To investigate the value of coronary calcium scoring (CCS) as a filter scan prior to coronary computed tomography angiography (CCTA).
Methods and Results
Between February 2008 and April 2011, 732 consecutive patients underwent clinically indicated CCTA. During this ‘control phase’, CCS was performed in all patients. In patients with CCS≥800, CCTA was not performed. During a subsequent ‘CCTA phase’ (May 2011–May 2012) another 200 consecutive patients underwent CCTA, and CCS was performed only in patients with increased probability for severe calcification according to age, gender and atherogenic risk factors. In patients where CCS was not performed, calcium scoring was performed in contrast-enhanced CCTA images. Significant associations were noted between CCS and age (r = 0.30, p<0.001) and coronary risk factors (χ2 = 37.9; HR = 2.2; 95%CI = 1.7–2.9, p<0.001). Based on these associations, a ≤3% pre-test probability for CCS≥800 was observed for males <61 yrs. and females <79 yrs. According to these criteria, CCS was not performed in 106 of 200 (53%) patients during the ‘CCTA phase’, including 47 (42%) males and 59 (67%) females. This resulted in absolute radiation saving of ∼1 mSv in 75% of patients younger than 60 yrs. Of 106 patients where CCS was not performed, estimated calcium scoring was indeed <800 in 101 (95%) cases. Non-diagnostic image quality due to calcification was similar between the ‘control phase’ and the ‘CCTA’ group (0.25% versus 0.40%, p = NS).
The value of CCS as a filter for identification of a high calcium score is limited in younger patients with intermediate risk profile. Omitting CCS in such patients can contribute to further dose reduction with cardiac CT studies.
Evaluations are essential to judge the success of public health programmes. In Europe, the proportion of public health programmes that undergo evaluation remains unclear. The European Centre for Disease Prevention and Control sought to determine the frequency of evaluations amongst European national public health programmes by using national hand hygiene campaigns as an example of intervention.
A cohort of all national hand hygiene campaigns initiated between 2000 and 2012 was utilised for the analysis. The aim was to collect information about evaluations of hand hygiene campaigns and their frequency. The survey was sent to nominated contact points for healthcare-associated infection surveillance in European Union and European Economic Area Member States.
Thirty-six hand hygiene campaigns in 20 countries were performed between 2000 and 2012. Of these, 50% had undergone an evaluation and 55% of those utilised the WHO hand hygiene intervention self-assessment tool. Evaluations utilised a variety of methodologies and indicators in assessing changes in hand hygiene behaviours pre and post intervention. Of the 50% of campaigns that were not evaluated, two thirds reported that both human and financial resource constraints posed significant barriers for the evaluation.
The study identified an upward trend in the number of hand hygiene campaigns implemented in Europe. It is likely that the availability of the internationally-accepted evaluation methodology developed by the WHO contributed to the evaluation of more hand hygiene campaigns in Europe. Despite this rise, hand hygiene campaigns appear to be under-evaluated. The development of simple, programme-specific, standardised guidelines, evaluation indicators and other evidence-based public health materials could help promote evaluations across all areas of public health.
Hand hygiene; Healthcare associated infections; Evaluation; Evidence-based public health
Antimicrobial Resistance and Infection Control would like to thank the following colleagues for their assistance with peer review of manuscripts for the journal in 2013.
