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.

Agreement in electrocardiogram interpretation in patients with septic shock.

OBJECTIVE: The reliability of electrocardiogram interpretation to diagnose myocardial ischemia in critically ill patients is unclear. In adults with septic shock, we assessed intra- and inter-rater agreement of electrocardiogram interpretation, and the effect of knowledge of troponin values on these interpretations. DESIGN: Prospective substudy of a randomized trial of vasopressin vs. norepinephrine in septic shock. SETTING: Nine Canadian intensive care units. PATIENTS: Adults with septic shock requiring at least 5 µg/min of norepinephrine for 6 hrs. INTERVENTIONS: Twelve-lead electrocardiograms were recorded before study drug, and 6 hrs, 2 days, and 4 days after study drug initiation. MEASUREMENTS: Two physician readers, blinded to patient data and group, independently interpreted electrocardiograms on three occasions (first two readings were blinded to patient data; third reading was unblinded to troponin). To calibrate and refine definitions, both readers initially reviewed 25 trial electrocardiograms representing normal to abnormal. Cohen's Kappa and the φ statistic were used to analyze intra- and inter-rater agreement. RESULTS: One hundred twenty-one patients (62.2 ± 16.5 yrs, Acute Physiology and Chronic Health Evaluation II 28.6 ± 7.7) had 373 electrocardiograms. Blinded to troponin, readers 1 and 2 interpreted 46.4% and 30.0% of electrocardiograms as normal, and 15.3% and 12.3% as ischemic, respectively. Intrarater agreement was moderate for overall ischemia (κ 0.54 and 0.58), moderate/good for "normal" (κ 0.69 and 0.55), fair to good for specific signs of ischemia (ST elevation, T inversion, and Q waves, reader 1 κ 0.40 to 0.69; reader 2 κ 0.56 to 0.70); and good/very good for atrial arrhythmias (κ 0.84 and 0.79) and bundle branch block (κ 0.88 and 0.79). Inter-rater agreement was fair for ischemia (κ 0.29), moderate for ST elevation (κ 0.48), T inversion (κ 0.52), and Q waves (κ 0.44), good for bundle branch block (κ 0.78), and very good for atrial arrhythmias (κ 0.83). Inter-rater agreement for ischemia improved from fair to moderate (κ 0.52, p = .028) when unblinded to troponin. CONCLUSIONS: In patients with septic shock, inter-rater agreement of electrocardiogram interpretation for myocardial ischemia was fair, and improved with troponin knowledge.

Development of melamine certified reference material in milk using two different isotope dilution mass spectrometry techniques.

A new certified reference material (CRM) of melamine in milk GLHK-11-02 was developed aiming to address the great demand from the testing community after the melamine crises. The material was prepared by adding an appropriate quantity of melamine into the skimmed milk samples and the final product was in the form of fine lyophilized powder. Characterization of the material relied on two newly developed gravimetric isotope dilution mass spectrometry (IDMS) methods, one using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and another gas chromatography-mass spectrometry (GC-MS). Experimental parameters with crucial effects on the performance of the two IDMS methods were thoroughly investigated. These included purity of standard used, equilibration time of isotopes, efficiency of extraction methods as well as possible interferences from the matrix and melamine analogues. Precision was found to be excellent with a coefficient of variation of 2.5% for the LC-IDMS/MS (n=46) and 1.9% for the GC-IDMS (n=30) respectively. Using one-tail Student's t-test at 95% confidence interval, analytical data sets generated from the two methods were found to exhibit no significant difference. Measurement accuracy of the methods was further verified through an Asia Pacific Metrology Program (APMP) pilot study. Analytical results of the present LC-IDMS/MS for the two milk test samples at the concentration level of about 0.45 and 3.5 mg kg(-1) were proven to be very good. There were excellent overlaps between our results and the assigned reference values, and the absolute deviation was less than 3.2%. Both the LC-IDMS/MS and GC-IDMS methods were shown to be sufficiently reliable and accurate for certification of the melamine CRM. Certified value of melamine in dry mass fraction in GLHK-11-02 was 1.14 mg kg(-1). Expanded uncertainty due to sample inhomogeneity, long term and short term stability and variability in the characterization procedure was at 7.1% or 0.08 mg kg(-1). The CRM is primarily used to provide a complete method validation for and to improve the technical competence of melamine analysis to food and chemical testing laboratories.

Chrysotile asbestos exposure associated with removal of automobile exhaust systems (ca. 1945-1975) by mechanics: results of a simulation study.

For decades, asbestos-containing gaskets were used in virtually every system that involved the transport of fluids or gases. Prior to the mid-1970s, some automobile exhaust systems contained asbestos gaskets either at flanges along the exhaust pipes or at the exhaust manifolds of the engine. A limited number of automobile mufflers were lined with asbestos paper. This paper describes a simulation study that characterized personal and bystander exposures to asbestos during the removal of automobile exhaust systems (ca. 1945-1975) containing asbestos gaskets. A total of 16 pre-1974 vehicles with old or original exhaust systems were studied. Of the 16 vehicles, 12 contained asbestos gaskets in the exhaust system and two vehicles had asbestos lining inside the muffler. A total of 82 samples (23 personal, 38 bystander, and 21 indoor background) were analyzed by Phase Contrast Microscopy (PCM) and 88 samples (25 personal, 41 bystander, and 22 indoor background) by Transmission Electron Microscopy (TEM). Only seven of 25 worker samples analyzed by TEM detected asbestos fibers and 18 were below the analytical sensitivity limit (mean 0.013 f/cc, range 0.001-0.074 f/cc). Applying the ratio of asbestos fibers:total fibers (including non-asbestos) as determined by TEM to the PCM results showed an average (1 h) adjusted PCM worker exposure of 0.018 f/cc (0.002-0.04 f/cc). The average (1 h) adjusted PCM airborne concentration for bystanders was 0.008 f/cc (range 0.0008-0.015 f/cc). Assuming a mechanic can replace four automobile single exhaust systems in 1 workday, the estimated 8-h time-weighted average (TWA) for a mechanic performing this work was 0.01 f/cc. Under a scenario where a mechanic might repeatedly conduct exhaust work, these results suggest that exposures to asbestos from work with automobile exhaust systems during the 1950s through the 1970s containing asbestos gaskets were substantially below 0.1 f/cc, the current PEL for chrysotile asbestos, and quite often were not detectable.