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1.
Sci Rep ; 13(1): 4621, 2023 03 21.
Article in English | MEDLINE | ID: mdl-36944685

ABSTRACT

The cosmopolitan distribution of humpback whales (Megaptera novaeangliae) is largely driven by migrations between winter low-latitude breeding grounds and summer high-latitude feeding grounds. Southern Hemisphere humpback whales faced intensive exploitation during the whaling eras and recently show evidence of population recovery. Gene flow and shared song indicate overlap between the western (A) and eastern (B1, B2) Breeding Stocks in the South Atlantic and Indian Oceans (C1). Here, we investigated photo-identification evidence of population interchange using images of individuals photographed during boat-based tourism and research in Brazil and South Africa from 1989 to 2022. Fluke images were uploaded to Happywhale, a global digital database for marine mammal identification. Six whales were recaptured between countries from 2002 to 2021 with resighting intervals ranging from 0.76 to 12.92 years. Four whales originally photographed off Abrolhos Bank, Brazil were photographed off the Western Cape, South Africa (feeding grounds for B2). Two whales originally photographed off the Western Cape were photographed off Brazil, one traveling to the Eastern Cape in the Southwestern Indian Ocean (a migration corridor for C1) before migrating westward to Brazil. These findings photographically confirm interchange of humpback whales across the South Atlantic and Indian Oceans and the importance of international collaboration to understand population boundaries.


Subject(s)
Humpback Whale , Animals , Atlantic Ocean , Seasons , Indian Ocean , Brazil
2.
Pharmaceuticals (Basel) ; 15(10)2022 Oct 13.
Article in English | MEDLINE | ID: mdl-36297372

ABSTRACT

Histone deacetylases (HDAC) are epigenetic enzymes responsible for repressing gene expression through the deacetylation of histone lysine residues. Therefore, inhibition of HDACs has become an interesting approach for the treatment of several diseases, including cancer, hematology, neurodegenerative, immune diseases, bacterial infections, and more. Resveratrol (RVT) has pleiotropic effects, including pan-inhibition of HDAC isoforms; however, its ability to interfere with membranes requires additional optimization to eliminate nonspecific and off-target effects. Thus, to explore RVT as a scaffold, we designed a series of novel HDAC-1 and -2 inhibitors containing the 2-aminobenzamide subunit. Using molecular modeling, all compounds, except unsaturated compounds (4) and (7), exhibited a similar mode of interaction at the active sites of HDAC 1 and 2. The docking score values obtained from the study ranged from -12.780 to -10.967 Kcal/mol. All compounds were synthesized, with overall yields ranging from 33% to 67.3%. In an initial screening, compounds (4), (5), (7), and (20)-(26), showed enzymatic inhibitory effects ranging from 1 to 96% and 6 to 93% against HDAC-1 and HDAC-2, respectively. Compound (5), the most promising HDAC inhibitor in this series, was selected for IC50 assays, resulting in IC50 values of 0.44 µM and 0.37 µM against HDAC-1 and HDAC-2, respectively. In a panel of selectivity against HDACs 3-11, compound (5) presented selectivity towards Class I, mainly HDAC-1, 2, and 3. All compounds exhibited suitable physicochemical and ADMET properties as determined using in silico simulations. In conclusion, the optimization of the RVT structure allows the design of selective HDAC inhibitors, mainly targeting HDAC-1 and HDAC-2 isoforms.

3.
J Environ Sci Health B ; 57(6): 450-457, 2022.
Article in English | MEDLINE | ID: mdl-35414314

ABSTRACT

The objectives of this study were to estimate the residual and half-life of [imazapic + imazapyr] and to infer on the impact of these residuals over time. The first experiment comprised the application of [imazapic + imazapyr] to Clearfield® rice. On the following summer cropping season (365 days later), undeformed soil samples 0-5 cm depth were collected and seeds of six species or varieties were sown as bioindicators of residuals (experiment 2), being assessed plant height and dry mass 20 days after emergence start. The third experiment comprised the cultivation of the same species submitted to ten increasing herbicide doses (0-280 g ha-1) to establish standard response curves, also assessing plant height and dry mass 20 days after emergence start. About 2.1-5.8% of the applied imazapic remains in soil after one year, for the label doses. Imazapyr was considered to be at negligible doses as its half-life is short, and less than 0.0000001% of the applied dose is expected to be in soil 365 days later. The expected imazapic half-life in lowland areas of Southern Brazil is longer than for dryland, being estimated as between 63 and 77 days (95% confidence interval), contrasting to the 60 days half-life previously estimated for dryland soils.


