Economic and budgetary impact evaluation of isavuconazole (Cresemba®) versus voriconazole (Vfend®) for the treatment of patients with possible invasive aspergillosis from the perspective of the Brazilian supplementary health system.

OBJECTIVES: This study aims to evaluate the cost-utility and the budgetary impact of isavuconazole compared to voriconazole in patients with suspected invasive aspergillosis (IA) from the perspective of the Brazilian supplementary health system (SHS). METHODS: In this model, a decision tree was developed and included patients with possible IA. Efficacy parameters were extracted from the clinical studies. Drug acquisition, hospitalization costs and adverse events were also collected. Alternative 3- and 10-year time horizon scenarios were used. In addition, deterministic and probabilistic sensitivity analyses were simulated. A budget impact analysis of isavuconazole versus voriconazole was performed, assuming a time horizon of 5 years. In addition, sensitivity analyses were conducted to assess the robustness of the model. Results are reported in Brazilian Real (BRL), year values 2022. RESULTS: The economic analysis of the base case showed that isavuconazole is associated with a saving of 95,174.00 BRL per patient compared to voriconazole. All other simulated scenarios showed that isavuconazole is dominant versus comparators when considering a willingness to pay 40,688.00 BRL/Quality-Adjusted Life Years (QALY). The results were considered robust by the sensitivity analyses. The budget impact analysis showed that the incorporation of isavuconazole generates savings to the SHS, compared to voriconazole, of approximately 20.5 million BRL in the first year. This reaches about 54 million BRL in the fifth incorporation year, considering the market penetration of 20% in the first year, and 50% in the fifth year. CONCLUSION: Compared with voriconazole, isavuconazole is regarded as a dominant treatment strategy for patients with suspected IA and generates savings for the SHS.

Rapid, systematic updating of movement by accumulated decision evidence.

Acting in the natural world requires not only deciding among multiple options but also converting decisions into motor commands. How the dynamics of decision formation influence the fine kinematics of response movement remains, however, poorly understood. Here we investigate how the accumulation of decision evidence shapes the response orienting trajectories in a task where freely-moving rats combine prior expectations and auditory information to select between two possible options. Response trajectories and their motor vigor are initially determined by the prior. Rats movements then incorporate sensory information as early as 60 ms after stimulus onset by accelerating or slowing depending on how much the stimulus supports their initial choice. When the stimulus evidence is in strong contradiction, rats change their mind and reverse their initial trajectory. Human subjects performing an equivalent task display a remarkably similar behavior. We encapsulate these results in a computational model that, by mapping the decision variable onto the movement kinematics at discrete time points, captures subjects' choices, trajectories and changes of mind. Our results show that motor responses are not ballistic. Instead, they are systematically and rapidly updated, as they smoothly unfold over time, by the parallel dynamics of the underlying decision process.

Performance of Metarhizium rileyi Nm017: nutritional supplementation to improve production and quality conidia.

This study aimed to analyze the effect of nutritional supplements on improving conidia production of Metarhizium rileyi Nm017 at laboratory scale (yields of conidia/substrate and biomass/substrate, and substrate consumption). Also, the influence on quality parameters were evaluated (germination at 36 and 48 h, enzymatic activity, and insecticidal activity on Helicoverpa zea). Six treatments (T1-T6) were assessed and all of them reached maximum conidia concentration after 7 days fermentation, a feasible production timetable. Yields from treatment T6 (yeast extract + V8 juice) were 1.5-threefold higher than the other treatments. Conidia from T6 reached germinations of 56% and 12% at 36 and 48 h, respectively, higher than T1 (without supplements), which had the lowest values found. M. rileyi conidia obtained from treatment T6 had the highest enzymatic activity (0.45 U chitinase g-1, 0.28 U lipase g-1, and 1.29 U protease g-1). However, treatments with the highest conidia yields and enzymatic activity were not positively correlated to the efficacy against H. zea. When M. rileyi was produced on T5 (yeast hydrolysate + V8 juice), conidia were 35% more virulent than treatment T6. The findings evidenced the noticeable impact of nutritional substrate amended for conidia production and quality. This work showed the relevance of insecticidal activity assessment as a selection criterion in the mass production development of a biocontrol agent.

