Effect of Using the HEART Score in Patients With Chest Pain in the Emergency Department: A Stepped-Wedge, Cluster Randomized Trial.

BACKGROUND: The HEART (History, Electrocardiogram, Age, Risk factors, and initial Troponin) score is an easy-to-apply instrument to stratify patients with chest pain according to their short-term risk for major adverse cardiac events (MACEs), but its effect on daily practice is unknown. OBJECTIVE: To measure the effect of use of the HEART score on patient outcomes and use of health care resources. DESIGN: Stepped-wedge, cluster randomized trial. (ClinicalTrials.gov: NCT01756846). SETTING: Emergency departments in 9 Dutch hospitals. PATIENTS: Unselected patients with chest pain presenting at emergency departments in 2013 and 2014. INTERVENTION: All hospitals started with usual care. Every 6 weeks, 1 hospital was randomly assigned to switch to "HEART care," during which physicians calculated the HEART score to guide patient management. MEASUREMENTS: For safety, a noninferiority margin of a 3.0% absolute increase in MACEs within 6 weeks was set. Other outcomes included use of health care resources, quality of life, and cost-effectiveness. RESULTS: A total of 3648 patients were included (1827 receiving usual care and 1821 receiving HEART care). Six-week incidence of MACEs during HEART care was 1.3% lower than during usual care (upper limit of the 1-sided 95% CI, 2.1% [within the noninferiority margin of 3.0%]). In low-risk patients, incidence of MACEs was 2.0% (95% CI, 1.2% to 3.3%). No statistically significant differences in early discharge, readmissions, recurrent emergency department visits, outpatient visits, or visits to general practitioners were observed. LIMITATION: Physicians were hesitant to refrain from admission and diagnostic tests in patients classified as low risk by the HEART score. CONCLUSION: Using the HEART score during initial assessment of patients with chest pain is safe, but the effect on health care resources is limited, possibly due to nonadherence to management recommendations. PRIMARY FUNDING SOURCE: Netherlands Organisation for Health Research and Development.

2D self-assembly of phenylene-vinylene tectons at the liquid-highly oriented pyrolytic graphite interface: from chain length effects to anisotropic guest-host dynamics.

Here we report the synthesis and characterization of a series of new phenylene-vinylene tectons. The study by scanning tunneling microscopy of their supramolecular self-assembly at the interface between a phenyloctane solution and highly oriented pyrolytic graphite  demonstrates that variation of concentration and length of alkyl chains led to the formation of different networks, a compact one and a nanoporous one, with a fine control of the lattice parameters. The study of guest-host properties of the nanoporous network revealed a selectivity toward guest compounds according to their shape and size. Moreover, the statistical analysis of pore-to-pore guest dynamics evidences an anisotropic diffusion process.

The value of clinical and laboratory diagnostics for chest pain patients at the emergency department.

BACKGROUND: The focus during the diagnostic process for patients with acute chest pain is to discriminate patients who can be safely discharged from those who are at risk for an acute coronary syndrome (ACS). In this study the diagnostic value of the clinical examination is compared with laboratory testing of troponin. METHODS: This study included 710 chest pain patients who presented at the ED of two hospitals in the Netherlands. Clinical examination and laboratory testing were combined in the recently developed HEART-score. The diagnostic values of clinical presentation, troponin and the HEART-score for a major adverse coronary event (MACE) and an ACS within 6 weeks were assessed. Furthermore, the improvement of HEART with the second troponin measurement after 6 h was assessed using the net reclassification improvement (NRI). RESULTS: The use of HEART (AUCMACE: 0.77; AUCACS: 0.82) obtains a higher diagnostic value than troponin (AUCMACE: 0.72; AUCACS: 0.74) or clinical evaluation (AUCMACE: 0.69; AUCACS: 0.74). Statistical significant different AUCs were obtained when HEART is compared to troponin or clinical evaluation (p<0.01). The use of the second troponin test (after 6 h of admission) within HEART resulted in an improvement of 8.0%. CONCLUSIONS: The HEART-score combines clinical evaluation and results from laboratory testing, which should be used together, to discriminate patients at risk of a cardiac event from patients who can be safely discharged. In addition, it is shown that a second troponin measurement slightly improves the discriminative ability of the HEART-score.

