Evaluation of pain, disruptive behaviour and anxiety in children aging 5-8 years old undergoing different modalities of local anaesthetic injection for dental treatment: a randomised clinical trial.

To evaluate the influence of different local anaesthetic techniques in pain, disruptive behaviour and anxiety in children´s dental treatment. This was a randomised and parallel clinical trial. The sample consisted of 105 children (5-8 years old) that were divided into three groups ( = 35) according to the anaesthetic technique: conventional anaesthesia (CA); vibrational anaesthesia (VBA); computer-controlled local anaesthesia delivery (CCLAD).

Recommendations from the Investigational New Drug/Investigational Device Exemption Task Force of the clInical and Translational Science Award Consortium: developing and implementing a sponsor-investigators training program.

Objective: The objective of this study was to provide recommendations for provision of training for sponsor and investigators at Academic Health Centers.

Background: A subgroup of the Investigational New Drug/Investigational Device Exemption (IND/IDE) Task Force of the Clinical and Translational Science Award (CTSA) program Regulatory Knowledge Key Function Committee was assembled to specifically address how clinical investigators who hold an IND/IDE and thus assume the role of sponsor-investigators are adequately trained to meet the additional regulatory requirements of this role.

Methods: The participants who developed the recommendations were representatives of institutions with IND/IDE support programs.

A roadmap for academic health centers to establish good laboratory practice-compliant infrastructure.

Prior to human clinical trials, nonclinical safety and toxicology studies are required to demonstrate that a new product appears safe for human testing; these nonclinical studies are governed by good laboratory practice (GLP) regulations. As academic health centers (AHCs) embrace the charge to increase the translation of basic science research into clinical discoveries, researchers at these institutions increasingly will be conducting GLP-regulated nonclinical studies. Because the consequences for noncompliance are severe and many AHC researchers are unfamiliar with Food and Drug Administration regulations, the authors describe the regulatory requirements for conducting GLP research, including the strict documentation requirements, the necessary personnel training, the importance of study monitoring, and the critical role that compliance oversight plays in the process.

Serial measurements of midregion proANP and copeptin in ambulatory patients with heart failure: incremental prognostic value of novel biomarkers in heart failure.

Background: Disease progression in heart failure (HF) reflects derangements in neurohormonal systems, and biomarkers of these systems can help to establish the diagnosis and assess the prognosis. Serial measurements of the precursor peptides of the natriuretic and vasopressin systems (midregional proatrial natriuretic peptide (MR-proANP) and C-terminal provasopressin (copeptin), respectively) should add incremental value to risk stratification in ambulatory patients with HF.

Methods And Results: A cohort of 187 patients with class III-IV HF was prospectively enrolled, with biomarkers collected every 3 months over 2 years and analysed in relation to death/transplantation.

Support for investigator-initiated clinical research involving investigational drugs or devices: the Clinical and Translational Science Award experience.

Purpose: Investigator-initiated research involving investigational drugs and devices is key to improving health. However, this requires the investigator to serve as a "sponsor-investigator," which can be complex and overwhelming. The Investigational New Drug/Investigational Device Exemption (IND/IDE) Taskforce of the Clinical and Translational Science Award (CTSA) consortium carried out a survey to examine how academic health centers (AHCs) assist sponsor-investigators with regulatory responsibilities.

Relation of ADRB1, CYP2D6, and UGT1A1 polymorphisms with dose of, and response to, carvedilol or metoprolol therapy in patients with chronic heart failure.

The response to beta blockers in patients with heart failure could be associated with the genotype of drug-metabolizing enzymes and/or drug targets. The purpose of the present study was to determine whether specific genetic polymorphisms in ADRB1 (encoding the beta1-adrenergic receptor), CYP2D6, and UGT1A1 correlated with dose of, or response to, metoprolol or carvedilol treatment in patients with heart failure. A cohort of patients with heart failure (n = 93), characterized as responders or nonresponders to metoprolol (n = 19) or carvedilol (n = 74) therapy, was retrospectively identified.

Response of novel biomarkers to BNP infusion in patients with decompensated heart failure: a multimarker paradigm.

Multibiomarker paradigms have been proposed to diagnose, define progression, and to monitor therapy of heart failure (HF) patients. The aim of this study was to evaluate the prognostic and therapy-monitoring potential of four novel biomarkers (copeptin, midregional proatrial natriuretic peptide (MR-proANP), neopterin, and procalcitonin) which have been shown to be elevated in the plasma of patients with HF and reported to have prognostic value. In a prospective study of 40 patients hospitalized for decompensated HF and who received nesiritide infusions as part of their care, blood was drawn before, during, and postinfusion and assayed for the novel biomarkers.

Improvement in health-related quality of life after hospitalization predicts event-free survival in patients with advanced heart failure.

Background: Health-related quality of life (HRQOL) is a major clinical outcome for heart failure (HF) patients. We aimed to determine the frequency, durability, and prognostic significance of improved HRQOL after hospitalization for decompensated HF.

Methods And Results: We analyzed HRQOL, measured serially using the Minnesota Living with Heart Failure Questionnaire (MLHFQ), for 425 patients who survived to discharge in a multicenter randomized clinical trial of pulmonary artery catheter versus clinical assessment to guide therapy for patients with advanced HF.