Subject(s)
Herbicides , Niacin , Oryza , Soil Pollutants , Brazil , Half-Life , Herbicides/analysis , Imidazoles , Niacin/analogs & derivatives , Nicotinic Acids , Soil , Soil Pollutants/analysis
4.
JAAD Int ; 6: 61-67, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35059660

ABSTRACT

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare and severe phenotype of psoriasis characterized by sudden outbreak of widespread coalescent sterile pustules associated with a spectrum of systemic symptoms. OBJECTIVE: We aimed to describe the epidemiology and treatment of GPP in Brazil from the public health care system perspective. METHODS: This was a retrospective public claims database study, using outpatient and inpatient databases, with information from January 2018 to August 2020, based on records of health resource utilization by patients with GPP. Outpatient treatment regimens and fatal inpatient outcomes were described. RESULTS: In total, 1458 outpatients of all ages were identified, of whom 53% were women. We estimated the GPP prevalence in Brazil to be between 0.7 and 0.9 per 100,000. Acitretin was the most commonly dispensed drug. Of all the outpatients, 769 outpatients could be tracked in the inpatient database, and 151 had hospital admissions during the study period. Of them, 5.3% had a fatal outcome during hospitalization. A primary skin condition or an infection was the most frequent hospitalization cause. LIMITATION: The International Classification of Diseases codes for GPP and psoriasis have not been previously validated in this context. CONCLUSION: GPP is a rare disease in Brazil and affects individuals of all ages and both sexes. Hospitalizations and disease-related deaths highlight the need for its prompt diagnosis, close medical follow-up, and effective treatment.

5.
Arq. bras. neurocir ; 40(3): 238-244, 15/09/2021.
Article in English | LILACS | ID: biblio-1362120

ABSTRACT

Spasticity is amotor disorder that leads to a resistance to passive jointmovement. Cerebral palsy is the most important cause of spasticity and can be caused by several factors, including multiple gestations, alcoholism, infections, hemorrhages, drowning, and traumatic brain injuries, among others. There aremany scales that help tomeasure andmonitor the degree of impairment of these patients. The initial treatment should focus on the causal factor, such as tumors, inflammation, degenerative diseases, hydrocephalus, etc. Subsequently, the treatment of spastic musculature includes oral or intrathecal myorelaxants, spinal cord electrostimulation, neurotomies, Lissauer tract lesion, dentatotomy and selective dorsal rhizotomy. The latter is a safetechnique, possibleto beperformed inmost centers with neurosurgical support, and it is effective in the treatment of severe spasticity. In this article, the authors describe the surgical technique and conduct a review the literature.


Subject(s)
Motor Neuron Disease/surgery , Rhizotomy/rehabilitation , Muscle Spasticity/surgery , Muscle Spasticity/etiology , Cerebral Palsy/complications , Minimally Invasive Surgical Procedures/methods , Rhizotomy/methods , Laminoplasty/methods , Muscle Relaxants, Central/therapeutic use
6.
Bioorg Chem ; 114: 105077, 2021 09.
Article in English | MEDLINE | ID: mdl-34130111

ABSTRACT

Fetal hemoglobin (HbF) induction constitutes a valuable and validated approach to treat the symptoms of sickle cell disease (SCD). Here, we synthesized pomalidomide-nitric oxide (NO) donor derivatives (3a-f) and evaluated their suitability as novel HbF inducers. All compounds demonstrated different capacities of releasing NO, ranging 0.3-30.3%. Compound 3d was the most effective HbF inducer for CD34+ cells, exhibiting an effect similar to that of hydroxyurea. We investigated the mode of action of compound 3d for HbF induction by studying the in vitro alterations in the levels of transcription factors (BCL11A, IKAROS, and LRF), inhibition of histone deacetylase enzymes (HDAC-1 and HDAC-2), and measurement of cGMP levels. Additionally, compound 3d exhibited a potent anti-inflammatory effect similar to that of pomalidomide by reducing the TNF-α levels in human mononuclear cells treated with lipopolysaccharides up to 58.6%. Chemical hydrolysis studies revealed that compound 3d was stable at pH 7.4 up to 24 h. These results suggest that compound 3d is a novel HbF inducer prototype with the potential to treat SCD symptoms.


Subject(s)
Anemia, Sickle Cell/drug therapy , Thalidomide/analogs & derivatives , Dose-Response Relationship, Drug , Humans , Molecular Structure , Structure-Activity Relationship , Thalidomide/chemical synthesis , Thalidomide/chemistry , Thalidomide/therapeutic use
7.
Int J Surg Case Rep ; 74: 234-237, 2020.
Article in English | MEDLINE | ID: mdl-32892127

ABSTRACT

INTRODUCTION: Extra-axial cerebellopontine angle (CPA) hemangioblastoma is a rare condition in which the correct differential diagnosis from other CPA lesions can affect the best treatment choice. These are benign tumors that are highly vascularized and mostly present in the cystic form. About twenty-six cases have been reported in the literature with this same location and with a noncystic aspect. PRESENTATION OF CASE: We report a case of a 63-year-old male with a complaint of progressive headache associated with imbalance and difficulty walking. Neurological examination showed discreet facial paresis, left dysmetria and mild gait ataxia. Magnetic resonance imaging (MRI) showed a solid mass with isointensity on T1-weighted sequences; hypointensity and a heterogeneous appearance on T2-weighted sequences; and intense homogeneous contrast enhancement located in the left CPA region extending superiorly to the tentorial notch. The first diagnosis was meningioma, but during the microsurgical suboccipital retrosigmoid approach, it was observed that the lesion was extremely bloody with several vessels on its surface. We achieved gross total resection, and the pathology confirmed hemangioblastoma. DISCUSSION: Although it is rare, hemangioblastoma should be one of the differential diagnoses when dealing with CPA solid lesions with high contrast enhancement and heterogeneity on T2-weighted MRI. Analysis of the radiological characteristics allows a greater chance of confirmation and is one of the main tools for surgical planning. CONCLUSION: Correct preoperative evaluation and the possibility that hemangioblastoma may arise from the CPA can avoid trans-operative risks mainly related to bleeding and can improve results.

