Pharmacokinetics and pharmacodynamics of fenoldopam mesylate for blood pressure control in pediatric patients

<p>Abstract</p> <p>Background</p> <p>Fenoldopam mesylate, a selective dopamine1-receptor agonist, is used by intravenous infusion to treat hypertension in adults. Fenoldopam is not approved by the FDA for use in children; reports describing its use in pediatrics are limited. In a multi-institutional, placebo controlled, double-blind, multi-dose trial we determined the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics and side-effect profile of fenoldopam in children.</p> <p>Methods</p> <p>Seventy seven (77) children from 3 weeks to 12 years of age scheduled for surgery in which deliberate hypotension would be induced were enrolled. Patients were randomly assigned to one of five, blinded treatment groups (placebo or fenoldopam 0.05, 0.2, 0.8, or 3.2 mcg/kg/min iv) for a 30-minute interval after stabilization of anesthesia and placement of vascular catheters. Following the 30-minute blinded interval, investigators adjusted the fenoldopam dose to achieve a target mean arterial pressure in the open-label period until deliberate hypotension was no longer indicated (e.g., muscle-layer closure). Mean arterial pressure and heart rate were continuously monitored and were the primary endpoints.</p> <p>Results</p> <p>Seventy-six children completed the trial. Fenoldopam at doses of 0.8 and 3.2 mcg/kg/min significantly reduced blood pressure (p < 0.05) during the blinded interval, and doses of 1.0–1.2 mcg/kg/min resulted in continued control of blood pressure during the open-label interval. Doses greater than 1.2 mcg/kg/min during the open-label period resulted in increasing heart rate without additional reduction in blood pressure. Fenoldopam was well-tolerated; side effects occurred in a minority of patients. The PK/PD relationship of fenoldopam in children was determined.</p> <p>Conclusion</p> <p>Fenoldopam is a rapid-acting, effective agent for intravenous control of blood pressure in children. The effective dose range is significantly higher in children undergoing anesthesia and surgery (0.8–1.2 mcg/kg/min) than as labeled for adults (0.05–0.3 mcg/kg/min). The PK and side-effect profiles for children and adults are similar.</p

Posttraumatic Stress Disorder Prevalence and Risk of Recurrence in Acute Coronary Syndrome Patients: A Meta-analytic Review

BACKGROUND:Acute coronary syndromes (ACS; myocardial infarction or unstable angina) can induce posttraumatic stress disorder (PTSD), and ACS-induced PTSD may increase patients' risk for subsequent cardiac events and mortality. OBJECTIVE:To determine the prevalence of PTSD induced by ACS and to quantify the association between ACS-induced PTSD and adverse clinical outcomes using systematic review and meta-analysis. DATA SOURCES:Articles were identified by searching Ovid MEDLINE, PsycINFO, and Scopus, and through manual search of reference lists. METHODOLOGY/PRINCIPAL FINDINGS:Observational cohort studies that assessed PTSD with specific reference to an ACS event at least 1 month prior. We extracted estimates of the prevalence of ACS-induced PTSD and associations with clinical outcomes, as well as study characteristics. We identified 56 potentially relevant articles, 24 of which met our criteria (N = 2383). Meta-analysis yielded an aggregated prevalence estimate of 12% (95% confidence interval [CI], 9%-16%) for clinically significant symptoms of ACS-induced PTSD in a random effects model. Individual study prevalence estimates varied widely (0%-32%), with significant heterogeneity in estimates explained by the use of a screening instrument (prevalence estimate was 16% [95% CI, 13%-20%] in 16 studies) vs a clinical diagnostic interview (prevalence estimate was 4% [95% CI, 3%-5%] in 8 studies). The aggregated point estimate for the magnitude of the relationship between ACS-induced PTSD and clinical outcomes (ie, mortality and/or ACS recurrence) across the 3 studies that met our criteria (N = 609) suggested a doubling of risk (risk ratio, 2.00; 95% CI, 1.69-2.37) in ACS patients with clinically significant PTSD symptoms relative to patients without PTSD symptoms. CONCLUSIONS/SIGNIFICANCE:This meta-analysis suggests that clinically significant PTSD symptoms induced by ACS are moderately prevalent and are associated with increased risk for recurrent cardiac events and mortality. Further tests of the association of ACS-induced PTSD and clinical outcomes are needed

HURP Expression-Assisted Risk Scores Identify Prognosis Distinguishable Subgroups in Early Stage Liver Cancer

