1,404 research outputs found
RAMESES publication standards: realist syntheses
PMCID: PMC3558331This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Bupropion SR for smoking cessation in smokers with cardiovascular disease: a multicentre, randomised study
Aim To investigate the safety and efficacy of bupropion sustained release (bupropion SR) in promoting abstinence from smoking in subjects with cardiovascular disease (CVD). Methods Six hundred twenty-nine subjects with CVD who smoked ≥10 cigarettes/day were randomised in a double-blind, multicentre study to receive bupropion SR (150mg twice daily) or placebo for 7 weeks, with a follow-up of 52 weeks. Primary efficacy endpoint: continuous abstinence from smoking from weeks 4 to 7. Secondary endpoints: continuous abstinence (weeks 4-12, 4-26 and 4-52) and weekly point prevalence abstinence. All participants received brief motivational support. Safety was evaluated throughout the study. Results Continuous smoking abstinence rates from weeks 4 to 7 were significantly higher in subjects receiving bupropion SR compared with placebo (43 vs. 19%, odds ratio [OR]=3.27, 95% confidence interval [CI] 2.24-4.84; \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \end{document}). Continuous abstinence rates from weeks 4 to 26 and 4 to 52 continued to be more than double for bupropion SR compared with placebo (27 vs. 11%; 22 vs. 9%, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \end{document}). Weekly point prevalence abstinence was significantly higher for participants who received bupropion SR compared with placebo at weeks 3, 7, 26 and 52 \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \end{document}. In both groups, there were no clinically significant changes in blood pressure and heart rate throughout the treatment phase. Overall, 6% of the participants \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \end{document} discontinued study medication due to an adverse event (bupropion SR, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \end{document}; placebo, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \end{document}). Conclusions After 7 weeks of bupropion SR treatment, more than twice as many smokers with CVD had quit smoking at 1 year compared with placebo. The safety profile of bupropion SR was similar to that previously observed in general smoking population
Reanalysis of two eclipsing binaries: EE Aqr and Z Vul
We study the radial-velocity and light curves of the two eclipsing binaries
EE Aqr and Z Vul. Using the latest version of the Wilson & Van Hamme (2003)
model, absolute parameters for the systems are determined. We find that EE Aqr
and Z Vul are near-contact and semi-detached systems, respectively. The primary
component of EE Aqr fills about 96% of its 'Roche lobe', while its secondary
one appears close to completely filling this limiting volume. In a similar way,
we find fill-out proportions of about 72 and 100% of these volumes for the
primary and secondary components of Z Vul respectively. We compare our results
with those of previous authors.Comment: 13 pages, 8 figures, 10 table
Pair Production from 10 GeV to 10 ZeV
At very high energies, pair production () exhibits many
interesting features. The momentum transfer from the target is very small, so
the reaction probes the macroscopic properties of the target, rather than
individual nuclei. Interference between interactions with different atoms
reduces the pair production cross section considerably below the Bethe-Heitler
values. At very high energies, photonuclear interactions may outnumber pair
production.
In contrast, in crystals, the interaction amplitudes may add coherently,
greatly increasing the cross sections. Pair production in matter-free magnetic
fields is also possible. The highest energy pair production occurs at high
energy particle colliders. This article will compare pair production in these
very different regimes.Comment: 37 pages with 9 figures. Invited Review for "Radiation Physics and
Chemistry" Version for publication, incorporating comments by the referee,
and by Gerhard Baur and Roman Le
In severe alcoholic hepatitis, serum keratin-18 fragments are diagnostic, prognostic, and theragnostic biomarkers.
INTRODUCTION: Up to 40% of patients with severe alcoholic hepatitis (AH) die within 6 months of presentation, making prompt diagnosis and appropriate treatment essential. We determined the associations between serum keratin-18 (K18) and histological features, prognosis, and differential response to prednisolone in patients with severe AH. METHODS: Total (K18-M65) and caspase-cleaved K18 (K18-M30) were quantified in pretreatment sera from 824 patients enrolled in the Steroids or Pentoxifylline for Alcoholic Hepatitis trial (87 with suitable histological samples) and disease controls. RESULTS: K18 fragments were markedly elevated in severe AH and strongly predicted steatohepatitis (alcoholic steatohepatitis) on biopsy (area under receiver operating characteristics: 0.787 and 0.807). Application of published thresholds to predict alcoholic steatohepatitis would have rendered biopsy unnecessary in 84% of all AH cases. K18-M30 and M65 were associated with 90-day mortality, independent of age and Model for End-stage Liver Disease score in untreated patients. The association for K18-M65 was independent of both age and Model for End-stage Liver Disease in prednisolone-treated patients. Modelling of the effect of prednisolone on 90-day mortality as a function of pretreatment serum K18 levels indicated benefit in those with high serum levels of K18-M30. At low pretreatment serum K18 levels, prednisolone was potentially harmful. A threshold of K18-M30 5 kIU/L predicted therapeutic benefit from prednisolone above this level (odds ratio: 0.433, 95% confidence interval: 0.19-0.95, P = 0.0398), but not below (odds ratio: 1.271, 95% confidence interval: 0.88-1.84, P = 0.199). Restricting prednisolone usage to the former group would have reduced exposure by 87%. DISCUSSION: In a large cohort of patients with severe AH, serum K18 strongly correlated with histological severity, independently associated with 90-day mortality, and predicted response to prednisolone therapy. Quantification of serum K18 levels could assist in clinical decision-making
Doctor Referral of Overweight People to Low Energy total diet replacement Treatment (DROPLET):pragmatic randomised controlled trial
Objective
To test the effectiveness and safety of a total diet replacement (TDR) programme for routine treatment of obesity in a primary care setting.
