1,188 research outputs found
Safety and efficacy of diaphragm pacing in patients with respiratory insufficiency due to amyotrophic lateral sclerosis (DiPALS): a multicentre, open-label, randomised controlled trial
Summary Background Non-invasive ventilation is part of the standard of care for treatment of respiratory failure in patients with amyotrophic lateral sclerosis (ALS). The NeuRx RA/4 Diaphragm Pacing System has received Humanitarian Device Exemption approval from the US Food and Drug Administration for treatment of respiratory failure in patients with ALS. We aimed to establish the safety and effi cacy of diaphragm pacing with this system in patients with respiratory muscle weakness due to ALS. Methods We undertook a multicentre, open-label, randomised controlled trial at seven specialist ALS and respiratory centres in the UK. Eligible participants were aged 18 years or older with laboratory supported probable, clinically probable, or clinically defi nite ALS; stable riluzole treatment for at least 30 days; and respiratory insuffi ciency. We randomly assigned participants (1:1), via a centralised web-based randomisation system with minimisation that balanced patients for age, sex, forced vital capacity, and bulbar function, to receive either non-invasive ventilation plus pacing with the NeuRx RA/4 Diaphragm Pacing System or non-invasive ventilation alone. Patients, carers, and outcome assessors were not masked to treatment allocation. The primary outcome was overall survival, defi ned as the time from randomisation to death from any cause. Analysis was by intention to treat. This trial is registered, ISRCTN number 53817913. Interpretation Addition of diaphragm pacing to standard care with non-invasive ventilation was associated with decreased survival in patients with ALS. Our results suggest that diaphragmatic pacing should not be used as a routine treatment for patients with ALS in respiratory failure. Finding
Long-term physical activity: an exogenous risk factor for sporadic amyotrophic lateral sclerosis?
OBJECTIVES: To conduct a geographically defined, UK-based case-control study, to examine any association between physical activity (PA) and amyotrophic lateral sclerosis (ALS). METHODS: A novel historical PA questionnaire was designed, validated, and subsequently administered in individual face-to-face interviews of 175 newly diagnosed sporadic ALS cases and 317 age- and sex-matched community controls. Historical PA energy expenditure and time spent in vigorous-intensity PA were derived from questionnaire data and compared between cases and controls. RESULTS: Participation in an extra 10kJ/kg/day of PA (equivalent to approximately 45minutes brisk walking) was consistently associated with an increased risk of ALS, with the strongest association observed for adulthood exercise-related PA (OR 1.47, 95% CI 1.10-1.97). An extra 10mins/day of vigorous PA was also associated with the odds of ALS (OR 1.03, 95% CI 1·01-1·05). Results were slightly attenuated following adjustment for smoking and educational attainment. CONCLUSIONS: To our knowledge this is the first study to demonstrate a positive association between ALS and PA participation using a specifically designed and validated historical PA questionnaire. Despite the well-established health benefits of PA, a high activity lifestyle may also be associated with elevated risk of ALS. Large-scale prospective studies in the future may help to confirm this association.This study was funded by a Medical Research Council/Motor Neurone Disease Association Lady Edith Wolfson Fellowship.This is the final version of the article. It first appeared from Taylor and Francis via https://doi.org/10.3109/21678421.2016.115457
Long-term physical activity: an exogenous risk factor for sporadic amyotrophic lateral sclerosis?
Objectives: To conduct a geographically defined, UK-based case-control study, to examine any association between physical activity (PA) and amyotrophic lateral sclerosis (ALS).
Methods: A novel historical PA questionnaire was designed, validated, and subsequently administered in individual face-to-face interviews of 175 newly diagnosed sporadic ALS cases and 317 age- and sex-matched community controls. Historical PA energy expenditure and time spent in vigorous-intensity PA were derived from questionnaire data and compared between cases and controls.
Results: Participation in an extra 10kJ/kg/day of PA (equivalent to approximately 45minutes brisk walking) was consistently associated with an increased risk of ALS, with the strongest association observed for adulthood exercise-related PA (OR 1.47, 95% CI 1.10-1.97). An extra 10mins/day of vigorous PA was also associated with the odds of ALS (OR 1.03, 95% CI 1·01-1·05). Results were slightly attenuated following adjustment for smoking and educational attainment.
Conclusions: To our knowledge this is the first study to demonstrate a positive association between ALS and PA participation using a specifically designed and validated historical PA questionnaire. Despite the well-established health benefits of PA, a high activity lifestyle may also be associated with elevated risk of ALS. Large-scale prospective studies in the future may help to confirm this association.This study was funded by a Medical Research Council/Motor Neurone Disease Association Lady Edith Wolfson Fellowship.This is the final version of the article. It first appeared from Taylor and Francis via https://doi.org/10.3109/21678421.2016.115457
Validation of the historical adulthood physical activity questionnaire (HAPAQ) against objective measurements of physical activity.
