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Background and ObjectivesThe goal of this work was to determine whether locally acting ACE-083 is safe and well tolerated and increases muscle volume, motor function, and quality of life (QoL) in adults with Charcot-Marie-Tooth disease (CMT) type 1.MethodsThis phase 2 study enrolled adults with CMT1 or CMTX (N = 63). Part 1 was open label and evaluated the safety and tolerability of different dose levels of ACE-083 for use in part 2. Part 2 was a randomized, placebo-controlled, 6-month study of 240 mg/muscle ACE-083 injected bilaterally into the tibialis anterior muscle, followed by a 6-month, open-label extension in which all patients received ACE-083. Pharmacodynamic endpoints included total muscle volume (TMV; primary endpoint), contractile muscle volume (CMV), and fat fraction. Additional secondary endpoints included 6-minute walk test, 10-m walk/run, muscle strength, and QoL. Safety was assessed with treatment-emergent adverse events (TEAEs) and clinical laboratory tests.ResultsIn part 1 (n = 18), ACE-083 was generally safe and well tolerated at all dose levels, with no serious adverse events, TEAEs of grade 3 or greater, or death reported. In part 2 (n = 45 enrolled, n = 44 treated), there was significantly greater change in TMV with ACE-083 compared with placebo (least-squares mean difference 13.5%;p= 0.0096). There was significant difference between ACE-083 and placebo for CMV and change in ankle dorsiflexion strength. Fat fraction and all other functional outcomes were not significantly improved by ACE-083. Moderate to mild injection-site reactions were the most common TEAEs.DiscussionDespite significantly increased TMV and CMV, patients with CMT receiving ACE-083 in tibialis anterior muscles did not demonstrate greater functional improvement compared with those receiving placebo.Trial Registration InformationClinical Trials Registration:NCT03124459.Classification of EvidenceThis study provides Class II evidence that intramuscular ACE-083 is safe and well tolerated and increases total muscle volume after 6 months of treatment in adults with CMT1 or CMTX.

Fieldwork at Amarna from autumn 2018 through autumn 2019 included excavation at a previously uninvestigated cemetery, the North Desert Cemetery, located approximately 600 metres south-west of the North Tombs. Several post excavation projects also continued. Those reported on here comprise the study of skeletal materials from the North Cliffs Cemetery, hair and textiles from the North Cliffs and North Desert Cemeteries, and pottery from the North Cliffs Cemetery. A site management and outreach project also continued.

ObjectiveA network meta-analysis (NMA) usually assesses multiple outcomes across several treatment comparisons. TheVitruvian plotaims to facilitate communication of multiple outcomes from NMAs to patients and clinicians.MethodsWe developed this tool following the recommendations on the communication of benefit–risk information from the available literature. We collected and implemented feedback from researchers, statisticians, methodologists, clinicians and people with lived experience of physical and mental health issues.ResultsWe present theVitruvian plot, which graphically presents absolute estimates and relative performance of competing interventions against a common comparator for several outcomes of interest. We use two alternative colour schemes to highlight either the strength of statistical evidence or the confidence in the evidence. Confidence in the evidence is evaluated across six domains (within-study bias, reporting bias, indirectness, imprecision, heterogeneity and incoherence) using the Confidence in Network Meta-Analysis (CINeMA) system.ConclusionsTheVitruvian plotallows reporting of multiple outcomes from NMAs, with colourings appropriate to inform credibility of the presented evidence.

Images of ancient Egyptians wearing distinctive, cone-shaped objects on their heads have, in the absence of physical examples, long elicited scholarly debate. Did people wear these cones, or were they a purely iconographic device? What was their function and meaning? Recent excavations at the Amarna cemeteries now provide the first material examples of head cones. Spectroscopic analyses indicate that their primary constituent is a biological wax, and not fat or incense, as sometimes speculated. The authors tentatively suggest that the Amarna cones were symbols meant to enhance the rebirth or personal fertility of the deceased in the afterlife.

Fieldwork at Amarna in autumn 2017 and spring 2018 included excavation at a previously uninvestigated pit-grave cemetery, the North Cliffs Cemetery, on the low desert near the North Tombs. Initial results suggest the burials here are closer in character to those at the South Tombs Cemetery (excavated 2006–13) than at the North Tombs Cemetery (excavated 2015, 2017). Several post-excavation projects continued on materials from the North and South Tombs Cemeteries, including skeletal remains, coffins, hair, textiles, head cones, pottery and botanical materials, in addition to the ongoing recording of Kom el-Nana relief fragments and pottery from the Stone Village. A new site management programme, in partnership with the Ministry of Antiquities, was also launched.

