Feasibility of extended ultrasound examination of the fetal brain between 24 and 37 weeks' gestation in low-risk pregnancies.

OBJECTIVES: To assess the feasibility of identifying fetal brain structures and anatomic landmarks included in the anterior complex (AC) and posterior complex (PC), as well as the proximal hemisphere (PH). METHODS: This was a prospective observational multicenter study of healthy pregnant women evaluated by ultrasound screening at 24 to 36 + 6 weeks' gestation. Six physicians performed transabdominal ultrasound, to obtain the planes required to visualize the AC, PC, and PH. Blind analysis by an expert and non-expert operator in fetal neurosonography was used to assess the structures included in each plane view. RESULTS: In the population studied (n=366), structure detection rates for AC were over 95 %, with an agreement of 96 % when comparing expert and non-expert examiners. Visualization of the corpus callosum crossing the midline was detected in over 97 and 96 % of cases for the AC and PC, respectively, with an agreement of over 96 %. The PH plane, particularly through the posterior access via the mastoid fontanelle, enabled visualization of the proximal anatomical structures in almost 95 % of cases. Detection of the corpus callosum through the AC and PC, both proximal/distal germinal matrix (AC) and proximal Sylvian fissure through the anterior access (PH) in the 24-25 + 6, 26-31 + 6 and 32-36 + 6 weeks' gestation groups were successful in over 96 % of cases with high level of agreement. CONCLUSIONS: Inclusion of AC, PC, and PH later in pregnancy proves feasible with a high level of agreement between both expert and non-expert operators.

Two-phase orthodontic treatment of two different types of tooth transposition in the same patient.

Orthodontic treatment is thoroughly planned considering the patient's facial and dental characteristics, the main complaint, treatment time and the orthodontist's experience. Transposition is a form of ectopia, in which two adjacent teeth exchange positions in the dental arch. Transposition can be partial or complete. This article reports the treatment of a female patient with two kinds of tooth transposition managed in the mixed and permanent dentitions. A girl, aged eight years and three months, came to routine paediatric consultation with an ectopic permanent mandibular left lateral incisor in the mixed dentition. Radiographic analysis indicated partial transposition of the permanent mandibular left lateral incisor and canine (Md.L2.C), and development of a complete tooth transposition between the permanent maxillary right first pre-molar and canine (Mx.C.P1). The patient was treated in two phases. The first, in the mixed dentition, and the second, in the permanent dentition with a three-year follow-up between them. These challenging treatment approaches are described in detail, including the mechanics used. The key points of this treatment were early diagnosis of the ectopic mandibular lateral incisor, use of light forces and interphase patient follow-up. These determined the best time to start the second treatment phase, enabling achievement of aesthetic and functional outcomes, and the results remained stable one year after the end of orthodontic treatment.

Feasibility and agreement of including anterior-posterior complexes and landmarks of the proximal hemisphere into basic examination of the fetal brain: A prospective study.

OBJECTIVE: To assess the feasibility of identifying structures included in anterior complex (AC) and posterior complex (PC), as well as a series of anatomic landmarks that could help to demonstrate the integrity of the cerebral proximal hemisphere (PH). METHODS: This was a prospective observational multicenter study of healthy pregnant women attending routine ultrasound screening at 20 + 0 to 33 + 6 weeks' gestation. Six physicians performed transabdominal (TA) ultrasound, in order to obtain the planes required to visualize the AC, PC, and PH. Blind analysis by a nonexpert and two experts in fetal neurosonography was used to assess the structures included in each plane view. RESULTS: In the population studied (n = 747), detection of the structure rates for AC, PC, and proximal hemisphere was of 94%, 93%, and 96%, respectively, with an agreement of 97%, 94%, and 98% when comparing an expert and a nonexpert in fetal brain examiner. Detection of structures in the proximal hemisphere was significantly higher when observed through the proximal hemisphere plane rather than the transventricular plane. CONCLUSION: Our results suggest that inclusion of AC and PC complexes visualization, as well as real-time access to the proximal hemisphere, is feasible and could improve the prenatal detection of fetal cerebral anomalies.

New Insights into the Anterior Complex.

