Bivalirudin versus heparin as an antithrombotic agent in patients who undergo percutaneous saphenous vein graft intervention with a distal protection device

Bivalirudin (Angiomax) is increasingly used as a substitute for heparin in a variety of percutaneous coronary interventions, and data on its usage in saphenous vein graft interventions are limited. This retrospective, observational study evaluated the efficacy and safety of bivalirudin compared with heparin as an antithrombotic regimen in patients who underwent saphenous vein graft intervention with distal protection devices. We found that bivalirudin use is clinically safe and feasible, with fewer vascular and ischemic complications compared with heparin.     

NMDA receptor function is regulated by the inhibitory scaffolding protein, RACK1

Phosphorylation regulates the function of ligand-gated ion channels such as the N-methyl d-aspartate (NMDA) receptor. Here we report a mechanism for modulation of the phosphorylation state and function of the NMDA receptor via an inhibitory scaffolding protein, RACK1. We found that RACK1 binds both the NR2B subunit of the NMDA receptor and the nonreceptor protein tyrosine kinase, Fyn. RACK1 inhibits Fyn phosphorylation of NR2B and decreases NMDA receptor-mediated currents in CA1 hippocampal slices. Peptides that disrupt the interactions between RACK1, NR2B, and Fyn induce phosphorylation and potentiate NMDA receptor-mediated currents. Therefore, RACK1 is a regulator of NMDA receptor function and may play a role in synaptic plasticity, addiction, learning, and memory.     

Should Health Care Providers be Accountable for Patients’ Care Experiences?

Measures of patients’ care experiences are increasingly used as quality measures in accountability initiatives. As the prominence and financial impact of patient experience measures have increased, so too have concerns about the relevance and fairness of including them as indicators of health care quality. Using evidence from the Consumer Assessment of Healthcare Providers and Systems (CAHPS®) surveys, the most widely used patient experience measures in the United States, we address seven common critiques of patient experience measures: (1) consumers do not have the expertise needed to evaluate care quality; (2) patient “satisfaction” is subjective and thus not valid or actionable; (3) increasing emphasis on improving patient experiences encourages health care providers and plans to fulfill patient desires, leading to care that is inappropriate, ineffective, and/or inefficient; (4) there is a trade-off between providing good patient experiences and providing high-quality clinical care; (5) patient scores cannot be fairly compared across health care providers or plans due to factors beyond providers’ control; (6) response rates to patient experience surveys are low, or responses reflect only patients with extreme experiences; and (7) there are faster, cheaper, and more customized ways to survey patients than the standardized approaches mandated by federal accountability initiatives.KEY WORDS: patient satisfaction, performance measurement, quality assessment, patient-centered care     

Recombinant Immunomodulating Lentogenic or Mesogenic Oncolytic Newcastle Disease Virus for Treatment of Pancreatic Adenocarcinoma

Oncolytic Newcastle disease virus (NDV) might be a promising new therapeutic agent for the treatment of pancreatic cancer. We evaluated recombinant NDVs (rNDVs) expressing interferon (rNDV-hIFNβ-F₀) or an IFN antagonistic protein (rNDV-NS1-F₀), as well as rNDV with increased virulence (rNDV-F_3aa) for oncolytic efficacy in human pancreatic adenocarcinoma cells. Expression of additional proteins did not hamper virus replication or cytotoxic effects on itself. However, expression of interferon, but not NS1, resulted in loss of multicycle replication. Conversely, increasing the virulence (rNDV-F_3aa) resulted in enhanced replication of the virus. Type I interferon was produced in high amounts by all tumor cells inoculated with rNDV-hIFNβ-F₀, while inoculation with rNDV-NS1-F₀ resulted in a complete block of interferon production in most cells. Inoculation of human pancreatic adenocarcinoma cells with rNDV-F_3aa caused markedly more cytotoxicity compared to rNDV-F₀, while inoculation with rNDV-hIFNβ-F₀ and rNDV-NS1-F₀ induced cytotoxic effects comparable to those induced by the parental rNDV-F₀. Evaluation in vivo using mice bearing subcutaneous pancreatic cancer xenografts revealed that only intratumoral injection with rNDV-F_3aa resulted in regression of tumors. We conclude that although lentogenic rNDVs harboring proteins that modulate the type I interferon pathway proteins do have an oncolytic effect, a more virulent mesogenic rNDV might be needed to improve oncolytic efficacy.     