BackgroundThis study was conducted in a general population of schoolchildren in Sweden, with the aim to assess the psychometric properties of a generic preference-based health related quality of life (HRQoL) instrument, the Swedish Child Health Utility 9D (CHU9D), among schoolchildren aged 7–15 years, and in subgroups aged 7–9, 10–12 and 13–15 years.MethodsIn total, 486 school aged children, aged 7–15 years, completed a questionnaire including the CHU9D, the Pediatric quality of life inventory 4.0 (PedsQL), KIDSCREEN-10, questions on general health, long-term illness, and sociodemographic characteristics. Psychometric testing was undertaken of feasibility, internal consistency reliability, test–retest reliability, construct validity, factorial validity, concurrent validity, convergent validity and divergent validity.ResultsThe CHU9D evidenced very few missing values, minimal ceiling, and no floor effects. The instrument achieved satisfactory internal consistency (Cronbach’s Alfa > 0.7) and strong test–retest reliability (r > 0.6). Confirmatory factor analyses supported the proposed one-factor structure of the CHU9D. For child algorithm, RMSEA = 0.05, CFI = 0.95, TLI = 0.94, and SRMR = 0.04. For adult algorithm RMSEA = 0.04, CFI = 0.96, TLI = 0.95, and SRMR = 0.04. The CHU9D utility value correlated moderately or strongly with KIDSCREEN-10 and PedsQL total scores (r > 0.5–0.7). The CHU9D discriminated as anticipated on health and on three of five sociodemographic characteristics (sex, age, and custody arrangement, but not socioeconomic status and ethnic origin).ConclusionsThis study provides evidence that the Swedish CHU9D is a feasible, reliable and valid measure of preference-based HRQoL in children. The study furthermore suggests that the CHU9D is appropriate for use among children 7–15 years of age in the general population, as well as among subgroups aged 7– 9, 10–12 and 13–15 years.

Background Several preference based measures are validated for adults in cost utility analysis, but less are available for children and many researchers have criticized the quality of pediatric economic studies. The objective of this study was to perform a Canadian French translation and linguistic validation of the Child Health Utility 9D (CHU9D) that was conceptually equivalent to the original English version for use in Canada. Methods The translation and linguistic validation were realized by ICON Clinical Research (UK) Limited in association with the developer of the CHU9D and Canadian collaborators. This was done in accordance with industry standards and the guidance of the Food and Drug Administration (FDA) for patient-reported outcome (PRO) instruments. Five steps were considered: concept elaboration; forward translation; back translation; linguistic validation; proofreading and final verification. Results The CHU9D Canadian French translation and linguistic validation were realized without any major difficulties. Only 3 changes were made after the forward translation and 5 after the back translation. The result of back translation was very similar to the original English version. Six additional changes suggested by the developer team were accepted and the linguistic validation with five children led to 2 additional changes. Most changes were generally to change one word to better sounding Canadian French. Conclusion We produced a Canadian French translation and cross-cultural adaptation of the Child Health Utility 9D (CHU9D). Before being used in clinical settings and research projects, the final Canadian French translation needs to be validated for metrological qualities of reliability and validity. Electronic supplementary material The online version of this article (10.1186/s12955-018-0998-4) contains supplementary material, which is available to authorized users.

© 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Objectives: To describe the use of a novel approach in health valuation of a discrete-choice experiment (DCE) including a cost attribute to value a recently developed classification system for measuring the quality-of-life impact (both health and treatment experience) of self-management for diabetes. Methods: A large online survey was conducted using DCE with cost on UK respondents from the general population (n = 1497) and individuals with diabetes (n = 405). The data were modeled using a conditional logit model with robust standard errors. The marginal rate of substitution was used to generate willingness-to-pay (WTP) estimates for every state defined by the classification system. Robustness of results was assessed by including interaction effects for household income. Results: There were some logical inconsistencies and insignificant coefficients for the milder levels of some attributes. There were some differences in the rank ordering of different attributes for the general population and diabetic patients. The WTP to avoid the most severe state was £1118.53 per month for the general population and £2356.02 per month for the diabetic patient population. The results were largely robust. Conclusions: Health and self-management can be valued in a single classification system using DCE with cost. The marginal rate of substitution for key attributes can be used to inform cost-benefit analysis of self-management interventions in diabetes using results from clinical studies in which this new classification system has been applied. The method shows promise, but found large WTP estimates exceeding the cost levels used in the survey.

Burial grounds are increasingly being considered as components of lived urban environments in the past. This paper considers how the ancient Egyptian city of Akhetaten, built by king Akhenaten (c. 1349–1332 bc), was constructed and experienced as a space inhabited both by the living and the dead. Drawing upon results from ongoing excavations at the burial grounds of the general population, it considers how the archaeological record of the settlement and its cemeteries segue and explores how the nature of burial landscapes and the need to maintain reflexive relationships between the living and the dead in the midst of a changing religious milieu contributed to the unique character of Akhetaten as a city. It asks what kind of city Akhetaten was, and what it was like to live through the Amarna period.

Background: The Pediatric Quality of Life Inventory™ 4.0 Short Form 15 Generic Core Scales (hereafter the PedsQL) and the Child Health Utility-9 Dimensions (CHU9D) are two generic instruments designed to measure health-related quality of life in children and adolescents in the general population and paediatric patient groups living with specific health conditions. Although the PedsQL is widely used among paediatric patient populations, presently it is not possible to directly use the scores from the instrument to calculate quality-adjusted life-years (QALYs) for application in economic evaluation because it produces summary scores which are not preference-based. Objective: This paper examines different econometric mapping techniques for estimating CHU9D utility scores from the PedsQL for the purpose of calculating QALYs for cost-utility analysis. Methods: The PedsQL and the CHU9D were completed by a community sample of 755 Australian adolescents aged 15–17 years. Seven regression models were estimated: ordinary least squares estimator, generalised linear model, robust MM estimator, multivariate factorial polynomial estimator, beta-binomial estimator, finite mixture model and multinomial logistic model. The mean absolute error (MAE) and the mean squared error (MSE) were used to assess predictive ability of the models. Results: The MM estimator with stepwise-selected PedsQL dimension scores as explanatory variables had the best predictive accuracy using MAE and the equivalent beta-binomial model had the best predictive accuracy using MSE. Conclusions: Our mapping algorithm facilitates the estimation of health-state utilities for use within economic evaluations where only PedsQL data is available and is suitable for use in community-based adolescents aged 15–17 years. Applicability of the algorithm in younger populations should be assessed in further research. Refereed/Peer-reviewed

