Machine Learning Improves the Identification of Individuals With Higher Morbidity and Avoidable Health Costs After Acute Coronary Syndromes.

OBJECTIVES: Traditional risk scores improved the definition of the initial therapeutic strategy in acute coronary syndrome (ACS), but they were not designed for predicting long-term individual risks and costs. In parallel, attempts to directly predict costs from clinical variables in ACS had limited success. Thus, novel approaches to predict cardiovascular risk and health expenditure are urgently needed. Our objectives were to predict the risk of major/minor adverse cardiovascular events (MACE) and estimate assistance-related costs. METHODS: We used a 2-step approach that: (1) predicted outcomes with a common pathophysiological substrate (MACE) by using machine learning (ML) or logistic regression (LR) and compared with existing risk scores; (2) derived costs associated with noncardiovascular deaths, dialysis, ambulatory-care-sensitive-hospitalizations (ACSH), strokes, and MACE. With consecutive ACS individuals (n = 1089) from 2 cohorts, we trained in 80% of the population and tested in 20% using a 4-fold cross-validation framework. The 29-variable model included socioeconomic, clinical/lab, and coronarography variables. Individual costs were estimated based on cause-specific hospitalization from the Brazilian Health Ministry perspective. RESULTS: After up to 12 years follow-up (mean = 3.3 ± 3.1; MACE = 169), the gradient-boosting machine model was superior to LR and reached an area under the curve (AUROC) of 0.891 [95% CI 0.846-0.921] (test set), outperforming the Syntax Score II (AUROC = 0.635 [95% CI 0.569-0.699]). Individuals classified as high risk (>90th percentile) presented increased HbA1c and LDL-C both at <24 hours post-ACS and 1-year follow-up. High-risk individuals required 33.5% of total costs and showed 4.96-fold (95% CI 3.71-5.48, P < .00001) greater per capita costs compared with low-risk individuals, mostly owing to avoidable costs (ACSH). This 2-step approach was more successful for finding individuals incurring high costs than predicting costs directly from clinical variables. CONCLUSION: ML methods predicted long-term risks and avoidable costs after ACS.

Metoprolol for prevention of bucking at orotracheal extubation: a double-blind, placebo-controlled randomised trial.

BACKGROUND: Respiratory responses to extubation can cause serious postoperative complications. Beta-blockers, such as metoprolol, can interfere with the cough pathway. However, whether metoprolol can effectively control respiratory reflexes during extubation remains unclear. The objective of this study is to evaluate the efficacy of intravenous metoprolol in attenuating respiratory responses to tracheal extubation. METHODS: Randomized, double-blinded, placebo-controlled trial. SETTING: Tertiary referral center located in Brasília, Brazil. Recruitment: June 2021 to December 2021. SAMPLE: 222 patients of both sexes with an American Society of Anesthesiologists (ASA) physical status I-III aged 18-80 years. Patients were randomly assigned to receive intravenous metoprolol 5 mg IV or placebo at the end of surgery. The primary outcome was the proportion of patients who developed bucking secondary to endotracheal tube stimulation of the tracheal mucosa during extubation. Secondary outcomes included coughing, bronchospasm, laryngospasm, Mean Blood Pressure (MAP), and Heart Rate (HR) levels. RESULTS: Two hundred and seven participants were included in the final analysis: 102 in the metoprolol group and 105 in the placebo group. Patients who received metoprolol had a significantly lower risk of bucking (43.1% vs. 64.8%, Relative Risk [RR = 0.66], 95% Confidence Interval [95% CI 0.51-0.87], p = 0.003). In the metoprolol group, 6 (5.9%) patients had moderate/severe coughing compared with 33 (31.4%) in the placebo group (RR = 0.19; 95% CI 0.08-0.43, p < 0.001). CONCLUSION: Metoprolol reduced the risk of bucking at extubation in patients undergoing general anesthesia compared to placebo.

Compared efficacy of rituximab, abatacept, and tocilizumab in patients with rheumatoid arthritis refractory to methotrexate or TNF inhibitors agents: a systematic review and network meta-analysis.