In industrialized countries with aging populations, heart failure affects 0.3–2% of the general population. The investigation of 24 h-ECG recordings revealed the potential of nonlinear indices of heart rate variability (HRV) for enhanced risk stratification in patients with ischemic heart failure (IHF). However, long-term analyses are time-consuming, expensive, and delay the initial diagnosis. The objective of this study was to investigate whether 30 min short-term HRV analysis is sufficient for comparable risk stratification in IHF in comparison to 24 h-HRV analysis. From 256 IHF patients [221 at low risk (IHFLR) and 35 at high risk (IHFHR)] (a) 24 h beat-to-beat time series (b) the first 30 min segment (c) the 30 min most stationary day segment and (d) the 30 min most stationary night segment were investigated. We calculated linear (time and frequency domain) and nonlinear HRV analysis indices. Optimal parameter sets for risk stratification in IHF were determined for 24 h and for each 30 min segment by applying discriminant analysis on significant clinical and non-clinical indices. Long- and short-term HRV indices from frequency domain and particularly from nonlinear dynamics revealed high univariate significances (p < 0.01) discriminating between IHFLR and IHFHR. For multivariate risk stratification, optimal mixed parameter sets consisting of 5 indices (clinical and nonlinear) achieved 80.4% AUC (area under the curve of receiver operating characteristics) from 24 h HRV analysis, 84.3% AUC from first 30 min, 82.2 % AUC from daytime 30 min and 81.7% AUC from nighttime 30 min. The optimal parameter set obtained from the first 30 min showed nearly the same classification power when compared to the optimal 24 h-parameter set. As results from stationary daytime and nighttime, 30 min segments indicate that short-term analyses of 30 min may provide at least a comparable risk stratification power in IHF in comparison to a 24 h analysis period.
risk stratification; heart rate variability; short-term; long-term; daytime; nighttime; nonlinear dynamics; ischemic cardiomyopathy
S100A8 and S100A9 belong to the damage associated molecular pattern molecules. They are upregulated in a number of inflammatory skin disorders. Due to their abundance in myeloid cells the main function of S100A8/A9 has been attributed to their role in inflammatory cells. However, it is becoming increasingly clear that they also exert important roles in epithelial cells. In this review we discuss the context-dependent function of S100A8/A9 in epithelial cells and its impact on wound healing, psoriasis and other skin diseases.
Psoriasis; Skin barrier dysfunction; Wound healing; Inflammation; S100/calgranulin–RAGE axis
Money is one of the most frequently passed items in the world. The aim of this study was to ascertain the survival status of bacteria including Staphylococcus aureus, Escherichia coli, and Vancomycin- Resistant Enterococci (VRE) on banknotes from different countries and the transmission of bacteria to people who come in contact with the banknotes. The survival rate was highest for the Romanian Leu yielding all three microorganisms used after both three and six hours of drying. Furthermore, the Leu was the only banknote to yield VRE after one day of drying. Other currencies either enabled the survival of Extended-Spectrum Beta-Lactamases (ESBL) and VRE (e.g. Euro), but not of MRSA, or the other way round (e.g. US Dollar). While a variety of factors such as community hygiene levels, people’s behaviour, and antimicrobial resistance rates at community level obviously have influence on the transmission of resistant microorganisms, the type of banknote-paper may be an additional variable to consider.
The aim of this study was to determine the long-term carriage rates and transmission dynamics of methicillin-resistant Staphylococcus aureus (MRSA) in pig farmers and their household members. During a 6-month period in 2009–2010, 4 pig farms in Denmark, Belgium, and the Netherlands, respectively, were studied for the presence of MRSA. The proportion of persistent carriers was significantly higher among farmers than among household members (87% vs. 11%) and significantly higher in household members from Belgium compared to those from Denmark and the Netherlands (29% vs. 0% vs. 6%). Determinant analysis of MRSA carriage revealed that pig contact was the most important determinant for MRSA carriage among household members and that the increased MRSA carriage rate observed among household members from Belgium is linked to country-specific differences in pig exposure.
These findings demonstrated that even in pig farms with very high carriage rates of MRSA both in livestock and farmers, the risk for household members to acquire MRSA is limited and still depends strongly on pig exposure. By restricting access to the stables and exposure to pigs, MRSA acquisition by household members could be greatly reduced.
Antimicrobial Resistance and Infection Control would like to thank the following colleagues for their assistance with peer review of manuscripts for the journal in 2012.
