How does age affect the relationship between weight and health utility during the middle years of childhood?

Purpose: The limited literature examining weight status and preference-based health-related quality of life (HRQL) in young children is equivocal. This study aims to examine how the association between weight status and preference-based HRQL changes as children develop between the ages of 6 and 10 years old. Methods: The Child Health Utility 9D (CHU-9D) was used to determine preference-based HRQL. Height and weight data were also collected and used to calculate z-BMI adjusted for age and gender. 1467 children were recruited from 54 schools across the West Midlands. Data were collected at four time points over 5 years. Impact of weight on dimensions of HRQL was assessed via the distribution of responses to CHU-9D dimensions by weight status. Multi-level regression analysis controlling for ethnicity, deprivation and other relevant co-variates was conducted to examine the relationship between weight and HRQL. Results: There was no evidence to suggest that the weight status impacted upon the distribution of responses to CHU-9D dimensions. Correspondingly, the multi-level regression analysis found no statistically significant differences in CHU-9D scores between underweight, healthy weight, overweight and obese children. Conclusions: The evidence surrounding the link between preference-based HRQL and weight status in children is limited. This study found no association between weight status and HRQL as measured by the CHU-9D in children between the ages of 5 and 10 years in the UK. Given this, it is recommended that future studies aiming to prevent obesity in children in their middle years do not rely solely on preference-based measures for economic evaluation, and instead focus on capturing clinical or wellbeing outcomes

Development of a childhood obesity prevention programme with a focus on UK South Asian communities

OBJECTIVE: We report the development of a childhood obesity prevention intervention for UK South Asian primary school-aged children, guided by the UK Medical Research Council (MRC) framework for complex intervention development and evaluation. METHODS: We combined information gained from a literature review, stakeholder focus groups, an expert group, review of local resources and mapping to the Analysis Grid for Environments Linked to Obesity (ANGELO framework) in an intervention development process. The study took place in 2007 in Birmingham, UK. RESULTS: Contextual information from the stakeholder focus groups was essential for informing intervention development. The expert group defined guiding principles for the intervention. Informing intervention design by assessing existing local resources addressed intervention sustainability. The use of the ANGELO framework ensured a comprehensive environmental approach to intervention development. The intervention consisted of two broad processes; increasing children's physical activity levels through school, and increasing skills of families through activity-based learning. The developed intervention is being evaluated in a major study. CONCLUSIONS: The intervention development process has resulted in a tailored intervention programme to prevent childhood obesity in UK South Asian communities, but also intervention processes that could be applied to other communities and tailored to local context

Relationship between weight status and health-related quality of life in school-age children in China

Background: Some studies from high-income countries suggest that overweight and/or obesity in children are negatively associated with health-related quality of life (HRQOL). However, the relationship between weight status and HRQOL is not well established in China, where obesity trends follow a different pattern compared with high-income countries. The risk of obesity is greater in children from higher socioeconomic backgrounds and higher in boys compared with girls. Objective: The aim of this study was to examine the relationship between weight status and HRQOL in children between 6 and 7 years old in this unique country context. Methods: Baseline HRQOL and demographic data were collected from children recruited to the CHIRPY DRAGON obesity prevention trial in China. HRQOL was measured using the Chinese version of the Child Health Utility-9D (CHU-9D-CHN) and the Pediatric Quality of Life Inventory™ (PedsQL™) instruments. CHU-9D-CHN utility scores were generated using 2 scoring algorithms (UK and Chinese tariffs). Height and weight measures were taken at school by trained researchers using standardized methods, and BMI z scores were calculated using the World Health Organization 2007 growth charts. The relationship between HRQOL and weight status was examined using multivariable analyses, adjusting for age, gender, and socioeconomic status. Results: Full data were available for 1539 children (mean age, 6 years). In both unadjusted and adjusted analyses, HRQOL, using both the CHU-9D-CHN and the PedsQL™, was marginally higher in children who were overweight or living with obesity compared with children with healthy weight, although this difference did not reach statistical significance. Separate analyses and models by gender showed that the relationship between weight status and HRQOL scores was similar in boys and girls. Conclusions: Our results suggest no statistically significant difference in HRQOL between children with overweight/obesity compared with those with healthy weight. These results have implications for the methods of economic evaluation for obesity treatment and prevention interventions within this population cohort and country setting, as there appears to be no discernible consequences on children’s HRQOL from living with overweight and obesity

