NHS Ayrshire and Arran

About: NHS Ayrshire and Arran is a healthcare organization based out in Ayr, United Kingdom. It is known for research contribution in the topics: Randomized controlled trial & Population. The organization has 278 authors who have published 313 publications receiving 6659 citations. The organization is also known as: Ayrshire and Arran NHS Board.

Exercise for preventing and treating osteoporosis in postmenopausal women

Abstract: Background Osteoporosis is a condition resulting in an increased risk of skeletal fractures due to a reduction in the density of bone tissue. Treatment of osteoporosis typically involves the use of pharmacological agents. In general it is thought that disuse (prolonged periods of inactivity) and unloading of the skeleton promotes reduced bone mass, whereas mechanical loading through exercise increases bone mass. Objectives To examine the effectiveness of exercise interventions in preventing bone loss and fractures in postmenopausal women. Search methods During the update of this review we updated the original search strategy by searching up to December 2010 the following electronic databases: the Cochrane Musculoskeletal Group's Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2010 Issue 12); MEDLINE; EMBASE; HealthSTAR; Sports Discus; CINAHL; PEDro; Web of Science; Controlled Clinical Trials; and AMED. We attempted to identify other studies by contacting experts, searching reference lists and searching trial registers. Selection criteria All randomised controlled trials (RCTs) that met our predetermined inclusion criteria. Data collection and analysis Pairs of members of the review team extracted the data and assessed trial quality using predetermined forms. For dichotomous outcomes (fractures), we calculated risk ratios (RRs) using a fixed-effect model. For continuous data, we calculated mean differences (MDs) of the percentage change from baseline. Where heterogeneity existed (determined by the I2 statistic), we used a random-effects model. Main results Forty-three RCTs (27 new in this update) with 4320 participants met the inclusion criteria. The most effective type of exercise intervention on bone mineral density (BMD) for the neck of femur appears to be non-weight bearing high force exercise such as progressive resistance strength training for the lower limbs (MD 1.03; 95% confidence interval (CI) 0.24 to 1.82). The most effective intervention for BMD at the spine was combination exercise programmes (MD 3.22; 95% CI 1.80 to 4.64) compared with control groups. Fractures and falls were reported as adverse events in some studies. There was no effect on numbers of fractures (odds ratio (OR) 0.61; 95% CI 0.23 to 1.64). Overall, the quality of the reporting of studies in the meta-analyses was low, in particular in the areas of sequence generation, allocation concealment, blinding and loss to follow-up. Authors' conclusions Our results suggest a relatively small statistically significant, but possibly important, effect of exercise on bone density compared with control groups. Exercise has the potential to be a safe and effective way to avert bone loss in postmenopausal women.

Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling

Abstract: The type I interferon system is integral to human antiviral immunity. However, inappropriate stimulation or defective negative regulation of this system can lead to inflammatory disease. We sought to determine the molecular basis of genetically uncharacterized cases of the type I interferonopathy Aicardi-Goutieres syndrome and of other undefined neurological and immunological phenotypes also demonstrating an upregulated type I interferon response. We found that heterozygous mutations in the cytosolic double-stranded RNA receptor gene IFIH1 (also called MDA5) cause a spectrum of neuroimmunological features consistently associated with an enhanced interferon state. Cellular and biochemical assays indicate that these mutations confer gain of function such that mutant IFIH1 binds RNA more avidly, leading to increased baseline and ligand-induced interferon signaling. Our results demonstrate that aberrant sensing of nucleic acids can cause immune upregulation.

Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1.

Abstract: Aicardi-Goutieres syndrome is an inflammatory disease occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report on 374 patients from 299 families with mutations in these seven genes. Most patients conformed to one of two fairly stereotyped clinical profiles; either exhibiting an in utero disease-onset (74 patients; 22.8% of all patients where data were available), or a post-natal presentation, usually within the first year of life (223 patients; 68.6%), characterized by a sub-acute encephalopathy and a loss of previously acquired skills. Other clinically distinct phenotypes were also observed; particularly, bilateral striatal necrosis (13 patients; 3.6%) and non-syndromic spastic paraparesis (12 patients; 3.4%). We recorded 69 deaths (19.3% of patients with follow-up data). Of 285 patients for whom data were available, 210 (73.7%) were profoundly disabled, with no useful motor, speech and intellectual function. Chilblains, glaucoma, hypothyroidism, cardiomyopathy, intracerebral vasculitis, peripheral neuropathy, bowel inflammation and systemic lupus erythematosus were seen frequently enough to be confirmed as real associations with the Aicardi-Goutieres syndrome phenotype. We observed a robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferon-stimulated gene transcripts in peripheral blood. We recorded a positive correlation between the level of cerebrospinal fluid interferon activity assayed within one year of disease presentation and the degree of subsequent disability. Interferon-stimulated gene transcripts remained high in most patients, indicating an ongoing disease process. On the basis of substantial morbidity and mortality, our data highlight the urgent need to define coherent treatment strategies for the phenotypes associated with mutations in the Aicardi-Goutieres syndrome-related genes. Our findings also make it clear that a window of therapeutic opportunity exists relevant to the majority of affected patients and indicate that the assessment of type I interferon activity might serve as a useful biomarker in future clinical trials.

Exploring change processes in compassion focused therapy in psychosis: Results of a feasibility randomized controlled trial

Abstract: Objectives Compassion focused therapy (CFT) was developed to stimulate capacities for soothing and affiliation to self and others as a way to regulate the threat system. This feasibility study aimed to assess the safety, the acceptability, the potential benefits, and associated change processes of using group CFT with people recovering from psychosis. Design A prospective, randomized, open-label, blinded end point evaluation design was used. Method Forty adult patients with a schizophrenia-spectrum disorder were randomized to CFT plus treatment as usual (TAU; n = 22) or to TAU alone (n = 18). Group CFT comprised 16 sessions (2 hr each, 1 x week). Participants were assessed prior to randomization and at the end of treatment. Assessments included semi-structured interviews to elicit narratives of recovery from psychosis and self-report measures. At the end of treatment, participants were rated on the Clinical Global Impression Scale. Narratives were coded using the Narrative Recovery Style Scale to provide measures of change in compassion and avoidance. Change processes were correlated with changes in depression, personal beliefs about illness, fear of recurrence, and positive and negative affect. Results Group CFT was associated with no adverse events, low attrition (18%), and high acceptability. Relative to TAU, CFT was associated with greater observed clinical improvement (p < 0.001) and significant increases in compassion (p = 0.015) of large magnitude. Relative to TAU, increases in compassion in the CFT group were significantly associated with reductions in depression (p = 0.001) and in perceived social marginalization (p = 0.002). Discussion Findings support the feasibility of group CFT in psychosis and suggest that changes in compassion can be achieved, which appear to reduce depression in particular. This is the first randomized controlled evaluation of CFT. Conclusion Compassion focused therapy appears as a safe, acceptable, promising, and evolving intervention for promoting emotional recovery from psychosis. Practitioner Points Compassion focused therapy appears safe to use with people recovering from psychosis. Compassion focused therapy was associated with significantly greater clinical improvement than Treatment as Usual. Relative to TAU, CFT was associated with a significant increase in compassion of large magnitude. Relative to TAU, in the CFT group increases in compassion were significantly associated with reductions in depression and in perceived social marginalization.