Cost-effectiveness analysis comparing companion diagnostic tests for EGFR, ALK, and ROS1 versus next-generation sequencing (NGS) in advanced adenocarcinoma lung cancer patients.

BACKGROUND: The treatment of choice for advanced non-small cell lung cancer is selected according to the presence of specific alterations. Patients should undergo molecular testing for relevant modifications and the mutational status of EGFR and translocation of ALK and ROS1 are commonly tested to offer the best intervention. In addition, the tests costs should also be taken in consideration. Therefore, this work was performed in order to evaluate the cost-effectiveness of a unique exam using NGS (next generation sequencing) versus other routinely used tests which involve RT-PCR and FISH. METHODS: The target population was NSCLC, adenocarcinoma, and candidates to first-line therapy. Two strategies were undertaken, strategy 1 corresponded to sequential tests with EGFR RT-PCR, then FISH for ALK and ROS1. Strategy 2 differed from 1 in that ALK and ROS1 translocation testing were performed simultaneously by FISH. Strategy 3 considered single test next-generation sequencing, a platform that includes EGFR, ALK and ROS1 genes. A decision tree analysis was used to model genetic testing options. From the test results, a microsimulation model was nested to estimate survival outcomes and costs of therapeutic options. RESULTS: The use of NGS added 24% extra true cases as well as extra costs attributed to the molecular testing. The ICER comparing NGS with sequential tests was US$ 3479.11/correct case detected. The NGS improved a slight gain in life years and QALYs. CONCLUSION: Our results indicated that, although precise, the molecular diagnosis by NGS of patients with advanced stage NSCLC adenocarcinoma histology was not cost-effective in terms of quality-adjusted life years from the perspective of the Brazilian supplementary health system.

Active and latent tuberculosis in refugees and asylum seekers: a systematic review and meta-analysis.

BACKGROUND: In 2018, there were 70.8 million refugees, asylum seekers and persons displaced by wars and conflicts worldwide. Many of these individuals face a high risk for tuberculosis in their country of origin, which may be accentuated by adverse conditions endured during their journey. We summarised the prevalence of active and latent tuberculosis infection in refugees and asylum seekers through a systematic literature review and meta-analyses by country of origin and host continent. METHODS: Articles published in Medline, EMBASE, Web of Science and LILACS from January 2000 to August 2017 were searched for, without language restriction. Two independent authors performed the study selection, data extraction and quality assessment. Random effect models were used to estimate average measures of active and latent tuberculosis prevalence. Sub-group meta-analyses were performed according to country of origin and host continent. RESULTS: Sixty-seven out of 767 identified articles were included, of which 16 entered the meta-analyses. Average prevalence of active and latent tuberculosis was 1331 per 100 thousand inhabitants [95% confidence interval (CI) = 542-2384] and 37% (95% CI = 23-52%), respectively, both with high level of heterogeneity (variation in estimative attributable to heterogeneity [I2] = 98.2 and 99.8%). Prevalence varied more according to countries of origin than host continent. Ninety-one per cent of studies reported routine screening of recently arrived immigrants in the host country; two-thirds confirmed tuberculosis bacteriologically. Many studies failed to provide relevant information. CONCLUSION: Tuberculosis is a major health problem among refugees and asylum seekers and should be given special attention in any host continent. To protect this vulnerable population, ensuring access to healthcare for early detection for prevention and treatment of the disease is essential.

The adoption of a new diagnostic technology for tuberculosis in two Brazilian cities from the perspective of patients and healthcare workers: a qualitative study.

BACKGROUND: This article presents the qualitative component linked to a larger study of implementation of the Xpert™ MTB/Rif technology in two Brazilian cities. Despite intrinsic advantages of new health technologies, its introduction can be disruptive to existing routines, and it is thus important to understand how these innovations are perceived by the different groups involved in its regular use. METHODS: This study was based on semi-structured interviews with patients, lab technicians, health care workers and managers involved with diagnosis and care of Tuberculosis (TB). The interviews had their content analyzed in order to abstract the different perspectives for the various actors. RESULTS: For patients the changes were not perceived as significant, since their greatest concerns were related to treatment and the stigma associated with TB. The professionals in general welcomed the new technique, which dramatically decreases the workload, time and reliability of diagnosis, in their view. However, we noted difficulties with the concomitant implementation of new IT technology for recording and reporting test results, which negatively impacted the time necessary to get lab diagnosis to physicians. CONCLUSIONS: Through this analysis we detected some bottlenecks in the surrounding environment, not necessarily linked to the technology itself but which could hamper considerably its advantages.