Supported self-management for patients with COPD who have recently been discharged from hospital:a systematic review and meta-analysis

Purpose: Although many hospitals promote self-management to chronic obstructive pulmonary disease (COPD) patients post discharge from hospital, the clinical effectiveness of this is unknown. We undertook a systematic review of the evidence as part of a Health Technology Assessment review. Methods: A comprehensive search strategy with no language restrictions was conducted across relevant databases from inception to May 2012. Randomized controlled trials of patients with COPD, recently discharged from hospital after an acute exacerbation and comparing a self-management intervention with control, usual care or other intervention were included. Study selection, data extraction, and risk of bias assessment were undertaken by two reviewers independently. Results: Of 13,559 citations, 836 full texts were reviewed with nine randomized controlled trials finally included in quantitative syntheses. Interventions were heterogeneous. Five trials assessed highly supported multi-component interventions and four trials were less supported with fewer contacts with health care professionals and mainly home-based interventions. Total sample size was 1,466 (range 33–464 per trial) with length of follow-up 2–12 months. Trials varied in quality; poor patient follow-up and poor reporting was common. No evidence of effect in favor of self-management support was observed for all-cause mortality (pooled hazard ratio =1.07; 95% confidence interval [0.74 to 1.55]; I2=0.0%, [n=5 trials]). No clear evidence of effect on all-cause hospital admissions was observed (hazard ratio 0.88 [0.61, 1.27] I2=66.0%). Improvements in St George’s Respiratory Questionnaire score were seen in favor of self-management interventions (mean difference =3.84 [1.29 to 6.40]; I2=14.6%), although patient follow-up rates were low. Conclusion: There is insufficient evidence to support self-management interventions post-discharge. There is a need for good quality primary research to identify effective approaches

Engaging stakeholders to level up COPD care in LMICs:lessons learned from the "Breathe Well" programme in Brazil, China, Georgia, and North Macedonia

BACKGROUND: Effective stakeholder engagement in health research is increasingly being recognised and promoted as an important pathway to closing the gap between knowledge production and its use in health systems. However, little is known about its process and impacts, particularly in low-and middle-income countries. This opinion piece draws on the stakeholder engagement experiences from a global health research programme on Chronic Obstructive Pulmonary Disease (COPD) led by clinician researchers in Brazil, China, Georgia and North Macedonia, and presents the process, outcomes and lessons learned.MAIN BODY: Each country team was supported with an overarching engagement protocol and mentored to develop a tailored plan. Patient involvement in research was previously limited in all countries, requiring intensive efforts through personal communication, meetings, advisory groups and social media. Accredited training programmes were effective incentives for participation from healthcare providers; and aligning research findings with competing policy priorities enabled interest and dialogue with decision-makers. The COVID-19 pandemic severely limited possibilities for planned engagement, although remote methods were used where possible. Planned and persistent engagement contributed to shared knowledge and commitment to change, including raised patient and public awareness about COPD, improved skills and practice of healthcare providers, increased interest and support from clinical leaders, and dialogue for integrating COPD services into national policy and practice.CONCLUSION: Stakeholder engagement enabled relevant local actors to produce and utilise knowledge for small wins such as improving day-to-day practice and for long-term goals of equitable access to COPD care. For it to be successful and sustained, stakeholder engagement needs to be valued and integrated throughout the research and knowledge generation process, complete with dedicated resources, contextualised and flexible planning, and commitment.</p

TargetCOPD : a pragmatic randomised controlled trial of targeted case finding for COPD versus routine practice in primary care : protocol