8.
Sci Rep ; 10(1): 13577, 2020 08 11.
Article in English | MEDLINE | ID: mdl-32782286

ABSTRACT

The association of immobility and camouflage is widespread as a defensive mechanism in prey from varied taxa. However, many experiments assessing the reaction of prey to predator cues are conducted under artificial laboratory conditions. In a previous experiment we observed the tadpoles of Ololygon machadoi (Hylidae) to respond to predator visual and/or chemical cues by choosing backgrounds that improve their disruptive properties, but detected no associated reduction of movement. Here we experimentally demonstrate this response in the species' natural habitat, on backgrounds where the tadpoles are likely to achieve their best camouflage. We also tested whether previous experiences could influence both background choice and immobility in O. machadoi tadpoles. These novel experimental results suggest that a defensive behavior-i.e., reduction of movement-in these tadpoles is more strongly expressed under the natural conditions where they evolved, compared to laboratory conditions where prey and predator were brought into closer contact. Besides, previous experiences are likely to play an important role in expressed defensive responses.


Subject(s)
Anura/physiology , Food Chain , Larva/physiology , Motor Activity/physiology , Predatory Behavior , Animals , Cues
9.
J. bras. econ. saúde (Impr.) ; 11(1): 49-56, Abril/2019.
Article in Portuguese | ECOS, LILACS | ID: biblio-1005722

ABSTRACT

Objetivo: Avaliar a custo-efetividade da empagliflozina adicionada ao cuidado usual para tratamento de diabetes mellitus tipo 2 (DM2) no cenário da saúde suplementar brasileira. Métodos: Foi utilizada simulação de eventos discretos, com dados de efetividade baseados no estudo EMPA-REG OUTCOME. Foram incluídos pacientes com DM2 e alto risco cardiovascular (histórico de cardiopatia isquêmica, acidente vascular cerebral ou doença vascular periférica). O horizonte temporal foi o tempo de vida; a taxa de desconto foi de 5% ao ano. Os dados de utilidade foram predominantemente de estudos brasileiros. Para estimar os custos de eventos/condições com diferença estatisticamente significativa no EMPA-REG OUTCOME (insuficiência cardíaca, diálise, morte cardiovascular), foi feita uma revisão sistemática, que identificou estudos com dados da saúde suplementar. O limiar de disposição a pagar utilizado foi 1 produto interno bruto (PIB) per capita (2017: R$ 31.587). Foram conduzidas análises de sensibilidade determinísticas e probabilísticas. Resultados: No caso-base, a empagliflozina gerou ganho de 0,66 ano de vida ajustado para qualidade (QALY) na comparação com o cuidado usual, com acréscimo de R$ 12.630 e relação de custo-efetividade incremental (RCEI) de R$ 18.895/QALY. Na análise determinística, nenhuma variação de parâmetro resultou em RCEI acima do limiar. A análise probabilística teve RCEI média de R$ 19.878/QALY (intervalo de credibilidade de 2,5% a 97,5%: R$ 5.237-R$ 36.451). Considerando 1 PIB per capita, 50% das simulações seriam custo-efetivas; para 2 PIB per capita, o percentual ultrapassaria 90%. Conclusão: Considerando o limiar de custo-efetividade adotado, de 1 PIB per capita, a empagliflozina se mostrou custo-efetiva em relação ao cuidado usual na perspectiva da saúde suplementar brasileira.


Objective: To evaluate the cost-effectiveness of empagliflozin added to usual care in type 2 diabetes mellitus (T2DM) in the private healthcare sector. Methods: We used a discrete events simulation model with effectiveness data based on the EMPA-REG OUTCOME trial. The population included patients with T2DM at high cardiovascular risk (history of ischemic heart disease, stroke, or peripheral vascular disease). A lifetime horizon and a 5% annual discount rate were used. The utility data used were predominantly from Brazilian studies. To estimate the cost of events/conditions with statistically significant difference in the EMPA-REG OUTCOME trial (heart failure, dialysis, cardiovascular death), a systematic review was performed to identify studies with data from the private healthcare system. A willingness-to-pay threshold of 1 GDP per capita (2017: R$ 31,587) was considered. Deterministic sensitivity analysis and a probabilistic sensitivity analysis were performed. Results: In the base case, empagliflozin generated incremental 0.66 QALY as compared to usual care, with an added cost of R$ 12,630 and incremental cost-effectiveness ratio (ICER) of R$ 18,895/QALY. None of the parameter variations evaluated by deterministic analysis generated ICERs above the cost-effectiveness threshold. Probabilistic sensitivity analysis revealed mean ICER of R$ 19,878/QALY (credibility interval 2.5% to 97.5%: R$ 5,237 to R$ 36,451). Considering 1 GDP per capita, 50% of the simulations would be cost-effective; considering 2 GDP per capita, over 90% would be cost-effective. Conclusion: Considering a threshold of 1 GDP per capita, the study shows that empagliflozin was cost-effective from the perspective of the Brazilian private healthcare sector.


