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Exploring strategies used following a group-based fatigue management programme for people with multiple sclerosis (FACETS) via the Fatigue Management Strategies Questionnaire (FMSQ). - BMJ open
To explore cross-sectional patterns of use of fatigue management strategies in people with multiple sclerosis (MS) who had attended a group-based fatigue management programme, Fatigue: Applying Cognitive behavioural and Energy effectiveness Techniques to lifeStyle ('FACETS'). In a multicentre randomised controlled trial (RCT) the FACETS programme was shown to reduce fatigue severity and improve self-efficacy and quality of life.A questionnaire substudy within a RCT involving the self-completed Fatigue Management Strategies Questionnaire (FMSQ). The FMSQ includes: (1) closed questions about the use and helpfulness of fatigue management strategies taught in FACETS and (2) open items about changes to lifestyle, attitudes or expectations, barriers or difficulties encountered and helpful strategies not covered in FACETS.All had a clinical diagnosis of MS, significant fatigue, were ambulatory and had attended at least 4 of 6 scheduled FACETS sessions.Participants (n=72) were posted the FMSQ with a prepaid return envelope 4â€…months after the end of the FACETS programme.82% (59/72) of participants returned the FMSQ. The fatigue management strategies most frequently used since attending FACETS were prioritisation (80%), pacing (78%), saying no to others (78%), grading tasks (75%) and challenging unhelpful thoughts (71%). Adding in those participants who were already using the respective strategies prior to FACETS, the three most used strategies at 4â€…months were prioritisation (55/59), grading (54/59) and pacing (53/58). Free-text comments illustrated the complex interplay between attitudes/expectations, behaviours, emotions and the environment. Issues related to expectations featured strongly in participants' comments. Expectations (from self and others) were both facilitators and barriers to effective fatigue management.Individuals' comments highlighted the complex, multifaceted nature of fatigue management. Revising expectations and a greater acceptance of fatigue were important shifts following the programme. Findings support the relevance of a cognitive behavioural approach for fatigue management. Booster sessions might be a useful addition to the FACETS programme.Current controlled trials ISRCTN76517470; Results.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
'HeART of Stroke (HoS)', a community-based Arts for Health group intervention to support self-confidence and psychological well-being following a stroke: protocol for a randomised controlled feasibility study. - BMJ open
Over 152,000 people in the UK have strokes annually and a third experience residual disability. Low mood also affects a third of stroke survivors; yet psychological support is poor. While Arts for Health interventions have been shown to improve well-being in people with mild-to-moderate depression post-stroke, their role in helping people regain sense of self, well-being and confidence has yet to be evaluated. The main aim of this study is to explore the feasibility of conducting a pragmatic multicentre randomised controlled trial to assess the effectiveness and cost-effectiveness of an Arts for Health group intervention ('HeART of Stroke' (HoS)) for stroke survivors. HoS is a 10-session artist-facilitated group intervention held in the community over 14 weeks. It offers a non-judgemental, supportive environment for people to explore sense of self, potentially enhancing well-being and confidence.Sixty-four people, up to 2 years post-stroke, recruited via secondary care research staff or community stroke/rehabilitation teams in two UK centres will be randomised to either HoS plus usual care or usual care only. Self-reported outcomes, measured at baseline and approximately 5 months postrandomisation, will include stroke-related, well-being, mood, self-esteem, quality of life and process measures. Analyses will focus on estimating key feasibility parameters (eg, rates of recruitment, retention, intervention attendance). We will develop outcome and resource use data collection methods to inform an effectiveness and cost-effectiveness analysis in the future trial. Interviews, with a sample of participants, will explore the acceptability of the intervention and study processes, as well as experiences of the HoS group.National Health Service (NHS), Research and Development and University ethical approvals have been obtained. Two peer-reviewed journal publications are planned plus one service user led publication. Findings will be disseminated at key national conferences, local stakeholder events and via institutional websites.ISRCTN99728983.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Mosquito genomics. Highly evolvable malaria vectors: the genomes of 16 Anopheles mosquitoes. - Science (New York, N.Y.)
Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16 anopheline mosquito species from diverse locations spanning ~100 million years of evolution. Comparative analyses show faster rates of gene gain and loss, elevated gene shuffling on the X chromosome, and more intron losses, relative to Drosophila. Some determinants of vectorial capacity, such as chemosensory genes, do not show elevated turnover but instead diversify through protein-sequence changes. This dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts.Copyright Â© 2015, American Association for the Advancement of Science.
One year follow-up of a pragmatic multi-centre randomised controlled trial of a group-based fatigue management programme (FACETS) for people with multiple sclerosis. - BMC neurology
Fatigue is one of the most common and debilitating symptoms of multiple sclerosis (MS). The aim was to evaluate the effectiveness at 1-year follow-up of a manualised group-based programme ('FACETS') for managing MS-fatigue.One-year follow-up of a pragmatic multi-centre randomised controlled trial. People with MS and significant fatigue were randomised to FACETS plus current local practice (FACETS) or current local practice alone (CLP), using concealed computer-generated randomisation. Participant blinding was not possible. Primary outcome measures were fatigue severity (Global Fatigue Severity subscale of the Fatigue Assessment Instrument), self-efficacy (MS-Fatigue Self-Efficacy) and disease-specific quality of life (MS Impact Scale).Between May 2008 and November 2009, 164 participants were randomised. Primary outcome data were available at 1Â year for 131 (80%). The benefits demonstrated at 4-months in the FACETS arm for fatigue severity and self-efficacy largely persisted, with a slight reduction in standardised effect sizes (SES) (-0.29, pâ€‰=â€‰0.06 and 0.34, pâ€‰=â€‰0.09, respectively). There was a significant difference on the MS Impact Scale favouring FACETS that had not been present at 4-months (SES -0.24, pâ€‰=â€‰0.046). No adverse events were reported.Improvements in fatigue severity and self-efficacy at 4-months follow-up following attendance of FACETS were mostly sustained at 1Â year with additional improvements in MS impact. The FACETS programme provides modest long-term benefits to people with MS-fatigue.ISRCTN76517470.
Testing the feasibility and acceptability of using the Nintendo Wii in the home to increase activity levels, vitality and well-being in people with multiple sclerosis (Mii-vitaliSe): protocol for a pilot randomised controlled study. - BMJ open
The benefits of physical activity for people with multiple sclerosis (pwMS) have been recognised. However, exercise regimens can be difficult to maintain over the longer term and pwMS may face unique barriers to physical activity engagement. Pilot research suggests the Nintendo Wii can be used safely at home by pwMS with minimal mobility/balance issues and may confer benefits. We have developed a home-based physiotherapist supported Wii intervention ('Mii-vitaliSe') for pwMS that uses commercial software. This is a pilot study to explore the feasibility of conducting a full scale clinical and cost-effectiveness trial of Mii-vitaliSe.30 ambulatory, relatively inactive pwMS will be randomised to receive Mii-vitaliSe immediately, or after 6 months. Outcomes, measured at baseline and 6 and 12 months later, will include balance, gait, mobility, hand dexterity and self-reported physical activity levels, fatigue, self-efficacy, mood and quality of life. Interviews conducted on a purposive sample of participants will explore experiences of participation in the study and barriers and facilitators to using the Wii. Mean recruitment, adherence rate and standard deviations (SDs) of potential primary outcomes for the full trial will be estimated and precision summarised using 95% confidence intervals (CIs). Interview transcripts will be thematically analysed using a generic qualitative approach.National Health Service (NHS; ref 12/SC/0420) and university ethical approvals have been obtained as has NHS Research and Development permission from the relevant trust. A home risk assessment will be undertaken for all potential participants. All adverse events will be closely monitored, documented and reported to the study Safety Monitoring Committee. At least one publication in a peer reviewed journal will be produced and research findings presented at a national and international conference. With service users, we will coproduce a summary of the findings for dissemination on our research unit's website and elsewhere.ISRCTN 49286846.
