ABSTRACT Introduction: The therapeutic plasma exchange (TPE) controls the systemic cytokine level and might improve the immune response in patients with severe Coronavirus (COVID-19) infection. To date, in developing countries, no study has explored the effectiveness and risk factors in a population with severe COVID-19 exposed to the TPE. Method: We described the risk factors associated with survival rates higher than 28 days and length of stay (LOS) in the intensive care unit (ICU) shorter than 15 days. Severe COVID-19 cases treated with TPE were included, from August 2020 to June 2021. Survival analysis with Kaplan-Meier curves, log-rank tests and multivariate logistic regressions were conducted to assess patient-related factors that could predict a higher survival rate and the ICU LOS. Results: A total of 99 patients with severe COVID-19 who had received TPE were followed during their hospital stay and for 28 days after discharge. The sample was composed of men (63%) aged 56 ± 16 years. The overall survival rate at 28 days was 80%. The ICU LOS (p = 0.0165) and mechanical ventilation (MV) (p = 0.00008) were considered factors that could increase the risk of death. Patient-related factors that influenced the 28-day mortality were the smoking status (OR = 5.8; 95%CI 1.5, 22) and history of oncologic or non-malignant hematologic diseases (OR = 5.9; 95%CI 1.2, 29). Conclusion: Patients with severe COVID-19 exposed to the TPE were associated with a 20% risk of death in a 28-day observation window, appearing to be lower than previous treatments. Active smoking, cancer and immunosuppressive conditions should be considered as relevant variables to be controlled in future trials on the TPE and COVID-19.

Abstract Background Randomized controlled trials (RCTs) and observational studies have compared the efficacy and safety of transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis. Objectives Compare TAVR and SAVR in patients with different surgical risks, population characteristics, and different transcatheter prosthetic valves. Methods An overview of systematic reviews (SRs) was conducted following a structured protocol. Results were grouped by surgical risk, population characteristics, and different valves. RCTs in the SRs were reanalyzed through meta-analyses, and the results were summarized using the GRADE method. The adopted level of statistical significance was 5%. Results Compared to SAVR, patients with high surgical risk using TAVR had a lower risk of (odds ratio, 95% confidence interval, absolute risk difference) atrial fibrillation (AF) (0.5, 0.29-0.86, -106/1000) and life-threatening bleeding (0.29, 0.2-0.42, -215/1000). Patients with intermediate surgical risk had a lower risk of AF (0.27, 0.23-0.33, -255/1000), life-threatening bleeding (0.15, 0.12-0.19, -330/1000), and acute renal failure (ARF) (0.4, 0.26-0.62, -21/1000). Patients with low surgical risk had a lower risk of death (0.58, 0.34-0.97, -16/1000), stroke (0.51, 0.28-0.94, -15/1000), AF (0.16, 0.12-0.2, -295/1000), life-threatening bleeding (0.17, 0.05-0.55, -76/1000), and ARF (0.27, 0.13-0.55, -21/1000), and had a higher risk of permanent pacemaker implantation (PPI) (4.22, 1.27-14.02, 141/1000). Newer generation devices had a lower risk of AF than older generations, and patients using balloon-expandable devices did not experience higher risks of PPI. Conclusions This paper provides evidence that patients at low, intermediate, and high surgical risks have better outcomes when treated with TAVR compared with SAVR.

Resumo Fundamento Ensaios clínicos randomizados (ECRs) e estudos observacionais compararam a eficácia e a segurança do implante valvar transcateter (TAVR) e da substituição cirúrgica da valva aórtica (SAVR) em pacientes com estenose aórtica grave. Objetivos Comparar TAVR e SAVR em pacientes com diferentes riscos cirúrgicos, características da população e diferentes válvulas protéticas transcateter. Métodos Uma overview das revisões sistemáticas (RSs) foi realizada seguindo um protocolo estruturado. Os resultados foram agrupados por risco cirúrgico, características da população e diferentes válvulas. Os ECRs foram reanalisados por meio de metanálises nas RSs, e os resultados foram resumidos por meio do método GRADE. O nível de significância estatística adotado foi de 5%. Resultados Em comparação com a SAVR, os pacientes com alto risco cirúrgico submetidos à TAVR tiveram um risco menor de ( odds ratio , intervalo de confiança de 95%, diferença absoluta de risco) fibrilação atrial (FA) (0,5, 0,29-0,86, -106/1000) e hemorragia com risco à vida (0,29, 0,2-0,42, -215/1000). Pacientes com risco cirúrgico intermediário apresentaram menor risco de FA (0,27, 0,23-0,33, -255/1.000), hemorragia com risco à vida (0,15, 0,12-0,19, -330/1.000) e insuficiência renal aguda (IRA) (0,4, 0,26-0,62, -21/1000). Pacientes com baixo risco cirúrgico tiveram menor risco de morte (0,58, 0,34-0,97, -16/1000), acidente vascular encefálico (AVE) (0,51, 0,28-0,94, -15/1000), FA (0,16, 0,12-0,2, -295/1000), hemorragia com risco à vida (0,17, 0,05-0,55, -76/1000) e IRA (0,27, 0,13-0,55, -21/1000) e tiveram maior risco de implante de marca-passo definitivo (IMD) (4,22, 1,27 -14.02, 141/1000). Os dispositivos de geração mais recente tiveram um risco menor de FA em comparação com as gerações mais antigas, e pacientes usuários de dispositivos expansíveis por balão não apresentaram riscos maiores de IMD. Conclusões Este artigo apresenta evidências de que pacientes com risco cirúrgico baixo, intermediário e alto apresentam melhores desfechos quando tratados com TAVR em comparação com a SAVR.

