Microcosting Analysis of Advanced Ovarian Cancer: Real-World Evidence From the Perspective of a Reference Public Brazilian Hospital.

OBJECTIVES: Evaluate the cost of advanced ovarian cancer, using the microcosting technique, based on real-world evidence from the perspective of a reference Brazilian public hospital. METHODS: Retrospective cohort study of patients newly diagnosed with advanced ovarian cancer in 2017 and followed-up for up to 5 years. A bottom-up microcosting method was applied, using the activity-based cost approach, which evaluates service costs based on activity consumption throughout patients' journey. RESULTS: The results indicate a median overall survival of 35.3 months and a median age of 57 years (33-80 years old). The average cost per patient was USD 34 991.595 over a period of 35.3 months, with admissions because of the disease progression and end-of-life care being the most relevant. CONCLUSIONS: The results show that the costs of activities currently involved in the treatment of advanced ovarian cancer represent an important economic impact for the public health system. These data can support future analyses on the impact of incorporating new technologies for the treatment of ovarian cancer and on the financing and sustainability of the Brazilian public healthcare system.

Análise de custo-utilidade da gosserrelina no tratamento de pacientes com leiomioma: uma perspectiva do Sistema Único de Saúde / Cost-utility analysis of goserelin in the treatment of patients with leiomyoma: a perspective from the Unified Health System

Objetivos: Gosserrelina é indicada para mulheres com leiomioma, por reduzir o risco associado às complicações clínicas. Este trabalho realizou uma análise de custo-utilidade comparando o uso e o não uso de gosserrelina em pacientes com leiomioma sob a perspectiva do Sistema Único de Saúde. Métodos: Um modelo de árvore de decisão foi estruturado para reproduzir o impacto clínico e econômico do uso de gosserrelina antes da miomectomia, cujo comparador seria o não uso de gosserrelina em pacientes elegíveis. Foram considerados: custos médicos diretos e eventos clínicos como complicações intra-hospitalares e tempo de internação. A razão de custo-utilidade incremental é representada pelo custo incremental da gosserrelina por anos de vida ajustado pela qualidade (QALY). Resultados: Em um cenário em que o acesso à gosserrelina é de 51% das pacientes, o custo incremental foi de R$ 629,08. Pacientes no grupo gosserrelina apresentaram um incremento de 0,0261 no QALY. A razão de custo-utilidade incremental foi de R$ 24.019,26 por QALY, ficando abaixo do limiar adotado pelo Ministério da Saúde. Ao variar o percentual de pacientes que recebem gosserrelina para 80% antes de um procedimento cirúrgico, houve um aumento de QALY para 0,5013, reduzindo custos de complicações e a razão de custo-utilidade incremental para R$ 10.581,07 por QALY. No cenário em que 100% das pacientes utilizam gosserrelina, há um aumento de QALY para 0,8290, reduzindo custos de complicações e a razão de custo-utilidade incremental para R$ 10.288,28 por QALY. Conclusão: O uso de gosserrelina possui custo-utilidade favorável, considerando os parâmetros utilizados nesta modelagem econômica. Quando o acesso à gosserrelina é maior, há um decremento expressivo no custo por QALY.

Objectives: Goserelin is indicated for women with leiomyoma to reduce the risk associated with clinical complications. This study conducted a cost-utility analysis comparing the use and non-use of goserelin in patients with leiomyoma from the perspective of the Brazilian Unified Health System. Methods: A decision tree model was structured to reproduce the clinical and economic impact of using goserelin before myomectomy, compared to not using it in eligible patients. Direct medical costs and clinical events such as in-hospital complications and length of stay were considered. The incremental cost-utility ratio is represented by the incremental cost of goserelin per quality-adjusted life year (QALY). Results: In a scenario where access to goserelin is 51% of patients, the incremental cost was R$ 629.08. Patients in the goserelin group showed an increase of 0.0261 in QALY. The incremental cost-utility ratio was R$ 24,019.26 per QALY, below the threshold adopted by the Ministry of Health. When the percentage of patients receiving goserelin was increased to 80% before surgery, there was an increase in QALY to 0.5013, reducing complication costs and the incremental cost-utility ratio to R$ 10,581.07 per QALY. In the scenario where 100% of patients use goserelin, QALY increased to 0.8290, reducing complication costs and the incremental cost-utility ratio to R$ 10,288.28 per QALY. Conclusions: The use of goserelin has a favorable cost utility, considering the parameters used in this economic modeling. When access to goserelin is higher, there is a significant decrease in the cost per QALY.