Yellow fever vaccine safety in immunocompromised individuals: a systematic review and meta-analysis.

BACKGROUND: Yellow fever (YF) is an arbovirus with variable severity, including severe forms with high mortality. The vaccination is the most effective measure to protect against the disease. Non-serious and serious adverse events have been described in immunocompromised individuals, but previous studies have failed to demonstrate this association. This systematic review assessed the risk of adverse events after YF vaccination in immunocompromised individuals compared with its use in non-immunocompromised individuals. METHODS: A search was conducted in the MEDLINE, LILACS, EMBASE, SCOPUS, DARE, Toxiline, Web of Science and grey literature databases for publications until February 2021. Randomized and quasi-randomized clinical trials and observational studies that included immunocompromised participants (individuals with HIV infection, organ transplants, with cancer, who used immunosuppressive drugs for rheumatologic diseases and those on immunosuppressive therapy for other diseases) were selected. The methodological quality of observational or non-randomized studies was assessed by the ROBINS-I tool. Two meta-analyses were performed, proportion and risk factor analyses, to identify the summary measure of relative risk (RR) in the studies that had variables suitable for combination. RESULTS: Twenty-five studies were included, most with risk of bias classified as critical. Thirteen studies had enough data to carry out the proposed meta-analyses. Seven studies without a comparator group had their results aggregated in the proportion meta-analysis, identifying an 8.5% [95% confidence interval (CI) 0.07-21.8] risk of immunocompromised individuals presenting adverse events after vaccination. Six cohort studies were combined, with an RR of 1.00 (95% CI 0.78-1.29). Subgroup analysis was performed according to the aetiology of immunosuppression and was also unable to identify an increased risk of adverse events following vaccination. CONCLUSIONS: It is not possible to affirm that immunocompromised individuals, regardless of aetiology, have a higher risk of adverse events after receiving the YF vaccine.

[Data processing of the Brazilian National System of Controlled Product Management for drug utilization research with antimicrobials]. / Tratamento de dados do Sistema Nacional de Gerenciamento de Produtos Controlados para estudos de utilização de medicamentos com antimicrobianos.

The Brazilian National System of Controlled Product Management (SNGPC) stores data on the dispensing of manufactured and compounded drugs and pharmaceutical inputs, whether controlled and antimicrobial, based on the records of private pharmacies and drugstores. This study assessed the quality of SNGPC data from the dispensing records of manufactured antibiotics, aiming to propose their use in drug utilization researchs (DURs), with a descriptive and retrospective design, analyzing the raw dataset of the SNGPC from January 2014 to December 2020. A total of 475,805,207 drug-dispensing records were collected. On average, antibiotics corresponded to 54.5% of the total records. The quality dimension "unreported" was systematically identified in the variables "active ingredient", "sex", "age" and "ICD-10". The amount of vials/bottles and packages ranged from one to 536 units and the amount of pharmaceutical inputs dispensed, from one to 7,500 units. Results show that 25% of the records exceed an individual therapy and the SNGPC has no critical mechanism to avoid dispensations outside the therapeutic standard for the class. Despite vulnerabilities due to data quality, which can be overcome, the SNGPC allows for the construction of different analytical plans, involving time and other aggregations, in the analysis of community use of antimicrobials and controlled drugs, which makes it a powerful source of data for DUR.

O Sistema Nacional de Gerenciamento de Produtos Controlados (SNGPC) armazena dados de dispensação de medicamentos industrializados, manipulados e insumos farmacêuticos sob controle especial e antimicrobianos, a partir dos registros de farmácias e drogarias privadas. Este trabalho explorou a qualidade dos dados inseridos no SNGPC, a partir dos registros de dispensação de antibióticos industrializados, com o objetivo de propor seu emprego em estudos de utilização de medicamentos (DUR). A pesquisa foi desenvolvida por meio de desenho descritivo e retrospectivo, examinando o conjunto dados brutos do sistema, para o período de janeiro de 2014 a dezembro de 2020. Um total de 475.805.207 registros de dispensação de medicamentos foi coletado. Os antibióticos corresponderam em média a 54,5% do total de registros. A dimensão de qualidade "não informado" foi identificada, sistematicamente, nas variáveis "princípio ativo", "sexo", "idade" e "CID-10". As quantidades de frascos e caixas variaram de 1 a 536 unidades, e as quantidades de formas farmacêuticas dispensadas de 1 a 7.500 unidades. Os resultados mostram que 25% dos registros extrapolam uma terapia individual e que o sistema não apresenta um mecanismo de crítica para evitar dispensações não conformes ao padrão terapêutico para a classe. Apesar das vulnerabilidades decorrentes da qualidade dos dados, que podem ser superadas, o SNGPC possibilita construir diferentes planos analíticos, envolvendo tempo e outras agregações, na investigação de uso comunitário de antimicrobianos e medicamentos sob controle especial, o que faz dele uma potente fonte de dados para DUR.

