A blended model to support brief interventions in primary care: A qualitative study of usability and acceptability of HealthEir in community pharmacy.

BACKGROUND: Brief interventions for lifestyle behaviour change are effective health promotion interventions. Primary care settings, including pharmacies, are the most frequently visited healthcare facilities and are well placed to provide brief health interventions. However, despite the evidence-based and policy guidance, barriers to brief interventions have limited their implementation. OBJECTIVES: This study aimed to explore the usability and acceptability of HealthEir, a blended model with digital, print, and communication elements designed to support the delivery of brief health-promoting interventions in pharmacy practice. METHODS: Usability tests using a think aloud protocol and set tasks (to assess usability) and semi-structured interviews (to assess acceptability) were conducted with fifteen patients and twelve pharmacists. Usability data were analysed deductively using Nielsen's five quality components of usability as a framework. Acceptability data were analysed using inductive thematic analysis. FINDINGS: All participants found HealthEir straightforward to use and completed the required tasks without assistance. A small number of patient and pharmacist participants identified opportunity for improvement of the digital element. Acceptability was also high, with individual comments from participants identifying opportunity for improvements to HealthEir, and two patients identifying privacy or safety concerns. The majority of comments regarding acceptability reflected wider social and cultural challenges such as perceptions of the roles of pharmacists and pharmacies and the low priority of preventative health interventions. CONCLUSION: HealthEir has been demonstrated to be a usable and acceptable support that has the potential to overcome barriers to delivery of brief interventions in pharmacies. Usability and acceptability testing identified minor changes that may further improve its design prior to piloting and implementation.

Research methods from human-centered design: Potential applications in pharmacy and health services research.

Challenges faced by health systems have become increasingly complex, and expanding the range of methodological options available via interdisciplinary collaboration is important to enable researchers to address them. As complexity increases, it can be more difficult to ensure solutions remain patient-centered. Human-centered design is an approach that focuses on engaging with and understanding the needs of all services users while retaining a systems perspective. Therefore, design professionals skilled in these approaches are increasingly collaborating within health systems in pharmacy and health research teams. This methodological paper considers the potential contribution of human-centered design approaches to optimising development, implementation, and sustainability of patient-centered interventions in pharmacy and health services research. It provides an overview of human-centered design principles and their application, and outlines the emerging roles of design professionals in pharmacy and health services research. It focuses on three key human-centered design methods that can most readily be used by pharmacy and health services researchers. Journey mapping, prototyping, and user testing are discussed in detail. Journey mapping enables holistic visualisation of patient experience from practical and emotional perspectives. It may be used to visualize current practice or model potential future services, and can be informed by quantitative and qualitative data derived from both primary and secondary research. Prototyping facilitates exploration of interventions such as new services quickly and at low-cost. Health services researchers can utilize prototypes for services, processes, experiences, physical objects, environments, spaces, or digital tools for example. Formative evaluation and user testing supports rapid iteration of prototypes to ensure that they meet patient and healthcare professional needs. Finally, challenges with interdisciplinary collaboration and strategies to maximize the potential of using human-centered design approaches in pharmacy and health services research to address complex challenges, enhance practice and deliver benefits for service users, patients, and health systems are discussed.

Differential roles of GABAB1 subunit isoforms on locomotor responses to acute and repeated administration of cocaine.

GABAB receptors are crucial modulators of the behavioural effects of drug abuse, and agonists and positive allosteric modulators show promise as pharmacological strategies for anti-addiction therapeutics. GABAB receptors are functional heterodimers of GABAB1 and GABAB2 subunits. The predominant neuronal GABAB1 subunit isoforms are GABAB1a and GABAB1b. Selective ablation of these isoforms in mice revealed differential behavioural responses in fear, cognition and stress sensitivity. However, the influence of the two GABAB1 isoforms on responses to drugs of abuse is unclear. Therefore we examined the responses of GABAB1 subunit isoform null mice to cocaine in acute locomotor activity and conditioned place preference (CPP) paradigms. During habituation for the acute locomotor activity assay, GABAB1b(-/-) mice showed higher levels of locomotor activity relative to wild-type (WT) and GABAB1a(-/-) mice, in accordance with previous studies. Acute cocaine (10 mg/kg) increased locomotor activity in habituated mice of all three genotypes, with GABAB1a(-/-) mice showing sustained hyperlocomotor responses 30 min after cocaine relative to WT and GABAB1b(-/-) mice. No genotypes demonstrated a cocaine-induced place preference, however, GABAB1a(-/-) mice demonstrated enhanced locomotor sensitisation to chronic cocaine in the CPP paradigm in comparison to WT mice, whereas GABAB1b(-/-) mice failed to develop locomotor sensitisation, despite higher levels of basal locomotor activity. These findings indicate that GABAB1a and GABAB1b isoforms differentially regulate behavioural responses to cocaine, with deletion of GABAB1a enhancing cocaine-induced locomotor activity and deletion of GABAB1b protecting from cocaine-induced sensitisation.

Activation but not blockade of GABAB receptors during early-life alters anxiety in adulthood in BALB/c mice.