Systematic Review of Nomograms Used for Predicting Pathological Complete Response in Early Breast Cancer.

Pathological complete response (pCR) is an important surrogate outcome to assess the effects of neoadjuvant chemotherapy (NAC). Nomograms to predict pCR have been developed with local data to better select patients who are likely to benefit from NAC; however, they were never critically reviewed regarding their internal and external validity. The purpose of this systematic review was to critically appraise nomograms published in the last 20 years (2010-2022). Articles about nomograms were searched in databases, such as PubMed/MEDLINE, Embase and Cochrane. A total of 1120 hits were found, and seven studies were included for analyses. No meta-analysis could be performed due to heterogeneous reports on outcomes, including the definition of pCR and subtypes. Most nomograms were developed in Asian centers, and nonrandomized retrospective cohorts were the most common sources of data. The most common subtype included in the studies was triple negative (50%). There were articles that included HER2+ (>80%). In one study, scholars performed additional validation of the nomogram using DFS and OS as outcomes; however, there was a lack of clarity on how such endpoints were measured. Nomograms to predict pCR cannot be extrapolated to other settings due to local preferences/availability of NAC. The main gaps identified in this review are also opportunities for future nomogram research and development.

Transcatheter Valve Replacement in Patients with Aortic Valve Stenosis: An Overview of Systematic Reviews and Meta-Analysis with Different Populations. / Implante Valvar Transcateter em Pacientes com Estenose Valvar Aórtica: Uma Overview de Revisões Sistemáticas e Metanálise Incluindo Múltiplas Populações.

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.

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.

Effects of therapeutic plasma exchange on a cohort of patients with severe coronavirus infection: real world evidence from Brazil

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.

Impact of the COVID-19 pandemic on the breast cancer early diagnosis program in Brazil.

During the COVID-19 pandemic, several screening exams were postponed, including mammograms. The aim of this study was to evaluate the impact of COVID-19 in mammographic screening in Brazil, considering 2015 to 2021. This was descriptive ecologic study based on the retrospective data of Brazil's mammographic screening program. A Brazilian national screening database (DATASUS - SISCAN (Cancer System Information)) was used as the data source, and the data in this database are publicly available for download and analysis. We report the number of screening rate from January 2015 to December 2021, using 2020 as reference year for COVID-19. From 2015 to 2021, 10,763,894 mammograms were performed and included in the analysis. Reductions of 39.6% and 13.3% were found in 2020 in 2021, respectively. During the pandemic's peak, the reduction was more pronounced, with maximum reductions of 82.4% in May 2020 and 34.8% in April 2021. There was an increase in the number of mammograms performed on high-risk patients from 11.2% in 2020 to 13.9% in 2021. This research demonstrated a decline in the breast cancer screening rate during the two years of the COVID-19 pandemic; this reduction will increase the burden of advanced breast cancer, potentially impacting morbidity and mortality related to this neoplasm.

Identification of an Optimal COVID-19 Booster Allocation Strategy to Minimize Hospital Bed-Days with a Fixed Healthcare Budget.

