SummaryBackgroundIntensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy.MethodsWe did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388.Findings3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001).InterpretationAmong patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice.FundingNational Institutes of Health Research Health Technology Assessment Programme, British Heart Foundation.

The second most common variant of double outlet right ventricle, the anomaly was originally distinguished by a transposed aorta arising entirely from the right ventricle, a pulmonary artery overriding a ventricular septal defect (VSD), side-by-side great vessels, and bilateral subarterial conus with absence of pulmonary-mitral fibrous continuity.1,2 Most surgical series have expanded the definition to include any double outlet right ventricle (with or without pulmonary-mitral continuity) with a subpulmonary VSD, in which left ventricular output flows preferentially to the pulmonary artery. [2][3][4] Despite >30 years of experience with various management strategies, Taussig-Bing anomaly continues to present a considerable surgical challenge. This is largely related to associated anomalies, the most significant of which may be the varying degrees of right ventricular outflow tract and aortic arch obstruction caused by a malaligned ventricular septum. 5 Today, primary arterial switch operation (ASO) with VSD closure is the gold standard for Taussig-Bing anomaly.2,6,7 Significant rates of reintervention, mortality, and neoaortic complications have been demonstrated in studies of this lesion, particularly in patients who had undergone palliative procedures such as pulmonary artery banding before definitive repair. 6,7 Since 1990, single-stage correction with primary ASO has been our institution's practice for all children with Taussig-Bing anomaly. We aimed to describe the long-term outcomes and functional status of patients managed with this surgical approach and to identify factors that predict mortality, reintervention, neoaortic insufficiency (AI), and neoaortic root dilation. Methods Patient SelectionAfter obtaining approval from the Institutional Review Board of Columbia University with a waiver of consent, we retrospectively reviewed our hospital and surgical databases for all admissions diagnosed with transposition of the great arteries or double outlet right ventricle. Patients with Taussig-Bing anomaly were identified as those with a transposed aorta and a pulmonary artery arising in Background-Studies of the arterial switch operation for Taussig-Bing anomaly demonstrate significant rates of reintervention and mortality, particularly after initial palliation to delay complete repair. We aimed to describe the longterm outcomes of our 21-year practice of single-stage arterial switch operation for all patients with Taussig-Bing anomaly. Methods and Results-A retrospective study was performed, and 43 patients with Taussig-Bing anomaly were identified between 1990 and 2011. Median age at arterial switch operation was 7 (range, 2-192) days, and median operative weight was 3.2 (1.4-6.2) kg. Aortic arch obstruction was present in 30 patients (70%). Hospital mortality was 7% (n=3). Follow-up was available for 37 hospital survivors at a mean of 8.1 (±6.3) years. Late mortality was 2% (n=1). At follow-up, all patients were in New York Heart Association functional class I. Freedom from transcatheter or surgical reinte...

Asymptomatic central venous catheter (CVC)–related thrombosis in children varies in incidence from 5% to 69%. The rate of acute and long-term complications, such as postthrombotic syndrome (PTS), from asymptomatic CVC-related thrombosis is unknown. This article reports the outcomes of a prospective study of 189 children in pediatric intensive care that aimed to determine the frequency of asymptomatic CVC-related thrombosis during hospital admission, and the incidence of residual CVC-related thrombosis and clinically significant PTS 2 years later. Risk factors associated with CVC-related thrombosis were also identified. This study is distinct from previous work as children identified to have asymptomatic CVC-related thrombosis were not treated (clinical team kept blinded) and the entire cohort was followed for 2 years to determine the natural history of asymptomatic thrombosis. Ultrasounds of 146 children determined a 21.9% incidence of acute CVC-related thrombosis. Two children were symptomatic. No radiological thrombosis extension or clinical embolization occurred in the 126 children assessed at follow-up. Using 2 recognized PTS scales, clinically significant PTS was reported in 2 children (1 symptomatic, 1 asymptomatic CVC-related thrombosis), however, neither had functional impairment. Cardiac arrest was a risk factor for CVC-related thrombosis during admission and femoral CVC placement was predictive of residual thrombosis 2 years later. This study challenges the notion that critically ill children with asymptomatic CVC-related thrombosis require anticoagulant treatment, as the results demonstrate that the incidence of acute or long-term complications is low. A larger confirmatory study of nontreatment of CVC-related thrombosis in critically ill children is justified.

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The complexity of managing children with chronic disease has led to an increase in the use of long-term warfarin therapy. Time in therapeutic range (TTR) is the preferred method for determining efficacy and stability of warfarin management. This study aimed to determine the TTR achievement and incidence of adverse events among pediatric warfarin patients managed by an anticoagulation clinic over 12 months and to compare TTR achievement between patients self-testing (PST) at home and those monitored using routine methods. International normalized ratio (INR) results reported for 2012 for children currently having their warfarin therapy managed by a dedicated pediatric anticoagulation clinic were analyzed. Warfarin-related adverse events were recorded. A total of 164 patients were included. In total, 93 children performed PST and 71 children tested their INR at a hospital or pathology service. TTR achievement for the cohort was 67.1% (95% confidence interval, 64.4-69.7). A total of 69.2% of INR tests conducted at home were within the TTR compared with 64.3% of INR tests conducted at a hospital or pathology service (P=0.07). One major bleeding event occurred and there was 1 thrombotic episode. PST demonstrated noninferior warfarin stability compared with routine methods. Routine outcome evaluation of pediatric anticoagulation management within single institutions is necessary to confirm the success of such programs.

The care of adolescents with complex chronic illness needs to be developmentally appropriate to encourage adherence, knowledge retention and self-management. There has been an increase in the number of adolescents requiring long-term or lifelong anticoagulation therapy, related to either an underlying illness or idiopathic deep vein thrombosis. The burden of anticoagulant therapy, the associated risks and the required lifestyle changes can significantly impact on psychosocial well-being in the adolescent patient. This review identifies issues pertinent to adolescent anticoagulation management and discusses strategies to support optimal management. The HEEADSSS (Home, Education and employment, Eating, Activities with peers, Drugs, Sexual activity, Suicide and depression, and Safety) framework was used to provide guidance in undertaking a psychosocial assessment of adolescents requiring anticoagulant therapy in conjunction with a structured education strategy. Adolescent anticoagulant management strategies employing developmentally appropriate assessment and education will likely result in improved therapeutic outcomes for the patient and potentially facilitate transition to adult-based care.