El Sistema Nacional de Gestión de Productos Controlados (SNGPC) almacena datos sobre la dispensación de medicamentos industrializados, manipulados, insumos farmacéuticos bajo control especial y de antimicrobianos con base en los registros de farmacias y de boticas privadas. Este trabajo analizó la calidad de los datos ingresados en el SNGPC relacionados a los registros de la dispensación de antibióticos industrializados, para proponer su posible aplicación en estudios sobre el uso de medicamentos (DUR); para ello, realizó un análisis descriptivo y retrospectivo del conjunto de datos brutos para el periodo de enero de 2014 a diciembre de 2020. Se recogieron un total de 475.805.207 registros de dispensación de medicamentos. Los antibióticos correspondieron en promedio al 54,5% del total de los registros. La dimensión de calidad "no informado" se identificó sistemáticamente en las variables "principio activo", "sexo", "edad" y "CIE-10". Las cantidades de viales y cajas oscilaron entre 1 y 536 unidades, y las cantidades de formas farmacéuticas dispensadas entre 1 y 7.500 unidades. Los resultados muestran que el 25% de los registros exceden una terapia individual y que el sistema no tiene un mecanismo crítico para evitar la dispensación que no se ajusta al patrón terapéutico de la clase. A pesar de las vulnerabilidades derivadas de la calidad de los datos, que pueden ser superadas, el SNGPC permite la construcción de diferentes planes analíticos, involucrando tiempo y otras agregaciones, en la investigación del uso comunitario de antimicrobianos y medicamentos bajo control especial, lo que hace que el Sistema sea una potente fuente de datos para DUR.

Theoretical model of sexual and reproductive health care: subsidies for evaluative research.

OBJECTIVE: To elaborate a Theoretical Model of Sexual and Reproductive Health care offered in Primary Health Care. METHOD: Documentary research, with a qualitative approach. Government documents and evaluative studies constituted the data sources, collected between August 2018 and June 2019, and analyzed based on the health evaluation literature. RESULTS: Promotion of Sexual and Reproductive Health and Clinical Care were two structural components of the theoretical model of sexual and reproductive health care in Primary Care. The model includes disease prevention activities, health promotion, treatments, and diagnoses related to sexual and reproductive health. CONCLUSION: The theoretical model developed in this study presents the theory that supports the operationalization of sexual and reproductive health care in primary care according to government regulations in Brazilian scenario and may be useful in future evaluative research on the subject.

A Systematic Review and a Meta-Analysis of the Yellow Fever Vaccine in the Elderly Population.

We conducted a systematic review and a meta-analysis to assess the risk of serious adverse events in the elderly after yellow fever vaccination compared to the non-elderly population. We searched multiple databases and grey literature, and we selected research without language and publication date restrictions. Studies were analyzed in a descriptive way and meta-analyzed and expressed in terms of prevalence ratio and risk ratio with a 95% confidence interval, depending on the degree of heterogeneity found. A total of 18 studies were included and 11 were meta-analyzed. The results obtained through the meta-analysis showed a risk of serious adverse events after yellow fever vaccination three times higher for the elderly when compared to the non-elderly population and five times higher for persons > 70 years. In relation to adverse event types, viscerotropic disease associated with the yellow fever vaccine had a risk that was six times higher when compared to the population < 60 years. The evidence found supports that the vaccine indication in individuals > 60 years of age should be based on a careful analysis of individual benefit-risk assessments. The results found suggest a higher risk of events for individuals > 70 years, especially for viscerotropic and neurotropic disease associated with YFV contraindicating the use of the YFV in this age group.

Efficacy and costs of nanocrystalline silver dressings versus 1% silver sulfadiazine dressings to treat burns in adults in the outpatient setting: A randomized clinical trial.