Background: Almost one-half of 12-15 year olds living in deprived areas of the UK have dental caries (tooth decay) with few oral health promotion programmes aimed at children of this age. Mobile phone based interventions such as Short Messaging Service (SMS) interventions have been found effective at changing certain behaviours and improving health outcomes. This protocol describes the BRIGHT Trial, investigating the clinical and cost-effectiveness of a behaviour change intervention; classroom-based session (CBS) embedded in the curriculum and a series of SMS delivered to participants twice daily to remind them to brush their teeth, compared to usual curriculum and no SMS for young people from deprived areas, on the incidence of dental caries. The objective of this study is to investigate the clinical and cost-effectiveness of a complex intervention to improve the oral health of young people living in deprived areas. Methods/design: This is a school-based, assessor-blinded, two-arm cluster-randomised controlled trial with an internal pilot trial. Overall, the trial will involve approximately 5,040 11-13 year olds in 42 schools with a three year follow-up. The trial will take place in secondary schools in England, Scotland and Wales. The primary outcome is the presence of carious lesions in permanent teeth at three years. Secondary outcomes are: frequency of twice-daily toothbrushing, plaque levels, gingivitis, child health-related quality of life and oral health-related quality of life. A cost-utility analysis will be conducted. Discussion: The findings of the trial have implications for embedding oral health interventions into school curricula guidance produced by national bodies including departments for education, dental public health and guideline development organisations. Trial registration: ISRCTN12139369, date of initial registration 10/5/2017, https://doi.org/10.1186/ISRCTN12139369. Keywords: Dental caries, caries prevention, prevention, behaviour change, randomised controlled trial, child dental health, m-health, short messaging service

On behalf of the Clinical Care Consortium for Telomere-associated Ailments (CCCTAA)., Vascular complications such as bleeding due to gastrointestinal telangiectatic anomalies, pulmonary arteriovenous malformations, hepatopulmonary syndrome, and retinal vessel abnormalities are being reported in patients with telomere biology disorders (TBDs) more frequently than previously described. The international clinical care consortium of telomere-associated ailments and family support group Dyskeratosis Congenita Outreach, Inc. held a workshop on vascular abnormalities in the TBDs at the National Cancer Institute in October 2017. Clinicians and basic scientists reviewed current data on vascular complications, hypotheses for the underlying biology and developed new collaborations to address the etiology and clinical management of vascular complications in TBDs.

In contrast to the recent proliferation of studies incorporating ordinal methods to generate health state values from adults, to date relatively few studies have utilised ordinal methods to generate health state values from adolescents. This paper reports upon a study to apply profile case best worst scaling methods to derive a new adolescent specific scoring algorithm for the Child Health Utility 9D (CHU9D), a generic preference based instrument that has been specifically designed for the estimation of quality adjusted life years for the economic evaluation of health care treatment and preventive programs targeted at young people. A survey was developed for administration in an on-line format in which consenting community based Australian adolescents aged 11-17 years (N = 1982) indicated the best and worst features of a series of 10 health states derived from the CHU9D descriptive system. The data were analyzed using latent class conditional logit models to estimate values (part worth utilities) for each level of the nine attributes relating to the CHU9D. A marginal utility matrix was then estimated to generate an adolescent-specific scoring algorithm on the full health = 1 and dead = 0 scale required for the calculation of QALYs. It was evident that different decision processes were being used in the best and worst choices. Whilst respondents appeared readily able to choose 'best' attribute levels for the CHU9D health states, a large amount of random variability and indeed different decision rules were evident for the choice of 'worst' attribute levels, to the extent that the best and worst data should not be pooled from the statistical perspective. The optimal adolescent-specific scoring algorithm was therefore derived using data obtained from the best choices only. The study provides important insights into the use of profile case best worst scaling methods to generate health state values with adolescent populations. Refereed/Peer-reviewed

Purpose: To derive children and adolescents’ preferences for health states defined by the Chinese version of Child Health Utility 9D (CHU9D-CHN) instrument in China that can be used to estimate quality-adjusted life years (QALYs) for economic evaluation. Methods: A profile case best–worst scaling (BWS) and a time trade-off (TTO) method were combined to derive a Chinese-specific tariff for the CHU9D-CHN. The BWS survey recruited students from primary and high schools using a multi-stage random sampling method and was administered in a classroom setting, whilst the TTO survey adopted an interviewer-administrated conventional TTO task and was administered to a convenience sample of undergraduate students. A latent class modelling framework was adopted for analysing the BWS data. Results: Two independent surveys were conducted in Nanjing, China, including a valid sample of 902 students (mean age 13 years) from the BWS survey and a valid sample of 38 students (mean age 18 years) from the TTO survey. The poolability of the best and the worst responses was rejected and the optimal result based on the best responses only. The optimal model suggests the existence of two latent classes. The BWS estimates were further re-anchored onto the QALY scale using the TTO generated health state values via a mapping approach. Conclusion: This study provides further insights into the use of the BWS method to generate health state values with young people and highlights the potential different decision rules that young people may employ for determining best vs. worst choices in this context. Refereed/Peer-reviewed

