Bloodstream infections in pediatric ECLS: usefulness of daily blood culture monitoring and predictive value of biological markers. The British Columbia experience

INTRODUCTION: The incidence of bloodstream infection (BSI) in extracorporeal life support (ECLS) is reported between 0.9 and 19.5%. In January 2006, the Extracorporeal Life Support Organization (ELSO) reported an overall incidence of 8.78% distributed as follows: respiratory: 6.5% (neonatal), 20.8% (pediatric); cardiac: 8.2% (neonatal) and 12.6% (pediatric). METHOD: At BC Children's Hospital (BCCH) daily surveillance blood cultures (BC) are performed and antibiotic prophylaxis is not routinely recommended. Positive BC (BC+) were reviewed, including resistance profiles, collection time of BC+, time to positivity and mortality. White blood cell count, absolute neutrophile count, immature/total ratio, platelet count, fibrinogen and lactate were analyzed 48, 24 and 0 h prior to BSI. A univariate linear regression analysis was performed. RESULTS: From 1999 to 2005, 89 patients underwent ECLS. After exclusion, 84 patients were reviewed. The attack rate was 22.6% (19 BSI) and 13.1% after exclusion of coagulase-negative staphylococci (n = 8). BSI patients were significantly longer on ECLS (157 h) compared to the no-BSI group (127 h, 95% CI: 106-148). Six BSI patients died on ECLS (35%; 4 congenital diaphragmatic hernias, 1 hypoplastic left heart syndrome and 1 after a tetralogy repair). BCCH survival on ECLS was 71 and 58% at discharge, which is comparable to previous reports. No patient died primarily because of BSI. No BSI predictor was identified, although lactate may show a decreasing trend before BSI (P = 0.102). CONCLUSION: Compared with ELSO, the studied BSI incidence was higher with a comparable mortality. We speculate that our BSI rate is explained by underreporting of "contaminants" in the literature, the use of broad-spectrum antibiotic prophylaxis and a higher yield with daily monitoring BC. We support daily surveillance blood cultures as an alternative to antibiotic prophylaxis in the management of patients on ECLS.

Differences across health care systems in outcome and cost-utility of surgical and conservative treatment of chronic low back pain: a study protocol

BACKGROUND: There is little evidence on differences across health care systems in choice and outcome of the treatment of chronic low back pain (CLBP) with spinal surgery and conservative treatment as the main options. At least six randomised controlled trials comparing these two options have been performed; they show conflicting results without clear-cut evidence for superior effectiveness of any of the evaluated interventions and could not address whether treatment effect varied across patient subgroups. Cost-utility analyses display inconsistent results when comparing surgical and conservative treatment of CLBP. Due to its higher feasibility, we chose to conduct a prospective observational cohort study. METHODS: This study aims to examine if1. Differences across health care systems result in different treatment outcomes of surgical and conservative treatment of CLBP2. Patient characteristics (work-related, psychological factors, etc.) and co-interventions (physiotherapy, cognitive behavioural therapy, return-to-work programs, etc.) modify the outcome of treatment for CLBP3. Cost-utility in terms of quality-adjusted life years differs between surgical and conservative treatment of CLBP.This study will recruit 1000 patients from orthopaedic spine units, rehabilitation centres, and pain clinics in Switzerland and New Zealand. Effectiveness will be measured by the Oswestry Disability Index (ODI) at baseline and after six months. The change in ODI will be the primary endpoint of this study.Multiple linear regression models will be used, with the change in ODI from baseline to six months as the dependent variable and the type of health care system, type of treatment, patient characteristics, and co-interventions as independent variables. Interactions will be incorporated between type of treatment and different co-interventions and patient characteristics. Cost-utility will be measured with an index based on EQol-5D in combination with cost data. CONCLUSION: This study will provide evidence if differences across health care systems in the outcome of treatment of CLBP exist. It will classify patients with CLBP into different clinical subgroups and help to identify specific target groups who might benefit from specific surgical or conservative interventions. Furthermore, cost-utility differences will be identified for different groups of patients with CLBP. Main results of this study should be replicated in future studies on CLBP.

