Change-points in antibiotic consumption in the community, European Union/European Economic Area, 1997-2017

Surveillance of antibiotic consumption in the community is of utmost importance to inform and evaluate control strategies. Data on two decades of antibiotic consumption in the community were collected from 30 EU/European Economic Area (EEA) countries. This article reviews temporal trends and the presence of abrupt changes in subgroups of relevance in antimicrobial stewardship.For the period 1997-2017, data on yearly antibiotic consumption in the community, aggregated at the level of the active substance, were collected using the WHO ATC classification and expressed in DDD (ATC/DDD index 2019) per 1000 inhabitants per day. We applied a range of non-linear mixed models to assess the presence of changes in the consumption of antibacterials for systemic use (ATC group J01) and eight antibiotic subgroups.For the majority of the studied groups, a country-specific change-point model provided the best fit. Depending on the antibiotic group/subgroup and on the country, change-points were spread out between 2000 and 2013.Due to the heterogeneity in antibiotic consumption in the community across EU/EEA countries, a country-specific change-point model provided the better fit. Given the limitations of this model, our recommendation for the included countries is to carefully interpret the country-specific results presented in this article and to use the tutorial included in this series to conduct their own change-point analysis when evaluating the impact of changes in regulations, public awareness campaigns, and other national interventions to improve antibiotic consumption in the community

Estimating the impact of school closure on social mixing behaviour and the transmission of close contact infections in eight European countries

BACKGROUND: Mathematical modelling of infectious disease is increasingly used to help guide public health policy. As directly transmitted infections, such as influenza and tuberculosis, require contact between individuals, knowledge about contact patterns is a necessary pre-requisite of accurate model predictions. Of particular interest is the potential impact of school closure as a means of controlling pandemic influenza (and potentially other pathogens). METHODS: This paper uses a population-based prospective survey of mixing patterns in eight European countries to study the relative change in the basic reproduction number (R0--the average number of secondary cases from a typical primary case in a fully susceptible population) on weekdays versus weekends and during regular versus holiday periods. The relative change in R0 during holiday periods and weekends gives an indication of the impact collective school closures (and prophylactic absenteeism) may have during a pandemic. RESULTS: Social contact patterns differ substantially when comparing weekdays to the weekend and regular to holiday periods mainly due to the reduction in work and/or school contacts. For most countries the basic reproduction number decreases from the week to weekends and regular to holiday periods by about 21% and 17%, respectively. However for other countries no significant decrease was observed. CONCLUSION: We use a large-scale social contact survey in eight different European countries to gain insights in the relative change in the basic reproduction number on weekdays versus weekends and during regular versus holiday periods. The resulting estimates indicate that school closure can have a substantial impact on the spread of a newly emerging infectious disease that is transmitted via close (non sexual) contacts

Original Studies Outcomes of a Dedicated Stent in Coronary Bifurcations with Large Side Branches: A Subanalysis of the Randomized TRYTON Bifurcation Study

Objectives: To examine the benefit of the Tryton dedicated side branch (SB) stent compared with provisional stenting in the treatment of complex bifurcation lesions involving large SBs. Background: The TRYTON Trial was designed to evaluate the utility of a dedicated SB stent to treat true bifurcation lesions involving large (!2.5 mm by visual estimation) SBs. Patient enrolled in the trial had smaller SB diameters than intended (59% SB 2.25 mm by Core Lab QCA). The TRYTON Trial did not meet its primary endpoint due to an increased rate of peri-procedural myocardial infarctions (MIs). Methods: The TRYTON Trial randomized 704 patients to the Tryton SB stent with main vessel DES versus provisional SB treatment with main vessel DES. The rates of the primary end point of target vessel failure and the secondary powered end point of angiographic percent diameter stenosis in the SB at 9 months were assessed and compared between the two treatment strategies among patients with a SB !2.25 mm diameter at Additional Supporting Information may be found in the online version of this article. Catheterization and Cardiovascular Interventions 00:00-00 V C 2015 Wiley Periodicals, Inc

Bleeding Events Before Coronary Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: Upstream administration of antithrombotic drugs to patients with non-ST-segment elevation acute coronary syndromes before coronary angiography is a common practice despite an incomplete understanding of the risks and benefits. OBJECTIVES: The authors analyzed the incidence of bleeding and ischemic events occurring before angiography and assessed their association with antithrombotic drugs and mortality risk. METHODS: All patients from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial with planned angiography after enrollment were included. Bleeding events were classified according to the ACUITY scale as major or nonmajor bleeding. Kaplan-Meier and Cox proportional hazards analyses were performed. RESULTS: Of 13,726 patients, 275 (2.0%) bled before angiography, including 52 (0.4%) with major bleeding. Forty-four (0.3%) experienced myocardial infarction. The median time from randomization to coronary angiography was 4.5 h (interquartile ratio [IQR]: 1.7 to 19.7 h) for patients who did not bleed while waiting for angiography and 27.9 h (IQR: 21.9 to 65.6 h) for patients who bled while waiting for angiography (p < 0.001). Bleeding events accrued linearly over time, reaching 10.4% at 96 h post-randomization. Independent predictors of bleeding before angiography included age (adjusted hazard ratio [HR]: 1.03 per year of age; 95% confidence interval [CI]: 1.01 to 1.04; p < 0.001), renal insufficiency (adjusted HR: 1.48; 95% CI: 1.07 to 2.04; p = 0.02), and use of multiple antithrombotic drugs (adjusted HR: 1.33; 95% CI: 1.14 to 1.56; p < 0.001). Bleeding before coronary angiography was associated with longer hospitalization (4.8 days [IQR: 3.0 to 8.9 days] vs. 3.0 days [IQR: 1.9 to 5.9 days]; p < 0.001). Patients who bled before angiography were more likely to die within 1 year than patients who did not bleed (8.5% vs. 4.1%; p < 0.001; adjusted HR: 1.89 (95% CI: 1.23 to 2.90; p = 0.004). CONCLUSIONS: Upstream antithrombotic treatment of patients with non-ST-segment elevation acute coronary syndromes awaiting coronary angiography is associated with excess bleeding with mortality implications. Bleeding avoidance strategies before angiogram, including early angiography, may negate the need to prolong upstream antithrombotic treatment and improve the overall risk-benefit balance for these patients. (Acute Catheterization and Urgent Intervention Triage Strategy [ACUITY]; NCT00093158)

Dedicated Bifurcation Stent for the Treatment of Bifurcation Lesions InvolvingLarge Side Branches: Outcomes From the Tryton Confirmatory Study

Objectives: The aim of this study was to prospectively study and confirm the safety and efficacy of the Tryton Side Branch Stent in the treatment of coronary artery bifurcations involving large side branches (SBs). Background The TRYTON Pivotal randomized controlled trial (RCT) was designed to compare the Tryton stent with standard provisional SB stenting in large vessels. The trial inadvertently enrolled patients with too small SBs ( < 2.25 mm). The overall trial did not meet its primary endpoint, because of an increased rate of periprocedural myocardial infarction in the Tryton stent arm. A post hoc analysis restricted to the intended population showed that the trial would have met its endpoint if only patients with SBs ≥2.25 mm in diameter (by core laboratory quantitative coronary angiography) had been enrolled.MethodsThe Tryton Confirmatory Study was a prospective, single-arm extension of the TRYTON Pivotal RCT that enrolled an additional 133 patients treated with the Tryton Side Branch Stent. It was designed to confirm the results of the post hoc analysis and emphasized the inclusion of appropriately sized SBs. The primary endpoint was noninferiority with regard to periprocedural myocardial infarction (creatine kinase myocardial band 3 times the upper limit of normal) compared with a performance goal based on the TRYTON Pivotal RCT.ResultsAmong the 133 enrolled patients, 132 (99.2%) had SBs ≥2.25 mm. Baseline clinical and angiographic parameters were similar in this study and the RCT. Periprocedural myocardial infarction occurred in 10.5% of patients, which was numerically lower than the provisional group in the TRYTON Pivotal RCT (11.9%). The 95% confidence bounds did not extend beyond the pre-defined performance goal of 17.9%, meeting the noninferiority primary endpoint.ConclusionsThe Tryton Confirmatory Study, in conjunction with the post hoc analysis of the intended population in the TRYTON Pivotal RCT, supports the safety and efficacy of the Tryton Side Branch Stent for treatment of bifurcation lesions involving large SBs

Outcomes of a dedicated stent in coronary bifurcations with large side branches: A subanalysis of the randomized TRYTON bifurcation study

Objectives: To examine the benefit of the Tryton dedicated side branch (SB) stent compared with provisional stenting in the treatment of complex bifurcation lesions involving large SBs. Background: The TRYTON Trial was designed to evaluate the utility of a dedicated SB stent to treat true bifurcation lesions involving large (>= 2.5 mm by visual estimation) SBs. Patient enrolled in the trial had smaller SB diameters than intended (59% SB = 2.25 mm diameter at baseline determined by Core Lab QCA. Results: Among the 704 patients enrolled in the TRYTON Trial, 289 patients (143 provisional and 146 Tryton stent; 41% of entire cohort) had a SB >= 2.25 mm. The primary end point of TVF was numerically lower in the Tryton group compared with the provisional group (11.3% vs. 15.6%, P=0.38), and was within the non-inferiority margin. No difference among the rates of clinically driven target vessel revascularization (3.5% vs. 4.3% P=0.77) or cardiac death (0% both groups) were seen. In-segment percent diameter stenosis of the SB was significantly lower in the Tryton group compared with the provisional group (30.4% vs. 40.6%, P=0.004). Conclusions: Analysis of the TRYTON Trial cohort of SB >= 2.25 mm supports the safety and efficacy of the Tryton SB stent compared with a provisional stenting strategy in the treatment of bifurcation lesions involving large SBs