Prediction of response to antiretroviral therapy by human experts and by the EuResist data‐driven expert system (the EVE study)

Objectives

The EuResist expert system is a novel data‐driven online system for computing the probability of 8‐week success for any given pair of HIV‐1 genotype and combination antiretroviral therapy regimen plus optional patient information. The objective of this study was to compare the EuResist system vs. human experts (EVE) for the ability to predict response to treatment.

Methods

The EuResist system was compared with 10 HIV‐1 drug resistance experts for the ability to predict 8‐week response to 25 treatment cases derived from the EuResist database validation data set. All current and past patient data were made available to simulate clinical practice. The experts were asked to provide a qualitative and quantitative estimate of the probability of treatment success.

Results

There were 15 treatment successes and 10 treatment failures. In the classification task, the number of mislabelled cases was six for EuResist and 6–13 for the human experts [mean±standard deviation (SD) 9.1±1.9]. The accuracy of EuResist was higher than the average for the experts (0.76 vs. 0.64, respectively). The quantitative estimates computed by EuResist were significantly correlated (Pearson r=0.695, P<0.0001) with the mean quantitative estimates provided by the experts. However, the agreement among experts was only moderate (for the classification task, inter‐rater κ=0.355; for the quantitative estimation, mean±SD coefficient of variation=55.9±22.4%).

Conclusions

With this limited data set, the EuResist engine performed comparably to or better than human experts. The system warrants further investigation as a treatment‐decision support tool in clinical practice.     

Induction of the endogenous gonadotrophin surge for oocyte maturation with intra-nasal gonadotrophin-releasing hormone analogue (buserelin): effective minimal dose

From 1985-1987, a total of 34 couples undergoing superovulation for a single in-vitro fertilization (IVF) cycle with clomiphene citrate and purified follicle stimulating hormone (FSH) or human menopausal gonadotrophin (HMG) were randomly allocated doses of intra-nasal buserelin to induce an endogenous gonadotrophin surge, prior to oocyte collection. The doses ranged from a single 25 microg dose to 100 microg every 4 h for 20 h. In three cycles the treatment was abandoned because of a poor ovarian response. In the remaining 31 cycles buserelin was given to induce the endogenous gonadotrophin surge, but there was evidence of premature luteinization in eight cycles and a premature gonadotrophin surge in four cycles. Although a single dose as low as 40 microg induced a surge and resulted in a pregnancy, a single dose of 50 microg proved the most effective minimal dose consistently to induce a gonadotrophin surge and oocyte maturation. Recent reports using gonadotrophin-releasing hormone (GnRH) analogues to induce a gonadotrophin surge has prompted publication of this previously unpublished data.      

Copper/Metal Ratios in the Gills of Rainbow Trout (Oncorhynchus mykiss) Provide Evidence of Copper Exposure Under Conditions of Mixed-Metal Exposure

Previous work has suggested that the ratio of copper residues to zinc in the gills of rainbow trout may indicate short-term exposure to increased levels of waterborne copper. However, the effect of exposure to a combination of increased copper and zinc concentrates in the water column was unknown. We exposed rainbow trout to 8 ± 2 g L^–1, 40 ± 2 g L^–1 and 90 ± 9 g L^–1 of waterborne copper and 21 ± 3 g L^–1, 129 ± 40 g L^–1, and 202 ± 40 g L^–1 of waterborne zinc in a 2-factor experiments and gill copper and zinc residues were examined. Other gill parameters analyzed included the concentrations of calcium, magnesium, sodium, and potassium, liver copper and zinc concentrations and plasma copper, calcium, sodium, and potassium are also reported here. Copper residues in the gill filaments were significantly higher in the highest level of copper exposure (high Cu, 4.06 g g^–1; low Cu 2.41 g g^–1; 0 Cu 2.01 g g^–1; P = 0.001), whereas no differences were seen in zinc concentrations at any treatment level. Gill sodium and plasma calcium concentrations were also decreased at the highest waterborne copper concentrations. Although copper–zinc ratios in the gills were significantly different between the highest and lowest copper treatments (P = 0.002, F = 6.59), copper–sodium and copper–magnesium ratios were more sensitive to waterborne copper exposure (P = 0.001, F = 17.91 and P = 0.002, F = 15.45, respectively). These copper–metal ratios may be better indicators of copper loading in the water column.