Abstract Background Large cohort studies provide conflicting evidence regarding the potential for oral macrolide antibiotics to increase the risk of serious cardiac events. Objectives This study ...performed a meta-analysis to examine the link between macrolides and risk of sudden cardiac death (SCD) or ventricular tachyarrhythmias (VTA), cardiovascular death, and death from any cause. Methods We performed a search of published reports by using MEDLINE (January 1, 1966, to April 30, 2015) and EMBASE (January 1, 1980, to April 30, 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. Results Thirty-three studies involving 20,779,963 participants were identified. Patients taking macrolides, compared with those who took no macrolides, experienced an increased risk of developing SCD or VTA (RR: 2.42; 95% CI: 1.61 to 3.63), SCD (RR: 2.52; 95% CI: 1.91 to 3.31), and cardiovascular death (RR: 1.31; 95% CI: 1.06 to 1.62). No association was found between macrolides use and all-cause death or any cardiovascular events. The RRs associated with SCD or VTA were 3.40 for azithromycin, 2.16 for clarithromycin, and 3.61 for erythromycin, respectively. RRs for cardiovascular death were 1.54 for azithromycin and 1.48 for clarithromycin. No association was noted between roxithromycin and adverse cardiac outcomes. Treatment with macrolides is associated with an absolute risk increase of 118.1 additional SCDs or VTA, and 38.2 additional cardiovascular deaths per 1 million treatment courses. Conclusions Administration of macrolide antibiotics is associated with increased risk for SCD or VTA and cardiovascular death but not increased all-cause mortality.
Early repolarization pattern (ERP) has been proved to increase risk of arrhythmia death in the general population, but its prognostic significance in patients with structural heart disease (SHD) is ...controversial.
The purpose of this study was to conduct a meta-analysis of studies assessing the association between ERP and risk of ventricular arrhythmias (VTAs) and sudden cardiac death (SCD) in patients with SHD.
We performed a literature search using MEDLINE (January 1, 1966, to September 25, 2016) and EMBASE (January 1, 1980, to September 25, 2016) with no restrictions. Studies that reported odds ratio (OR) estimates with 95% confidence intervals (CIs) for the associations of interest were included.
The search yielded 19 observational studies, involving 7268 patients that reported 1127 cases of VTAs or SCD. In the selected studies, the point estimates of the ORs were consistently greater than 1. Compared with those without ERP, patients with ERP experienced a significantly increased risk of developing VTAs or SCD (OR 4.76; 95% CI 3.62-6.26), ventricular fibrillation (OR 7.14; 95% CI 4.31-11.82), and SCD (OR 4.07; 95% CI 1.58-10.51). The results were consistent and statistically significant in all subgroups. ERP with J-point elevation in inferior leads, notching configuration, and horizontal or descending ST segment connote higher risk.
ERP is associated with a significant increased risk of VTAs or SCD in patients with SHD. Future research should attempt to understand the exact mechanisms for the arrhythmia risk and to introduce ERP in the risk stratification in this patient group.
Abstract Background : Cancer that originates in the bone, termed primary bone cancer , is rare. Osteosarcoma (OS) occurs primarily in growing bone tissue and is more prevalent in children and ...adolescents. OS in adults is rare, with 3 to 5 cases per million population per year worldwide. There are limited data on treatment-related prognosis and adverse reactions in adults reported in the literature. Objectives : The aims of this study were to investigate factors that influence serum methotrexate (MTX) concentrations used in chemotherapy in Chinese adult patients with OS, and to determine the correlations (based on age, sex, and dosage), if any, between MTX and prognosis, in terms of disease-free survival (DFS) and overall survival (OAS), and tolerability. Methods : Adult patients aged ≥30 years with OS received ≥3 courses (2 courses before surgery and 3–4 courses postsurgery) of high-dose MTX (6 or 8 g/m2 ) combined chemotherapy. The regimen consisted of day 1: MTX + folinic acid (herein referred to as citrovorum factor rescue); day 8: cisplatin; days 21 to 25: ifosfamide + mesna; and day 21: doxorubicin. Serum MTX concentrations were assessed immediately after the end of infusion (baseline) and at 24 and 48 hours using high-performance liquid chromatography. Changes in serum MTX concentrations, factors that influence serum MTX concentrations, and the relationship between serum MTX concentrations and prognosis and tolerability (determined by adverse reactions) were analyzed. Patients received a second course of treatment after a 3-week period. Results : Ninety patients (58 men, 32 women; age range, 30–67 years) with OS were included in the study. A total of 532 courses of combined chemotherapy were administered. The serum MTX concentrations ranged widely at baseline (244.31–929.68 mol/L, Cmin and Cmax , respectively) and at 24 hours (0.73–28.24 mol/L, respectively), suggesting that the serum MTX concentrations varied significantly between different individuals and within the same individual at different time points. The serum MTX concentrations in ~23% of cases (122/532) determined at 24 and/or 48 hours were numerically higher than the safety values (according to Nirenberg's reference: irreversible damage if MTX concentration was >10 umol/L and > 1 umol/L at 24 and 48 hours, respectively). No correlation was found between high serum MTX concentration at baseline and high serum MTX concentration at 24 hours ( r = 0.401). The prevalences of the 3 most common adverse reactions in these patients were depressed white blood cell count (44.03%), dental ulcer (23.0%), and rash (18.0%). However, in the remaining 410 courses in which serum MTX concentrations were lower than the safety values, these prevalences were 14.6%, 3–9%, and 2.4%, respectively. Neither age nor sex was significantly associated with MTX Cmax , but dosage was ( P < 0.05). Patients with a serum MTX Cmax concentration >500 μmol/L at baseline had a significantly longer DFS rate than those with ≤500 umol/L ( P = 0.040). There were no significant between-group differences in the OAS rates. conclusions : In these Chinese patients with OS, serum MTX concentrations measured at different time points were varied. The findings suggest that adverse reactions occurred in patients whose serum MTX concentrations at 24 and/or 48 hours were higher than the safety values. The dosage appeared to have influenced MTX Cmax , while sex and age did not, and the Cmax was significantly related to DFS but not OAS.
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