Healthcare decision-makers face difficult decisions regarding COVID-19 booster selection given limited budgets and the need to maximize healthcare gain. A constrained optimization (CO) model was developed to identify booster allocation strategies that minimize bed-days by varying the proportion of the eligible population receiving different boosters, stratified by age, and given limited healthcare expenditure. Three booster options were included: B1, costing US $1 per dose, B2, costing US $2, and no booster (NB), costing US $0. B1 and B2 were assumed to be 55%/75% effective against mild/moderate COVID-19, respectively, and 90% effective against severe/critical COVID-19. Healthcare expenditure was limited to US$2.10 per person; the minimum expected expense using B1, B2, or NB for all. Brazil was the base-case country. The model demonstrated that B1 for those aged <70 years and B2 for those ≥70 years were optimal for minimizing bed-days. Compared with NB, bed-days were reduced by 75%, hospital admissions by 68%, and intensive care unit admissions by 90%. Total costs were reduced by 60% with medical resource use reduced by 81%. This illustrates that the CO model can be used by healthcare decision-makers to implement vaccine booster allocation strategies that provide the best healthcare outcomes in a broad range of contexts.

Effects of therapeutic plasma exchange on a cohort of patients with severe coronavirus infection: real world evidence from Brazil.

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.

Implante Valvar Transcateter em Pacientes com Estenose Valvar Aórtica: Uma Overview de Revisões Sistemáticas e Metanálise Incluindo Múltiplas Populações / Transcatheter Valve Replacement in Patients with Aortic Valve Stenosis: An Overview of Systematic Reviews and Meta-Analysis with Different Populations

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.

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.

Risk of acute kidney injury and cost-effectiveness analysis comparing vancomycin and linezolid for the treatment of pediatric patients infected with Gram-positive bacteria / Risco de lesão renal aguda e custo-efetividade comparando vancomicina e linezolida para o tratamento de pacientes pediátricos infectados por bactérias Gram-positivas

Objective: This study aimed to compare the occurrence of acute kidney injury (AKI) in pediatric patients who used vancomycin (VAN) or linezolid (LNZ) to treat Gram-positive coccus (GPC) infections and to assess which treatment (VAN or LNZ) is the most cost-effective considering a pediatric hospital perspective. Methods: A retrospective cohort was performed to evaluate the occurrence of nephrotoxicity in pediatric patients without previous AKI, with GPC infections that used LNZ, or VAN monitored by serum VAN levels. Initially, descriptive analysis and Fisher and chisquare test were performed for this comparison. Then, a cost-effectiveness analysis was conducted through a decision tree model. The outcomes of interest were the rate of AKI related to the drug and the rate of admission to the intensive care unit (ICU) and cure. Results: In patients without previous acute kidney injury (AKI), 20% developed nephrotoxicity associated with VAN versus 9.6% in the LNZ group (p = 0.241). As there was no difference in nephrotoxicity between VAN andlinezolid (LNZ), vancomycin (VAN) monitored by serum VAN levels can optimize and rationalize the treatment. The nephrotoxicity risk criterion should not guide the prescription for LNZ. Furthermore, the average global cost of treatment with VAN was approximately R$ 43,000, while for LNZ, it was R$ 71,000. Conclusion: VAN was considered dominant (lower cost and greater effectiveness) over LNZ for treating patients with GPC infection.

Objetivo: Este estudo objetivou comparar a ocorrência de lesão renal aguda (LRA) em pacientes pediátricos que usaram vancomicina (VAN) ou linezolida (LNZ) para tratar infecções por cocos Gram-positivos (CGP) e avaliar qual tratamento (VAN ou LNZ) é o mais custo-efetivo considerando a perspectiva de um hospital pediátrico. Métodos: Foi realizada uma coorte retrospectiva para avaliar a ocorrência de nefrotoxicidade em pacientes pediátricos sem LRA prévia, com infecções por CGP que utilizaram LNZ ou VAN, combinada com vancocinemia. Para essa comparação, inicialmente foram realizados análise descritiva e testes de Fisher e qui-quadrado. Em seguida, foi realizada uma análise de custo-efetividade por meio de um modelo de árvore de decisão. Os desfechos de interesse foram a taxa de LRA relacionada ao medicamento e a taxa de internação em unidade de terapia intensiva e cura. Resultados: Nos pacientes sem LRA prévia, 20% deles desenvolveram nefrotoxicidade associada à VAN versus 9,6% no grupo LNZ (p = 0,241). Como não houve diferença na nefrotoxicidade entre VAN e LNZ, a VAN combinada com a vancocinemia pode otimizar e racionalizar o tratamento, e a prescrição de LNZ não deve ser guiada pelo critério de risco de nefrotoxicidade. Além disso, o custo médio global do tratamento com VAN foi de aproximadamente R$ 43.000, enquanto para LNZ foi de R$ 71.000. Conclusão: Assim, a VAN foi considerada dominante (menor custo e maior eficácia) sobre a LNZ para o tratamento de pacientes com infecção por CGP.