From raw microalgae to bioplastics: Conversion of Chlorella vulgaris starch granules into thermoplastic starch.

Microalgae are emerging as a promising feedstock for bioplastics, with Chlorella vulgaris yielding significant amounts of starch. This polysaccharide is convertible into thermoplastic starch (TPS), a biodegradable plastic of industrial relevance. In this study, we developed a pilot-scale protocol for extracting and purifying starch from 430 g (dry weight - DW) of starch-enriched Chlorella vulgaris biomass. More than 200 gDW of starch were recovered, with an extraction yield and starch purity degree reaching 98 and 87 %, respectively. We have characterized this extracted starch and processed it into TPS using twin-screw extrusion and injection molding. Microalgal starch showed similar properties to those of native plant starch, but with smaller granules. We compared the mechanical properties of microalgal TPS with two controls, namely a commercial TPS and a TPS prepared from commercial potato starch granules. TPS prepared from microalgal starch showed a softer and more ductile behavior compared to the reference materials. This study demonstrates the feasibility of recovering high-purity microalgal starch at pilot scale with high yields, and highlights the potential of microalgal starch for the production of TPS using industrially relevant processes.

The impact of the HEART risk score in the early assessment of patients with acute chest pain: design of a stepped wedge, cluster randomised trial.

BACKGROUND: Chest pain remains a diagnostic challenge: physicians do not want to miss an acute coronary syndrome (ACS), but, they also wish to avoid unnecessary additional diagnostic procedures. In approximately 75% of the patients presenting with chest pain at the emergency department (ED) there is no underlying cardiac cause. Therefore, diagnostic strategies focus on identifying patients in whom an ACS can be safely ruled out based on findings from history, physical examination and early cardiac marker measurement. The HEART score, a clinical prediction rule, was developed to provide the clinician with a simple, early and reliable predictor of cardiac risk. We set out to quantify the impact of the use of the HEART score in daily practice on patient outcomes and costs. METHODS/DESIGN: We designed a prospective, multi-centre, stepped wedge, cluster randomised trial. Our aim is to include a total of 6600 unselected chest pain patients presenting at the ED in 10 Dutch hospitals during an 11-month period. All clusters (i.e. hospitals) start with a period of 'usual care' and are randomised in their timing when to switch to 'intervention care'. The latter involves the calculation of the HEART score in each patient to guide clinical decision; notably reassurance and discharge of patients with low scores and intensive monitoring and early intervention in patients with high HEART scores. Primary outcome is occurrence of major adverse cardiac events (MACE), including acute myocardial infarction, revascularisation or death within 6 weeks after presentation. Secondary outcomes include occurrence of MACE in low-risk patients, quality of life, use of health care resources and costs. DISCUSSION: Stepped wedge designs are increasingly used to evaluate the real-life effectiveness of non-pharmacological interventions because of the following potential advantages: (a) each hospital has both a usual care and an intervention period, therefore, outcomes can be compared within and across hospitals; (b) each hospital will have an intervention period which enhances participation in case of a promising intervention; (c) all hospitals generate data about potential implementation problems. This large impact trial will generate evidence whether the anticipated benefits (in terms of safety and cost-effectiveness) of using the HEART score will indeed be achieved in real-life clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov 80-82310-97-12154.

Consumption of diagnostic procedures and other cardiology care in chest pain patients after presentation at the emergency department.