Subject(s)
Humans , Cost-Benefit Analysis , Diabetes Mellitus, Type 2 , Supplemental Health
10.
Biomed J ; 41(5): 298-305, 2018 10.
Article in English | MEDLINE | ID: mdl-30580793

ABSTRACT

Geraniol is a monoterpene alcohol that is derived from the essential oils of aromatic plants, with anti-inflammatory, antimicrobial, antioxidant and neuroprotective properties. This study characterized the effect of geraniol on behavior and brainwave patterns in rats. Male rats were submitted to administration of geraniol (25, 50 and 100 mg/kg). The hole board (HB) and open field (OF) tests were performed to evaluate anxiety and motor behavior, respectively. In addition, barbiturate-induced sleeping time (BIST) was used to analyze sedative effect. Finally, electrocorticogram (ECoG) recordings were used to characterize brain-wave patterns. The results showed that geraniol treatment in rats decreased the distance traveled, rearing numbers and lead to increase in immobility time in HB and OF tests. In BIST test, geraniol treatment increased sleep duration but not sleep latency in the animals. Furthermore, geraniol-treated animals demonstrated an increase in the percentage of delta waves in the total spectrum power. Taken together, our results suggested that geraniol exerted a depressant effect on the central nervous system of rats.


Subject(s)
Antioxidants/pharmacology , Behavior, Animal/drug effects , Central Nervous System/drug effects , Terpenes/pharmacology , Acyclic Monoterpenes , Animals , Barbiturates/pharmacology , Hypnotics and Sedatives/pharmacology , Male , Rats, Wistar , Sleep/drug effects
11.
Int J Endocrinol ; 2018: 2089471, 2018.
Article in English | MEDLINE | ID: mdl-30224918

ABSTRACT

Considering controversial data about the relationship between body size and prognosis of differentiated thyroid cancer (DTC), the current study aimed to assess the influence of body weight, body mass index (BMI), and body surface area (BSA) on DTC. We conducted a retrospective analysis of patients' records from the Thyroid Cancer Unit, assessing body size measures, clinical and laboratory prognostic factors, and disease evolution. 337 patients, aged 45.95 ± 13.04 years old, with BMI of 27.87 ± 5.13 kg/m2 and BSA of 1.74 ± 0.18 m2 were enrolled. After 9.5 ± 6.9 years of follow-up, 87.29% of patients were disease-free and 12.71% had persistent disease; no patient had deceased. Patients aged <45 years old with extrathyroidal invasion tumor had greater baseline body weight and BSA than those without extrathyroidal invasion (median 79.5 kg versus 67 kg and 1.85 m2 versus 1.74 m2). Women with poorly differentiated tumor and patients aged ≥45 years old with distant metastasis presented greater weight loss during follow-up compared to patients without such characteristics (median -2 kg versus +1.5 kg and -3 kg versus +1 kg, respectively). The relationship between body size and DTC evolution was not observed. In conclusion, higher weight and BSA were associated with a greater chance of extrathyroidal tumor invasion in younger patients. Specific subgroups of patients with aggressive disease presented higher weight loss. Young patients with higher BSA should be carefully treated due to possible worse prognosis related to increased incidence of extrathyroid invasion. Findings related to tumor aggressiveness and weight loss in specific groups deserve further mechanistic studies.

12.
Rev. SOBECC ; 23(3): 124-129, jul.-set. 2018.
Article in Portuguese | LILACS, BDENF - Nursing | ID: biblio-911443

ABSTRACT

Objetivo: Determinar a prevalência de pacientes em risco de desenvolvimento de lesões decorrentes do posicionamento cirúrgico. Método: Estudo transversal, realizado em hospital privado localizado na região sul do Brasil. Amostra aleatória com 378 pacientes adultos submetidos a cirurgias eletivas entre janeiro e setembro de 2017. Foi aplicada a Escala de Avaliação de Risco para o Desenvolvimento de Lesões Decorrentes do Posicionamento Cirúrgico (ELPO) após indução anestésica e realizada análise descritiva. Resultados: A prevalência de pacientes com alto risco de desenvolvimento de lesões foi de 19,05% (n=72). O posicionamento identificado como de maior risco foi a litotomia (59,72%; n=43). O escore médio da ELPO na amostra estudada foi 16,317 (desvio padrão=3,6176) e a mediana foi de 16, o que significa baixo risco de desenvolvimento de lesões. Conclusão: A ELPO permitiu determinar a prevalência de risco para lesões em pacientes submetidos a procedimentos eletivos, identificando que o risco está mais relacionado com a posição cirúrgica do que com o porte da cirurgia


Objective: To determine the prevalence of patients at risk of developing lesions due to surgical positioning. Method: A cross-sectional study was carried out in a private hospital in southern Brazil. Randomized sample with 378 adult patients submitted to elective surgeries between January and September 2017. The Risk Assessment Scale for the Development of Injuries due to Surgical Positioning (ELPO) was used after anesthetic induction and a descriptive analysis was performed. Results: The prevalence of patients at high risk of developing lesions was 19.05% (n=72). The lithotomic position was identified as the one with greatest risk (59.72%; n=43). The mean ELPO score in the sample was 16.317 (standard deviation=3.6176) and the median was 16, meaning low risk of developing lesions. Conclusion: ELPO allowed to determine the prevalence of risk for lesions in patients submitted to elective procedures, identifying that the risk is more related to surgical position than to the size of the surgery


