Ground truth labels challenge the validity of sepsis consensus definitions in critical illness.

BACKGROUND: Sepsis is the leading cause of death in the intensive care unit (ICU). Expediting its diagnosis, largely determined by clinical assessment, improves survival. Predictive and explanatory modelling of sepsis in the critically ill commonly bases both outcome definition and predictions on clinical criteria for consensus definitions of sepsis, leading to circularity. As a remedy, we collected ground truth labels for sepsis. METHODS: In the Ground Truth for Sepsis Questionnaire (GTSQ), senior attending physicians in the ICU documented daily their opinion on each patient's condition regarding sepsis as a five-category working diagnosis and nine related items. Working diagnosis groups were described and compared and their SOFA-scores analyzed with a generalized linear mixed model. Agreement and discriminatory performance measures for clinical criteria of sepsis and GTSQ labels as reference class were derived. RESULTS: We analyzed 7291 questionnaires and 761 complete encounters from the first survey year. Editing rates for all items were > 90%, and responses were consistent with current understanding of critical illness pathophysiology, including sepsis pathogenesis. Interrater agreement for presence and absence of sepsis was almost perfect but only slight for suspected infection. ICU mortality was 19.5% in encounters with SIRS as the "worst" working diagnosis compared to 5.9% with sepsis and 5.9% with severe sepsis without differences in admission and maximum SOFA. Compared to sepsis, proportions of GTSQs with SIRS plus acute organ dysfunction were equal and macrocirculatory abnormalities higher (p < 0.0001). SIRS proportionally ranked above sepsis in daily assessment of illness severity (p < 0.0001). Separate analyses of neurosurgical referrals revealed similar differences. Discriminatory performance of Sepsis-1/2 and Sepsis-3 compared to GTSQ labels was similar with sensitivities around 70% and specificities 92%. Essentially no difference between the prevalence of SIRS and SOFA ≥ 2 yielded sensitivities and specificities for detecting sepsis onset close to 55% and 83%, respectively. CONCLUSIONS: GTSQ labels are a valid measure of sepsis in the ICU. They reveal suspicion of infection as an unclear clinical concept and refute an illness severity hierarchy in the SIRS-sepsis-severe sepsis spectrum. Ground truth challenges the accuracy of Sepsis-1/2 and Sepsis-3 in detecting sepsis onset. It is an indispensable intermediate step towards advancing diagnosis and therapy in the ICU and, potentially, other health care settings.

Pull-out forces of headless compression screws in variations of synthetic bone models imitating different types of scaphoid fractures in good bone quality.

Screw osteosynthesis using headless compression screws has become the accepted gold standard for the surgical treatment of scaphoid fractures. Optimal screw specifications remain controversially discussed. We aimed to investigate the influence of bone model composition on screw stability tests using headless compression screws in different scaphoid fracture models. We conducted pull-out tests using Acutrak2®mini, HCS®, HKS®, HBS®, Herbert/Whipple® and Twinfix® screws. To imitate cortical and cancellous bone, two-layer polyurethane (PU) models with two distinct densities were produced. The cylinders were cut at different positions to replicate fracture localisations at increasing distances. The maximum pull-out force required to achieve up to 1 mm of pull-out distance (Nto 1 mm) was measured. Acutrak2®mini and HCS® followed by Twinfix® showed the greatest average pull-out forces. Nto 1 mm was, on average, greater in the cortico-cancellous model than in the cancellous cylinder with the Acutrak2®mini and the Herbert/Whipple® screws, while it was the least with the HBS® and the Twinfix® screws; there were also differences between the HCS® and HKS®. There were no differences between the different fracture simulations in the synthesis strength using either the HKS® or HBS®. The pull-out forces of the HCS® and Twinfix® remained high also in simulations with the smaller screw base fragments. Varying imitations of cancellous and cortico-cancellous bone and fracture localisation reveal important information about the ex vivo strength of screw syntheses. The grip of the cortical structure should be used with the screws that fit more firmly in cortico-cancellous bone.

Is antibacterial treatment intensity lower in elderly patients? A retrospective cohort study in a German surgical intensive care unit.