BACKGROUND: Nanocrystalline silver dressings can reduce the number of changes, facilitating burn wound management. However, the evidence regarding their efficacy and cost-consequences compared to well-established treatments, such as 1% silver sulfadiazine, is still scarce. OBJECTIVE: To determine the efficacy, safety, and costs of nanocrystalline silver dressings compared to 1% silver sulfadiazine dressings to treat adult patients with burns. STUDY DESIGN AND SETTING: Randomized, single-center, single-blind trial conducted at a referral hospital in São Paulo, Brazil. METHODS: 100 adult patients were randomized 1:1 to nanocrystalline silver (n = 50) or 1% silver sulfadiazine (n = 50). The primary outcome was the proportion of participants with complete re-epithelization at day 15 after randomization. Secondary outcomes included the number of dressing changes, direct medical costs (in international dollars, I$), pain intensity, the incidence of infections, number of patients undergoing surgery, and adverse events. RESULTS: On day 15, the proportion of patients who reached the primary outcome did not differ significantly between participants treated with nanocrystalline silver dressings (24 [48%]) and those treated with 1% silver sulfadiazine dressings (26 [52%]); risk difference of -4.0 percentage points (95% confidence interval [CI], -17 to 9; P = 0.56). The number of patients undergoing surgical intervention was similar between groups (6% vs. 6%), and no local or serious adverse events were reported. The mean (standard deviation, SD) number of dressing changes in the nanocrystalline silver group was 4.1 (2.3), and the corresponding estimate in the 1% silver sulfadiazine group was 9.6 (6.7); mean difference of -5.56 (95% CI), -7.57 to -3.55, P < 0.001). Treatment with nanocrystalline silver dressing incurred significant cost reductions in medical materials, human resources, and administrative labor. However, the mean total cost with nanocrystalline silver dressing was higher compared to 1% silver sulfadiazine dressings: I$496.37 (445.90) vs. I$274.73 (182.76); mean difference = 221.63 (95% CI, 89.04 to 354.23, P = 0.001). The main driver of higher mean total costs among nanocrystalline silver-treated participants was the purchase cost of the dressings, representing 79.3% of the total cost in the nanocrystalline silver group but only 15.2% in the 1% silver sulfadiazine group. CONCLUSION: We found no evidence of a difference between nanocrystalline silver and 1% silver sulfadiazine dressings regarding efficacy and safety outcomes. Nanocrystalline silver dressings were associated with an increase in the total costs, but they could result in important savings for an institution (less changes of dressings, reducing human resources burden), especially if acquisition costs can be decreased. Additional cost-effectiveness studies are warranted. TRIAL REGISTRATION NUMBER: NCT02108535.

Testing COVID-19 in Brazil: fragmented efforts and challenges to expand diagnostic capacity at the Brazilian Unified National Health System.

Since the first recorded case of COVID-19 on February 26, 2020, Brazil has seen an exponential growth in the number of cases and deaths. The national testing approach has been insufficient to correctly use this tool in the support of containing the epidemic in the country. In this communication, we discuss efforts and challenges to scale-up COVID-19 testing at the Brazilian Unified National Health System (SUS). This communication presents the initial results of the research project created to investigate the political, industrial, technological, and regulatory aspects that may affect the diagnostic and testing capacity for COVID-19 in Brazil. The paper draws on the review of academic literature, media publication, and collection of public data on tests purchase and regulation. It enlists initiatives to enhance PCR testing, national production and development of technologies, as well as regulatory measures to fast-track new tests. Our analysis indicates some points of reflection. Firstly, the lack of a consistent national strategy to fight COVID-19 exarcebated supply problems of diagnostic components. If the country was eventually able to circumvent this situation, it still faces a more structural dependency on the importation of diagnostic components. Secondly, the discontinued funding and distribution of tests may have implied health policy fragmentation and the growing importance of local governments and non-state actors to fighting the epidemics within SUS. Finally, initiatives established since the second semester of 2020 have expanded the testing capacity at SUS. However, it has not been sufficient to control the progress of the epidemic in the country.

Dynamics of patents, orphan drug designation, licensing, and revenues from drugs for rare diseases: The market expansion of eculizumab.

