Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case-control study using centralized ultrasensitive 454 pyrosequencing.

OBJECTIVES: It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART. METHODS: This Europe-wide case-control study included ART-naive subjects infected with drug-susceptible HIV-1 as revealed by population sequencing, who achieved virological suppression on first-line ART including one NNRTI. Cases experienced virological failure and controls were subjects from the same cohort whose viraemia remained suppressed at a matched time since initiation of ART. Blinded, centralized 454 pyrosequencing with parallel bioinformatic analysis in two laboratories was used to identify MVs in the 1%-25% frequency range. ORs of virological failure according to MV detection were estimated by logistic regression. RESULTS: Two hundred and sixty samples (76 cases and 184 controls), mostly subtype B (73.5%), were used for the analysis. Identical MVs were detected in the two laboratories. 31.6% of cases and 16.8% of controls harboured pre-existing MVs. Detection of at least one MV versus no MVs was associated with an increased risk of virological failure (OR = 2.75, 95% CI = 1.35-5.60, P = 0.005); similar associations were observed for at least one MV versus no NRTI MVs (OR = 2.27, 95% CI = 0.76-6.77, P = 0.140) and at least one MV versus no NNRTI MVs (OR = 2.41, 95% CI = 1.12-5.18, P = 0.024). A dose-effect relationship between virological failure and mutational load was found. CONCLUSIONS: Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART.

Neurology and psychiatry: waking up to opportunities of sleep. : State of the art and clinical/research priorities for the next decade.

In recent years, evidence has emerged for a bidirectional relationship between sleep and neurological and psychiatric disorders. First, sleep-wake disorders (SWDs) are very common and may be the first/main manifestation of underlying neurological and psychiatric disorders. Secondly, SWDs may represent an independent risk factor for neuropsychiatric morbidities. Thirdly, sleep-wake function (SWF) may influence the course and outcome of neurological and psychiatric disorders. This review summarizes the most important research and clinical findings in the fields of neuropsychiatric sleep and circadian research and medicine, and discusses the promise they bear for the next decade. The findings herein summarize discussions conducted in a workshop with 26 European experts in these fields, and formulate specific future priorities for clinical practice and translational research. More generally, the conclusion emerging from this workshop is the recognition of a tremendous opportunity offered by our knowledge of SWF and SWDs that has unfortunately not yet entered as an important key factor in clinical practice, particularly in Europe. Strengthening pre-graduate and postgraduate teaching, creating academic multidisciplinary sleep-wake centres and simplifying diagnostic approaches of SWDs coupled with targeted treatment strategies yield enormous clinical benefits for these diseases.

Cohort profile: Antiretroviral Therapy Cohort Collaboration (ART-CC).

The advent of effective combination antiretroviral therapy (ART) in 1996 resulted in fewer patients experiencing clinical events, so that some prognostic analyses of individual cohort studies of human immunodeficiency virus-infected individuals had low statistical power. Because of this, the Antiretroviral Therapy Cohort Collaboration (ART-CC) of HIV cohort studies in Europe and North America was established in 2000, with the aim of studying the prognosis for clinical events in acquired immune deficiency syndrome (AIDS) and the mortality of adult patients treated for HIV-1 infection. In 2002, the ART-CC collected data on more than 12,000 patients in 13 cohorts who had begun combination ART between 1995 and 2001. Subsequent updates took place in 2004, 2006, 2008, and 2010. The ART-CC data base now includes data on more than 70,000 patients participating in 19 cohorts who began treatment before the end of 2009. Data are collected on patient demographics (e.g. sex, age, assumed transmission group, race/ethnicity, geographical origin), HIV biomarkers (e.g. CD4 cell count, plasma viral load of HIV-1), ART regimen, dates and types of AIDS events, and dates and causes of death. In recent years, additional data on co-infections such as hepatitis C; risk factors such as smoking, alcohol and drug use; non-HIV biomarkers such as haemoglobin and liver enzymes; and adherence to ART have been collected whenever available. The data remain the property of the contributing cohorts, whose representatives manage the ART-CC via the steering committee of the Collaboration. External collaboration is welcomed. Details of contacts are given on the ART-CC website (www.art-cohort-collaboration.org).