Estimating long-term multivariate progression from short-term data. - Alzheimer's & dementia : the journal of the Alzheimer's Association
Diseases that progress slowly are often studied by observing cohorts at different stages of disease for short periods of time. The Alzheimer's Disease Neuroimaging Initiative (ADNI) follows elders with various degrees of cognitive impairment, from normal to impaired. The study includes a rich panel of novel cognitive tests, biomarkers, and brain images collected every 6 months for as long as 6 years. The relative timing of the observations with respect to disease pathology is unknown. We propose a general semiparametric model and iterative estimation procedure to estimate simultaneously the pathological timing and long-term growth curves. The resulting estimates of long-term progression are fine-tuned using cognitive trajectories derived from the long-term "Personnes AgÃ©es Quid" study.We demonstrate with simulations that the method can recover long-term disease trends from short-term observations. The method also estimates temporal ordering of individuals with respect toÂ disease pathology, providing subject-specific prognostic estimates of the time until onset of symptoms. When the method is applied to ADNI data, the estimated growth curves are in general agreement with prevailing theories of the Alzheimer's disease cascade. Other data sets with common outcome measures can be combined using the proposed algorithm.Software to fit the model and reproduce results with the statistical software R is available as the grace package. ADNI data can be downloaded from the Laboratory of NeuroImaging.Copyright Â© 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
A pragmatic parallel arm multi-centre randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based fatigue management programme (FACETS) for people with multiple sclerosis. - Journal of neurology, neurosurgery, and psychiatry
Fatigue is a common and troubling symptom for people with multiple sclerosis (MS).To evaluate the effectiveness and cost-effectiveness of a six-session group-based programme for managing MS-fatigue (Fatigue: Applying Cognitive behavioural and Energy effectiveness Techniques to lifeStyle (FACETS)).Three-centre parallel arm randomised controlled trial with economic evaluation. Patients with MS and significant fatigue were randomised to FACETS plus current local practice (FACETS) or current local practice alone (CLP), using concealed computer-generated randomisation. Participant blinding was not possible. Primary outcomes were fatigue severity (Fatigue Assessment Instrument), self-efficacy (Multiple Sclerosis-Fatigue Self-Efficacy) and disease-specific quality of life (Multiple Sclerosis Impact Scale (MSIS-29)) at 1 and 4 months postintervention (follow-up 1 and 2). Quality adjusted life years (QALYs) were calculated (EuroQoL 5-Dimensions questionnaire and the Short-form 6-Dimensions questionnaire).Between May 2008 and November 2009, 164 patients were randomised; primary outcome data were available for 146 (89%). Statistically significant differences favour the intervention group on fatigue self-efficacy at follow-up 1 (mean difference (MD) 9, 95% CI (4 to 14), standardised effect size (SES) 0.54, p=0.001) and follow-up 2 (MD 6, 95% CI (0 to 12), SES 0.36, p=0.05) and fatigue severity at follow-up 2 (MD -0.36, 95% CI (-0.63 to -0.08), SES -0.35, p=0.01) but no differences for MSIS-29 or QALYs. No adverse events reported. Estimated cost per person for FACETS is Â£453; findings suggest an incremental cost-effectiveness ratio of Â£2157 per additional person with a clinically significant improvement in fatigue.FACETS is effective in reducing fatigue severity and increasing fatigue self-efficacy. However, it is difficult to assess the additional cost in terms of cost-effectiveness (ie, cost per QALY) as improvements in fatigue are not reflected in the QALY outcomes, with no significant differences between FACETS and CLP. The strengths of this trial are its pragmatic nature and high external validity.Current Controlled Trials ISRCTN76517470.