Interrelation of peri-operative morbidity and ASA class assignment in patients undergoing gynaecological surgery

OBJECTIVE: The aim of this study was to estimate intra- and post-operative risk using the American Society of Anaesthesiologists (ASA) classification which is an important predictor of an intervention and of the entire operating programme. STUDY DESIGN: In this retrospective study, 4435 consecutive patients undergoing elective and emergency surgery at the Gynaecological Clinic of the University Hospital of Zurich were included. The ASA classification for pre-operative risk assessment was determined by an anaesthesiologist after a thorough physical examination. We observed several pre-, intra- and post-operative parameters, such as age, body-mass-index, duration of anaesthesia, duration of surgery, blood loss, duration of post-operative stay, complicated post-operative course, morbidity and mortality. The investigation of different risk factors was achieved by a multiple linear regression model for log-transformed duration of hospitalisation. RESULTS: Age and obesity were responsible for a higher ASA classification. ASA grade correlates with the duration of anaesthesia and the duration of the surgery itself. There was a significant difference in blood loss between ASA grades I (113+/-195 ml) and III (222+/-470 ml) and between classes II (176+/-432 ml) and III. The duration of post-operative hospitalisation could also be correlated with ASA class. ASA class I=1.7+/-3.0 days, ASA class II=3.6+/-4.3 days, ASA class III=6.8+/-8.2 days, and ASA class IV=6.2+/-3.9 days. The mean post-operative in-hospital stay was 2.5+/-4.0 days without complications, and 8.7+/-6.7 days with post-operative complications. Multiple linear regression model showed that not only the ASA classification contained an important information for the duration of hospitalisation. Parameters such as age, class of diagnosis, post-operative complications, etc. also have an influence on the duration of hospitalisation. CONCLUSION: This study shows that the ASA classification can be used as a good and early available predictor for the planning of an intervention in gynaecological surgery. The ASA classification helps the surgeon to assess the peri-operative risk profile of which important information can be derived for the planning of the operation programme.

Increased risk of hepatocellular carcinoma among patients with hepatitis C cirrhosis and diabetes mellitus

Recent studies suggest that diabetes mellitus increases the risk of developing hepatocellular carcinoma (HCC). The aim of this study is to quantify the risk of HCC among patients with both diabetes mellitus and hepatitis C in a large cohort of patients with chronic hepatitis C and advanced fibrosis. We included 541 patients of whom 85 (16%) had diabetes mellitus. The median age at inclusion was 50 years. The prevalence of diabetes mellitus was 10.5% for patients with Ishak fibrosis score 4, 12.5% for Ishak score 5, and 19.1% for Ishak score 6. Multiple logistic regression analysis showed an increased risk of diabetes mellitus for patients with an elevated body mass index (BMI) (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.00-1.11; P = 0.060) and a decreased risk of diabetes mellitus for patients with higher serum albumin levels (OR, 0.81; 95% CI, 0.63-1.04; P = 0.095). During a median follow-up of 4.0 years (interquartile range, 2.0-6.7), 11 patients (13%) with diabetes mellitus versus 27 patients (5.9%) without diabetes mellitus developed HCC, the 5-year occurrence of HCC being 11.4% (95% CI, 3.0-19.8) and 5.0% (95% CI, 2.2-7.8), respectively (P = 0.013). Multivariate Cox regression analysis of patients with Ishak 6 cirrhosis showed that diabetes mellitus was independently associated with the development of HCC (hazard ratio, 3.28; 95% CI, 1.35-7.97; P = 0.009). CONCLUSION: For patients with chronic hepatitis C and advanced cirrhosis, diabetes mellitus increases the risk of developing HCC.

