Estimated dates of detectable infection (EDDIs) as an improvement upon Fiebig staging for HIV infection dating.

Accurate methods for determining the duration of HIV infection at the individual level are valuable in many settings, including many critical research studies and in clinical practice (especially for acute infection). Since first published in 2003, the 'Fiebig staging system' has been used as the primary way of classifying early HIV infection into five sequential stages based on HIV test result patterns in newly diagnosed individuals. However, Fiebig stages can only be assigned to individuals who produce both a negative and a positive test result on the same day, on specific pairs of tests of varying 'sensitivity'. Further, in the past 16 years HIV-testing technology has evolved substantially, and three of the five key assays used to define Fiebig stages are no longer widely used. To address these limitations, we developed an improved and more general framework for estimating the duration of HIV infection by interpreting any combination of diagnostic test results, whether obtained on single or multiple days, into an estimated date of detectable infection, or EDDI. A key advantage of the EDDI method over Fiebig staging is that it allows for the generation of a point estimate, as well as an associated credibility interval for the date of first detectable infection, for any person who has at least one positive and one negative HIV test of any kind. The tests do not have to be run on the same day; they do not have to be run during the acute phase of infection and the method does not rely on any special pairing of tests to define 'stages' of infection. The size of the interval surrounding the EDDI (and therefore the precision of the estimate itself) depends largely on the length of time between negative and positive tests. The EDDI approach is also flexible, seamlessly incorporating any assay for which there is a reasonable diagnostic delay estimate. An open-source, free online tool includes a user-updatable curated database of published diagnostic delays. HIV diagnostics have evolved tremendously since that original publication more than 15 years ago, and it is time to similarly evolve the methods used to estimate timing of infection. The EDDI method is a flexible and rigorous way to estimate the timing of HIV infection in a continuously evolving diagnostic landscape.

Moving towards a reliable HIV incidence test - current status, resources available, future directions and challenges ahead.

In 2011 the Incidence Assay Critical Path Working Group reviewed the current state of HIV incidence assays and helped to determine a critical path to the introduction of an HIV incidence assay. At that time the Consortium for Evaluation and Performance of HIV Incidence Assays (CEPHIA) was formed to spur progress and raise standards among assay developers, scientists and laboratories involved in HIV incidence measurement and to structure and conduct a direct independent comparative evaluation of the performance of 10 existing HIV incidence assays, to be considered singly and in combinations as recent infection test algorithms. In this paper we report on a new framework for HIV incidence assay evaluation that has emerged from this effort over the past 5 years, which includes a preliminary target product profile for an incidence assay, a consensus around key performance metrics along with analytical tools and deployment of a standardized approach for incidence assay evaluation. The specimen panels for this evaluation have been collected in large volumes, characterized using a novel approach for infection dating rules and assembled into panels designed to assess the impact of important sources of measurement error with incidence assays such as viral subtype, elite host control of viraemia and antiretroviral treatment. We present the specific rationale for several of these innovations, and discuss important resources for assay developers and researchers that have recently become available. Finally, we summarize the key remaining steps on the path to development and implementation of reliable assays for monitoring HIV incidence at a population level.

[Effect of dopexamine on the hemodynamics of coronary surgery patients with and without bisoprolol blockade]. / Der Einfluss von Dopexamin auf die Hämodynamik koronarchirurgischer Patienten mit und ohne Bisoprolol-Blockade.

Patients with coronary artery disease undergoing coronary artery bypass grafting can develop perioperative low cardiac output failure requiring positive inotropic support. Commonly, the sympathetic amines, dopamine, dobutamine or adrenaline are used in low-output state. However, patients on long-term cardioselective beta-blocking therapy may experience problems with such a treatment. Dopexamine, a new synthetic amine, possesses positive inotropic effects by indirect stimulation of the beta 1-receptors and direct stimulation of the beta 2-receptors. We therefore studied the hemodynamic efficacy of dopexamine in patients with and without beta-receptor blockade. In 12 patients with coronary artery disease classed as NYHA II or III, six without any beta-blocker medication, and six with beta 1-blocker medication (bisoprolol 5 mg), anesthesia was induced with high-dose fentanyl (0.05 mg/kg) and pancuronium (0.1 mg/kg). The patients were normoventilated with a mask (O2:air 1:1, tidal volume 10 ml/kg with a rate of 10/min) for 5 min and then intubated. Following intubation anesthesia was continued with 0.025 mg/kg/h fentanyl. In anesthesia steady state the patients of both groups were treated with 2 micrograms/kg/min dopexamine over a period of 15 min and then with 4 micrograms/kg/min dopexamine over a further period of 15 min. Measurements of cardiovascular dynamics included heart rate (HR), cardiac index (CI), stroke volume index (SVI), mean arterial blood pressure (MAP), coronary perfusion pressure (CPP), systemic vascular resistance (SVR), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), right atrium pressure (RAP), pressure work index (PWI) and arterial-mixed venous oxygen content difference (AVDO2), which were monitored or calculated by standard formulas.(ABSTRACT TRUNCATED AT 250 WORDS)