The use of green protic ionic liquids in the crystallization of isoniazid: Evaluation of physicochemical and biological properties of drug.

This study evaluated the synthesis of protic ionic liquids (PILs), 2-hydroxy ethylammonium formate (2-HEAF) and 2-hydroxy ethylammonium acetate (2-HEAA), and their applicability in the crystallization process of the active pharmaceutical ingredient isoniazid (INH) as anti-solvent. Isoniazid is an antibiotic used in the treatment of tuberculosis infections, being used as a first-line chemotherapeutic agent against Mycobacterium tuberculosis. Futhermore, this investigation was conducted in order to evaluate how these PILs can influence the habit, solubility, stability, and therapeutic efficiency of the obtained isoniazid crystals. The 2-HEAF and 2-HEAA PILs were easily formed in reactions between ethanolamine and carboxylic acids (formic or acetic acid), and they have no toxicity against Artemia salina. The PILs were able to crystallize isoniazid, influencing the crystal habit and size. The greatest variations in the hydrogen signals of the NH2 and NH groups of the amine and low variations in the chemical shifts of the hydrogens of the cation of the ethanolamine group from 2-HEAA and 2-HEAF indicate that PILs establish possibly weak interactions with INH. The obtained crystals were amorphous and showed higher solubility in water than standard INH. Moreover, these crystals showed therapeutic efficiency inantimycobacterial activity to inhibit the growth of Mycobacterium tuberculosis. The INH:2-HEAF only degraded 5.1 % (w/w), however, INH:2-HEAA degraded 32.8 % (w/w) after 60 days in an accelerated atmosphere. Then, the 2-HEAA and 2-HEAF were able to crystallize isoniazid, being a new application for these PILs. The used PILs also influenced the characteristics of isoniazid crystals.

Cost-Effectiveness of Technologies for the Treatment of Spinal Muscular Atrophy: A Systematic Review of Economic Studies.

OBJECTIVES: This study aims to systematically collect data on cost-effectiveness analyses that assess technologies to treat type I and II spinal muscular atrophy and evaluate their recommendations. METHODS: A structured electronic search was conducted in 4 databases. Additionally, a complementary manual search was conducted. Complete economic studies that evaluated nusinersen, risdiplam, onasemnogene abeparvovec (OA), and the best support therapy (BST) from the health system's perspective were selected. The incremental cost-effectiveness ratios were compared with various thresholds for the analysis. The review was registered a priori in PROSPERO (CRD42022365391). RESULTS: Twenty studies were included in the analyses. They were all published between 2017 and 2022 and represent the recommendations in 8 countries. Most studies adopted 5, 6, or 10-state Markov models. Some authors took part in multiple studies. Four technologies were evaluated: BST (N = 14), nusinersen (N = 19), risdiplam (N = 5), and OA (N = 9). OA, risdiplam, and nusinersen were considered inefficient compared with the BST. Risdiplam and OA were generally regarded as cost-effective when compared with nusinersen. Because nusinersen is not a cost-effective drug, no recommendation can be derived from this result. Risdiplam and OA were compared in 2 studies that presented opposite results. CONCLUSIONS: Nusinersen, risdiplam, and OA are being adopted worldwide as a treatment for spinal muscular atrophy. Despite that, the pharmacoeconomic analyses show that the technologies are not cost-effective compared with the BST. The lack of controlled studies for risdiplam and OA hamper any conclusions about their face-to-face comparison.

Vulnerabilidade socioeconômica e microcefalia relacionada ao Zika vírus no Brasil / Socioeconomic vulnerability and microcephaly related to Zika virus in Brazil

