Recebido em 5/12/02; aceito em 7/7/03 NATURAL PRODUCTS FOR DENGUE TRANSMISSION CONTROL-LARVICIDAL ACTIVITY OF Myroxylon balsamum (RED OIL) AND OF TERPENOIDS AND PHENYLPROPANOIDS. The bioassay-guided fractionation of the hexane extract obtained from the medicinal plant Myroxylon balsamum (red oil) was conducted in preparative thin layer chromatography on silica gel. The obtained fractions and some terpenoids and phenylpropanoids were assayed as larvicidal on third instar Aedes aegypti larvae, NPPN colony. The results indicate that the sesquiterpene nerolidol was the active constituent in the extract and that the sesquiterpenes were more active than the monoterpenes and phenylpropanoids utilized in this study. Lipophilicity seems to be an important property for the activity since the compounds with hydroxyl, carbonyl and methoxyl groups were less active. The results confirm also that essential oils can be a good tool for the control of dengue.Keywords: essential oil constituents; Aedes aegypti; Myroxylon balsamum. INTRODUÇÃOO dengue é uma infecção reemergente que vem preocupando as autoridades sanitárias de todo o mundo em virtude de sua circulação nos cinco continentes e grande potencial para assumir formas graves e letais. No período compreendido entre 1955 e 1995 foram registrados cerca de 3 milhões de casos de febre hemorrágica do dengue e 58 mil mortes 1 . Com o surgimento de formas resistentes do mosquito aos inseticidas convencionais utilizados, tem crescido a procura por extratos vegetais e substâncias naturais que sejam efetivas no combate ao mosquito adulto e/ou à larva de Aedes aegypti e que sejam isentas de toxicidade para o meio ambiente. Resistência a inseticidas convencionais é um dos principais obstáculos ao controle de insetos pestes de importância na agricultura e na medicina. A resistência resulta no aumento da freqüência de aplicação de inseticida, dosagens crescentes, rendimentos diminuídos, danos ambientais e surgimento de doenças, quando os vetores não podem ser controlados. Segundo a Organização Mundial de Saúde (OMS), o custo da resistência de insetos a inseticidas pode alcançar anualmente US$ 1,4 bilhões nos Estados Unidos 2 . Plantas, como organismos que co-evoluem com insetos e outros microorganismos, são fontes naturais de substâncias inseticidas e antimicrobianas, já que as mesmas são produzidas pelo vegetal em resposta a um ataque patogênico. Inúmeras substâncias acumulamse no vegetal para sua defesa contra microorganismos, algumas delas sendo denominadas de fitoalexinas 3 . As plantas sintetizam e emitem inúmeros compostos voláteis (ácidos, aldeídos e terpenos) para atrair polinizadores e se defender de herbívoros 4 . No que concerne à defesa contra herbívoros, as plantas desenvolveram dois tipos de defesa, a direta e a indireta. Na defesa direta estão envolvidas substâncias como sílica, metabólitos secundários, enzimas e proteínas, além de órgãos como tricomas e espinhos que afetam diretamente a performance do inseto. Na defesa indireta estão envolvidas substân-cias emitidas pela p...

University teaching hospitals usually provide tertiary care and are subject to early adoption of new technologies, which may compromise healthcare systems when uncritically adopted. Knowledge on the decision-making process -drug selection by drug selection committees or DTCs -is crucial to improve the quality of care. There are no models for studying the selection of drugs in Brazilian healthcare services. This study aims to discuss DTC structure and the processes regarding adoption of medicines in tertiary university hospitals in Brazil and to propose an analytical structure for providing direction for the future. State of the art content regarding drug selection processes and DTC procedures was reviewed in three databases. Information on the medicine selection process in a Brazilian gold standard teaching hospital was collected through observations and a review of existing procedures. A structured discussion on medicine selection and DTC procedures in tertiary hospitals ensued. This discussion resulted in findings that were organized in three dimensions, composing an analytical framework for the application in tertiary Brazilian hospitals (i) motivations for the adoption of drugs; (ii) necessary structural and organizational aspects for decision-making; and (iii) criteria and methods employed by the decision-making process. We believe that the suggested framework is compatible with tertiary Brazilian hospitals, because a gold standard in the country was able to conduct all its procedures in the light of WHO and international recommendations. We hope to contribute in producing knowledge which may hopefully be adopted in tertiary hospitals across Brazil.Timely and evidence-based adoption of medical technologies and medicines is critical for improving patient care [1][2][3]. Researchers, physicians and patient groups tend to welcome new technologies [4] that may pose risks to patients and might compromise the effectiveness of healthcare systems. Also, lack of evidence-based procedures and clear policies for handling conflict of interests may challenge the provision of equitable services and therapy to all in need [1][2][3][4][5].Possible advances of novel pharmaceuticals may be limited. A study in France perceived that only 17 of 984 (1.7%) medicines launched were real advances in pharmacotherapy studied during the period of 2001 to 2010 [6,7]. Unfortunately, the intense marketing practices to health professionals and the public by manufacturers generate undue expectations and induce demand for innovations if not critically balanced in technique-oriented healthcare facilities [8][9][10][11]. This is not in the best interest of physicians, patients or health authorities.Brazil is a middle-income country that in July 2013 had an estimated population size of 200.1 million inhabitants [12]. The Brazilian Public Health System (Sistema Unico de Saude -SUS) was initiated in 1990 and adopts comprehensive universal care as a principle. Over the years, a trend to establish parallel subsystems (reimbursed private ...