Metabolic predictors of inflammation, adhesion, and coagulability in healthy younger-aged adults

Elevated levels of inflammatory biomarkers are associated with the pathophysiology of cardiovascular diseases and are predictors of cardiovascular events. The objective of this study was to determine the unique contributions of metabolic factors as predictors of inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)), adhesion (soluble intercellular adhesion molecule-1 (sICAM-1)), and coagulation (D-dimer) in healthy younger-aged adults. Participants were 83 women and 92 men (mean age 30.04 years, s.d. +/- 4.8, range 22-39) of normal weight to moderate obese weight (mean BMI 24.4 kg/m(2), s.d. +/- 3.35, range 17-32). The primary data analytical approaches included Pearson correlation and multiple linear regression. Circulating levels of CRP, IL-6, sICAM-1, and D-dimer were determined in plasma. Higher levels of CRP were independently associated with higher BMI, a greater waist-to-hip ratio, female gender, and higher triglycerides (P < 0.001). Higher IL-6 levels were independently associated with a greater waist-to-hip ratio (P < 0.01). Higher levels of sICAM-1 were independently associated with higher BMI, higher triglycerides, and lower insulin resistance (P < 0.001). Higher D-dimer levels were independently associated with higher BMI and being female (P < 0.001). Having a higher BMI was most consistently associated with elevated biomarkers of inflammation, adhesion, and coagulation in this sample of healthy younger-aged adults, although female gender, insulin resistance, and lipid levels were also related to the biomarkers. The findings provide insight into the adverse cardiovascular risk associated with elevated body weight in younger adults.

Effect of vascular targeting agent in rat tumor model: dynamic contrast-enhanced versus diffusion-weighted MR imaging

PURPOSE: To compare dynamic contrast material-enhanced magnetic resonance (MR) imaging and diffusion-weighted MR imaging for noninvasive evaluation of early and late effects of a vascular targeting agent in a rat tumor model. MATERIALS AND METHODS: The study protocol was approved by the local ethics committee for animal care and use. Thirteen rats with one rhabdomyosarcoma in each flank (26 tumors) underwent dynamic contrast-enhanced imaging and diffusion-weighted echo-planar imaging in a 1.5-T MR unit before intraperitoneal injection of combretastatin A4 phosphate and at early (1 and 6 hours) and later (2 and 9 days) follow-up examinations after the injection. Histopathologic examination was performed at each time point. The apparent diffusion coefficient (ADC) of each tumor was calculated separately on the basis of diffusion-weighted images obtained with low b gradient values (ADC(low); b = 0, 50, and 100 sec/mm(2)) and high b gradient values (ADC(high); b = 500, 750, and 1000 sec/mm(2)). The difference between ADC(low) and ADC(high) was used as a surrogate measure of tissue perfusion (ADC(low) - ADC(high) = ADC(perf)). From the dynamic contrast-enhanced MR images, the volume transfer constant k and the initial slope of the contrast enhancement-time curve were calculated. For statistical analyses, a paired two-tailed Student t test and linear regression analysis were used. RESULTS: Early after administration of combretastatin, all perfusion-related parameters (k, initial slope, and ADC(perf)) decreased significantly (P < .001); at 9 days after combretastatin administration, they increased significantly (P < .001). Changes in ADC(perf) were correlated with changes in k (R(2) = 0.46, P < .001) and the initial slope (R(2) = 0.67, P < .001). CONCLUSION: Both dynamic contrast-enhanced MR imaging and diffusion-weighted MR imaging allow monitoring of perfusion changes induced by vascular targeting agents in tumors. Diffusion-weighted imaging provides additional information about intratumoral cell viability versus necrosis after administration of combretastatin.

Oscillometric measurement of ankle-brachial index in patients with suspected peripheral disease: comparison with Doppler method

