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Background: Although not always avoidable, drug-drug interaction (DDI) is an example of a predictable adverse event. Warfarin is a narrow therapeutic window oral anticoagulant that has been described to interact with antimicrobials (AM), affecting therapy efficacy and/or safety of anticoagulant and/or antimicrobial treatment. Aim: To evaluate the intrarater agreement on information about potential DDI between warfarin and AM present in the Municipal Essential Medicines List of Porto Alegre (REMUME/POA), Rio Grande do Sul, Brazil, between different electronic databases (EDB). Method: This descriptive analysis evaluated the EDB UpToDate®, Drugs.com®, Medscape®, and Micromedex® on information about DDI mechanism, severity classification, and clinical management. Results: Amongst the 20 AM listed, 17 had a potential DDI with warfarin described in at least one EDB. Total agreement rate between EDB regarding classification of DDI was 30%; as for partial concordance, rates among 2 and 3 EDB were respectively 25% and 45%. Most concordant EDB were UpToDate® and Drugs.com® (85%). For mechanism of DDI, the overall concordance rate was 12%; partial agreement was 35% and 23.5% on two and three EDB, respectively. Overall agreement rate for clinical management of DDI was 18%; partial agreement between 2 and 3 EDB was 29% and 53%, respectively. Conclusion: Overall concordance rate is relatively low, considering the information obtained for the three aspects evaluated. The partial concordance rate, however, is higher, reaching 45% of the drugs with concordant DDI classification for three out of four EDB. Further studies are needed to evaluate the robustness of the evidence employed by EDB.

Background The prevalence of drug–drug interactions (DDIs) in hospital settings is variable, and elderly patients are considered a high risk population for DDIs. There are no systematic reviews describing the prevalence of DDIs in hospitalised elderly patients. Objectives To assess and summarise the available data on the prevalence of DDIs in hospitalised elderly patients and to describe which drugs, drug classes and drug combinations are most commonly involved in DDIs. Data source A systematic electronic literature search was conducted on Medline/PubMed, Embase, Lilacs, SciElo, Web of Science, Cinahl, Scopus, Cochrane, OpenGrey, Capes Thesis Bank, OasisBR, OpenAire and abstracts from scientific events, without limitation on language or period of publication. Study selection was completed on 21 September 2018. Study eligibility criteria, participants and interventions Original observational studies that reported the prevalence of actual or potential DDIs during hospitalisation in patients aged 60 years or older were included. The main outcome measure was prevalence of DDIs and number of DDIs per patient. Subgroup analysis was performed in studies that reported the prevalence of DDIs in geriatric units. Study appraisal and synthesis methods Study quality was assessed using the Agency for Healthcare Research and Quality methodological checklist for cross sectional and prevalence studies. Results 34 studies were included, involving 9577 patients. The prevalence of DDIs ranged from 8.34% to 100%. In studies conducted in geriatric units, the prevalence ranged from 80.5% to 90.5%. The number of DDIs per patient ranged from 1.2 to 30.6. Single drugs most commonly involved in DDIs were furosemide, captopril, warfarin and dipyrone. Drug classes mostly involved were potassium sparing diuretics and angiotensin converting enzyme inhibitors. Limitations The main limitation is the heterogeneity between the included studies that precluded a meta-analysis. Several different methods were used to identify DDIs, majorly, and potential DDIs. Few studies have reported measures to control the quality of the collected data. Conclusions and implications of key findings The prevalence of DDIs ranged widely, and the variation may reflect differences in the conditions of the elderly patients and level of attention (or complexity of care), as well as methodological differences, especially the methods and/or software used to identify DDIs. Systematic review registration number CRD42018096720

Natural killer (NK) cell activity is regulated by activating and inhibitory signals transduced by killer cell immunoglobulin-like receptors (KIR). Diversity in KIR gene repertoire among individuals may affect disease outcome. Sepsis development and severity may be influenced by genetic factors affecting the immune response. Here, we examined sixteen KIR genes and their human leucocyte antigen (HLA) class I ligands in critical patients, aiming to identify patterns that could be associated with sepsis. Male and female patients (ages ranging between 14 and 94years-old) were included. DNA samples from 211 patients with sepsis and 60 controls (critical care patients with no sepsis) collected between 2004 and 2010 were included and genotyped for KIR genes using the polymerase chain reaction method with sequence-specific oligonucleotide (PCR-SSO), and for HLA genes using the polymerase chain reaction method with sequence-specific primers (PCR-SSP). The frequencies of activating KIR2DS1 and KIR3DS1 in sepsis patients when compared to controls were 41.23% versus 55.00% and 36.49% versus 51.67% (p=0.077 and 0.037 respectively before Bonferroni correction). These results indicate that activating KIR genes 2DS1 and 3DS1 may more prevalent in critical patients without sepsis than in patients with sepsis, suggesting a potential protective role of activating KIR genes in sepsis.