Effects of clinical heterogeneity on Pregnancy-Associated Breast Cancer survival: a systematic review with meta-analysis

Pregnancy-associated breast cancer is defined as a diagnosis of breast cancer during pregnancy or within 1 year of childbirth. Current evidence shows that Pregnancy-associated breast cancer is associated with poor prognosis; however, no systematic review has summarized and explored how baseline characteristics could impact survival. We aimed to explore the impact of breast cancer characteristics on death and disease relapse. A systematic review with meta-analyses was conducted by searching articles in the main databases (Medline, Embase, and Cochrane) and congress abstracts. Summarized death and disease-free survival hazard ratios were recalculated, and all meta-analyses used a random-effects model. Heterogeneity was reported using the I2 method. A total of 7143 studies were identified and only 30 studies were included. Pregnancy-associated breast cancer is associated with a 96% (HR 1.96; 95%CI 1.58­2.35) higher risk of death and 82% (HR 1.82; 95%CI 1.45­2.20) risk of death or disease relapse in comparison to a population of non-pregnancy-associated breast cancer or nulliparous breast cancer. Through sensitivity analyses, we identified that clinical outcomes were impacted, possibly due to Ki-67 levels, poorly differentiated tumors, and triple-negative breast cancer frequency in the study. As relevant sources of inconsistencies, such clinical cancer-related characteristics should be better investigated as potential confounders for upcoming Pregnancy-associated breast cancer therapeutic strategies.

Demographic and Clinical Outcomes of Brazilian Patients With Stage III or IV Non-Small-Cell Lung Cancer: Real-World Evidence Study on the Basis of Deterministic Linkage Approach.

PURPOSE: Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer and accounts for 80%-90% of the cases. In Brazil, between 2018 and 2019, lung cancer was ranked as the second most frequent cancer among men and the fourth among women. The primary objectives were to describe the journey and survival rates of patients with advanced NSCLC treated in the Brazilian private health care system (HCS). MATERIALS AND METHODS: A retrospective cohort study was based on the search in administrative databases to analyze the Brazilian private HCS. Patients with advanced NSCLC diagnosed between 2011 and 2016 were included. The data on demographics, cancer-related information, treatment-related information, and resources used were collected. Survival analyses were performed using the semiparametric Kaplan-Meier method to assess mortality by NSCLC stage, with NSCLC diagnosis as the index date. RESULTS: A total of 5,016 patients were included. Most patients were between 60 and 69 years old (33.6%) and had completed elementary school (52.2%). There was a greater proportion of men (58.1% v 41.9%), and the majority of patients had stage IV NSCLC (67%). It took an average of 31 days, from the first consultation, to have diagnosis. In 44% of the cases, a clinical oncologist was the first specialist in the HCS that the patient was referred to. After the diagnosis, the median time to start of treatment was 35 days. Chemotherapy alone was the most common treatment regimen (32%). The median overall survival was 11.5 months and 6 months for stage II and IV NSCLC, respectively. CONCLUSION: This study provides contemporary data on stage III and IV NSCLC in private health care in Brazil, which has shown a high rate of metastatic disease diagnoses, high health care-related costs, and low survival rates.

