Longitudinal change in everyday function and behavioral symptoms in frontotemporal dementia

Background: The relationship between behavioral changes and functional decline in frontotemporal dementia (FTD) is not well understood. Methods: Thirty-nine patients (21 behavioral variant FTD [bvFTD], 18 semantic variant primary progressive aphasia [svPPA]) were followed up longitudinally (2–4 years follow-up). Functional (Disability Assessment for Dementia) and behavioral (Cambridge Behavioural Inventory Revised) assessments were included for between-group (pairwise comparisons, mixed model analysis) and within-group analyses (bivariate correlations). Results: Functionally, patients with bvFTD were more impaired than patients with svPPA at baseline and continued to be at follow-up, despite similar disease duration. By contrast, behavioral impairments differed between patient groups at baseline and at follow-up. At baseline, patients with bvFTD exhibited higher levels of apathy and changes in eating than patients with svPPA; disinhibited and stereotypical behaviors were similar. Over the years, patients with bvFTD showed reduction in disinhibition and stereotypical behavior while apathy and eating changes increased. By contrast, all measured behaviors increased in patients with svPPA over time. Finally, only apathy made longitudinal contributions to functional disability in patients with svPPA, whereas apathy and stereotypical behavior were associated with increased disability in patients with bvFTD. Conclusions: Despite shared overlapping baseline behavioral symptoms, patients with bvFTD are more functionally impaired than patients with svPPA. Apathy has a strong role in disability for both bvFTD and svPPA, but stereotypical behaviors only contributed to functional deficits in patients with bvFTD. Our findings suggest that rigid/compulsive behaviors may in fact support activity engagement in patients with svPPA. Taken together, our results indicate that interventions to reduce disability in the FTD spectrum require an alternative rationale in comparison to Alzheimer disease dementia, and should carefully weigh the interaction of behavioral symptoms and functional status

Behavioral-variant frontotemporal dementia: Distinct phenotypes with unique functional profiles

Objective: To identify distinct behavioral phenotypes of behavioral variant frontotemporal dementia (bvFTD), and elucidate differences in functional, neuroimaging, and progression to residential care placement. Methods: Eighty-eight patients with bvFTD were included in a cluster analysis applying levels of disinhibition and apathy (Cambridge Behavioural Inventory-Revised) to identify phenotypic subgroups. Between-group (Kruskal-Wallis; Mann-Whitney U) functional differences (Disability Assessment for Dementia), and time to residential care placement (survival analyses) were examined. Cortical thickness differences (whole brain MRI) were analyzed in bvFTD patients versus healthy controls (n=30) and between phenotypic subgroups. Results: Four phenotypic subgroups were identified: “Primary severe apathy” (n=26), “Severe apathy and disinhibition” (n=26), “Mild apathy and disinhibition” (n=27), “Primary severe disinhibition” (n= 9). Severely apathetic phenotypes were more functionally impaired and had more extensive brain atrophy than those with mild apathy or severe disinhibition alone. Further imaging analyses indicated that the right middle temporal region is critical for the development of disinhibition, an association that remains with disease progression and in the context of severe apathy. Finally, no difference in time to residential care admission was found between phenotypes. Conclusions: This study reveals that different clinical behavioral phenotypes of bvFTD have differing profiles of functional decline and distinct patterns of associated cortical changes. These findings emphasize the importance of apathy in functional impairment, highlight the role of the right temporal region in disinhibition and suggest that disability may be a sensitive outcome measure for treatments targeting reduction of apathy. These phenotypes could also support understanding of prognosis and clinical management

Positive behaviour support in frontotemporal dementia: a pilot study

Frontotemporal dementia (FTD) is a progressive neurodegenerative brain condition clinically characterized by marked changes in behaviour that impact the individuals’ relationships and community participation, and present challenges for families. Family carers of individuals with FTD find apathy and disinhibition particularly challenging leading to high levels of stress and burden. Positive behaviour support (PBS) as a behaviour intervention framework has never been trialled in FTD. This pilot study examined the functional basis of apathetic and disinhibited behaviours in four FTD dyads and explored the acceptability of a PBS intervention. The PBS programme was provided by an occupational therapist in the participants’ homes. Measures collected at baseline and post-intervention (M = 3.9 months) assessed: function of behaviours, challenging behaviours, and qualitative outcomes pertaining to the acceptability of the PBS approach. PBS was an acceptable intervention for all four dyads. “Sensory” and “tangible” were the most common functions contributing to the maintenance of behaviour changes, and aspects of apathetic and disinhibited behaviours improved following intervention. This study demonstrates the acceptability and potential benefit of a PBS programme to provide support in FTD. A more rigorous trial will be an important next step in developing improved services tailored to the needs of this unique population