OBJECTIVE: The HEART score serves risk stratification of chest pain patients at the emergency department (ED). Quicker and more solid decisions may be taken in these patients with application of this score. An analysis of medical consumption of 122 acute chest pain patients admitted before the introduction of this score may be indicative of possible savings. METHODS: Numbers of cardiology investigations and clinical admission days were counted. Charged cost of medicine was divided into three categories: ED, in-hospital, and outpatient clinic. RESULTS: The total cost of care was 469,631, with an average of 3849 per patient. Seventy-five percent of this cost was due to hospitalisation under the initial working diagnosis of acute coronary syndrome (ACS). This diagnosis was confirmed in only 29/122 (24 %) of the patients. The low-risk group (41 patients with HEART scores 0-3) included one patient with a previously scheduled CABG. In the remaining 40 patients, hospitalisation occurred in 12/40 (30 %) patients and 30/40 (75 %) patients visited the outpatient clinic. The total cost of medical care after presentation of these 40 patients was 37,641; there were no cases where a new diagnosis of coronary artery disease was made. When medical care in this subgroup is declared redundant, major savings on national medical care budgets could be made. CONCLUSION: If the HEART score were to be routinely applied, diagnostic pathways could be shortened and costs reduced, in particular in low-risk patients.

T cell diversity and TcR repertoires in teleost fish.

In vertebrates, the diverse and extended range of antigenic motifs is matched to large populations of lymphocytes. The concept of immune repertoire was proposed to describe this diversity of lymphocyte receptors--IG and TR--required for the recognition specificity. Immune repertoires have become useful tools to describe lymphocyte and receptor populations during the immune system development and in pathological situations. In teleosts, the presence of conventional T cells was first proposed to explain graft rejection and optimized specific antibody production. The discovery of TR genes definitely established the reality of conventional T cells in fish. The development of genomic and EST databases recently led to the description of several key T cell markers including CD4, CD8, CD3, CD28, CTLA4, as well as important cytokines, suggesting the existence of different T helper (Th) subtypes, similar to the mammalian Th1, Th2 and Th17. Over the last decade, repertoire studies have demonstrated that both public and private responses occur in fish as they do in mammals, and in vitro specific cytotoxicity assays have been established. While such typical features of T cells are similar in both fish and mammals, the structure of particular repertoires such as the one of gut intra-epithelial lymphocytes seems to be very different. Future studies will further reveal the particular characteristics of teleost T cell repertoires and adaptive responses.

Identification of a T cell receptor beta chain variable region, V beta 20, that is differentially expressed in various strains of mice.

A cDNA library of TCR beta chain transcripts from BALB/c thymocytes was constructed using anchored polymerase chain reaction (PCR). Screening of this library led to the identification of a V beta gene segment, V beta 20, structurally related to V beta 3 and V beta 17. Genomic analysis of mice displaying deletions in their V beta loci, together with mapping of cosmid clones, situated V beta 20 2.5 kb beside V beta 17. The expression of V beta 20 was estimated by PCR in mice of different H-2 and Mls types. Peripheral T cells from H-2k and H-2d mice did not express V beta 20, whereas in I-E-negative mice (C57Bl/6 and SJL), V beta 20 transcripts were detected. The lack of V beta 20 transcripts in (C57Bl/6 x CBA/J)F1, (C57Bl/6 x BALB/c)F1, and in congenic B6.H-2k mice suggests that the differential use of V beta 20 is due to an I-E-mediated clonal deletion process. The involvement of the Mls super antigens was excluded by analysis of all Mls type combinations. The nature of the V beta 20-deleting element(s) is discussed in the context of the I-E/superantigen systems controlling the expression of V beta 11 and V beta 17.

Ontogeny of the immune system: gamma/delta and alpha/beta T cells migrate from thymus to the periphery in alternating waves.