Análise de impacto orçamentário de dispositivos contraceptivos na saúde suplementar brasileira / Budget impact analysis of contraceptive devices on Brazilian supplementary health

Objetivo: Analisar o impacto orçamentário da adoção de dispositivos contraceptivos reversíveis de longa duração em uma operadora de plano de saúde localizada no Sul do Brasil. Especificamente, analisamos a incorporação do implante subdérmico de etonogestrel (Implanon®) como alternativa ao sistema intrauterino de levonorgestrel (DIU Mirena® ou DIU Kyleena®), ao longo de um período de 15 anos. Métodos: Realizamos uma análise do impacto orçamentário incremental, considerando a inclusão gradual do implante subdérmico de etonogestrel. Foram considerados dados de uma operadora de planos de saúde com mais de 600.000 beneficiários. O horizonte temporal de 15 anos permitiu uma avaliação abrangente dos efeitos financeiros. Resultados: Identificamos 5.345 pacientes elegíveis para a utilização de contraceptivos reversíveis de longa duração. No cenário em que somente o sistema intrauterino de levonorgestrel era adotado, projetou-se um impacto orçamentário total de R$ 746.379.857,80 ao longo de 15 anos. No cenário alternativo, com a incorporação gradual do implante subdérmico, o impacto orçamentário total foi calculado em R$ 689.800.196,83. Isso resultou em um impacto orçamentário incremental negativo de -R$ 56.579.660,97 ao longo do período. Conclusão: A análise de impacto orçamentário realizada indica um potencial benefício financeiro ao adotar o implante subdérmico de etonogestrel como alternativa ao sistema intrauterino de levonorgestrel para contracepção. Esse achado sugere possíveis reduções de custos na área de saúde suplementar no Brasil, reforçando a importância de avaliar opções economicamente viáveis.

Objective: To analyze the budgetary impact of the adoption of long-acting reversible contraceptive devices in a health plan operator located in southern Brazil. Specifically, we analyzed the incorporation of the etonogestrel subdermal implant (Implanon®) as an alternative to the levonorgestrel intrauterine system (Mirena® IUD or Kyleena® IUD), over a period of 15 years. Methods: We performed an analysis of the incremental budgetary impact, considering the gradual inclusion of the etonogestrel subdermal implant. Data from a health plan operator with more than 600,000 beneficiaries were considered. The 15-year time horizon allowed for a comprehensive assessment of the financial effects. Results: We identified 5,345 patients eligible for the use of long-acting reversible contraceptives. In the scenario where only the levonorgestrel intrauterine system was adopted, a total budget impact of BRL 746,379,857.80 was projected over 15 years. In the alternative scenario, with the gradual incorporation of the subdermal implant, the total budgetary impact was calculated at BRL 689,800,196.83. This resulted in a negative incremental budgetary impact of -R$56,579,660.97 over the period. Conclusion: The budget impact analysis carried out indicates a potential financial benefit in adopting the etonogestrel subdermal implant as an alternative to the levonorgestrel intrauterine system for contraception. This finding suggests possible cost reductions in the supplementary healthcare area in Brazil, reinforcing the importance of evaluating economically viable options.

Temporal integration is a robust feature of perceptual decisions.

Making informed decisions in noisy environments requires integrating sensory information over time. However, recent work has suggested that it may be difficult to determine whether an animal's decision-making strategy relies on evidence integration or not. In particular, strategies based on extrema-detection or random snapshots of the evidence stream may be difficult or even impossible to distinguish from classic evidence integration. Moreover, such non-integration strategies might be surprisingly common in experiments that aimed to study decisions based on integration. To determine whether temporal integration is central to perceptual decision-making, we developed a new model-based approach for comparing temporal integration against alternative 'non-integration' strategies for tasks in which the sensory signal is composed of discrete stimulus samples. We applied these methods to behavioral data from monkeys, rats, and humans performing a variety of sensory decision-making tasks. In all species and tasks, we found converging evidence in favor of temporal integration. First, in all observers across studies, the integration model better accounted for standard behavioral statistics such as psychometric curves and psychophysical kernels. Second, we found that sensory samples with large evidence do not contribute disproportionately to subject choices, as predicted by an extrema-detection strategy. Finally, we provide a direct confirmation of temporal integration by showing that the sum of both early and late evidence contributed to observer decisions. Overall, our results provide experimental evidence suggesting that temporal integration is an ubiquitous feature in mammalian perceptual decision-making. Our study also highlights the benefits of using experimental paradigms where the temporal stream of sensory evidence is controlled explicitly by the experimenter, and known precisely by the analyst, to characterize the temporal properties of the decision process.

