Reducing Asthma Attacks in Children using Exhaled Nitric Oxide as a biomarker to inform treatment strategy: a randomised trial (RAACENO).

BACKGROUND: Childhood asthma is a common condition. Currently there is no validated objective test which can be used to guide asthma treatment in children. This study tests the hypothesis that the addition of fractional exhaled nitric oxide (FENO) monitoring in addition to standard care reduces the number of exacerbations (or attacks) in children with asthma. METHODS: This is a multi-centre, randomised controlled study. Children will be included of age 6-16 years who have a diagnosis of asthma, currently use inhaled corticosteroids (ICSs) and have had an exacerbation in the previous 12 months. Exclusion criteria include being unable to provide FENO measurement at baseline assessment, having another chronic respiratory condition and being currently treated with maintenance oral steroids. Participants will be recruited in both primary and secondary care settings and will be randomised to either receive asthma treatment guided by FENO plus symptoms (FENO group) or asthma treatment guided by symptoms only (standard care group). Within the FENO group, different treatment decisions will be made dependent on changes in FENO. Participants will attend assessments 3, 6, 9 and 12 months post randomisation. The primary outcome is asthma exacerbation requiring prescription and/or use of an oral corticosteroid over 12 months as recorded by the participant/parent or in general practitioner records. Secondary outcomes include time to first attack, number of attacks, asthma control score and quality of life. Adherence to ICS treatment is objectively measured by an electronic logging device. Participants are invited to participate in a "phenotyping" assessment where skin prick reactivity and bronchodilator response are determined and a saliva sample is collected for DNA extraction. Qualitative interviews will be held with participants and research nurses. A health economic evaluation will take place. DISCUSSION: This study will evaluate whether FENO can provide an objective index to guide and stratify asthma treatment in children. TRIAL REGISTRATION: ISRCTN, ISRCTN67875351. Registered on 12 April 2017. Prospectively registered.

Comparison of one-year costs of type 2 diabetes treatment with insulin glargine or insulin detemir in a basal supported oral therapy (BOT) in Germany.

OBJECTIVE: A one-year cost analysis comparing basal insulin analogues glargine (IG, Lantus) versus detemir (ID, Levemir) in combination with oral antidiabetic drugs (basal supported oral therapy; BOT) in insulin naive Type 2 diabetes patients in Germany based on the results of a randomized controlled clinical trial (RCT). The trial demonstrated equivalent treatment efficacy. MATERIALS AND METHODS: Total direct diabetes treatment costs were estimated from the perspective of the German statutory health insurance (SHI) for the time horizon of one-year. Simulated resources included medication (insulin, oral antidiabetic drugs) and consumable items (needles, blood glucose test strips and lancets). Initial and final insulin doses per kg body weight and proportion of patients with once/twice daily insulin injection were taken from the above mentioned RCT. Unit costs were taken from official German price lists and sources. Deterministic-(DTA) and probabilistic sensitivity analyses (PSA) on resource use and unit costs were performed to test robustness of the results. RESULTS: Average annual treatment costs per patient (base case) were euro 849 for glargine and euro 1,334 for detemir resulting in cost savings of euro 486 per patient per year (36%). Costs of insulins were euro 469 (IG) and euro 746 (ID). Costs of consumable items amounted at euro 380 (IG) and euro 588 (ID) respectively. Sensitivity analyses confirmed the findings in favor of insulin glargine. PSA results found cost savings ranging from euro 429 to euro 608 (5th/95th percentiles). CONCLUSIONS: The current model estimated that insulin glargine was associated with lower annual treatment costs of euro 486 (36%) compared to the use of insulin detemir while the same glycemic control is expected to be achieved.

Measuring the effects of seating on people with profound and multiple disabilities--a preliminary study.

This paper describes a preliminary study to investigate a range of approaches that might be used for measuring the effects of special seating on people with profound and multiple disabilities and their carers. A number of tools are proposed for measuring the effects on quality of life, function and carer satisfaction. The results of applying these tools to measure the effects of intervention with customized molded seating on nine people with multiple disabilities are described. The results suggest that these tools are sensitive to this intervention, showing a general beneficial effect with good carer satisfaction. The study points the way towards application of these tools to people with a wider range of disabilities and to different interventions.

Interpreting reported health-care benefits.

When reading published reports on the benefits of different treatments or health-care programmes, readers are generally interested in judging the applicability of the results to their own settings. Thus they need to be able to identify what consequences (and costs) were included in the evaluation. This short paper describes the different categories of 'benefit' that may arise from health-care interventions and explains some of the methodological considerations in their measurement. It provides simple advice on avoiding the common pitfalls when interpreting the value offered by a particular treatment or configuration of health services.