The embryonic thymus is colonized by the influx of hemopoietic progenitors in waves. To characterize the T cell progeny of the initial colonization waves, we used intravenous adoptive transfer of bone marrow progenitors into congenic embryos. The experiments were performed in birds because intravenous cell infusions can be performed more efficiently in avian than in mammalian embryos. Progenitor cells, which entered the vascularized thymus via interlobular venules in the capsular region and capillaries located at the corticomedullary junction, homed to the outer cortex to begin thymocyte differentiation. The kinetics of differentiation and emigration of the T cell progeny were analyzed for the first three waves of progenitors. Each progenitor wave gave rise to gamma/delta T cells 3 d earlier than alpha/beta T cells. Although the flow of T cell migration from the thymus was uninterrupted, distinct colonization and differentiation kinetics defined three successive waves of gamma/delta and alpha/beta T cells that depart sequentially the thymus en route to the periphery. Each wave of precursors rearranged all three TCR Vgamma gene families, but displayed a variable repertoire. The data indicate a complex pattern of repertoire diversification by the progeny of founder thymocyte progenitors.

Value of Repeated Troponin Measurements to Improve the Safety of the HEART Score for Chest Pain Patients at the Emergency Department.

OBJECTIVE: The HEART score is a clinical decision support tool for physicians to stratify the risk of major adverse cardiac events (MACE) in patients presenting with chest pain at the emergency department. The score includes 5 elements, including troponin level. Our aim was to compare safety and efficiency of the HEART scores calculated by using the first representative troponin (ie, based on time since symptom onset) compared to the original HEART score, where calculation was based on the first available troponin measurement, irrespective of duration of symptoms. METHODS: We performed a secondary analysis on patients from the HEART-impact trial (2013-2014, the Netherlands). Two HEART scores were calculated for all patients: a HEART score with a T (troponin) element score based on the first available troponin (HEART-first) and 1 with a T element score based on the first representative troponin (ie, at least 3 hours after symptom onset; HEART-representative). We compared all patients' scores and risk categories between HEART-first and HEART-representative. Furthermore, we compared safety (proportion of patients with MACE receiving a low score) and efficiency (proportion of patients with a low score) between HEART-first and HEART-representative. RESULTS: We included 1222 patients. In 882 (72%) patients, the first troponin was representative, resulting in the same HEART-first and HEART-representative score. In the remaining 340 patients the use of HEART-representative led to a different score than HEART-first in 43 patients (3.5%). Out of the 222 patients with MACE, 11 patients (5.0%) received a low score by using HEART-first compared with 10 patients (4.5%) when using HEART-representative (P = 0.83). The number of patients with a low score was similar (P = 0.93) when using the HEART-first (464/1222; 38%) or HEART-representative score (462/1222; 38%). CONCLUSIONS: Using a representative troponin measurement changed the value of the HEART score in only 3.5% of patients and had no impact on safety and efficiency of the HEART score. These results suggest there is no need to wait for a representative troponin measurement and should encourage physicians to adhere to the original HEART score guidelines.

Genetic structure of a wide-spectrum chicken gene pool.

The genetic structure of 65 chicken populations was studied using 29 simple sequence repeat loci. Six main clusters which corresponded to geographical origins and histories were identified: Brown Egg Layers; predominantly Broilers; native Chinese breeds or breeds with recent Asian origin; predominantly breeds of European derivation; a small cluster containing populations with no common history and populations that had breeding history with White Leghorn. Another group of populations that shared their genome with several clusters was defined as 'Multi-clusters'. Gallus gallus gallus (Multi-clusters), one of the subspecies of the Red Jungle Fowl, which was previously suggested to be one of the ancestors of the domesticated chicken, has almost no shared loci with European and White Egg layer populations. In a further sub-clustering of the populations, discrimination between all the 65 populations was possible, and relationships between each were suggested. The genetic variation between populations was found to account for about 34% of the total genetic variation, 11% of the variation being between clusters and 23% being between populations within clusters. The suggested clusters may assist in future studies of genetic aspects of the chicken gene pool.

Chest pain in the emergency room: value of the HEART score.