BACKGROUND: Demographic change concurrent with medical progress leads to an increasing number of elderly patients in intensive care units (ICUs). Antibacterial treatment is an important, often life-saving, aspect of intensive care but burdened by the associated antimicrobial resistance risk. Elderly patients are simultaneously at greater risk of infections and may be more restrictively treated because, generally, treatment intensity declines with age. We therefore described utilization of antibacterials in ICU patients older and younger than 80 years and examined differences in the intensity of antibacterial therapy between both groups. METHODS: We analysed 17,464 valid admissions from the electronic patient data management system of our surgical ICU from April 2006 - October 2013. Antibacterial treatment rates were defined as days of treatment (exposed patient days) relative to patient days of ICU stay and calculated for old and young patients. Rates were compared in zero-inflated Poisson regression models adjusted for patients' sex, mean SAPS II- and TISS-scores, and calendar years yielding adjusted rate ratios (aRRs). Rate ratios exceeding 1 represent higher rates in old patients reflecting greater treatment intensity in old compared to younger patients. RESULTS: Observed antibacterial treatment rates were lower in patients 80 years and older compared to younger patients (30.97 and 39.73 exposed patient days per 100 patient days in the ICU, respectively). No difference in treatment intensity, however, was found from zero-inflated Poisson regression models permitting more adequate consideration of patient days with low treatment probability: for all antibacterials the adjusted rate ratio (aRR) was 1.02 (95%CI: 0.98-1.07). Treatment intensities were higher in elderly patients for penicillins (aRR 1.37 (95%CI: 1.26-1.48)), cephalosporins (aRR 1.20 (95%CI: 1.09-1.31)), carbapenems (aRR 1.35 (95%CI: 1.20-1.50)), fluoroquinolones (aRR 1.17 (95%CI: 1.05-1.30), and imidazoles (aRR 1.34 (95%CI: 1.23-1.46)). CONCLUSIONS: Elderly patients were generally less likely to be treated with antibacterials. This observation, however, did not persist in patients with comparable treatment probability. In these, antibacterial treatment intensity did not differ between younger and older ICU patients, for some antibacterial classes treatment intensity was even higher in the latter. Patient-level covariates are instrumental for a nuanced evaluation of age-effects in antibacterial treatment in the ICU.

Detection of inspiratory recruitment of atelectasis by automated lung sound analysis as compared to four-dimensional computed tomography in a porcine lung injury model.

BACKGROUND: Cyclic recruitment and de-recruitment of atelectasis (c-R/D) is a contributor to ventilator-induced lung injury (VILI). Bedside detection of this dynamic process could improve ventilator management. This study investigated the potential of automated lung sound analysis to detect c-R/D as compared to four-dimensional computed tomography (4DCT). METHODS: In ten piglets (25 ± 2 kg), acoustic measurements from 34 thoracic piezoelectric sensors (Meditron ASA, Norway) were performed, time synchronized to 4DCT scans, at positive end-expiratory pressures of 0, 5, 10, and 15 cmH2O during mechanical ventilation, before and after induction of c-R/D by surfactant washout. 4DCT was post-processed for within-breath variation in atelectatic volume (Δ atelectasis) as a measure of c-R/D. Sound waveforms were evaluated for: 1) dynamic crackle energy (dCE): filtered crackle sounds (600-700 Hz); 2) fast Fourier transform area (FFT area): spectral content above 500 Hz in frequency and above -70 dB in amplitude in proportion to the total amount of sound above -70 dB amplitude; and 3) dynamic spectral coherence (dSC): variation in acoustical homogeneity over time. Parameters were analyzed for global, nondependent, central, and dependent lung areas. RESULTS: In healthy lungs, negligible values of Δ atelectasis, dCE, and FFT area occurred. In lavage lung injury, the novel dCE parameter showed the best correlation to Δ atelectasis in dependent lung areas (R2 = 0.88) where c-R/D took place. dCE was superior to FFT area analysis for each lung region examined. The analysis of dSC could predict the lung regions where c-R/D originated. CONCLUSIONS: c-R/D is associated with the occurrence of fine crackle sounds as demonstrated by dCE analysis. Standardized computer-assisted analysis of dCE and dSC seems to be a promising method for depicting c-R/D.

The colonization with Candida species is more harmful in the second trimester of pregnancy.

