The effects of lead time and visual aids in TTO valuation: a study of the EQ-VT framework

__Abstract__ __Background__ The effect of lead time in time trade-off (TTO) valuation is not well understood. The purpose of this study was to investigate the effects on health-state valuation of the length of lead time and the way the lead-time TTO task is displayed visually. __Methods__ Using two general population samples, we compared three lead-time TTO variants: 10 years of lead time in full health preceding 5 years of unhealthy time (standard); 5 years of lead time preceding 5 years of unhealthy time (experimental); and 10 years of lead time and 5 years of unhealthy time, presented with a visual aid to highlight the point where the lead time ends (experimental). Participants were randomized to receive one of the lead-time variants, as administered by a computer software program. __Results__ Health-state values generated by TTO valuation tasks using a longer lead time were slightly lower than those generated by tasks using a shorter lead time. When lead time and unhealthy time were presented with visual aids highlighting the difference between the lead time and unhealthy time, respondents spent more time considering health states with a value close to 0. __Conclusions__ Different lead-time time trade-off variants should be carefully studied in order to achieve the best measurement of health-state values using this new method

Time to tweak the TTO: results from a comparison of alternative specifications of the TTO

Abstract This article examines the effect that different specifications of the time trade-off (TTO) valuation task may have on values for EQ-5D-5L health states. The new variants of the TTO, namely lead-time TTO and lag-time TTO, along with the classic approach to TTO were compared using two durations for the health states (15 and 20 years). The study tested whether these methods yield comparable health-state values. TTO tasks were administered online. It was found that lag-time TTO produced lower values than lead-time TTO and that the difference was larger in the longer time frame. Classic TTO values most resembled those of the lag-time TTO in a 20-year time frame in terms of mean absolute difference. The relative importance of different domains of health was systematically affected by the duration of the health state. In the tasks with a 10-year health-state duration, anxiety/ depression had the largest negative impact on health-state values; in the tasks with a 5-year duration, the pain/discomfort domain had the largest negative impact

Long-term CD4+ lymphocyte response following HAART initiation in a U.S. Military prospective cohort

<p>Abstract</p> <p>Background</p> <p>Among HIV-infected persons initiating highly active antiretroviral therapy (HAART), early CD4+ lymphocyte count increases are well described. However, whether CD4+ levels continue to increase or plateau after 4-6 years is controversial.</p> <p>Methods</p> <p>To address this question and identify other determinants of CD4+ response, we analyzed data for 1,846 persons from a prospective HIV military cohort study who initiated HAART, who had post-HAART CD4+ measurements, and for whom HIV seroconversion (SC) date was estimated.</p> <p>Results</p> <p>CD4+ count at HAART initiation was ≤ 200 cells/mm³for 23%, 201-349 for 31%, 350-499 for 27%, and ≥500 for 19%. The first 6 months post-HAART, the greatest CD4+ increases (93-151 cells) occurred, with lesser increases (22-36 cells/year) through the first four years. Although CD4+ changes for the entire cohort were relatively flat thereafter, HIV viral load (VL) suppressors showed continued increases of 12-16 cells/year. In multivariate analysis adjusting for baseline CD4+ and post-HAART time interval, CD4+ responses were poorer in those with: longer time from HIV SC to HAART start, lower pre-HAART CD4+ nadir, higher pre-HAART VL, and clinical AIDS before HAART (P < 0.05).</p> <p>Conclusions</p> <p>Small but positive long-term increases in CD4+ count in virally suppressed patients were observed. CD4+ response to HAART is influenced by multiple factors including duration of preceding HIV infection, and optimized if treatment is started with virally suppressive therapy as early as possible.</p

Cumulative Viral Load and Virologic Decay Patterns after Antiretroviral Therapy in HIV-Infected Subjects Influence CD4 Recovery and AIDS

The impact of viral load (VL) decay and cumulative VL on CD4 recovery and AIDS after highly-active antiretroviral therapy (HAART) is unknown.Three virologic kinetic parameters (first year and overall exponential VL decay constants, and first year VL slope) and cumulative VL during HAART were estimated for 2,278 patients who initiated HAART in the U.S. Military HIV Natural History Study. CD4 and VL trajectories were computed using linear and nonlinear Generalized Estimating Equations models. Multivariate Poisson and linear regression models were used to determine associations of VL parameters with CD4 recovery, adjusted for factors known to correlate with immune recovery. Cumulative VL higher than the sample median was independently associated with an increased risk of AIDS (relative risk 2.38, 95% confidence interval 1.56-3.62, p<0.001). Among patients with VL suppression, first year VL decay and slope were independent predictors of early CD4 recovery (p = 0.001) and overall gain (p<0.05). Despite VL suppression, those with slow decay during the first year of HAART as well as during the entire therapy period (overall), in general, gained less CD4 cells compared to the other subjects (133 vs. 195.4 cells/µL; p = 0.001) even after adjusting for potential confounders.In a cohort with free access to healthcare, independent of established predictors of AIDS and CD4 recovery during HAART, cumulative VL and virologic decay patterns were associated with AIDS and distinct aspects of CD4 reconstitution

Hepatitis B Vaccine Antibody Response and the Risk of Clinical AIDS or Death

Whether seroresponse to a vaccine such as hepatitis B virus (HBV) vaccine can provide a measure of the functional immune status of HIV-infected persons is unknown.This study evaluated the relationship between HBV vaccine seroresponses and progression to clinical AIDS or death. (HR 3.40; 95% CI, 1.39–8.32).