Cerebral perfusion CT: Current state of the art : P44

Purpose: The aim of this educational poster is to introduce the technical principles of cerebral perfusion CT and to provide examples of its clinical applications and potential limitations in the everyday emergency practice. Methods and materials: Cerebral perfusion CT is a well established investigatory tool for many vascular and parenchymal brain dysfunctions. CT perfusion maps allow a semiquantitative assessment of cerebral perfusion. Results: Currently, cerebral perfusion CT has a pivotal role in differentiating reversible from irreversible ischemic parenchymal insult besides its integral role in grading vasospasm after subarachnoid hemorrhage. Furthermore, cerebral perfusion CT can be coupled to acetazolamide administration in order to assess the cerebrovascular reserve capacity before performing extra-/intra-cranial bypass surgery in patients with cerebral vascular insufficiency. Cerebral perfusion CT can also identify diffuse abnormalities of cerebral perfusion in children with traumatic brain injury showing a low initial GCS in order to predict the final outcome regarding the late occurrence of irreversible parenchymal damage. Cerebral Perfusion CT is also able to detect focal parenchymal perfusion abnormalities in acute epileptic seizures. Conclusion: Cerebral perfusion CT can be integrated in the management of many vascular, traumatic and functional disorders of the brain.

Trends of pre-hospital emergency medical services activity over 10 years : a population-based registry analysis

BACKGROUND: The number of requests to pre-hospital emergency medical services (PEMS) has increased in Europe over the last 20 years, but epidemiology of PEMS interventions has little be investigated. The aim of this analysis was to describe time trends of PEMS activity in a region of western Switzerland. METHODS: Use of data routinely and prospectively collected for PEMS intervention in the Canton of Vaud, Switzerland, from 2001 to 2010. This Swiss Canton comprises approximately 10% of the whole Swiss population. RESULTS: We observed a 40% increase in the number of requests to PEMS between 2001 and 2010. The overall rate of requests was 35/1000 inhabitants for ambulance services and 10/1000 for medical interventions (SMUR), with the highest rate among people aged ≥ 80. Most frequent reasons for the intervention were related to medical problems, predominantly unconsciousness, chest pain respiratory distress, or cardiac arrest, whereas severe trauma interventions decreased over time. Overall, 89% were alive after 48 h. The survival rate after 48 h increased regularly for cardiac arrest or myocardial infarction. CONCLUSION: Routine prospective data collection of prehospital emergency interventions and monitoring of activity was feasible over time. The results we found add to the understanding of determinants of PEMS use and need to be considered to plan use of emergency health services in the near future. More comprehensive analysis of the quality of services and patient safety supported by indicators are also required, which might help to develop prehospital emergency services and new processes of care.

Les débuts de la communication à trois. Interactions visuelles triadiques entre père, mère et bébé

Plusieurs auteurs ont montré que les échanges visuels entre des mères dépressives ou psychotiques et leur bébé présentent de multiples perturbations : dans cet article, les auteurs proposent une étude exploratoire portant sur les échanges visuels père-mère- bébé (9-18 semaines) dans deux groupes de familles, un groupe suivi pour des difficultés du post-partum et un groupe témoin. Les observations sont réalisées dans le cadre d'un jeu à trois structuré selon diverses modalités d'interaction (un parent joue avec l'enfant en présence de l'autre parent / les deux parents jouent conjointement avec le bébé). Les variables retenues concernent d'une part le niveau d'attention visuelle conjointe des partenaires, d'autre part l'évolution de cette attention visuelle au cours du jeu. Les résultats révèlent que les échanges visuels sont plus intenses dans les familles fonctionnelles, ce qui semble indiquer que l'engagement visuel triadique établi par les partenaires peut être représentatif du fonctionnement de la triade à un moment donné de son développement. D'autre part, l'analyse de l'évolution de l'engagement visuel au travers des différents contextes de jeu amène les auteurs à proposer l'hypothèse d'une « alliance triadique » établie conjointement par les trois partenaires et formant la matrice de leurs échanges dyadiques et triadiques. De façon plus générale, les auteurs supposent que l'établissement de cette alliance joue un rôle déterminant pour le développement et l'autonomisa- tion du bébé au sein de sa famille. Disorders in the visual interaction between depressive or psychotic mothers and their baby have been widely described : in this paper, the authors propose an exploratory study of father-mother-infant visual interaction (infants are 9-18 weeks old) in two groups of families, voluntary families and families in therapy for post-par turn disorders. The observations are gathered during a three-partner play, involving different kinds of triadic interaction (one parent plays with the infant, the other parent being « only present » / both parents play together with the child). The analyses have focused on the amount of visual attention shared by the partners and on the evolution of visual interaction during the game. Results show that triadic interaction is more intense in functional triads, which means that shared visual attention may be representative of the more general functioning of the family at a definite stage of its development. Furthermore, considering the sequential organization of visual interaction throughout the game led the authors to the construct of a « triadic alliance », jointly established by the three partners and providing a matrix for their dyadic and triadic interaction. On a more general level, such an alliance could play an important role for the development and the autonomy of the baby within his j her family.