Acute Demyelinating Disease after Oral Therapy with Herbal Extracts

Central nervous system demyelinating processes such as multiple sclerosis and acute disseminated encephalomyelitis constitute a group of diseases not completely understood in their physiopathology. Environmental and toxic insults are thought to play a role in priming autoimmunity. The aim of the present report is to describe a case of acute demyelinating disease with fatal outcome occurring 15 days after oral exposure to herbal extracts

GWIPS-viz: development of a ribo-seq genome browser

We describe the development of GWIPS-viz (http://gwips.ucc.ie), an online genome browser for viewing ribosome profiling data. Ribosome profiling (ribo-seq) is a recently developed technique that provides genome-wide information on protein synthesis (GWIPS) in vivo. It is based on the deep sequencing of ribosome-protected messenger RNA (mRNA) fragments, which allows the ribosome density along all mRNA transcripts present in the cell to be quantified. Since its inception, ribo-seq has been carried out in a number of eukaryotic and prokaryotic organisms. Owing to the increasing interest in ribo-seq, there is a pertinent demand for a dedicated ribo-seq genome browser. GWIPS-viz is based on The University of California Santa Cruz (UCSC) Genome Browser. Ribo-seq tracks, coupled with mRNA-seq tracks, are currently available for several genomes: human, mouse, zebrafish, nematode, yeast, bacteria (Escherichia coli K12, Bacillus subtilis), human cytomegalovirus and bacteriophage lambda. Our objective is to continue incorporating published ribo-seq data sets so that the wider community can readily view ribosome profiling information from multiple studies without the need to carry out computational processing

Exploring synergistic interactions and catalysts in complex interventions: longitudinal, mixed methods case studies of an optimised multi-level suicide prevention intervention in four european countries (Ospi-Europe)

Background: The Medical Research Council (MRC) Framework for complex interventions highlights the need to explore interactions between components of complex interventions, but this has not yet been fully explored within complex, non-pharmacological interventions. This paper draws on the process evaluation data of a suicide prevention programme implemented in four European countries to illustrate the synergistic interactions between intervention levels in a complex programme, and to present our method for exploring these. Methods: A realist evaluation approach informed the process evaluation, which drew on mixed methods, longitudinal case studies. Data collection consisted of 47 semi-structured interviews, 12 focus groups, one workshop, fieldnoted observations of six programme meetings and 20 questionnaires (delivered at six month intervals to each of the four intervention sites). Analysis drew on the framework approach, facilitated by the use of QSR NVivo (v10). Our qualitative approach to exploring synergistic interactions (QuaSIC) also developed a matrix of hypothesised synergies that were explored within one workshop and two waves of data collection. Results: All four implementation countries provided examples of synergistic interactions that added value beyond the sum of individual intervention levels or components in isolation. For instance, the launch ceremony of the public health campaign (a level 3 intervention) in Ireland had an impact on the community-based professional training, increasing uptake and visibility of training for journalists in particular. In turn, this led to increased media reporting of OSPI activities (monitored as part of the public health campaign) and also led to wider dissemination of editorial guidelines for responsible reporting of suicidal acts. Analysis of the total process evaluation dataset also revealed the new phenomenon of the OSPI programme acting as a catalyst for externally generated (and funded) activity that shared the goals of suicide prevention. Conclusions: The QuaSIC approach enabled us to develop and refine our definition of synergistic interactions and add the innovative concept of catalytic effects. This represents a novel approach to the evaluation of complex interventions. By exploring synergies and catalytic interactions related to a complex intervention or programme, we reveal the added value to planned activities and how they might be maximised

Does fish larval dispersal differ between high and low latitudes?