Defective recovery of QT dispersion following transcatheter aortic valve implantation: frequency, predictors and prognosis

Background Corrected QT dispersion (cQTD) has been correlated with non-uniform ventricular repolarisation and increased mortality. In patients with aortic stenosis, cQTD has been shown improved after surgical valve replacement, but the effects of transcatheter aortic valve implantation (TAVI) are unknown. Therefore, we sought to explore the frequency, predictors and prognostic effects of defective cQTD recovery at 6 months after TAVI. Methods A total of 222 patients underwent TAVI with the Medtronic-CoreValve System between November 2005 and January 2012. Patients who were on classⅠor Ⅲ antiarrhythmics or on chronic haemodialysis or who developed atrial fibrillation, a new bundle branch block or became pacemaker dependent after TAVI were excluded. As a result, pre-, post- and follow-up ECG (median: 6 months) analysis was available in 45 eligible patients. Defective cQTD recovery was defined as any progression beyond the baseline cQTD at 6 months. Results In the 45 patients, the mean cQTD was 47 ± 23 ms at baseline, 45 ± 17 ms immediately after TAVI and 40 ± 16 ms at 6 months (15% reduction, P = 0.049). Compared to baseline, cQTD at 6 months was improved in 60% of the patients whereas defective cQTD recovery was present in 40%. cQTD increase immediately after TAVI was an independent predictor of defective cQTD recovery at 6 months (per 10 ms increase; OR: 1.89, 95% CI: 1.15–3.12). By univariable analysis, defective cQTD recovery was associated with late mortality (HR: 1.52, 95% CI: 1.05–2.17). Conclusions Despite a gradual reduction of cQTD after TAVI, 40% of the patients had defective recovery at 6 months which was associated with late mortality. More detailed ECG analysis after TAVI may help to avoid late death.     

Modeling strategy to identify patients with primary immunodeficiency utilizing risk management and outcome measurement

This study seeks to generate analytic insights into risk management and probability of an identifiable primary immunodeficiency defect. The Jeffrey Modell Centers Network database, Jeffrey Modell Foundation’s 10 Warning Signs, the 4 Stages of Testing Algorithm, physician-reported clinical outcomes, programs of physician education and public awareness, the SPIRIT® Analyzer, and newborn screening, taken together, generates P values of less than 0.05%. This indicates that the data results do not occur by chance, and that there is a better than 95% probability that the data are valid. The objectives are to improve patients’ quality of life, while generating significant reduction of costs. The advances of the world’s experts aligned with these JMF programs can generate analytic insights as to risk management and probability of an identifiable primary immunodeficiency defect. This strategy reduces the uncertainties related to primary immunodeficiency risks, as we can screen, test, identify, and treat undiagnosed patients. We can also address regional differences and prevalence, age, gender, treatment modalities, and sites of care, as well as economic benefits. These tools support high net benefits, substantial financial savings, and significant reduction of costs. All stakeholders, including patients, clinicians, pharmaceutical companies, third party payers, and government healthcare agencies, must address the earliest possible precise diagnosis, appropriate intervention and treatment, as well as stringent control of healthcare costs through risk assessment and outcome measurement. An affected patient is entitled to nothing less, and stakeholders are responsible to utilize tools currently available. Implementation offers a significant challenge to the entire primary immunodeficiency community.     

Patterns of internet use and mental health of high school students in Istria County,Croatia: cross-sectional study

Aim

To examine associations between different forms of internet use and a number of psychological variables related to mental health in adolescents.

Methods

A cross-sectional survey was carried out on a representative sample of students (N = 1539) from all high schools in the region of Istria in Croatia (14-19 years). The associations between four factors of internet use and nine mental health indicators were analyzed using canonical correlation analysis.