Design
Pragmatic, two arm, parallel group, open label, individually randomised controlled trial.
Setting
10 primary care practices in Oxfordshire, UK.
Participants
278 adults who were obese and seeking support to lose weight: 138 were assigned to the TDR programme and 140 to usual care. 73% of participants were re-measured at 12 months.
Interventions
The TDR programme comprised weekly behavioural support for 12 weeks and monthly support for three months, with formula food products providing 810 kcal/day (3389 kJ/day) as the sole food during the first eight weeks followed by reintroduction of food. Usual care comprised behavioural support for weight loss from a practice nurse and a diet programme with modest energy restriction.
Main outcome measures
The primary outcome was weight change at 12 months analysed as intention to treat with mixed effects models. Secondary outcomes included biomarkers of cardiovascular and metabolic risk. Adverse events were recorded.
Results
Participants in the TDR group lost more weight (−10.7 kg) than those in the usual care group (−3.1 kg): adjusted mean difference −7.2 kg (95% confidence interval −9.4 to −4.9 kg). 45% of participants in the TDR group and 15% in the usual care group experienced weight losses of 10% or more. The TDR group showed greater improvements in biomarkers of cardiovascular and metabolic risk than the usual care group. 11% of participants in the TDR group and 12% in the usual care group experienced adverse events of moderate or greater severity.
Conclusions
Compared with regular weight loss support from a practice nurse, a programme of weekly behavioural support and total diet replacement providing 810 kcal/day seems to be tolerable, and leads to substantially greater weight loss and greater improvements in the risk of cardiometabolic disease
Impaired regeneration in LGMD2A supported by increased Pax7 positive satellite cell content and muscle specific microRNA dysregulation
Introduction—Recent in vitro studies suggest that CAPN3 deficiency leads initially to accelerated myofiber formation followed by depletion of satellite cells (SC). In normal muscle, upregulation of miR-1 and miR-206 facilitates transition from proliferating SCs to differentiating myogenic progenitors.
Methods—We examined the histopathological stages, Pax7 SC content, and muscle specific microRNA expression in biopsy specimens from well-characterized LGMD 2A patients to gain insight into disease pathogenesis.
Results—Three distinct stages of pathological changes were identified that represented the continuum of the dystrophic process from prominent inflammation with necrosis and regeneration to prominent fibrosis, which correlated with age and disease duration. Pax7-positive SCs were highest in fibrotic group and correlated with down-regulation of miR-1, miR-133a, and miR-206.
Conclusions—These observations, and other published reports, are consistent with microRNA dysregulation leading to inability of Pax7-positive SCs to transit from proliferation to differentiation. This results in impaired regeneration and fibrosis.This work was supported by NIH NIAMS U54 AR050733-05, Jesse’s Journey, and the muscular Dystrophy Associatio
Enterprise Education Competitions: A Theoretically Flawed Intervention?