ObjectiveThis article presents the development of the Dutch value set for the Child Health Utility 9D, a pediatric preference-based measure of quality of life that can be used to generate quality-adjusted life-years.MethodsA large online survey was conducted using a discrete choice experiment including a duration attribute with adult members of the Netherlands general population (N = 1276) who were representative in terms of age, gender, marital status, employment, education, and region. Respondents were asked which of two health states they prefer, where each health state was described using the nine dimensions of the Child Health Utility 9D (worried, sad, pain, tired, annoyed, school work/homework, sleep, daily routine, able to join in activities) and duration. The data were modeled using conditional logit with robust standard errors to produce utility values for every health state described by the Child Health Utility 9D.ResultsThe majority of the dimension level coefficients were monotonic, leading to a decrease in utility as severity increases. There was, however, evidence of some logical inconsistencies, particularly for the school work/homework dimension. The value set produced was based on the ordered model and ranges from –0.568 for the worst state to 1 for the best state.ConclusionThe valuation of the Child Health Utility 9D using online discrete choice experiment with duration with adult members of the Dutch general population was feasible and produced a valid model for use in cost utility analysis. Normative questions are raised around the valuation of pediatric preference-based measures, including the appropriate perspective for imagining hypothetical pediatric health states.

© The Author(s) 2018. Objective. Self-management is becoming increasingly important in diabetes but is neglected in conventional preference-based measures. The objective of this paper was to generate health state utility values for a novel classification system measuring the quality-of-life impact of self-management for diabetes, which can be used to generate quality-adjusted life years (QALYs). Methods. A large online survey was conducted using a discrete choice experiment (DCE), with duration as an additional attribute, on members of the UK general population (n = 1,493) to elicit values for health (social limitations, mood, vitality, hypoglycaemia) and non-health (stress, hassle, control, support) aspects of self-management in diabetes. The data were modelled using a conditional fixed-effects logit model and utility estimates were anchored on the one to zero (full health to dead) scale. Results. The model produced significant and consistent coefficients, with one logical inconsistency and 3 insignificant coefficients for the milder levels of some attributes. The anchored utilities ranged from 1 for the best state to −0.029 for the worst state (meaning worse than dead) defined by the classification system. Conclusion. The results presented here can potentially be used to generate utility values capturing the day to day impact of interventions in diabetes on both health and self-management. These utility values can potentially be used to generate QALYs for economic models of the cost-effectiveness of interventions in diabetes.

Objective: The aim was to conduct an empirical assessment of the measurement properties of the preference-based Child Health Utility 9D (CHU9D) versus the non-preference-based Pediatric Quality of Life Inventory (PedsQL)™ 4.0 Short Form 15 Generic Core Scales (referred to as ‘PedsQL’) in an Australian community-based sample of adolescents. Method: An online survey including the CHU9D, the PedsQL, a self-reported general health question, and socio-demographic questions was administered to adolescents (aged 15–17 years). Descriptive summary statistics and psychometric analyses were conducted to assess levels of agreement and convergent validity between the instruments. Results: A total of 775 adolescents (mean ± SD age 15.8 ± 0.8 years) completed the survey. The mean ± SD scores of the CHU9D and the PedsQL were 0.72 ± 0.22 and 72.86 ± 16.56, respectively. For both instruments, there were significant differences in health-related quality of life scores according to self-reported health status and socio-economic status. Overall, both the Spearman’s correlation (r = 0.63) and the intraclass correlation coefficient (0.77) suggested a high level of agreement conclusions: The findings indicate good levels of agreement overall between the CHU9D and PedsQL and provide further support for the validity of the application of the CHU9D in the economic evaluation of adolescent health care treatment and service programmes. Refereed/Peer-reviewed

Objectives: To examine the performance of two recently developed preference-based instruments-the Child Health Utility 9D (CHU9D) and the EuroQol five-dimensional questionnaire Youth version (EQ-5D-Y)-in assessing the health-related quality of life (HRQOL) of Australian adolescents. Methods: An online survey including the CHU9D and the EQ-5D-Y, self-reported health status, and a series of sociodemographic questions was developed for administration to a community-based sample of adolescents (aged 11-17 years). Individual responses to both instruments were translated into utilities using scoring algorithms derived from the Australian adult general population. Results: A total of 2020 adolescents completed the online survey. The mean ± SD utilities of the CHU9D and the EQ-5D-Y were very similar (0.82 ± 0.13 and 0.83 ± 0.19, respectively), and the intraclass correlation coefficient (0.80) suggested good levels of agreement. Both instruments were able to discriminate according to varying levels of self-reported health status (P < 0.001). Although exhibiting good levels of agreement overall, some wide divergences were apparent at an individual level. Conclusions: The study results are encouraging and illustrate the potential for both the CHU9D and the EQ-5D-Y to be more widely used for measuring and valuing the HRQOL of adolescent populations in Australia and internationally. Generating adolescent-specific scoring algorithms pertaining to each instrument and an empirical comparison of the resulting utilities is a natural next step. More evidence is required from the application of the CHU9D and the EQ-5D-Y in specific patient groups in adolescent health settings to inform the choice of instrument for measuring and valuing the HRQOL for the economic evaluation of adolescent health care treatments and services Refereed/Peer-reviewed

The main objective of this study was to compare and contrast adolescent and adult values for the Child Health Utility-9D (CHU9D), a new generic preference-based measure of health-related quality of life designed for application in the economic evaluation of treatment and preventive programmes for children and adolescents. Previous studies have indicated that there may be systematic differences in adolescent and adult values for identical health states. An online survey including a series of best-worst scaling discrete choice experiment questions for health states defined by the CHU9D was administered to two general population samples comprising adults and adolescents, respectively. The results highlight potentially important age-related differences in the values attached to CHU9D dimensions. Adults, in general, placed less weight upon impairments in mental health (worried, sad, annoyed) and more weight upon moderate to severe levels of pain relative to adolescents. The source of values (adults or adolescents) has important implications for economic evaluation and may impact significantly upon healthcare policy.