BACKGROUND: Chest pain is one of the most common causes of presentation to the emergency room. The diagnosis of non-ST-elevation acute coronary syndrome typically causes uncertainty. Classical considerations for risk stratification are History, ECG, Age, Risk factors and Troponin (HEART). Each can be scored with zero, one or two points, depending on the extent of the abnormality. The HEART score is the sum of these five considerations. Methods. Clinical data from 122 patients referred to the emergency room for chest pain were analysed. The predictive value of the HEART score for reaching an endpoint was evaluated in 120/122 patients. RESULTS: Twenty-nine patients reached one or more endpoints: an acute myocardial infarction was diagnosed in 16 patients, 20 underwent revascularisation and two died. The HEART score in the patients with and without an endpoint was 6.51+/-1.84 and 3.71+/-1.83 (p<0.0001) respectively. A HEART score of 0-3 points holds a risk of 2.5% for an endpoint and supports an immediate discharge. With a risk of 20.3%, a HEART score of 4-6 points implies admission for clinical observation. A HEART score >/=7points, with a risk of 72.7%, supports early invasive strategies. CONCLUSION: The HEART score facilitates accurate diagnostic and therapeutic choices. The HEART score is an easy, quick and reliable predictor of outcome in chest pain patients. (Neth Heart J 2008;16:191-6.).

Comparison of the GRACE, HEART and TIMI score to predict major adverse cardiac events in chest pain patients at the emergency department.

BACKGROUND: The performance of the GRACE, HEART and TIMI scores were compared in predicting the probability of major adverse cardiac events (MACE) in chest pain patients presenting at the emergency department (ED), in particular their ability to identify patients at low risk. METHODS: Chest pain patients presenting at the ED in nine Dutch hospitals were included. The primary outcome was MACE within 6weeks. The HEART score was determined by the treating physician at the ED. The GRACE and TIMI score were calculated based on prospectively collected data. Performance of the scores was compared by calculating AUC curves. Additionally, the number of low-risk patients identified by each score were compared at a fixed level of safety of at least 95% or 98% sensitivity. RESULTS: In total, 1748 patients were included. The AUC of GRACE, HEART, and TIMI were 0.73 (95% CI: 0.70-0.76%), 0.86 (95% CI: 0.84-0.88%) and 0.80 (95% CI: 0.78-0.83%), respectively (all differences in AUC highly statistically significant). At an absolute level of safety of at least 98% sensitivity, the GRACE score identified 231 patients as "low risk" in which 2.2% a MACE was missed; the HEART score identified 381 patients as "low risk" with 0.8% missed MACE. The TIMI score identified no "low risk" patients at this safety level. CONCLUSIONS: The HEART score outperformed the GRACE and TIMI scores in discriminating between those with and without MACE in chest pain patients, and identified the largest group of low-risk patients at the same level of safety.

Prognostic Factors in Chest Pain Patients: A Quantitative Analysis of the HEART Score.

OBJECTIVES: Risk stratification for chest pain patients at the emergency department is recommended in several guidelines. The history, ECG, age, risk factors, and troponin (HEART) score is based on medical literature and expert opinion to estimate the risk of a major adverse cardiac event. We aimed to assess the predictive effects of the 5 HEART components and to compare performances of the original HEART score and a model based on regression analysis. METHODS: We analyzed prospectively collected data from 2388 patients, of whom 407 (17%) had a major adverse cardiac event within 6 weeks (acute myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, significant stenosis with conservative treatment and death due to any cause). RESULTS: Univariate regression analysis showed the same ordering of predictive effects as used in the HEART score. Based on multivariable logistic regression analysis, an adjusted score showed slightly better calibration and discrimination (c statistic HEART, 0.83, HEART-adj, 0.85). In comparison to HEART, HEART-adj proved in a decision curve analysis clinically useful for decision thresholds over 25%. Nevertheless, the original HEART classified patients better than HEART-adj (net reclassification improvement = 14.1%). CONCLUSION: The previously chosen weights of the 5 elements of the HEART score are supported by multivariable statistical analyses, although some improvement in calibration and discrimination is possible by adapting the score. The gain in clinical usefulness is relatively small and supports the use of either the original or adjusted HEART score in daily practice.

