The MenFAS Study: Understanding Mental Fatigue after Stroke

tle:16698a34-b981-4e5a-bce1-e48f90c2c2aa:d6bd9758-527a-46cd-bfe2-c433766e8fca:1Mental fatigue is a highly distressing symptom after stroke, and motor factors alone cannot explain the persistence of severe fatigue even many months after the stroke. Evolving theories suggest that mental fatigue is associated with cognitive impairment in general, and perhaps dysfunction in the cognitive domain of attention in particular. However, the relationship between attention and mental fatigue after stroke has rarely been examined and given the negative impact of mental fatigue on participation, an understanding of underlying mechanisms mediating mental fatigue is clinically significant. Furthermore, there is insufficient evidence of the efficacy of any intervention strategy to treat or prevent post-stroke fatigue (PSF) that considers real world context and environment, such as attention or contextual factors and their potential effect on PSF. A systematic review to describe the full extent of the evidence, was extended across the post Acquired Brain Injury (ABI) fatigue literature, which included stroke populations. Analysis found sustained attentional performance had stronger associations with fatigue after ABI, though inconsistencies in measurement were shown. A synthesis of the theory base underlined the complexities involved in the domain of attention, and the need for focused measurement strategy to understand the mechanisms of fatigue. Taken together insights gained supported the development of a novel measurement strategy designed to capture the momentary lived experience of fatigue and traits of fatigue (mental and physical fatigue) within the context of the task, in the home environment. A cross sectional observation study pre-trialling the use of a novel measurement strategy involving 32 patients at the early phase (>2 months) post-stroke experiencing PSF, confirmed a relationship between sustained attention and mental and physical fatigue within a very short time-frame, in the home environment. Linear regressions (R2) revealed a statistically significant relationship between sustaining attention on the MCCPT and trait fatigue: Accuracy & FSMC sum score (R2=.141, p = .034), Accuracy & FSMC cognitive score (R2=.153, p = .027), Accuracy & FSMC motor score (R2=.152, p = .027). The pre/post study design provided insights into the mutli-dimensional facets of fatigue, with further burdens on executive attentional involved in motor control indicated. Participants experienced higher levels of fatigue in the moments following completion of the attentional task (R2=.107, p = .068), rather than before. A novel occupation-focused intervention support system to manage PSF was developed to investigate, in a sample of 29 stroke survivors at the early phase of stroke (> 2months), the extent of the impact of altering attentional focus on both fatigue levels and subsequent task performance. This feasibility trial demonstrated how investigating the impact of altering attentional focus (with noise-cancelling earphones) is feasible, acceptable, and safe within the community. Study findings supported the use of this trial design within the community. Preliminary findings offer potential further insights into how attentional mechanisms and contexts interact at the sub-acute phase of recovery. In a short time-frame (>12 minutes), increased focus appears to place greater demands on attentional processes involved in motor functioning processes, i.e. Inhibition. Over the longer term (such as a standard therapy session, <45 minutes) altering contextual noise (with noise-cancelling earphones) led to better performance (-12.6, 95% CI [-7.1, -4.7], t (28) = - 4.7, p = <.001) but at a higher cost in terms of fatigue. Conclusion: This thesis provides novel insights into the role played by sustained attention in the development of mental fatigue at the early phase post-stroke. The initial findings are promising for both research and clinical practice with potential implications for furthering knowledge of who is at risk of developing symptoms of mental fatigue. A larger definitive trial replicated with this trial design, would add to the generalisability of the findings. Furthermore, it may shed a light on possible prevention strategies, and provide suitable guidance on self-management strategies for those affected by mental fatigue that is grounded in empirical evidence

Is there evidence for a relationship between cognitive impairment and fatigue after acquired brain injury: a systematic review and meta-analysis