BACKGROUND: This study examines the dynamics of the eculizumab patenting, orphan designation, and marketing authorization process in different countries and regulatory systems and analyzes drug revenues since its first marketing authorization. METHODS: A retrospective case study was conducted. Multiple information sources were used to: determine the status of eculizumab patents; examine the designation of orphan drug status by US, European, Japanese, and Brazilian regulatory authorities to determine registration status and approved clinical indications; estimate the prevalence of associated clinical conditions; investigate the history of the drug manufacturer, Alexion Pharmaceuticals, Inc., and its financialized business model; and examine global eculizumab sales revenues since its first marketing authorization. RESULTS: Our search yielded 32 patent families divided into 98 applications. The first patent granted was filed in 1995 by Alexion Pharmaceuticals, Inc. in the US. Eculizumab has always been as an orphan drug, except in the Brazilian regulatory agency. All clinical indications approved thus far refer to rare diseases (e.g., paroxysmal nocturnal hemoglobinuria syndrome, atypical hemolytic-uremic syndrome, refractory and generalized myasthenia gravis, and neuromyelitis optica spectrum disorder). Alexion's revenues amounted to more than US$25 billion between 2007 and 2019, showing a growing trend. Eculizumab led sales from the beginning, being the only product in the company's portfolio until 2015. In 2019, the drug accounted for 79.1% of all revenues. DISCUSSION: Our findings show that a strategy focused on obtaining orphan drug designation, expanding therapeutic indications and the geographic range of marketing approvals, extending monopoly periods, and prioritizing public procurement niches has enhanced revenues and helped the company achieve leadership in a highly specific and profitable market.

[Mother's understanding of care produced by health team in a pediatric hospital]. / Compreensão das mães sobre a produção do cuidado pela equipe de saúde de um hospital infantil.

The purpose of this paper was to understand how the mothers perceive some aspects of care provided to their children. That was a qualitative study whose data were obtained by means of semi-structured interviews. Seven interviews were carried out with children's caregivers who were hospitalized in a public hospital in Fortaleza, CE, Brazil, in 2006. For data analysis it was used a referential related to the elaborated thematics. Five thematics appeared: Caring in the sense of establishing procedures, Identifying the caring professional, the Professional and the specialized and/or painful care, Night Care, and Difficulties in the relationship between caregivers and professionals. We can conclude that health care is still very much limited to technical procedures, knowing how to do, there is also a gap regarding to the importance and meaning of more humanized care, integral to with human beings.

The case of eculizumab: litigation and purchases by the Brazilian Ministry of Health.

OBJECTIVES: This study examined the purchases of eculizumab, a high-cost monoclonal antibody used in the treatment of rare diseases by Brazilian federal agencies, in terms of purchased quantities, expenditures, and prices. METHODS: Eculizumab purchases made between March 2007 and December 2018 were analyzed, using secondary data extracted from the Federal Government Purchasing System (SIASG in Portuguese). The following aspects were assessed: number of purchases, purchased quantities, number of daily doses defined per 1,000 inhabitants per year, annual expenditures, and prices. The prices were adjusted by the National Broad Consumer Price Index for December 2018. Linear regression was used for trend analysis. RESULTS: All acquisitions by federal agencies were made by the Brazilian Ministry of Health. The purchases began in 2009 with tender waiver to comply with legal demand. There was an increasing trend in the number of purchases and quantities acquired over time. Two hundred and eighty-three purchases were made, totaling 116,792 units purchased, 28.2% of them in 2018. The adjusted total expenses summed more than R$ 2.44 billion. After market approval by the Brazilian Health Regulatory Agency, the weighted average price fell approximately 35%, to values under the Medicines Market Chamber of Regulation established prices. CONCLUSION: Eculizumab represented extremely significant expenditures for the Brazilian Ministry of Health during the period. All purchases were made to meet demands from lawsuits, outside the competitive environment. The market approval of eculizumab promoted an important price reduction. This study indicates the relevance of licensing and the need for permanent monitoring and auditing of drug purchases to meet legal demands.

Cost-Effectiveness Analysis of Point-of-Care Rapid Testing Versus Laboratory-Based Testing for Antenatal Screening of Syphilis in Brazil.

