SwissScoring--a nationwide survey of SAPS II assessing practices and its accuracy.

OBJECTIVE The first description of the simplified acute physiology score (SAPS) II dates back to 1993, but little is known about its accuracy in daily practice. Our purpose was to evaluate the accuracy of scoring and the factors that affect it in a nationwide survey. METHODS Twenty clinical scenarios, covering a broad range of illness severities, were randomly assigned to a convenience sample of physicians or nurses in Swiss adult intensive care units (ICUs), who were asked to assess the SAPS II score for a single scenario. These data were compared to a reference that was defined by five experienced researchers. The results were cross-matched with demographic characteristics and data on the training and quality control for the scoring, structural and organisational properties of each participating ICU. RESULTS A total of 345 caregivers from 53 adult ICU providers completed the SAPS II evaluation of one clinical scenario. The mean SAPS II scoring was 42.6 ± 23.4, with a bias of +5.74 (95%CI 2.0-9.5) compared to the reference score. There was no evidence of bias variation according to the case severity, ICU size, linguistic area, profession (physician vs. nurse), experience, initial SAPS II training, or presence of a quality control system. CONCLUSION This nationwide survey revealed substantial variability in the SAPS II scoring results. On average, SAPS II scoring was overestimated by more than 13%, irrespective of the profession or experience of the scorer or of the structural characteristics of the ICUs.

Multivariable adjustments counteract spectrum and test review bias in accuracy studies

OBJECTIVES: The STAndards for Reporting studies of Diagnostic accuracy (STARD) for investigators and editors and the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) for reviewers and readers offer guidelines for the quality and reporting of test accuracy studies. These guidelines address and propose some solutions to two major threats to validity: spectrum bias and test review bias. STUDY DESIGN AND SETTING: Using a clinical example, we demonstrate that these solutions fail and propose an alternative solution that concomitantly addresses both sources of bias. We also derive formulas that prove the generality of our arguments. RESULTS: A logical extension of our ideas is to extend STARD item 23 by adding a requirement for multivariable statistical adjustment using information collected in QUADAS items 1, 2, and 12 and STARD items 3-5, 11, 15, and 18. CONCLUSION: We recommend reporting not only variation of diagnostic accuracy across subgroups (STARD item 23) but also the effects of the multivariable adjustments on test performance. We also suggest that the QUADAS be supplemented by an item addressing the appropriateness of statistical methods, in particular whether multivariable adjustments have been included in the analysis.

Automatic algorithm for monitoring systolic pressure variation and difference in pulse pressure

BACKGROUND: Difference in pulse pressure (dPP) reliably predicts fluid responsiveness in patients. We have developed a respiratory variation (RV) monitoring device (RV monitor), which continuously records both airway pressure and arterial blood pressure (ABP). We compared the RV monitor measurements with manual dPP measurements. METHODS: ABP and airway pressure (PAW) from 24 patients were recorded. Data were fed to the RV monitor to calculate dPP and systolic pressure variation in two different ways: (a) considering both ABP and PAW (RV algorithm) and (b) ABP only (RV(slim) algorithm). Additionally, ABP and PAW were recorded intraoperatively in 10-min intervals for later calculation of dPP by manual assessment. Interobserver variability was determined. Manual dPP assessments were used for comparison with automated measurements. To estimate the importance of the PAW signal, RV(slim) measurements were compared with RV measurements. RESULTS: For the 24 patients, 174 measurements (6-10 per patient) were recorded. Six observers assessed dPP manually in the first 8 patients (10-min interval, 53 measurements); no interobserver variability occurred using a computer-assisted method. Bland-Altman analysis showed acceptable bias and limits of agreement of the 2 automated methods compared with the manual method (RV: -0.33% +/- 8.72% and RV(slim): -1.74% +/- 7.97%). The difference between RV measurements and RV(slim) measurements is small (bias -1.05%, limits of agreement 5.67%). CONCLUSIONS: Measurements of the automated device are comparable with measurements obtained by human observers, who use a computer-assisted method. The importance of the PAW signal is questionable.

A test of genetic association among male nuptial coloration, female mating preference, and male aggression bias within a polymorphic population of cichlid fish

Both inter- and intrasexual selection have been implicated in the origin and maintenance of species-rich taxa with diverse sexual traits. Simultaneous disruptive selection by female mate choice and male-male competition can, in theory, lead to speciation without geographical isolation if both act on the same male trait. Female mate choice can generate discontinuities in gene flow, while male-male competition can generate negative frequency-dependent selection stabilizing the male trait polymorphism. Speciation may be facilitated when mating preference and/or aggression bias are physically linked to the trait they operate on. We tested for genetic associations among female mating preference, male aggression bias and male coloration in the Lake Victoria cichlid Pundamilia. We crossed females from a phenotypically variable population with males from both extreme ends of the phenotype distribution in the same population (blue or red). Male offspring of a red sire were significantly redder than males of a blue sire, indicating that intra-population variation in male coloration is heritable. We tested mating preferences of female offspring and aggression biases of male offspring using binary choice tests. There was no evidence for associations at the family level between female mating preferences and coloration of sires, but dam identity had a significant effect on female mate preference. Sons of the red sire directed significantly more aggression to red than blue males, whereas sons of the blue sire did not show any bias. There was a positive correlation among individuals between male aggression bias and body coloration, possibly due to pleiotropy or physical linkage, which could facilitate the maintenance of color polymorphism.