BACKGROUND: Many people with clinically significant chronic obstructive pulmonary disease (COPD) remain undiagnosed worldwide. There are a number of small studies which have examined possible methods of case finding through primary care, but no large RCTs that have adequately assessed the most cost-effective approach. METHODS/DESIGN: In this study, using a cluster randomised controlled trial (RCT) in 56 general practices in the West Midlands, we plan to investigate the effectiveness and cost-effectiveness of a Targeted approach to case finding for COPD compared with routine practice. Using an individual patient RCT nested in the Targeted arm, we plan also to compare the effectiveness and cost-effectiveness of Active case finding using a postal questionnaire (with supplementary opportunistic questionnaires), and Opportunistic-only case finding during routine surgery consultations. All ever-smoking patients aged 40-79 years, without a current diagnosis of COPD and registered with participating practices will be eligible. Patients in the Targeted arm who report positive respiratory symptoms (chronic cough or phlegm, wheeze or dyspnoea) using a brief questionnaire will be invited for further spirometric assessment to ascertain whether they have COPD or not. Post-bronchodilator spirometry will be conducted to ATS standards using an Easy One spirometer by trained research assistants. The primary outcomes will be new cases of COPD and cost per new case identified, comparing targeted case finding with routine care, and two types of targeted case finding (active versus opportunistic). A multilevel logistic regression model will be used to model the probability of detecting a new case of COPD for each treatment arm, with clustering of patients (by practice and household) accounted for using a multi-level structure. A trial-based analysis will be undertaken using costs and outcomes collected during the trial. Secondary outcomes include the feasibility, efficiency, long-term cost-effectiveness, patient and primary care staff views of each approach. DISCUSSION: This will be the largest RCT of its kind, and should inform how best to identify undiagnosed patients with COPD in the UK and other similar healthcare systems. Sensitivity analyses will help local policy-makers decide which sub-groups of the population to target first. TRIAL REGISTRATION: Current controlled trials ISRCTN14930255 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2466-14-157) contains supplementary material, which is available to authorized users

Case-finding and improving patient outcomes for chronic obstructive pulmonary disease in primary care: the BLISS research programme including cluster RCT