Author Posting. © The Author(s), 2013. This is the author's version of the work. It is posted here by permission of The Royal Society for personal use, not for redistribution. The definitive version was published in Proceedings of the Royal Society B Biological Sciences 280 (2013): 20130327, doi:10.1098/rspb.2013.0327.Several factors lead to expectations that the scale of larval dispersal and population connectivity of marine animals differs with latitude. We examine this expectation for demersal shorefishes, including relevant mechanisms, assumptions, and evidence. We explore latitudinal differences in: 1) biological (e.g., species composition, spawning mode, pelagic larval duration (PLD)), 2) physical (e.g., water movement, habitat fragmentation), and 3) biophysical factors (primarily temperature, which could strongly affect development, swimming ability, or feeding). Latitudinal differences exist in taxonomic composition, habitat fragmentation, temperature, and larval swimming, and each could influence larval dispersal. Nevertheless, clear evidence for latitudinal differences in larval dispersal at the level of broad faunas is lacking. For example, PLD is strongly influenced by taxon, habitat, and geographic region, but no independent latitudinal trend is present in published PLD values. Any trends in larval dispersal may be obscured by a lack of appropriate information, or use of ‘off the shelf’ information that is biased with regard to the species assemblages in areas of concern. Biases may also be introduced from latitudinal differences in taxa or spawning modes, as well as limited latitudinal sampling. We suggest research to make progress on the question of latitudinal trends in larval dispersal.TK was supported by the Norwegian Research Council through project MENUII #190286. JML was supported by ARC Discovery Grant DP110100695. JEC and RRW were supported by the Partnership for the Interdisciplinary Study of Coastal Oceans, funded by The David and Lucille Packard Foundation and the Gordon and Betty Moore Foundation.2014-03-2

Enhancing caregivers’ understanding of dementia and tailoring activities in frontotemporal dementia:two case studies

PURPOSE: To describe the intervention process and results of the Tailored Activities Program (TAP) in two people diagnosed with Frontotemporal Dementia (FTD). METHOD: TAP is an occupational therapy (OT) community-based intervention program that prescribes personalised activities to reduce difficult behaviours of dementia. The OT works with carers over a 4-month period (assessment, activity prescription, and generalisation of strategies). Study measures were collected (blind researcher) pre- and post- intervention: cognition, functional disability, behavioural symptoms, and Caregiver Confidence and Vigilance. RESULTS: A 51-year-old woman with behavioural-variant FTD could consistently engage in more activities post-intervention, with scores indicating improvements to behaviour, function, and caregiver confidence. A 63-year-old man with semantic variant FTD engaged well in the prescribed activities, with scores reflecting reduced carer distress regarding challenging behaviours and improved caregiver vigilance. CONCLUSIONS: TAP is efficacious in FTD, allowing for differences in approach for FTD subtype, where behavioural symptoms are very severe and pervasive

A pilot study of rapid benchtop sequencing of Staphylococcus aureus and Clostridium difficile for outbreak detection and surveillance

OBJECTIVES: To investigate the prospects of newly available benchtop sequencers to provide rapid whole-genome data in routine clinical practice. Next-generation sequencing has the potential to resolve uncertainties surrounding the route and timing of person-to-person transmission of healthcare-associated infection, which has been a major impediment to optimal management. DESIGN: The authors used Illumina MiSeq benchtop sequencing to undertake case studies investigating potential outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile. SETTING: Isolates were obtained from potential outbreaks associated with three UK hospitals. PARTICIPANTS: Isolates were sequenced from a cluster of eight MRSA carriers and an associated bacteraemia case in an intensive care unit, another MRSA cluster of six cases and two clusters of C difficile. Additionally, all C difficile isolates from cases over 6 weeks in a single hospital were rapidly sequenced and compared with local strain sequences obtained in the preceding 3 years. MAIN OUTCOME MEASURE: Whole-genome genetic relatedness of the isolates within each epidemiological cluster. RESULTS: Twenty-six MRSA and 15 C difficile isolates were successfully sequenced and analysed within 5 days of culture. Both MRSA clusters were identified as outbreaks, with most sequences in each cluster indistinguishable and all within three single nucleotide variants (SNVs). Epidemiologically unrelated isolates of the same spa-type were genetically distinct (≥21 SNVs). In both C difficile clusters, closely epidemiologically linked cases (in one case sharing the same strain type) were shown to be genetically distinct (≥144 SNVs). A reconstruction applying rapid sequencing in C difficile surveillance provided early outbreak detection and identified previously undetected probable community transmission. CONCLUSIONS: This benchtop sequencing technology is widely generalisable to human bacterial pathogens. The findings provide several good examples of how rapid and precise sequencing could transform identification of transmission of healthcare-associated infection and therefore improve hospital infection control and patient outcomes in routine clinical practice