Multi-attribute utility instruments (MAUIs) are increasingly being used to generate utility data, which can be used to calculate quality-adjusted life-years (QALYs). These QALY data can then be incorporated into a cost-utility analysis as part of an economic evaluation, to inform health care resource allocation decisions. Many health care decision-making bodies around the world, such as the National Institute for Health and Care Excellence, require the use of generic MAUIs. Recently, there has been a call for greater input of patients into the development of patient-reported outcome measures, and this is now actively encouraged. By incorporating the views of patients, greater validity of an instrument is expected and it is more likely that patients will be able to self-complete the instrument, which is the ideal when obtaining information about a patient's health-related quality of life. This paper examines the stages of MAUI development and the scope for patient and/or public involvement at each stage. The paper then reviews how much the main generic MAUIs have incorporated the views of patients/the public into the development of their descriptive systems at each of these stages, and the implications of this. The review finds that the majority of MAUIs had very little input from patients/the public. Instead, existing literature and/or the views of experts were used. If we wish to incorporate patient/public views into future development of MAUIs, qualitative methods are recommended.

Cognitive Behavioral Therapy (CBT) is an evidence-based treatment for dental anxiety; however, access to therapy is limited. The current study aimed to develop a self-help CBT resource for reducing dental anxiety in children, and to assess the feasibility of conducting a trial to evaluate the treatment efficacy and cost-effectiveness of such an intervention. A mixed methods design was employed. Within phase 1, a qualitative “person-based” approach informed the development of the self-help CBT resource. This also employed guidelines for the development and evaluation of complex interventions. Within phase 2, children, aged between 9 and 16 y, who had elevated self-reported dental anxiety and were attending a community dental service or dental hospital, were invited to use the CBT resource. Children completed questionnaires, which assessed their dental anxiety and health-related quality of life (HRQoL) prior to and following their use of the resource. Recruitment and completion rates were recorded. Acceptability of the CBT resource was explored using interviews and focus groups with children, parents/carers and dental professionals. For this analysis, the authors adhered to the Mixed Methods Appraisal Tool criteria. There were 24 families and 25 dental professionals participating in the development and qualitative evaluation of the CBT resource for children with dental anxiety. A total of 56 children agreed to trial the CBT resource (66% response rate) and 48 of these children completed the study (86% completion rate). There was a significant reduction in dental anxiety (mean score difference = 7.7, t = 7.9, df = 45, P < 0.001, Cohen’s d ES = 1.2) and an increase in HRQoL following the use of the CBT resource (mean score difference = -0.03, t = 2.14, df = 46, P < 0.05, Cohen’s d ES = 0.3). The self-help approach had high levels of acceptability to stakeholders. These findings provide preliminary evidence for the effectiveness and acceptability of the resource in reducing dental anxiety in children and support the further evaluation of this approach in a randomized control trial. Knowledge Transfer Statement: This study details the development of a guided self-help Cognitive Behavioral Therapy resource for the management of dental anxiety in children and provides preliminary evidence for the feasibility and acceptability of this approach with children aged between 9 and 16 y. The results of this study will inform the design of a definitive trial to examine the treatment- and cost-effectiveness of the resource for reducing dental anxiety in children.

Background The prevalence of diabetes mellitus (DM) is increasing dramatically, placing considerable financial burden on the healthcare budget of each country. Patient self-management is crucial for the control of blood glucose, which largely determines the chances of developing diabetes-related complications. Self-management interventions vary widely, and a method is required for assessing the impact of self-management. This paper describes the development of a questionnaire intended for use to measure the impact of self-management in diabetes. Methods An iterative development process was undertaken to identify the attributes of self-management using 5 steps. First, a literature review was undertaken to identify and understand themes relating to self-management of DM to inform a topic guide. Second, the topic guide was further refined following consultation with a Patient and Public Involvement group. Third, the topic guide was used to inform semi-structured interviews with patients with Type 1 DM (T1DM) and Type 2 DM (T2DM) to identify how self-management of DM affects individuals. Fourth, the research team considered potential attributes alongside health attributes from an existing measure (Diabetes Health Profile, DHP) to produce an instrument reflecting both health and self-management outcomes simultaneously. Finally, a draft instrument was tested in a focus group to determine the wording and acceptability. Results Semi-structured interviews were carried out with 32 patients with T1DM and T2DM. Eight potential attributes were identified: fear/worry/anxiety, guilt, stress, stigma, hassle, control, freedom, and feeling supported. Four of these self-management attributes were selected with four health attributes (mood, worry about hypos (hypoglycaemic episodes), vitality and social limitations) to produce the Health and Self-Management in Diabetes (HASMIDv1) questionnaire. Conclusions HASMIDv1 is a short questionnaire that contains eight items each with four response levels to measure the impact of self-management in diabetes for both T1DM and T2DM. The measure was developed using a mixed-methods approach that involved semi-structured interviews with people with diabetes. The measure has high face validity. Ongoing research is being undertaken to assess the validity of this questionnaire for measuring the impact of self-management interventions in economic evaluation. Electronic supplementary material The online version of this article (doi:10.1186/s12955-017-0719-4) contains supplementary material, which is available to authorized users.