PURPOSE: Vaginal colonization with Candida species (spp.) during pregnancy has been associated with impaired pregnancy outcomes. There is a reduction in spontaneous preterm birth among women with recurrent asymptomatic colonization of Candida who were treated with clotrimazole. This study aimed to evaluate the impact of the trimester of vulvovaginal colonization with Candida species. METHODS: Data from all women, who were tested positive for the vaginal colonization with Candida spp. during the first or second trimester of pregnancy, and who registered for a planned birth at our tertiary referral center between 2005 and 2014 were retrospectively analyzed. Their preterm birth rate served as the primary outcome variable. Secondary outcome variables were neonatal birthweight and Apgar score. RESULTS: Overall, 1066 women were eligible for the study. In 673 women (63%), who were diagnosed with Candida spp. during the first trimester of pregnancy, the rate of preterm birth was 10% (N = 64). In 393 women (37%), who were diagnosed with candidosis during the second trimester, the preterm birth rate was 18% (N = 71; p = 0.0002). Neonates of women, who presented with vulvovaginal candidosis during the first trimester, had a mean birthweight of 3243 g, compared to 2989 g in the group with a second trimester colonization (p < 0.0001). CONCLUSION: Women who are colonized with Candida spp. during the second trimester of pregnancy have higher rates of preterm birth and lower neonatal birthweight than those who are colonized during the first trimester of their pregnancy. Screening programs for asymptomatic Candida colonization should take this information into account.

Evaluation of the vaginal flora in pregnant women receiving opioid maintenance therapy: a matched case-control study.

BACKGROUND: Vaginal infections are a risk factor for preterm delivery. In this study, we sought to evaluate the vaginal flora of pregnant women receiving opioid maintenance therapy (OMT) in comparison to non-dependent, non-maintained controls. METHODS: A total of 3763 women with singleton pregnancies who underwent routine screening for asymptomatic vaginal infections between 10 + 0 and 16 + 0 gestational weeks were examined. Vaginal smears were Gram-stained, and microscopically evaluated for bacterial vaginosis, candidiasis, and trichomoniasis. In a retrospective manner, data of 132 women receiving OMT (cases) were matched for age, ethnicity, parity, education, previous preterm delivery, and smoking status to the data of 3631 controls. The vaginal flora at antenatal screening served as the primary outcome measure. Secondary outcome measures were gestational age and birth weight. RESULTS: In the OMT group, 62/132 (47 %) pregnant women received methadone, 39/132 (29.5 %) buprenorphine, and 31/132 (23.5 %) slow-release oral morphine. Normal or intermediate flora was found in 72/132 OMT women (54.5 %) and 2865/3631 controls [78.9 %; OR 0.49 (95 % CI, 0.33-0.71); p < 0.001]. Candidiasis occurred more frequently in OMT women than in controls [OR 2.11 (95 % CI, 1.26-3.27); p < 0.001]. Findings were inconclusive regarding bacterial vaginosis (± candidiasis) and trichomoniasis. Compared to infants of the control group, those of women with OMT had a lower mean birth weight [MD -165.3 g (95 % CI, -283.6 to -46.9); p = 0.006]. CONCLUSIONS: Pregnant women with OMT are at risk for asymptomatic vaginal infections. As recurrent candidiasis is associated with preterm delivery, the vulnerability of this patient population should lead to consequent antenatal infection screening at early gestation.

Acetylic Salicylic Acid for the Treatment of Chronic Obstructive Pulmonary Disease: A Randomized, Double-Blind, Placebo-Controlled Trial.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death in the world. Current treatment options provide relief from symptoms rather than stop disease progress. Results from various preclinical experiments suggest a causal benefit of acetylic salicylic acid (ASA) in the treatment of COPD. Hence, this study set out to examine the clinical benefit of ASA in the treatment of COPD. COPD patients (Global Initiative for Chronic Obstructive Lung Disease II-III) received either once daily 500 mg of ASA or a matching placebo for 12 weeks in addition to their preexisting medication. Clinical response in terms of pulmonary function testing, symptomatic response and adverse events were assessed. After 40 subjects were included, the study was stopped and an interim analysis was performed. The addition of ASA to the treatment of subjects with COPD had no effect on clinical features or spirometry (forced expiratory volume in 1 s: F = 0.49, d.f.1 = 1, d.f.2 = 74, p = 0.486) and non-pulmonary markers. COPD represents a complex of different diseases, although currently classified mainly by markers of lung function. If future trials test the effects of anti-inflammatory therapies, COPD subpopulations should be predefined based on inflammatory features.

Nonselective ß blockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis.