COVID-19 in real world: Survival and medical costs of hospitalized patients in Brazil´s first wave.

OBJECTIVE: To evaluate survival and direct medical costs of patients admitted in private hospitals with COVID-19 during the first wave. METHODS: A retrospective, observational study analyzing survival and the economic data retrieved on hospitalized patients with COVID-19. Data from March 2020 to December 2020. The direct cost of hospitalization was estimated using the microcosting method with each individual hospitalization. RESULTS: 342 cases were evaluated. Median age of 61.0 (95% CI 57.0‒65.0). 194 (56.7%) were men. The mortality rate was higher in the female sex (p = 0.0037), ICU (p < 0.001), mechanical ventilation (p<0.001) and elderly groups. 143 (41.8%) patients were admitted to the ICU (95% CI 36.6%-47.1%), of which 60 (41.9%) required MV (95% CI 34.0%-50.0%). Global LOS presented median of 6.7 days (95% CI 6.0-7.2). Mean costs were US$ 7,060,00 (95% CI 5,300.94-8,819,00) for each patient. Mean cost for patients discharged alive and patients deceased was US$ 5,475.53 (95% CI 3,692.91-7,258.14) and US$ 12,955.19 (95% CI 8,106.61-17,803.76), respectively (p < 0.001). CONCLUSIONS: Patients admitted with COVID-19 in these private hospitals point to great economic impact, mainly in the elderly and high-risk patients. It is key to better understand such costs in order to be prepared to make wise decisions during the current and future global health emergencies.

Recurrent networks endowed with structural priors explain suboptimal animal behavior.

The strategies found by animals facing a new task are determined both by individual experience and by structural priors evolved to leverage the statistics of natural environments. Rats quickly learn to capitalize on the trial sequence correlations of two-alternative forced choice (2AFC) tasks after correct trials but consistently deviate from optimal behavior after error trials. To understand this outcome-dependent gating, we first show that recurrent neural networks (RNNs) trained in the same 2AFC task outperform rats as they can readily learn to use across-trial information both after correct and error trials. We hypothesize that, although RNNs can optimize their behavior in the 2AFC task without any a priori restrictions, rats' strategy is constrained by a structural prior adapted to a natural environment in which rewarded and non-rewarded actions provide largely asymmetric information. When pre-training RNNs in a more ecological task with more than two possible choices, networks develop a strategy by which they gate off the across-trial evidence after errors, mimicking rats' behavior. Population analyses show that the pre-trained networks form an accurate representation of the sequence statistics independently of the outcome in the previous trial. After error trials, gating is implemented by a change in the network dynamics that temporarily decouple the categorization of the stimulus from the across-trial accumulated evidence. Our results suggest that the rats' suboptimal behavior reflects the influence of a structural prior that reacts to errors by isolating the network decision dynamics from the context, ultimately constraining the performance in a 2AFC laboratory task.

COVID-19 in real world: Survival and medical costs of hospitalized patients in Brazils first wave

ABSTRACT Objective: To evaluate survival and direct medical costs of patients admitted in private hospitals with COVID-19 during the first wave. Methods: A retrospective, observational study analyzing survival and the economic data retrieved on hospitalized patients with COVID-19. Data from March 2020 to December 2020. The direct cost of hospitalization was estimated using the microcosting method with each individual hospitalization. Results: 342 cases were evaluated. Median age of 61.0 (95% CI 57.0-65.0). 194 (56.7%) were men. The mortality rate was higher in the female sex (p = 0.0037), ICU (p < 0.001), mechanical ventilation (p<0.001) and elderly groups. 143 (41.8%) patients were admitted to the ICU (95% CI 36.6%-47.1%), of which 60 (41.9%) required MV (95% CI 34.0%-50.0%). Global LOS presented median of 6.7 days (95% CI 6.0-7.2). Mean costs were US$ 7,060,00 (95% CI 5,300.94-8,819,00) for each patient. Mean cost for patients discharged alive and patients deceased was US$ 5,475.53 (95% CI 3,692.91-7,258.14) and US$ 12,955.19 (95% CI 8,106.61 -17,803.76), respectively (p < 0.001). Conclusions: Patients admitted with COVID-19 in these private hospitals point to great economic impact, mainly in the elderly and high-risk patients. It is key to better understand such costs in order to be prepared to make wise decisions during the current and future global health emergencies.