OBJECTIVES: Severe consequences of mother-to-child transmission of syphilis and high increasing incidence of congenital syphilis remains an important public health problem in Brazil. Our objective was to assess the cost-effectiveness of a rapid point-of-care test (RT) and treatment of positive mothers immediately compared with a laboratory-based standard test (ST) with treatment at next follow-up visit. METHODS: A decision analytic model was developed to estimate the incremental cost-effectiveness ratio (ICER) between antenatal syphilis screening strategies. The model was built with lifetime horizon from Brazilian health system perspective using 3% and 5% discount rates. A hypothetical cohort of pregnant women at reproductive age were used in the model. Health outcomes: low birth weight, stillbirths, neonatal deaths and congenital syphilis were estimated in disability-adjusted life-years (DALYs) lost. Microcosting study and secondary data provided parameters of direct medical costs. Probabilistic sensitivity analysis was undertaken. RESULTS: For base case, the mean cost per pregnant woman screened was $2.63 (RT) and $2.48 (ST), respectively. Maternal syphilis was associated with a loss of 0.0043 DALYs (RT) and 0.0048 DALYs (ST) per mother screened. Expected value of incremental cost per DALY averted was $298.08. After 10 000 probabilistic sensitivity analysis model runs, incremental cost and health benefits were $0.15 (95% credible interval -1.56 to 1.92) and 0.00042 DALYs (95% credible interval -0.0036 to 0.0044), respectively, with a mean ICER of $357.44 per DALY. Screening with RT has a 58% chance of being the optimal strategy at a threshold of $3,200 per DALY. CONCLUSIONS: In Brazil, antenatal screening with syphilis RT and immediate treatment is likely to be cost-effective compared with standard screening and must be prioritized in local settings.

Challenges and opportunities for telehealth during the COVID-19 pandemic: ideas on spaces and initiatives in the Brazilian context. / Desafios e oportunidades para telessaúde em tempos da pandemia pela COVID-19: uma reflexão sobre os espaços e iniciativas no contexto brasileiro.

COVID-19 has created enormous challenges for health systems worldwide, with the rapidly growing number of deaths and critical patients with pneumonia requiring ventilatory support. Alternative methods to control the spread of the disease such as social isolation, extreme quarantine measures, and contact tracing have been used around the world. However, these measures may not be totally effective to fight COVID-19, in step with the necessary national preparations to meet the new patient care demands. A wide range of digital technologies can be used to enhance these public health strategies, and the pandemic has sparked increasing use of telehealth. This field has grown considerably in Brazil in recent years. Still, despite the intense proliferation of recommendations and rules, until the current pandemic the country still lacked a fully consolidated regulatory framework. The emergence of COVID-19 marks a key moment in the expansion of applications and use of telehealth for improving the health system's response to the current crisis. The article discusses telehealth's contribution to the fight against COVID-19 and the recent initiatives triggered in Brazil as opportunities for the consolidation of telemedicine and improvement of the Brazilian Unified National Health System. The authors conclude that telehealth offers capabilities for remote screening, care and treatment, and assists monitoring, surveillance, detection, prevention, and mitigation of the impacts on healthcare indirectly related to COVID-19. The initiatives triggered in this process can reshape the future space of telemedicine in health services in the territory.

Three decades of telemedicine in Brazil: Mapping the regulatory framework from 1990 to 2018.

This study characterized the evolution of Brazilian public telemedicine policy in the Brazilian Unified Health System for 30 years from 1988 to 2019 by analyzing its legal framework. We identified 79 telemedicine-related legislations from the federal government (laws, decrees, and ordinances) and 31 regulations of federal councils of health professionals. Three historical phases were established according to the public policy cycle, and material was classified according to the purpose of the normative documents. The content analysis was based on the advocacy coalition framework model. Of the federal legislations, 8.9% were for the Formulation/Decision-Making phase, 43% for the Organization/Implementation phase, and 48.1% for the Expansion/Maturation phase of telemedicine policy in Brazil. The Federal Council of Medicine was the most active in standardizing telemedicine and was responsible for 21 (67.7%) regulations. The first legislations were passed in 2000; however, the coalitions discussed topics related to telemedicine and created their belief systems from the 1990's. The time cycle which included formulation and decision making for Brazilian telemedicine policy, extended until 2007 with the creation of several technical working groups. The expansion and maturation of telemedicine services began in 2011 with the decentralization of telemedicine policy actions across the country. Telemedicine centers which performed telediagnosis influenced the computerization of primary health care units. We conclude that Brazilian telemedicine field has greatly grown and changed in recent years. However, despite the proliferation of legislations and regulations in the period studied, there is still no fully consolidated process for setting up a wholly defined regulatory framework for telemedicine in Brazil.

[The incorporation of nusinersen by the Brazilian Unified National Health System: critical thoughts on the institutionalization of health technology assessment in Brazil]. / A incorporação do nusinersena no Sistema Único de Saúde: uma reflexão crítica sobre a institucionalização da avaliação de tecnologias em saúde no Brasil.

