat and perlite substrate (1:1 v/v).

Chemistry and Bioactivity of Microsorum scolopendria (Polypodiaceae): Antioxidant Effects on an Epithelial Damage Model.

Microsorum scolopendia (MS), which grows on the Chilean island of Rapa Nui, is a medicinal fern used to treat several diseases. Despite being widely used, this fern has not been deeply investigated. The aim of this study was to perform a characterization of the polyphenolic and flavonoid identity, radical scavenging, antimicrobial, and anti-inflammatory properties of MS rhizome and leaf extracts (RAE and HAE). The compound identity was analyzed through the reversed-phase high-performance liquid chromatography (RP-HPLC) method coupled with mass spectrometry. The radical scavenging and anti-inflammatory activities were evaluated for DPPH, ORAC, ROS formation, and COX inhibition activity assay. The antimicrobial properties were evaluated using an infection model on Human Dermal Fibroblast adult (HDFa) cell lines incubated with Staphylococcus aureus and Staphylococcus epidermidis. The most abundant compounds were phenolic acids between 46% to 57% in rhizome and leaf extracts, respectively; followed by flavonoids such as protocatechic acid 4-O-glucoside, cirsimaritin, and isoxanthohumol, among others. MS extract inhibited and disaggregated the biofilm bacterial formed and showed an anti-inflammatory selective property against COX-2 enzyme. RAE generated a 64% reduction of ROS formation in the presence of S. aureus and 87.35% less ROS in the presence of S. epidermidis on HDFa cells. MS has great therapeutic potential and possesses several biological properties that should be evaluated.

Risk factors for hospitalization and death due to COVID-19 among frail community-dwelling elderly people: a retrospective cohort study.

BACKGROUND: Advanced age, multiple chronic diseases and frailty have been correlated with worse prognosis among coronavirus disease 2019 (COVID-19) inpatients. OBJECTIVE: To investigate potential risk factors for hospitalization and death due to COVID-19 among frail community-dwelling elderly people. DESIGN AND SETTING: Retrospective cohort study of patients followed up at a geriatric outpatient clinic in Belo Horizonte, Minas Gerais, Brazil. METHODS: The associations of demographic characteristics (age and sex) and clinical characteristics (frailty, multimorbidity, number of medications with long-term use, obesity, smoking, diabetes mellitus, pulmonary diseases, cardiovascular diseases, cerebrovascular disease, and chronic kidney disease) with the risk of hospitalization and death due to COVID-19 were explored using a multivariable logistic regression model. RESULTS: 5,295 patients (mean age 78.6 ± 9.4 years; 72.6% females) were included. After adjustments, the number of medications with long-term use was found to increase the odds of hospitalization due to COVID-19 (odds ratio, OR: 1.13; 95% confidence interval, CI: 1.06-1.22). Frailty, multimorbidity and diabetes mellitus also increased the odds of hospitalization (OR: 1.06, 95% CI: 1.02-1.09; OR: 1.17, 95% CI: 1.09-1.26; and OR: 2.27, 95% CI: 1.45-3.54, respectively) and the odds of death due to COVID-19 (OR: 1.07, 95% CI: 1.00-1.14; OR: 1.16, 95% CI: 1.03-1.32; and OR: 2.69, 95% CI: 1.79-6.14, respectively). CONCLUSIONS: Multimorbidity, frailty and diabetes mellitus increased the odds of hospitalization and death due to COVID-19 and the number of medications with long-term use increased the odds of hospitalization due to COVID-19 among frail community-dwelling elderly people.

Socioeconomic, Clinical, and Molecular Features of Breast Cancer Influence Overall Survival of Latin American Women.

Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60-month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by Chi-squared and Fisher's exact tests and the OS by Kaplan-Meier method. Log-rank test was used to determine differences between cumulative probability curves. Multivariable adjustment was carried out by entering potential confounders in the Cox regression model. The OS at 60 months was 83.9%. Multivariable-adjusted death hazard differences were found for women living in Argentina (2.27), Chile (1.95), and Uruguay (2.42) compared with Mexican women, for older (≥60 years) (1.84) compared with younger (≤40 years) women, for basal-like subtype (5.8), luminal B (2.43), and HER2-enriched (2.52) compared with luminal A subtype, and for tumor clinical stages IIB (1.91), IIIA (3.54), and IIIB (3.94) compared with stage IIA women. OS was associated with country of residence, PAM50 intrinsic subtype, age, and tumor stage at diagnosis. While the latter is known to be influenced by access to care, including cancer screening, timely diagnosis and treatment, including access to more effective treatment protocols, it may also influence epigenetic changes that, potentially, impact molecular subtypes. Data derived from heretofore understudied populations with unique geographic ancestry and sociocultural experiences are critical to furthering our understanding of this complexity.