BACKGROUND: Lifetime physical activity energy expenditure (PAEE) is an important determinant of risk for many chronic diseases but remains challenging to measure. Previously reported historical physical activity (PA) questionnaires appear to be reliable, but their validity is less well established. METHODS: We sought to design and validate an historical adulthood PA questionnaire (HAPAQ) against objective PA measurements from the same individuals. We recruited from a population-based cohort in Cambridgeshire, UK, (Medical Research Council Ely Study) in whom PA measurements, using individually calibrated heart rate monitoring, had been obtained in the past, once between 1994 and 1996 and once between 2000 and 2002. 100 individuals from this cohort attended for interview. Historical PA within the domains of home, work, transport, sport and exercise was recalled using the questionnaire by asking closed questions repeated for several discrete time periods from the age of 20 years old to their current age. The average PAEE from the 2 periods of objective measurements was compared to the self-reported data from the corresponding time periods in the questionnaire. RESULTS: Significant correlations were observed between HAPAQ-derived and objectively measured total PAEE for both time periods (Spearman r = 0.44; P < 0.001). Similarly, self-reported time spent in vigorous PA was significantly correlated with objective measurements of vigorous PA (Spearman r = 0.40; P < 0.001). CONCLUSIONS: HAPAQ demonstrates convergent validity for total PAEE and vigorous PA. This instrument will be useful for ranking individuals according to their past PA in studies of chronic disease aetiology, where activity may be an important underlying factor contributing to disease pathogenesis.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are
Decision-making and referral processes for patients with motor neurone disease: a qualitative study of GP experiences and evaluation of a new decision-support tool
Background
The diagnosis of motor neurone disease (MND) is known to be challenging and there may be delay in patients receiving a correct diagnosis. This study investigated the referral process for patients who had been diagnosed with MND, and whether a newly-developed tool (The Red Flags checklist) might help General Practitioners (GPs) in making referral decisions.
Methods
We carried out interviews with GPs who had recently referred a patient diagnosed with MND, and interviews/surveys with GPs who had not recently referred a patient with suspected MND. We collected data before the Red Flags checklist was introduced; and again one year later. We analysed the data to identify key recurring themes.
Results
Forty two GPs took part in the study. The presence of fasciculation was the clinical feature that most commonly led to consideration of a potential MND diagnosis. GPs perceived that their role was to make onward referrals rather than attempting to make a diagnosis, and delays in correct diagnosis tended to occur at the specialist level. A quarter of participants had some awareness of the newly-developed tool; most considered it useful, if incorporated into existing systems.
Conclusions
While fasciculation is the most common symptom associated with MND, other bulbar, limb or respiratory features, together with progression should be considered. There is a need for further research into how decision-support tools should be designed and provided, in order to best assist GPs with referral decisions. There is also a need for further work at the level of secondary care, in order that referrals made are re-directed appropriately
Controls on CO2 storage security in natural reservoirs and implications for CO2 storage site selection
For carbon capture and storage to successfully contribute to climate mitigation efforts, the captured and stored CO2 must be securely isolated from the atmosphere and oceans for a minimum of 10,000 years. As it is not possible to undertake experiments over such timescales, here we investigate natural occurrences of CO2, trapped for 104 -106 yr to understand the geologic controls on long term storage performance. We present the most comprehensive natural CO2 reservoir dataset compiled to date, containing 76 naturally occurring natural CO2 stores, located in a range of geological environments around the world. We use this dataset to perform a critical analysis of the controls on long-term CO2 retention in the subsurface. We find no evidence of measureable CO2 migration at 66 sites and hence use these sites as examples of secure CO2 retention over geological timescales. We find unequivocal evidence of CO2 migration to the Earth’s surface at only 6 sites, with inconclusive evidence of migration at 4 reservoirs. Our analysis shows that successful CO2 retention is controlled by: thick and multiple caprocks, reservoir depths of >1200m, and high density CO2. Where CO2 has migrated to surface, the pathways by which it has done so are focused along faults, illustrating that CO2 migration via faults is the biggest risk to secure storage. However, we also find that many naturally occurring CO2 reservoirs are fault bound illustrating that faults can also securely retain CO2 over geological timescales. Hence, we conclude that the sealing ability of fault or damage zones to CO2 must be fully characterised during the appraisal process to fully assess the risk of CO2 migration they pose. We propose new engineered storage site selection criteria informed directly from on our observations from naturally occurring CO2 reservoirs. These criteria are similar to, but more prescriptive than, existing best-practise guidance for selecting sites for engineered CO2 storage and we believe that if adopted will increase CO2 storage security in engineered CO2 stores
Head up ; an interdisciplinary, participatory and co-design process informing the development of a novel neck support for people living with progressive neck muscle weakness
This paper presents the Head-Up project that aims to provide innovative head support to help improve posture, relieve pain and aid communication for people living with progressive neck muscle weakness. The initial focus is motor neurone disease. The case study illustrates collaborative, interdisciplinary research and new product development underpinned by participatory design.
