Ashley Agus

Evaluating early administration of the hydroxymethylglutaryl-CoA reductase inhibitor simvastatin in the prevention and treatment of delirium in critically ill ventilated patients (MoDUS trial): study protocol for a randomized controlled trial

BackgroundThe incidence of delirium in ventilated patients is estimated at up to 82%, and it is associated with longer intensive care and hospital stays, and long-term cognitive impairment and mortality. The pathophysiology of delirium has been linked with inflammation and neuronal apoptosis. Simvastatin has pleiotropic properties; it penetrates the brain and, as well as reducing cholesterol, reduces inflammation when used at clinically relevant doses over the short term. This is a single centre randomised, controlled trial which aims to test the hypothesis that treatment with simvastatin will modify delirium incidence and outcomes.Methods/DesignThe ongoing study will include 142 adults admitted to the Watford General Hospital Intensive Care Unit who require mechanical ventilation in the first 72 hours of admission. The primary outcome is the number of delirium- and coma-free days in the first 14 days. Secondary outcomes include incidence of delirium, delirium- and coma-free days in the first 28 days, days in delirium and in coma at 14 and 28 days, number of ventilator-free days at 28 days, length of critical care and hospital stay, mortality, cognitive decline and healthcare resource use. Informed consent will be taken from patient’s consultee before randomisation to receive either simvastatin (80 mg) or placebo once daily. Daily data will be recorded until day 28 after randomisation or until discharge from the ICU if sooner. Surviving patients will be followed up on at six months from discharge. Plasma and urine samples will be taken to investigate the biological effect of simvastatin on systemic markers of inflammation, as related to the number of delirium- and coma-free days, and the potential of cholinesterase activity and beta-amyloid as predictors of the risk of delirium and long-term cognitive impairment.DiscussionThis trial will test the efficacy of simvastatin on reducing delirium in the critically ill. If patients receiving the statin show a reduced number of days in delirium compared with the placebo group, the inflammatory theory implicated in the pathogenesis of delirium will be strengthened.Trial registrationThe trial was registered with the International Standard Randomised Controlled Trial Registry (ISRCTN89079989) on 26 March 2013.

Public perceptions of coronary events risk factors: a discrete choice experiment

Objectives To assess public perceptions of coronary heart disease (CHD) risk factors. Design Discrete choice experiment questionnaire. Setting Six provincial centres in Northern Ireland. Participants 1000 adults of the general public in Northern Ireland. Primary and secondary outcomes The general publics perception of CHD risk factors. The effect of having risk factor(s) on that perception. Results Two multinomial logit models were created. One was a basic model (no heterogeneity permitted), while the other permitted heterogeneity based on respondents’ characteristics. In both models individuals with very high cholesterol were perceived to be at the highest risk of having a coronary event. Respondents who reported having high cholesterol perceived the risk contribution of very high cholesterol to be greater than those who reported having normal cholesterol. Similar findings were observed with blood pressure and smoking. Respondents who were male and older perceived the contribution of age and gender to be lower than respondents who were female and younger. Conclusions Respondents with different risk factors perceived such factors differently. These divergent perceptions of CHD risk factors could be a barrier to behavioural change. This brings into focus the need for more tailored health promotion campaigns to tackle CHD.

Clinical and Cost-Effectiveness of Procalcitonin Test for Prodromal Meningococcal Disease–A Meta-Analysis

Background Despite vaccines and improved medical intensive care, clinicians must continue to be vigilant of possible Meningococcal Disease in children. The objective was to establish if the procalcitonin test was a cost-effective adjunct for prodromal Meningococcal Disease in children presenting at emergency department with fever without source. Methods and Findings Data to evaluate procalcitonin, C-reactive protein and white cell count tests as indicators of Meningococcal Disease were collected from six independent studies identified through a systematic literature search, applying PRISMA guidelines. The data included 881 children with fever without source in developed countries.The optimal cut-off value for the procalcitonin, C-reactive protein and white cell count tests, each as an indicator of Meningococcal Disease, was determined. Summary Receiver Operator Curve analysis determined the overall diagnostic performance of each test with 95% confidence intervals. A decision analytic model was designed to reflect realistic clinical pathways for a child presenting with fever without source by comparing two diagnostic strategies: standard testing using combined C-reactive protein and white cell count tests compared to standard testing plus procalcitonin test. The costs of each of the four diagnosis groups (true positive, false negative, true negative and false positive) were assessed from a National Health Service payer perspective. The procalcitonin test was more accurate (sensitivity=0.89, 95%CI=0.76-0.96; specificity=0.74, 95%CI=0.4-0.92) for early Meningococcal Disease compared to standard testing alone (sensitivity=0.47, 95%CI=0.32-0.62; specificity=0.8, 95% CI=0.64-0.9). Decision analytic model outcomes indicated that the incremental cost effectiveness ratio for the base case was £-8,137.25 (US

A Cost Analysis of a Remote Home Support Programme for Infants with Major Congenital Heart Disease: Evidence from a Randomized Controlled Trial

-13,371.94) per correctly treated patient. Conclusions Procalcitonin plus standard recommended tests, improved the discriminatory ability for fatal Meningococcal Disease and was more cost-effective; it was also a superior biomarker in infants. Further research is recommended for point-of-care procalcitonin testing and Markov modelling to incorporate cost per QALY with a life-time model.

