Exploring an increased role for Australian community pharmacy in mental health professional service delivery: evaluation of the literature

Background: Australian general practitioners primarily treat mental health problems by prescribing medication dispensed by community pharmacists. Pharmacists therefore have regular interactions with mental health consumers and carers.Aims: This narrative review explored the potential role of community pharmacy in mental health services.Method: Medline, CINAHL, ProQuest, Emerald, PsycINFO, Science Direct, PubMed, Web of Knowledge and IPA were utilised. The Cochrane Library as well as grey literature and “lay” search engines such as GoogleScholar were also searched.Results: Four systematic reviews and ten community pharmacy randomised controlled trials were identified. Various relevant reviews outlining the impact of community pharmacy based disease state or medicines management services were also identified.Conclusion: International studies involving professional service interventions for mental health consumers could be contextualised for the Australian setting. Australian studies of pharmacy professional services for chronic physical health conditions provided further guidance for the expansion of community pharmacy mental health professional services

Inconsistent emotion recognition deficits across stimulus modalities in Huntington's disease

This study has been supported by the European Union - PADDINGTON project, Contract no. HEALTH-F2-2010-261358. SJT acknowledges support of the National Institute for Health Research through the Dementias and Neurodegenerative Research Network, DeNDRoN.Background: Recognition of negative emotions is impaired in Huntington's Disease (HD). It is unclear whether these emotion-specific problems are driven by dissociable cognitive deficits, emotion complexity, test cue difficulty, or visuoperceptual impairments. This study set out to further characterise emotion recognition in HD by comparing patterns of deficits across stimulus modalities; notably including for the first time in HD, the more ecologically and clinically relevant modality of film clips portraying dynamic facial expressions. Methods: Fifteen early HD and 17 control participants were tested on emotion recognition from static facial photographs, non-verbal vocal expressions and one second dynamic film clips, all depicting different emotions. Results: Statistically significant evidence of impairment of anger, disgust and fear recognition was seen in HD participants compared with healthy controls across multiple stimulus modalities. The extent of the impairment, as measured by the difference in the number of errors made between HD participants and controls, differed according to the combination of emotion and modality (p=0.013, interaction test). The largest between-group difference was seen in the recognition of anger from film clips. Conclusions: Consistent with previous reports, anger, disgust and fear were the most poorly recognised emotions by the HD group. This impairment did not appear to be due to task demands or expression complexity as the pattern of between-group differences did not correspond to the pattern of errors made by either group; implicating emotion-specific cognitive processing pathology. There was however evidence that the extent of emotion recognition deficits significantly differed between stimulus modalities. The implications in terms of designing future tests of emotion recognition and care giving are discussed.PostprintPeer reviewe

Submerged in the mainstream? A case study of an immigrant learner in a New Zealand primary classroom

Immigrant children from diverse language backgrounds face not only linguistic challenges when enrolled in mainstream English-medium classrooms, but also difficulties adjusting to an unfamiliar learning community. The culture of primary school classrooms in New Zealand typically reflects conventions across three dimensions: interactional, instructional task performance and cognitive-academic development. All three dimensions are underpinned by the culturally specific discourse conventions involved in language socialisation. New learners may be helped by classmates or their teacher to understand and successfully use these conventions, but left on their own they may sink rather than swim. This is a case study of one Taiwanese 11-year old boy, 'John', who entered a New Zealand primary classroom midway through the school year. John's basic conversational ability was sound, but he did not possess the interactive classroom skills needed to operate in the new culture of learning. Selected from a wider study of the classroom, transcript data from audio-recorded excerpts of John's interactions over several months with his teacher and classmates are interpreted from perspectives derived from sociocultural and language socialisation theories. The article concludes with a brief consideration of the extent to which John constructed, or was constrained from constructing meaningful learning experiences, and suggestions for further research and reflection