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Introdução: Pacientes transplantados renais necessitam do uso de imunossupressores para bloquear a resposta imunológica e prevenir a rejeição. A adesão ao tratamento imunossupressor é essencial para a sobrevida do enxerto. O aumento da incidência de rejeição e consequente perda do enxerto são fortemente associados a não adesão. Objetivo: Revisar a literatura existente a respeito da não adesão ao tratamento imunossupressor em pacientes transplantados renais. Métodos: Foi realizado um levantamento literário do período de janeiro de 2002 a outubro de 2012 nas plataformas de dados PubMed, Scielo e Lilacs. Resultados: Não há consenso quanto à nomenclatura e definição da não adesão. A prevalência varia conforme o estudo (1,6 a 50%). São utilizados diferentes métodos para mensurar a não adesão. Múltiplos fatores interferem na ocorrência da não adesão e, como consequência desta, há maior incidência de desfechos clínicos e econômicos negativos. As intervenções envolvem abordagens multidimensionais e a inclusão do farmacêutico clínico na equipe multidisciplinar de transplante mostra-se favorável. Conclusões: É necessária a padronização da nomenclatura e da definição da não adesão. Deve ser determinada qual combinação de métodos de mensuração é mais precisa. A avaliação dos fatores preditores para a não adesão deve conter uma amostra que represente todos os tipos de pacientes, e deve permitir o delineamento de perfis de risco. A eficácia das intervenções deve ser testada através de estudos randomizados; já a avaliação da não adesão, dos fatores de risco e dos desfechos necessita ser realizada em estudos longitudinais e prospectivos.

Os objetivos do presente estudo foram avaliar o tratamento com tuberculostáticos para verificar o índice de abandono nos esquemas terapêuticos (2RHZ/4RH e 2RHZE/4RH), e identificar fatores preditivos ao abandono do tratamento. Foram utilizados dados de literatura e aqueles disponibilizados pelo Serviço Municipal de Infectologia de Caxias do Sul no período de 2011 a 2013. O teste qui-quadrado de Pearson ou o teste exato de Fisher foram utilizados para a comparação de associação, entre o desfecho do tratamento e as variáveis. Os esquemas terapêuticos avaliados nesse estudo não atingiram as metas da OMS para o controle da tuberculose. Os fatores preditivos do abandono ao tratamento foram: sexo masculino, faixa etária entre 20-39 anos, baixa escolaridade, caso novo e presença de comorbidades. Desses fatores os que apresentaram significância estatística associados ao desfecho do tratamento foram o ingresso (caso novo) e a presença de comorbidades. Para se atingir o controle da tuberculose é necessário a diminuição dos índices de abandono ao tratamento.

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are common syndromes that affect both clinical and surgical patients. This study describes the effects of a potent and specific N-methyl-d-aspartate receptor antagonist (MK-801) against oxidative stress in acute lung injury induced by intratracheal lipopolysaccharide (LPS) injection. This study was performed using male Wistar rats weighing 200-250g. Rats were randomly divided into four groups: control with isotonic saline instillation (n=6); LPS (100μg/100g of body weight) treated with saline (n=6); LPS treated with MK-801 (0.3mg/kg, intraperitoneally; n=6); LPS treated with MK-801 (0.3mg/kg, intratracheally; n=6). Twelve hours after the LPS instillation, rats were anesthetized and a bronchoalveolar lavage (BAL) was performed in order to determine the alveolar-capillary membrane alterations and the inflammatory infiltrate level. Blood and lung samples were isolated and assayed for oxidative stress variables and histopathologic analysis. The use of MK-801 decreased bronchoalveolar lavage fluid protein, LDH activity and inflammatory cells. Indeed, the treatment with MK-801 significantly attenuated lung oxidative damage and histopathologic alterations after LPS instillation. Our data provide the first experimental demonstration that MK-801 decreases oxidative stress and limits inflammatory response and alveolar disarray in lipopolysaccharide-induced acute lung injury.