The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients.

Purposes: Most molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches. Patients and Methods: We collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes. Results: PAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors. Conclusions: This is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America. Clinical Trial Registration: ClinicalTrials.gov (Identifier: NCT02326857).

Mangroves as traps for environmental damage to metals: The case study of the Fundão Dam.

This essay is a conceptual framework for testing the causal mechanisms of system degradation by metals in the mangrove ecosystem. The Fundão Dam collapse caused massive damage to the marine environment on the Southern Atlantic and Brazilian coast, reaching various kilometers from its origin, becoming a source of contamination. Along this Brazilian coast are vast mangrove areas with high biodiversity, different geomorphology, and distinct ecological functioning. These mangroves support fisheries' productivity in the Tropical South Atlantic, in connection with Abrolhos Reef. Brazil does not have a protocol to monitor environmental damage in this ecosystem, and we proposed to develop a way to identify the impact and quantify it. Along the estuaries, to assess the damage, the plots were demarked in three regions: the upper, middle, and lower estuary, and in both types of forest: fridge and basin. Samples of sediment and leaves were collected bi-monthly to evaluate metal concentrations, especially iron and manganese, the most abundant metals in Fundão Dam. The monitoring also evaluated the forest structure, dynamics of the crabs' population, and flora productivity. First-year monitoring identifies a high concentration of iron or manganese in the sediment above the NOAAs' recommendation in all the estuaries. The concentration of Fe and Mn in sediment varies seasonally in magnitude, concentration, and types of metals between estuaries, sectors, and forests. The behavior of biological indicators in the presence of metals (type and concentration) differed between fauna and flora species. The monitoring recognized that the tailings mining from Fundão Dam impacted all estuaries by different magnitudes and persistence. These differences are due to geomorphology diversity, climate, and oceanographic influences.

Social isolation relaxation and the effective reproduction number (Rt) of COVID-19 in twelve Brazilian cities.

We analyzed the social isolation relaxation strategies adopted by the twelve biggest Brazilian cities in 2020, in relation to the number of cases, number of deaths and the effective reproduction number (Rt), which are internationally considered the fundamental epidemiological criteria for allowing wider population mobility in public spaces. The Brazilian central government has not set unique guidelines neither for closure nor for opening, and states and cities have taken the lead in strategy definition. Until July 31 2020, in Belém do Pará, Fortaleza, Manaus, Recife and Rio de Janeiro, where the epidemic peak had already been surpassed, and in Salvador and São Paulo, in which the peak seemed to be already reached, the Rt curve followed a decreasing path after the openings. Porto Alegre, a city in which the epidemic curve was flattened, had an increase in Rt after the start of relaxation. In Belo Horizonte, Brasília, Curitiba and Goiânia, where the curve was also flattened, the Rt remained stable after the opening. The decision on how to operationalize the relaxation of social isolation and the speed with which it happened was heterogeneous among the cities studied. Also, broad population testing strategies were not done in any of the cities.

A encruzilhada da judicialização da saúde no Brasil sob a perspectiva do Direito Comparado / Comparative law and the crossroads of the judicialization of health in Brazil / El derecho comparado y la encrucijada de la judicialización de la salud en Brasil