OBJECTIVE: To introduce visualization of the germinal matrix (GM), external angle of the frontal horn, and periventricular white matter while evaluating the anterior complex (AC) during basic ultrasound assessment of the fetal brain. CASE PRESENTATIONS: This is a retrospective observational study of healthy women with singleton pregnancies, with no increased risk of fetal central nervous system anomalies, attending routine ultrasound screening at 20-32 weeks' gestation. Seventeen cases are presented in which an abnormal aspect of the GM or external angle of the frontal horn or periventricular white matter on AC evaluation has allowed a prenatal diagnosis of peri-intraventricular hemorrhage, subependymal cysts, connatal cysts, periventricular venous hemorrhagic infarction, and white matter injury. CONCLUSION: An extended AC evaluation could significantly improve the -diagnosis of hemorrhagic/cystic/hypoxic-ischemic lesions during the performance of a basic ultrasound study of the fetal brain.

Genetic diversity of human papillomavirus types 35, 45 and 58 in cervical cancer in Brazil.

In Brazil, most studies of intra-type variants of human papillomavirus (HPV) have focused on HPV16 and HPV18, but other high-risk HPV types have not been studied. Here, we report the prevalence of lineages and variants of HPV35, HPV45 and HPV58 in cervical cancers from the Amazonian and Southeast Brazilian regions. The most frequent sublineages were A1 for HPV35, B2 for HPV45, and A2 for HPV58. The Southeast region had a higher frequency of the B2 sublineage of HPV45, and for HPV35, the genetic and nucleotide sequence diversity were higher in the Southeast region, suggesting that regional factors are influencing the diversity and lineage prevalence.

Two-Dimensional Ultrasound Evaluation of the Fetal Cerebral Aqueduct: Improving the Antenatal Diagnosis and Counseling of Aqueductal Stenosis.

OBJECTIVE: To describe a technique for the visualization and measurement of cerebral aqueduct diameter through a 2D sagittal median plane, and to report its aspect and measurement in fetuses with aqueductal stenosis (AS). METHODS: This was a cross-sectional study of 207 morphologically normal fetuses in low-risk pregnancies between 20 and 36 weeks of gestation. The cerebral aqueduct was visualized transvaginally in a midsagittal plane, and measurements of its greatest diameter (ampulla) were taken independently by an expert and a nonexpert sonographer. In addition, the aqueduct morphology from 7 fetuses with AS and complete follow-up were compared to the reference range. RESULTS: Aqueductal measurements were obtained in 206 of 207 normal fetuses. Aqueductal growth occurred linearly with gestational age. Our method demonstrated excellent interobserver reproducibility. Among the 7 fetuses with AS, the aqueductal lumen could not be identified in 6 and had a funneling aspect in 1. DISCUSSION: Our study demonstrated that it is possible to visualize and measure the cerebral aqueduct directly through a 2D ultrasound median plane. In fetuses with severe ventriculomegaly, the morphology and width of this structure could represent a relevant tool in improving AS diagnosis, differentiating it from other causes of significant ventricular dilation that carry a different outcome.

Genetic diversity of HPV16 and HPV18 in Brazilian patients with invasive cervical cancer.

Cervical cancer is the fourth most common cancer among women, and ∼70-80% of these cancers are associated with two human papillomavirus types: HPV16 and HPV18. Several studies have reported that intra-type diversity is associated with the progression of infection to invasive cancer. Herein, we report the genetic diversity of HPV16 and HPV18 in a cohort of 594 Brazilian women with invasive cervical cancer and describe the prevalence of lineages and intra-type diversity prior to the implementation of the public immunization program in Brazil. HPV detection and genotyping were performed using PCR, PGMY/GP primers, and DNA extracted from fresh tumors. The HPV16 (378 women) and HPV18 (80 women) lineages were identified by PCR and sequencing of the LCR and E6 fragments, followed by SNV comparison and phylogenetic analysis. In our cohort, was found a higher frequency of the lineage A (in 217 women), followed by lineage D (in 97 women) and lineages B and C (in 10 women each) for HPV16; and a higher frequency of lineage A (in 56 women) followed by lineage B (in 15 women) in HPV18. The genetic diversity of HPV16 indicated a recent expansion of specific variants or a selective advantage that is associated with invasive cancer; this pattern was not observed for HPV18.

Exploring microalgal and cyanobacterial metabolites with antiprotozoal activity against Leishmania and Trypanosoma parasites.