Resumo Objetivo: Realizar uma análise descritiva dos gastos privados diretos domiciliares em saúde e da vulnerabilidade socioeconômica associados à condição de microcefalia, uma das manifestações mais evidentes da síndrome congênita do Zika vírus (SCZ). O surto de microcefalia e outros distúrbios neurológicos em crianças menores de um ano de idade foi associado à infecção pelo vírus Zika, durante a epidemia ocorrida no período de 2015-2016 no Brasil. Método: Noventa e seis entrevistas foram realizadas em dois centros especializados de atendimento às crianças acometidas por microcefalia nas cidades do Rio de Janeiro e Fortaleza. O questionário estruturado abrangeu características sociodemográficas, gastos com desembolso direto associados com a doença e estratégias adotadas pelas famílias para lidarem com os desafios financeiros impostos pela anomalia congênita. Resultados: Os domicílios eram majoritariamente chefiados por não-brancos e pertenciam às classes C e D-E. Os gastos com medicamentos contabilizaram 78% dos gastos médicos, enquanto as despesas com transporte representaram 46% do gasto privado não-médico. A maioria dos domicílios enfrentaram endividamento e redução do consumo doméstico, inclusive de alimentos, a fim de fazer face às despesas incorridas pela doença. Conclusão: A microcefalia parece reforçar a vulnerabilidade socioeconômica das famílias, reforçando o círculo vicioso característico da abordagem conceitual da armadilha saúde-pobreza.

Abstract Objective: To carry out a descriptive analysis of direct private household health expenditures and socioeconomic vulnerability associated with the condition of Microcephaly, one of the most evidence manifestations of Congenital Zika Syndrome (CZS). The outbreak of microcephaly and other neurological disorders in children under one year of age was linked to Zika virus infection during the 2015-2016 epidemic in Brazil. Method: Ninety-six interviews were carried out in two specialized care centers for children with microcephaly in the cities of Rio de Janeiro and Fortaleza, Brazil. The structured questionnaire covered sociodemographic characteristics, out-of-pocket expenditures associated with the disease, and strategies adopted by families to deal with the financial challenges imposed by the congenital anomaly. Results: The households were mostly headed by non-whites and belonged to classes C and D-E. Expenditures on medicines accounted for 78% of medical expenses, while transportation represented 46% of private non-medical expenses. Most households faced debt and reduced domestic consumption, including food, to meet the expenses incurred by the disease. Conclusion: Microcephaly appears to reinforce the socioeconomic vulnerability of families, reinforcing the vicious circle characteristic of the health-poverty trap conceptual approach.

External validation of the unifying concept for the quantitative assessment of functional mitral regurgitation.

PURPOSE: A novel conceptual framework was introduced to enhance the quantitative assessment of functional mitral regurgitation (FMR) and improve risk stratification. However, the data was derived from a single-center cohort and lack external validation. We aimed to validate the proposed algorithm using a different patient population. METHODS: Patients with at least mild FMR and reduced left ventricular ejection fraction (< 50%) were retrospectively identified at a single-center. The cohort was stratified in low, intermediate and high-risk according to the proposed framework, on the basis of effective regurgitant orifice area (EROA) and regurgitant volume (RegVol). Patients within the intermediate-risk group were subsequently reclassified into either the low-risk category (Regurgitant Fraction, RegFrac < 50%) or the high-risk category (RegFrac ≥ 50%) based on their regurgitant fraction. The primary endpoint was all-cause mortality. RESULTS: A total of 572 patients were included. During a median follow-up of 3.8 years there were 254 deaths (44%). On multivariable analysis, the proposed thresholds for FMR severity remained independently associated with all-cause mortality (adjusted hazard ratio: 1.488; 95% confidence interval [CI]: 1.110-2.013; p-value = 0.010). This algorithm demonstrated superior discriminative ability (C-statistic: 0.664) compared to contemporary guidelines (C-statistic: 0.522; p-value for comparison < 0.001). Additionally, it resulted in a significant improvement in the net reclassification index (0.162; p-value < 0.001). CONCLUSIONS: Within our cohort, the application of the proposed concept demonstrated a significant association with a higher risk of all-cause mortality. Moreover, this conceptual framework showcased the potential to improve the accuracy of risk prediction beyond current guidelines.

Peak left atrial longitudinal strain is associated with all-cause mortality in patients with ventricular functional mitral regurgitation.