RESUMO Objetivo: Descreve se uma criança do sexo feminino, com quatro meses de idade, que necessitou de varfarina 0.7 mg/kg/dia (5 mg). Discutem se os fatores de risco clinicamente relevantes para prescrição de altas doses do anticoagulante em crianças. Descrição do caso: Em novembro de 2015, uma criança de 5 kg (36 semanas, pré termo) foi admitida no pronto atendimento por status epilepticus e febre. Diazepam, fenitoína e ceftriaxona foram prescritos inicialmente. A pesquisa no líquor revelou presença de sete leucócitos, 150 mg/dL de proteínas, 1 mg/dL de glucose e cocos Gram positivos. Em tomografia de crânio, foram observados sinais hipodensos em cerebelo, lobo temporal e núcleos de base à esquerda, sugerindo vasculite infecciosa por meningite pneumocócica. Após o quadro agudo da encefalite, a criança desenvolveu uma trombose e necessitou de anticoagulação com enoxaparina e, posteriormente, com varfarina. Dez dias de tratamento com o segundo fármaco foram necessários para atingir relação normalizada internacional (RNI) terapêutica, tendo sido realizados cinco ajustes de dose desde a primeira prescrição de varfarina. Comentários: Os fatores de risco determinantes para necessidade de doses maiores de varfarina foram idade e uso de nutrição enteral. Fenobarbital e prednisona também podem ter contribuído para o uso de uma das maiores doses de varfarina já relatadas na literatura. A despeito da importância dos testes de polimorfismo genético, os pediatras devem estar atentos para identificar os fatores que contribuem para a prescrição de maiores doses de varfarina, de forma a minimizar os riscos de trombose, reduzindo os custos com internação e exames laboratoriais.

ABSTRACT Objective: To report a case of a 4-month old girl that required 0.7 mg/kg/day (5 mg) of warfarin and discuss relevant risk factors for requiring higher doses. Case Description: In November 2015, a 5 kg female infant (36-week preterm) was admitted to the hospital due to status epilepticus and fever. Diazepam, phenytoin and ceftriaxone were prescribed. Cerebrospinal fluid contained 7 leukocytes, 150 mg/dL proteins, 1 mg/dL glucose and gram positive cocci were observed. Cranial tomography suggested hypodense signs in the cerebellum, right temporal lobe and left basal nuclei, which was consistent with pneumococcal meningitis-induced infectious vasculitis. She required low molecular weight heparin and warfarin for post-encephalitis thrombosis. About 10 days were required to achieve therapeutic INR, and warfarin was adjusted five times since the initial prescription. Comments: The risk factors for higher warfarin doses were age and enteral tube feeding. Phenobarbital and prednisone might also have contributed with one of the highest warfarin dose ever reported. Despite current importance given to genetics testing, clinicians should attempt to identify common contributing factors for prolonged non-therapeutic INR, to minimize the risk of coagulation, and to reduce costs of hospital stay and laboratory exams.

Resumo Objetivo: Serviços de Farmácia Clínica (SFC) são considerados um padrão de atendimento à saúde e são endossados pela Joint Commission International, pela American Academy of Pediatrics e pelo American College of Clinical Pharmacy. No Brasil, experiências isoladas vêm surgindo discretamente e a importância desses serviços para o cuidado de crianças e adolescentes tem levado a resultados interessantes, mas que certamente são sub-relatados. Este artigo tem como objetivo discutir o efeito da implantação de um SFC à beira do leito em uma Unidade de Cuidados Intensivos Pediátricos (UCIP) brasileira. Métodos: Este é um estudo transversal, feito em uma UCIP de hospital da comunidade com 12 leitos, em Campo Largo, Brasil. Foram incluídos indivíduos com<18 anos internados em UCIP para análise descritiva, quando receberam uma intervenção do SFC. Resultados: De 53 pacientes acompanhados, foram detectados 141 Problemas Relacionados a Medicamentos (PRM) evitáveis que foram resolvidos em conjunto com os médicos (89% de aceitação de todas as intervenções). As intervenções mais comuns para melhorar a terapia medicamentosa foram: prevenção de soluções intravenosas incompatíveis (21%) e doses inadequadas (17% devido a doses baixas e altas). Entre os dez principais medicamentos associados à PRM, cinco eram antimicrobianos. Ao analisar a correlação entre o PRM e tempo de permanência na UCIP, verificamos que 74% de todas as variações no tempo de permanência eram associadas com o número de PRM. Conclusões: Reações adversas a medicamentos devido a PRM evitáveis podem ser prevenidas por SFC em uma colaboração multifacetada com outros profissionais de saúde. Tais problemas podem ser evitados por meio de estratégias ativas e baseadas em evidências para reduzir a morbidade relacionada a medicamentos.