Neglected tropical diseases (NTD) like Leishmaniasis and trypanosomiasis affect millions of people annually, while currently used antiprotozoal drugs have serious side effects. Drug research based on natural products has shown that microalgae and cyanobacteria are a promising platform of biochemically active compounds with antiprotozoal activity. These unicellular photosynthetic organisms are rich in polyunsaturated fatty acids, pigments including phycocyanin, chlorophylls and carotenoids, polyphenols, bioactive peptides, terpenes, alkaloids, which have proven antioxidant, antimicrobial, antiviral, antiplasmodial and antiprotozoal properties. This review provides up-to-date information regarding ongoing studies on substances synthesized by microalgae and cyanobacteria with notable activity against Leishmania spp., Trypanosoma cruzi, and Trypanosoma brucei, the causative agents of Leishmaniasis, Chagas disease, and human African trypanosomiasis, respectively. Extracts of several freshwater or marine microalgae have been tested on different strains of Leishmania and Trypanosoma parasites. For instance, ethanolic extract of Chlamydomonas reinhardtii and Tetraselmis suecica have biological activity against T. cruzi, due to their high content of carotenoids, chlorophylls, phenolic compounds and flavonoids that are associated with trypanocidal activity. Halophilic Dunaliella salina showed moderate antileishmanial activity that may be attributed to the high ß-carotene content in this microalga. Peptides such as almiramides, dragonamides, and herbamide that are biosynthesized by marine cyanobacteria Lyngbya majuscula were found to have increased activity in micromolar scale IC50 against L. donovani, T. Cruzi, and T. brucei parasites. The cyanobacterial peptides symplocamide and venturamide isolated from Symploca and Oscillatoria species, respectively, and the alkaloid nostocarbonile isolated from Nostoc have shown promising antiprotozoal properties and are being explored for pharmaceutical and medicinal purposes. The discovery of new molecules from microalgae and cyanobacteria with therapeutic potential against Leishmaniasis and trypanosomiasis may address an urgent medical need: effective and safe treatments of NTDs.

Evolution of fetal subependymal cysts throughout gestation.

Subependymal cysts are secondary to brain germinal matrix hemorrhage or infarction and are associated with fetal chromosomal and metabolic conditions, as well as infections. They are found in 1-3% of neonates in the first days of life and have been described in fetuses, although much less frequently. We report the prenatal diagnosis of a case of subependymal cysts first visualized at 12 weeks' gestation and its evolution throughout pregnancy and after birth. As far as we know, this is the first time that such a condition is described before 16 weeks' gestation as well as its longitudinal evolution. Knowledge that subependymal cysts can be seen as early as 12 weeks' gestation and their natural evolution is important to avoid equivocal diagnoses. The prognosis of isolated subependymal cysts remains uncertain.

Short-term effects of the COVID-19 pandemic on cancer screening, diagnosis and treatment procedures in Brazil: a descriptive study, 2019-2020. / Efeitos de curto prazo da pandemia de COVID-19 na realização de procedimentos de rastreamento, investigação diagnóstica e tratamento do câncer no Brasil: estudo descritivo, 2019-2020.

OBJECTIVE: To analyze the short-term effects of the COVID-19 pandemic on cancer screening, diagnosis and treatment in Brazil. METHODS: This was a descriptive study using data from the Outpatient and Hospital Information Systems, and the Cancer Information System. Monthly percentage variation of cancer screening, diagnosis and treatment procedures in 2019 and 2020 was calculated, as well as waiting time for cervical and breast cancer tests. RESULTS: In 2020 cytopathology tests fell by 3,767,686 (-44.6%), screening mammograms fell by 1,624,056 (-42.6%), biopsies fell by 257,697 (-35.3%), cancer surgery fell by 25,172 (-15.7%), and radiotherapy procedures fell by 552 (-0.7%), compared to 2019. Time intervals for performing cervical and breast cancer screening exams were little affected. CONCLUSION: Cancer control actions were impacted by the pandemic, making it necessary to devise strategies to mitigate the effects of possible delays in diagnosis and treatment.

Covid-19 in Brazil in 2020: impact on deaths from cancer and cardiovascular diseases.