Objetivo: Determinar la prevalencia de pacientes en riesgo de desarrollo de lesiones derivadas del posicionamento quirúrgico. Método: Estudio transversal, realizado em um hospital privado em el Sur de Brasil. Muestra aleatoria con 387 pacientes adultos sometidos a cirugías electivas entre enero y septiembre de 2017. Se aplicó la Escala de Evaluación de Riesgo para el Desarrollo de Lesiones Transcurrentes del Posicionamiento Quirúrgico (ELPO) después de la inducción anestésica y análisis descriptivo. Resultados: La prevalencia de pacientes con alto riesgo de desarrollo de lesiones fue del 19,05% (n=72). El posicionamiento identificado como de mayor riesgo fue la litotomía (59,72%, n=43). El score promedio de la ELPO en la muestra estudiada fue 16,317 (desviación estándar=3,6176) y la mediana fue de 16, lo que significa bajo riesgo de desarrollo de lesiones. Conclusión: La ELPO permitió determinar la prevalencia de riesgo para lesiones en pacientes sometidos a procedimientos electivos, identificando que el riesgo está más relacionado con la posición quirúrgica que con el porte de la cirugía


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Risk Assessment , Perioperative Care , Pressure Ulcer , Pain, Postoperative , Elective Surgical Procedures , Patient Positioning
13.
Eur J Med Chem ; 154: 341-353, 2018 Jun 25.
Article in English | MEDLINE | ID: mdl-29852459

ABSTRACT

N-oxide derivatives 5(a-b), 8(a-b), and 11(a-c) were designed, synthesized and evaluated in vitro and in vivo as potential drugs that are able to ameliorate sickle cell disease (SCD) symptoms. All of the compounds demonstrated the capacity to releasing nitric oxide at different levels ranging from 0.8 to 30.1%, in vivo analgesic activity and ability to reduce TNF-α levels in the supernatants of monocyte cultures. The most active compound (8b) protected 50.1% against acetic acid-induced abdominal constrictions, while dipyrone, which was used as a control only protected 35%. Compounds 8a and 8b inhibited ADP-induced platelet aggregation by 84% and 76.1%, respectively. Both compounds increased γ-globin in K562 cells at 100 µM. The mechanisms involved in the γ-globin increase are related to the acetylation of histones H3 and H4 that is induced by these compounds. In vitro, the most promising compound (8b) was not cytotoxic, mutagenic and genotoxic.


Subject(s)
Anemia, Sickle Cell/drug therapy , Drug Discovery , Histones/metabolism , Oxadiazoles/pharmacology , gamma-Globins/biosynthesis , Acetic Acid/antagonists & inhibitors , Acetic Acid/pharmacology , Acetylation , Anemia, Sickle Cell/metabolism , Dose-Response Relationship, Drug , Humans , K562 Cells , Molecular Structure , Nitric Oxide/metabolism , Oxadiazoles/chemical synthesis , Oxadiazoles/chemistry , Structure-Activity Relationship
14.
J. bras. econ. saúde (Impr.) ; 10(1): 29-35, Abr. 2018.
Article in Portuguese | LILACS, ECOS | ID: biblio-884392

ABSTRACT

Objetivo: Avaliar, por meio de dados do mundo real (DATASUS) e análises estatísticas, o impacto da inclusão do tiotrópio no tratamento da doença pulmonar obstrutiva crônica (DPOC), comparando o índice de hospitalização e custos associados à internação nos estados que possuem o tiotrópio padronizado em suas diretrizes de tratamento comparados aos estados que não o incluem. Método: Estudo retrospectivo histórico realizado entre 2013 e 2015, a partir de dados obtidos do DATASUS, portais de compras públicas estaduais e Secretarias de Saúde Estaduais. Todos os índices foram normalizados pelo número da população, de acordo com os dados atualizados do IBGE. Foi utilizado o teste Z para avaliar a significância estatística dos resultados. Resultados: A análise combinada do grupo com tiotrópio apresentou 52,4% menos hospitalizações em comparação ao grupo sem tiotrópio (90,0/100.000 versus 43,3/100.000, respectivamente, p < 0,01). O gasto total para o sistema único de saúde com hospitalização por DPOC foi de R$ 2,3 milhões e R$ 4,8 milhões para o grupo com tiotrópio vs. grupo sem tiotrópio, respectivamente (p = 0,0003). Houve diferença significativa entre os grupos quanto ao número total e gastos totais de internação por DPOC, nos estados nos quais o tiotrópio estava padronizado e nos estados sem o tiotrópio padronizado. Conclusão: A análise dos resultados sugere redução significativa no número de internações por DPOC e seus respectivos gastos nos estados nos quais o tiotrópio está padronizado.