QUESTION UNDER STUDY: Purpose was to validate accuracy and reliability of automated oscillometric ankle-brachial (ABI) measurement prospectively against the current gold standard of Doppler-assisted ABI determination. METHODS: Oscillometric ABI was measured in 50 consecutive patients with peripheral arterial disease (n = 100 limbs, mean age 65 +/- 6 years, 31 men, 19 diabetics) after both high and low ABI had been determined conventionally by Doppler under standardised conditions. Correlation was assessed by linear regression and Pearson product moment correlation. Degree of inter-modality agreement was quantified by use of Bland and Altman method. RESULTS: Oscillometry was performed significantly faster than Doppler-assisted ABI (3.9 +/- 1.3 vs 11.4 +/- 3.8 minutes, P <0.001). Mean readings were 0.62 +/- 0.25, 0.70 +/- 0.22 and 0.63 +/- 0.39 for low, high and oscillometric ABI, respectively. Correlation between oscillometry and Doppler ABI was good overall (r = 0.76 for both low and high ABI) and excellent in oligo-symptomatic, non-diabetic patients (r = 0.81; 0.07 +/- 0.23); it was, however, limited in diabetic patients and in patients with critical limb ischaemia. In general, oscillometric ABI readings were slightly higher (+0.06), but linear regression analysis showed that correlation was sustained over the whole range of measurements. CONCLUSIONS: Results of automated oscillometric ABI determination correlated well with Doppler-assisted measurements and could be obtained in shorter time. Agreement was particularly high in oligo-symptomatic non-diabetic patients.

Renal resistance index in renal allograft recipients: a role for ADMA

BACKGROUND: Renal resistance index, a predictor of kidney allograft function and patient survival, seems to depend on renal and peripheral vascular compliance and resistance. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and therefore influences vascular resistance. STUDY DESIGN: We investigated the relationship between renal resistance index, ADMA, and risk factors for cardiovascular diseases and kidney function in a cross-sectional study. SETTING ; PARTICIPANTS: 200 stable renal allograft recipients (133 men and 67 women with a mean age of 52.8 years). PREDICTORS: Serum ADMA concentration, pulse pressure, estimated glomerular filtration rate and recipient age. OUTCOME: Renal resistance index. MEASUREMENTS: Renal resistance index measured by color-coded duplex ultrasound, serum ADMA concentration measured by liquid chromatography-tandem mass spectrometry, estimated glomerular filtration rate (Nankivell equation), arterial stiffness measured by digital volume pulse, Framingham and other cardiovascular risk factors, and evaluation of concomitant antihypertensive and immunosuppressive medication. RESULTS: Mean serum ADMA concentration was 0.72 +/- 0.21 (+/-SD) micromol/L and mean renal resistance index was 0.71 +/- 0.07. Multiple stepwise regression analysis showed that recipient age (P < 0.001), pulse pressure (P < 0.001), diabetes (P < 0.01) and ADMA concentration (P < 0.01) were independently associated with resistance index. ADMA concentrations were correlated with estimated glomerular filtration rate (P < 0.01). LIMITATIONS: The cross-sectional nature of this study precludes cause-effect conclusions. CONCLUSIONS: In addition to established cardiovascular risk factors, ADMA appears to be a relevant determinant of renal resistance index and allograft function and deserves consideration in prospective outcome trials in renal transplantation.

Relationship between inflammation and cognitive function in obstructive sleep apnea

OBJECTIVES: Obstructive sleep apnea (OSA) can have adverse effects on cognitive functioning, mood, and cardiovascular functioning. OSA brings with it disturbances in sleep architecture, oxygenation, sympathetic nervous system function, and inflammatory processes. It is not clear which of these mechanisms is linked to the decrease in cognitive functioning. This study examined the effect of inflammatory parameters on cognitive dysfunction. MATERIALS AND METHODS: Thirty-nine patients with untreated sleep apnea were evaluated by polysomnography and completed a battery of neuropsychological tests. After the first night of evaluation in the sleep laboratory, blood samples were taken for analysis of interleukin 6, tumor necrosis factor-alpha (TNF-alpha), and soluble TNF receptor 1 (sTNF-R1). RESULTS: sTNF-R1 significantly correlated with cognitive dysfunction. In hierarchical linear regression analysis, measures of obstructive sleep apnea severity explained 5.5% of the variance in cognitive dysfunction (n.s.). After including sTNF-R1, percentage of variance explained by the full model increased more than threefold to 19.6% (F = 2.84, df = 3, 36, p = 0.05). Only sTNF-R1 had a significant individual relationship with cognitive dysfunction (beta = 0.376 t = 2.48, p = 0.02). CONCLUSIONS: sTNF-R1 as a marker of chronic inflammation may be associated with diminished neuropsychological functioning in patients with OSA.