Characterising white matter in Huntington's disease

Background: Investigating early white matter (WM) change in Huntington’s Disease (HD) can improve our understanding of the way in which disease spreads from the striatum. Objectives: Here, we provide a detailed characterisation of pathology-related WM change in HD. We first examined WM microstructure using diffusion-weighted imaging, then investigated both underlying biological properties of WM and products of WM damage including iron, myelin plus neurofilament light (NfL), a biofluid marker of axonal degeneration – in parallel with the mutant huntingtin protein (mHTT). Methods: We examined WM change in HD gene-carriers from the HD-CSF cohort, baseline visit. We used standard diffusion MRI to measure metrics including fractional anisotropy (FA), a marker of WM integrity, and diffusivity; a novel diffusion model (NODDI) to measure axonal density and organisation; T1 and T2 weighted structural MRI images to derive proxy iron content and myelin-contrast measures; and biofluid concentrations of NfL (in CSF and plasma) and mHTT (in CSF). Results: HD gene-carriers displayed reduced FA and increased diffusivity compared to controls, both of which were also associated with disease progression, CSF and mHTT levels. HD gene-carriers also displayed proxy measures of reduced myelin-contrast and iron in the striatum. Conclusion: Collectively, these findings present a more complete characterisation of HD-related microstructural brain changes. Correlation between reduced FA, increased axonal orientation and biofluid markers suggest that axonal breakdown is associated with increased WM degeneration, while higher quantitative T2 signal and lower myelin-contrast may indicate a process of demyelination limited to the striatum

Multiparameter MR Imaging in the 6-OPRI

BACKGROUND AND PURPOSE: Inherited prion diseases represent over 15% of human prion cases and are a frequent cause of early onset dementia. The purpose of this study was to define the distribution of changes in cerebral volumetric and microstructural parenchymal tissues in a specific inherited human prion disease mutation combining VBM with VBA of cerebral MTR and MD. MATERIALS AND METHODS: VBM and VBA of cerebral MTR and MD were performed in 16 healthy control participants and 9 patients with the 6-OPRI mutation. An analysis of covariance consisting of diagnostic grouping with age and total intracranial volume as covariates was performed. RESULTS: On VBM, there was a significant reduction in gray matter volume in patients compared with control participants in the basal ganglia, perisylvian cortex, lingual gyrus, and precuneus. Significant MTR reduction and MD increases were more anatomically extensive than volume differences on VBM in the same cortical areas, but MTR and MD changes were not seen in the basal ganglia. CONCLUSIONS: Gray matter and WM changes were seen in brain areas associated with motor and cognitive functions known to be impaired in patients with the 6-OPRI mutation. There were some differences in the anatomic distribution of MTR-VBA and MD-VBA changes compared with VBM, likely to reflect regional variations in the type and degree of the respective pathophysiologic substrates. Combined analysis of complementary multiparameter MR imaging data furthers our understanding of prion disease pathophysiology

The temporal event-based model: Learning event timelines in progressive diseases

Timelines of events, such as symptom appearance or a change in biomarker value, provide powerful signatures that characterise progressive diseases. Understanding and predicting the timing of events is important for clinical trials targeting individuals early in the disease course when putative treatments are likely to have the strongest effect. However, previous models of disease progression cannot estimate the time between events and provide only an ordering in which they change. Here, we introduce the temporal event-based model (TEBM), a new probabilistic model for inferring timelines of biomarker events from sparse and irregularly sampled datasets. We demonstrate the power of the TEBM in two neurodegenerative conditions: Alzheimer's disease (AD) and Huntington's disease (HD). In both diseases, the TEBM not only recapitulates current understanding of event orderings but also provides unique new ranges of timescales between consecutive events. We reproduce and validate these findings using external datasets in both diseases. We also demonstrate that the TEBM improves over current models; provides unique stratification capabilities; and enriches simulated clinical trials to achieve a power of 80% with less than half the cohort size compared with random selection. The application of the TEBM naturally extends to a wide range of progressive conditions

Evaluation of multi-modal, multi-site neuroimaging measures in Huntington's disease: Baseline results from the PADDINGTON study.

BACKGROUND: Macro- and micro-structural neuroimaging measures provide valuable information on the pathophysiology of Huntington's disease (HD) and are proposed as biomarkers. Despite theoretical advantages of microstructural measures in terms of sensitivity to pathology, there is little evidence directly comparing the two. METHODS: 40 controls and 61 early HD subjects underwent 3 T MRI (T1- and diffusion-weighted), as part of the PADDINGTON study. Macrostructural volumetrics were obtained for the whole brain, caudate, putamen, corpus callosum (CC) and ventricles. Microstructural diffusion metrics of fractional anisotropy (FA), mean-, radial- and axial-diffusivity (MD, RD, AD) were computed for white matter (WM), CC, caudate and putamen. Group differences were examined adjusting for age, gender and site. A formal comparison of effect sizes determined which modality and metrics provided a statistically significant advantage over others. RESULTS: Macrostructural measures showed decreased regional and global volume in HD (p < 0.001); except the ventricles which were enlarged (p < 0.01). In HD, FA was increased in the deep grey-matter structures (p < 0.001), and decreased in the WM (CC, p = 0.035; WM, p = 0.053); diffusivity metrics (MD, RD, AD) were increased for all brain regions (p < 0.001). The largest effect sizes were for putamen volume, caudate volume and putamen diffusivity (AD, RD and MD); each was significantly larger than those for all other metrics (p < 0.05). CONCLUSION: The highest performing macro- and micro-structural metrics had similar sensitivity to HD pathology quantified via effect sizes. Region-of-interest may be more important than imaging modality, with deep grey-matter regions outperforming the CC and global measures, for both volume and diffusivity. FA appears to be relatively insensitive to disease effects