The aim was to conduct an empirical assessment of the measurement properties of the preference-based Child Health Utility 9D (CHU9D) versus the non-preference-based Pediatric Quality of Life Inventory (PedsQL)™ 4.0 Short Form 15 Generic Core Scales (referred to as 'PedsQL') in an Australian community-based sample of adolescents.An online survey including the CHU9D, the PedsQL, a self-reported general health question, and socio-demographic questions was administered to adolescents (aged 15-17 years). Descriptive summary statistics and psychometric analyses were conducted to assess levels of agreement and convergent validity between the instruments.A total of 775 adolescents (mean ± SD age 15.8 ± 0.8 years) completed the survey. The mean ± SD scores of the CHU9D and the PedsQL were 0.72 ± 0.22 and 72.86 ± 16.56, respectively. For both instruments, there were significant differences in health-related quality of life scores according to self-reported health status and socio-economic status. Overall, both the Spearman's correlation (r = 0.63) and the intraclass correlation coefficient (0.77) suggested a high level of agreement.The findings indicate good levels of agreement overall between the CHU9D and PedsQL and provide further support for the validity of the application of the CHU9D in the economic evaluation of adolescent health care treatment and service programmes.

Background The aim was to estimate an exchange rate between EQ-5D-3L and the Adult Social Care Outcome Tool (ASCOT) using preference-based mapping via common time trade-off (TTO) valuations. EQ-5D and ASCOT are useful for examining cost-effectiveness within the health and social care sectors, respectively, but there is a policy need to understand overall benefits and compare across sectors to assess relative value for money. Standard statistical mapping is unsuitable since it relies on conceptual overlap of the measures but EQ-5D and ASCOT have different conceptualisations of quality of life. Methods We use a preference-based mapping approach to estimate the exchange rate using common TTO valuations for both measures. A sample of health states from each measure was valued using TTO by 200 members of the UK adult general population. Regression analyses are used to generate separate equations between EQ-5D-3L and ASCOT values using their original value set and TTO values elicited here. These are solved as simultaneous equations to estimate the relationship between EQ-5D-3L and ASCOT. Results The relationship for moving from ASCOT to EQ-5D-3L is a linear transformation with an intercept of −0.0488 and gradient of 0.978. This enables QALY gains generated by ASCOT and EQ-5D to be compared across different interventions. Conclusions This paper estimated an exchange rate between ASCOT and EQ-5D-3L using a preference-based mapping approach that does not compromise the descriptive systems of the two measures. This contributes to the development of preference-based mapping through the use of TTO as the common metric used to estimate the exchange rate between measures.

The authors report a summary of the results of six seasons of excavation at one of the cemeteries of Tell el-Amarna, the celebrated city of the ‘monotheistic’ revolutionary, Akhenaten. The osteology shows a workforce enduring stress and injuries to bone and muscle. The burial rites indicate low investment and personal interpretations as to spiritual meaning. In this exploration of a slice of a whole Egyptian urban society, the contrast between the working lives of the elite and its workforce becomes striking.

Objectives To describe how qualitative methods can be used in the development of descriptive systems of preference-based measures (PBMs) of health-related quality of life. Methods The requirements of the National Institute for Health and Clinical Excellence and other agencies together with the increasing use of patient-reported outcome measures has led to an increase in the demand for PBMs. Recently, interest has grown in developing new PBMs and while previous research on PBMs has mainly focused on the methods of valuation, research into the methods of developing descriptive systems is an emerging field. Results Traditionally, descriptive systems of PBMs were developed by using top-down methods, where content was derived from existing measures, the literature, or health surveys. A contrasting approach is a bottom-up methodology, which takes the views of patients or laypeople on how their life is affected by their health. This approach generally requires the use of qualitative methods. Qualitative methods lend themselves well to the development of PBMs. They also ensure that the measure has appropriate language, content validity, and responsiveness to change. While the use of qualitative methods in the development of non-PBMs is fairly standard, their use in developing PBMs was until recently nonexistent. Conclusions In this article, we illustrate the use of qualitative methods by presenting two case studies of recently developed PBMs, one generic and one condition specific. We outline the stages involved, discuss the strengths and weaknesses of the approach, and compare with the top-down approach used in the majority of PBMs to date.

Background: Childhood dental anxiety is very common, with 10-20% of children and young people reporting high levels of dental anxiety. It is distressing and has a negative impact on the quality of life of young people and their parents as well as being associated with poor oral health. Affected individuals may develop a lifelong reliance on general anaesthetic or sedation for necessary dental treatment thus requiring the support of specialist dental services. Children and young people with dental anxiety therefore require additional clinical time and can be costly to treat in the long-term. The reduction of dental anxiety through the use of effective psychological techniques is, therefore, of high importance. However, there is a lack of high quality research investigating the impact of Cognitive Behavioural Therapy (CBT) approaches when applied to young people’s dental anxiety. \ud \ud Methods/Design: The first part of the study will develop a profile of dentally anxious young people using a prospective questionnaire sent to a consecutive sample of 100 young people referred to the Paediatric Dentistry Department, Charles Clifford Dental Hospital, in Sheffield. The second part will involve interviewing a purposive sample of 15-20 dental team members on their perceptions of a CBT self-help resource for dental anxiety, their opinions on whether they might use such a resource with patients, and their willingness to recruit participants to a future randomised controlled trial (RCT) to evaluate the resource. The third part of the study will investigate the most appropriate outcome measures to include in a trial, the acceptability of the resource, and retention and completion rates of treatment with a sample of 60 dentally anxious young people using the CBT resource. \ud \ud Discussion: This study will provide information on the profile of dentally anxious young people who could potentially be helped by a guided self-help CBT resource. It will gain the perceptions of dental care team members of guided self-help CBT for dental anxiety in young people, and their willingness to recruit participants to a trial. Acceptability of the resource to participants, and retention and completion rates will also be investigated to inform a future RCT.\ud Keywords: Dental anxiety, CBT, children, young people, feasibility study, CBT self-help, low intensity, qualitative research