BACKGROUND: Our aim was to compare the efficacy of rituximab, tocilizumab, and abatacept in individuals with rheumatoid arthritis (RA) refractory to treatments with MTX or TNFi agents. METHODS: We searched 6 databases until January 2023 for phase 2-4 RCTs evaluating patients with RA refractory to MTX or TNFi therapy treated with rituximab, abatacept, and tocilizumab (intervention arm) compared to controls. Study data were independently assessed by two investigators. The primary outcome was considered as achieving ACR70 response. RESULTS: The meta-analysis included 19 RCTs, with 7,835 patients and a mean study duration of 1.2 years. Hazard ratios for achieving an ACR70 response at six months were not different among the bDMARDs, however, we found high heterogeneity. Three factors showing a critical imbalance among the bDMARD classes were identified: baseline HAQ score, study duration, and frequency of TNFi treatment in control arm. Multivariate meta-regression adjusted to these three factors were conducted for the relative risk (RR) for ACR70. Thus, heterogeneity was attenuated (I2 = 24%) and the explanatory power of the model increased (R2 = 85%). In this model, rituximab did not modify the chance of achieving an ACR70 response compared to abatacept (RR = 1.773, 95%CI 0.113-10.21, p = 0.765). In contrast, abatacept was associated with RR = 2.217 (95%CI 1.554-3.161, p < 0.001) for ACR70 compared to tocilizumab. CONCLUSION: We found high heterogeneity among studies comparing rituximab, abatacept, and tocilizumab. On multivariate metaregressions, if the conditions of the RCTs were similar, we estimate that abatacept could increase the chance of reaching an ACR70 response by 2.2-fold compared to tocilizumab.

The framing of time-dependent machine learning models improves risk estimation among young individuals with acute coronary syndromes.

Acute coronary syndrome (ACS) is a common cause of death in individuals older than 55 years. Although younger individuals are less frequently seen with ACS, this clinical event has increasing incidence trends, shows high recurrence rates and triggers considerable economic burden. Young individuals with ACS (yACS) are usually underrepresented and show idiosyncratic epidemiologic features compared to older subjects. These differences may justify why available risk prediction models usually penalize yACS with higher false positive rates compared to older subjects. We hypothesized that exploring temporal framing structures such as prediction time, observation windows and subgroup-specific prediction, could improve time-dependent prediction metrics. Among individuals who have experienced ACS (nglobal_cohort = 6341 and nyACS = 2242), the predictive accuracy for adverse clinical events was optimized by using specific rules for yACS and splitting short-term and long-term prediction windows, leading to the detection of 80% of events, compared to 69% by using a rule designed for the global cohort.

The I405V and Taq1B polymorphisms of the CETP gene differentially affect sub-clinical carotid atherosclerosis.

BACKGROUND: Cholesteryl ester transfer protein (CETP) plays a major role in lipid metabolism, but studies on the association of CETP polymorphisms with risks of cardiovascular disease are inconsistent. This study investigated whether the CETP gene I405V and Taq1B polymorphisms modified subclinical atherosclerosis in an asymptomatic Brazilian population sample. METHODS: The polymorphisms were analyzed using polymerase chain reaction in 207 adult volunteers. Serum lipid profiles, oxLDL Ab titers, C-reactive protein and tumor necrosis factor-α concentrations and CETP and phospholipid transfer protein (PLTP) activities were determined, and common carotid artery intima-media thickness (cIMT) was measured using ultrasonography. RESULTS: No differences in cIMT were observed between the presence or absence of the minor B2 and V alleles in either polymorphism. However, inverse correlations between mean cIMT and CETP activity in the presence of these polymorphisms were observed, and positive correlations of these polymorphisms with PLTP activity and oxLDL Ab titers were identified. Moreover, logistic multivariate analysis revealed that the presence of the B2 allele was associated with a 5.1-fold (CI 95%, OR: 1.26 - 21.06) increased risk for cIMT, which was equal and above the 66th percentile and positively interacted with age. However, no associations with the V allele or CETP and PLTP activities were observed. CONCLUSIONS: None of the studied parameters, including CETP activity, explained the different relationships between these polymorphisms and cIMT, suggesting that other non-determined factors were affected by the genotypes and related to carotid atherosclerotic disease.