BACKGROUND & AIMS: Nonselective ß blockers (NSBBs) reduce portal pressure and the risk for variceal hemorrhage in patients with cirrhosis. However, development of spontaneous bacterial peritonitis (SBP) in these patients could preclude treatment with NSBBs because of their effects on the circulatory reserve. We investigated the effects of NSBBs in patients with cirrhosis and ascites with and without SBP. METHODS: We performed a retrospective analysis of data from 607 consecutive patients with cirrhosis who had their first paracentesis at the Medical University of Vienna from 2006 through 2011. Cox models were calculated to investigate the effect of NSBBs on transplant-free survival time and adjusted for Child-Pugh stage and presence of varices. RESULTS: NSBBs increased transplant-free survival in patients without SBP (hazard ratio = 0.75; 95% confidence interval: 0.581-0.968; P = .027) and reduced days of nonelective hospitalization (19.4 days/year for patients on NSBBs vs 23.9 days/year for patients not taking NSBBs). NSBBs had only moderate effects on systemic hemodynamics at patients' first paracentesis. However, at the first diagnosis of SBP, the proportion of hemodynamically compromised patients with systolic arterial pressure <100 mm Hg was higher among those who received NSBBs (38% vs 18% of those not taking NSBBs; P = .002), as was the proportion of patients with arterial pressure <82 mm Hg (64% of those taking NSBBs vs 44% of those not taking NSBBs; P = .006). Among patients with SBP, NSBBs reduced transplant-free survival (hazard ratio = 1.58; 95% confidence interval: 1.098-2.274; P = .014) and increased days of nonelective hospitalization (29.6 days/person-year in patients on NSBBs vs 23.7 days/person-year in those not taking NSBBs). A higher proportion of patients on NSBBs had hepatorenal syndrome (24% vs 11% in those not taking NSBBs; P = .027) and grade C acute kidney injury (20% vs 8% for those not taking NSBBs; P = .021). CONCLUSIONS: Among patients with cirrhosis and SBP, NSBBs increase the proportion who are hemodynamically compromised, time of hospitalization, and risks for hepatorenal syndrome and acute kidney injury. They also reduce transplant-free survival. Patients with cirrhosis and SBP should not receive NSBBs.

Influence of inspiration to expiration ratio on cyclic recruitment and derecruitment of atelectasis in a saline lavage model of acute respiratory distress syndrome.

OBJECTIVE: Cyclic recruitment and derecruitment of atelectasis can occur during mechanical ventilation, especially in injured lungs. Experimentally, cyclic recruitment and derecruitment can be quantified by respiration-dependent changes in PaO2 (ΔPaO2), reflecting the varying intrapulmonary shunt fraction within the respiratory cycle. This study investigated the effect of inspiration to expiration ratio upon ΔPaO2 and Horowitz index. DESIGN: Prospective randomized study. SETTING: Laboratory investigation. SUBJECTS: Piglets, average weight 30 ± 2 kg. INTERVENTIONS: At respiratory rate 6 breaths/min, end-inspiratory pressure (Pendinsp) 40 cm H2O, positive end-expiratory pressure 5 cm H2O, and FIO2 1.0, measurements were performed at randomly set inspiration to expiration ratios during baseline healthy and mild surfactant depletion injury. Lung damage was titrated by repetitive surfactant washout to induce maximal cyclic recruitment and derecruitment as measured by multifrequency phase fluorimetry. Regional ventilation distribution was evaluated by electrical impedance tomography. Step changes in airway pressure from 5 to 40 cm H2O and vice versa were performed after lavage to calculate PO2-based recruitment and derecruitment time constants (TAU). MEASUREMENTS AND MAIN RESULTS: In baseline healthy, cyclic recruitment and derecruitment could not be provoked, whereas in model acute respiratory distress syndrome, the highest ΔPaO2 were routinely detected at an inspiration to expiration ratio of 1:4 (range, 52-277 torr [6.9-36.9 kPa]). Shorter expiration time reduced cyclic recruitment and derecruitment significantly (158 ± 85 torr [21.1 ± 11.3 kPa] [inspiration to expiration ratio, 1:4]; 25 ± 12 torr [3.3 ± 1.6 kPa] [inspiration to expiration ratio, 4:1]; p < 0.0001), whereas the PaO2/FIO2 ratio increased (267 ± 50 [inspiration to expiration ratio, 1:4]; 424 ± 53 [inspiration to expiration ratio, 4:1]; p < 0.0001). Correspondingly, regional ventilation redistributed toward dependent lung regions (p < 0.0001). Recruitment was much faster (TAU: fast 1.6 s [78%]; slow 9.2 s) than derecruitment (TAU: fast 3.1 s [87%]; slow 17.7 s) (p = 0.0078). CONCLUSIONS: Inverse ratio ventilation minimizes cyclic recruitment and derecruitment of atelectasis in an experimental model of surfactant-depleted pigs. Time constants for recruitment and derecruitment, and regional ventilation distribution, reflect these findings and highlight the time dependency of cyclic recruitment and derecruitment.