Can delayed time to referral to a tertiary level urologist with an abnormal PSA level affect subsequent Gleason grade in the opportunistically screened population? - The Prostate
There is growing conflict in the literature describing the effect of delayed treatment on outcomes following radical prostatectomy. There is also evidence to suggest progression of low-risk prostate cancer to develop higher grades and volumes of prostate cancer during active surveillance. It is unknown as to what affect a delay in referral of those men with abnormal screened-PSA levels have on subsequent Gleason grade.We identified 350 men through our rapid access prostate clinic who underwent TRUS biopsy for abnormal age-related PSA and/or abnormal clinical examination. Clinicopathological findings were compared for those with positive versus negative TRUS biopsies, and for those with initial delays in referral (<12 months, 12-18 months, and >18 months). We used ANOVA and Student's t-tests amongst other statistical tools to examine significance of clinical findings.Of the 350 men who underwent TRUS biopsy, those with a delay in referral of 12 months or more were significantly associated with higher PSA titers, clinically palpable disease and likelihood of diagnosis with prostate cancer. A delay of 18 months or more led to a significantly higher risk of being diagnosed with a leading grade 4 prostate cancer, which was further supported using PSA velocity as a diagnostic tool (change >0.4â€‰ng/ml/year).We recommend that repeated asymptomatic abnormal age-related PSA readings and/or abnormal clinical examination in the screened population be referred without delay to a urologist for further assessment, enrolment into an active surveillance program or definitive subsequent treatment.Copyright Â© 2013 Wiley Periodicals, Inc.
Emerging evidence for Gleason grade migration and distance impact in prostate cancer? An analysis of the rapid access prostate clinic in a tertiary referral center: St. Vincent's University Hospital, Dublin (2009-2011). - Irish journal of medical science
Recent evidence has suggested that the introduction of rapid access prostate cancer programs has led to a more streamlined pathway for patients, and was designed to ultimately reduce referral delays.To identify the initial impact of the introduction of the rapid access prostate clinic on Gleason grading within the prostate cancer cohort, as well as the impact of distance from a tertiary referral center on subsequent Gleason grading.A prospective database was maintained from those men attended the rapid access prostate clinic in St. Vincent's University Hospital. Data relating to demographics, biopsy results, retrospective PSA readings, and subsequent treatment pathways were all recorded and analyzed. Statistical significance was taken at p<0.05.Prospective data from the rapid access prostate clinic illustrated similar results in patient demographics, Gleason grade and choice of treatment outcomes to other published institutions, however, for the first time demonstrate emerging evidence of the effect of the rapid access prostate clinic leading to a downward shift in Gleason grade over a 2-year period, as well as data showing an inverse correlation between leading Gleason grade and distance from our tertiary referral center.These results suggest that the introduction of the rapid access prostate clinic has initially begun to demonstrate an initial downgrading in Gleason scoring patterns. Our data also reflects a poorer Gleason score in those patients living further away from the rapid access prostate clinic. This may be in part attributed to a surge in referrals of those patients previously managed outside a tertiary institution, and suggests that patients should undergo prompt referral following suspicion for prostate cancer.
Knowing is half the battle: targeting virulence factors of group A Streptococcus for vaccine and therapeutics. - Current drug targets
Group A Streptococcus (GAS) is a leading human pathogen that causes a multitude of diseases from pharyngitis, and impetigo, to more severe outcomes such as rheumatoid arthritis and necrotizing fasciitis. GAS remains a global burden as currently no vaccine exists that is completely effective. In this review we highlight recent studies on the virulence of GAS and present several approaches that have extended those findings into aims at combating GAS disease. These and other studies such as recent genome-wide efforts into host-pathogen relationships of GAS disease will likely reveal new targets of intervention. Given the recent rise in GAS strains that have acquired resistance to several types of antibiotics, it is crucial that we continue to increase our knowledge of the mechanisms underlying GAS disease.
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