PURPOSE: Chronic mitral regurgitation promotes left atrial (LA) remodeling. However, the significance of LA dysfunction in the setting of ventricular functional mitral regurgitation (FMR) has not been fully investigated. Our aim was to assess the prognostic impact of peak atrial longitudinal strain (PALS), a surrogate of LA function, in patients with FMR and reduced left ventricular ejection fraction (LVEF). METHODS: Patients with at least mild ventricular FMR and LVEF < 50% under optimized medical therapy who underwent transthoracic echocardiography at a single center were retrospectively identified in the laboratory database. PALS was assessed by 2D speckle tracking in the apical 4-chamber view and the study population was divided in two groups according to the best cut-off value of PALS, using receiver operating characteristics (ROC) curve analysis. The primary endpoint-point was all-cause mortality. RESULTS: A total of 307 patients (median age 70 years, 77% male) were included. Median LVEF was 35% (IQR: 27 - 40%) and median effective regurgitant orifice area (EROA) was 15mm2 (IQR: 9 - 22mm2). According to current European guidelines, 32 patients had severe FMR (10%). During a median follow-up of 3.5 years (IQR 1.4 - 6.6), 148 patients died. The unadjusted mortality incidence per 100 persons-years increased with progressively lower values of PALS. On multivariable analysis, PALS remained independently associated with all-cause mortality (adjusted hazard ratio 1.052 per % decrease; 95% CI: 1.010 - 1.095; P = 0.016), even after adjustment for several (n = 14) clinical and echocardiographic confounders. CONCLUSION: PALS is independently associated with all-cause mortality in patients with reduced LVEF and ventricular FMR.

Secondary mitral regurgitation: Maintaining coherence with the American Society of Echocardiography grading guidelines, which proportionality concept best predicts prognosis in the real world?

INTRODUCTION: Proportionality of secondary mitral regurgitation (sMR) may be a key factor in deciding whether a patient may benefit from mitral intervention. The aim of this study was to evaluate the prognostic value of two different concepts of proportionality and assess their ability to improve MR stratification proposed by the American Society of Echocardiography (ASE) guidelines. METHODS: We conducted a retrospective analysis in patients with reduced left ventricular ejection fraction (LVEF) (<50%) and at least mild sMR. Proportionality status was calculated using formulas proposed by a) Grayburn et al. - disproportionate sMR defined as EROALVEDV >0.14; b) Lopes et al. - disproportionate sMR whenever measured EROA>theoretical EROA (determined as 50%×LVEF×LVEDVMitralVTI). Primary endpoint was all-cause mortality. RESULTS: A total of 572 patients (69±12 years; 76% male) were included. Mean LVEF was 33±9%, with a median left ventricular end-diastolic volume of 174 mL [136;220] and a median effective regurgitant orifice area of 14 mm2 [8;22]. During mean follow-up of 4.1±2.7 years, there were 254 deaths. There was considerable disagreement (p<0.001) between both formulas: of 96 patients with disproportionate sMR according to Lopes' criteria, 46 (48%) were considered proportionate according to Grayburn's; and of 62 patients with disproportionate sMR according to Grayburn's, 12 (19%) were considered proportionate according to Lopes' formula. In multivariate analysis, only Lopes' definition of disproportionate sMR maintained independent prognostic value (hazard ratio 1.5; 95% confidence interval 1.07-2.1, p=0.018) and improved the risk stratification of ASE sMR classification. CONCLUSION: Of the two formulas available to define disproportionate sMR, Lopes' model emerged as the only one with independent prognostic value while improving the risk stratification proposed by the ASE guidelines.

Out-of-pocket expenditures associated with congenital zika syndrome in Brazil: an analysis of household health spending / Gastos out-of-pocket associados à síndrome congênita do vírus Zika no Brasil: uma análise dos gastos domiciliares em saúde

Objective: The study aims to estimate catastrophic health expenditures associated with the diagnosis and follow-up treatment of Congenital Zika Syndrome (CZS) in children affected during the 2015-2016 epidemic in Brazil. Catastrophic health expenditures are defined as health spending that exceeds a predefined proportion of the household's total expenditures, exposing family members to financial vulnerability. Methods: Ninety-six interviews were held in the cities of Fortaleza and Rio de Janeiro in a convenience sample, using a questionnaire on sociodemographic characteristics and private household expenditures associated with the syndrome, which also allowed estimating catastrophic expenditures resulting from care for CZS. Results: Most of the mothers interviewed in the study were brown, under 34 years of age, unemployed, and reported a monthly family income of two minimum wages or less. Spending on medicines accounted for 77.6% of the medical expenditures, while transportation and food were the main components of nonmedical expenditures, accounting for 79% of this total. The affected households were largely low-income and suffered catastrophic expenditures due to the disease. Considering the family income metric, in 41.7% of the households, expenses with the child's disease exceeded 10% of the household income. Conclusion: Public policies should consider the financial and healthcare needs of these families to ensure adequate support for individuals affected by CZS.