Healthcare use, costs and quality of life in patients with end-stage kidney disease receiving conservative management: results from a multi-centre observational study (PACKS)

A Cost Analysis of a Remote Home Support Programme for Infants with Major Congenital Heart Disease: Evidence from a Randomized Controlled Trial Objective: Paediatric cardiology is a highly centralised subspecialty with patients living often living large distances from the tertiary care centre. A tele homecare programme for infants with major congenital heart disease (CHD) was devised to support patients and families during the stressful and vulnerable period following discharge from hospital. This study aimed to describe the costs and potential savings of a telemedicine home support programme for infants with major congenital heart disease (CHD). Methods: A randomized controlled trial was performed at a UK tertiary paediatric cardiology centre. Infants with major CHD discharged home were randomized to one of three groups: Two intervention groups (Video support and Telephone support) and one control group (standard care). Patients in the two intervention groups received regular, standardised remote consultations. Video support initially provided by ISDN lines and later by a home broadband (IP) connection. The main outcome measure was a comparison of total cost to NHS of participants including cost of study interventions and health service utilisation.

Steps Towards Alcohol Misuse Prevention Programme (STAMPP): a school-based and community-based cluster randomised controlled trial

Background: Previous research has explored the cost of providing renal replacement therapies in patients with end-stage kidney disease and their quality of life. This is the first study to examine the healthcare costs of patients receiving conservative care without dialysis for end-stage kidney disease. This alternative to dialysis is an option for patients who prefer a supportive and palliative care approach. Aim: Descriptive cost and quality of life analyses alongside a UK-based multi-centre observational study in patients receiving conservative management for end-stage kidney disease. Design: Health service use was recorded up to 12 months after making the decision to receive conservative management. Mean costs were calculated for each 3-month time period. The annual cost was calculated in two ways: by using only patients with complete cost data and by using all available data weighted by the number of patients at each time point. Setting: In total, 42 patients who opted for conservative management over dialysis were recruited. Results: Mean costs were £1622 (0–3 months), £1008 (3–6 months), £554 (6–9 months) and £2626 (9–12 months). Mean annual cost based on complete data (n = 8) was £5511, and the weighted mean annual cost was £5620. Conclusion: The importance of this study is twofold. First, it provides substantive new information for health and social care planning of conservative management by demonstrating where demand exists for services, in both the United Kingdom and other countries with a comparable health service structure. Second, methodologically, it indicates that it is feasible to collect service use data directly from this patient population.

Erratum to: Cost-utility analysis of a pharmacy-led self-management programme for patients with COPD

Objectives To assess the effectiveness of a combined classroom curriculum and parental intervention (the Steps Towards Alcohol Misuse Prevention Programme (STAMPP)), compared with alcohol education as normal (EAN), in reducing self-reported heavy episodic drinking (HED) and alcohol-related harms (ARHs) in adolescents. Setting 105 high schools in Northern Ireland (NI) and in Scotland. Participants Schools were stratified by free school meal provision. Schools in NI were also stratified by school type (male/female/coeducational). Eligible students were in school year 8/S1 (aged 11–12 years) at baseline (June 2012). Intervention A classroom-based alcohol education intervention, coupled with a brief alcohol intervention for parents/carers. Primary outcomes (1) The prevalence of self-reported HED in the previous 30 days and (2) the number of self-reported ARHs in the previous 6 months. Outcomes were assessed using two-level random intercepts models (logistic regression for HED and negative binomial for number of ARHs). Results At 33 months, data were available for 5160 intervention and 5073 control students (HED outcome), and 5234 and 5146 students (ARH outcome), respectively. Of those who completed a questionnaire at either baseline or 12 months (n=12 738), 10 405 also completed the questionnaire at 33 months (81.7%). Fewer students in the intervention group reported HED compared with EAN (17%vs26%; OR=0.60, 95% CI 0.49 to 0.73), with no significant difference in the number of self-reported ARHs (incident rate ratio=0.92, 95% CI 0.78 to 1.05). Although the classroom component was largely delivered as intended, there was low uptake of the parental component. There were no reported adverse effects. Conclusions Results suggest that STAMPP could be an effective programme to reduce HED prevalence. While there was no significant reduction in ARH, it is plausible that effects on harms would manifest later. Trial registration number ISRCTN47028486; Post-results.

Cost-utility analysis of a pharmacy-led self-management programme for patients with COPD

The online version of the original article can be found underdoi:10.1007/s11096-011-9524-z.M. R. Khdour J. C. McElnayClinical and Practice Research Group (CPRG), Schoolof Pharmacy, Medical Biology Centre, Queen’s UniversityBelfast, 97 Lisburn Road, Belfast BT9 7BL, UKA. M. Agus (&) G. E. CrealeyN.I. Clinical Research Support Centre, Education and ResearchBuilding, The Royal Group of Hospitals, Grosvenor Road,Belfast BT12 6BA, UKe-mail: ashley.agus@crsc.n-i.nhs.ukJ. C. Kidney B. M. SmythDepartment of Respiratory Medicine, Mater Hospital,Belfast BT14 6AB, UK