In April 2019, a ruling was signed for the incorporation of the drug nusinersen by the Brazilian Unified National Health System (SUS). Nusinersen is the most expensive drug ever incorporated by the SUS and is used to treat type I 5q spinal muscular atrophy. The incorporation has been described as a milestone in decision-making on new technologies in the SUS, enabled through a risk-sharing agreement. The article discusses the process involved in the incorporation of nusinersen, highlighting the context, timing, and technical issues, in addition to possible consequences for the institutionalization of health technology assessment (HTA) in the SUS. The study used an exploratory method, reviewing public information produced by the Commission for Incorporation of Technologies in the SUS (CONITEC) and searches in government databanks on prices and purchases. A timeline was produced, describing the key points in the process of incorporation. There were two formal requests for the drug's incorporation. The first was submitted by the Division of Science, Technology, and Strategic Inputs (SCTIE) of the Brazilian Ministry of Health and was turned down unanimously in November 2018. This was followed by a petition by the head of the SCTIE to the Attorney General's Office (AGU) to overrule the recommendation by the CONITEC plenary. The AGU recommended a new submission, made by the drug's manufacturing company, which was approved unanimously in March 2019. The was no addition of new evidence or a price reduction to justify the change of decision. No elements were identified in the risk-sharing agreement. This suggests problems of transparency and accountability, as well as risks in the process of institutionalization of HTA that had been underway in the SUS.

Em abril de 2019, foi assinada a portaria de incorporação do medicamento nusinersena no Sistema Único de Saúde (SUS). É o medicamento mais caro já incorporado ao SUS, para uso no tratamento de atrofia muscular espinhal 5q tipo I. A incorporação é referida como um marco na tomada de decisão sobre novas tecnologias no SUS, a ser viabilizada por meio de acordo de partilha de risco. O trabalho discute o processo de incorporação do nusinersena, destacando aspectos contextuais, temporais e técnicos, além de possíveis consequências para a institucionalização da avaliação de tecnologias em saúde (ATS) no SUS. Seguiu método exploratório, com revisão de informações públicas produzidas pela Comissão de Incorporação de Tecnologias no SUS (CONITEC) e busca em bancos de dados governamentais de preços e compras. Foi produzida linha temporal descrevendo os pontos-chave do processo de incorporação. Houve dois pedidos de incorporação do medicamento. O primeiro, submetido pela Secretaria de Ciência, Tecnologia e Insumos Estratégicos (SCTIE) do Ministério da Saúde, negado por unanimidade, em novembro de 2018. Seguiu-se o pedido do Secretário da SCTIE à Advocacia-Geral da União (AGU), para que pudesse decidir de forma contrária à recomendação do plenário da CONITEC. A AGU recomendou uma nova submissão, feita pela empresa produtora e aprovada por unanimidade, em março de 2019. Não houve acréscimo de novas evidências ou redução de preço que justificassem a mudança de decisão. Não foram identificados os elementos constituintes do acordo de partilha de risco. São sinalizados problemas de transparência e accountability, bem como riscos ao processo de institucionalização da ATS que vinha em curso no SUS.

Resumen: En abril de 2019, se firmó el decreto de incorporación del medicamento nusinersén en el Sistema Único de Salud brasileño (SUS). Es el medicamento más caro que se ha incorporado al SUS para su uso en el tratamiento de la atrofia muscular espinal 5q tipo I. La incorporación del mismo está considerada como un marco de referencia en la toma de decisiones sobre nuevas tecnologías en el SUS, que puede ser viable mediante el acuerdo de distribución de riesgo. El trabajo discute el proceso de incorporación del nusinersén, destacando aspectos contextuales, temporales y técnicos, además de posibles consecuencias para la institucionalización de la evaluación de tecnologías en salud (ETS) en el SUS. El trabajo siguió el método exploratorio, con una revisión de la información pública, generada por la Comisión de Incorporación de Tecnologías en el SUS (CONITEC) y la búsqueda en bancos de datos gubernamentales de precios y compras. Se creó una línea temporal, describiendo los puntos-clave del proceso de incorporación. Hubo dos peticiones de incorporación del medicamento. La primera, sometida a la Secretaría de Ciencia, Tecnología e Insumos Estratégicos (SCTIE) del Ministerio de Salud, rechazada por unanimidad, en noviembre de 2018. A lo que le siguió la petición del Secretario de la SCTIE a la Abogacía-General de la Unión (AGU), para que pudiese decidir en otro sentido respecto a la recomendación del pleno de la CONITEC. La AGU recomendó una nueva remisión, realizada por la empresa productora y aprobada por unanimidad, en marzo de 2019. No se produjo un incremento de nuevas evidencias o una reducción del precio que justificasen el cambio de decisión. No se identificaron los elementos constituyentes del acuerdo de distribución de riesgo. Se señalaron los problemas de transparencia y rendición de cuentas, así como riesgos para el proceso de institucionalización de la ETS que estaba en curso en el SUS.

