A pragmatic randomised controlled trial of the Welsh National Exercise Referral Scheme: protocol for trial and integrated economic and process evaluation

Background: The benefits to health of a physically active lifestyle are well established and there is evidence that a sedentary lifestyle plays a significant role in the onset and progression of chronic disease. Despite a recognised need for effective public health interventions encouraging sedentary people with a medical condition to become more active, there are few rigorous evaluations of their effectiveness. Following NICE guidance, the Welsh national exercise referral scheme was implemented within the context of a pragmatic randomised controlled trial. Methods/Design: The randomised controlled trial, with nested economic and process evaluations, recruited 2,104 inactive men and women aged 16+ with coronary heart disease (CHD) risk factors and/or mild to moderate depression, anxiety or stress. Participants were recruited from 12 local health boards in Wales and referred directly by health professionals working in a range of health care settings. Consenting participants were randomised to either a 16 week tailored exercise programme run by qualified exercise professionals at community sports centres (intervention), or received an information booklet on physical activity (control). A range of validated measures assessing physical activity, mental health, psycho-social processes and health economics were administered at 6 and 12 months, with the primary 12 month outcome measure being 7 day Physical Activity Recall. The process evaluation explored factors determining the effectiveness or otherwise of the scheme, whilst the economic evaluation determined the relative cost-effectiveness of the scheme in terms of public spending. Discussion: Evaluation of such a large scale national public health intervention presents methodological challenges in terms of trial design and implementation. This study was facilitated by early collaboration with social research and policy colleagues to develop a rigorous design which included an innovative approach to patient referral and trial recruitment, a comprehensive process evaluation examining intervention delivery and an integrated economic evaluation. This will allow a unique insight into the feasibility, effectiveness and cost effectiveness of a national exercise referral scheme for participants with CHD risk factors or mild to moderate anxiety, depression, or stress and provides a potential model for future policy evaluations. Trial registration: Current Controlled Trials ISRCTN4768044

Identification of novel translational urinary biomarkers for acetaminophen-induced acute liver injury using proteomic profiling in mice

Contains fulltext : 108207.pdf (publisher's version ) (Open Access)Drug-induced liver injury (DILI) is the leading cause of acute liver failure. Currently, no adequate predictive biomarkers for DILI are available. This study describes a translational approach using proteomic profiling for the identification of urinary proteins related to acute liver injury induced by acetaminophen (APAP). Mice were given a single intraperitoneal dose of APAP (0-350 mg/kg bw) followed by 24 h urine collection. Doses of >/=275 mg/kg bw APAP resulted in hepatic centrilobular necrosis and significantly elevated plasma alanine aminotransferase (ALT) values (p<0.0001). Proteomic profiling resulted in the identification of 12 differentially excreted proteins in urine of mice with acute liver injury (p<0.001), including superoxide dismutase 1 (SOD1), carbonic anhydrase 3 (CA3) and calmodulin (CaM), as novel biomarkers for APAP-induced liver injury. Urinary levels of SOD1 and CA3 increased with rising plasma ALT levels, but urinary CaM was already present in mice treated with high dose of APAP without elevated plasma ALT levels. Importantly, we showed in human urine after APAP intoxication the presence of SOD1 and CA3, whereas both proteins were absent in control urine samples. Urinary concentrations of CaM were significantly increased and correlated well with plasma APAP concentrations (r = 0.97; p<0.0001) in human APAP intoxicants, who did not present with elevated plasma ALT levels. In conclusion, using this urinary proteomics approach we demonstrate CA3, SOD1 and, most importantly, CaM as potential human biomarkers for APAP-induced liver injury

Anal incontinence, urinary incontinence and sexual problems in primiparous women – a comparison between women with episiotomy only and women with episiotomy and obstetric anal sphincter injury

Background: Obstetric anal sphincter injuries (OASIS) might cause anal incontinence (AI) and sexual dysfunction, and might be associated with urinary incontinence (UI). Episiotomy has been identified both as a risk and a protective factor of OASIS. Lately, episiotomies with specific characteristics have shown to be protective against the risk of OASIS. However, little is known about episiotomy characteristics and pelvic floor dysfunction. This study investigates AI, UI, and sexual problems in primiparous women with episiotomy, comparing women with and without OASIS. Associations between episiotomy characteristics and AI, UI, and sexual problems were assessed. Methods: This is a matched case–control study investigating 74 women with one vaginal birth, all with an episiotomy. Among these, 37 women sustained OASIS and were compared to 37 women without OASIS. The two groups were matched for vacuum/forceps. AI, UI and sexual problem symptoms were obtained from St. Mark’s scoring-tool and self-administered questionnaires. The episiotomy characteristics were investigated and results assessed for the whole group. Results: The mean time from birth was 34.5 months (range1.3-78.2) for those with OASIS and 25.9 months (range 7.0-57.4) for those without OASIS, respectively. More women with OASIS reported AI: 14 (38%) vs. 3 (8%) p = 0.05 (OR 4.66, 95% CI 1.34-16.33) as well as more problem with sexual desire p = 0.02 (OR 7.62, 95% CI 1.30-44.64) compared to women without OASIS. We found no association between episiotomy with protective characteristics and dysfunctions. Conclusion: Women with OASIS had more AI and sexual problems than those without OASIS. Episiotomy characteristics varied greatly between the women. Episiotomy with protective characteristics was not associated with increased dysfunctions. OASIS should be avoided, and correct episiotomy used if indicated

Technologies for Biomarkers in Periodontics

[No Abstract Available