Aromatic Compound-Dependent Staphylococcus aureus

Staphylococcus aureus nasal carriage is a risk factor for individuals suffering from trauma, surgical procedures, invasive devices, and/or decreased immunity. Recently, we demonstrated that artificial nasal colonization with an attenuated S. aureus mutant reduced by bacterial interference with the colonization of pathogenic strains of S. aureus. This could be an optional tool to diminish the rate of S. aureus infections in hospitalized patients. The aim of this study was to construct a safe ΔaroA mutant of S. aureus and to discriminate it from nasal colonizing and osteomyelitis S. aureus isolates by SmaI pulsed-field gel electrophoresis (PFGE) typing. The ΔaroA mutant, named RD17, exhibited an LD50 (3.2 × 106 colony-forming unit (CFU)) significantly higher than that of the parental strain (2.2 × 103 CFU). The colony number of the RD17 mutants recovered from nares of leukopenic mice was similar to that observed in the animals of the control group. Therefore, the ΔaroA mutant was demonstrated to be safe due to maintaining low growth levels in the nares regardless of immune status of the animals. PFGE typing allowed the unequivocal identification of the S. aureus and differentiation of aroA mutants in nasal colonizing and osteomyelitis isolates. This information could be important to discriminate endogenous infections from laboratory strains of S. aureus

Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

<p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

Sudden death profilaxis in heart failure

Sudden cardiac death (SCD) is the leading cause of mortality in heart failure (HF). Today the implantable cardioverter-defibrillator (ICD) has become a commonplace therapy around the world for patients with both ischemic and non-ischemic cardiomyopathy and an ejection fraction (EF) < or = 35%. However, EF alone does not discriminate between the modes of death from HF (sudden arrhythmic death vs. non-sudden death). Other risk statifiers, such as electrophysiologic study and microvolt T-wave alternans testing, should therefore be used in the appropriate settings to minimize the number of unnecessary device implants. In addition, left ventricular mechanical dyssynchrony has now become recognized as an additional major marker of cardiac mortality. Its assessment should entail echocardiography rather than measurement of the QRS duration. This will allow us to better integrate the ability of cardiac resynchronization therapy (CRT) in enhancing cardiac function with the ability of an ICD in preventing SCD. This review aims to: 1) give a synthesis of the published evidence regarding the value of implantable ICDs and CRT in the primary prophylaxis of SCD in HF; 2) discuss controversial clinical issues in this area; and 3) recommend practical device-based management strategies

An academic ECG core lab perspective of the FDA initiative for digital ECG capture and data management in large-scale clinical trials

Maximal utility of accessible data is attractive to all partners in clinical research, whether it directly improves patient care or more accurately allows identification of the safety and efficacy of a new drug or procedure. The Food and Drug Administration (FDA) has presented a guideline draft addressing digitization of electrocardiogram (ECG) data in clinical trials to improve the standards for collection, analysis, and storage of safety information on new medical therapies. This FDA initiative has led to discussions and collaboration among the FDA, the pharmaceutical industry, the electrocardiographj, manufacturers, and the academic as well as the nonacademic EGG core labs. In this article, we present a broad-based viewpoint from two groups of academic EGG core labs, the Alliance of Academic EGG Core Labs and the Virtual Electronic EGG Corelab International Consortium. We have chosen to widen the perspective from using digitized EGG data in safety trials only, as addressed by the FDA guideline draft, to a discussion on the possibilities and the potential problems when using digitized EGG data also in large clinical trials focusing on efficacy measurements. We conclude that the benefit of digital data mining is probably well worth an initial incremental effort and expense

Validation of a Brief Form of the Self-Administered Multidimensional Prognostic Index: The SELFY-BRIEF-MPI Project

In clinical practice, self-administered and brief tools to promptly identify older people at risk of frailty are required. The Multidimensional Prognostic Index (MPI), derived from the Comprehensive Geriatric Assessment (CGA) seems reliable enough to serve this purpose, but despite the several versions developed over the past 15 years, it lacks a self-administered and brief version. In this study, we aimed to evaluate the agreement between an abbreviated form of the SELFY-MPI (i.e., SELFY-BRIEF-MPI) and the standard version of the MPI. Four Italian hospitals consecutively enrolled outpatients and inpatients &gt;65 years. The sample included 105 participants (mean age = 78.8 years, 53.3% females). Overall, the two versions showed non-statistically significant differences (Standard-MPI 0.42 ± 0.19 vs. SELFY-BRIEF-MPI 0.41 ± 0.18; p = 0.104) and a very strong correlation (R = 0.86, p &lt; 0.001). The Bland–Altman Plot revealed that only 5/105 measurements (4.76%) were outside the limits of agreement. The accuracy of the SELFY-BRIEF-MPI in identifying frail people (defined as a Standard-MPI &gt; 0.66) was optimal (area under the curve, AUC = 0.90, p &lt; 0.001). To predict multidimensional frailty, a SELFY-BRIEF-MPI score of 0.60 exhibited the greatest sensitivity/specificity ratio. In conclusion, the SELFY-BRIEF-MPI reported a good agreement with the standard version of the MPI, indicating its application in the screening of multidimensional frailty among older people

Standards for the function of an academic 12-lead electrocardiographic core laboratory

An academic 12-lead electrocardiogram (ECG) core laboratory aims to provide the highest possible quality ECG recording, measurement, and storage to aid clinicians in research into important cardiovascular outcomes and to maximize the credibility of scientific results based solely, or in part, on ECG data. This position paper presents a guide for the structure and function of an academic ECG core laboratory. The key functional aspects are: 1) Data collection, 2) Staff composition, 3) Diagnostic measurement and definition standards, 4) Data management, 5) Academic considerations, 6) Economic consideration, and 7) Accreditation. An ECG Core Laboratory has the responsibility for rapid and accurate analysis and responsible management of the electrocardiographic data in multicenter clinical trials. Academic Laboratories, in addition, provide leadership in research protocol generation and production of research manuscripts for submission to the appropriate peer-review journals

The correlation between presenting ST-segment depression and the final size of acute myocardial infarcts in patients with acute coronary syndromes

The use of reperfusion therapy in patients with ST elevation acute coronary syndromes had been established. However, reperfusion therapy is usually considered contra-indicated in those with ST depression, despite the knowledge that regional posterior infarction is typically indicated by ST depression maximal in leads V 1 to V 3 and nonregional subendocardial infarction is typically indicated by marked ST depression maximal in other leads. This study of patients with non-ST-elevation acute coronary syndromes investigates the quantitative relationship between presenting ST depression and final QRS changes in both of these subgroups. The final QRS score was significantly higher (2.44 points) than that of a control group with not ST depression, (1.55 points) in the group with maximal ST depression in V 1 to V 3 ( P=0.04). However, in the entire population, there was a highly significant correlation ( P=.003) between the sum of the presenting ST depression and the final QRS score. Trials of reperfusion therapy will be required to determine if such evolution to electrocardiogram documented acute myocardial infarction can be prevented in patient with marked ST depression acute coronary syndromes