Background. Impairment of circadian rhythm is associated with various clinical problems. It not only has a negative impact on quality of life but can also be associated with a significantly poorer prognosis. Eurythmy therapy (EYT) is an anthroposophic movement therapy aimed at reducing fatigue symptoms and stress levels. Objective. This analysis of healthy subjects was conducted to examine whether the improvement in fatigue symptoms was accompanied by improvements in the circadian rhythm of heart rate variability (HRV). Design. Twenty-three women performed 10 hours of EYT over six weeks. Electrocardiograms (ECGs) were recorded before and after the EYT trial. HRV was quantified by parameters of the frequency and time domains and the nonlinear parameters of symbolic dynamics. Results. The day-night contrast with predominance of vagal activity at night becomes more pronounced after the EYT training, and with decreased Ultralow and very low frequencies, the HRV shows evidence of calmer sleep. During the night, the complexity of the HRV is significantly increased indicated by nonlinear parameters. Conclusion. The analysis of the circadian patterns of cardiophysiological parameters before and after EYT shows significant improvements in HRV in terms of greater day-night contrast caused by an increase of vagal activity and calmer and more complex HRV patterns during sleep.
To determine costs and effects of selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) as compared with standard care (ie, no SDD/SOD (SC)) from a healthcare perspective in Dutch Intensive Care Units (ICUs).
A post hoc analysis of a previously performed cluster-randomised trial (NEJM 2009;360:20).
13 Dutch ICUs.
Patients with ICU-stay of >48 h that received SDD (n=2045), SOD (n=1904) or SC (n=1990).
SDD or SOD.
Primary and secondary outcome measures
Effects were based on hospital survival, expressed as crude Life Years Gained (cLYG). The incremental cost-effectiveness ratio (ICER) was calculated, with corresponding cost acceptability curves. Sensitivity analyses were performed for discount rates, costs of SDD, SOD and mechanical ventilation.
Total costs per patient were €41 941 for SC (95% CI €40 184 to €43 698), €40 433 for SOD (95% CI €38 838 to €42 029) and €41 183 for SOD (95% CI €39 408 to €42 958). SOD and SDD resulted in crude LYG of +0.04 and +0.25, respectively, as compared with SC, implying that both SDD and SOD are dominant (ie, cheaper and more beneficial) over SC. In cost-effectiveness acceptability curves probabilities for cost-effectiveness, compared with standard care, ranged from 89% to 93% for SOD and from 63% to 72% for SDD, for acceptable costs for 1 LYG ranging from €0 to €20 000. Sensitivity analysis for mechanical ventilation and discount rates did not change interpretation. Yet, if costs of the topical component of SDD and SOD would increase 40-fold to €400/day and €40/day (maximum values based on free market prices in 2012), the estimated ICER as compared with SC for SDD would be €21 590 per LYG. SOD would remain cost-saving.
SDD and SOD were both effective and cost-saving in Dutch ICUs.
“The Chennai Declaration” is the result of the first ever joint meeting of medical societies in India addressing antibiotic resistance. The declaration is not a policy by itself, but a call for a national policy. The Declaration has looked into all major aspects of the problem of antimicrobial resistance, has suggested practical solutions, explained in detail the responsibility of each and every stakeholder.
The immature autonomic nervous system (ANS) in premature infants regulates heart rate (HR) and respiration different during quiet sleep (QS) and active sleep (AS). Little information is available about ANS regulation in these subjects. The aim of this study was to investigate changes in autonomic regulation and cardiorespiratory coupling during AS and QS in five very preterm neonates with gestational age (GA) 26–31 weeks, applying univariate and bivariate linear and non-linear dynamics methods to the recorded cardiorespiratory signals. During QS univariate linear indices revealed lower standard deviations and entropies, indicating decreased heart rate (HR) variability. More balanced sympatho-vagal behavior of the ANS was revealed by decreased low frequency (LF), increased high frequency (HF), and a trend toward lower ratio LF/HF in QS. Applied non-linear indices (probabilities, entropies, and fractal measures) quantifying the complexity and scaling behavior of HR regulation processes were significantly altered in QS in comparison to AS. This reflects a lower short-term variability, less complexity, and a loss of fractal-like correlation properties of HR dynamics in QS. One major finding is that cardiorespiratory coupling is not yet completely developed in very preterm neonates with 26–31 weeks GA. Significantly different regulation patterns in bivariate oscillations of HR and respiration during AS and QS could be recognized. These patterns were characterized on the one hand by predominant monotonous regulating sequences originating from respiration independently from HR time series in AS, and to a minor degree in QS, and on the other hand by some prominent HR regulation sequences in QS independent of respiratory regulation. We speculate that these findings might be suitable for monitoring preterm neonates and for detecting disorders in the developing cardiorespiratory system.
