Potential performance of a 0 h/1 h algorithm and a single cut-off measure of high-sensitivity troponin T in a diverse population: main results of the IN-HOPE study.

AIMS: Chest pain is a major cause of medical evaluation at emergency department (ED) and demands observation to exclude the diagnosis of acute myocardial infarction (AMI). High-sensitivity cardiac troponin assays used as isolated measure and by 0- and 1-h algorithms are accepted as a rule-in/rule-out strategy, but there is a lack of validation in specific populations. METHODS AND RESULTS: The IN-HOspital Program to systematizE Chest Pain Protocol (IN-HOPE study) is a multicentre study that prospectively included patients admitted to the ED due to suspected symptoms of AMI at 16 sites in Brazil. Medical decisions of all patients followed the standard approach of 0 h/3 h protocol, but, in addition, blood samples were also collected at 0 and 1 h and sent to a central laboratory (core lab) to measure high-sensitivity cardiac troponin T (hs-cTnT). To assess the theoretical performance of 0 h/1 h algorithm, troponin < 12 ng/L with a delta < 3 was considered rule-out while a value ≥ 52 or a delta ≥ 5 was considered a rule-in criterion (the remaining were considered as observation group). The main objective of the study was to assess, in a population managed by the 0 h/3 h protocol, the accuracy of 0 h/1 h algorithm overall and in groups with a higher probability of AMI. All patients were followed up for 30 days, and potential events were adjudicated. In addition to the prospective cohort, a retrospective analysis was performed assessing all patients with hs-cTnT measured during the year of 2021 but not included in the prospective cohort, regardless of the indication of the test. A total of 5.497 patients were included (583 in the prospective and 4.914 in the retrospective analysis). The prospective cohort had a mean age of 57.3 (± 14.8) and 45.6% of females with a mean HEART score of 4.0 ± 2.2. By the core lab analysis, 74.4% would be eligible for a rule-out approach (45.3% of them with a HEART score > 3) while 7.3% would fit the rule-in criteria. In this rule-out group, the negative predictive value for index AMI was 100% (99.1-100) overall and regardless of clinical scores. At 30 days, no death or AMI occurred in the rule-out group of both 0/1 and 0/3 h algorithms while 52.4% of the patients in the rule-in group (0 h/1 h) were considered as AMI by adjudication. In the observation group (grey zone) of 0 h/1 h algorithm, GRACE discriminated the risk of these patients better than HEART score. In the retrospective analysis, 1.091 patients had a troponin value of <5 ng/L and there were no cardiovascular deaths at 30 days in this group. Among all 4.914 patients, the 30-day risk of AMI or cardiovascular death increased according to the level of troponin: 0% in the group < 5 ng/L, 0.6% between 5 and 14 ng/L, 2.2% between 14 and 42 ng/L, 6.3% between 42 and 90 ng/L, and 7.7% in the level ≥ 90 ng/L. CONCLUSION: In this large multicentre study, a 0 h/1 h algorithm had the potential to classify as rule-in or rule-out in almost 80% of the patients. The rule-out protocol had high negative predictive value regardless of clinical risk scores. Categories of levels of hs-cTn T also showed good accuracy in discriminating risk of the patients with a very favourable prognosis for cardiovascular death in the group with value < 5 ng/L. CLINICALTRIALS.GOV: NCT04756362.

Potential performance of a 0 h/1 h algorithm and a single cut-off measure of high-sensitivity troponin T in a diverse population: main results of the IN-HOPE study