Objective: To evaluate the impact of the inclusion of tiotropium in the treatment of chronic obstructive pulmonary disease (COPD) using real world data (DATASUS) and statistical analyzes, comparing hospitalization rates and costs associated with hospitalization in states where tiotropium is reimbursed in their treatment guidelines compared to states where tiotropium is not included. Method: A retrospective historical study conducted between 2013 and 2015, based on data obtained from DATASUS, state public purchasing portals and State Health Secretariats. All indexes were normalized by the number of the population, according to the IBGE updated data. The Z tests were used to evaluate the statistical significance of the results. Results: The combined analysis of the tiotropium reimbursed group presented 52.4% fewer hospitalizations compared to the tiotropium non-reimbursed group (90.0/100,000 versus 43.3/100,000, respectively). The total expenditure for the public healthcare system with hospitalization for COPD was R$ 2.3 million and R$ 4.8 million for the tiotropium group vs. the non-tiotropium group, respectively. Statistical analysis, both in total number and total costs of hospitalization for COPD, showed a statistically significant difference in the states in which tiotropium was reimbursed vs non-reimbursed. Conclusion: Analysis of the results suggests a significant reduction in the number of hospitalizations due to COPD in the states in which tiotropium is reimbursed, as well as a reduction in the total expenditure related to hospitalizations associated with COPD.


Subject(s)
Humans , Hospitalization , Lung Diseases , Tiotropium Bromide
15.
J. bras. econ. saúde (Impr.) ; 10(1): 56-63, Abr. 2018.
Article in Portuguese | LILACS, ECOS | ID: biblio-884395

ABSTRACT

Objetivo: Realizar uma análise de custo-utilidade de empagliflozina em pacientes com diabetes mellitus tipo 2 (DM2) e alto risco cardiovascular. Métodos: O modelo empregado foi uma simulação de eventos discretos, com dados baseados na incidência de eventos cardiovasculares do ensaio clínico EMPA-REG OUTCOME. A população-alvo foi de sujeitos com DM2 e alto risco cardiovascular (histórico de cardiopatia isquêmica, acidente vascular cerebral ou doença vascular periférica). O horizonte temporal foi o de tempo de vida; a taxa de desconto, de 5% ao ano; e a perspectiva, a do Sistema Único de Saúde (SUS). Os dados de utilidade foram obtidos de estudos brasileiros e internacionais. Os custos refletiram valores desembolsados pelo SUS. Foram conduzidas análises de sensibilidade determinísticas nos principais parâmetros e probabilística para avaliar a robustez global dos resultados. Resultados: No caso-base, a empagliflozina gerou 0,66 ano de vida ajustados para qualidade (QALY) a mais, com custo de R$ 19.176 maior, gerando relação de custo-efetividade incremental (RCEI) de R$ 28.960/QALY. As análises de sensibilidade univariadas mostraram oscilações da RCEI entre R$ 23.644 e R$ 38.850/QALY, sendo este valor mais alto de RCEI resultante da variação do valor de utilidade de pacientes com diabetes. Na análise probabilística, os percentis 2,5% e 97,5% foram de R$ 22.336 a R$ 39.571/QALY. Conclusão: O estudo mostrou uma RCEI de R$ 28.960/QALY, estando abaixo do valor de uma vez o produto interno bruto (PIB) per capita (R$ 30.407 em 2016), sendo, portanto, uma tecnologia custo-efetiva, considerando esse limiar. Na análise probabilística, o intervalo de credibilidade mostrou que a RCEI pode oscilar entre 0,73 e 1,30 PIB per capita, sendo, portanto, uma estimativa robusta.


Objective: To perform a cost-utility analysis of empagliflozin in type 2 diabetes (T2D) patients with high cardiovascular risk. Methods: The model was a discrete events simulation, with data based on the incidence of cardiovascular events in the EMPA-REG OUTCOME clinical trial. The target population was composed by patients with T2D and high cardiovascular risk (history of ischemic heart disease, stroke or peripheral vascular disease). We used a lifetime horizon, 5% discount rate and the Brazilian Public Healthcare System (SUS) perspective. Utility data were based both on Brazilian and international data. Costs employed reflected reimbursement SUS values. We conducted deterministic sensitivity analysis in main model parameters and a probabilistic sensitivity analysis to globally evaluate robustness of the results. Results: In the base case, empagliflozin generated incremental 0.66 QALY and R$ 19,176, resulting in an incremental cost-effectiveness ratio (ICER) of R$ 28,960/QALY. Univariate sensitivity analysis showed variations in the ICER between R$ 23,644 and R$ 38,850/QALY, with the diabetes status utility the variable with most influence in the ICER. In the probabilistic sensitivity analysis, 2.5% and 97.5% percentiles were R$ 22,336 and R$ 39,571/QALY. Conclusion: The study showed an ICER of R$ 28,960/QALY, which is below the value of one GDP per capita in Brazil (R$ 30,407 in 2016), which would therefore be deemed cost-effective under this threshold. In probabilistic sensitivity analysis, credible interval ranged between 0.73 and 1.30 per capita GDP, therefore showing robust results.