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The Specialized Pharmaceutical Services Component (CEAF) ensures the dispensing of high-cost medicines for the treatment of specific diseases. The fact that these medicines are mandatory though access is only through legal injunctions, suggests flaws in the management of pharmaceutical services. This paper analyzed adherence to Clinical Protocols and Therapeutic Guidelines (PCDT) in the dispensing of these CEAF medicines. Qualitative research was also conducted in facilities with different characteristics in the State of Rio de Janeiro. It was noted that the lack of adequate structure in the units studied, including trained personnel, compromises the dispensing CEAF medicines in all facilities. The CEAF dispensing procedure, heavily dependent on interaction between prescribers and dispensers, is not carried out as would be expected. It is possible that inadequate performance is also linked to flaws in the planning and organization of services. The results indicate barriers in adherence to PCDT by health professionals, prejudicing health system users and possibly leading them to access medicines by legal means. It is believed that characteristics of the investigated facilities are similar to others in Brazil, and the barriers identified may be the same, compromising healthcare.

The current frame of reference on adherence to pharmacotherapy includes a set of behaviors experienced by the user, with observation of the detailed and continuous history of the use of each dose of the medication. Indicators based on pharmacy records have been used to measure adherence. The current review aimed to identify and describe indicators based on pharmacy records and to discuss their adequacy and limitations for measuring adherence. An exploratory literature review was conducted in three databases using the terms "adherence", "pharmacy records/administrative data", and "measure" to compose the descriptors for the selection of 81 articles and the elaboration of a chart with the denomination, sources, methods for calculation, description, and interpretation of the operational and referential meaning of 14 indicators. Given the most recent taxonomy for adherence proposed in the literature, we concluded that the indicators can be useful for identifying patients with medication-seeking behavior-related problems and analysis of persistence. The distance between supply-related events and difficulties in treatment follow-up can influence an analysis based exclusively on the use of these indicators.

IntroductionAlthough it is an essential component of the treatment of acute lymphoid leukemia in children, asparaginase causes adverse reactions that sometimes make it impossible to use it fully. Hypersensitivity reactions are the most frequent and may lead to early discontinuation of treatment. The present study aimed to investigate suspicions of adverse reactions during the infusion of asparaginase in a pediatric cohort.MethodsA retrospective observational study was carried out at a university pediatric institute in the state of Rio de Janeiro. Information regarding clinical features and characteristics of adverse reactions was collected from hospital medical records. Suspicions of adverse reactions were classified regarding causality and severity.ResultsSeventy-three suspicions of adverse reactions were recorded during asparaginase infusion in 72 children in the study period. Allergic hypersensitivity reactions were suspected in 60.5% of the cases. Of these, 25% of the reactions occurred during induction and 61.1% in concomitant use with vincristine, findings that diverge from other studies. High-risk classification and younger age were considered risk factors for these reactions. A total of 72.4% of the reactions were classified as grade 1 or 2, which suggest that not all are related to antibody formation; this highlights the importance of differential diagnosis with other reactions, such as non-allergic hypersensitivity and hyperammonemia.ConclusionThe implementation of the differential diagnosis of reactions related to infusion of asparaginase with ammonia dosage and classification of the grade of reactions is crucial to facilitate the identification and proper management of each type of reaction.

Background: Microbial drug resistance is one of the biggest public health problems. Antibiotic consumption is an essential factor for the emergence and spread of multiresistant bacteria. Therefore, we aimed to analyze the antibiotics consumption in the Intensive Care Unit (ICU), identifying trends in the antibiotics use profile and microbiological isolates throughout the COVID-19 pandemic.Methods: We performed this retrospective observational study in intensive care units of a Brazilian tertiary hospital from January 2019 to December 2020. The primary outcome was antimicrobial consumption in the ICU, measured by defined daily doses (DDDs) per 100 bed-days. As a secondary outcome, bacterial infections (microbiological isolates) were calculated in the same fashion. Outcomes trends were analyzed using Joinpoint regression models, considering constant variance (homoscedasticity) and first-order autocorrelation assumptions. A monthly percent change (MPC) was estimated for each analyzed segment.Results: Seven thousand and nine hundred fifty-three patients had data available on prescribed and received medications and were included in the analyses. Overall, the use of antibiotics increased over time in the ICU. The reserve group (World Health Organization Classification) had an increasing trend (MPC = 7.24) from February to April 2020. The azithromycin consumption (J01FA) increased rapidly, with a MPC of 5.21 from January to April 2020. Polymyxin B showed a relevant increase from March to June 2020 (MPC = 6.93). The peak of the antibiotic consumption of Reserve group did not overlap with the peak of the pathogenic agents they are intended to treat.Conclusion: Overall antimicrobial consumption in ICU has increased in the context of the COVID-19 pandemic. The peaks in the antimicrobial’s use were not associated with the rise of the pathogenic agents they intended to treat, indicating an empirical use, which is especially concerning in the context of treating multidrug-resistant (MDR) infections. This fact may contribute to the depletion of the therapeutic arsenal for MDR treatment.

This is the first manuscript, and it is related to the challenges identified in the DUR area in the LatAm region. Drug utilization researchers in LatAm voluntarily participated in multiple discussions contributed with local data and reviewed successive drafts and the final document.