BACKGROUND: Chest pain is a major cause of medical evaluation at emergency department (ED) and demands observation to exclude the diagnosis of acute myocardial infarction (AMI). High-sensitivity cardiac troponin assays used as isolated measure and by 0 h and 1 h algorithms are accepted as a rule-in/rule-out strategy but there is a lack of validation in specific populations. METHODS: The IN-HOspital Program to systematizE chest pain protocol (In Hope study) is a multicentre study that prospectively included patients admitted to the ED due to suspected symptoms of AMI at 16 sites in Brazil. Medical decisions of all patients followed the standard approach of 0/3-h protocol but, in addition, blood samples were also collected at 0 and 1 hour and sent to a central laboratory (core lab) to measure high-sensitivity troponin T (hs-cTnT). To assess the theoretical performance of 0/1-h algorithm, troponin < 12 ng/L with a delta <--- 3 was considered rule out while a value ≥ 52 and/or a delta ≥ 5 was considered a rule in criteria (the remaining were considered as observation group). The main objective of the study was to assess, in a population managed by the 0/3-h protocol, the accuracy of 0/1-h algorithm overall and in groups with higher probability of AMI. All patients were followed for 30 days, and potential events were adjudicated. In addition to the prospective cohort, a retrospective analysis was performed assessing all patients with hs-cTnT measured during the year of 2021 but not included in the prospective cohort, regardless the indication of the test. RESULTS: A total of 5.497 patients were included (583 in the prospective and 4.914 in the retrospective analysis). The prospective cohort had a mean age of 57.3 (± 14.8) and 45.6% of females with a mean HEART score of 4.0 ± 2.2. By the core lab analysis, 74.4% would be eligible for a rule-out approach (45.3% of HEART score > 3) while 7.3% would fit the rule-in criteria. In this rule-out group, the negative predictive value for index AMI was 100% (99.1-100) overall and regardless clinical scores. At 30 days, no death or AMI occurred in the rule-out group of both 0/1 and 0/3-hour while 52.4% of the patients in the rule-in group (0/1-hour) were considered as AMI by adjudication. In the observation group (grey zone) of 0/1- hour algorithm, GRACE discriminated the risk of these patients better than HEART score. In the retrospective analysis, 1.091 patients had a troponin value < 5 ng/L and there were no cardiovascular deaths at 30 days in this group. Among all 4.914 patients, the 30-day risk of AMI or cardiovascular death increased according to the level of troponin: 0% in the group < 5 ng/L, 0.6% between 5 and 14 ng/L, 2.2% between 14 and 42 ng/L, 6.3% between 42 and 90 ng/L and 7.7% in the level ≥ 90 ng/L. CONCLUSIONS: In this large multicentre study, a 0/1-h algorithm had the potential to classify as rule in or out almost 80% of the patients. The rule-out protocol had high negative predictive value regardless of clinical risk scores. Categories of levels of hs-cTn T also showed good accuracy in discriminating risk of the patients with a very favourable prognosis for cardiovascular death in the group with values < 5 ng/L.

Real world evidence of the use of metamizole (dipyrone) by the Brazilian population. A retrospective cohort with over 380,000 patients.

OBJECTIVE: To determine under which health conditions metamizole (dipyrone) is used as a single drug or as fixed-dose combination. METHODS: Two retrospective cohorts of Brazilian patients treated with metamizole between January 2015 and December 2017 were analyzed: a metamizole-based cohort (Cohort 1) and a symptoms-based cohort (Cohort 2). Anonymized patient data was obtained from Amil Clinical Data Warehouse. The number of patients with symptoms was described by age and sex. RESULTS: The sample size of the two cohorts consisted of 384,668 patients. In patients using metamizole (Cohort 1), the most common reason for medication was the treatment of some form of pain (81%), followed by fever (19%). Headache was the most common (19%) specified pain class, followed by sore throat (8%), muscular pain (6%), and abdominal pain (5%). In adult patients (n=276,279; 71.8%), metamizole was used as a monotherapy or associated with another drug, for any sort of pain, in over 88% of the patients. General pain was the main reason for metamizole use in children (61%). CONCLUSION: Real world evidence to evaluate Brazilian patients' therapeutic options is unusual and yet to be more explored using digital tools enabling better data registration. The present study confirmed that metamizole is widely used as a non-anti-inflammatory drug, and also showed the management of pain and fever as the most frequent indications in all age groups studied.Registry in Clinical Trials Database: REBEC Database: 10507.