Sepsis is a systemic response to an infection that leads to a generalized inflammatory reaction. There is an intimate relationship between procoagulant and proinflammatory activities, and coagulation abnormalities are common in septic patients. Pharmaceutical studies have focused to the development of substances that act on coagulation abnormalities and on the link between coagulation and inflammation. Fructose-1,6-bisphosphate (FBP) is a high-energy glycolitic metabolite that in the past two decades has been shown therapeutic effects in great number of pathological situations, including sepsis. The aims of this study were to assess the effects of FBP on platelet aggregation in vitro and ex vivo in healthy and septic rats and evaluate the use of FBP as a treatment for thrombocytopenia and coagulation abnormalities in abdominal sepsis in rat. FBP inhibited platelet aggregation (P < 0.001) in vitro in healthy rats from the smallest dose tested, 2.5 mM, in a dose-dependent manner. The mean effective dose calculated was 10.6 mM. The highest dose tested, 40 mM, completely inhibited platelet aggregation (P < 0.001) induced by ADP. Platelet aggregation in plasma from septic rats was inhibited only with higher doses of FBP, starting from 20 mM (P < 0.001). The calculated mean effective dose was 19.3 mM. Ex vivo platelet aggregation in septic rats was significantly lower (P < 0.05) than healthy rats and the treatment with FBP, at the dose of 2 g/kg, diminished the platelet aggregation at the extension of 27% (P < 0.001), suggesting that FBP is a potent platelet aggregation inhibitor in vivo. Moreover, treatment with FBP 2 g/kg prevented thrombocytopenia (P < 0.001), prolongation of prothrombin and partial thromboplastin time (P < 0.001), but not fibrinogen, in septic rats. The most important findings in this study are that FBP is a potent platelet aggregation inhibitor, in vitro and ex vivo. It presents protective effects on coagulation abnormalities, which can represent a treatment against DIC. The mechanisms for these effects remain under investigation.

Tacrolimus (FK 506), a potent immunosuppressive drug used in prevention and treatment of rejection of transplanted organs, exhibits efficacy related to its blood levels and has a narrow therapeutic index. These factors require frequent monitoring of patients blood levels, in attempt to adjust the dose to reach the best drug concentration with minimum side effects. In this historic study, the authors evaluated tacrolimus blood profile in patients submitted to pancreas transplantation between June 2002 and March 2004. The results show that blood levels were, mostly, within subtherapeutic (39.1%) and toxic (43.4%) ranges. Considering post-transplantation period, subtherapeutic levels were more frequent until three months after the graft receiving (51.1%) and between three and six months (41.9%), whereas toxic levels were more common six months after the transplantation (63%). Patients who received pancreas/kidney transplantation showed a tendency to present toxic levels. The same did not happen with the patients who received isolated pancreas and pancreas after kidney; these patients presented subtherapeutic blood levels in all post-transplantation periods. The results found in this study reassure the importance of therapeutic monitoring to achieve the adequate blood levels of tacrolimus following pancreas transplantation. O tacrolimus (FK506), um potente imunossupressor utilizado na profilaxia e no tratamento de rejeições pós-transplante, exibe eficácia relacionada com sua concentração sangüínea e possui estreita janela terapêutica. Esses fatores requerem o freqüente monitoramento dos níveis sangüíneos em pacientes que fazem uso do fármaco, tendo como objetivo o ajuste de dose para uma concentração terapêutica ótima com efeitos colaterais mínimos. Este estudo retrospectivo foi realizado através do acesso à base de dados do Laboratório de Patologia Clínica do Hospital São Lucas, da Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), e teve por objetivo analisar o perfil das concentrações sanguíneas de tacrolimus em pacientes transplantados de pâncreas, no período de junho de 2002 a março de 2004. Os resultados mostram que as concentrações se encontravam, em sua maioria, em níveis subterapêuticos (39,1%) e tóxicos (43,4%). Considerando-se o período pós-transplante, níveis subterapêuticos foram mais freqüentes nos períodos de zero a três meses (51,1%) e de três a seis meses (41,9%) após o transplante, enquanto níveis tóxicos (63%) foram mais freqüentes após seis meses. Pacientes que receberam pâncreas/rim simultâneo apresentaram, de maneira geral, mais concentrações em níveis tóxicos; o mesmo não aconteceu em pacientes que receberam pâncreas isolado e pâncreas pós-rim. Os pacientes que receberam pâncreas isolado e pâncreas pós-rim tenderam a apresentar níveis subterapêuticos em todos os períodos pós-transplante considerados. Os resultados obtidos neste trabalho demonstram a importância do monitoramento terapêutico, uma vez que seus resultados orientam o ajuste das doses.