Epidemiology of amyotrophic lateral sclerosis and effect of riluzole on disease course.

OBJECTIVES: To assess the epidemiology of ALS in Austria and to evaluate the long-term effect of riluzole treatment on survival. METHODS: Hospital discharge and riluzole prescription databases were used to identify ALS cases from January 2008 to June 2012. Using the capture-recapture method we evaluated the incidence and prevalence of ALS and patients' survival in dependence of age, gender and riluzole treatment. RESULTS: The corrected incidence and prevalence of ALS were 3.13/100,000 person-years (95% CI, 2.77 to 3.50) and 9.14/100,000 persons (95% CI, 8.53 to 9.79), respectively. Median survival from diagnosis was 676 days (95% CI, 591 to 761). A younger age at diagnosis was associated with a longer survival. Gender did not appear to affect survival time. Riluzole therapy was associated with a survival advantage only for the initial treatment period. The adjusted hazard ratio of mortality for using riluzole increased continually over time resulting in an apparent reversal of its beneficial effect after 6 months of therapy. CONCLUSIONS: We report incidence and prevalence estimates that are on the upper end of the wide range discussed in literature. Riluzole seems to exert a beneficial effect only in the first 6 months of therapy.

Effect of asymptomatic vaginal colonization with Candida albicans on pregnancy outcome.

INTRODUCTION: Vaginal infection is a major causative factor of preterm delivery. The present study was performed to evaluate the effect of asymptomatic vaginal colonization with Candida albicans at early gestation on pregnancy outcome. MATERIAL AND METHODS: From 2005 to 2014, a total of 8447 women with singleton pregnancies between 10(+0) and 16(+0) gestational weeks were routinely subjected to an antenatal infection screen-and-treat program. Vaginal smears were Gram-stained and microscopically evaluated, and data were retrospectively analyzed. Women exposed to Candida received clotrimazole and were re-tested after 4-6 weeks. Treatment was repeated in case of recurrence. Women with normal or intermediate vaginal flora were considered as non-exposed. Bacterial vaginosis and trichomoniasis were assessed and treated as well. Descriptive data analysis, chi-squared testing and multiple regression analysis with adjustment for potential confounders were performed. Rates of asymptomatic vaginal infections, preterm delivery and low birthweight served as the main outcomes measures. RESULTS: A normal or intermediate flora was found in 6708 (79.4%) of the screened women; 1142 women (13.5%) showed asymptomatic C. albicans infection. Of this group, 185 women (2.2%) had a recurrence of Candida on vaginal smears. Compared with the non-exposed women with normal or intermediate flora, those with recurrent candidiasis had higher rates of preterm delivery (11.9% vs. 9.5%) and of low birthweight (10.8% vs. 8.0%), as confirmed in the multiple model (p = 0.02). CONCLUSIONS: Recurrent asymptomatic vaginal colonization with Candida in early pregnancy is associated with preterm delivery and low birthweight. Routine screening and consequent treatment for candidiasis could improve pregnancy outcomes.

Routine Use of an Antenatal Infection Screen-and-Treat Program to Prevent Preterm Birth: Long-Term Experience at a Tertiary Referral Center.