BackgroundChronic obstructive pulmonary disease is a major contributor to morbidity, mortality and health service costs but is vastly underdiagnosed. Evidence on screening and how best to approach this is not clear. There are also uncertainties around the natural history (prognosis) of chronic obstructive pulmonary disease and how it impacts on work performance.ObjectivesWork package 1: to evaluate alternative methods of screening for undiagnosed chronic obstructive pulmonary disease in primary care, with clinical effectiveness and cost-effectiveness analyses and an economic model of a routine screening programme. Work package 2: to recruit a primary care chronic obstructive pulmonary disease cohort, develop a prognostic model [Birmingham Lung Improvement StudieS (BLISS)] to predict risk of respiratory hospital admissions, validate an existing model to predict mortality risk, address some uncertainties about natural history and explore the potential for a home exercise intervention. Work package 3: to identify which factors are associated with employment, absenteeism, presenteeism (working while unwell) and evaluate the feasibility of offering formal occupational health assessment to improve work performance.DesignWork package 1: a cluster randomised controlled trial with household-level randomised comparison of two alternative case-finding approaches in the intervention arm. Work package 2: cohort study – focus groups. Work package 3: subcohort – feasibility study.SettingPrimary care settings in West Midlands, UK.ParticipantsWork package 1: 74,818 people who have smoked aged 40–79 years without a previous chronic obstructive pulmonary disease diagnosis from 54 general practices. Work package 2: 741 patients with previously diagnosed chronic obstructive pulmonary disease from 71 practices and participants from the work package 1 randomised controlled trial. Twenty-six patients took part in focus groups. Work package 3: occupational subcohort with 248 patients in paid employment at baseline. Thirty-five patients took part in an occupational health intervention feasibility study.InterventionsWork package 1: targeted case-finding – symptom screening questionnaire, administered opportunistically or additionally by post, followed by diagnostic post-bronchodilator spirometry. The comparator was routine care. Work package 2: twenty-three candidate variables selected from literature and expert reviews. Work package 3: sociodemographic, clinical and occupational characteristics; occupational health assessment and recommendations.Main outcome measuresWork package 1: yield (screen-detected chronic obstructive pulmonary disease) and cost-effectiveness of case-finding; effectiveness of screening on respiratory hospitalisation and mortality after approximately 4 years. Work package 2: respiratory hospitalisation within 2 years, and barriers to and facilitators of physical activity. Work package 3: work performance – feasibility and acceptability of the occupational health intervention and study processes.ResultsWork package 1: targeted case-finding resulted in greater yield of previously undiagnosed chronic obstructive pulmonary disease than routine care at 1 year [n = 1278 (4%) vs. n = 337 (1%), respectively; adjusted odds ratio 7.45, 95% confidence interval 4.80 to 11.55], and a model-based estimate of a regular screening programme suggested an incremental cost-effectiveness ratio of £16,596 per additional quality-adjusted life-year gained. However, long-term follow-up of the trial showed that at ≈4 years there was no clear evidence that case-finding, compared with routine practice, was effective in reducing respiratory admissions (adjusted hazard ratio 1.04, 95% confidence interval 0.73 to1.47) or mortality (hazard ratio 1.15, 95% confidence interval 0.82 to 1.61). Work package 2: 2305 patients, comprising 1564 with previously diagnosed chronic obstructive pulmonary disease and 741 work package 1 participants (330 with and 411 without obstruction), were recruited. The BLISS prognostic model among cohort participants with confirmed airflow obstruction (n = 1894) included 6 of 23 candidate variables (i.e. age, Chronic Obstructive Pulmonary Disease Assessment Test score, 12-month respiratory admissions, body mass index, diabetes and forced expiratory volume in 1 second percentage predicted). After internal validation and adjustment (uniform shrinkage factor 0.87, 95% confidence interval 0.72 to 1.02), the model discriminated well in predicting 2-year respiratory hospital admissions (c-statistic 0.75, 95% confidence interval 0.72 to 0.79). In focus groups, physical activity engagement was related to self-efficacy and symptom severity. Work package 3: in the occupational subcohort, increasing dyspnoea and exposure to inhaled irritants were associated with lower work productivity at baseline. Longitudinally, increasing exacerbations and worsening symptoms, but not a decline in airflow obstruction, were associated with absenteeism and presenteeism. The acceptability of the occupational health intervention was low, leading to low uptake and low implementation of recommendations and making a full trial unfeasible.LimitationsWork package 1: even with the most intensive approach, only 38% of patients responded to the case-finding invitation. Management of case-found patients with chronic obstructive pulmonary disease in primary care was generally poor, limiting interpretation of the long-term effectiveness of case-finding on clinical outcomes. Work package 2: the components of the BLISS model may not always be routinely available and calculation of the score requires a computerised system. Work package 3: relatively few cohort participants were in paid employment at baseline, limiting the interpretation of predictors of lower work productivity.ConclusionsThis programme has addressed some of the major uncertainties around screening for undiagnosed chronic obstructive pulmonary disease and has resulted in the development of a novel, accurate model for predicting respiratory hospitalisation in people with chronic obstructive pulmonary disease and the inception of a primary care chronic obstructive pulmonary disease cohort for longer-term follow-up. We have also identified factors that may affect work productivity in people with chronic obstructive pulmonary disease as potential targets for future intervention.Future workWe plan to obtain data for longer-term follow-up of trial participants at 10 years. The BLISS model needs to be externally validated. Our primary care chronic obstructive pulmonary disease cohort is a unique resource for addressing further questions to better understand the prognosis of chronic obstructive pulmonary disease.Trial registrationCurrent Controlled Trials ISRCTN14930255.FundingThis project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 9, No. 13. See the NIHR Journals Library website for further project information

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes