AimsTo investigate if recent technical and procedural developments in percutaneous coronary intervention (PCI) significantly influence outcomes in appropriately selected patients with three-vessel (3VD) coronary artery disease.Methods and resultsThe SYNTAX II study is a multicenter, all-comers, open-label, single arm study that investigated the impact of a contemporary PCI strategy on clinical outcomes in patients with 3VD in 22 centres from four European countries. The SYNTAX-II strategy includes: heart team decision-making utilizing the SYNTAX Score II (a clinical tool combining anatomical and clinical factors), coronary physiology guided revascularisation, implantation of thin strut bioresorbable-polymer drug-eluting stents, intravascular ultrasound (IVUS) guided stent implantation, contemporary chronic total occlusion revascularisation techniques and guideline-directed medical therapy. The rate of major adverse cardiac and cerebrovascular events (MACCE [composite of all-cause death, cerebrovascular event, any myocardial infarction and any revascularisation]) at one year was compared to a predefined PCI cohort from the original SYNTAX-I trial selected on the basis of equipoise 4-year mortality between CABG and PCI. As an exploratory endpoint, comparisons were made with the historical CABG cohort of the original SYNTAX-I trial. Overall 708 patients were screened and discussed within the heart team; 454 patients were deemed appropriate to undergo PCI. At one year, the SYNTAX-II strategy was superior to the equipoise-derived SYNTAX-I PCI cohort (MACCE SYNTAX-II 10.6% vs. SYNTAX-I 17.4%; HR 0.58, 95% CI 0.39–0.85, P = 0.006). This difference was driven by a significant reduction in the incidence of MI (HR 0.27, 95% CI 0.11–0.70, P = 0.007) and revascularisation (HR 0.57, 95% CI 0.37–0.9, P = 0.015). Rates of all-cause death (HR 0.69, 95% CI 0.27–1.73, P = 0.43) and stroke (HR 0.69, 95% CI 0.10–4.89, P = 0.71) were similar. The rate of definite stent thrombosis was significantly lower in SYNTAX-II (HR 0.26, 95% CI 0.07–0.97, P = 0.045).ConclusionAt one year, clinical outcomes with the SYNTAX-II strategy were associated with improved clinical results compared to the PCI performed in comparable patients from the original SYNTAX-I trial. Longer term follow-up is awaited and a randomized clinical trial with contemporary CABG is warranted.ClinicalTrials.gov IdentifierNCT02015832
Delamanid, a nitro-dihydro-imidazooxazole derivative, has been developed by Otsuka Pharmaceutical for the treatment of multidrug-resistant tuberculosis (MDR-TB). Delamanid received its first global approval for the treatment of MDR-TB in the European Union (EU), for use in combination with optimised background therapy. It is also under review for marketing in Japan for MDR-TB, the first drug application filed in Japan for this indication. Delamanid has been granted orphan drug status in both the EU and Japan. This article summarizes the milestones in the development of delamanid leading to this first approval for MDR-TB.
AimTo compare mortality rates for cardiovascular disease, cancer, and respiratory disease between adults with cerebral palsy (CP) and the general population.MethodA cohort study was conducted using data from adults with CP in England, identified through a primary care data set (the Clinical Practice Research Datalink), with linked data on death registrations from the Office for National Statistics. Cause of death was categorized according to International Classification of Diseases codes. Standardized mortality ratios (SMRs) were calculated to compare mortality rates between adults with CP and the general population, adjusted for age, sex, and calendar year.ResultsNine hundred and fifty‐eight adults with CP were identified (52.5% males, 47.5% females; median age at start of follow‐up 31y [interquartile range 22–43y]) and followed for a total of 7693 person‐years. One hundred and forty‐two patients (15%) died during follow‐up. Adults with CP had an increased risk of death due to cardiovascular disease (SMR: 3.19, 95% confidence interval [CI] 2.20–4.62) and respiratory disease (SMR: 13.59, 95% CI 9.89–18.67), but not from malignant neoplasms (SMR: 1.42, 95% CI 0.83–2.45).InterpretationWe found that adults with CP in England have increased risk of death due to diseases of the circulatory and respiratory systems, supporting findings from two studies that compared cause‐specific mortality rates between adults with CP in the USA and the general population. Further research is required into primary and secondary prevention of cardiovascular and respiratory disease in people with CP worldwide.What this paper adds Adults with cerebral palsy (CP) in England have 14‐fold increased risk of mortality due to diseases of the respiratory system.They have a 3‐fold increased risk of mortality due to diseases of the circulatory system.Adults with CP had an increased risk of death due to cerebrovascular disease and ischaemic heart disease.The elevated risk of ischaemic heart disease, however, did not reach statistical significance at the 5% per cent level.
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