Subject(s)
Humans , Cardiovascular Diseases , Cost-Benefit Analysis , Diabetes Mellitus, Type 2
16.
Brain Res Bull ; 139: 9-15, 2018 05.
Article in English | MEDLINE | ID: mdl-29378222

ABSTRACT

Parkinson's disease (PD) is a neurodegenerative disease characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra pars compact (SNpc), with consequent depletion of dopamine in the striatum, which gives rise to the characteristic motor symptoms of PD. Although its etiology is unknown, several studies have suggested that oxidative stress plays a critical function in the pathophysiology of PD, and antioxidant agents could be helpful to slown down the dopaminergic neurodegeneration. Carvacrol (CA) is a phenolic monoterpene found in essential oils of many aromatic plants that presents antioxidant and neuroprotective effects. This study aimed to assess the effect of CA in a reserpine (RES)-induced rat model of PD. Male Wistar rats received 15 s.c. injections of 0.1 mg/kg RES or vehicle, every other day, concomitantly to daily i.p. injections of CA (12.5 or 25 mg/kg) or vehicle. Across the treatment, the animals were submitted to behavioral evaluation in the catalepsy test (performed daily), open field test (7th day) and assessment of vacuous chewing movements (12th, 20th and 30th days). Upon completion of behavioral tests, rats were perfused and their brains underwent tyrosine hydroxylase (TH) immunohistochemical analysis. Our results showed that CA (12.5 e 25 mg/kg) prevented the increase in catalepsy behavior and number of vacuous chewing movements, but failed to revert the decreased open-field locomotor activity induced by RES. In addition, CA in both doses prevented the decrease in TH immunostaining induced by RES in the SNpc and dorsal striatum. Taken together, our results suggest that CA shows a protective effect in a rat model of PD, preventing motor and neurochemical impairments induced by RES. Thus, the use of CA as a promising new strategy for the prevention and/or treatment of PD may be considered.


Subject(s)
Antiparasitic Agents/therapeutic use , Antipsychotic Agents/toxicity , Monoterpenes/therapeutic use , Parkinsonian Disorders/chemically induced , Reserpine/toxicity , Tyrosine 3-Monooxygenase/metabolism , Analysis of Variance , Animals , Catalepsy/diagnosis , Catalepsy/etiology , Cymenes , Disease Models, Animal , Dose-Response Relationship, Drug , Exploratory Behavior/drug effects , Locomotion/drug effects , Male , Mastication/drug effects , Parkinsonian Disorders/physiopathology , Rats , Rats, Wistar , Vesicular Monoamine Transport Proteins/metabolism
17.
Exp Hematol ; 58: 35-38, 2018 02.
Article in English | MEDLINE | ID: mdl-29108926

ABSTRACT

Fetal hemoglobin (HbF) induction by hydroxyurea (HU) therapy is associated with decreased morbidity and mortality in sickle cell anemia (SCA) patients, but not all patients respond to or tolerate HU. This provides a rationale for developing novel HbF inducers to treat SCA. Thalidomide analogs have the ability to induce HbF production while inhibiting the release of tumor necrosis factor-alpha. Molecular hybridization of HU and thalidomide was used to synthesize 3- (1,3-dioxoisoindolin-2-yl) benzyl nitrate (compound 4C). In this study, we show that compound 4C increases HbF production in a transgenic SCA mouse model and reduces the production of pro-inflammatory cytokines by SCA mouse monocytes cultured ex vivo. Therefore, compound 4C is a novel drug designed to treat SCA with a unique combination of HbF-inducing and anti-inflammatory properties.


Subject(s)
Anemia, Sickle Cell/drug therapy , Cytokines/metabolism , Fetal Hemoglobin/biosynthesis , Hydroxyurea , Thalidomide , Anemia, Sickle Cell/genetics , Anemia, Sickle Cell/metabolism , Anemia, Sickle Cell/pathology , Animals , Cytokines/genetics , Disease Models, Animal , Fetal Hemoglobin/genetics , Hydroxyurea/analogs & derivatives , Hydroxyurea/chemical synthesis , Hydroxyurea/chemistry , Hydroxyurea/pharmacology , Inflammation/drug therapy , Inflammation/genetics , Inflammation/metabolism , Inflammation/pathology , Mice , Mice, Knockout , Thalidomide/analogs & derivatives , Thalidomide/chemical synthesis , Thalidomide/chemistry , Thalidomide/pharmacology
18.
Endocr Res ; 43(2): 73-79, 2018 May.
Article in English | MEDLINE | ID: mdl-29083246

ABSTRACT

OBJECTIVE: TSH-suppression is a therapy for thyroid cancer management, but it may lead to adverse effects, which should be balanced with its benefits. Previous studies evaluating the consequences of TSH suppression on insulin sensitivity have only been done with indirect techniques, and results were controversial. Therefore, we aimed to assess insulin sensitivity in patients with thyroid cancer and suppressed thyroid-stimulating hormone (TSH) with the most appropriate direct method (hyperinsulinemic-euglycemic clamp) in order to get a more conclusive response about the topic. METHODS: A group of 20 non-obese and non-diabetic thyroid cancer patients with suppressed TSH underwent a hyperinsulinemic-euglycemic clamp to evaluate insulin sensitivity. Their results were compared to the results of a sex and body mass index (BMI) -paired control group composed of 20 healthy volunteers. RESULTS: Patients were all female, aged 36.8 ± 10.2 years-old, with mean TSH 0.1 ± 0.1 µIU/mL and mean BMI 26.2 ± 3.3 kg/m2. Insulin sensitivity, determined by the insulin-stimulated glucose uptake (M-value), was lower in the patients group (4.2 ± 1.6 mg/min*kg versus 5.8 ± 1.7, age-adjusted p-value = 0.0205). CONCLUSION: This study shows for the first time that subclinical thyrotoxicosis in patients with thyroid cancer is associated with insulin resistance, as measured by hyperinsulinemic-euglycemic clamp technique. Such finding may be taken into consideration by clinicians when balancing risks and benefits of TSH-suppression therapy in thyroid cancer patients.


