Eligibility for Low-Dose Rivaroxaban Based on the COMPASS Trial: Insights from the Veterans Affairs Healthcare System

Cardiovascular Drugs and Therapy - Low-dose rivaroxaban reduced major adverse cardiac and limb events among patients with stable atherosclerotic vascular disease (ASCVD) in the COMPASS trial. The...     

Summary Report of PQRI Workshop on Nanomaterial in Drug Products: Current Experience and Management of Potential Risks

At the Product Quality Research Institute (PQRI) Workshop held last January 14–15, 2014, participants from academia, industry, and governmental agencies involved in the development and regulation of nanomedicines discussed the current state of characterization, formulation development, manufacturing, and nonclinical safety evaluation of nanomaterial-containing drug products for human use. The workshop discussions identified areas where additional understanding of material attributes, absorption, biodistribution, cellular and tissue uptake, and disposition of nanosized particles would continue to inform their safe use in drug products. Analytical techniques and methods used for in vitro characterization and stability testing of formulations containing nanomaterials were discussed, along with their advantages and limitations. Areas where additional regulatory guidance and material characterization standards would help in the development and approval of nanomedicines were explored. Representatives from the US Food and Drug Administration (USFDA), Health Canada, and European Medicines Agency (EMA) presented information about the diversity of nanomaterials in approved and newly developed drug products. USFDA, Health Canada, and EMA regulators discussed the applicability of current regulatory policies in presentations and open discussion. Information contained in several of the recent EMA reflection papers was discussed in detail, along with their scope and intent to enhance scientific understanding about disposition, efficacy, and safety of nanomaterials introduced in vivo and regulatory requirements for testing and market authorization. Opportunities for interaction with regulatory agencies during the lifecycle of nanomedicines were also addressed at the meeting. This is a summary of the workshop presentations and discussions, including considerations for future regulatory guidance on drug products containing nanomaterials.KEY WORDS: nanomaterials, nanomedicine, nanotechnology, PQRI, risk management, USFDA     

Effects of a novel pesticide-particle conjugate on viability and reactive oxygen species generation in neuronal (PC12) cells

Development of new methods and compounds to eradicate insect vectors are desperately needed. To that end, our team has previously described the synthesis and characterization of a conjugate comprised of a silver nanoparticle core encapsulated by the pyrethroid pesticide, deltamethrin (pesticide encapsulated silver nanoparticle termed “PENS”). For this current work, the PENS conjugate was tested in neuronal cultured cells to compare the cytotoxic responses to the unconjugated pesticide deltamethrin – a known neurotoxic agent and pristine silver nanoparticles. The PC12 (pheochromocytoma of the rat adrenal medulla) cell line was chosen as a model neuronal culture system. Cells were exposed to known concentrations of PENS, deltamethrin or silver nanoparticle suspensions to assess the degree of toxicity in vitro. After 24 hours of incubation, cell viability and intracellular reactive oxygen species (ROS) were measured. Bright field images of high dose exposures to dosing solutions were also acquired to evaluate cell morphology. Exposure to PENS resulted in a 17% decline in viability at the highest concentration of 45?µM while exposure to deltamethrin caused a 47% decrease. These results suggest that cellular viability was less adversely affected by PENS than by the deltamethrin. Also, ROS production following PENS exposure indicated that the newly developed conjugate was responding in a similar manner as that of cells treated with deltamethrin only.     

Premature Atherosclerotic Cardiovascular Disease Risk Among Patients with Inflammatory Bowel Disease

BackgroundRecent literature has shown an association between atherosclerotic cardiovascular disease and inflammatory bowel disease, potentially mediated through chronic inflammatory pathways. However, there is a paucity of data demonstrating this relationship among young patients with premature atherosclerotic cardiovascular disease.MethodsUsing data from the nationwide Veterans wIth premaTure AtheroscLerosis (VITAL) registry, we assessed the association between extremely premature and premature atherosclerotic cardiovascular disease (age at diagnosis: ≤40 years and ≤55 years, respectively) and inflammatory bowel disease. Patients were compared with age-matched controls without atherosclerotic cardiovascular disease. Multivariable regression models adjusted for traditional risk factors.ResultsWe identified 147,600 patients and 9485 patients with premature and extremely premature atherosclerotic cardiovascular disease, respectively. Compared with controls, there was a higher prevalence of overall inflammatory bowel disease among premature (0.96% vs 0.84%; odds ratio [OR] 1.14; 95% confidence interval [CI], 1.08-1.21) and extremely premature (1.36% vs 0.75%; OR 1.82; 95% CI, 1.52-2.17) patients. After adjustment, these associations attenuated in both premature and extremely premature groups (OR 1.07; 95% CI, 1.00-1.14 and OR 1.61; 95% CI, 1.34-1.94, respectively).ConclusionInflammatory bowel disease is associated with higher odds of extremely premature atherosclerotic cardiovascular disease, especially for those age ≤40 years. With increasing age, this risk is attenuated by traditional cardiometabolic factors such as obesity, hypertension, diabetes, smoking, and dyslipidemia. Prospective studies are needed to assess the role of early intervention to decrease cardiovascular risk among young patients with inflammatory bowel disease.     

When diplomacy fails: difficulty understanding hints following severe traumatic brain injury

Background: In the absence of aphasia, many people with severe traumatic brain injuries (TBI) have difficulty with communication. In particular, they have difficulty understanding conversational inference. Poor social cognition is also prevalent following TBI.

Aims: This study aimed to examine the role of social cognition in the ability to recognise conversational inference in the form of hints.

Methods and procedures: 31 adults (22 men: mean age 45 years) with chronic (mean time since injury = 15.12 years) and severe TBI (mean post traumatic amnesia (PTA) of 32.74 days) and 24 adults (14 men: mean age 46.1 years) from the community participated. They were compared for their comprehension of two kinds of video vignettes in which professional actors made progressively more explicit hints. In one version, the conversational tone was neutral, in the other emotional. They were also assessed on an independent measure of social cognition (TASIT).

Outcomes & results: The adults with TBI recognised neutral hints at a normal rate but, unlike the community controls, were not facilitated by overtly emotional hints. Social cognition performance was related to performance on both types of hint. Improved performance on the emotional hints was not uniquely predicted by social cognition but, rather, by processing speed and possibly also stress in the group with TBI.

Conclusions: People with TBI appear to have difficulty using emotional cues to infer speaker meaning. This may reflect cognitive slowing and also anxiety and stress. This has implications for both remediation of such deficits and for educating others who interact with people with TBI.     

Feasibility of an intervention for men on androgen deprivation therapy: A research protocol

Androgen deprivation therapy (ADT) is a treatment used across the prostate cancer disease spectrum and works by suppressing testicular androgen production to castrate levels. Although ADT can provide survival benefits, it is also associated with increased risk for cardiovascular disease, metabolic syndrome, increased visceral fat mass, dyslipidemia, decreased arterial compliance, and diminished health‐related quality of life. The Staying Strong And Healthy protocol is a telephone‐delivered intervention led by a nurse coordinator to minimize the increased cardiovascular and metabolic risks associated with ADT. This study will evaluate the feasibility of the protocol and provides the foundation for future behavioral interventions across diverse populations of men on ADT.