Results

The four canonical functions suggested a significant association between different types of internet use and specific indicators of mental health (P < 0.001). Problematic internet use, more typical among boys, was associated with general aggressive behavior and substance abuse (P < 0.001). Experiences of harassment, more typical among girls, were associated with health complaints, symptoms of depression, loneliness, and fear of negative evaluation (P < 0.001). Using the internet for communication and entertainment was associated with better relationships with peers (P < 0.001), while use of the internet for academic purposes was associated with conscientiousness (P < 0.001).

Conclusion

The results suggest that different patterns of internet use are significantly associated with specific sets of positive and negative mental health indicators. The data support the assumption that internet use can have both positive and adverse effects on the mental health of youth.New technologies, and especially the use of computers and the internet, are part of the everyday lives of young people and have a significant impact on their psychological development. Indeed, this mass use of new media technologies presents parents and society with a challenge to protect and support the positive development of children and youth. To date, a number of studies have examined the positive and negative aspects of using internet technologies.Literature points to several positive aspects of internet use (1,2): for information acquiring, communication, and social networking, entertainment, and online shopping. More specifically, adolescents use the internet as a useful source of information about school assignments, daily events, interests and hobbies, or health and sexuality concerns. In these instances, online activities aimed at connecting with peers have a significant place. Visiting social networking sites and using communication tools such as email, chat, forums, and discussion groups enables the creation of friendships and social groups and contributes to the development of personal identity (3). The use of computers and the internet (cyberspace) has also been argued to provide opportunities for new and faster learning, exercising one''s self-control, considering different opinions, expressing one''s attitudes and tolerance, and developing skills in critical thinking and decision-making (4). Best et al (5) found that use of online communication technologies contributed to increased self-confidence, better perception of social support, greater social capital, positive experimenting with one’s own identity, and greater opportunities for open self-disclosure. Conversely, adolescents who do not use the internet might trail behind in the development of such positive attitudes and traits and risk being rejected by their peers (6). Finally, Livingstone et al (7) found that a certain amount of risk exposure was useful in building resilience.In contrast to these positive influences of internet use, harmful effects of internet abuse range from exposure to inappropriate sexual content, pornography, and violence (2,7) to humiliation and cyber-bullying (6,8-10) and internet addiction (11,12). Research has confirmed the link between internet abuse and social isolation, depression and, anxiety (1,5,13,14), alcohol and drug abuse and gambling (15), and problems with physical health (16). Ybarra and Mitchell (17) found a connection between experiences of threats or humiliation in the virtual world and absences from school, lower school achievement, substance use disorders, delinquency and depression. Fekkes et al (18) point to the association between victimizing experiences and a number of physical, emotional, and behavioral problems, such as headaches, tension, fatigue, loss of appetite, enuresis, and sleeping problems. Slonje and Smith (19) define such experiences as a product of cyber-bullying and argue that this can be viewed as another form of aggressive behavior. Gender has emerged as a significant predictor of the manner in which the internet is used. Specifically, girls tend to experience victimizing experiences, while boys more frequently demonstrate antisocial behavior (20,21).Although many studies have identified both positive and negative correlates of internet use, there have been only a few studies using complex multivariate analyses to identify broader patterns of internet use and adolescent mental health (22,23). Less is known about how adolescents exhibiting different personalities and different emotional and behavioral patterns engage in internet use and what might be the consequences of this engagement. The aim of this study was to determine the specific patterns of internet use and mental health among adolescents. The following hypotheses were tested:H1: Problematic internet use is associated with externalized symptoms and other negative indicators of mental health. Exposure to victimizing and disturbing content on the internet is associated with internalized symptoms and negative indicators of mental health.H2: Prosocial internet use (aimed at connecting with peers and entertainment) and internet use for school purposes are associated with positive aspects of mental health.H3: Problematic internet use is present more often in young men, while exposure to disturbing content on the internet is more frequently experienced by young women.