The study was initiated by a two-day stakeholder workshop followed by early proof-of-concept modeling and patient need evidence building. The work subsequently led to a successful NIHR i4i application funding a 24-month iterative design process, patenting, CE marking and clinical evaluation.
The evaluation has informed amendments to the proposed design we refer to here as the Sheffield Support Snood (SSS). The outcome positively demonstrates use and performance improvements over current neck orthoses and, the process of multidisciplinary and user engagement has created a sense of ownership by MND participants, who have since acted as advocates for the product.</p
Rapid identification of human muscle disease with fibre optic Raman spectroscopy
The diagnosis of muscle disorders (“myopathies”) can be challenging and new biomarkers of disease are required to enhance clinical practice and research. Despite advances in areas such as imaging and genomic medicine, muscle biopsy remains an important but time-consuming investigation. Raman spectroscopy is a vibrational spectroscopy application that could provide a rapid analysis of muscle tissue, as it requires no sample preparation and is simple to perform. Here, we investigated the feasibility of using a miniaturised, portable fibre optic Raman system for the rapid identification of muscle disease. Samples were assessed from 27 patients with a final clinico-pathological diagnosis of a myopathy and 17 patients in whom investigations and clinical follow-up excluded myopathy. Multivariate classification techniques achieved accuracies ranging between 71–77%. To explore the potential of Raman spectroscopy to identify different myopathies, patients were subdivided into mitochondrial and non-mitochondrial myopathy groups. Classification accuracies were between 74–89%. Observed spectral changes were related to changes in protein structure. These data indicate fibre optic Raman spectroscopy is a promising technique for the rapid identification of muscle disease that could provide real time diagnostic information. The application of fibre optic Raman technology raises the prospect of in vivo bedside testing for muscle diseases which would significantly streamline the diagnostic pathway of these disorders
Optical Sensor for Diverse Organic Vapors at ppm Concentration Ranges
A broadly responsive optical organic vapor sensor is described that responds to low concentrations of organic vapors without significant interference from water vapor. Responses to several classes of organic vapors are highlighted, and trends within classes are presented. The relationship between molecular properties (vapor pressure, boiling point, polarizability, and refractive index) and sensor response are discussed
The association of lesion eccentricity with plaque morphology and components in the superficial femoral artery: a high-spatial-resolution, multi-contrast weighted CMR study
<p>Abstract</p> <p>Background</p> <p>Atherosclerotic plaque morphology and components are predictors of subsequent cardiovascular events. However, associations of plaque eccentricity with plaque morphology and plaque composition are unclear. This study investigated associations of plaque eccentricity with plaque components and morphology in the proximal superficial femoral artery using cardiovascular magnetic resonance (CMR).</p> <p>Methods</p> <p>Twenty-eight subjects with an ankle-brachial index less than 1.00 were examined with 1.5T high-spatial-resolution, multi-contrast weighted CMR. One hundred and eighty diseased locations of the proximal superficial femoral artery (about 40 mm) were analyzed. The eccentric lesion was defined as [(Maximum wall thickness- Minimum wall thickness)/Maximum wall thickness] ≥ 0.5. The arterial morphology and plaque components were measured using semi-automatic image analysis software.</p> <p>Results</p> <p>One hundred and fifteen locations were identified as eccentric lesions and sixty-five as concentric lesions. The eccentric lesions had larger wall but similar lumen areas, larger mean and maximum wall thicknesses, and more calcification and lipid rich necrotic core, compared to concentric lesions. For lesions with the same lumen area, the degree of eccentricity was associated with an increased wall area. Eccentricity (dichotomous as eccentric or concentric) was independently correlated with the prevalence of calcification (odds ratio 3.78, 95% CI 1.47-9.70) after adjustment for atherosclerotic risk factors and wall area.</p> <p>Conclusions</p> <p>Plaque eccentricity is associated with preserved lumen size and advanced plaque features such as larger plaque burden, more lipid content, and increased calcification in the superficial femoral artery.</p
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