OBJECTIVE: To analyze the impact of the covid-19 pandemic on mortality from cancer and cardiovascular diseases (CVD) as underlying cause and comorbidity in Brazil and Brazilian regions in 2020. METHODS: We used the 2019 and 2020 databases of the Mortality Information System (SIM) to analyze deaths occurring between March and December of each year that had cancer or CVD as the underlying cause or comorbidity. Deaths from covid-19 in 2020 were also analyzed. To estimate the Standardized Mortality Ratio (SMR) and the excess of deaths, 2019 data were considered as standard. RESULTS: Between March and December 2020, there were 181,377 deaths from cancer and 291,375 deaths from cardiovascular diseases in Brazil, indicating reduction rates of 9.7% and 8.8%, respectively, compared to the same period of the previous year. The pattern was maintained in the five Brazilian regions, with lower variation for cancer (-8.4% in the South to -10.9% in the Midwest). For CVD, the variation was greater, from -2.2% in the North to -10.5 in the Southeast and South. In the same period of 2020, these diseases were classified as comorbidities in 18,133 deaths from cancer and 188,204 deaths from cardiovascular diseases, indicating a proportional excess compared to data from 2019, of 82.1% and 77.9%, respectively. This excess was most significant in the Northern Region, with a ratio of 2.5 between observed and expected deaths for the two conditions studied. CONCLUSIONS: Excess deaths from cancer and CVD as comorbidities in 2020 may indicate that covid-19 had an important impact among patients with these conditions.

Cervical cancer screening, treatment and prophylaxis in Brazil: Current and future perspectives for cervical cancer elimination.

As a middle-income country, Brazil has one of the largest public health systems worldwide, which deals with free and universal access to health care. Regarding cervical cancer, the country possesses a large infrastructure for the screening of premalignant and malignant lesions, but yet based on old technology, having Papanicolaou as the major screening method, followed by colposcopy and treatment. Also, large disparities in access are present, which makes effectiveness of screening and treatment in different regions of the country highly unequal. In this review, we describe and evaluate the current screening, treatment and prophylactic (HPV vaccination) strategies to combat cervical cancer in Brazil, and discuss potential incorporation of more recent technologies in these areas in the country to pave its way toward cervical cancer elimination.

Rethinking Cervical Cancer Screening in Brazil Post COVID-19: A Global Opportunity to Adopt Higher Impact Strategies.

The World Health Organization global call to eliminate cervical cancer encourages countries to consider introducing or improving cervical cancer screening programs. Brazil's Unified Health System (SUS) is among the world's largest public health systems offering free cytology testing, follow-up colposcopy, and treatment. Yet, health care networks across the country have unequal infrastructure, human resources, equipment, and supplies resulting in uneven program performance and large disparities in cervical cancer incidence and mortality. An effective screening program needs multiple strategies feasible for each community's reality, facilitating coverage and follow-up adherence. Prioritizing those at highest risk with tests that better stratify risk will limit inefficiencies, improving program impact across different resource settings. Highly sensitive human papillomavirus (HPV)-DNA testing performs better than cytology and, with self-collection closer to homes and workplaces, improves access, even in remote regions. Molecular triage strategies like HPV genotyping can identify from the same self-collected sample, those at highest risk requiring follow-up. If proven acceptable, affordable, cost-effective, and efficient in the Brazilian context, these strategies would increase coverage while removing the need for speculum exams for routine screening and reducing follow-up visits. SUS could implement a nationwide organized program that accommodates heterogenous settings across Brazil, informing a variety of screening programs worldwide.

General anaesthesia versus other types of anaesthesia in patients undergoing surgery for treatment of cutaneous melanoma: a systematic review and meta-analysis.

General and local anaesthetics alter tumour behaviour in experimental models. Objectives: To investigate the relationship between general anaesthesia and recurrence or survival in patients who received surgery for malignant melanoma. A meta-analysis was performed based on a comprehensive literature search. Controlled and observational studies of patients undergoing surgery for melanoma under general anaesthesia, compared with other types of anaesthesia, were included. The primary outcomes were overall survival and disease-free survival. The secondary outcomes included cancer-specific survival, cost analysis, and adverse events. Risk of bias was assessed. Individual study information was summarized. The meta-analysis was performed using a random-effects model. The GRADE approach was used to summarise the certainty of evidence. Eight studies were included (n = 5,832). The use of general anaesthesia was not associated with any statistical difference in overall survival (p = 0.087; 1 NRS; n= 104; very low certainty of evidence) or disease-free survival (HR: 1.266; 95% CI: 0.904-1.773; p = 0.169; 1 NRS; n = 281; very low certainty of evidence). However, general anaesthesia was associated with worse melanoma-specific survival (HR: 1.46; 95% CI: 1.22-1.68: p < 0.00001; 3 NRS; n = 4654; low certainty of evidence). Three studies reported increased intraoperative costs associated with the use of general anaesthesia (3 NRT; n = 513; very low certainty of evidence). No study adequately reported other primary or secondary outcomes. General anaesthesia may reduce melanoma-specific survival in patients undergoing surgery for treatment of cutaneous melanoma. We are uncertain whether general anaesthesia impacts the other reported outcomes.