Objetivo: impacto da judicialização da saúde em diversas partes do mundo aponta para uma encruzilhada entre diversas formas de lidar com o fenômeno, em razão disso, o objetivo é contribuir para esse debate a partir de um panorama da judicialização no Brasil e um comparativo com experiências de outros países. Metodologia: tratou-se de revisão narrativa sobre o tema da judicialização da saúde em perspectiva comparada. A pesquisa foi dividida em duas etapas: contextualização da judicialização da saúde no cenário internacional, utilizando método comparativo na perspectiva do Direito Comparado, e a revisão narrativa sobre a judicialização da saúde no Brasil. Foram utilizados 46 trabalhos: 19 internacionais e 27 brasileiros. Resultados: duas abordagens diferentes para a judicialização da saúde se destacam nos estudos comparativos: a latino-americana e a sul-africana. Na primeira, o fenômeno apresenta maior magnitude com as decisões privilegiando o mínimo existencial, é especialmente complexo no Brasil, Colômbia e Costa Rica; na segunda a reserva do possível se sobressai nas decisões. A análise dos trabalhos realizados no Brasil subsidiou a construção de uma linha do tempo, proporcionando um panorama geral da judicialização no Brasil, e a trajetória desse fenômeno fluido, que se modificou ao longo do tempo à medida que novas problemáticas e formas de lidar foram surgindo e se desenvolvendo. Conclusões: o estudo evidencia que a judicialização da saúde é um fenômeno multifacetado, trazendo à tona um dilema entre vários caminhos a seguir. Porém, é um tema carente de estudos sobre o ponto de vista do usuário e dos desfechos sanitários decorrentes das ações judiciais. A complexidade do fenômeno culmina na diversidade de intervenções nos países, gerando conflitos entre garantir o direito à saúde e limitações orçamentárias. Conclui-se que a judicialização tem pontos positivos e negativos: ela é solução, mas também é problema.

Objective: the impact of the judicialization of health in various parts of the world points to a crossroads between diverse waysof dealing with the phenomenon, therefore, the work aims to contribute to this debate from an overview of judicialization in Brazil and a comparison with experiences from other countries. Methodology: this was a narrative review on the theme of the judicialization of health in a comparative perspective. The research was divided into two stages: contextualization of the judicialization of health in the international scenario, using a comparative method from the perspective of Comparative Law, and a narrative review on the judicialization of healthin Brazil. Forty-six works were used: 19 international and 27 Brazilian. Results: two different approaches to the judicialization of health stand out in comparative studies: the Latin American and the South African. In the first, the phenomenon presents greater magnitude with decisions favoring the minimum existential, it is especially complex in Brazil, Colombia, and Costa Rica; in the second, the reserve of the possible stands out in the decisions. The analysis of the work conducted in Brazil supported the construction of a timeline providing an overview of judicialization in Brazil, and the trajectory of this fluid phenomenon, which changed over time as new issues and ways of dealing with it emerged and developing. Conclusions: the study shows that the judicialization of health is a multifaceted phenomenon, bringing to light a dilemma between several paths to be followed. However, it is a subject that lacks studies on the user's point of view, and on the health outcomes resultedfrom lawsuits. The complexity of the phenomenon culminates in the diversity of interventions in countries, generating conflicts between guaranteeing the right to health and budgetary limitations. It is concluded that judicialization has positive and negative points:it is a solution, but it is also a problem.

Objetivo: el impacto de la judicialización de la salud en diferentes partes del mundo apunta a una encrucijada entre diferentes formas de abordar el fenómeno, por lo que el trabajo tiene como objetivo contribuir a este debate desde un panorama de la judicialización en Brasil y una comparación con experiencias. de otros países Metodología: se trató de una revisión narrativa sobre el tema de la judicialización de la salud en perspectiva comparada. La investigación se dividió en dos etapas: la contextualización de la judicialización de la salud en el escenario internacional, utilizando un método comparativo desde la perspectiva del Derecho Comparado, y la revisión narrativa sobre la judicialización de la salud en Brasil. Se utilizaron 46 obras: 19 internacionales y 27 brasileñas. Resultados: en los estudios comparados se destacan dos enfoques distintos de la judicialización de la salud: el latinoamericano y el sudafricano. En el primero, el fenómeno presenta mayor magnitud con decisiones a favor del mínimo existencial, es especialmente complejo en Brasil, Colombia y Costa Rica; en el segundo, la reserva de lo posible se destaca en las decisiones. El análisis del trabajo realizado en Brasil apoyó la construcción de un cronograma que brinde un panorama de la judicialización en Brasil, y la trayectoria de este fenómeno fluido, que cambió con el tiempo a medida que surgían y se desarrollaban nuevos temas y formas de abordarlo. Conclusiones: el estudio muestra que la judicialización de la salud es un fenómeno multifacético, que saca a la luz un dilema entre varios caminos a seguir. Sin embargo, es un tema que carece de estudios sobre el punto de vista del usuario y sobre los resultados de salud derivados de los juicios. La complejidad del fenómeno culmina en la diversidad de intervenciones en los países, generando conflictos entre la garantía del derecho a la salud y las limitaciones presupuestarias. Se concluye que la judicialización tiene puntos positivos y negativos; es una solución, pero también es un problema.