PRAT tool: a harmonization of antimicrobial stewardship program interventions

Objective: The Antimicrobial Stewardship Program (ASP) in hospitals aims to promote the rational use of antimicrobials, providing better results to patients (increasing effectiveness and decreasing the risk of adverse events), hospital epidemiology (impact on levels of microbial resistance), and enable cost-effectiveness studies. Therefore, a tool (called PRAT­ antimicrobial therapy-related problem) is suggested in this paper. This unvalidated tool is the initial step towards organizing the antimicrobial therapy-related interventions to improve the use of this drug class, mainly by suggesting a harmonized registry process of ASP interventions. Methods: Therefore, this work presents the PRAT tool, developed based on the 10 years' experience of ASP at Pequeno Príncipe Hospital, inspired by the classification for drug-related problems of the Pharmaceutical Care Network Europe and according to a collaborative work using the Delphi technique. Results: This tool allows the identification and exact description of the antimicrobial therapy-related problem in 17 domains and 67 subcategories. Based on this identification, it suggests how to classify this problem (effectiveness, safety and need/indication) and what interventions can be conducted. Conclusion: This tool has the potential to establish a profile of antimicrobial-related problems, allowing prioritization to be visualized through the most (and least) interventions made in a given period, and might be useful in improving the quality of care through settings, by means of targeted educational interventions. Furthermore, if there is a harmonization of terminology for the classification of antimicrobial therapy-related problems, other hospitals can adopt it, and so the tool can improve research and comparison between institutions (benchmarking).

Interventions to Reduce Problems Related to the Readability and Comprehensibility of Drug Packages and Labels: A Systematic Review.

OBJECTIVE: The aim of the study was to evaluate the effectiveness of interventions designed to reduce problems with readability and comprehensibility in drug labels. METHODS: A systematic review of observational and experimental studies was conducted using MEDLINE (via PubMed), Embase, and Scopus databases. Two independent reviewers selected articles and collected data about study design, interventions, and outcomes. RESULTS: Of 1786 studies screened, 17 were included in this systematic review. The main findings were described according to the type of intervention in the drug package or label: color-coded labels (7 studies); changes in information layout (5 studies); changes in font size (3 studies); and interventions involving look-alike/sound-alike (LASA) drugs (3 studies). Color changes were important both for healthcare professionals to improve safety in hospital practice and for medication users to differentiate between the types of insulin. Layout changes were effective and included highlighting key information, such as medication name, dose, and instructions. Increased font size yielded good results in the recognition and identification of medications mainly for the population with impaired vision. This review was limited by the heterogeneity of interventions and populations studied, as well as the small number of high-quality studies, which prevented meta-analysis across any one intervention or outcome. CONCLUSIONS: All studies reported positive results for the proposed interventions. In the case of LASA drug names, the use of resources beyond Tall Man lettering (such as color and highlighting) reduced recognition errors, which may contribute to the development of new strategies to improve safety in the use of LASA drugs.

Vancomycin-associated Nephrotoxicity and Risk Factors in Critically Ill Children Without Preexisting Renal Injury.

BACKGROUND: A recent systematic review concluded that critically ill pediatric patients have higher odds of vancomycin-related nephrotoxicity [odds ratio (OR): 3.61, 95% CI: 1.21-10.74]. We aimed to assess the incidence and risk factors for vancomycin-associated nephrotoxicity in critically ill children without preexisting renal injury. METHODS: A cohort of children admitted to a pediatric intensive care unit, from 2011 to 2016 treated with vancomycin without preexisting renal injury. The main diagnosis, therapeutic interventions and medications administered in this period were evaluated. Generalized estimating equation models were used to assess the association between clinical covariates and the dependent variable pediatric risk, injury, failure, loss, end-stage renal disease (pRIFLE). RESULTS: Hundred ten patients, representing 1177 vancomycin days, were analyzed. Vancomycin-associated nephrotoxicity was seen in 11.8%. In a multivariate model, higher vancomycin doses were not associated with poorer renal function (P = 0.08). Higher serum vancomycin levels were weakly associated with pRIFLE classification (OR: 1.05, 95% CI: 1.02-1.07). Furosemide or amphotericin B in addition to the vancomycin treatment was associated with impaired renal function (OR: 2.56, 95% CI: 1.38-4.8 and OR: 7.7 95% CI: 2.55-23, respectively). CONCLUSIONS: Vancomycin-associated nephrotoxicity in acute ill children without preexisting renal injury, measured with pRIFLE, is close to 11.8%. Furosemide and amphotericin B in addition to the vancomycin treatment are strong predictors of worse pRIFLE scores. The influence of acute kidney injury status at pediatric intensive care unit admission and the method used for renal function assessment might influence the incidence of vancomycin-associated nephrotoxicity and its associated risk factors.