Moving towards a strategy to accelerate cervical cancer elimination in a high-burden city-Lessons learned from the Amazon city of Manaus, Brazil.

The World Health Organization Call to Eliminate Cervical Cancer resonates in cities like Manaus, Brazil, where the burden is among the world's highest. Manaus has offered free cytology-based screening since 1990 and HPV immunization since 2013, but the public system is constrained by many challenges and performance is not well-defined. We obtained cervical cancer prevention activities within Manaus public health records for 2019 to evaluate immunization and screening coverage, screening by region and neighborhood, and the annual Pink October screening campaign. We estimated that among girls and boys age 14-18, 85.9% and 64.9% had 1+ doses of HPV vaccine, higher than rates for age 9-13 (73.4% and 43.3%, respectively). Of the 90,209 cytology tests performed, 24.9% were outside the target age and the remaining 72,230 corresponded to 40.1% of the target population (one-third of women age 25-64). The East zone had highest screening coverage (49.1%), highest high-grade cytology rate (2.5%) and lowest estimated cancers (38.1/100,000) compared with the South zone (32.9%, 1.8% and 48.5/100,000, respectively). Largest neighborhoods had fewer per capita screening locations, resulting in lower coverage. During October, some clinics successfully achieved higher screening volumes and high-grade cytology rates (up to 15.4%). Although we found evidence of some follow-up within 10 months post-screening for 51/70 women (72.9%) with high-grade or worse cytology, only 18 had complete work-up confirmed. Manaus has successfully initiated HPV vaccination, forecasting substantial cervical cancer reductions by 2050. With concerted efforts during campaigns, some clinics improved screening coverage and reached high-risk women. Screening campaigns in community locations in high-risk neighborhoods using self-collected HPV testing can achieve widespread coverage. Simplifying triage and treatment with fewer visits closer to communities would greatly improve follow-up and program effectiveness. Achieving WHO Cervical Cancer Elimination goals in high-burden cities will require major reforms for screening and simpler follow-up and treatment.

Effects of Oral Magnesium Supplementation on Vascular Function: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: The effects of magnesium (Mg) supplementation on vascular function have been evaluated in some randomized controlled trials (RCT) but their results are conflicting. AIM: A systematic review and meta-analysis were conducted to summarize the effects of oral Mg supplementation on vascular function in RCT. METHODS: The databases MEDLINE (PubMed), Embase, Web of Science and Cochrane Library were accessed from inception to May 27, 2019. Intergroup differences (treatment vs. control group) related to changes in flow-mediated dilation (FMD) and pulse wave velocity (PWV), expressed as mean and standard deviation, were used to evaluate the effect of Mg supplementation on these outcomes. The results of the meta-analysis were expressed using a random-effects model. The heterogeneity between studies was evaluated using the I2 statistic. RESULTS: The oral supplementation of Mg had no significant effect on FMD (mean difference 2.13; 95% CI - 0.56, 4.82; p = 0.12) and PWV (mean difference - 0.54, 95% CI - 1.45, 0.36, p = 0.24). Heterogeneity for both outcomes (FMD and PWV) was high (I2 = 99%, p < 0.001). However, in subgroup analyses, oral Mg significantly improved FMD in studies longer than 6 months, in unhealthy subjects, in individuals older than 50 years, or in those with body mass index (BMI) ≥ 25 kg/m2. The reduced number of RCT and the heterogeneity among them were the main limitations. CONCLUSIONS: This meta-analysis suggest that oral Mg supplementation may improve endothelial function when conducted at least for 6 months and in unhealthy, overweight or older individuals. Registration number: PROSPERO CRD42019111462.

Semi-quantitative determination of ash element content for freeze-dried, defatted, sulfated and pyrolysed biomass of Scenedesmus sp.