Hepatoma up-regulated protein (HURP) is a component of the chromatin-dependent pathway for spindle assembly. We examined the prognostic predictive value of HURP in human hepatocellular carcinoma (HCC).HURP expression was evaluated by immunocytochemistry of fine needle aspirated hepatoma cells in 97 HCC patients with Barcelona Clinic Liver Cancer (BCLC) stage A. Subsequently, these patients underwent partial hepatectomy (n = 18) or radiofrequency ablation (n = 79) and were followed for 2 to 35 months. The clinicopathological parameters were submitted for survival analysis.HURP expression in aspirated HCC cells was detected in 19.6% patients. Kaplan-Meier survival analysis showed that positive HURP expression (P = 0.023), cytological grading ≥3 (P = 0.008), AFP ≥35 ng/mL (P = 0.039), bilirubin ≥1.3 mg/dL (P = 0.010), AST ≥50 U/L (P = 0.003) and ALT ≥35 U/L (P = 0.005) were all associated with a shorter disease-free survival. A stepwise multivariate Cox proportional hazard model revealed that positive HURP expression (HR, 2.334; 95% CI, 1.165-4.679, P = 0.017), AST ≥50 U/L (HR, 3.697; 95% CI, 1.868-7.319, p<0.001), cytological grade ≥3 (HR, 4.249; 95% CI, 2.061-8.759, P<0.001) and tumor number >1 (HR, 2.633; 95% CI, 1.212-5.722, P = 0.014) were independent predictors for disease-free survival. By combining the 4 independent predictors, patients with different risk scores (RS) showed distinguishable disease-free survival (RS≤1 vs. RS = 2, P = 0.001; RS = 2 vs. RS = 3, P<0.001). In contrast, the patients cannot be separated into prognosis distinguishable subgroups by using AJCC/UICC TNM staging system.HCC patients with BCLC stage A can be separated into three prognosis-distinguishable groups by use of a risk score that is based upon HURP expression in aspirated HCC cells, ALT, cytological grade and tumor number

Exploring the journey to services

Firms are increasingly providing services to complement their product offerings. The vast majority of studies on the service journey, also known as servitization or service transition, examine the challenges and enablers of the process of change through cases studies. Investigations that provide an in-depth longitudinal analysis of the steps involved in the service journey are much rarer. Such a detailed understanding is required in order to appreciate fully how firms can leverage the enablers while overcoming the challenges of servitization. This study investigates what does a service journey look like? It analyzes in some detail the actual service journeys undertaken by three firms in the well-being, engineering and learning sectors. The paper offers four contributions. First, in the change literature, there are two dominant theories: The punctuated equilibrium model and the continuous change model. This study demonstrates that servitization follows a continuous change rather than a punctuated equilibrium. It shows that such continuous change is neither logical nor structured but much more emergent and intuitive in nature. Second, the study provides empirical evidence to support a contingency view of the dominance and sequencing of the different process models of change across the change journey. Third, this research shows the pace of service development and when the coexistence of basic, intermediate and complex services occurs. Finally, it contributes to the literature in the service field by presenting three actual service journeys and the associated seven stages of the service strategy model that organizations should consider when managing their service journeys

Changing trends in mastitis

<p>Abstract</p> <p>The global dairy industry, the predominant pathogens causing mastitis, our understanding of mastitis pathogens and the host response to intramammary infection are changing rapidly. This paper aims to discuss changes in each of these aspects. Globalisation, energy demands, human population growth and climate change all affect the dairy industry. In many western countries, control programs for contagious mastitis have been in place for decades, resulting in a decrease in occurrence of <it>Streptococcus agalactiae </it>and <it>Staphylococcus aureus </it>mastitis and an increase in the relative impact of <it>Streptococcus uberis </it>and <it>Escherichia coli </it>mastitis. In some countries, <it>Klebsiella </it>spp. or <it>Streptococcus dysgalactiae </it>are appearing as important causes of mastitis. Differences between countries in legislation, veterinary and laboratory services and farmers' management practices affect the distribution and impact of mastitis pathogens. For pathogens that have traditionally been categorised as contagious, strain adaptation to human and bovine hosts has been recognised. For pathogens that are often categorised as environmental, strains causing transient and chronic infections are distinguished. The genetic basis underlying host adaptation and mechanisms of infection is being unravelled. Genomic information on pathogens and their hosts and improved knowledge of the host's innate and acquired immune responses to intramammary infections provide opportunities to expand our understanding of bovine mastitis. These developments will undoubtedly contribute to novel approaches to mastitis diagnostics and control.</p

Using rigorous methods to advance behaviour change science

The field of behaviour change suffers from significant fragmentation and poor reporting. Here, we describe two large-scale initiatives — the Human Behaviour Change Project and Science of Behavior Change programme — that aim to introduce complementary systematic and rigorous methods to advance the science of behaviour change