Adverse events associated with aprepitant pediatric bone cancer patients.

An eight-year long case series follow-up study with pediatric bone cancer patients was conducted to compare the occurrence of adverse events associated with aprepitant with official sources of drug information (manufacturer's leaflet, clinical trials, and European Medicines Agency leaflet). All patients admitted were analyzed, representing 192 aprepitant cycles. Anorexia, febrile neutropenia, and headache were observed in frequencies over 43.8 per 100 patients, which was higher than previous estimates. Adverse events were classified as probable or possible, by using Naranjo score. The increased rates of adverse events, especially on the risk febrile neutropenia, warrant further safety studies on this population.

Análise de impacto orçamentário: uma revisão prática de conceitos e aplicações para o gestor / Budget impact analysis: a practical review of concepts and applications for the manager

Avaliações econômicas em saúde são essenciais para a tomada de decisão de gestores, visto que as inovações no setor nem sempre podem ser incorporadas conforme as expectativas dos usuários e da indústria. Logo, a análise de impacto orçamentário (AIO), uma das principais ferramentas da avaliação de tecnologias em saúde (ATS), permite aos gestores estimar o potencial número de indivíduos elegíveis para determinada tecnologia ao longo dos anos, prever quanto será necessário gastar para incorporar a tecnologia ou, eventualmente, se haverá economia nos cofres do pagador com a inclusão dela. Com a crescente publicação de artigos científicos sobre AIO no Brasil, surge a preocupação a respeito da qualidade metodológica desses estudos. O objetivo desta revisão é apresentar recomendações-chave para a elaboração de uma AIO adequada e expor a utilidade prática da AIO para a tomada de decisão de gestores de saúde por meio da análise de quatro estudos publicados. O formato de apresentação de uma AIO possibilita rápido entendimento e possui atributos que permitem evidenciar o maior valor de produtos e serviços de saúde junto aos tomadores de decisão em saúde, contribuindo para as melhores escolhas do ponto de vista clínico e econômico, nos sistemas público e privado. Porém, cabe ressaltar que alguns estudos ainda carecem de evidências de mundo real ou dados epidemiológicos para as estimativas e trabalham de maneira insuficiente as ferramentas para a redução de incertezas paramétricas.

Health economics evaluations are essential for decision makers, since innovations can not always be incorporated according to expectations of users and industry. Therefore, the Budget Impact Analysis (BIA), one of the main tools in Health Technology Assessment (HTA), allows managers to estimate the potential number of individuals eligible for a given technology over the years, to predict how much it will be necessary to spend for incorporate the technology or, eventually, whether there will be savings in the payer's coffers with the inclusion of the same. With the growing publication of scientific articles on BIA in Brazil, there is concern about the methodological quality of these studies. The objective of this review is to present key recommendations to elaborate an adequate BIA, commenting on four published studies, aiming to expose the practical utility of BIA for health managers. The presentation format of the BIA provides a quick understanding and has attributes that allows evidence of the highest value of health products and services among health decision makers, contributing to the best clinical and economic choices in public and private health systems. However, it should be noted in some studies there is still a lack of real-world evidence or epidemiological data for the estimates and insufficient using of tools to reduce parametric uncertainties.