Women economic empowerment via cash transfer and microcredit programs is enough to decrease intimate partner violence? Evidence from a systematic review.

Intimate partner violence (IPV) is a worldwide public health problem. Many proposals aiming to eliminate its occurrence include the empowerment of women through their socio-economic development. In this context, some studies suggested that microcredit programs (MP) and cash transfer programs (CTP) are initiatives that can also reduce the risk of IPV. Others pointed to an opposite effect. The objective of this study was to investigate the influence of women's economic empowerment in MP and CTP on the risk of physical, psychological and sexual violence through a systematic review. Papers/documents selection was conducted by two researchers according to the following criteria: published in English, Portuguese or Spanish; primary data; assessing the effect of MP or CTP on IPV; in heterosexual couples; on women beneficiaries of the intervention; using a comparator group eligible for an MP or CTP; and focusing on risk IPV as the outcomes. Our results showed that the impact of MP are mixed when it comes to physical and physical/sexual violence. Even so, the review suggests that the effect of MP on sexual violence is trivial or nonexistent. Regarding the impact of CTPs, the present study showed that the effects on physical, physical/sexual, psychological, and sexual violence were also heterogeneous. Women more empowered and with some autonomy could be at risk. Despite that, participation in the empowerment program should be encouraged for poor women and families. However, parallel interventions to lead with IPV should be addressed to the main actions to reduce the risk of increasing IPV prevalence in certain scenarios.

Cost-effectiveness of QuantiFERON-TB Gold In-Tube versus tuberculin skin test for diagnosis and treatment of Latent Tuberculosis Infection in primary health care workers in Brazil.

OBJECTIVES: The goal of this study was to perform a cost-effectiveness analysis from the public health system perspective, comparing five strategies for Latent Tuberculosis Infection (LTBI) diagnosis in primary health care workers in Brazil. DESIGN: Analytical model for decision making, characterized by cost-effectiveness analysis. SETTING: Primary Care Level, considering primary health care workers in Brazil. PARTICIPANTS: An analytical model for decision making, characterized by a tree of probabilities of events, was developed considering a hypothetical cohort of 10,000 primary health care workers, using the software TreeAge Pro™ 2013 to simulate the clinical and economic impacts of new diagnostic technology (QuantiFERON®-TB Gold in-Tube) versus the traditional tuberculin skin test. METHODS: This model simulated five diagnostic strategies for LTBI in primary health care workers (HCW) in Brazil: tuberculin skin testing using ≥5 mm cut-off, tuberculin skin testing ≥10 mm cut-off, QuantiFERON®-TB Gold in-Tube, tuberculin skin testing using ≥5 mm cut-off confirmed by QuantiFERON®-TB Gold In-Tube if TST positive, tuberculin skin testing using ≥10 mm cut-off confirmed by QuantiFERON®-TB Gold In-Tube if TST positive. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome measures are the number of individuals correctly classified by the test and the number of Tuberculosis cases avoided. RESULTS: The most cost-effective strategy was the tuberculin skin test considering ≥10mm cut-off. The isolated use of the QuantiFERON®-TB Gold In-Tube revealed the strategy of lower efficiency with incremental cost-effectiveness ratio (ICER) of US$ 146.05 for each HCW correctly classified by the test. CONCLUSIONS: The tuberculin skin test using ≥10 mm cut-off was the most cost-effective strategy in the diagnosis of Latent Tuberculosis Infection in primary health care works in Brazil.

[The rights of the child in family and in society: cartography of laws and resolutions]. / A criança e seus direitos na familia e na sociedade: uma cartografia das leis e resoluções.

This research is a documental review of laws, resolutions and others documents related to children and adolescents' rights existing in Brazil and overseas, aiming thus a comprehension and greater knowledge about the child and his rights. The documents chosen were: 1959's Pronouncement of Child Rights; 1988's Federal Constitution of Brazil; 1988's Letter of Hospitalized Child: 1990's Statute of Child and Adolescent; and the Rights of Child and Adolescent hospitalized (Resolution 41/95). We did floating reading of all documents, mentioning relevant articles to theme, highlighting some considerations. We conclude that already exist legislations that protect the right of child, though it is necessary to ensure the use of these rights.