Scoping review of interventions to de-implement potentially harmful non-steroidal anti-inflammatory drugs (NSAIDs) in healthcare settings.

Objectives: Potentially harmful non-steroidal anti-inflammatory drugs (NSAIDs) utilisation persists at undesirable rates worldwide. The purpose of this paper is to review the literature on interventions to de-implement potentially harmful NSAIDs in healthcare settings and to suggest directions for future research.

Design: Scoping review.

A Scoping Review of Interventions to De-implement Potentially Harmful Nonsteroidal Anti-inflammatory Drugs (NSAIDs) in Healthcare Settings.

Objectives: Potentially harmful nonsteroidal anti-inflammatory drugs (NSAIDs) utilization persists at undesirable rates throughout the world. The purpose of this paper is to review the literature on interventions to de-implement potentially harmful NSAIDs in healthcare settings and to suggest directions for future research.

Design: Scoping review.

Reinforcer pathology in cocaine use disorder: Temporal window determines cocaine valuation.

Aims: The Experimental Medicine Approach offers a unique perspective to determine clinical behavior change by engaging a target underlying the cause of a disorder. The present work engaged a novel target of addiction, Reinforcer Pathology, in two studies to test changes in behavior among individuals with cocaine use disorder.

Methods: In Study 1, n = 44 participants engaged the temporal window with episodic future thinking (EFT), a positive prospection exercise.

The phenotype of recovery V: Does delay discounting predict the perceived risk of relapse among individuals in recovery from alcohol and drug use disorders.

Background: Substance use recovery is a dynamic process. Relapse, often part of the recovery process, is a persistent problem for individuals seeking freedom from their harmful substance use and has become a focus of research on the improvement of recovery outcomes. Delay discounting is associated with substance use disorder severity, both its negative outcomes and the propensity to relapse.

Reinforcer pathology: Narrative of hurricane-associated loss increases delay discounting, demand, and consumption of highly palatable snacks in the obese.

Reinforcer pathology is derived from the integration of two measures: (a) self-control (i.e., delay discounting), and (b) reward valuation (i.

Episodic future thinking reduces delay discounting and cigarette demand: an investigation of the good-subject effect.

Episodic future thinking (EFT), an intervention involving mental simulation of future events, has been shown to reduce both delay discounting and cigarette self-administration. In the present study, we extended these findings by showing that EFT in a web-based sample of smokers reduces delay discounting and intensity of demand for cigarettes (ad libitum consumption) in a hypothetical purchase task. No effect was observed on elasticity of demand (sensitivity to price) or cigarette craving.

Discovery of a Series of Indazole TRPA1 Antagonists.

A series of TRPA1 antagonists is described which has as its core structure an indazole moiety. The physical properties and DMPK profiles are discussed. Good exposure was obtained with several analogs, allowing efficacy to be assessed in rodent models of inflammatory pain.

Subtype-Selective Small Molecule Inhibitors Reveal a Fundamental Role for Nav1.7 in Nociceptor Electrogenesis, Axonal Conduction and Presynaptic Release.

Human genetic studies show that the voltage gated sodium channel 1.7 (Nav1.7) is a key molecular determinant of pain sensation.

A preclinical physiological assay to test modulation of knee joint pain in the spinal cord: effects of oxycodone and naproxen.

Sensory processing in the spinal cord during disease states can reveal mechanisms for novel treatments, yet very little is known about pain processing at this level in the most commonly used animal models of articular pain. Here we report a test of the prediction that two clinically effective compounds, naproxen (an NSAID) and oxycodone (an opiate), are efficacious in reducing the response of spinal dorsal horn neurons to noxious knee joint rotation in the monosodium iodoacetate (MIA) sensitized rat. The overall objective for these experiments was to develop a high quality in vivo electrophysiology assay to confidently test novel compounds for efficacy against pain.

The role of answer fluency and perceptual fluency as metacognitive cues for initiating analytic thinking.

Although widely studied in other domains, relatively little is known about the metacognitive processes that monitor and control behaviour during reasoning and decision-making. In this paper, we examined the conditions under which two fluency cues are used to monitor initial reasoning: answer fluency, or the speed with which the initial, intuitive answer is produced (Thompson, Prowse Turner, & Pennycook, 2011), and perceptual fluency, or the ease with which problems can be read (Alter, Oppenheimer, Epley, & Eyre, 2007). The first two experiments demonstrated that answer fluency reliably predicted Feeling of Rightness (FOR) judgments to conditional inferences and base rate problems, which subsequently predicted the amount of deliberate processing as measured by thinking time and answer changes; answer fluency also predicted retrospective confidence judgments (Experiment 3b).

In vitro and in vivo pharmacological characterisation of the potent and selective vasopressin V(1A) receptor antagonist 4-[4-(4-Chloro-phenyl)-5-[1,2,3]triazol-2-ylmethyl-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl-(3,5-difluoro-phenyl) methanone (PF-00738245).

The dysregulation of arginine vasopressin (AVP) release and activation of vasopressin receptors plays an important role in disease conditions including polycystic kidney disease, congestive heart failure and dysmenorrhoea. The development of potent and selective vasopressin receptor ligands is needed to help dissect the function of the specific subtypes in disease pathogenesis. Here we report the pharmacological characterisation of PF-00738245 in in vitro binding and functional assays using cells expressing vasopressin V(₁A), V(₁B) or V₂ receptors.

Current concepts in assessment of microvascular endothelial function using laser Doppler imaging and iontophoresis.

Effective evaluation of endothelial function is a powerful tool for determining patients at risk of development and progression of cardiovascular disease. As an alternative to invasive tests of endothelial function, several noninvasive methods have been developed, including the use of laser Doppler flowmetry/imaging to measure cutaneous perfusion accompanied by iontophoresis of acetylcholine and sodium nitroprusside. It is clear from previous studies that this technique provides an easy, validated, and reproducible method for investigators to assess and monitor endothelial function in patients with a variety of pathologic conditions, but it may also be used to examine disease progression over time and responsiveness to treatment, thereby facilitating clinical trials.