Objetivo: O estudo tem como objetivo estimar os gastos catastróficos em saúde associados ao diagnóstico e acompanhamento do tratamento da síndrome congênita do Zika (SCZ) em crianças afetadas durante a epidemia de 2015-2016 no Brasil. Gastos catastróficos em saúde são definidos como gastos com saúde que excedem uma proporção predefinida dos gastos totais do domicílio, expondo os membros da família à vulnerabilidade financeira. Métodos: Foram realizadas 96 entrevistas nas cidades de Fortaleza e Rio de Janeiro numa amostra de conveniência, por meio de questionário sobre características sociodemográficas e gastos privados domiciliares associados à síndrome, o que também permitiu estimar gastos catastróficos decorrentes do cuidado à SCZ. Resultados: A maioria das mães entrevistadas no estudo era parda, com menos de 34 anos, desempregada e com renda familiar mensal igual ou inferior a dois salários mínimos. Os gastos com medicamentos representaram 77,6% dos gastos médicos, enquanto transporte e alimentação foram os principais componentes dos gastos não médicos, respondendo por 79% desse total. Os domicílios afetados eram, em grande parte, de baixa renda e sofreram gastos catastróficos devido à doença. Considerando a métrica de renda familiar, em 41,7% dos domicílios, os gastos com a doença da criança ultrapassaram 10% da renda familiar. Conclusão: As políticas públicas devem considerar as necessidades financeiras e de saúde dessas famílias para garantir o suporte adequado aos indivíduos acometidos pela SCZ.

Transcutaneous Nerve Electrostimulation (TENS) in Pain Relief During Labor: A Scope Review.

OBJECTIVE: To map health evidence on the effectiveness of transcutaneous nerve electrostimulation (TENS) therapy in pain relief during delivery. METHODS: This is a scoping review in the PubMed, LILACS, Cochrane, VHL, PEDRO, and SciELO databases, through the descriptors electric stimulation, transcutaneous and labor, obstetric and their synonyms. RESULTS: A total of 263 studies were identified, of which 54 duplicates were excluded. After sorting by titles and abstracts, there were 24 articles for reading, remaining 6. The six studies evaluated the reduction of pain through the visual analogue scale (VAS). CONCLUSION: The findings indicate that the use of TENS as a nonpharmacological strategy for pain relief in labor has positive results.

OBJETIVO: Mapear evidências em saúde sobre a eficácia da terapia por estimulação elétrica nervosa transcutânea (TENS, na sigla em inglês) no alívio da dor durante o parto. MéTODOS: Trata-se de uma revisão de escopo nas bases de dados PubMed, LILACS, Cochrane, VHL, PEDRO e SciELO, através dos descritores estimulação eléctrica, transcutânea e trabalho, obstetrícia e os seus sinônimos. RESULTADOS: Foram identificados 263 estudos, dos quais 54 duplicados foram excluídos. Após a classificação por títulos e resumos, 24 artigos foram selecionados para leitura, restando 6. Os seis estudos avaliaram a redução da dor através da escala visual analógica (EVA). CONCLUSãO: Os resultados indicam que a utilização de TENS como estratégia não farmacológica para o alívio da dor no parto tem resultados positivos.

Assessing proportionate and disproportionate functional mitral regurgitation with individualized thresholds.

