Noninvasive markers of liver fibrosis: on-treatment changes of serum markers predict the outcome of antifibrotic therapy.

AIM: The utility of noninvasive serum markers to longitudinally monitor liver fibrosis is not established. METHODS: A total of 70 patients with chronic hepatitis C who had previously failed antiviral therapy were randomized to receive pegylated interferon with or without silymarin for 24 months. Enhanced Liver Fibrosis (ELF) tests (hyularonic acid, terminal peptide of procollagen III, tissue inhibitor of matrix metaloproteinase-1) were performed on patient sera obtained before, during and at the end of the study (0, 12, 24 months) and liver histology obtained before and at the end of the study. RESULTS: At 24 months, absolute changes in Ishak fibrosis stage and ELF ranged from -4 to +4 and from -2.41 to +2.68, respectively. Absolute changes in ELF at 12 months were significantly associated with changes in both ELF and histology at 24 months. A model combining both baseline ELF and change of ELF at 12 months could predict the 24-month ELF (R=0.609, P<1×10), a decrease in ELF at 24 months [area under the curve (AUC): 0.80-0.85] and an increase in ELF at 24 months (AUC: 0.81-0.85). Furthermore, a model combining both baseline histologic stage and ELF together with the change of ELF at 12 months could predict 24-month histology (R=0.601, P<1×10, AUC: 0.88-0.92), histologic fibrosis regression (AUC: 0.81-0.84) and progression (AUC: 0.86-0.91). CONCLUSION: Our observations suggest that a change in the serum marker ELF predicts changes in liver fibrosis over a longer period. These data support the use of ELF as a surrogate marker of liver fibrosis evolution in monitoring antifibrotic treatments, thus permitting 'response-guided' therapy by the early identification of patients who will benefit from prolonged treatment.

Changing nursing student attitudes to consumer participation in mental health services: a survey study of traditional and lived experience-led education.

Mental health policy emphasises the importance of consumer participation in mental health services. To align education with policy and orient future healthcare services to active consumer involvement, the potential of academics with a lived experience of mental illness to impact on student attitudes towards consumer participation needs to be examined. A cohort comparative study was undertaken comparing attitudinal change between undergraduate nursing students undertaking two different mental health courses, one nurse-led (n  =  61) and one lived experience-led. Attitudes were measured through the Mental Health Consumer Participation Questionnaire. Within-cohort change was assessed via dependent sample t-tests, and degree of change was observed in each cohort, by comparing effect sizes. For the nurse-led course, attitudes on consumer involvement t (60)  =  -1.79, p < 0.005 (95% CI: -2.84, -0.74) and consumer as staff t (60)  =  -4.12, p < 0.005 (95% CI: -3.34, -1.16), positively changed with effect size r of 0.40 and 0.47, respectively. For the lived experience-led course, attitudes on consumer capacity t (109)  =  -3.63, p < 0.005 (95% CI: -0.48, -1.41) and consumer as staff, t (109)  =  -5.63, p < 0.005 (95% CI: -0.97, -0.46), positively changed, effect size r of 0.33 and 0.47, respectively. Mental health nursing education has a positive and selective influence on attitudes to consumer participation. Lived experience-led education was more beneficial in changing attitudes to consumer capacity and both types of education had similar positive effects on attitudes to consumers as staff.

A randomised controlled trial of structured nurse-led outpatient clinic follow-up for dyspeptic patients after direct access gastroscopy.

BACKGROUND: Dyspepsia is a common disorder in the community, with many patients referred for diagnostic gastroscopy by their General Practitioner (GP). The National Institute of Clinical Excellence (NICE) recommends follow-up after investigation for cost effective management, including lifestyle advice and drug use. An alternative strategy may be the use of a gastro-intestinal nurse practitioner (GNP) instead of the GP. The objective of this study is to compare the effectiveness and costs of systematic GNP led follow-up to usual care by GPs in dyspeptic patients following gastroscopy. RESULTS: Direct access adult dyspeptic patients referred for gastroscopy; without serious pathology, were followed-up in a structured nurse-led outpatient clinic. Outcome measurement used to compare the two study cohorts (GNP versus GP) included Glasgow dyspepsia severity (Gladys) score, Health Status Short Form 12 (SF12), ulcer healing drug (UHD) use and costs. One hundred and seventy five patients were eligible after gastroscopy, 89 were randomised to GNP follow-up and 86 to GP follow-up. Follow-up at 6 months was 81/89 (91%) in the GNP arm and 79/86 (92%) in the GP arm. On an intention to treat analysis, adjusted mean differences (95%CI) at follow-up between Nurse and GP follow-up were: Gladys score 2.30 (1.4-3.2) p < 0.001, SF12 140.6 (96.5-184.8) p =< 0.001 and UHD costs pound39.60 ( pound24.20- pound55.10) p =< 0.001, all in favour of nurse follow-up. CONCLUSION: A standardised and structured follow-up by one gastrointestinal nurse practitioner was effective and may save drug costs in patients after gastroscopy. These findings need replication in other centres.

Antimicrobial peptide therapeutics for cystic fibrosis.

Greater than 90% of lung infections in cystic fibrosis (CF) patients are caused by Pseudomonas aeruginosa, and the majority of these patients subsequently die from lung damage. Current therapies are either targeted at reducing obstruction, reducing inflammation, or reducing infection. To identify potential therapeutic agents for the CF lung, 150 antimicrobial peptides consisting of three distinct structural classes were screened against mucoid and multidrug-resistant clinical isolates of P. aeruginosa, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Staphylococcus aureus. Five peptides that retained potent antimicrobial activities in physiological salt and divalent cation environment were further characterized in vivo using a rat chronic lung infection model. All animals were inoculated intratracheally with 10(4) P. aeruginosa mucoid PAO1 cells in agar beads. Three days following inoculation treatment was initiated. Animals were treated daily for 3 days with 100 microl of peptide solution (1 mg/ml) in 10 mM sodium citrate, which was deposited via either intratracheal instillation or aerosolization. Control animals received daily exposure to vehicle alone. At the end of the treatment the lungs of the animals were removed for quantitative culture. Four peptides, HBCM2, HBCM3, HBCPalpha-2, and HB71, demonstrated significant reduction in Pseudomonas bioburden in the lung of rats. Further in vivo studies provided direct evidence that anti-inflammatory activity was associated with three of these peptides. Therefore, small bioactive peptides have the potential to attack two of the components responsible for the progression of lung damage in the CF disease: infection and inflammation.