Clinical trial and detection of SARS-CoV-2 by a commercial breath analysis test based on Terahertz technology.

Public health threats such as the current COVID-19 pandemics have required prompt action by the local, national, and international authorities. Rapid and noninvasive diagnostic methods may provide on-site detection and immediate social isolation, used as tools to rapidly control virus spreading. Accordingly, the aim of the present study was to evaluate a commercial breath analysis test (TERA.Bio®) and deterministic algorithm for detecting the SARS-CoV-2 spectral signature of Volatile Organic Compounds present in exhaled air samples of suspicious persons from southern Brazil. A casuistic total of 70 infected and 500 non-infected patients were sampled, tested, and results later compared to RT-qPCR as gold standard. Overall, the test showed 92.6% sensitivity and 96.0% specificity. No statistical correlation was observed between SARS-CoV-2 positivity and infection by other respiratory diseases. Further studies should focus on infection monitoring among asymptomatic persons. In conclusion, the breath analysis test herein may be used as a fast, on-site, and easy-to-apply screening method for diagnosing COVID-19.

Uma revisão integrativa das sequelas da COVID-19 / An integrative review of sequelae of COVID-19 / Una revisión integradora de las secuelas del COVID-19

Objetivo: Identificar na literatura disponível as sequelas de saúde desenvolvidas pela população adoecida pela COVID-19. Métodos: Revisão integrativa com publicações recuperadas a partir do acesso ao Medline via PubMed e ao Portal Regional da Biblioteca Virtual em Saúde (BVS) em abril de 2021 que responderam à questão norteadora: Quais as principais sequelas de saúde desenvolvidas pela população adoecida pela COVID-19?. A estratégia de busca incluiu os descritores: Coronavirus Infections, COVID-19, SARS-COV-2, Complications, Disease, Adult, Long COVID. Identificaram-se 348 publicações, 196 da BVS e 152 no PubMed. Após análise dos critérios de inclusão/exclusão, permaneceram 66 publicações para leitura na íntegra, restando 27 artigos que compuseram a amostra. Resultados: As evidências selecionadas dos 27 artigos permitiram identificação das principais sequelas: neurológicas, saúde mental, cardíacas, no olfato e paladar, vasculares, cutâneas, respiratórias e gastrointestinais. A maior prevalência de sequelas neurológicas ocorreu em mulheres, bem como as cardíacas nos homens; não havendo distinção da prevalência de sintomas de saúde mental entre homens e mulheres. Conclusão: Com base nesses achados, evidenciou-se a importância do acompanhamento em longo prazo das pessoas que tiveram COVID-19, uma vez que os sintomas desenvolvidos como sequelas não são exclusivos dessa doença e podem impactar na qualidade de vida.

Objective: To identify, in the literature available, the health sequelae developed by the population affected by COVID-19. Methods: This is an integrative review of publications retrieved from Medline via PubMed and the Regional Portal of the Virtual Health Library (Biblioteca Virtual em Saúde ­ BVS) in April 2021 that answered the research question: What are the main health sequelae developed by the population affected by COVID-19? The search strategy included the descriptors: Coronavirus Infections, COVID-19, SARS-COV-2, Complications, Disease, Adult, Long COVID. 348 publications were identified: 196 on BVS and 152 on PubMed. After analyzing the inclusion/exclusion criteria, 66 publications remained for full reading, with a final 27 articles included in the sample. Results: The selected evidence from the 27 articles allowed the identification of the main sequelae: neurological, mental health, cardiac, smell and taste, vascular, cutaneous, respiratory and gastrointestinal sequelae. The highest prevalence of neurological sequelae was found in women, whereas cardiac sequelae were found mostly in men; there was no difference in the prevalence of mental health symptoms between men and women. Conclusion: Based on these findings, the importance of long-term follow-up of people who had COVID-19 was highlighted since the symptoms developed as sequelae are not exclusive to this disease and can impact quality of life.