Although the underlying pathophysiology of anxiety disorders is unknown it is clear that a combination of genetic and environmental factors in early life predispose to disease risk. Preclinical research increasingly suggests an important role for the GABAB receptor in modulating anxiety behaviour, with GABAB receptor deficient mice having increased anxiety behaviour. Previous studies have highlighted critical windows during development where adult anxiety behaviour is primed. However, little is known regarding the role played by the GABAB receptors in the developmental processes that underlie adult anxiety behaviour. To this end, we treated male BALB/c mouse pups with the either the selective GABAB receptor agonist, R-baclofen (2 mg/kg, s.c), the GABAB receptor antagonist CGP 52432 (10 mg/kg and 30 mg/kg) or vehicle from postnatal days (P) 14-28. The anxiety behaviour of these mice was then assessed in adulthood (P62 onwards) in a battery of behavioural tests comprising; the stress induced hyperthermia (SIH) test, defensive marble burying (DMB), elevated-plus maze (EPM) and the forced swim test (FST). Postnatal R-baclofen treatment resulted in increased anxiety-like behaviour in the EPM as shown by approach-avoidance and ethological measures. Other behavioural measures were not significantly altered. Interestingly, blockade of GABAB receptors with CGP52432 in early life caused no alterations in emotional behaviour. These data suggest that during early life GABAB receptor signalling can play a functional role in programing anxiety behaviour in adulthood. The underlying neurodevelopmental processes underlying these effects remain to be discovered.

GABAB receptor ligands do not modify conditioned fear responses in BALB/c mice.

The GABA(B) receptor has been well characterised as a substrate of unconditioned anxiety behaviour. Indeed, the anxiolytic effects of positive modulators of the GABA(B) receptor have been demonstrated across a range of behavioural tests of innate anxiety, whereas GABA(B) receptor deficient mice have an elevated anxiety phenotype. However, the role of the GABA(B) receptor in regulating conditioned anxiety behaviour; an important facet of the preclinical study of anxiety disorders such as post-traumatic stress disorder is less well understood. In vitro data suggests that the GABA(B) receptor plays an important role in regulating the neural circuitry that underpins conditioned fear learning and extinction, but whether these effects translate into alterations in conditioned anxiety behaviour has not been widely investigated. This represents a crucial deficit in the preclinical characterisation of these drugs as putative anxiolytic agents. Using the highly anxious mouse strain, BALB/c, and an auditory fear conditioning protocol, we sought to characterise the GABA(B) receptor positive modulator GS39783 and GABA(B) receptor antagonist CGP52432, two compounds not previously evaluated for their effects on conditioned fear. Neither GS39783 nor CGP52432 altered freezing behaviour irrespective of whether drugs were administered before the acquisition, recall or extinction training sessions. These findings suggest limitations to the potential role of GABA(B) receptor active drugs as clinical agents in the treatment of anxiety.

The age of anxiety: role of animal models of anxiolytic action in drug discovery.

Anxiety disorders are common, serious and a growing health problem worldwide. However, the causative factors, aetiology and underlying mechanisms of anxiety disorders, as for most psychiatric disorders, remain relatively poorly understood. Animal models are an important aid in giving insight into the aetiology, neurobiology and, ultimately, the therapy of human anxiety disorders. The approach, however, is challenged with a number of complexities. In particular, the heterogeneous nature of anxiety disorders in humans coupled with the associated multifaceted and descriptive diagnostic criteria, creates challenges in both animal modelling and in clinical research. In this paper, we describe some of the more widely used approaches for assessing the anxiolytic activity of known and potential therapeutic agents. These include ethological, conflict-based, hyponeophagia, vocalization-based, physiological and cognitive-based paradigms. Developments in the characterization of translational models are also summarized, as are the challenges facing researchers in their drug discovery efforts in developing new anxiolytic drugs, not least the ever-shifting clinical conceptualization of anxiety disorders. In conclusion, to date, although animal models of anxiety have relatively good validity, anxiolytic drugs with novel mechanisms have been slow to emerge. It is clear that a better alignment of the interactions between basic and clinical scientists is needed if this is to change.

Restraint stress-induced brain activation patterns in two strains of mice differing in their anxiety behaviour.

Genetically identical inbred mouse strains are one of the most useful tools in dissecting the genetic basis of complex disorders. C57BL/6 and BALB/c mice differ markedly in emotionality. In particular, BALB/c mice are more stress-sensitive and have been proposed to be a model of pathological anxiety. There is a paucity of studies investigating whether brain activation in response to a stressor is different in these two strains. To this end, having confirmed that the strains differ in anxiety responses in a light-dark box test, we then examined if restraint stress induced increases in c-Fos protein expression in selective regions of the mouse brain. The areas of interest analysed were the paraventricular nucleus (PVN) of the hypothalamus, prefrontal cortex (PFC), the paraventricular thalamic nucleus (PV) and the hippocampus. These areas were chosen due to their known involvement in stress response. Our data demonstrate that BALB/c showed a similar cellular activation pattern to stress, with respect to c-Fos expression, in the PVN, PV and in the hippocampus. On the other hand, BALB/c showed markedly blunted stress-induced brain activation compared with stressed C57BL/6 mice in both the CG1 and CG2 regions of the PFC. The lower levels of stress-induced activity in high anxiety BALB/c mice, possibly indicate a circuit dysregulation at the cortico-limbic level in response to stress.