Neurocognition and quality of life after reinitiating antiretroviral therapy in children randomized to planned treatment interruption

Objective: Understanding the effects of antiretroviral treatment (ART) interruption on neurocognition and quality of life (QoL) are important for managing unplanned interruptions and planned interruptions in HIV cure research. Design: Children previously randomized to continuous (continuous ART, n=41) vs. planned treatment interruption (PTI, n=47) in the Pediatric European Network for Treatment of AIDS (PENTA) 11 study were enrolled. At study end, PTI children resumed ART. At 1 and 2 years following study end, children were assessed by the coding, symbol search and digit span subtests of Wechsler Intelligence Scale for Children (6-16 years old) or Wechsler Adult Intelligence Scale ( 6517 years old) and by Pediatrics QoL questionnaires for physical and psychological QoL. Transformed scaled scores for neurocognition and mean standardized scores for QoL were compared between arms by t-test and Mann-Whitney U test, respectively. Scores indicating clinical concern were compared (<7 for neurocognition and <70 for QoL tests). Results: Characteristics were similar between arms with a median age of 12.6 years, CD4 + of 830 cells/\u3bcl and HIV RNA of 1.7 log 10 copies/ml. The median cumulative ART exposure was 9.6 in continuous ART vs. 7.7 years in PTI (P=0.02). PTI children had a median of 12 months off ART and had resumed ART for 25.2 months at time of first assessment. Neurocognitive scores were similar between arms for all tests. Physical and psychological QoL scores were no different. About 40% had low neurocognitive and QoL scores indicating clinical concern. Conclusion: No differences in information processing speed, sustained attention, short-term memory and QoL functioning were observed between children previously randomized to continuous ART vs. PTI in the PENTA 11 trial

Inventory management.

A critical aspect of blood transfusion is the timely provision of high quality blood products. This task remains a significant challenge for many blood services and blood systems reflecting the difficulty of balancing the recruitment of sufficient donors, the optimal utilization of the donor's gift, the increasing safety related restrictions on blood donation, a growing menu of specialized blood products and an ever-growing imperative to increase the efficiency of blood product provision from a cost perspective. As our industry now faces questions about our standard practices including whether or not the age of blood has a negative impact on recipients, it is timely to take a look at our collective inventory management practices. This International Forum represents an effort to get a snap shot of inventory management practices around the world, and to understand the range of different products provided for patients. In addition to sharing current inventory management practices, this Forum is intended to foster an exchange of ideas around where we see our field moving with respect to various issues including specialty products, new technologies, and reducing recipient risk from blood transfusion products

ESC Core Curriculum for the General Cardiologist (2013)

Preface The previous Core Curriculum for the General Cardiologist defined a model for cardiology training in Europe and it has been adopted as the standard for regulating training, for access to the specialty (certification), and for revalidation in several countries.1 During the last 5 years we have witnessed profound changes in cardiological practice. The work of both hospital and independent cardiologists has been better integrated with that of general practitioners. It has taken into account the requirements of national authorities, re-imbursement organizations, and hospital administrations. Cardiologists face changing patient expectations. General cardiologists, interventional cardiologists, anaesthetists, and cardiac surgeons work together in Heart Teams.2,3 The age of cardiac patients has increased and they are presenting with more co-morbidities. Knowledge, technology, and treatment are constantly advancing: new imaging modalities have become widely available. Stent technology has evolved and competes with cardiac surgery for all but complex cases.2 Percutaneous valve implantations are increasingly successful.4 Interventional electrophysiology and device therapy have become cornerstones in the practice of cardiology.5,6 Care of the patient with heart failure is now a multi-disciplinary undertaking.7 New powerful anti-thrombotic and anticoagulant therapies have been introduced and are often used in combination, with clear benefits but increased bleeding risks.6,8,9 Use of diagnostic and therapeutic tools and the approaches to management of common conditions have been systematically clarified in regularly updated ESC consensus guideline documents. Against the background of these developments, the Board of the ESC decided in 2011 to revise and update the Core Curriculum. The chairman of the Committee for Education 2010–2012, Otto A. Smiseth, delegated this project to a task force, whose members were drawn from general cardiologists. The 2013 version of the Core Curriculum outlines the knowledge and skills of the general clinically oriented cardiologist, rather than those required for the sub-specialties. The document provides a framework for training and certification, continuous medical education (CME), and recertification. The Core Curriculum will inevitably continue to evolve as authors and reviewers are aware that there are still important differences in training and means throughout Europe and ESC member states. In the Core Curriculum, the ESC is setting a standard that national societies can use in their dealings with political institutions and national authorities. A deliberate decision was taken to outline an optimal rather than a minimum standard, allowing for the fact that not every training system will be able, or may not wish, to adopt the full curriculum. In countries (or centres) that are currently unable to deliver training in all its aspects, the Core Curriculum can and should be used as a benchmark to promote improvement. The 2013 Core Curriculum defines the clinical, patient-oriented, training of the general cardiologist. The overall structure of the previous version has been retained, but the table format has been abandoned to limit the number of printed pages and to make the document more easily searchable on-line. In most subject areas, there was a wide if not unanimous consensus among the task force members on the training required for the cardiologist of the future. The document recommends that acquisition of competence in general cardiology requires at least 6 years of full-time postgraduate training, of which 4 years are devoted to cardiology. The general aspects of training and all individual chapters have been updated. The document focuses on knowledge of mechanisms of disease, clinical and communication skills, empathy for the patient and their relatives, and teamwork. A clear boundary has been set between the competencies required of the general cardiologist and those of the sub-specialist.10–13 The first part of the curriculum covers general aspects of training, and is followed by a comprehensive description of the specific components in 28 chapters. Each of the chapters includes statements of the objectives, and is further sub-divided into the required knowledge, skills and behaviours, and attitudes. Some chapters have been renamed and/or sub-divided into sub-sections. The most salient changes are summarized here. Non-invasive imaging (Chapter 2.3) has been divided into five sections: Non-invasive imaging (general aspects), Echocardiography, Cardiac magnetic resonance (CMR), Cardiac X-ray computed tomography, and Nuclear techniques. Cardiovascular prevention (Chapter 2.7) has been divided into sections on Cardiovascular risk factors and Arterial hypertension. Cardiac tumours (Chapter 2.12) has been replaced by a new and broader chapter on Oncology and the heart. The chapter Cardiac Rehabilitation and Exercise Physiology (Chapter 2.19) has become Physical activity and Sport in primary and secondary prevention and includes sections on Sports cardiology and Cardiac rehabilitation. A new chapter entitled Acute cardiovascular care (Chapter 2.27) has been added. The Cardiac consult (Chapter 2.28) has been expanded and divided into sections dealing with the patient undergoing non-cardiac surgery, the patient with neurological symptoms or diseases, and the patient with conditions not presenting primarily as cardiovascular disease [elderly patients, patients with diabetes, chronic kidney disease (CKD), erectile dysfunction, and others]. The 2013 Core Curriculum underwent a thorough review process based on the template of the review of the ESC guidelines. The document does not include minimum or optimal numbers of procedures to be undertaken, and does not address periodic evaluation, certification, or revalidation. This does not obviate the importance of regular, structured, and formally documented assessment, which is crucial to implementation of the curriculum. This should include knowledge-based assessments (formative and summative), formally observed procedures and practices, a log-book, and a recognition of the potential of simulation techniques in both training and assessment