PurposeFatigue is a major symptom of ABI. Greater fatigue is associated with cognitive impairment. Our aim was to systematically review, describe and analyse the literature on the extent of this relationship.MethodsFive databases were searched from inception. Studies were included where: participants had a defined clinical diagnosis of ABI which included TBI, stroke or subarachnoid haemorrhage; a fatigue measure was included; at least one objective cognitive measure was used. Three reviewers individually identified studies and determined quality using the Quality Assessment Tool for Observational Cohort and Cross-sectional Studies.ResultsSixteen of the 412 identified studies, investigating the relationship between cognitive dysfunction and fatigue, comprising a total of 1,745 participants, were included. Quality ranged from fair to good. Meta-analysis found fatigue was significantly associated with an overall pattern of cognitive slowing on tasks of sustained attention. A narrative synthesis found weak associations with fatigue and information processing, attention, memory and executive function.ConclusionAnalysis found sustained attentional performance had stronger associations with fatigue after ABI. Whereas, weak associations were found between fatigue and information processing, attention and to some extent memory and executive function. More focused research on specific cognitive domains is needed to understand the mechanisms of fatigue.Implications for RehabilitationCognitive dysfunction is associated with higher fatigue levels after stroke, traumatic brain injury or subarachnoid haemorrhage.Management of cognitive dysfunction may improve fatigue and participation in meaningful activities after stroke, traumatic brain injury or subarachnoid haemorrhage.Intervention strategies that reduce cognitive load during everyday activities (e.g., grading the burden on attentional resources), may potentially be effective in managing post-ABI fatigue.Agreement on core measures could facilitate integration of findings into clinical practice

Three-dimensional measurement of intervertebral kinematics in vitro using optical motion analysis

Measurement of the stiffness of spinal motion segments is widely used for evaluating the stability of spinal implant constructs. A three-dimensional motion analysis technique has been developed that allows accurate measurement of the relative movement of the vertebral bodies about a well-defined anatomical axis system. The position of marker clusters on each vertebra is tracked using digital infrared cameras (Qualisys AB, Gothenburg). Landmarks are identified using a marked pointer, and an anatomical coordinate system is defined for each vertebra. The transformation relating the upper and lower vertebrae is calculated, using the joint coordinate system approach of Grood and Suntay to find the rotations and translations in each anatomical plane. The stiffness of vertebrectomy constructs was investigated using a Synex vertebral body replacement and an anterior rod with one or two screws in each vertebral body, with or without damage to the posterior longitudinal ligament (PLL). A moment of 2 N m was applied about each anatomical axis, and the range of motion about each axis was calculated. The range of motion in flexion-extension and lateral bending was significantly greater with only one screw. When the PLL was cut, there was no significant increase in the range of motion

Dectin-2 recognises mannosylated O-antigens of human opportunistic pathogens and augments lipopolysaccharide activation of myeloid cells

Lipopolysaccharide (LPS) consists of a relatively conserved region of lipid A and core-oligosaccharide, and a highly variable region of O-antigen polysaccharide. While lipid A is known to bind to the toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex, the role of the O-antigen remains unclear. Here we report a novel molecular interaction between dendritic cell-associated C-type lectin-2 (Dectin-2) and the mannosylated O-antigen found in a human opportunistic pathogen Hafnia alvei PCM 1223, which has a repeating unit of [-Man-α1,3-Man-α1,2-Man-α1,2-Man-α1,2-Man-α1,3-]. H. alvei LPS induced higher levels of TNFα and IL-10 from mouse bone marrow-derived dendritic cells (BM-DCs), when compared to Salmonella enterica O66 LPS which has a repeat of [-Gal-α1,6-Gal-α1,4-[Glc-β1,3]GalNAc-α1,3-GalNAc-β1,3-]. In a cell-based reporter assay, Dectin-2 was shown to recognise H. alvei LPS. This binding was inhibited by mannosidase treatment of H. alvei LPS and by mutations in the carbohydrate-binding domain of Dectin-2, demonstrating that H. alvei LPS is a novel glycan ligand of Dectin-2. The enhanced cytokine production by H. alvei LPS was Dectin-2 dependent, as Dectin-2 knockout BM-DCs failed to do so. This receptor crosstalk between Dectin-2 and TLR4 involved events including spleen tyrosine kinase (Syk) activation and receptor juxtaposition. Furthermore, another mannosylated LPS from Escherichia coli O9a, also bound to Dectin-2 and augmented TLR4 activation of BM-DCs. Taken together, these data indicate that mannosylated O-antigens from several gram-negative bacteria augment TLR4 responses through interaction with Dectin-2