The demand for including enterprise in the education system, at all levels and for all pupils is now a global phenomenon. Within this context, the use of competitions and competitive learning activities is presented as a popular and effective vehicle for learning. The purpose of this chapter is to illustrate how a realist method of enquiry – which utilises theory as the unit of analysis – can shed new light on the assumed and unintended outcomes of enterprise education competitions. The case developed here is that there are inherent flaws in assuming that competitions will ‘work’ in the ways set out in policy and guidance. Some of the most prevalent stated outcomes – that competitions will motivate and reward young people, that they will enable the development of entrepreneurial skills, and that learners will be inspired by their peers – are challenged by theory from psychology and education. The issue at stake is that the expansion of enterprise education policy into primary and secondary education increases the likelihood that more learners will be sheep dipped in competitions, and competitive activities, without a clear recognition of the potential unintended effects. In this chapter, we employ a realist-informed approach to critically evaluate the theoretical basis that underpins the use of competitions and competitive learning activities in school-based enterprise education. We believe that our findings and subsequent recommendations will provide those who promote and practice the use of competitions with a richer, more sophisticated picture of the potential flaws within such activities.Peer reviewedFinal Published versio
Safety Profile of Good Manufacturing Practice Manufactured Interferon \u3b3-Primed Mesenchymal Stem/Stromal Cells for Clinical Trials
Mesenchymal stem/stromal cells (MSCs) are widely studied by both academia and industry for a broad array of clinical indications. The collective body of data provides compelling evidence of the clinical safety of MSC therapy. However, generally accepted proof of therapeutic efficacy has not yet been reported. In an effort to generate a more effective therapeutic cell product, investigators are focused on modifying MSC processing protocols to enhance the intrinsic biologic activity. Here, we report a Good Manufacturing Practice-compliant two-step MSC manufacturing protocol to generate MSCs or interferon \u3b3 (IFN\u3b3) primed MSCs which allows freshly expanded cells to be infused in patients on a predetermined schedule. This protocol eliminates the need to infuse cryopreserved, just thawed cells which may reduce the immune modulatory activity. Moreover, using (IFN\u3b3) as a prototypic cytokine, we demonstrate the feasibility of priming the cells with any biologic agent. We then characterized MSCs and IFN\u3b3 primed MSCs prepared with our protocol, by karyotype, in vitro potential for malignant transformation, biodistribution, effect on engraftment of transplanted hematopoietic cells, and in vivo toxicity in immune deficient mice including a complete post-mortem examination. We found no evidence of toxicity attributable to the MSC or IFN\u3b3 primed MSCs. Our data suggest that the clinical risk of infusing MSCs or IFN\u3b3 primed MSCs produced by our two-step protocol is not greater than MSCs currently in practice. While actual proof of safety requires phase I clinical trials, our data support the use of either cell product in new clinical studies
Leadership in Community Nursing - Report of a study carried out by Queen Margaret University Edinburgh, NHS Lanarkshire and NHS Forth Valley
Study funded by Queens Nursing Institute ScotlandIn response to national and local agendas, both NHS Lanarkshire and NHS Forth Valley maintain a strong commitment to the development of those in clinical leadership positions. Queen Margaret University programmes in Nursing incorporate leadership as a core element in preparation for practice, and QMU have accredited NHS Lanarkshire's leadership educational programme for several years. This project emerged from that collaboration, from ideas about the nature of leadership and the recognition that few empirical studies exist in nursing in general, and fewer specifically in community nursing.
The two data collection sites were not involved in pilot work of the Review of Nursing in the Community (SEHD 2006) although all staff were working in this context of policy drivers encouraging change (SE 2005a, SE 2005b, Pollock 2007, Kennedy et al 2009, RCN 2009a 2009b).sch_nurAntrobus S, Kitson A (1999) Nursing leadership: influencing and shaping health policy and nursing practice. Journal of Advanced Nursing 29 (3) 746 - 753
Boumans, N.P. & Landeweerd, J.A. (1993) Leadership in the Nursing Unit: Relationships with Nurses' Well-being. Journal of Advanced Nursing 18 pp.767-775.
Bowles A, Bowles N B (2000) A comparative study of transformational leadership in nursing development units and conventional clinical settings. Journal of Nursing Management 8 69 - 76
Cain M (2005) Essential qualities of an effective clinical leader. Dimensions of Critical Care Nursing 24 (1) 32-4
Cook M J, Leathard H L (2004) Learning for clinical leadership. Journal of Nursing Management 12 436 - 444
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Kennedy C, Elliott L, Rush R, Hogg R, Cameron S, Currie M, Hall S, Miller M, Plunkett, S Lauder W (2009) Review of Community Nursing: baseline study. Available at:
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McKenna H, Keeney S, Bradley M (2004) Nurse leadership within primary care: the perceptions of community nurse, GPs, policy makers and members of the public. Journal of Nursing Management 12 69 - 76
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http://www.rcn.org.uk/__data/assets/pdf_file/0006/238092/RCN_vision_for_Community_Nursing_in_Scotland.pdf
Royal College of Nursing (2009b) A Sustainable Future: Voices on a Vision
http://www.rcn.org.uk/__data/assets/pdf_file/0015/238101/A_Sustainable_Future_Voices_on_a_Vision.pdf
Scottish Executive (2005a) Building a health service fit for the future: a national framework for service change in the NHS in Scotland (The Kerr Report-) Edinburgh, Scottish Executive
http://www.scotland.gov.uk/Resource/Doc/924/0012112.pdf
Scottish Executive (2005b) Delivering for Health Edinburgh, Scottish Executive http://www.scotland.gov.uk/Publications/2005/11/02102635/26356
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Wong CA, Cummings G G (2007) Relationship between nurse leadership and patient outcomes - a systematic review. Journal of Nursing Management. 15 (5) 508 - 521pub4561pu
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