Subject(s)
Insulin Resistance , Thyroid Neoplasms/blood , Thyroid Neoplasms/drug therapy , Thyrotropin/blood , Thyroxine/adverse effects , Adult , Cross-Sectional Studies , Female , Glucose Clamp Technique , Humans , Thyrotropin/drug effects
19.
J. bras. econ. saúde (Impr.) ; 9(1): http://www.jbes.com.br/images/v9n1/73.pdf, Abril, 2017.
Article in Portuguese | LILACS, ECOS | ID: biblio-833563

ABSTRACT

Objetivo: Comparar os custos e efetividade do afatinibe versus pemetrexede associado a cisplatina (PEM/CIS), erlotinibe e gefitinibe no tratamento de primeira linha de pacientes com câncer de pulmão não pequenas células (CPNPC) com mutação no receptor de fator de crescimento epidermoide (EGFR+) localmente avançado ou metastático, no Sistema de Saúde Suplementar brasileiro. Métodos: O modelo de Markov foi utilizado para estimar anos de vida livres de progressão (PFLY), anos de vida (LY), anos de vida ajustados pela qualidade (QALY) e desfechos clínicos por sete anos. Utilizaram-se dados de sobrevida, segurança e utilidade dos estudos LUX-Lung 1, 3 e 6 e LUCEOR. A eficácia comparativa versus gefitinibe e erlotinibe foi estimada utilizando modelos bayesianos de comparação indireta. A utilização dos recursos foi estimada por painel de especialistas, e custos diretos foram estimados utilizando-se bases de dados oficiais. Resultados: Afatinibe mostrou aumento da sobrevida livre de progressão (0,41 PFLY), sobrevida global (0,16 LY) e qualidade de vida (0,21 QALY) com custo incremental (R$ 8.549), resultando em razão de custo-efetividade incremental (RCEI) de R$ 20.639/PFLY. Comparado ao erlotinibe, o afatinibe mostrou aumento de 0,46 PFLY, 0,13 LY e 0,20 QALY, com menor custo (-R$ 21.327). Comparado ao gefitinibe, o afatinibe mostrou incrementos de 0,53 PFLY, 0,37 LY, 0,34 QALY, com custo incremental de R$ 24.890, resultando em RCEI de R$ 46.709/PFLY. Considerando-se três vezes o PIB per capita como limiar de custo-efetividade (R$ 86.628), o afatinibe é custo-efetivo versus PEM/CIS e gefitinibe e dominante quando comparado ao erlotinibe. Conclusão: Sugere-se que o afatinibe é uma opção custo-efetiva quando comparado ao PEM/CIS, erlotinibe e gefitinibe no tratamento de primeira linha de pacientes com CPNPC EGFR+.


Objective: To compare costs and effectiveness of afatinib versus pemetrexed plus cisplatin (PEM/ CIS), erlotinib and gefitinib, as first line treatment in patients with locally advanced or metastatic epidermal growth factor receptor mutation (EGFR+) non-small cell lung cancer (NSCLC) in the Brazilian Private Healthcare System. Methods: A Markov model was used to estimate 7year progression-free life years (PFLY), life years (LY), quality-adjusted life years (QALY) and clinical outcomes of afatinib. Partitioned survival, safety and utility data from the LUX-Lung 1, 3 and 6 and LUCEOR trials were used. Comparative effectiveness versus gefitinib and erlotinib was estimated using Bayesian indirect treatment comparison. Resource use was estimated by an expert panel and direct costs were estimated from official databases. Results: Compared with PEM/CIS, afatinib was associated with increased progression free survival (0.41 PFLY), increased overall survival (0.16 LY) and increased quality of life (0.21 QALY) with incremental cost (BRL 8,549), resulting in an incremental cost-effectiveness ratio (ICER) of BRL 20.639/PFLY. Compared to erlotinib, afatinib was associated with additional 0.46 PFLY, 0.13 LY and 0.20 QALYs with lower cost (- BRL 21,327). When compared to gefitinib, afatinib was associated with incremental 0.53 PFLY, 0.37 LY and 0.34 QALY and increased cost (BRL 24,890), resulting in an ICER of BRL 46,709/PFLY. Considering 3 PIB per capita as a threshold (BRL 86,628), afatinib is a cost-effective technology versus PEM/CIS and gefitinib and dominant when compared to erlotinib. Conclusion: Findings suggest that afatinib is a cost-effective option, when compared to PEM/CIS, erlotinib and gefitinib, as first line treatment in EGFR+ NSCLC patients.


Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung , Cost-Benefit Analysis , Lung Neoplasms
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