BACKGROUND: Vaginal infection in early pregnancy is associated with preterm birth. This study evaluates long-term results after integrating an antenatal screen-and-treat program for asymptomatic vaginal infections into routine pregnancy care. METHODS: We retrospectively analyzed data of all women with singleton high-risk pregnancies delivering at our tertiary referral center between 2005 and 2014. The intervention group included women who presented for a prenatal visit for a planned birth between 10 + 0 and 16 + 0 gestational weeks. Women were routinely screened for asymptomatic infections using Gram stain. In cases of bacterial vaginosis, candidiasis or trichomoniasis, women were treated according to our clinical protocol. The control group included women who did not undergo the program. Prenatal care was equal in both groups. Preterm birth served as the primary outcome variable. RESULTS: Of the 20,052 women with singleton pregnancies, 8,490 (42.3%) participated in the antenatal prevention program. The mean gestational age at birth was 38.8 ± 2.6 weeks and 37.5 ± 4.3 weeks in the intervention and control groups, respectively (p < 0.001). The incidence of preterm birth was significantly lower in the intervention group than in the control group (9.7% vs 22.3%; p < 0.001). Low-birthweight neonates, stillbirths, and late miscarriages were less frequent in the intervention group (p < 0.001). CONCLUSIONS: Long-term results support the use of an antenatal infection screen-and-treat program to prevent preterm birth. If integrated into routine pregnancy care at a high-risk obstetrical setting, this simple public health intervention could lead to a significant reduction in preterm birth, low infant birthweight, and adverse pregnancy outcomes.

Migration background is associated with caries in Viennese school children, even if parents have received a higher education.

BACKGROUND: A low level of education and the migration background of parents are associated with the development of caries in children. The aim of this study was to evaluate whether a higher educational level of parents can overcome risks for the development of caries in immigrants in Vienna, Austria. METHODS: The educational level of the parents, the school type, and the caries status of 736 randomly selected twelve-year-old children with and without migration background was determined in this cross sectional study. In children attending school in Vienna the decayed, missing, and filled teeth (DMFT) index was determined. For statistical analysis, a mixed negative-binomial-model was used. RESULTS: The caries status of the children with migration background was significantly worse compared to that of the native Viennese population. A significant interaction was found between migration background and the educational level of the parents (p = 0.045). No interaction was found between the school type and either the migration background (p = 0.220) or the education level of the parents (p = 0.08). In parents with a higher scholarly education level, migration background (p < 0.01) and school type (p = 0.018) showed an association with DMFT values. In parents with a low education level, however, migration background and school type had no significant association with DMFT values. CONCLUSION: These data indicate that children with a migration background are at higher risk to acquire caries than other Viennese children, even when the parents have received a higher education.

Preload Responsiveness in Patients With Acute Respiratory Distress Syndrome Managed With Extracorporeal Membrane Oxygenation.

A restrictive fluid strategy is recommended in patients with acute respiratory distress syndrome (ARDS) managed with venovenous extracorporeal membrane oxygenation (VV ECMO). However, there are no established predictors for preload responsiveness in these patients. In 20 ARDS patients managed with VV ECMO, transesophageal echocardiography was used to repeatedly evaluate dynamic parameters of the left (velocity and stroke volume variation) and right ventricular outflow tract (velocity [respiratory variations of the maximal Doppler velocity in the truncus pulmonalis {ΔV max TP}] and velocity time integral [respiratory variation of the velocity time integral measured in the truncus pulmonalis {ΔVTI_TP}] variation in the truncus pulmonalis), the diameter variation in the superior and inferior vena cava and stroke volume variation measured by pulse contour analysis (SVV_PCA). Patients were categorized as responders and nonresponders according to an increase in stroke volume measured by echocardiography during a Passive Leg Raise Test with a cutoff value ≥10%. The final analysis includes 86 measurements. Predictive values for preload responsiveness were found for ΔV max TP (area under the curve [AUC] of 0.64), ΔVTI_TP (AUC 0.67), and SVV_PCA (AUC 0.74). In conclusion, SVV_PCA and, to a lesser extent, ΔV max TP and ΔVTI_TP are the most accurate parameters to predict preload responsiveness in ARDS patients managed with VV ECMO. Transesophageal echocardiography offers no advantages over pulse contour analysis for predicting preload responsiveness and provides only intermittent monitoring and assessment.

On the importance of tail ratios for psychological science.

Even small group-mean differences (whether combined with variance differences or not) or variance differences alone (absent mean differences) can generate marked and sometimes surprising imbalances in the representation of the respective groups compared in the distributional tail regions. Such imbalances in group representation, quantified as tail ratios, have general importance in the context of any threshold, susceptibility, diathesis-stress, selection, or similar models (including the study of sex differences), as widely conceptualized and applied in the psychological, social, medical, and biological sciences. However, commonly used effect-size measures, such as Cohen's d, largely exploit data information around the center of distributions, rather than from the tails, thereby missing potentially important patterns found in the tail regions. This account reviews the background and history of tail ratios, emphasizes their importance for psychological research, proposes a consensus approach for defining and interpreting them, introduces a tail-ratio calculator, and outlines future research agenda.