Medical consumption compared for TIMI and HEART score in chest pain patients at the emergency department: a retrospective cost analysis.

OBJECTIVE: To investigate which risk score (TIMI score or HEART score) identifies the largest population of low-risk patients at the emergency department (ED). Furthermore, we retrospectively calculated the corresponding expected decrease in medical consumption if these patients would have been discharged from the ED. METHODS: We performed analyses in two hospitals of the multicentre prospective validation study of the HEART score, executed in 2008 and 2009. Patients with chest pain presenting to the ED were included and information was collected on major adverse cardiac events (MACEs) and on hospital admissions and diagnostic procedures within 6 weeks. The TIMI and HEART score were calculated for each patient. RESULTS: We analysed 640 patients (59% male, mean age of 60, cumulative incidence of MACE 17%). An estimated total of €763 468 was spent during follow-up on hospital admission and diagnostic procedures. In total, 256 (40%) patients had a HEART score of 0-3 and were considered low risk (miss rate 1.6%), a total of €64 107 was spent on diagnostic procedures and hospital admission after initial presentation in this group. In comparison, 105 (16%) patients with TIMI score of 0 were considered low risk (miss rate 0%), with a total of €14 670 spent on diagnostic procedures and initial hospital admission costs. With different cut-offs for low risk, HEART 0-2 (miss rate 0.7%), would have resulted in a total of €25 365 in savings, compared with €71 905 when an alternative low risk cut-off for TIMI of TIMI≤1 would be used (miss rate 3.0%). CONCLUSIONS: The HEART score identifies more patients as low risk compared with the TIMI score, which may lead to a larger reduction in diagnostic procedures and costs in this low-risk group. Future studies should prospectively investigate whether adhering to the HEART score in clinical practice and early discharge of low-risk patients is safe and leads to a reduction in medical consumption.

Activation of the fibrinolytic system during intracoronary streptokinase administration.

Serial biochemical studies were performed in 12 patients treated with intracoronary streptokinase infusion for acute myocardial infarction, in order to study the method of activation of the fibrinolytic system during local administration of a relatively low dose of this drug and to determine correlations between systemic effects and reperfusion. Plasma samples were obtained before and every 15 minutes during the infusion of streptokinase and after completion of the therapy. Streptokinase dosage in this study was 211,000 +/- 88,000 IU (+/- SD). The average time from the onset of symptoms to the start of infusion was 2 hours 50 minutes (range 1 hour 10 minutes to 3 hours 30 minutes). Reperfusion occurred in six patients and temporary recanalization in three; in three patients no recanalization was achieved. Fibrinolytic assays of pretreatment plasma samples revealed elevated levels of plasminogen activators, presumably caused by the release of tissue-type plasminogen activator after a condition of stress. Plasminogen concentrations decreased from 94 +/- 17% to 44 +/- 30%. Alpha 2-antiplasmin fell from 84 +/- 27% to 12 +/- 19%; in seven patients no plasmin inhibitor activity was measurable at the completion of the infusion. Free plasmin occurred in samples only when this inhibitor had disappeared. This resulted in a lytic state leading to degradation of fibrinogen, the levels of which fell from 2.9 +/- 0.7% to 1.5 +/- 1.1%. Fibrinogen degradation products, measured in plasma with monoclonal antibodies, increased exponentially during streptokinase infusion in at least four patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasmin inhibitors in the prevention of systemic effects during thrombolytic therapy: specific role of the plasminogen-binding form of alpha 2-antiplasmin.