Placebo effect characteristics observed in a single, international, longitudinal study in Huntington's disease.

Item does not contain fulltextBACKGROUND: Classically, clinical trials are based on the placebo-control design. Our aim was to analyze the placebo effect in Huntington's disease. METHODS: Placebo data were obtained from an international, longitudinal, placebo-controlled trial for Huntington's disease (European Huntington's Disease Initiative Study Group). One-hundred and eighty patients were evaluated using the Unified Huntington Disease Rating Scale over 36 months. A placebo effect was defined as an improvement of at least 50% over baseline scores in the Unified Huntington Disease Rating Scale, and clinically relevant when at least 10% of the population met it. RESULTS: Only behavior showed a significant placebo effect, and the proportion of the patients with placebo effect ranged from 16% (first visit) to 41% (last visit). Nondepressed patients with better functional status were most likely to be placebo-responders over time. CONCLUSIONS: In Huntington's disease, behavior seems to be more vulnerable to placebo than overall motor function, cognition, and function1 maart 201

Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes

Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure

Suicidal ideation in a European Huntington's disease population

Previous studies indicate increased prevalences of suicidal ideation, suicide attempts, and completed suicide in Huntington's disease (HD) compared with the general population. This study investigates correlates and predictors of suicidal ideation in HD. METHODS: The study cohort consisted of 2106 HD mutation carriers, all participating in the REGISTRY study of the European Huntington's Disease Network. Of the 1937 participants without suicidal ideation at baseline, 945 had one or more follow-up measurements. Participants were assessed for suicidal ideation by the behavioural subscale of the Unified Huntington's Disease Rating Scale (UHDRS). Correlates of suicidal ideation were analyzed using logistic regression analysis and predictors were analyzed using Cox regression analysis. RESULTS: At baseline, 169 (8.0%) mutation carriers endorsed suicidal ideation. Disease duration (odds ratio [OR]=0.96; 95% confidence interval [CI]: 0.9-1.0), anxiety (OR=2.14; 95%CI: 1.4-3.3), aggression (OR=2.41; 95%CI: 1.5-3.8), a previous suicide attempt (OR=3.95; 95%CI: 2.4-6.6), and a depressed mood (OR=13.71; 95%CI: 6.7-28.0) were independently correlated to suicidal ideation at baseline. The 4-year cumulative incidence of suicidal ideation was 9.9%. Longitudinally, the presence of a depressed mood (hazard ratio [HR]=2.05; 95%CI: 1.1-4.0) and use of benzodiazepines (HR=2.44; 95%CI: 1.2-5.0) at baseline were independent predictors of incident suicidal ideation, whereas a previous suicide attempt was not predictive. LIMITATIONS: As suicidal ideation was assessed by only one item, and participants were a selection of all HD mutation carriers, the prevalence of suicidal ideation was likely underestimated. CONCLUSIONS: Suicidal ideation in HD frequently occurs. Assessment of suicidal ideation is a priority in mutation carriers with a depressed mood and in those using benzodiazepines