The concept of quality of life is necessarily vague. The meaning of the term is often dependent on the user and the population or individual under consideration. Many have tried to define it and measure it, though no consensus view on what it means or how it should be assessed has emerged. Often in economic evaluations of healthcare interventions, it is restricted to mean health-related quality of life, though even this leaves a yawning chasm from which significant debate arises. This is no different when researchers turn their attention to measuring and valuing the quality of life of children or those at the end of life. There exist important differences between children and adults that affect the ways in which we must understand and measure health-related quality of life. These include important physical and cognitive differences between children and adults, differences in the types and severity of illnesses that affect children and methodological and ethical issues related to conducting research in children. This chapter provides an overview of the difficulties in measuring and valuing paediatric quality of life, with a particular emphasis on doing so in populations of children with terminal or life-limiting illnesses. It raises a number of questions researchers should ask themselves when deciding how to measure quality of life for the purposes of economic evaluation in children with life-limiting illnesses, in particular, what domains of health should be measured, who should undertake the measurement and using which instrument.

Objectives: Kids in Control OF Food (KICk-OFF) is a 5-day structured education program for 11- to 16-year-olds with type 1 diabetes mellitus (T1DM) who are using multiple daily insulin injections. This study evaluates the cost-effectiveness of the KICk-OFF education program compared with the usual care using data from the KICk-OFF trial.Methods: The short-term within-trial analysis covers the 2-year postintervention period. Data on glycated hemoglobin (HbA1c), severe hypoglycemia, and diabetic ketoacidosis (DKA) were collected over a 2-year follow-up period. Sub-group analyses have been defined on the basis of baseline HbA1c being below 7.5 percent (58.5 mmol/mol) (low group), between 7.5 percent and 9.5 percent (80.3 mmol/mol) (medium group), and over 9.5 percent (high group). The long-term cost-effectiveness evaluation has been conducted by using The Sheffield Type 1 Diabetes Policy Model, which is a patient-level simulation model on T1DM. It includes long-term microvascular (retinopathy, neuropathy, and nephropathy) and macrovascular (myocardial infarction, stroke, revascularization, and angina) diabetes-related complications and acute adverse events (severe hypoglycemia and DKA).Results: The most favorable within-trial scenario for the KICk-OFF arm led to an incremental cost-effectiveness ratio (ICER) of £23,688 (base year 2009) with a cost-effectiveness probability of 41.3 percent. Simulating the long-term complications using the full cohort data, the mean ICER for the base case was £28,813 (base year 2011) and the probability of the KICk-OFF intervention being cost-effective at £20,000/QALY threshold was 42.6 percent, with considerable variation due to treatment effect duration. For the high HbA1c sub-group, the KICk-OFF arm was “dominant” (meaning it provided better health gains at lower costs than usual care) over the usual care arm in each scenario considered.Conclusions: For the whole study population, the cost-effectiveness of KICk-OFF depends on the assumption for treatment effect duration. For the high baseline HbA1c sub-group, KICk-OFF arm was estimated to be dominant over the usual care arm regardless of the assumption on the treatment effect duration.

Objective Our objective was to assess the psychometric performance of the Health Utilities Index 2 and 3 in a pediatric population following admission to a pediatric intensive care unit. Design As part of a larger study of pediatric intensive care outcomes, children were followed up at 6 and 12 months post admission from pediatric intensive care using the Health Utilities Index 2 and 3. We evaluated and compared the psychometric performance of the Health Utilities Index 2 and 3 in this population by assessing their practicality, reliability, and limited information regarding validity. Setting Twenty-two pediatric intensive care units in the United Kingdom. Patients A total of 685 children aged 5 yrs and over. Interventions The Health Utilities Index 2 and 3, which are both generic preference-based measures of health-related quality of life, were completed by proxy and children over 11 yrs of age were invited to self-complete. Measurement and main results Both Health Utilities Index 2 and 3 demonstrated good practicality, with excellent completion rates (>97%) and a mean time to complete of around 8 mins. Both Health Utilities Index 2 and 3 demonstrated very good inter-rater reliability and evidence of sensitivity to change. At 6 months after admission, mean scores of the Health Utilities Index 2 and 3 were different in some groups of children with different degrees of in-hospital severity of illness, but those differences were not found at 12 months of follow-up. Conclusions The Health Utilities Index 2 and 3 both perform well in a pediatric intensive care setting whether by self-complete or proxy complete. Evidence of good inter-rater reliability gives confidence that the measures can be reliably used with a proxy completer, such as parent or caregiver. Additional research is important to investigate their construct validity further in this population, ideally using baseline data collected at the time of hospital stay in pediatric intensive care and other measures of health status at the times of follow-up.