AIMS: The concept of proportionate/disproportionate functional mitral regurgitation (FMR) has been limited by the lack of a simple way to assess it and by the paucity of data showing its prognostic superiority. The aim of this study was to evaluate the prognostic value of an individualized method of assessing FMR proportionality. METHODS AND RESULTS: We retrospectively identified 572 patients with at least mild FMR and reduced left ventricular ejection fraction (<50%) under medical therapy. To determine FMR proportionality status, we used an approach where a simple equation determined the individualized theoretical regurgitant volume (or effective regurgitant orifice area) threshold associated with haemodynamically significant FMR. Then, we compared the measured with the theoretical value to categorize the population into non-severe, proportionate, and disproportionate FMR. The primary endpoint was all-cause mortality. During a median follow-up of 3.8 years (interquartile range: 1.8-6.2), 254 patients died. The unadjusted mortality incidence per 100 persons-year rose as the degree of FMR disproportionality worsened. On multivariable analysis, disproportionate FMR remained independently associated with all-cause mortality [adjusted hazard ratio: 1.785; 95% confidence interval (CI): 1.249-2.550; P = 0.001]. The FMR proportionality concept showed greater discriminative power (C-statistic 0.639; 95% CI: 0.597-0.680) than the American (C-statistic 0.583; 95% CI: 0.546-0.621; P for comparison <0.001) and European guidelines (C-statistic 0.584; 95% CI: 0.547-0.620; P for comparison <0.001). When added to any of the before-mentioned guidelines, FMR proportionality also improved risk stratification by reclassifying patients into lower and higher risk subsets. CONCLUSION: Disproportionate FMR is independently associated with all-cause mortality and improves the risk stratification of current guidelines.

Plant invasion affects vegetation structure and sediment nitrogen stocks in subtropical mangroves.

Plant invasion can primarily affect the structure and functioning of terrestrial and aquatic ecosystems. Although there is evidence that plant invasion can modify organic matter dynamics in mangroves, it is uncertain whether and to which extent these changes can affect carbon (C) and nitrogen (N) dynamics in the sediment-plant system. Here, we measured: (i) the structure of native vegetation and C and N in the sediment-plant system in subtropical mangroves subjected to aquatic macrophytes invasion in southeastern Brazil. We answered the following questions: i) Do invaded mangroves differ in aboveground biomass compared to non-invaded mangroves?; ii) Are there C4 macrophytes in these sites? iii) What are the C and N stocks in sediment of invaded mangroves? We quantified C and N concentrations and the isotopic signature of such elements (δ13C and δ15N) in the sediment-plant system, the C and N stocks in the sediment (0-20 cm depth), and mangrove aboveground biomass. Mangrove aboveground biomass was lower at invaded compared to non-invaded sites reflecting the species displacement in invaded sites. The sediment at invaded mangroves did not significantly contribute to C4 sources because of the large predominance of both mangrove and invasive C3 plants. While sediment C stocks were similar among study sites (∼47 Mg ha-1), N stocks were lower at invaded (2.7 Mg ha-1) comparing to non-invaded (3.2 Mg ha-1) mangroves. The lower N stocks at invaded sites can reflect the higher leaf N concentrations and lower C:N ratios of invasive plants compared to mangroves. Thus, the effects of macrophytes invasion in subtropical mangroves are more apparent for vegetation structure and N stocks. C stocks alteration is expected the be detectable in the future.

The effect of an orally-dosed Caralluma Fimbriata extract on appetite control and body composition in overweight adults.

To examine the effect of a Caralluma Fimbriata extract (CFE) on biomarkers of satiety and body composition in overweight adults. A double-blind, randomised, placebo controlled trial to examine the effect of a Caralluma Fimbriata extract (CFE) on biomarkers of satiety and body composition in overweight adults. Eighty-three men and women aged between 20 and 50 years of age completed 16 weeks of daily supplementation with either CFE or placebo. Plasma cardiometabolic (lipid profile, glucose, insulin) and satiety (ghrelin, leptin, neuropeptideY) biomarkers, body composition, diet history and gastrointenstinal function were assessed at baseline, weeks 4, 8, 12 and 16. Subjects in the CFE and placebo groups were well matched and predominatly female 93% and 87.5%, with a mean age of 40.9 ± 6.7 and 39.5 ± 7.5 years and body mass index (BMI) of 30.0 ± 3.1 and 30.2 ± 2.9 kg/m2 respectively. There was a significant difference in plasma leptin concentration change between groups at week 16 (p = 0.04), with the placebo group increasing concentration (2.27 ± 4.80 ng/mL) while the CFE group (0.05 ± 4.69 ng/mL) remained the same. At week 16, the CFE group had significantly reduced their calorie intake from baseline compared to the placebo group (245 cal vs 15.8 cal respectively p < 0.01). The CFE group also had a significant reduction in waist circumference of 2.7 cm compared to an increase of 0.3 cm in the placebo group (p = 0.02). A weight increase from baseline was seen in the placebo group that was not observed in the CFE group (1.33 kg weight gain vs 0.37 kg weight loss respectively; p = 0.03). The placebo group also had a significant increase in fat mass, android fat mass, BMI and leptin compared to the CFE group (p = 0.04, 0.02, < 0.01 respectively). CFE was effective at maintaining bodyweight during a non-calorie controlled diet compared to a placebo. The mechanism responsible for this action is requiring further research and could be due to an increase in satiety receptor sensitivity.