Real world evidence of the use of metamizole (dipyrone) by the Brazilian population. A retrospective cohort with over 380,000 patients

ABSTRACT Objective To determine under which health conditions metamizole (dipyrone) is used as a single drug or as fixed-dose combination. Methods Two retrospective cohorts of Brazilian patients treated with metamizole between January 2015 and December 2017 were analyzed: a metamizole-based cohort (Cohort 1) and a symptoms-based cohort (Cohort 2). Anonymized patient data was obtained from Amil Clinical Data Warehouse. The number of patients with symptoms was described by age and sex. Results The sample size of the two cohorts consisted of 384,668 patients. In patients using metamizole (Cohort 1), the most common reason for medication was the treatment of some form of pain (81%), followed by fever (19%). Headache was the most common (19%) specified pain class, followed by sore throat (8%), muscular pain (6%), and abdominal pain (5%). In adult patients (n=276,279; 71.8%), metamizole was used as a monotherapy or associated with another drug, for any sort of pain, in over 88% of the patients. General pain was the main reason for metamizole use in children (61%). Conclusion Real world evidence to evaluate Brazilian patients' therapeutic options is unusual and yet to be more explored using digital tools enabling better data registration. The present study confirmed that metamizole is widely used as a non-anti-inflammatory drug, and also showed the management of pain and fever as the most frequent indications in all age groups studied. Registry in Clinical Trials Database: REBEC Database: 10507

Cost Modifications during the Early Years of the Use of the National Cardiovascular Data Registry for Quality Improvement.

OBJECTIVES: Quality improvement (QI) initiatives based on data from international registries have been reported previously; however, there is a lack of information on the impact on the costs of medical care associated with the use of these tools. METHODS: Patients admitted due to myocardial infarction (MI), included in the ACTION Registry® and CathPCI Registry®, in a private Brazilian hospital (i.e., the reference hospital) were analyzed. The costs of care of these patients were compared to the costs of MI admissions in nine similar hospitals not included in the same QI program. Regression models were used to analyze the cost change over time between the two groups of hospitals. Readmission rates were compared using logistic regression, adjusting for the same variables as in the cost model. RESULTS: Overall, the annual medical cost inflation in Brazil was higher than the annual cost trend in the reference hospital during the period of analysis. Moreover, the annual in-hospital costs indicate that the reference hospital has a statistically significant 6% lower cost trend for patients with acute MI, compared to patients with the same diagnostic code in the comparison hospitals group, in an adjusted analysis (p-value=0.041). Using multivariable analysis, the readmission rates were also found to be significantly lower in the reference hospital than in the comparison hospitals, with an odds ratio of 0.68 (p-value=0.042). CONCLUSION: The use of the NCDR® as a benchmark to guide QI programs outside the United States was associated with the positive impact of bending the cost curve to below that of national medical inflation and the comparison hospitals' costs, with a lower incidence of hospital readmission.

Development and Implementation of a Clinical Pathway to Reduce Inappropriate Admissions Among Patients with Community-Acquired Pneumonia in a Private Health System in Brazil: An Observational Cohort Study and a Promising Tool for Efficiency Improvement.

PURPOSE: Patients with community-acquired pneumonia (CAP) at low risk of death by CURB-65 scoring system are usually unnecessarily treated as inpatients generating additional economic and clinical burden. We aimed to implement an evidence-based clinical pathway to reduce hospital admissions of low-risk CAP and investigate factors related to mortality and readmissions within 30 days. PATIENTS AND METHODS: From November 2015 to August 2017, a clinical pathway was implemented at 20 hospitals. We included patients aged >18 years, with a diagnosis of CAP by the attendant physician. The main outcome was the monthly proportion of low-risk CURB-65 admission after the implementation of the clinical pathway. Logistic regression models were performed to assess variables associated with mortality and readmission in the admitted population within 30 days. RESULTS: We included 10,909 participants with suspected CAP. The proportion of low-risk CAP admitted decreased from 22.1% to 12.8% in the period. Among participants with low risk, there has been no perceptible increase in deaths (0.80%) or readmissions (6.92%). Regression analysis identified that CURB-65 variables, presence of pleural effusion (OR= 1.74; 95%CI=1.08-2.8; p=0.02) and leucopenia (OR= 2.47; 95%CI=1.11-5.48; p=0.02) were independently associated with 30-day mortality, whereas a prolonged hospital stay (OR= 2.09; 95%CI=1.14-3.83; p=0.01) was associated with 30-day readmission in the low-risk population. CONCLUSION: The implementations of a clinical pathway diminished the proportion of low-risk CAP admissions with no apparent increase in clinical outcomes within 30 days. Nonetheless, additional factors influence the clinical decision about the site of care management in low-risk CAP.

