HALT (Hernia Active Living Trial): protocol for a feasibility study of a randomised controlled trial of a physical activity intervention to improve quality of life in people with bowel stoma with a bulge/parastomal hernia

Background Parastomal hernia (PSH) can be repaired surgically, but results to date have been disappointing, with reported recurrence rates of 30 to 76%. Other types of intervention are therefore needed to improve the quality of life of people with PSH. One potential intervention is physical activity. We hypothesise that the intervention will increase core activation and control across the abdominal wall at a site of potential weakness and thus reduce the risk of PSH progression. Increases in physical activity will improve body image and quality of life (QoL). Methods Subjects and sample There were approximately 20 adults with a bowel stoma and PSH. People with previous PSH repair will be excluded as well as people who already do core training. Study design This is a feasibility study of a randomised controlled trial with 2 months follow-up, in 2 sites using mixed methods. Stage 1 involves intervention development and in stage 2, intervention and trial parameters will be assessed. Intervention A theoretically informed physical activity intervention was done, targeting people with PSH. Main outcome of feasibility study The main outcome is the decision by an independent Study Steering Committee whether to proceed to a full randomised controlled trial of the intervention. Other outcomes We will evaluate 4 intervention parameters—fidelity, adherence, acceptability and safety and 3 trial parameters (eligible patients’ consent rate, acceptability of study design and data availability rates for following endpoints): I. Diagnosis and classification of PSH II. Muscle activation III. Body composition (BMI, waist circumference) IV. Patient reported outcomes: QoL, body image and physical functioning V. Physical activity; VI. Psychological determinants of physical activity Other data Included are other data such as interviews with all participants about the intervention and trial procedures. Data analysis and statistical power As this is a feasibility study, the quantitative data will be analysed using descriptive statistics. Audio-recorded qualitative data from interviews will be transcribed verbatim and analysed thematically. Discussion The feasibility and acceptability of key intervention and trial parameters will be used to decide whether to proceed to a full trial of the intervention, which aims to improve body image, quality of life and PSH progression. Trial registration ISRCTN1520759

Trophic structure in the Gulf of Lions marine ecosystem (north-western Mediterranean Sea) and fishing impacts

International audienceThe Gulf of Lions ecosystemwas described using the Ecopath mass-balancemodel to characterise its structure and functioning and to examine the effects of themultispecific fisheries operating in this area. The model is composed of 40 compartments, including 1 group of seabirds, 2 groups of cetaceans, 18 groups of fish, 12 groups of invertebrates, 5 groups of primary producers, detritus and discards. Input datawere based on several recurrent scientific surveys, two alternative datasets for fishing data, stock assessment outputs, stomach content analyses and published information. Results showed that the functional groups were organised into five trophic levels with the highest one represented by dolphins, anglerfish, Atlantic bluefin tuna, European hake and European conger. European pilchard and European anchovy dominated in terms of fish biomass and catch. Other fish with high biomass such as Atlantic mackerel and blue whiting were highly important in the food web. Seabirds, dolphins and cuttlefish-squids represented keystone species. Important coupled pelagic-demersal-benthic interactions were described. The 7 different fisheries analysed were operating at mean trophic levels situated between 2.6 for small artisanal boats, and 4.1 for purse seines (>24 m) targeting large pelagic fish, indicating an intensively exploited ecosystem. Large trawlers (24-40 m) had the highest impact on most of the groups considered; while purse seines (12-24 m) targeting small pelagic fish had the lowest impact. Preliminary results highlighted the importance of data sources for further ecosystem and fisheries analyses and management scenarios

Estimated burden of cardiovascular disease and value-based price range for evolocumab in a high-risk, secondary-prevention population in the US payer context

<p><b>Aim:</b> To estimate real-world cardiovascular disease (CVD) burden and value-based price range of evolocumab for a US-context, high-risk, secondary-prevention population.</p> <p><b>Materials and methods:</b> Burden of CVD was assessed using the UK-based Clinical Practice Research Datalink (CPRD) in order to capture complete CV burden including CV mortality. Patients on standard of care (SOC; high-intensity statins) in CPRD were selected based on eligibility criteria of FOURIER, a phase 3 CV outcomes trial of evolocumab, and categorized into four cohorts: high-risk prevalent atherosclerotic CVD (ASCVD) cohort (<i>n</i> = 1448), acute coronary syndrome (ACS) (<i>n</i> = 602), ischemic stroke (IS) (<i>n</i> = 151), and heart failure (HF) (<i>n</i> = 291) incident cohorts. The value-based price range for evolocumab was assessed using a previously published economic model. The model incorporated CPRD CV event rates and considered CV event reduction rate ratios per 1 mmol/L reduction in low-density lipoprotein-cholesterol (LDL-C) from a meta-analysis of statin trials by the Cholesterol Treatment Trialists Collaboration (CTTC), i.e. CTTC relationship.</p> <p><b>Results:</b> Multiple-event rates of composite CV events (ACS, IS, or coronary revascularization) per 100 patient-years were 12.3 for the high-risk prevalent ASCVD cohort, and 25.7, 13.3, and 23.3, respectively, for incident ACS, IS, and HF cohorts. Approximately one-half (42%) of the high-risk ASCVD patients with a new CV event during follow-up had a subsequent CV event. Combining these real-world event rates and the CTTC relationship in the economic model, the value-based price range (credible interval) under a willingness-to-pay threshold of $150,000/quality-adjusted life-year gained for evolocumab was$11,990 ($9,341–$14,833) to $16,856 ($12,903–$20,678) in ASCVD patients with baseline LDL-C levels ≥70 mg/dL and ≥100 mg/dL, respectively.</p> <p><b>Conclusion:</b> Real-world CVD burden is substantial. Using the observed CVD burden in CPRD and the CTTC relationship, the cost-effectiveness analysis showed that, accounting for uncertainties, the expected value-based price for evolocumab is higher than its current annual cost, as long as the payer discount off list price is greater than 20%.</p