Domestic Violence and Health Care: Opening Pandora¿s Box ¿ Challenges and Dilemmas

In this article we take a critical stance toward the rational progressive narrative surrounding the integration of domestic violence within health care. Whilst changes in recent UK policy and practice have resulted in several tangible benefits, it is argued that there may be hidden dilemmas and challenges. We suggest that the medical model of care and its discursive practices position women as individually accountable for domestic violence-related symptoms and injuries. This may not only be ineffective in terms of service provision but could also have the potential to reduce the political significance of domestic violence as an issue of concern for all women. Furthermore, it is argued that the use of specific metaphors enables practitioners to distance themselves from interactions that may prove to be less comfortable and provide less than certain outcomes. Our analysis explores the possibilities for change that might currently be available. This would appear to involve a consideration of alternative discourses and the reformulation of power relations and subject positions in health care

ExprTarget: An Integrative Approach to Predicting Human MicroRNA Targets

Variation in gene expression has been observed in natural populations and associated with complex traits or phenotypes such as disease susceptibility and drug response. Gene expression itself is controlled by various genetic and non-genetic factors. The binding of a class of small RNA molecules, microRNAs (miRNAs), to mRNA transcript targets has recently been demonstrated to be an important mechanism of gene regulation. Because individual miRNAs may regulate the expression of multiple gene targets, a comprehensive and reliable catalogue of miRNA-regulated targets is critical to understanding gene regulatory networks. Though experimental approaches have been used to identify many miRNA targets, due to cost and efficiency, current miRNA target identification still relies largely on computational algorithms that aim to take advantage of different biochemical/thermodynamic properties of the sequences of miRNAs and their gene targets. A novel approach, ExprTarget, therefore, is proposed here to integrate some of the most frequently invoked methods (miRanda, PicTar, TargetScan) as well as the genome-wide HapMap miRNA and mRNA expression datasets generated in our laboratory. To our knowledge, this dataset constitutes the first miRNA expression profiling in the HapMap lymphoblastoid cell lines. We conducted diagnostic tests of the existing computational solutions using the experimentally supported targets in TarBase as gold standard. To gain insight into the biases that arise from such an analysis, we investigated the effect of the choice of gold standard on the evaluation of the various computational tools. We analyzed the performance of ExprTarget using both ROC curve analysis and cross-validation. We show that ExprTarget greatly improves miRNA target prediction relative to the individual prediction algorithms in terms of sensitivity and specificity. We also developed an online database, ExprTargetDB, of human miRNA targets predicted by our approach that integrates gene expression profiling into a broader framework involving important features of miRNA target site predictions

sodC-Based Real-Time PCR for Detection of Neisseria meningitidis

Real-time PCR (rt-PCR) is a widely used molecular method for detection of Neisseria meningitidis (Nm). Several rt-PCR assays for Nm target the capsule transport gene, ctrA. However, over 16% of meningococcal carriage isolates lack ctrA, rendering this target gene ineffective at identification of this sub-population of meningococcal isolates. The Cu-Zn superoxide dismutase gene, sodC, is found in Nm but not in other Neisseria species. To better identify Nm, regardless of capsule genotype or expression status, a sodC-based TaqMan rt-PCR assay was developed and validated. Standard curves revealed an average lower limit of detection of 73 genomes per reaction at cycle threshold (Ct) value of 35, with 100% average reaction efficiency and an average R2 of 0.9925. 99.7% (624/626) of Nm isolates tested were sodC-positive, with a range of average Ct values from 13.0 to 29.5. The mean sodC Ct value of these Nm isolates was 17.6±2.2 (±SD). Of the 626 Nm tested, 178 were nongroupable (NG) ctrA-negative Nm isolates, and 98.9% (176/178) of these were detected by sodC rt-PCR. The assay was 100% specific, with all 244 non-Nm isolates testing negative. Of 157 clinical specimens tested, sodC detected 25/157 Nm or 4 additional specimens compared to ctrA and 24 more than culture. Among 582 carriage specimens, sodC detected Nm in 1 more than ctrA and in 4 more than culture. This sodC rt-PCR assay is a highly sensitive and specific method for detection of Nm, especially in carriage studies where many meningococcal isolates lack capsule genes