Profiles of serial changes in cardiac troponin T concentrations and outcome in ambulatory patients with chronic heart failure.

Objectives: The purpose of this study was to determine whether different profiles of cardiac troponin T (cTnT) values assessed over time would yield incremental prognostic information on clinically stable outpatients with heart failure (HF).

Background: cTnT levels were used to estimate prognosis in HF; however, most studies evaluated hospitalized patients using single measurements.

Methods: A cohort of 172 New York Heart Association functional class III to IV outpatients was prospectively studied with serial cTnT measurements collected every 3 months over a 2-year period.

Role for precursor Pro-B type natriuretic peptide in assessing response to therapy and prognosis in patients with decompensated heart failure treated with nesiritide.

Background: ProBNP, the precursor peptide to BNP and NT-proBNP (NP), circulates in patients with chronic heart failure (HF) and appears to be the predominant form of NP. This heterogeneity may confound interpretation of NP concentrations. The aim of this study was to evaluate the response to therapy and prognostic influence of proBNP in a cohort of patients admitted to hospital for decompensated HF.

Only large reductions in concentrations of natriuretic peptides (BNP and NT-proBNP) are associated with improved outcome in ambulatory patients with chronic heart failure.

Background: Concentrations of B-type natriuretic peptides (BNPs), including N-terminal pro-B-type natriuretic peptide (NT-proBNP), can be used to estimate prognosis in chronic heart failure. Large biologic variability, however, limits the usefulness of serial measurements in individual patients. As a result, the magnitude of change in peptide concentrations that is clinically meaningful remains to be established.

Multi-center validation of the Response Biomedical Corporation RAMP NT-proBNP assay with comparison to the Roche Diagnostics GmbH Elecsys proBNP assay.

Background: NT-proBNP measurements aid in the evaluation of patients with suspected heart failure (HF) and may facilitate risk stratification in patients with HF and acute coronary syndrome (ACS). Point-of-care (POC) assays may provide more timely results and potentially improve patient outcomes.

Methods: We evaluated the analytical performance of the Response Biomedical Corporation whole blood RAMP amino-terminal pro-B type natriuretic peptide (NT-proBNP) POC assay compared to the Roche Elecsys proBNP (NT-proBNP) assay.

Serial biomarker measurements in ambulatory patients with chronic heart failure: the importance of change over time.

Background: Cardiac troponin T (cTnT) and B-type natriuretic peptide (BNP) have been used to estimate prognosis in heart failure; however, most studies have evaluated decompensated patients with single measurements. To determine if there are advantages to serial measurements, we evaluated stable chronic heart failure patients every 3 months for 2 years.

Methods And Results: A cohort of 190 New York Heart Association class III-IV heart failure patients was prospectively enrolled from June 2001 to January 2004.

Troponin, B-type natriuretic peptides and outcomes in severe heart failure: differences between ischemic and dilated cardiomyopathies.

Background: Ischemic (ISCM) and idiopathic dilated (IDCM) cardiomyopathies have different responses to therapy and outcomes. Both may demonstrate elevations in troponin and B-type natriuretic peptides, but biomarker levels have not been reported to differ as a function of the etiology of heart failure (HF). Accordingly, we compared these biomarkers in patients with chronic HF.

Prediction of rehospitalization and death in severe heart failure by physicians and nurses of the ESCAPE trial.

Background: The predictive accuracy of physician investigators and nurse coordinators in estimating the risk of rehospitalization and death was determined for 373 hospitalized patients with severe advanced heart failure enrolled in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial.

Methods And Results: Estimates were made at discharge, and patients were followed for 6 months after hospitalization. A statistical prognostic model was developed from clinical and laboratory data for the end points of rehospitalization and death.

Smart strategic planning for cardiovascular services.

Strategic planning for cardiovascular services should include formation of a cardiovascular advisory committee composed of key stakeholders. The strategic plan should include an internal assessment, external market analysis, review of operations, development of strategies and initiatives, and a financial analysis. The organization's mission and vision, as well as its financial situation, need to be considered in formulating strategies.

Lower rather than higher levels of B-type natriuretic peptides (NT-pro-BNP and BNP) predict short-term mortality in end-stage heart failure patients treated with nesiritide.

Elevated plasma natriuretic peptides in heart failure (HF) usually indicate a poor outcome and low levels a compensated state. In advanced chronic HF, however, low levels may reflect an impaired neurohormonal response. To assess this hypothesis, this study analyzed whether N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) and B-type natriuretic peptide (BNP) levels were related to mortality in 40 patients treated for decompensated chronic HF.

Biomarker responses during and after treatment with nesiritide infusion in patients with decompensated chronic heart failure.

Background: Objective methods to assess the adequacy of medication therapy for patients with advanced heart failure are lacking. Serial measurements of biomarkers might be beneficial. Therapy guided by N-terminal pro-B-type natriuretic peptide (NT-proBNP) might be helpful because NT-proBNP should be lowered by therapies that decrease endogenous BNP secretion.