Anticoagulation Therapy in Patients with Non-valvular Atrial Fibrillation in a Private Setting in Brazil: A Real-World Study / Terapia de Anticoagulação em Pacientes com Fibrilação Atrial não Valvar em Ambiente de Cuidado de Saúde Privado no Brasil: Um Estudo de Mundo Real

Abstract Background: The safety and effectiveness of warfarin depend on anticoagulation control quality. Observational studies associate poor control with increased morbidity, mortality and healthcare costs. Objectives: To develop a profile of non-valvular atrial fibrillation (NVAF) patients treated with warfarin in a Brazilian private ambulatory and hospital setting, evaluate the quality of anticoagulation control, and its association with clinical and economic outcomes. Methods: This retrospective study, through a private health insurance dataset in Brazil, identified NVAF patients treated with warfarin between 01 MAY 2014 to 30 APRIL 2016, described their anticoagulation management, and quantified disease-related costs. Data on demographics, clinical history, concomitant medication and time in therapeutic range (TTR) of international normalized ratio (INR) values were retrieved. Patients were grouped into TTR quartiles, with good control defined as TTR ≥ 65% (Rosendaal method). Major bleeds and all-cause direct medical costs were calculated and compared between good and poor control subgroups. P-values < 0.05 were considered statistically significant. Results: The analysis included 1220 patients (median follow-up: 1.5 years; IQR: 0.5-2.0). On average, each patient received 0.95 monthly INR measurements (mean INR: 2.60 ± 0.88, with 26.1% of values < 2 and 24.8% > 3), (median TTR: 58%; IQR: 47-68%), (mean TTR: 56.6% ± 18.9%). Only 31% of patients were well-controlled (mean TTR: 78% ± 10%), with 1.6% having major bleeds within median follow-up, and direct medical costs per member per year (PMPY) of R$25,352(± R$ 37,762). Poorly controlled patients (69%) were associated with 3.3 times more major bleeds (5.3% vs. 1.6%; p < 0.01) and 40% higher costs (R$35,384 vs. R$25,352; p < 0.01). Conclusions: More than 60% of the patients were below the desired target and the associated costs were higher.

Resumo Fundamento: A segurança e a eficácia da varfarina dependem da qualidade do controle da anticoagulação. Estudos observacionais associam controle deficiente com aumento de morbidade, mortalidade e custos com saúde. Objetivos: Desenvolver um perfil de pacientes com fibrilação atrial não valvar (FANV) tratados com varfarina em ambiente ambulatorial e hospitalar privado brasileiro, avaliar a qualidade do controle da anticoagulação e sua associação com resultados clínicos e econômicos. Métodos: Este estudo retrospectivo, por meio de um conjunto de dados de seguros privados de saúde no Brasil, identificou pacientes com FANV tratados com varfarina entre 01 de maio de 2014 a 30 de abril de 2016, descreveu seu manejo da anticoagulação e quantificou os custos relacionados à doença. Foram recuperados dados demográficos, histórico clínico, medicação concomitante e tempo na faixa terapêutica (TTR) dos valores da razão normalizada internacional (RNI). Os pacientes foram agrupados em quartis de TTR, com um bom controle sendo definido como TTR ≥65% (método de Rosendaal). Sangramentos maiores e custos médicos diretos por todas as causas foram calculados e comparados entre subgrupos de controle bons e ruins. Valores de p < 0,05 foram considerados estatisticamente significantes. Resultados: A análise incluiu 1220 pacientes (mediana de seguimento: 1,5 anos; IIQ: 0,5-2,0). Em média, cada paciente recebeu 0,95 medidas mensais de RNI (RNI média: 2,60 ± 0,88, com 26,1% dos valores < 2 e 24,8% > 3), (mediana de TTR: 58%; IIQ: 47-68%), (TTR médio: 56,6% ± 18,9%). Apenas 31% dos pacientes estavam bem controlados (TTR médio: 78% ± 10%), com 1,6% apresentando grandes sangramentos na mediana do seguimento e custos médicos diretos por membro por ano (PMPY) de R$25.352 (± R$37.762). Pacientes com controle abaixo do ideal (69%) foram associados a 3,3 vezes mais sangramentos graves (5,3% vs. 1,6%; p <0,01) e custos 40% maiores (R$35.384 vs. R$25.352; p < 0,01). Conclusões: Mais de 60% dos pacientes estavam abaixo da meta desejada e os custos associados foram significativamente maiores nesta população.