Objetivo: Identificar en la literatura disponible las secuelas de salud desarrolladas por la población enfermada por COVID-19. Métodos: Revisión integradora con publicaciones recuperadas a partir del acceso al Medline por PubMed y al Portal Regional dela Biblioteca Virtual en Salud (BVS) en abril de 2021 que contestaron a la cuestión norteadora: ¿Cuáles las principales secuelas de salud desarrolladas por la población enfermada por COVID-19?. La estrategia de búsqueda incluyó los descriptores: Coronavirus Infections, COVID-19, SAR-COV-2, Complications, Desease, Adult, Long COVID. Fueron identificadas 348 publicaciones, 196 de la BVS Y 152 en PubMed. Después del análisis de los criterios de inclusión/exclusión, permanecieron 66 publicaciones para lectura completa, restando 27 artículos que compusieron la muestra. Resultados: Las evidencias seleccionadas de los 27 artículos permitieron la identificación de las principales secuelas: neurológicas, salud mental, cardíacas, en el olfato y paladar, vasculares, cutáneas, respiratorias y gastrointestinales. La mayor prevalencia de secuelas neurológicas ocurrió en mujeres, y las cardíacas en los hombres; no habiendo distinción de la prevalencia de síntomas de salud mental entre hombres y mujeres. Conclusión: Con base en estos hallazgos, se evidenció la importancia del acompañamiento a largo plazo de las personas que tuvieron COVID-19, ya que los síntomas desarrollados como secuelas no son exclusivos de esta enfermedad y pueden impactar en la calidad de vida.

Nationwide Access to Endovascular Treatment for Acute Ischemic Stroke in Portugal.

INTRODUCTION: Since the publication of endovascular treatment trials and European Stroke Guidelines, Portugal has re-organized stroke healthcare. The nine centers performing endovascular treatment are not equally distributed within the country, which may lead to differential access to endovascular treatment. Our main aim was to perform a descriptive analysis of the main treatment metrics regarding endovascular treatment in mainland Portugal and its administrative districts. MATERIAL AND METHODS: A retrospective national multicentric cohort study was conducted, including all ischemic stroke patients treated with endovascular treatment in mainland Portugal over two years (July 2015 to June 2017). All endovascular treatment centers contributed to an anonymized database. Demographic, stroke-related and procedure-related variables were collected. Crude endovascular treatment rates were calculated per 100 000 inhabitants for mainland Portugal, and each district and endovascular treatment standardized ratios (indirect age-sex standardization) were also calculated. Patient time metrics were computed as the median time between stroke onset, first-door, and puncture. RESULTS: A total of 1625 endovascular treatment procedures were registered. The endovascular treatment rate was 8.27/100 000 inhabitants/year. We found regional heterogeneity in endovascular treatment rates (1.58 to 16.53/100 000/year), with higher rates in districts closer to endovascular treatment centers. When analyzed by district, the median time from stroke onset to puncture ranged from 212 to 432 minutes, reflecting regional heterogeneity. DISCUSSION: Overall endovascular treatment rates and procedural times in Portugal are comparable to other international registries. We found geographic heterogeneity, with lower endovascular treatment rates and longer onset-to-puncture time in southern and inner regions. CONCLUSION: The overall national rate of EVT in the first two years after the organization of EVT-capable centers is one of the highest among European countries, however, significant regional disparities were documented. Moreover, stroke-onset-to-first-door times and in-hospital procedural times in the EVT centers were comparable to those reported in the randomized controlled trials performed in high-volume tertiary hospitals.