autonomic regulation; cardiorespiratory coupling; preterm newborns; sleep states; non-linear dynamics
Decreased heart rate variability (HRV) was shown for unmedicated patients with schizophrenia and their first-degree relatives, implying genetic associations. This is known to be an important risk factor for increased cardiac mortality in other diseases. The interaction of cardio-respiratory function and respiratory physiology has never been investigated in the disease although it might be closely related to the pattern of autonomic dysfunction. We hypothesized that increased breathing rates and reduced cardio-respiratory coupling in patients with acute schizophrenia would be associated with low vagal function. We assessed variability of breathing rates and depth, HRV and cardio-respiratory coupling in patients, their first-degree relatives and controls at rest. Control subjects were investigated a second time by means of a stress task to identify stress-related changes of cardio-respiratory function. A total of 73 subjects were investigated, consisting of 23 unmedicated patients, 20 healthy, first-degree relatives and 30 control subjects matched for age, gender, smoking and physical fitness. The LifeShirt®, a multi-function ambulatory device, was used for data recording (30 minutes). Patients breathe significantly faster (p<.001) and shallower (p<.001) than controls most pronouncedly during exhalation. Patients' breathing is characterized by a significantly increased amount of middle- (p<.001), high- (p<.001), and very high frequency fluctuations (p<.001). These measures correlated positively with positive symptoms as assessed by the PANSS scale (e.g., middle frequency: r = 521; p<.01). Cardio-respiratory coupling was reduced in patients only, while HRV was decreased in patients and healthy relatives in comparison to controls. Respiratory alterations might reflect arousal in acutely ill patients, which is supported by comparable physiological changes in healthy subjects during stress. Future research needs to further investigate these findings with respect to their physiological consequences for patients. These results are invaluable for researchers studying changes of biological signals prone to the influence of breathing rate and rhythm (e.g., functional imaging).
In vivo imaging and quantification of amyloid-β plaque (Aβ) burden in small-animal models of Alzheimer's disease (AD) is a valuable tool for translational research such as developing specific imaging markers and monitoring new therapy approaches. Methodological constraints such as image resolution of positron emission tomography (PET) and lack of suitable AD models have limited the feasibility of PET in mice. In this study, we evaluated a feasible protocol for PET imaging of Aβ in mouse brain with [11C]PiB and specific activities commonly used in human studies. In vivo mouse brain MRI for anatomical reference was acquired with a clinical 1.5 T system. A recently characterized APP/PS1 mouse was employed to measure Aβ at different disease stages in homozygous and hemizygous animals. We performed multi-modal cross-validations for the PET results with ex vivo and in vitro methodologies, including regional brain biodistribution, multi-label digital autoradiography, protein quantification with ELISA, fluorescence microscopy, semi-automated histological quantification and radioligand binding assays. Specific [11C]PiB uptake in individual brain regions with Aβ deposition was demonstrated and validated in all animals of the study cohort including homozygous AD animals as young as nine months. Corresponding to the extent of Aβ pathology, old homozygous AD animals (21 months) showed the highest uptake followed by old hemizygous (23 months) and young homozygous mice (9 months). In all AD age groups the cerebellum was shown to be suitable as an intracerebral reference region. PET results were cross-validated and consistent with all applied ex vivo and in vitro methodologies. The results confirm that the experimental setup for non-invasive [11C]PiB imaging of Aβ in the APP/PS1 mice provides a feasible, reproducible and robust protocol for small-animal Aβ imaging. It allows longitudinal imaging studies with follow-up periods of approximately one and a half years and provides a foundation for translational Alzheimer neuroimaging in transgenic mice.