Modern sea surface productivity and temperature estimations off Chile as detected by coccolith accumulation rates

Recent coccoliths from 74 surface sediment samples recovered from the southeastern Pacific off Chile were examined quantitatively to investigate modern regional gradients of sea surface productivity and temperature. All findings are based on coccolith accumulation rates. Therefore an approach was designed to estimate recent sedimentation rates based on 210Pb and bulk chemistry analyses of the same set of surface samples. Highest total coccolith accumulation rates were found off north-central Chile, where seasonal upwelling takes place. Based on a multiple linear regression between calculated coccolith accumulation rates and World Ocean Atlas derived sea surface temperatures, a calibration model to reconstruct annual average temperatures of the uppermost 75 m of the water column is provided. The model was cross-validated and the SST estimates were compared with SST observed and SST estimates based on diatoms and planktonic foraminifera, showing a good correlation.

Predictors of depressed mood 12 months after injury. Contribution of self-efficacy and social support

Abstract Purpose: There is evidence that depressed mood and perception of pain are related in patients with chronic illness. However, how individual resources such as self-efficacy and social support play a role in this association remains unclear. The aim of this study was to investigate the influence of both variables as either moderator or mediator. Method: In a longitudinal study, 274 injured workers (M = 43.24 years) were investigated. Data were collected on sociodemographics, depressed mood, pain, social support, and self-efficacy at three months post-injury, and depressed mood one year post-injury. Results: Hierarchical multiple linear regression analyses revealed that pain (β = 0.14; p < 0.01) and social support (β = -0.18; p < 0.001) were significant predictors of depressed mood. Self-efficacy moderated the relationship of pain (β = -0.12; p < 0.05) and depressed mood after one year. Lower self-efficacy in combination with pain had a stronger impact than higher self-efficacy and pain on depressed mood. Social support did not moderate the association. Conclusions: Self-efficacy for managing pain is important in the development of depressed mood. According to the results of this study, we suggest that the detection of low social support and low self-efficacy might be important in long-term rehabilitation process. Implications for Rehabilitation Risk for depressed mood one year after an accident is high: One in five workers report depressed mood. Protective factors for depressed mood in injured workers needs to be considered in the rehabilitation. Focusing on resources like social support and self-efficacy could be protective against depressed mood. The early detection of low social support and low self-efficacy might be important in long-term rehabilitation processes

Effects of weight on blood pressure at rest and during exercise.

Body weight (BW) and blood pressure (BP) have a close relationship, which has been accounted for by hormonal changes. No previous study has evaluated the effect of wearing an external weight vest on BP to determine whether there is a simple mechanism between BW and BP. Seventeen healthy volunteers underwent weight reduction (WR) through caloric restriction. Before and after WR, BW, body fat percentage and BP at rest and during exercise were measured. Before and after WR, exercise testing was performed twice with the random allocation of a weight vest (10 kg) during one of the tests. Linear regression was used to detect independent associations between BP and the weight vest, BW and body fat percentage. BW decreased from 89.4 ± 15.4 kg to 79.1 ± 14.0 kg following WR (P<0.001). WR led to significant decreases in BP at rest (from 130.0/85.9 mm Hg to 112.5/77.8 mm Hg, P<0.001 for systolic and diastolic BPs) and during exercise. The weight vest significantly increased BP at rest (to 136.1/90.7 mm Hg before and 125.8/84.6 mm Hg after WR) and during exercise. Linear regression analysis identified an independent association between the weight vest and BP (P=0.006 for systolic BP and P=0.009 for diastolic BP at rest). This study demonstrates that wearing an external weight vest has immediate effects on BP at rest and during exercise independent of BW or body fat. More research is needed to understand the physiological mechanisms between weight and BP.

