Economic evidence for the prevention and treatment of atopic eczema: a protocol for a systematic review

Background: Eczema, synonymous with atopic eczema or atopic dermatitis, is a chronic skin disease that has a similar impact on health-related quality of life as other chronic diseases. The proposed research aims to provide a comprehensive systematic assessment of the economic evidence base available to inform economic modelling and decision making on interventions to prevent and treat eczema at any stage of the life course. Whilst the Global Resource of Eczema Trials (GREAT) database collects together the effectiveness evidence for eczema there is currently no such systematic resource on the economics of eczema. It is important to gain an overview of the current state of the art of economic methods in the field of eczema in order to strengthen the economic evidence base further. Methods/design: The proposed study is a systematic review of the economic evidence surrounding interventions for the prevention and treatment of eczema. Relevant search terms will be used to search MEDLINE, EMBASE, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, Health Technology Assessment, Cumulative Index to Nursing and Allied Health Literature, Econ Lit, Scopus, Cost-Effectiveness Analysis Registry and Web of Science in order to identify relevant evidence. To be eligible for inclusion studies will be primary empirical studies evaluating the cost, utility or full economic evaluation of interventions for preventing or treating eczema. Two reviewers will independently assess studies for eligibility and perform data abstraction. Evidence tables will be produced presenting details of study characteristics, costing methods, outcome methods and quality assessment. The methodological quality of studies will be assessed using accepted checklists. Discussion: The systematic review is being undertaken to identify the type of economic evidence available, summarise the results of the available economic evidence and critically appraise the quality of economic evidence currently available to inform future economic modelling and resource allocation decisions about interventions to prevent or treat eczema. We aim to use the review to offer guidance about how to gather economic evidence in studies of eczema and/or what further research is necessary in order to inform this

Measurement properties of quality of life measurement instruments for infants, children and adolescents with eczema: protocol for a systematic review

Background: Eczema is a common chronic or chronically relapsing skin disease that has a substantial impact on quality of life (QoL). By means of a consensus-based process, the Harmonising Outcome Measures in Eczema (HOME) initiative has identified QoL as one of the four core outcome domains to be assessed in all eczema trials. Few measurement instruments exist to measure QoL in infants and children with eczema, but there is a great variability in both content and quality (for example, reliability and validity) of the instruments used, and it is not always clear if the best instrument is being used. Therefore, the aim of the proposed research is a comprehensive systematic assessment of the measurement properties of the existing measurement instruments that were developed and/or validated for the measurement of patient-reported QoL in infants and children with eczema. Methods/Design: This study is a systematic review of the measurement properties of patient-reported measures of QoL developed and/or validated for infants and children with eczema. Medline via PubMed and EMBASE will be searched using a selection of relevant search terms. Eligible studies will be primary empirical studies evaluating, describing, or comparing measurement properties of QoL instruments for infants and children with eczema. Eligibility assessment and data abstraction will be performed independently by two reviewers. Evidence tables will be generated for study characteristics, instrument characteristics, measurement properties, and interpretability. The adequacy of the measurement properties will be assessed using predefined criteria. Methodological quality of studies will be assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. A best evidence synthesis will be undertaken if more than one study has investigated a particular measurement property. Discussion: The proposed systematic review will produce a comprehensive assessment of measurement properties of existing QoL instruments in infants and children with eczema. We aim to identify one best currently available instrument to measure QoL in infants and/or children with eczema

‘It's like the bad guy in a movie who just doesn't die’ : a qualitative exploration of young people's adaptation to eczema and implications for self‐care

Background Eczema is a common childhood inflammatory skin condition, affecting more than one in five children. A popular perception is that children ‘outgrow eczema’, although epidemiological studies have shown that, for many, eczema follows a lifelong episodic course. Objectives To explore the perceptions of young people about the nature of their eczema and how these perceptions relate to their self‐care and adapting to living with eczema. Methods This is a secondary inductive thematic analysis of interviews conducted for Healthtalk.org. In total 23 interviews with young people with eczema were included. Of the 23 participants, 17 were female and six male, ranging from 17 to 25 years old. Results Participants generally experienced eczema as an episodic long‐term condition and reported a mismatch between information received about eczema and their experiences. The experience of eczema as long term and episodic had implications for self‐care, challenging the process of identifying triggers of eczema flare‐ups and evaluating the success of treatment regimens. Participants’ experiences of eczema over time also had implications for adaptation and finding a balance between accepting eczema as long term and hoping it would go away. This linked to a gradual shift in treatment expectations from ‘cure’ to ‘control’ of eczema. Conclusions For young people who continue to experience eczema beyond childhood, a greater focus on self‐care for a long‐term condition may be helpful. Greater awareness of the impact of early messages around ‘growing out of’ eczema and provision of high‐quality information may help patients to manage expectations and support adaptation to treatment regimens

Loss-of-function variants of the filaggrin gene are associated with atopic eczema and associated phenotypes in Swedish families

Recent studies have identified 2 loss-of-function variants, R501X and 2282del4, in the filaggrin gene as predisposing factors in the development of eczema. In this study, representing the first analysis of the variants in a Swedish population, we analysed transmission in 406 multiplex eczema families with mainly adult patients. In accordance with previous studies we found association between the filaggrin gene variants and atopic eczema (p=9.5x10(-8)). The highest odds ratio for the combined alllele, 4.73 (1.98-11.29), p=3.6x10(-8), was found for the subgroup with a severe eczema phenotype, and association was also found with raised allergen-specific IgE, allergic asthma and allergic rhinoconjunctivitis occurring in the context of eczema. Our results support an important role for the filaggrin gene variants R501 X and 2282del4 in the development and severity of atopic eczema and indicate a possible role for the subsequent progression into eczema-associated phenotypes.</p