Introdução: A aprovação do tratamento endovascular para o acidente vascular cerebral isquémico obrigou à reorganização dos cuidados de saúde em Portugal. Os nove centros que realizam tratamento endovascular não estão distribuídos equitativamente pelo território, o que poderá causar acesso diferencial a tratamento. O principal objetivo deste estudo é realizar uma análise descritiva da frequência e métricas temporais do tratamento endovascular em Portugal continental e seus distritos. Material e Métodos: Estudo de coorte nacional multicêntrico, incluindo todos os doentes com acidente vascular cerebral isquémico submetidos a tratamento endovascular em Portugal continental durante um período de dois anos (julho 2015 a junho 2017). Foram colhidos dados demográficos, relacionados com o acidente vascular cerebral e variáveis do procedimento. Taxas de tratamento endovascular brutas e ajustadas (ajuste indireto a idade e sexo) foram calculadas por 100 000 habitantes/ano para Portugal continental e cada distrito. Métricas de procedimento como tempo entre instalação, primeira porta e punção foram também analisadas. Resultados: Foram registados 1625 tratamentos endovasculares, indicando uma taxa bruta nacional de tratamento endovascular de 8,27/100 000 habitantes/ano. As taxas de tratamento endovascular entre distritos variaram entre 1,58 e 16,53/100 000/ano, com taxas mais elevadas nos distritos próximos a hospitais com tratamento endovascular. O tempo entre sintomas e punção femural entre distritos variou entre 212 e 432 minutos. Discussão: A análise nacional a taxas de tratamento endovascular e tempos de atuação é comparável a outros registos internacionais. Verificaram-se heterogeneidades geográficas, com taxas de tratamento endovascular menores e maior tempo para tratamento nos distritos do sul e interior. Conclusão: Portugal continental apresenta uma taxa nacional de tratamento endovascular elevada, apresentando, contudo, assimetrias regionais no acesso. As métricas temporais foram comparáveis com as observadas nos ensaios clínicos piloto.

Proactive and reactive accumulation-to-bound processes compete during perceptual decisions.

Standard models of perceptual decision-making postulate that a response is triggered in reaction to stimulus presentation when the accumulated stimulus evidence reaches a decision threshold. This framework excludes however the possibility that informed responses are generated proactively at a time independent of stimulus. Here, we find that, in a free reaction time auditory task in rats, reactive and proactive responses coexist, suggesting that choice selection and motor initiation, commonly viewed as serial processes, are decoupled in general. We capture this behavior by a novel model in which proactive and reactive responses are triggered whenever either of two competing processes, respectively Action Initiation or Evidence Accumulation, reaches a bound. In both types of response, the choice is ultimately informed by the Evidence Accumulation process. The Action Initiation process readily explains premature responses, contributes to urgency effects at long reaction times and mediates the slowing of the responses as animals get satiated and tired during sessions. Moreover, it successfully predicts reaction time distributions when the stimulus was either delayed, advanced or omitted. Overall, these results fundamentally extend standard models of evidence accumulation in decision making by showing that proactive and reactive processes compete for the generation of responses.

Análise de custo-efetividade de um painel genético no câncer de mama precoce na saúde suplementar brasileira / Cost-effectiveness analysis of a genetic panel in early breast cancer in Brazilian supplementary health

Objetivo: Avaliar o custo-efetividade do uso de um painel genético de 21 genes em pacientes adultas diagnosticadas com câncer de mama em estádio inicial em uma operadora de saúde com mais de 500.000 vidas. Métodos: Foi utilizada uma coorte prospectiva seguida de um estudo de custo-efetividade entre os pacientes que utilizaram Oncotype DX® em 2020. Calcularam-se as despesas totais de cada esquema de quimioterapia (QT), somando-se os custos dos produtos e taxas de infusão. Resultados: Das 35 pacientes que utilizaram o teste de 21 genes no período avaliado, 60% (n = 21) não necessitaram de QT. Quando aplicadas simulações, houve custo evitado de R$ -1.945.448,88 (custos incrementais potenciais de R$ -6.488.207,56 até R$ 443.485,26, dependendo do esquema de QT escolhido). Conclusão: A inserção do teste de 21 genes na jornada do tratamento de câncer de mama na saúde suplementar evidenciou significativa relevância, pois contribuiu com o uso adequado da terapêutica, garantindo a sustentabilidade do sistema de saúde. Apresentando-se como uma opção custo-efetiva para a maioria dos esquemas de QT em comparação com a sua não utilização no tratamento, para a saúde suplementar brasileira