Biological nitrogen fixation across major biomes in Latin America: Patterns and global change effects.

Biological nitrogen fixation (BNF) supports terrestrial primary productivity and plays key roles in mediating human-induced changes in global nitrogen (N) and carbon cycling. However, there are still critical uncertainties in our understanding of the amount of BNF occurring across terrestrial ecosystems, and of how terrestrial BNF will respond to global change. We synthesized BNF data from Latin America, a region reported to sustain some of the highest BNF rates on Earth, but that is underrepresented in previous data syntheses. We used meta-analysis and modeling approaches to estimate BNF rates across Latin America's major biomes and to evaluate the potential effects of increased N deposition and land-use change on these rates. Unmanaged tropical and subtropical moist forests sustained observed and predicted total BNF rates of 10 ± 1 and 14 ± 1 kg N ha-1 y-1, respectively, supporting the hypothesis that these forests sustain lower BNF rates than previously thought. Free-living BNF accounted for two-thirds of the total BNF in these forests. Despite an average 30% reduction of free-living BNF in response to experimental N-addition, our results suggest free-living BNF rate responses to current and projected N deposition across tropical and subtropical moist forests are small. In contrast, the conversion of unmanaged ecosystems to crop and pasture lands increased BNF rates across all terrestrial biomes, mostly in savannas, grasslands, and dry forests, increasing BNF rates 2-fold. The information obtained here provides a more comprehensive understanding of BNF patterns for Latin America.

Proposta de análise integrada de emergências em saúde pública por arboviroses: o caso do Zika vírus no Brasil / Proposal for integrated analysis of public health emergencies involving arboviruses: the case of the Zika virus in Brazil

RESUMO A mudança no padrão de ocorrência da microcefalia associada à infecção pelo Zika Vírus em gestantes no Brasil resultou na decretação de emergência em saúde pública de importância nacional e internacional. Esforços coordenados e multisetoriais foram demandados, mas nem sempre houve respostas efetivas ou preparação das populações afetadas. A epidemia de Zika repercutiu nas políticas públicas, incluindo a de saúde, seja na investigação científica, seja na proposição de medidas de controle, diagnóstico, prevenção e tratamento. Objetivou-se apresentar proposta de análise integrada para abordagem de futuras emergências sanitárias com foco nas arboviroses. Partindo da experiência brasileira da epidemia e literatura relacionada, articularam-se quatro dimensões: vulnerabilidades e risco; condições e impactos socioeconômicos na população; desenvolvimento e emprego de tecnologias e pesquisas; e resposta e reprogramação do sistema de saúde. Pretende-se viabilizar loci específicos de investigação, para mensuração de possíveis desfechos e geração de novas evidências sobre os efeitos da epidemia nos sistemas de saúde. O conhecimento científico e suas lacunas são considerados os principais elementos integradores dessas dimensões analíticas, de forma a contribuir com resposta mais oportuna e efetiva em futuras emergências. Além do conhecimento adquirido, faz-se necessário agregar capacidade de enfrentar futuras emergências relacionadas com as epidemias de arboviroses.

ABSTRACT The change in the pattern of occurrence of microcephaly associated with Zika virus infection in pregnant women in Brazil resulted in the declaration of a Public Health Emergency of National and International Concern. Coordinated and inter-sector efforts were required, but there were not always effective responses or preparation of the affected populations. The Zika epidemic impacted public policies, including health policy, both in scientific research, proposals for control measures, diagnosis, prevention, and treatment. The study aimed to propose an integrated analysis for the approach to future health emergencies, with a focus on arboviral infections. Based on the Brazilian experience with the Zika epidemic and the related literature, the analysis links four dimensions: vulnerabilities and risk; the population's socioeconomic conditions and impacts; development and use of technologies and research; and the health system's response and reprogramming. The aim is to allow specific research focuses to measure the possible outcomes and generate new evidence on the epidemic's effect on health systems. Scientific knowledge and its gaps are the main integrating elements in these analytic dimensions, aimed at contributing with a more timely and effective response in future emergencies. Besides the acquired knowledge, it is necessary to add capacity to confront future emergencies related to arbovirus epidemics.