Do early-life exposures explain why more advantaged children get eczema? Findings from the U.K. Millennium Cohort Study

Background: Atopic dermatitis (eczema) in childhood is socially patterned, with higher incidence in more advantaged populations. However, it is unclear what factors explain the social differences. Objectives: To identify early-life risk factors for eczema, and to explore how early-life risk factors explain any differences in eczema. Methods: We estimated odds ratios (ORs) for ever having had eczema by age 5 years in 14 499 children from the U.K. Millennium Cohort Study (MCS), with a focus on maternal, antenatal and early-life risk factors and socioeconomic circumstances (SECs). Risk factors were explored to assess whether they attenuated associations between SECs and eczema. Results: Overall 35·1% of children had ever had eczema by age 5 years. Children of mothers with degree-level qualifications vs. no educational qualifications were more likely to have eczema (OR 1·52, 95% confidence interval 1·31–1·76), and there was a gradient across the socioeconomic spectrum. Maternal atopy, breastfeeding (1–6 weeks and ≥ 6 months), introduction of solids under 4 months or cow's milk under 9 months, antibiotic exposure in the first year of life and grime exposure were associated with an increased odds of having eczema. Female sex, Pakistani and Bangladeshi ethnicity, smoking during pregnancy, exposure to environmental tobacco smoke and having more siblings were associated with reduced odds for eczema. Controlling for maternal, antenatal and early-life characteristics (particularly maternal smoking during pregnancy, breastfeeding and number of siblings) reduced the OR for eczema to 1·26 (95% confidence interval 1·03–1·50) in the group with the highest educational qualifications compared with the least. Conclusions: In a representative U.K. child cohort, eczema was more common in more advantaged children. This was explained partially by early-life factors including not smoking during pregnancy, breastfeeding and having fewer siblings

Genetic characterization of human coxsackievirus A6 variants associated with atypical hand, foot and mouth disease: a potential role of recombination in emergence and pathogenicity

Human coxsackievirus A6 (CVA6) is an enterically transmitted enterovirus. Until recently, CVA6 infections were considered as being of minor clinical significance, and only rarely aetiologically linked with hand, foot and mouth disease (HFMD) associated with other species A enteroviruses (particularly EV71 and CVA16). From 2008 onwards, however, CVA6 infections have been associated with several outbreaks worldwide of atypical HFMD (aHFMD) accompanied by a varicelliform rash. We recently reported CVA6-associated eczema herpeticum occurring predominantly in children and young adults in Edinburgh in January and February 2014. To investigate genetic determinants of novel clinical phenotypes of CVA6, we genetically characterized and analysed CVA6 variants associated with eczema herpeticum in Edinburgh in 2014 and those with aHFMD in CAV isolates collected from 2008. A total of eight recombinant forms (RFs) have circulated worldwide over the past 10 years, with the particularly recent appearance of RF-H associated with eczema herpeticum cases in Edinburgh in 2014. Comparison of phylogenies and divergence of complete genome sequences of CVA6 identified recombination breakpoints in 2A-2C, within VP3, and between 5' untranslated region and VP1. A Bayesian temporal reconstruction of CVA6 evolution since 2004 provided estimates of dates and the actual recombination events that generated more recently appearing recombination groups (RF-E, -F, -G and -H). Associations were observed between recombination groups and clinical presentations of herpangina, aHFMD and eczema herpeticum, but not with VP1 or other structural genes. These observations provided evidence that NS gene regions may potentially contribute to clinical phenotypes and outcomes of CVA6 infection

Implications of the problem orientated medical record (POMR) for research using electronic GP databases: a comparison of the Doctors Independent Network Database (DIN) and the General Practice Research Database (GPRD).

Background The General Practice Research Database (GPRD) and Doctor's Independent Network Database (DIN), are large electronic primary care databases compiled in the UK during the 1990s. They provide a valuable resource for epidemiological and health services research. GPRD (based on VAMP) presents notes as a series of discrete episodes, whereas DIN is based on a system (MEDITEL) that used a Problem Orientated Medical Record (POMR) which links prescriptions to diagnostic problems. We have examined the implications for research of these different underlying philosophies. Methods Records of 40,183 children from 141 practices in DIN and 76,310 from 464 practices in GRPD who were followed to age 5 were used to compare the volume of recording of prescribing and diagnostic codes in the two databases. To assess the importance and additional value of the POMR within DIN, the appropriateness of diagnostic linking to skin emollient prescriptions was investigated. Results Variation between practices for both the number of days on which prescriptions were issued and diagnoses were recorded was marked in both databases. Mean number of "prescription days" during the first 5 years of life was similar in DIN (19.5) and in GPRD (19.8), but the average number of "diagnostic days" was lower in DIN (15.8) than in GPRD (22.9). Adjustment for linkage increased the average "diagnostic days" to 23.1 in DIN. 32.7% of emollient prescriptions in GPRD appeared with an eczema diagnosis on the same day compared to only 19.4% in DIN; however, 86.4% of prescriptions in DIN were linked to an earlier eczema diagnosis. More specifically 83% of emollient prescriptions appeared under a problem heading of eczema in the 121 practices that were using problem headings satisfactorily. Conclusion Prescribing records in DIN and GPRD are very similar, but the usage of diagnostic codes is more parsimonious in DIN because of its POMR structure. Period prevalence rates will be underestimated in DIN unless this structure is taken into account. The advantage of the POMR is that in 121 of 141 practices using problem headings as intended, most prescriptions can be linked to a problem heading providing a specific reason for their issue