Effects of study precision and risk of bias in networks of interventions: a network meta-epidemiological study

BACKGROUND Empirical research has illustrated an association between study size and relative treatment effects, but conclusions have been inconsistent about the association of study size with the risk of bias items. Small studies give generally imprecisely estimated treatment effects, and study variance can serve as a surrogate for study size. METHODS We conducted a network meta-epidemiological study analyzing 32 networks including 613 randomized controlled trials, and used Bayesian network meta-analysis and meta-regression models to evaluate the impact of trial characteristics and study variance on the results of network meta-analysis. We examined changes in relative effects and between-studies variation in network meta-regression models as a function of the variance of the observed effect size and indicators for the adequacy of each risk of bias item. Adjustment was performed both within and across networks, allowing for between-networks variability. RESULTS Imprecise studies with large variances tended to exaggerate the effects of the active or new intervention in the majority of networks, with a ratio of odds ratios of 1.83 (95% CI: 1.09,3.32). Inappropriate or unclear conduct of random sequence generation and allocation concealment, as well as lack of blinding of patients and outcome assessors, did not materially impact on the summary results. Imprecise studies also appeared to be more prone to inadequate conduct. CONCLUSIONS Compared to more precise studies, studies with large variance may give substantially different answers that alter the results of network meta-analyses for dichotomous outcomes.

8p23 beta-defensin copy number determination by single-locus pseudogene-based paralog ratio tests risk bias due to low-frequency sequence variations.

BACKGROUND The copy number variation (CNV) in beta-defensin genes (DEFB) on human chromosome 8p23 has been proposed to contribute to the phenotypic differences in inflammatory diseases. However, determination of exact DEFB CN is a major challenge in association studies. Quantitative real-time PCR (qPCR), paralog ratio tests (PRT) and multiplex ligation-dependent probe amplification (MLPA) have been extensively used to determine DEFB CN in different laboratories, but inter-method inconsistencies were observed frequently. In this study we asked which one is superior among the three methods for DEFB CN determination. RESULTS We developed a clustering approach for MLPA and PRT to statistically correlate data from a single experiment. Then we compared qPCR, a newly designed PRT and MLPA for DEFB CN determination in 285 DNA samples. We found MLPA had the best convergence and clustering results of the raw data and the highest call rate. In addition, the concordance rates between MLPA or PRT and qPCR (32.12% and 37.99%, respectively) were unacceptably low with underestimated CN by qPCR. Concordance rate between MLPA and PRT (90.52%) was high but PRT systematically underestimated CN by one in a subset of samples. In these samples a sequence variant which caused complete PCR dropout of the respective DEFB cluster copies was found in one primer binding site of one of the targeted paralogous pseudogenes. CONCLUSION MLPA is superior to PRT and even more to qPCR for DEFB CN determination. Although the applied PRT provides in most cases reliable results, such a test is particularly sensitive to low-frequency sequence variations preferably accumulating in loci like pseudogenes which are most likely not under selective pressure. In the light of the superior performance of multiplex assays, the drawbacks of such single PRTs could be overcome by combining more test markers.

Controlling for culture-specific response bias using ipsatization and response style indicators: Family orientation in seventeen cultures and two generations

Within-subject standardization (ipsatization) has been advocated as a possible means to control for culture-specific responding (e.g., Fisher, 2004). However, the consequences of different kinds of ipsatization procedures for the interpretation of mean differences remain unclear. The current study compared several ipsatization procedures with ANCOVA-style procedures using response style indicators for the construct of family orientation with data from 14 cultures and two generations from the Value-of-Children-(VOC)-Study (4135 dyads). Results showed that within-subject centering/standardizing across all Likert-scale items of the comprehensive VOC-questionnaire removed most of the original cross-cultural variation in family orientation and lead to a non-interpretable pattern of means in both generations. Within-subject centering/standardizing using a subset of 19 unrelated items lead to a decrease to about half of the original effect size and produced a theoretically meaningful pattern of means. A similar effect size and similar mean differences were obtained when using a measure of acquiescent responding based on the same set of items in an ANCOVA-style analysis. Additional models controlling for extremity and modesty performed worse, and combinations did not differ from the acquiescence-only model. The usefulness of different approaches to control for uniform response styles (scalar equivalence not given) in cross- cultural comparisons is discussed.

Effects of stereotypic behaviour and chronic mild stress on judgement bias in laboratory mice

Cognitive processes are influenced by underlying affective states, and tests of cognitive bias have recently been developed to assess the valence of affective states in animals. These tests are based on the fact that individuals in a negative affective state interpret ambiguous stimuli more pessimistically than individuals in a more positive state. Using two strains of mice we explored whether unpredictable chronic mild stress (UCMS) can induce a negative judgement bias and whether variation in the expression of stereotypic behaviour is associated with variation in judgement bias. Sixteen female CD-1 and 16 female C57BL/6 mice were trained on a tactile conditional discrimination test with grade of sandpaper as a cue for differential food rewards. Once they had learned the discrimination, half of the mice were subjected to UCMS for three weeks to induce a negative affective state. Although UCMS induced a reduced preference for the higher value reward in the judgement bias test, it did not affect saccharine preference or hypothalamic–pituitary–adrenal (HPA) activity. However, UCMS affected responses to ambiguous (intermediate) cues in the judgement bias test. While control mice showed a graded response to ambiguous cues, UCMS mice of both strains did not discriminate between ambiguous cues and tended to show shorter latencies to the ambiguous cues and the negative reference cue. UCMS also increased bar-mouthing in CD-1, but not in C57BL/6 mice. Furthermore, mice with higher levels of stereotypic behaviour made more optimistic choices in the judgement bias test. However, no such relationship was found for stereotypic bar-mouthing, highlighting the importance of investigating different types of stereotypic behaviour separately.