A graph-based integration of multimodal brain imaging data for the detection of early mild cognitive impairment (E-MCI)

Alzheimer's disease (AD) is the most common cause of dementia in older adults. By the time an individual has been diagnosed with AD, it may be too late for potential disease modifying therapy to strongly influence outcome. Therefore, it is critical to develop better diagnostic tools that can recognize AD at early symptomatic and especially pre-symptomatic stages. Mild cognitive impairment (MCI), introduced to describe a prodromal stage of AD, is presently classified into early and late stages (E-MCI, L-MCI) based on severity. Using a graph-based semi-supervised learning (SSL) method to integrate multimodal brain imaging data and select valid imaging-based predictors for optimizing prediction accuracy, we developed a model to differentiate E-MCI from healthy controls (HC) for early detection of AD. Multimodal brain imaging scans (MRI and PET) of 174 E-MCI and 98 HC participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort were used in this analysis. Mean targeted region-of-interest (ROI) values extracted from structural MRI (voxel-based morphometry (VBM) and FreeSurfer V5) and PET (FDG and Florbetapir) scans were used as features. Our results show that the graph-based SSL classifiers outperformed support vector machines for this task and the best performance was obtained with 66.8% cross-validated AUC (area under the ROC curve) when FDG and FreeSurfer datasets were integrated. Valid imaging-based phenotypes selected from our approach included ROI values extracted from temporal lobe, hippocampus, and amygdala. Employing a graph-based SSL approach with multimodal brain imaging data appears to have substantial potential for detecting E-MCI for early detection of prodromal AD warranting further investigation

Test-Retest Reliability of Diffusion Tensor Imaging in Huntington's Disease.

Diffusion tensor imaging (DTI) has shown microstructural abnormalities in patients with Huntington's Disease (HD) and work is underway to characterise how these abnormalities change with disease progression. Using methods that will be applied in longitudinal research, we sought to establish the reliability of DTI in early HD patients and controls. Test-retest reliability, quantified using the intraclass correlation coefficient (ICC), was assessed using region-of-interest (ROI)-based white matter atlas and voxelwise approaches on repeat scan data from 22 participants (10 early HD, 12 controls). T1 data was used to generate further ROIs for analysis in a reduced sample of 18 participants. The results suggest that fractional anisotropy (FA) and other diffusivity metrics are generally highly reliable, with ICCs indicating considerably lower within-subject compared to between-subject variability in both HD patients and controls. Where ICC was low, particularly for the diffusivity measures in the caudate and putamen, this was partly influenced by outliers. The analysis suggests that the specific DTI methods used here are appropriate for cross-sectional research in HD, and give confidence that they can also be applied longitudinally, although this requires further investigation. An important caveat for DTI studies is that test-retest reliability may not be evenly distributed throughout the brain whereby highly anisotropic white matter regions tended to show lower relative within-subject variability than other white or grey matter regions

Compensation in Preclinical Huntington's Disease: Evidence From the Track-On HD Study

BACKGROUND: Cognitive and motor task performance in premanifest Huntington's disease (HD) gene-carriers is often within normal ranges prior to clinical diagnosis, despite loss of brain volume in regions involved in these tasks. This indicates ongoing compensation, with the brain maintaining function in the presence of neuronal loss. However, thus far, compensatory processes in HD have not been modeled explicitly. Using a new model, which incorporates individual variability related to structural change and behavior, we sought to identify functional correlates of compensation in premanifest-HD gene-carriers. METHODS: We investigated the modulatory effects of regional brain atrophy, indexed by structural measures of disease load, on the relationship between performance and brain activity (or connectivity) using task-based and resting-state functional MRI. FINDINGS: Consistent with compensation, as atrophy increased performance-related activity increased in the right parietal cortex during a working memory task. Similarly, increased functional coupling between the right dorsolateral prefrontal cortex and a left hemisphere network in the resting-state predicted better cognitive performance as atrophy increased. Such patterns were not detectable for the left hemisphere or for motor tasks. INTERPRETATION: Our findings provide evidence for active compensatory processes in premanifest-HD for cognitive demands and suggest a higher vulnerability of the left hemisphere to the effects of regional atrophy