Resistance to antibiotics has increased dramatically over the past few years and has now reached a level that places future patients in real danger. Microorganisms such as Escherichia coli and Klebsiella pneumoniae, which are commensals and pathogens for humans and animals, have become increasingly resistant to third-generation cephalosporins. Moreover, in certain countries, they are also resistant to carbapenems and therefore susceptible only to tigecycline and colistin. Resistance is primarily attributed to the production of beta-lactamase genes located on mobile genetic elements, which facilitate their transfer between different species. In some rare cases, Gram-negative rods are resistant to virtually all known antibiotics. The causes are numerous, but the role of the overuse of antibiotics in both humans and animals is essential, as well as the transmission of these bacteria in both the hospital and the community, notably via the food chain, contaminated hands, and between animals and humans. In addition, there are very few new antibiotics in the pipeline, particularly for Gram-negative bacilli. The situation is slightly better for Gram-positive cocci as some potent and novel antibiotics have been made available in recent years. A strong and coordinated international programme is urgently needed. To meet this challenge, 70 internationally recognized experts met for a two-day meeting in June 2011 in Annecy (France) and endorsed a global call to action ("The Pensières Antibiotic Resistance Call to Action"). Bundles of measures that must be implemented simultaneously and worldwide are presented in this document. In particular, antibiotics, which represent a treasure for humanity, must be protected and considered as a special class of drugs.
antibiotic resistance; antibiotic stewardship; infection control; hand hygiene; surveillance networks; care bundles; environment; regulations; human medicine; animal medicine
Pre-emptive isolation of suspected methicillin-resistant Staphylococcus aureus (MRSA) carriers is a cornerstone of successful MRSA control policies. Implementation of such strategies is hampered when using conventional cultures with diagnostic delays of three to five days, as many non-carriers remain unnecessarily isolated. Rapid diagnostic testing (RDT) reduces the amount of unnecessary isolation days, but costs and benefits have not been accurately determined in intensive care units (ICUs).
Embedded in a multi-center hospital-wide study in 12 Dutch hospitals we quantified cost per isolation day avoided using RDT for MRSA, added to conventional cultures, in ICUs. BD GeneOhm™ MRSA PCR (IDI) and Xpert MRSA (GeneXpert) were subsequently used during 17 and 14 months, and their test characteristics were calculated with conventional culture results as reference. We calculated the number of pre-emptive isolation days avoided and incremental costs of adding RDT.
A total of 163 patients at risk for MRSA carriage were screened and MRSA prevalence was 3.1% (n = 5). Duration of isolation was 27.6 and 21.4 hours with IDI and GeneXpert, respectively, and would have been 96.0 hours when based on conventional cultures. The negative predictive value was 100% for both tests. Numbers of isolation days were reduced by 44.3% with PCR-based screening at the additional costs of €327.84 (IDI) and €252.14 (GeneXpert) per patient screened. Costs per isolation day avoided were €136.04 (IDI) and €121.76 (GeneXpert).
In a low endemic setting for MRSA, RDT safely reduced the number of unnecessary isolation days on ICUs by 44%, at the costs of €121.76 to €136.04 per isolation day avoided.
Methicillin-resistant Staphylococcus aureus is an increasing problem in the Caribbean. We investigated the molecular epidemiology of MRSA isolates on Cuba.
The predominant clone was of the spa type t149, followed by community-associated MRSA USA300.
We report the first molecular typing results of MRSA isolates from Cuba.
MRSA; Cuba; Caribbean; Infection control; Hospital-associated-infection; Low-resource setting
The structures of staphylococcal cassette chromosome mec (SCCmec) elements carried by 31 clonal complex 398 (CC398) methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from the participants at a conference were analyzed. The SCCmecs were classified into novel types, namely, IX, X, V(5C2&5) subtype c, and IVa. Type V(5C2&5) subtype c, IX, and X SCCmecs carried genes conferring resistance to metals. The structures of SCCmecs from CC398 strains were distinct from those normally found in humans, adding to the evidence that humans are not the original host for CC398.
Nosocomial infections and their control are a world-wide challenge. The prevalence of nosocomial infections is generally higher in developing countries with limited resources than industrialized countries. In this paper we aimed to further explain the differences with regard to infection control challenges between Turkey, a country with "limited" resources, and the Netherlands, a country with "reasonable" resources. Infrastructure of hospitals, low compliance of hand hygiene, understaffing, overcrowding, heavy workload, misuse of personal protective equipments, late establishment of infection control programme are major problems in limited-resources countries. These problems cause high infection rates and spread of multi-drug resistant pathogens. To improve the control and prevention of infections in countries with limited resources, a multi-facet approach is needed.