Comparison of pain-resilient working individuals to population-based case controls with/without momentary low back pain

Background: Few studies have examined the 20% of individuals who never experience an episode of low back pain (LBP). To date, no investigation has been undertaken that examines a group who claim to have never experienced LBP in their lifetime in comparison to two population-based case–control groups with and without momentary LBP. This study investigates whether LBP-resilient workers between 50 and 65 years had better general health, demonstrated more positive health behaviour and were better able to achieve routine activities compared with both case–control groups. Methods: Forty-two LBP-resilient participants completed the same pain assessment questionnaire as a population-based LBP sample from a nationwide, large-scale cross-sectional survey in Switzerland. The LBP-resilient participants were pairwise compared to the propensity score-matched case controls by exploring differences in demographic and work characteristics, and by calculating odds ratios (ORs) and effect sizes. A discriminant analysis explored group differences, while the multiple logistic regression analysis specified single indicators which accounted for group differences. Results: LBP-resilient participants were healthier than the case controls with momentary LBP and achieved routine activities more easily. Compared to controls without momentary LBP, LBP-resilient participants had a higher vitality, a lower workload, a healthier attitude towards health and behaved more healthily by drinking less alcohol. Conclusions: By demonstrating a difference between LBP-resilient participants and controls without momentary LBP, the question that arises is what additional knowledge can be attained. Three underlying traits seem to be relevant about LBP-resilient participants: personality, favourable work conditions and subjective attitudes/attributions towards health. These rationales have to be considered with respect to LBP prevention.

Reference Values and Factors Associated With Renal Resistive Index in a Family-Based Population Study

Increased renal resistive index (RRI) has been recently associated with target organ damage and cardiovascular or renal outcomes in patients with hypertension and diabetes mellitus. However, reference values in the general population and information on familial aggregation are largely lacking. We determined the distribution of RRI, associated factors, and heritability in a population-based study. Families of European ancestry were randomly selected in 3 Swiss cities. Anthropometric parameters and cardiovascular risk factors were assessed. A renal Doppler ultrasound was performed, and RRI was measured in 3 segmental arteries of both kidneys. We used multilevel linear regression analysis to explore the factors associated with RRI, adjusting for center and family relationships. Sex-specific reference values for RRI were generated according to age. Heritability was estimated by variance components using the ASSOC program (SAGE software). Four hundred women (mean age±SD, 44.9±16.7 years) and 326 men (42.1±16.8 years) with normal renal ultrasound had mean RRI of 0.64±0.05 and 0.62±0.05, respectively (P<0.001). In multivariable analyses, RRI was positively associated with female sex, age, systolic blood pressure, and body mass index. We observed an inverse correlation with diastolic blood pressure and heart rate. Age had a nonlinear association with RRI. We found no independent association of RRI with diabetes mellitus, hypertension treatment, smoking, cholesterol levels, or estimated glomerular filtration rate. The adjusted heritability estimate was 42±8% (P<0.001). In a population-based sample with normal renal ultrasound, RRI normal values depend on sex, age, blood pressure, heart rate, and body mass index. The significant heritability of RRI suggests that genes influence this phenotype.

Quantification of pleural effusion from single area measurements on CT

The objective of this study was to determine if area measurements of pleural fluid on computed tomography (CT) reflect the actual pleural fluid volume (PEvol) as measured at autopsy, to establish a formula to estimate the volume of pleural effusion (PEest), and to test the accuracy and observer reliability of PEest.132 human cadavers, with pleural effusion were divided into phase 1 (n = 32) and phase 2 (n = 100). In phase 1, PEvol was compared to area measurements on axial (axA), sagittal (sagA), and coronal (corA) CT images. Linear regression analysis was used to create a formula to calculate PEest. In phase 2, intra-class correlation (ICC) was used to assess inter-reader reliability and determine the agreement between PEest and PEvol. PEvol correlated to a higher degree to axA (r s mean = 0.738; p < 0.001) than to sagA (r s mean = 0.679, p < 0.001) and corA (r s mean = 0.709; p < 0.001). PEest can be established with the following formula: axA × 0.1 = PEest. Mean difference between PEest and PEvol was less than 40 mL (ICC = 0.837-0.874; p < 0.001). Inter-reader reliability was higher between two experienced readers (ICC = 0.984-0.987; p < 0.001) than between an inexperienced reader and both experienced readers (ICC = 0.660-0.698; p < 0.001). Pleural effusions may be quantified in a rapid, reliable, and reasonably accurate fashion using single area measurements on CT.