Glucose-Lowering and the Risk of Cardiovascular Events With Antidiabetic Therapies: A Systematic Review and Additive-Effects Network Meta-Analysis.

Aim: To assess the impact of the HbA1c levels achieved with antidiabetic therapies (ADTs) on the risk of MACE. Methods: A systematic search was performed in PubMed, Cochrane, and ClinicalTrials. gov for RCTs published up to March 2022 reporting the occurrence of MACE and all-cause mortality in individuals with T2DM treated with all marketed ADTs, including a sample size ≥100 individuals in each study arm and follow-up ≥24 weeks. A systematic review and additive-effects network meta-analysis with random effects and a multivariate meta-regression were utilized to assess the impact of achieved HbA1c on incident MACE. Results: We included 126 RCTs with 143 treatment arms, 270,874 individuals, and 740,295 individuals-years who were randomized to an active treatment vs. control group. Among all ADTs, only therapy with SGLT2i, GLP1-RA, or pioglitazone similarly reduced the risk of MACE compared to placebo. The achievement of HbA1c ≤ 7.0% in RCTs with the 3 drug classes in the active arm was associated with an adjusted HR of 0.91 (95% CI 0.80, 0.97; p = 0.017) compared with HbA1c>7.0%, without affecting all-cause mortality. These results, however, were not maintained among all ADTs. Conclusions: Achieving lower glucose levels with SGLT2i, GLP1-RA, or pioglitazone is linearly associated with a reduced risk of MACEs, without affecting all-cause mortality. Systematic Review Registration: www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020213127, identifier: CRD42020213127.

Clinical and economic impact of coronary artery bypass graft and percutaneous coronary intervention in young individuals with acute coronary syndromes and multivessel disease: A real-world comparison in a middle-income country.

Background: In recent decades, the world watched a dramatic increase in the incidence of acute coronary syndromes (ACS) among young individuals (≤55 years-old) and a relative decrease in the elderly. The management of ACS in young patients with multivessel disease still needs to be elucidated, as these individuals maintain a long life expectancy. Research Question: To compare clinical outcomes and care costs in individuals with premature ACS and multivessel disease undergoing coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI). Methods and Results: Participants included all individuals ≤55 years-old admitted with ACS to public hospitals in Brasília (Brazil) between 2013 and 2015 and who underwent cardiac catheterization with SYNTAX score ≥23 or Duke category 6. Outcomes were adjudicated with death certificates and data from medical records. The primary outcome was the occurrence of major adverse cardiovascular events (MACE), defined as death due to cardiovascular causes, recurrent hospitalizations due to cardiovascular ischemic events, and incident heart failure New York Heart Association III-IV. As secondary outcome we assessed indirect and direct costs by evaluating the cost of lost productivity (in international dollars (Int$) per year) due to illness and death, outpatient costs and costs with new hospitalizations. Multivariate and principal components (PC) adjusted analyzes were performed. Results: Among 1,088 subjects (111 CABG and 977 PCI) followed for 6.2 years (IQR: 1.1), 304 primary events were observed. MACE was observed in 20.7% of the CABG group and 28.8% of the PCI group (p = 0.037). In multivariate analyses, PCI was associated with a hazard ratio (HR) = 1.227 (95% CI: 1.004-1.499; p = 0.0457) for MACE, and in PC-adjusted HR = 1.268 (95% CI: 1.048-1.548; p = 0.0271) compared with CABG. Despite direct costs were equivalent, the cost due to the loss of labor productivity was higher in the PCI group (Int$ 4,511 (IQR: 18,062)/year vs Int$ 3,578 (IQR: 13,198)/year; p = 0.049], compared with CABG. Conclusions: Among young individuals with ACS and multivessel disease, surgical strategy was associated with a lower occurrence of MACE and lower indirect costs in the long-term.