Objective: To evaluate the cost-effectiveness of the use of a genetic panel of 21 genes in adult patients diagnosed with early stage breast cancer in a healthcare provider with more than 500,000 lives. Methods: A prospective cohort study was conducted, followed by cost-effectiveness, among patients who used Oncotype DX® , in 2020. The total costs of each chemotherapy scheme (QT) were calculated, adding the costs of the products and infusion fees. Results: Of the 35 patients who used 21 gene tests in the evaluation period, 60% (n = 21) did not require QT. When simulations were applied, there was an avoided cost of R$ -1.945.448,88 (Potentials incremental costs from -R$ 6.488.207,56 to +R$ 443.485,26, depending on the chosen QT scheme). Conclusion: The insertion of 21-Gene recurrence score in the breast cancer treatment journey in supplementary health showed significant relevance, as it contributes to the appropriate use of therapy, guaranteeing the sustainability of the health system. Presenting itself as a cost-effective option for most QT schemes compared to not being used in treatment, for Brazilian supplementary health System

Flexible categorization in perceptual decision making.

Perceptual decisions rely on accumulating sensory evidence. This computation has been studied using either drift diffusion models or neurobiological network models exhibiting winner-take-all attractor dynamics. Although both models can account for a large amount of data, it remains unclear whether their dynamics are qualitatively equivalent. Here we show that in the attractor model, but not in the drift diffusion model, an increase in the stimulus fluctuations or the stimulus duration promotes transitions between decision states. The increase in the number of transitions leads to a crossover between weighting mostly early evidence (primacy) to weighting late evidence (recency), a prediction we validate with psychophysical data. Between these two limiting cases, we found a novel flexible categorization regime, in which fluctuations can reverse initially-incorrect categorizations. This reversal asymmetry results in a non-monotonic psychometric curve, a distinctive feature of the attractor model. Our findings point to correcting decision reversals as an important feature of perceptual decision making.

Terahertz Spectroscopy Applied to Diagnostics in Public Health: A Review

Abstract Terahertz (THz) spectroscopy is an emerging technology that is that is bringing a number of technical breakthroughs in several scientific applications. This review aimed to describe potential applications of THz spectroscopy at the biochemistry and molecules detection for food industry, environment monitoring and diagnostics, and present the importance of such technological platform in disease control and Public Health.

Author Correction: Response outcomes gate the impact of expectations on perceptual decisions.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

High-Throughput Task to Study Memory Recall During Spatial Navigation in Rodents.

Spatial navigation is one of the most frequently used behavioral paradigms to study memory formation in rodents. Commonly used tasks to study memory are labor-intensive, preventing the simultaneous testing of multiple animals with the tendency to yield a low number of trials, curtailing the statistical power. Moreover, they are not tailored to be combined with neurophysiology recordings because they are not based on overt stereotyped behavioral responses that can be precisely timed. Here we present a novel task to study long-term memory formation and recall during spatial navigation. The task consists of learning sessions during which mice need to find the rewarding port that changes from day to day. Hours after learning, there is a recall session during which mice search for the location of the memorized rewarding port. During the recall sessions, the animals repeatedly poke the remembered port over many trials (up to ∼20) without receiving a reward (i.e., no positive feedback) as a readout of memory. In this task, mice show memory of port locations learned on up to three previous days. This eight-port maze task requires minimal human intervention, allowing for simultaneous and unsupervised testing of several mice in parallel, yielding a high number of recall trials per session over many days, and compatible with recordings of neural activity.

Elective surgeries in the "new normal" post-COVID-19 pandemic: to test or do not test?

The new coronavirus (SARS-CoV-2) pandemic has been wreaking havoc all over the planet. In a precautionary measure, populations have been forced and kept under quarantine to contain the outbreak of the COVID-19 disease. The quarantine primary goal is to avoid the overload to the hospitals, which should be available for the care of COVID-19 patients. However, the virus does not have a uniform spread throughout the planet, and Brazil is no different. Although all the world's attention is now on the COVID-19 pandemic, there is no similar pattern of spread, and other diseases are still a real problem. Given the risks of transmission between patients and healthcare providers, there is a great challenge for healthcare institutions who must balance resources to assure safe care to patients and professionals while they take care of other disease patients, and perform surgical procedures that need to be carried out. Under such circumstances, as COVID-19 can also present pre- or asymptomatic transmission, it can be challenging to identify patients who are carrying and spreading the virus. Studies and information on mandatory testing for who are candidates to undergo elective surgery are scarce. Thus, the authors have reviewed the literature, and discuss the need to test these patients under the current context.