Long-term assessment of the Ross procedure in adults: Clinical and echocardiographic follow-up at 20 years.

INTRODUCTION: The Ross procedure is an alternative to standard aortic valve (AV) replacement in young and middle-aged patients. However, durability and incidence of reoperation remain a concern for most cardiac surgeons. Our aim was to assess very long-term clinical and echocardiographic outcomes of the Ross procedure. METHODS: We conducted a single-center retrospective analysis of 56 consecutive adult patients who underwent the Ross procedure. Mean age at surgery was 44±12 years (range, 16-65 years) and 55% were male. Clinical endpoints included overall mortality and the need for valve reoperation due to graft failure. The echocardiographic endpoint was the presence of any graft deterioration. Median clinical follow-up was 20 years (1120 patient/years). RESULTS: Indications for surgery were dominant aortic stenosis in 50% and isolated aortic regurgitation in 21%. Concomitant mitral valve repair was performed in 21% and a subcoronary technique was most commonly used (86%). Overall long-term survival was 91%, 80% and 77% at 15, 20 and 24 years, respectively. The survival rate was similar to the age- and gender-matched general population (p=0.44). During the follow-up period, freedom from graft reoperation was 80%. Eleven patients (31%) developed moderate AV regurgitation, three (8.6%) developed moderate pulmonary regurgitation and one (2.9%) presented moderate pulmonary stenosis. CONCLUSION: The Ross procedure, mostly using a subcoronary approach, proved to have good clinical and hemodynamic results, with low reoperation rates in long-term follow-up. Moderate autograft regurgitation was a frequent finding but had no significant clinical impact.

"Factors associated with non-small cell lung cancer treatment costs in a Brazilian public hospital".

BACKGROUND: The present study estimated the cost of advanced non-small cell lung cancer care for a cohort of 251 patients enrolled in a Brazilian public hospital and identified factors associated with the cost of treating the disease, considering sociodemographic, clinical and behavioral characteristics of patients, service utilization patterns and survival time. METHODS: Estimates were obtained from the survey of direct medical cost per patient from the hospital's perspective. Data was collected from medical records and available hospital information systems. The ordinary least squares (OLS) method with logarithmic transformation of the dependent variable for the analysis of cost predictors was used to take into account the positive skewness of the costs distribution. RESULTS: The average cost of NSCLC was US$ 5647 for patients, with 71% of costs being associated to outpatient care. The main components of cost were daily hospital bed stay (22.6%), radiotherapy (15.5%) and chemotherapy (38.5%). The OLS model reported that, with 5% significance level, patients with higher levels of education, with better physical performance and less advanced disease have higher treatment costs. After controlling for the patient's survival time, only education and service utilization patterns were statistically significant. Individuals who were hospitalized or made use of radiotherapy or chemotherapy had higher costs. The use of these outpatient and hospital services explained most of the treatment cost variation, with a significant increase of the adjusted R2 of 0.111 to 0.449 after incorporation of these variables in the model. The explanatory power of the complete model reached 62%. CONCLUSIONS: Inequities in disease treatment costs were observed, pointing to the need for strategies that reduce lower socioeconomic status and population's hurdles to accessing cancer care services.

Pretreatment of cashew apple bagasse using protic ionic liquids: Enhanced enzymatic hydrolysis.

To enhance the enzymatic digestibility of cashew apple bagasse (CAB) feedstock in order to produce sugar fermentation-derived bioproducts, the CAB was subjected to three different pretreatments with the ionic liquid 2-hydroxyl-ethylammonium acetate (2-HEAA) and characterized by FTIR, NMR and chemical methods. All conditions were able to delignify CAB, however the best lignin removal (95.8%) was achieved through the method performed with 8.7% w/w of CAB/2-HEAA ratio at 130°C for 24h. Although the cellulose crystallinity has been increased in CAB treated with the ionic liquid, but this fact did not influence its digestibility. Nevertheless, the pretreatment with 2-HEAA enhanced significantly the cellulose digestibility, increasing the glucose yield from 48 to 747.72mgglucose/gCAB. Furthermore, 2-HEAA pretreatment was efficient even with reused ionic liquid, obtaining high glucose concentration.