BACKGROUND: Energy demand by mankind has become one of the most important aspects of our society. A promising technology that seeks to provide part of the energy demand and to obtain high-value products is the thermochemical conversion of microalgae biomass. Inorganic species presented in microalgae biomass may act as catalysts for thermochemical reactions and are responsible for notorious ash-related issues during thermochemical decomposition. RESULTS: In this study, the freeze-dried biomass of Scenedesmus sp. was used to evaluate the lipid extraction methodology regarding a sonication bath as pretreatment technique for cell disruption followed by vortex mixing and n-hexane as solvent. It is also presented the lipid and amino acid profiles for Scenedesmus sp. The freeze-dried biomass was pyrolysed through a TGA (thermogravimetric analysis), with heating rates of 20 °C/min, from 100 to 650 °C. The ash and sulfated ash contents were accurately determined by combustion of biomass in a muffle furnace. The element component of ashes of the freeze-dried, defatted, pyrolysed and sulfated biomasses was determined by means of scanning electron microscope (SEM) fitted with energy dispersive spectroscopy (EDS). The lipid content obtained for Scenedesmus sp. dry biomass was 16.72% (± 0.03). The content of the sulfated ash obtained was 17.81 ± 0.15%. The SEM-EDS technique identified different mineral compounds in ashes, allowing to quantify Mg, P, S, K, Ca, Fe, Co and Br, as well as oxides. CONCLUSION: The results suggest a possible strategy to evaluate in a semi-quantitative manner the ash composition of freeze-dryed, defatted, sulfated and pyrolysed biomass of Scenedesmus sp. and its feasibility in using Scenedesmus sp. biomass in different thermochemical conversion strategies to achieve processes with positive energy ratio, representing potential use both environmental and energetically.

Breast Cancer Quality of Life and Health-state Utility at a Brazilian Reference Public Cancer Center.

Objectives: To evaluate health-related-quality-of-life and derive health-state-utility (HSU) from breast cancer patients, before and after routine therapy at a Brazilian reference public cancer center.Methods: In a prospective cohort study, a consecutive sample of outpatients newly diagnosed with breast cancer was submitted to two interviews (baseline, 6-month) to complete EQ-5D-3L/VAS and EORTC-QLQ-C30/BR23 questionnaires. Demographic and clinical information was reviewed from medical records.Results: For 196 patients, EQ-5D domains of pain/discomfort and anxiety/depression were mainly affected, but partially improved overtime, while mobility/usual activities/self-care worsened after therapy. EORTC-QLQ-C30/BR23 scales mostly affected were emotional functioning, insomnia, pain, sexual enjoyment and future self-health perspective at baseline, while financial difficulties, insomnia, fatigue and therapy side-effects at follow-up. Overtime mean scores were 71.4 (95%CI68.5-74.4) and 76.1 (95%CI73.3-78.8) for EQ-5D-VAS, and 0.712 (95%CI0.686-0.737) and 0.732 (95%CI0.707-0.757) for HSU. HSU was 0.689 (95%CI0.648-0.730) in stages III-IV, and 0.692 (95%CI0.652-0.731) under two/three chemotherapy regimens.Conclusion: In a context of impairments in emotional functioning, sexual enjoyment, symptoms burden, and poor future self-health perspective, breast cancer produced a mean HSU of 0.712. After routine care, there was a small improvement in quality of life, with lower HSU particularly in advanced disease and multiple chemotherapy regimens.

Custo-utilidade de terapias-alvo comparadas à dacarbazina para o tratamento de primeira linha do melanoma avançado não-cirúrgico e metastático no Sistema Único de Saúde do Brazil.

OBJECTIVE: To estimate the incremental cost-utility ratio (ICUR) of isolated and combined targeted therapy regimens compared to dacarbazine for first-line treatment of advanced and metastatic melanoma with BRAF V600 mutation. METHODS: A Markov model with three health states (no progression, progression and death), monthly duration cycle and 10-year time horizon was constructed to compare targeted therapy regimens (vemurafenib, dabrafenib, vemurafenib/cobimetinib and dabrafenib/trametinib) with dacarbazine chemotherapy under the Brazilian public health perspective. One-way and probabilistic sensitivity analyses were performed. RESULTS: Mean cost was R$5662.50 ($1490.13) for dacarbazine, R$175 937.18 (46 299.26) for vemurafenib, R$167 461.70 ($44 068.87) for dabrafenib, R$425 901 ($112 079.21) for vemurafenib/cobimetinib and R$411 799.81 ($108 368.37) for dabrafenib/trametinib, whereas QALY was 0.91 for dacarbazine, 1.08 for vemurafenib, 1.12 for dabrafenib, 1.64 for vemurafenib/cobimetinib and 1.56 for dabrafenib/trametinib. The ICUR was estimated from R$572 165.76 ($150 569.94) to R$1 012 524.56 ($266 453.83) per patient, and the most impactful parameters were risk of progression and death, and treatment cost. CONCLUSION: The incorporation of targeted therapies in the Brazilian public health system would produce an additional expenditure of at least 19 times the national GDP per capita to increase in one year the quality-adjusted survival of each patient with advanced/metastatic BRAF-mutant melanoma.