Anticoagulation Therapy in Patients with Non-valvular Atrial Fibrillation in a Private Setting in Brazil: A Real-World Study.

BACKGROUND: The safety and effectiveness of warfarin depend on anticoagulation control quality. Observational studies associate poor control with increased morbidity, mortality and healthcare costs. OBJECTIVES: To develop a profile of non-valvular atrial fibrillation (NVAF) patients treated with warfarin in a Brazilian private ambulatory and hospital setting, evaluate the quality of anticoagulation control, and its association with clinical and economic outcomes. METHODS: This retrospective study, through a private health insurance dataset in Brazil, identified NVAF patients treated with warfarin between 01 MAY 2014 to 30 APRIL 2016, described their anticoagulation management, and quantified disease-related costs. Data on demographics, clinical history, concomitant medication and time in therapeutic range (TTR) of international normalized ratio (INR) values were retrieved. Patients were grouped into TTR quartiles, with good control defined as TTR ≥ 65% (Rosendaal method). Major bleeds and all-cause direct medical costs were calculated and compared between good and poor control subgroups. P-values < 0.05 were considered statistically significant. RESULTS: The analysis included 1220 patients (median follow-up: 1.5 years; IQR: 0.5-2.0). On average, each patient received 0.95 monthly INR measurements (mean INR: 2.60 ± 0.88, with 26.1% of values < 2 and 24.8% > 3), (median TTR: 58%; IQR: 47-68%), (mean TTR: 56.6% ± 18.9%). Only 31% of patients were well-controlled (mean TTR: 78% ± 10%), with 1.6% having major bleeds within median follow-up, and direct medical costs per member per year (PMPY) of R$25,352(± R$ 37,762). Poorly controlled patients (69%) were associated with 3.3 times more major bleeds (5.3% vs. 1.6%; p < 0.01) and 40% higher costs (R$35,384 vs. R$25,352; p < 0.01). CONCLUSIONS: More than 60% of the patients were below the desired target and the associated costs were higher.

Cost modifications during the early years of the use of the national cardiovascular data registry for quality improvement

OBJECTIVES: Quality improvement (QI) initiatives based on data from international registries have been reported previously; however, there is a lack of information on the impact on the costs of medical care associated with the use of these tools. METHODS: Patients admitted due to myocardial infarction (MI), included in the ACTION Registry® and CathPCI Registry®, in a private Brazilian hospital (i.e., the reference hospital) were analyzed. The costs of care of these patients were compared to the costs of MI admissions in nine similar hospitals not included in the same QI program. Regression models were used to analyze the cost change over time between the two groups of hospitals. Readmission rates were compared using logistic regression, adjusting for the same variables as in the cost model. RESULTS: Overall, the annual medical cost inflation in Brazil was higher than the annual cost trend in the reference hospital during the period of analysis. Moreover, the annual in-hospital costs indicate that the reference hospital has a statistically significant 6% lower cost trend for patients with acute MI, compared to patients with the same diagnostic code in the comparison hospitals group, in an adjusted analysis (p-value=0.041). Using multivariable analysis, the readmission rates were also found to be significantly lower in the reference hospital than in the comparison hospitals, with an odds ratio of 0.68 (p-value=0.042). CONCLUSION: The use of the NCDR® as a benchmark to guide QI programs outside the United States was associated with the positive impact of bending the cost curve to below that of national medical inflation and the comparison hospitals' costs, with a lower incidence of hospital readmission.