Surveillance program for former PCB-exposed workers of a transformer and capacitor recycling company, family members, employees of surrounding companies, and area residents--executive summary.

In a German company polychlorinated biphenyls (PCB)-containing transformers and capacitors were recycled on a large scale. Human biomonitoring revealed a high PCB body burden in workers of the recycling company, in surrounding locations of this plant, in companies in the neighborhood of this plant, and in family members of these employees. In order to clarify whether possible adverse health effects occurred or may occur in the future, a prospective surveillance program was initiated. After an extensive literature search, an interdisciplinary group of experts developed a surveillance program based on current knowledge with respect to possible adverse health effects that might occur in the recycling process of transformers and capacitors. Exposure to various hazardous substances (PCB, polychlorinated dibenzo-p-dioxins and dibenzo-furans [PCDD/F], metals, solvents) was considered. Criteria derived from human biomonitoring results of PCB were used for admission to the program. Participants in the surveillance program are first informed about risks and aims of the program. Subsequently, physicians started a detailed documentation of participants' general and occupational history, with their complaints, diseases, and nutritional habits, as well as information regarding their living areas, by means of a standardized questionnaire. In addition, separate examinations were performed to detect possible neurological, immunological, (neuro)psychological, hormonal, and skin effects. Moreover, DNA exposure as assessed by the comet assay and antioxidative status were determined. The program will be offered at yearly intervals for 3 years, and then at 5 and 10 years after program onset. Until now the program has proved to be feasible, and acceptance among workers and their families has been high. Based on the results, criteria will be developed to define adverse health effects that might be attributable to a hazardous substance exposure.

Maintaining oxygen delivery is crucial to prevent intestinal ischemia in critical ill patients.

BACKGROUND: Intestinal ischemia is a common complication with obscure pathophysiology in critically ill patients. Since insufficient delivery of oxygen is discussed, we investigated the influence of oxygen delivery, hemoglobin, arterial oxygen saturation, cardiac index and the systemic vascular resistance index on the development of intestinal ischemia. Furthermore, we evaluated the predictive power of elevated lactate levels for the diagnosis of intestinal ischemia. METHODS: In a retrospective case-control study data (mean oxygen delivery, minimum oxygen delivery, systemic vascular resistance index) of critical ill patients from 02/2009-07/2017 were analyzed using a proportional hazard model. General model fit and linearity were tested by likelihood ratio tests. The components of oxygen delivery (hemoglobin, arterial oxygen saturation and cardiac index) were individually tested in models. RESULTS: 59 out of 874 patients developed intestinal ischemia. A mean oxygen delivery less than 250ml/min/m2 (LRT vs. null model: p = 0.018; LRT for non-linearity: p = 0.012) as well as a minimum oxygen delivery less than 400ml/min/m2 (LRT vs null model: p = 0.016; LRT for linearity: p = 0.019) were associated with increased risk of the development of intestinal ischemia. We found no significant influence of hemoglobin, arterial oxygen saturation, cardiac index or systemic vascular resistance index. Receiver operating characteristics analysis for elevated lactate levels, pH, CO2 and central venous saturation was poor with an area under the receiver operating characteristic of 0.5324, 0.52, 0.6017 and 0.6786. CONCLUSION: There was a significant correlation for mean and minimum oxygen delivery with the incidence of intestinal ischemia for values below 250ml/min/m2 respectively 400ml/min/m2. Neither hemoglobin, arterial oxygen saturation, cardiac index, systemic vascular resistance index nor elevated lactate levels could be identified as individual risk factors.

Wrist movements induce torque and lever force in the scaphoid: an ex vivo study.

PURPOSE: We hypothesised that intercarpal K-wire fixation of adjacent carpal bones would reduce torque and lever force within a fractured scaphoid bone. METHODS: In eight cadaver wrists, a scaphoid osteotomy was stabilised using a locking nail, which also functioned as a sensor to measure isometric torque and lever forces between the fragments. The wrist was moved through 80% of full range of motion (ROM) to generate torque and force within the scaphoid. Testing was performed with and without loading of the wrist and K-wire stabilisation of the adjacent carpal bones. RESULTS: Average torque and lever force values were 49.6 ± 25.1 Nmm and 3.5 ± 0.9 N during extension and 41 ± 26.7 Nmm and 8.1 ± 2.8 N during flexion. Torque and lever force did not depend on scaphoid size, individual wrist ROM, or deviations of the sensor versus the anatomic axis. K-wire fixation did not produce significant changes in average torque and lever force values except with wrist radial abduction (P = 0.0485). Other than wrist extension, torque direction was not predictable. CONCLUSION: In unstable scaphoid fractures, we suggest securing rotational stability with selected implants for functional postoperative care. Wrist ROM within 20% extension and radial abduction to 50% flexion limit torque and lever force exacerbation between scaphoid fragments.