Abstract Objective: Clinical Pharmacy Services (CPS) are considered standard of care and is endorsed by the Joint Commission International, the American Academy of Pediatrics, and the American College of Clinical Pharmacy. In Brazil, single experiences have been discreetly arising and the importance of these services to children and adolescents care has led to interesting results, but certainly are under reported. This short report aims to discuss the effect of implementing a bedside CPS at a Brazilian Pediatric Intensive Care Unit (PICU). Methods: This is a cross-sectional study conducted in a 12 bed PICU community hospital, from Campo Largo/Brazil. Subjects with<18 years old admitted to PICU were included for descriptive analysis if received a CPS intervention. Results: Of 53 patients accompanied, we detected 141 preventable drug-related problems (DRPs) which were solved within clinicians (89% acceptance of all interventions). The most common interventions performed to improve drug therapy included: preventing incompatible intravenous solutions (21%) and a composite of inadequate doses (17% due to low, high and non-optimized doses). Among the top ten medications associated with DRPs, five were antimicrobials. By analyzing the correlation between DRPs and PICU length of stay, we found that 74% of all variations on length of stay were associated with the number of DRPs. Conclusions: Adverse drug reactions due to avoidable DRPs can be prevented by CPS in a multifaceted collaboration with other health care professionals, who should attempt to use active and evidence-based strategies to reduce morbidity related to medications.

Abstract There is a lack of formal economic analysis to assess the efficiency of antimicrobial stewardship programs. Herein, we conducted a cost-effectiveness study to assess two different strategies of Antimicrobial Stewardship Programs. A 30-day Markov model was developed to analyze how cost-effective was a Bundled Antimicrobial Stewardship implemented in a university hospital in Brazil. Clinical data derived from a historical cohort that compared two different strategies of antimicrobial stewardship programs and had 30-day mortality as main outcome. Selected costs included: workload, cost of defined daily doses, length of stay, laboratory and imaging resources used to diagnose infections. Data were analyzed by deterministic and probabilistic sensitivity analysis to assess model's robustness, tornado diagram and Cost-Effectiveness Acceptability Curve. Bundled Strategy was more expensive (Cost difference US$ 2119.70), however, it was more efficient (US$ 27,549.15 vs 29,011.46). Deterministic and probabilistic sensitivity analysis suggested that critical variables did not alter final Incremental Cost-Effectiveness Ratio. Bundled Strategy had higher probabilities of being cost-effective, which was endorsed by cost-effectiveness acceptability curve. As health systems claim for efficient technologies, this study conclude that Bundled Antimicrobial Stewardship Program was more cost-effective, which means that stewardship strategies with such characteristics would be of special interest in a societal and clinical perspective.

Objectives: To assess a bundled Antimicrobial Stewardship Program and its effect on mortality. Data:Eight months of clinical electronic medical records and Antimicrobial Stewardship Program registries were used as source of data.Method: This is a historical cohort study conducted in a Brazilian University Hospital. Eligible patients were admitted to general wards or intensive care units and had an antimicrobial therapy prescribed and assessed by different strategies: Bundled Antimicrobial Stewardship Program (bundled intervention consisted of clinical pharmacist chart review, discussion with microbiologist and infectious disease physicians, local education and continuous follow-up) or Conventional Antimicrobial Stewardship Program (clinical pharmacist chart review and discussion with infectious disease physician). Primary outcome from this study was 30-day mortality, which was compared between groups, by using Kaplan-Meier survival curve and log-rank test. Other outcomes included Defined Daily Doses per 1000 patient-days and occurrence of resistant bacteria.Results: From 533 patients, 491 were eligible for the study, of which 191 patients were included to Antimicrobial Stewardship Program and 300 to Conventional strategy. In general, they were likely to be male and age was similar in groups (58.9 vs 55.5 years, p= 0.38). Likewise, Charlson Comorbidity Index was not statistically different between groups (2.6 vs 2.7, p= 0.2). Bloodstream site infections were frequently diagnosed in both groups (30.89% vs 26%, p= 0.24). Other less common sites of infections were central nervous system and lungs. The ASP group had higher survival rates (p< 0.01) and the risk difference was 10.8% (95% CI: 2.41-19.14). There were less Defined Daily Doses per 1000 patient-days (417 vs 557.2, p< 0.05) and higher rates of resistant bacteria identified in the ASP group (83% vs 17%).Conclusion: Bundled ASP was the most effective strategy, with reduced mortality and Defined Daily Doses per 1000 patient-days.