To delineate the role of plasmin inhibitors, especially the two molecular forms of alpha 2-antiplasmin (that is, the plasminogen-binding and the nonplasminogen-binding forms), in the control of systemic effects during thrombolytic therapy, the consumption of plasmin inhibitors and the degree of fibrinogen breakdown were studied in 35 patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA) or streptokinase. At a low degree of plasminogen activation (in six patients treated with rt-PA), plasminogen-binding alpha 2-antiplasmin was consumed first. At a higher degree of plasminogen activation (in 20 patients), plasminogen-binding alpha 2-antiplasmin became exhausted (less than 20%) and other plasmin inhibitors (that is, nonplasminogen-binding alpha 2-antiplasmin and alpha 2-macroglobulin) were consumed. After extensive plasminogen activation (in nine patients treated with streptokinase), plasminogen-binding alpha 2-antiplasmin consumption was complete and nonplasminogen-binding alpha 2-antiplasmin and alpha 2-macroglobulin were consumed to about 30% to 50% of the pretreatment level. No significant C1-inactivator consumption occurred, even at extreme degrees of plasminogen activation. Fibrinogen breakdown as a marker for systemic effects correlated strongly with consumption of plasminogen-binding alpha 2-antiplasmin. Fibrinogen breakdown did occur, but only when the amount of plasminogen-binding alpha 2-antiplasmin was decreased to less than 20% of the pretreatment level. The other plasmin inhibitors could not prevent fibrinogen breakdown. These results were confirmed by in vitro studies. It is concluded that plasminogen-binding alpha 2-antiplasmin is the most important inhibitor of plasmin in the circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of intensive versus moderate lipid lowering on endothelial function and vascular responsiveness to angiotensin II in stable coronary artery disease.

Recent evidence has demonstrated that intensive lipid-lowering therapy with a high-dose statin provides significant clinical benefit beyond moderate lipid-lowering therapy. However, dose-dependent effects of short-term statin therapy on vascular function have not been demonstrated. We studied endothelial function and vascular responsiveness to angiotensin II in patients who had coronary artery diseased and were randomized to receive low- or high-dose atorvastatin (10 or 80 mg, respectively) or placebo. Internal thoracic artery segments were obtained during coronary bypass surgery and studied in vitro. Endothelium-dependent vasodilation was increased with atorvastatin therapy (p = 0.035) but was significantly increased further in patients who received 80 mg compared with those who received 10 mg of atorvastatin (p = 0.05). Endothelium improvement was accompanied by decreased vascular response to angiotensin II (p = 0.039). These findings suggest a mechanism for the clinical benefit of intensive lipid-lowering treatment in coronary heart disease.

Group B streptococcus neonatal invasive infections, France 2007-2012.

Streptococcus agalactiae (group B streptococcus (GBS)) is the leading cause of invasive infections among newborns in industrialized countries, with two described syndromes: early-onset disease (EOD) and late-onset disease (LOD). Since the introduction in many countries of intrapartum antibioprophylaxis (IAP), the incidence of EOD has dramatically decreased, whereas that of LOD remains unchanged. We describe the clinical and bacteriological characteristics of 438 GBS neonatal invasive infections notified to the French National Reference Centre for Streptococci in France from 2007 to 2012. Clinical data were retrieved from hospitalization reports or questionnaires. Capsular type, assignment to the hypervirulent clonal complex (CC)17 and antibiotic susceptibility profiles were determined. One hundred and seventy-four (39.7%) and 264 (60.3%) isolates were responsible for EOD, including death in utero, and LOD, respectively. EOD was associated with bacteraemia (n = 103, 61%) and LOD with meningitis (n = 145, 55%). EOD was mainly due to capsular polysaccharide (CPS) III isolates (n = 99, 57%) and CPS Ia isolates (n = 40, 23%), and CPS III isolates were responsible for 80% (n = 211) of LOD cases. CC17 accounted for 80% (n = 121) of CPS III isolates responsible for meningitis (n = 151; total cases of meningitis, 188). Bad outcome risk factors were low gestational age and low birthweight. LOD represents almost 60% of cases of neonatal GBS disease in France and other countries in which IAP has been implemented. This observation reinforces the need to develop new prevention strategies targeting CC17, which is predominant in GBS neonatal infections.