Cardiac ischemia in patients with septic shock randomized to vasopressin or norepinephrine.

INTRODUCTION: Cardiac troponins are sensitive and specific biomarkers of myocardial necrosis. We evaluated troponin, CK, and ECG abnormalities in patients with septic shock and compared the effect of vasopressin (VP) versus norepinephrine (NE) on troponin, CK, and ECGs. METHODS: This was a prospective substudy of a randomized trial. Adults with septic shock randomly received, blinded, a low-dose infusion of VP (0.01 to 0.03 U/min) or NE (5 to 15 µg/min) in addition to open-label vasopressors, titrated to maintain a mean blood pressure of 65 to 75 mm Hg. Troponin I/T, CK, and CK-MB were measured, and 12-lead ECGs were recorded before study drug, and 6 hours, 2 days, and 4 days after study-drug initiation. Two physician readers, blinded to patient data and drug, independently interpreted ECGs. RESULTS: We enrolled 121 patients (median age, 63.9 years (interquartile range (IQR), 51.1 to 75.3), mean APACHE II 28.6 (SD 7.7)): 65 in the VP group and 56 in the NE group. At the four time points, 26%, 36%, 32%, and 21% of patients had troponin elevations, respectively. Baseline characteristics and outcomes were similar between patients with positive versus negative troponin levels. Troponin and CK levels and rates of ischemic ECG changes were similar in the VP and the NE groups. In multivariable analysis, only APACHE II was associated with 28-day mortality (OR, 1.07; 95% CI, 1.01 to 1.14; P=0.033). CONCLUSIONS: Troponin elevation is common in adults with septic shock. We observed no significant differences in troponin, CK, and ECGs in patients treated with vasopressin and norepinephrine. Troponin elevation was not an independent predictor of mortality. TRIAL REGISTRATION: Controlled-trials.com ISRCTN94845869.

Who is stressed? Comparing cortisol levels between individuals.

UNLABELLED: Cortisol is the most commonly used biomarker to compare physiological stress between individuals. Its use, however, is frequently inappropriate. Basal cortisol production varies markedly between individuals. Yet, in naturalistic studies that variation is often ignored, potentially leading to important biases. OBJECTIVES: Identify appropriate analytical tools to compare cortisol across individuals and outline simple simulation procedures for determining the number of measurements required to apply those methods. METHODS: We evaluate and compare three alternative methods (raw values, Z-scores, and sample percentiles) to rank individuals according to their cortisol levels. We apply each of these methods to first morning urinary cortisol data collected thrice weekly from 14 cycling Mayan Kaqchiquel women. We also outline a simple simulation to estimate appropriate sample sizes. RESULTS: Cortisol values varied substantially across women (ranges: means: 1.9-2.7; medians: 1.9-2.8; SD: 0.26-0.49) as did their individual distributions. Cortisol values within women were uncorrelated. The accuracy of the rankings obtained using the Z-scores and sample percentiles was similar, and both were superior to those obtained using the cross-sectional cortisol values. Given the interindividual variation observed in our population, 10-15 cortisol measurements per participant provide an acceptable degree of accuracy for across-women comparisons. CONCLUSIONS: The use of single raw cortisol values is inadequate to compare physiological stress levels across individuals. If the distributions of individuals' cortisol values are approximately normal, then the standardized ranking method is most appropriate; otherwise, the sample percentile method is advised. These methods may be applied to compare stress levels across individuals in other populations and species.

A national review of vertical HIV transmission.

OBJECTIVES: Prevention of vertical HIV transmission has evolved significantly in Canada over the last two decades. The aim of this analysis is to describe the surveillance programme used, rate of vertical HIV transmission and changing epidemiology of HIV-affected pregnancies in Canada. DESIGN: National perinatal HIV surveillance programme. METHODS: From 1990, annual retrospective data was collected on demographic and clinical characteristics of HIV-infected mothers and their infants referred to 22 participating sites across Canada either before/during pregnancy or within 3 months after delivery. Factors impacting HIV transmission and demographic features were explored. RESULTS: Two thousand, six hundred and ninety-two mother-infant pairs were identified. The overall rate of vertical HIV transmission was 5.2%, declining to 2.9% since 1997. The rate of transmission for mothers who received HAART was 1%, and 0.4% if more than 4 weeks of HAART was given. Forty percent of women delivered by caesarean section, with no difference in transmission rate compared with vaginal delivery for women treated with HAART (1.4 vs. 0.6%, P = 0.129) but significant risk reduction for those who did not receive HAART (3.8 vs. 10.3%, P = 0.016). Black women were the largest group; proportions of black and aboriginal women increased significantly over time (P < 0.001 for both). Heterosexual contact was the most common risk category for maternal infection (65%), followed by injection drug use (IDU) (25%). CONCLUSION: Vertical HIV transmission in Canada has decreased dramatically for women treated with HAART therapy. All pregnant women should be evaluated for HIV infection and programmes expanded to reach vulnerable populations including aboriginal, immigrant and IDU women.

Short-term cancer mortality projections: a comparative study of prediction methods.

This paper provides a systematic comparison of cancer mortality and incidence projection methods used at major national health agencies. These methods include Poisson regression using an age-period-cohort model as well as a simple log-linear trend, a joinpoint technique, which accounts for sharp changes, autoregressive time series and state-space models. We assess and compare the reliability of these projection methods by using Canadian cancer mortality data for 12 cancer sites at both the national and regional levels. Cancer sites were chosen to provide a wide range of mortality frequencies. We explore specific techniques for small case counts and for overall national-level projections based on regional-level data. No single method is omnibus in terms of superior performance across a wide range of cancer sites and for all sizes of populations. However, the procedures based on age-period-cohort models used by the Association of the Nordic Cancer Registries tend to provide better performance than the other methods considered. The exception is when case counts are small, where the average of the observed counts over the recent 5-year period yields better predictions.