Interpreting reported health-care costs.

This short paper describes the different categories of health-care costs and methodological considerations in cost measurement. It provides simple advice on avoiding some of the common pitfalls in cost interpretation and should help readers in assessing the usefulness of reported costs.

Faecal occult blood screening for colorectal cancer: is it cost-effective?

Recently published evidence from two large-scale clinical trials conducted in England and in Denmark suggests that faecal occult blood screening for colorectal cancer significantly reduces mortality. However, before screening can be advocated as part of national health policy, its cost-effectiveness must be demonstrated. The English screening trial has been the subject of a detailed economic evaluation over the past 10 years In this paper, cost-effectiveness estimates of screening are presented, based on cost and outcome data combined in a mathematical model developed from the trial's clinical findings The estimates of cost per quality-adjusted life-year gained from colorectal cancer screening show the procedure to be of similar cost-effectiveness to breast cancer screening in the short term. Over the longer term, however, the estimates for colorectal cancer screening appear superior.

Symptoms before and after surgery for colorectal cancer.

Questionnaires were completed by a sample (n = 53) of patients at two points in time, prior to surgery for colorectal cancer and three months thereafter. The questionnaires comprised the Nottingham Health Profile, as a general health status measure, and a specific checklist of 30 symptoms. Of the physical symptoms, loss of appetite, rectal bleeding and urgency of bowel movement appeared to decline after treatment, whilst other potential symptoms, such as vomiting, appeared to occur only rarely, both before and after surgery. Pre-treatment symptoms of psychological distress appeared to have dissipated by three months, suggesting that they were more likely to have resulted from the anticipation of treatment rather from the disease itself. A logistic regression model suggests that the presence of certain symptoms, such as rectal bleeding and heartburn, is more likely to be associated with the presence of late- as opposed to early-stage cancer.

Cost-effectiveness of screening for colorectal cancer: a simulation model.

Colorectal cancer is a major cause of mortality in Western countries, although early detection of the disease is known to improve survival. Recent developments in medical technology have made mass population screening a practicable proposition and a number of randomized controlled trials of screening are currently being conducted. This paper reports on the construction of a computer simulation model of the cost-effectiveness of colorectal cancer screening, being developed in conjunction with a major UK trial. Based on accumulated trial data and semi-Markov descriptions of the disease process, the model will facilitate the assessment of the cost-effectiveness of a variety of screening modalities, with a view to informing policy in the future.

Determinants of persistent compliance with screening for colorectal cancer.

Mass population screening for colorectal cancer is currently being evaluated by means of randomized controlled trials. These trials point to the likelihood that, if implemented, the level of both initial and sustained compliance will prevent the full potential of screening being realised. The paper opens by reviewing the evidence on determinants of compliance, both initial and longer term, although little empirical evidence on adherence to repeated screening is currently available. The paper then presents the results of a survey of persistent compliers and non-compliers within the English screening trial, in order to identify those characteristics most closely associated with persistent compliance behaviour. Persistent compliers are found, inter alia, to be of higher socio-economic classes than persistent non-compliers, to have more personal and family experiences of illness and to visit their dentists more regularly. The results suggest that generalized attempts at compliance enhancement would be ineffectual against the prevailing background characteristics of the non-compliant population, and that the more overt targeting of efforts in this respect is to be preferred.

Colorectal cancer screening and quality of life.

To evaluate the quality of life of patients following surgery for colorectal cancer, and to compare the quality of life between patients whose cancer was detected as a result of faecal occult blood screening with that of patients whose cancer presented symptomatically, an analysis was conducted within the context of the randomized controlled trial of colorectal cancer screening, University Hospital, Nottingham, UK. A total of 418 survivors of the trial's test and control groups and 33 randomly selected cancer patients completed quality of life questionnaires (Nottingham Health Profile and Health Measurement Questionnaire). The mode of entry to diagnosis and treatment (screening vs. non-screening) appeared to exert no major impact on post-intervention quality of life. The stage of cancer progression was not closely related to outcome life quality. A quality of life coefficient for surviving patients based on the Rosser classification was estimated to lie within the range 0.948-0.981. This figure accords well with the estimates of other studies of interventions in populations of similar age. Overall, there are no grounds for believing that faecal occult blood screening for colorectal cancer per se significantly influences patients' post-intervention quality of life.

Convergent validity of two measures of the quality of life.

In the paper, a test of convergent validity is undertaken for two methods of quality of life assessment, one based on a shortened version of the Health Measurement Questionnaire and the other based on professional clinical judgement. The Nottingham Health Profile is used as the comparator, and the data derive from a sample of colorectal cancer patients. Criteria for convergent validity are established and both methods yield outcomes broadly consistent with such criteria.