Expansion of HCV treatment access to people who have injected drugs through effective translation of research into public health policy:Scotland's experience

Seven years have elapsed since the Scottish Government launched its Hepatitis C Action Plan – a Plan to improve services to prevent transmission of infection, particularly among people who inject drugs (PWID), identify those infected and ensure those infected receive optimal treatment. The Plan was underpinned by industrial scale funding (around £100 million, in addition to the general NHS funding, will have been invested by 2015), and a web of accountable national and local multi-disciplinary multi-agency networks responsible for the planning, development and delivery of services. Initiatives ranged from the introduction of testing in specialist drug services through finger-prick blood sampling by non-clinical staff, to the setting of government targets to ensure rapid scale-up of antiviral therapy. The Plan was informed by comprehensive national monitoring systems, indicating the extent of the problem not just in terms of numbers infected, diagnosed and treated but also the more penetrative data on the number advancing to end-stage liver disease and death, and also through compelling modelling work demonstrating the potential beneficial impact of scaling-up therapy and the mounting cost of not acting. Achievements include around 50% increase in the proportion of the infected population diagnosed (38% to 55%); a sustained near two-and-a-half fold increase in the annual number of people initiated onto therapy (470 to 1050) with more pronounced increases among PWID (300 to 840) and prisoners (20 to 140); and reversing of an upward trend in the overall number of people living with chronic infection. The Action Plan has demonstrated that a Government-backed, coordinated and invested approach can transform services and rapidly improve the lives of thousands. Cited as “an impressive example of a national strategy” by the Global Commission on Drug Policy, the Scottish Plan has also provided fundamental insights of international relevance into the management of HCV among PWID

Is there evidence for a relationship between cognitive impairment and fatigue after acquired brain injury : a systematic review and meta-analysis

Purpose: Fatigue is a major symptom of ABI. Greater fatigue is associated with cognitive impairment. Our aim was to systematically review, describe and analyse the literature on the extent of this relationship. Methods: Five databases were searched from inception. Studies were included where: participants had a defined clinical diagnosis of ABI which included TBI, stroke or subarachnoid haemorrhage; a fatigue measure was included; at least one objective cognitive measure was used. Three reviewers individually identified studies and determined quality using the Quality Assessment Tool for Observational Cohort and Cross-sectional Studies. Results: Sixteen of the 412 identified studies, investigating the relationship between cognitive dysfunction and fatigue, comprising a total of 1,745 participants, were included. Quality ranged from fair to good. Meta-analysis found fatigue was significantly associated with an overall pattern of cognitive slowing on tasks of sustained attention. A narrative synthesis found weak associations with fatigue and information processing, attention, memory and executive function. Conclusion: Analysis found sustained attentional performance had stronger associations with fatigue after ABI. Whereas, weak associations were found between fatigue and information processing, attention and to some extent memory and executive function. More focused research on specific cognitive domains is needed to understand the mechanisms of fatigue

The lumbar global fusion - anterior or posterior first?

Objective: Controversy exists as to whether the biomechanical properties of a 360° lumbar fusion are influenced by the order in which the anterior and posterior components of the procedure are performed. Methods: The fusion technique used Mager screws to effect the posterior fusion and a Syncage implant (Stratec) to effect the anterior component of the fusion. Isolated motion segments from five calf spines were tested in each of two groups. In the first group the posterior fusion was performed first and in the second group the anterior fusion was performed first. Loads were applied as a dead weight of 2Nm in each range of movement of the spine (flexion/extension, lateral flexion and rotation). The range of movement was measured using the Qualisys motion analysis system, using external marker clusters attached to the vertebral bodies. Each motion segment was tested prior to instrumentation, post anterior or posterior instrumentation and with both anterior and posterior instrumentation. Results: Ranges of movement following 360° instrumentation were decreased in all planes. When posterior fixation was performed first; flexion/extension reduced to 55% compared to 26% with anterior fixation first (p=0.020), in lateral flexion 34% v 18% (p=0.382), and in rotation 73% v 18%(p=0.034). Conclusions: The 360° fusion construct has reduced range of movement if the anterior first approach is used as compared to posterior first approach. Posterior fixation should not be performed prior to anterior fixation as this results in a significant loss of stability in both flexion/extension and rotatio