Nitrogen dynamics in subtropical fringe and basin mangrove forests inferred from stable isotopes.

Mangroves exhibit low species richness compared to other tropical forests, but great structural and functional diversity. Aiming to contribute to a better understanding of the functioning of mangrove forests, we investigated nitrogen (N) dynamics in two physiographic types of mangroves (fringe and basin forests) in southeastern Brazil. Because fringe forests are under great influence of tidal flushing we hypothesized that these forests would exhibit higher N cycling rates in sediment and higher N losses to the atmosphere compared to basin forests. We quantified net N mineralization and nitrification rates in sediment and natural abundance of N stable isotopes (δ15N) in the sediment-plant-litter system. The fringe forest exhibited higher net N mineralization rates and δ15N in the sediment-plant-litter system, but net nitrification rates were similar to those of the basin forest. The results of the present study suggest that fringe forests exhibit higher N availability and N cycling in sediment compared to basin forests.

Logical Inconsistencies in 3 Preference Elicitation Methods for EQ-5D Health States: A Study in the Brazilian Population.

BACKGROUND: . Logical inconsistency for health states preferences occurs when one logically worse health state, in terms of quality of life, is ranked higher than a logically better health state. OBJECTIVE: . This study explores the presence of inconsistent responses for the EQ-5D health states valuations in a Brazilian population survey. It compares the level of inconsistency in 3 preference-based methods: ranking, visual analog scale (VAS), and time tradeoff (TTO). The influence of EQ-5D health state descriptions is explored by examining the distance between states using a city-block metric as an indicator of proximity. Moreover, it examines the association between formal education and the presence of inconsistencies, as well as the effect of removing inconsistent respondents on the estimation of social value sets from TTO and VAS. METHODS: . Data came from a valuation study with 3362 literate individuals aged between 18 and 64 years living in urban areas of Minas Gerais state, Brazil. Logical inconsistency was assessed using the percentage of inconsistent respondents and inconsistency rate. A logistic model was estimated to assess the association between formal education and the logical inconsistency. Societal preferences were estimated excluding inconsistent respondents considering city-block metric. RESULTS: . The percentage of inconsistent respondents and inconsistency rate are similar for TTO and ranking and lower for VAS. The probability of being inconsistent is higher among less educated groups in ranking and TTO. Inconsistency decreases with distance for all 3 methods. The removal of inconsistent individuals by considering city-block distance improves TTO estimation of social value sets. CONCLUSION: . Findings suggest that removal of inconsistencies in TTO should consider city-block distance. For VAS, inconsistencies are not associated with formal education and do not affect social value set estimation.

Comparação de métodos de valoração de preferências sociais por estados de saúde / Comparison of valuation methods of health states societal preferences

Este artigo explora a equivalência entre três métodos de aferição de preferências por estados de saúde: Ranking, Visual Analogue Scale (VAS) e Time Trade-off (TTO). As preferências são utilizadas em avaliações de tecnologias em saúde. Utilizando dados de um estudo de avaliação com base no sistema descritivo EQ-5D, em Minas Gerais, realiza-se a transformação das informações ordinais em cardinais por meio do modelo logit condicional. Os resultados mostram que apesar da ordenação das preferências ser similar entre os três métodos analisados, diferenças expressivas na magnitude dos valores são observadas, com consequências importantes para a tomada de decisões quanto à alocação de recursos em saúde.

This paper aims to analyze the equivalence between three valuation methods for eliciting health states preferences: Ranking, Visual Analogue Scale (VAS) and Time Trade-off (TTO). Preferences are used in health technology assessment. Data come from a survey in Minas Gerais using the EQ-5D descriptive system. The transformation of ordinal preferences into cardinal preferences was performed using the conditional logit model. The results show that despite the ranking of preferences to be similar among the three methods, significant differences in values are observed and play important consequences for making decision regarding allocation of health resources.