Impact of different consensus definition criteria on sepsis diagnosis in a cohort of critically ill patients-Insights from a new mathematical probabilistic approach to mortality-based validation of sepsis criteria.

BACKGROUND: Sepsis-3 definition uses SOFA score to discriminate sepsis from uncomplicated infection, replacing SIRS criteria that were criticized for being inaccurate. Eligibility of sepsis-3 criteria for sepsis diagnosis and the applied validation methodology using mortality as endpoint are topic of ongoing debate. We assessed the impact of different criteria on sepsis diagnosis in our ICU and devised a mathematical approach for mortality-based validation of sepsis criteria. As infectious status is often unclear at clinical deterioration, we integrated non-infected patients into analysis. METHODS: Suspected infection, SOFA and SIRS were captured for an ICU cohort of a university center over one year. For raw scores (SIRS/SOFA) and sepsis criteria (SIRS≥2/SOFA≥2/SOFA_change≥2) frequencies and associations with in-hospital mortality were assessed. Using a mathematical approach, we estimated the correlation between sepsis and in-hospital mortality serving as reference for evaluation of observed mortality correlations of sepsis criteria. RESULTS: Of 791 patients, 369 (47%) were infected and 422 (53%) non-infected, with an in-hospital mortality of 39% and 15%. SIRS≥2 indicated sepsis in 90% of infected patients, SOFA≥2 in 99% and SOFA_change≥2 in 77%. In non-infected patients, SIRS, SOFA and SOFA_change were ≥2 in 78%, 88% and 58%. In AUROC analyses neither SOFA nor SIRS displayed superior mortality discrimination in infected compared to non-infected patients. The mathematically estimated correlation of sepsis and in-hospital mortality was 0.10 in infected and 0 in non-infected patients. Among sepsis criteria, solely SIRS≥2 agreed with expected correlations in both subgroups (infected: r = 0.19; non-infected: r = 0.02). CONCLUSIONS: SOFA≥2 yielded a more liberal sepsis diagnosis than SIRS≥2. None of the criteria showed an infection specific occurrence that would be essential for reliable sepsis detection. However, SIRS≥2 matched the mortality association pattern of a valid sepsis criterion, whereas SOFA-based criteria did not. With this study, we establish a mathematical approach to mortality-based evaluation of sepsis criteria.

A quantitative CT parameter for the assessment of pulmonary oedema in patients with acute respiratory distress syndrome.

OBJECTIVES: The aim of this study was to establish quantitative CT (qCT) parameters for pathophysiological understanding and clinical use in patients with acute respiratory distress syndrome (ARDS). The most promising parameter is introduced. MATERIALS AND METHODS: 28 intubated patients with ARDS obtained a conventional CT scan in end-expiratory breathhold within the first 48 hours after admission to intensive care unit (ICU). Following manual segmentation, 137 volume- and lung weight-associated qCT parameters were correlated with 71 clinical parameters such as blood gases, applied ventilation pressures, pulse contour cardiac output measurements and established status and prognosis scores (SOFA, SAPS II). RESULTS: Of all examined qCT parameters, excess lung weight (ELW), i.e. the difference between a patient's current lung weight and the virtual lung weight of a healthy person at the same height, displayed the most significant results. ELW correlated significantly with the amount of inflated lung tissue [%] (p<0.0001; r = -0.66) and was closely associated with the amount of extravascular lung water (EVLW) (p<0.0001; r = 0.72). More substantially than the oxygenation index (PaO2/FiO2) or any other clinical parameter it correlated with the patients' mean SOFA- (p<0.0001, r = 0.69) and SAPS II-Score (p = 0.0005, r = 0.62). Patients who did not survive intensive care treatment displayed higher values of ELW in the initial CT scans. CONCLUSIONS: ELW could serve as a non-invasive method to quantify the amount of pulmonary oedema. It might serve as an early radiological marker of severity in patients with ARDS.