External carotid artery stenting in symptomatic internal carotid artery occlusion.

We report the case of a patient with an anterior ischemic stroke due to tandem occlusion of the left M2 segment and ipsilateral internal carotid artery (ICA), with concomitant severe stenosis of the ipsilateral external carotid artery (ECA) and contralateral ICA, and moderate stenosis of the left vertebral artery (VA); as thrombectomy was not possible, stenting of the right ICA was performed. Two days after significant recovery, the patient showed neurological deterioration when in upright position, and brain magnetic resonance imaging confirmed decreased cerebral blood flow on the left hemisphere. Stenting of the left ECA and balloon angioplasty of the ipsilateral VA were performed in order to increase collateral flow, with an almost complete resolution of symptoms. This case highlights the importance of assessing the collateralization pattern when an ICA occlusion is present, and the potential need to revascularize an ipsilateral stenotic ECA.

Custo-minimização da troca entre imunoglobulinas de diferentes vias e marcas: sustentabilidade relacionada ao tratamento na saúde suplementar / Cost minimizing the switching between immunoglobulin of different routes and brands: of treatment-related in the supplementary health

Objetivo: Avaliar custo-minimização da troca entre as versões intravenosa (IVIg) e subcutânea (SCIg) das imunoglobulinas (Ig) em operadora de saúde com mais de 500.000 vidas. Métodos: Estudo retrospectivo, transversal, descritivo, seguido de custo-minimização entre os pacientes que utilizaram IVIg, de 1º de outubro de 2018 a 30 de setembro de 2019. Simulou-se a troca entre as IVIg e SCIg, objetivando descrever a economia de uma hipotética substituição. Estabeleceram-se como critérios de exclusão: o não pagamento e a liberação com dose acima de 60.000 mg. Após exclusão, calcularam-se as despesas totais, somando-se os custos do produto e taxas de infusão. Resultados: Evidenciou-se que 133 pacientes, totalizando 1.175 liberações, utilizaram IVIg no período avaliado. Identificou-se a utilização de 34.797.500 mg de IVIg, por 10 especialidades, totalizando R$ 12.408.192,50 de despesas. Quando aplicada simulação, há uma potencial economia de recursos de até 29,83%, dependendo da SCIg escolhida. Conclusão: A análise econômica no tratamento com imunoglobulinas evidenciou significativa relevância, pois contribui com o uso adequado da terapêutica garantindo a sustentabilidade do sistema de saúde. Medicamentos subcutâneos apresentam-se como uma opção custo-minimizatória em comparação ao tratamento intravenoso para saúde suplementar brasileira.

Objective: Cost-minimization evaluation of the switch from intravenous (IVIg) to subcutaneous (SCIg) immunoglobulin (Ig) in a Brazilian Health Maintenance Organization (HMO), with more than 500.000 lives. Methods: This is a retrospective, transversal and descriptive study, followed by a cost-minimization analysis among patients using IVIg between 2018, October, 1st and 2019, September, 30th. The simulation was performed supposing the exchange from IVIg to SCIg, in order to calculate possible savings. Exclusion criteria: non-payment (gloss), and infusions with doses above 60.000 miligrams. After exclusion, total expenditures were calculated by summing product and infusion costs. Results: There were133 patients, with1,175 IVIg infusion events in the period evaluated. It was identified the use of 34,797,500 milligrams of IVIg, for 10 specialties, with R$ 12,408,192.50 of final expenditure. The simulation previews hypothetical reduction in the final cost of up to 29.83%, depending on the SCIg brand chosen. Conclusion: The economic analysis in the treatment with immunoglobulins showed significant relevance, as it contributes to the appropriate use of therapy ensuring the sustainability of the health system. Subcutaneous drugs are a cost-minimizing option compared to intravenous treatment for Brazilian HMOs.