Infection control; developing country; limited resource; multi-drug resistant pathogen
Newborn mammals suffering from moderate hypoxia during or after birth are able to compensate a transitory lack of oxygen by adapting their vital functions. Exposure to hypoxia leads to an increase in the sympathetic tone causing cardio-respiratory response, peripheral vasoconstriction and vasodilatation in privileged organs like the heart and brain. However, there is only limited information available about the time and intensity changes of the underlying complex processes controlled by the autonomic nervous system.
In this study an animal model involving seven piglets was used to examine an induced state of circulatory redistribution caused by moderate oxygen deficit. In addition to the main focus on the complex dynamics occurring during sustained normocapnic hypoxia, the development of autonomic regulation after induced reoxygenation had been analysed. For this purpose, we first introduced a new algorithm to prove stationary conditions in short-term time series. Then we investigated a multitude of indices from heart rate and blood pressure variability and from bivariate interactions, also analysing respiration signals, to quantify the complexity of vegetative oscillations influenced by hypoxia.
The results demonstrated that normocapnic hypoxia causes an initial increase in cardiovascular complexity and variability, which decreases during moderate hypoxia lasting one hour (p < 0.004). After reoxygenation, cardiovascular complexity parameters returned to pre-hypoxic values (p < 0.003), however not respiratory-related complexity parameters.
In conclusion, indices from linear and nonlinear dynamics reflect considerable temporal changes of complexity in autonomous cardio-respiratory regulation due to normocapnic hypoxia shortly after birth. These findings might be suitable for non-invasive clinical monitoring of hypoxia-induced changes of autonomic regulation in newborn humans.
Methicillin-resistant Staphylococcus aureus clonal complex (CC) 398 has emerged from pigs to cause human infections in Europe and North America. We used a new 62-strain S. aureus microarray (SAM-62) to compare genomes of isolates from three geographical areas (Belgium, Denmark, and Netherlands) to understand how CC398 colonizes different mammalian hosts. The core genomes of 44 pig isolates and 32 isolates from humans did not vary. However, mobile genetic element (MGE) distribution was variable including SCCmec. φ3 bacteriophage and human specificity genes (chp, sak, scn) were found in invasive human but not pig isolates. SaPI5 and putative ruminant specificity gene variants (vwb and scn) were common but not pig specific. Virulence and resistance gene carriage was host associated but country specific. We conclude MGE exchange is frequent in CC398 and greatest among populations in close contact. This feature may help determine epidemiological associations among isolates of the same lineage.
methicillin-resistant Staphylococcus aureus; host specificity; mobile genetic elements; zoonoses; bacteriophages
Recent studies revealed cardiac autonomic dysfunction in patients with acute schizophrenia, which appears to be mainly related to reduced vagal and increased sympathetic modulation. To understand the significance of cardiac autonomic function in patients with schizophrenia, we extended these studies to relatives of patients. In this study, we assessed cardiac autonomic modulation in healthy first-degree relatives of patients with schizophrenia (n = 36) to investigate a putative genetic influence. Data were compared with control subjects matched for age, gender, and physical activity as well as to patients suffering from schizophrenia. First-degree relatives showed an attenuated, yet identical pattern in autonomic dysfunction as patients with decreased vagal modulation of heart rate, decreased baroreflex sensitivity, but no difference in blood pressure variability could be detected. The patients' relatives also showed a similar pattern in regards to QT variability. In addition, the subgroup comparison of offspring vs. siblings showed a significant difference in heart rate variability suggesting a higher degree of heritability in offspring. In conclusion, the pattern of autonomic dysfunction seen in patients and relatives might indicate underlying disease-inherent genetic vulnerability, especially because autonomic parameters are heritable. In addition, these findings may be of value to identify the high-risk group of patients' relatives in regards to serious cardiovascular events so that early preventive measures can be taken.
autonomic nervous system; schizophrenia; vagal; offspring; heart rate variability; baroreflex sensitivity; genetic