This article appeared in a journal published by Elsevier Ltd. Under Elsevier's copyright, mandated authors are not permitted to make work available in an institutional repository., The Child Health Utility-9D (CHU-9D) and the Assessment of Quality of Life-6D (AQOL-6D) presently represent the only two generic preference-based instruments developed for application with young people with both adult- and adolescent-specific scoring algorithms. The main objective of this study was to compare and contrast the application of adult and adolescent scoring algorithms for the CHU-9D and AQOL-6D in valuing the health of a community-based sample of adolescents., Australian National Health & Medical Research Council

INTRODUCTION:Preference-based measures of health-related quality of life play a key role in the calculation of Quality-Adjusted Life Years (QALYs) for Health Technology Assessment (HTA). The Child Health Utility 9D (CHU9D) is a new preference-based instrument designed specifically for application in children and adolescents (aged 7 to 17 years). This study aimed to compare Chinese and Australian adolescent population preferences for CHU9D health states using profile case best worst scaling (BWS) methods.METHODS:Fifty CHU9D health states (blocked into five survey versions) were generated for valuation using a fractional factorial design. Study participants were recruited through an online panel company in Australia, and through primary and secondary schools in China. A latent class modelling framework was adopted for econometric analysis.RESULTS:A total of 1,982 respondents (51 percent female) in Australia and 902 respondents (43 percent female) in China provided useable survey responses. Latent class analysis indicated the existence of preference heterogeneity for both population groups. In the Australian sample, respondents in Class I placed the most importance on the mental health dimensions of the CHU9D (for example, Worried and Annoyed) and the least importance on daily activities (for example, Activities, Daily routine, Sleep), whilst respondents in Class II placed equal weights on all attributes. In the Chinese sample, respondents in Class I placed the most importance on the Activities dimension of the CHU9D and the least importance on the Annoyed dimension, whist Class II placed the most importance on the Schoolwork dimension and the least importance on Pain.CONCLUSIONS:This study has provided important cross-country insights into the use of profile case BWS methods to elicit health state preferences with young people for application in HTA in children and adolescents. The differential latent classes identified between Australia and China highlights the necessity to derive country-specific adolescent scoring algorithms for the CHU9D instrument for application in HTA.

QALYs are increasingly being utilized as a health outcome measure to calculate the benefits of new treatments and interventions within cost-utility analyses for economic evaluation. Cost-utility analyses of adolescent-specific treatment programmes are scant in comparison with those reported upon for adults and tend to incorporate the views of clinicians or adults as the main source of preferences. However, it is not clear that the views of adults are in accordance with those of adolescents on this issue. Hence, the treatments and interventions most highly valued by adults may not correspond with those most highly valued by adolescents. Ordinal methods for health state valuation may be more easily understood and interpreted by young adolescent samples than conventional approaches. The availability of young adolescent-specific health state values for the estimation of QALYs will provide new insights into the types of treatment programmes and health services that are most highly valued by young adolescents.The first objective of this study was to assess the feasibility of applying best-worst scaling (BWS) discrete-choice experiment (DCE) methods in a young adolescent sample to value health states defined by the Child Health Utility 9D (CHU9D) instrument, a new generic preference-based measure of health-related quality of life developed specifically for application in young people. The second objective was to compare BWS DCE questions (where respondents are asked to indicate the best and worst attribute for each of a number of health states, presented one at a time) with conventional time trade-off (TTO) and standard gamble (SG) questions in terms of ease of understanding and completeness.A feasibility study sample of consenting young adolescent school children (n16) aged 1113 years participated in a face-to-face interview in which they were asked to indicate the best and worst attribute levels from a series of health states defined by the CHU9D, presented one at a time. Participants were also randomly allocated to receive additional conventional TTO or SG questions and prompted to indicate how difficult they found them to complete.The results indicate that participants were able to readily choose 'best' and 'worst' dimension levels in each of the CHU9D health states presented to them and provide justification for their choices. Furthermore, when presented with TTO or SG questions and prompted to make comparisons, participants found the BWS DCE task easier to understand and complete.The results of this feasibility study suggest that BWS DCE methods are potentially more readily understood and interpretable by vulnerable populations (e.g. young adolescents). These findings lend support to the potential application of BWS DCE methods to undertake large-scale health state valuation studies directly with young adolescent population samples. © 2011 Adis Data Information BV. All rights reserved.

Use of preference-based measures (PBM) of health-related quality of life (HRQoL) is increasing. PBMs allow the calculation of quality-adjusted life years, which can be used in decision making. Research in the field of pediatric PBMs is lacking. This work is the first stage in the development of a new generic, pediatric PBM of HRQoL. Seventy-four qualitative interviews were undertaken with children to find out how health affects their lives. Sampling was purposive, balancing primarily for health within age, with gender and ethnicity as secondary criteria. Interviews covered a wide range of health conditions, and children were successfully able to articulate how their health affected their lives. Eleven dimensions of HRQoL were identified, covering social, emotional, and physical aspects, in common with other generic pediatric HRQoL measures, but differ by including feeling jeal'ous and feeling tired/weak and not including dimensions related to parental, family, or behavioral issues.

The use of preference-based measures (PBMs) of health-related quality of life (HRQoL) is increasing in health care resource allocation decisions. Whilst there are measures widely used for this purpose in adults, research in the paediatric field is more limited. This paper reports on how the descriptive system for a new paediatric generic PBM of HRQoL was developed from dimensions identified in previous research.\ud \ud Existing scales from the paediatric literature were reviewed for suitability, and scales were also developed empirically, based on qualitative interview data from children, by taking adverbial phrases and confirming the ordinality by a ranking exercise with children. The resulting scales were applied to the dimensions from the previous research.\ud \ud No suitable scales were found in the paediatric literature, so the empirically derived scales were used resulting in seven different types. Children were successfully able to rank these to determine the ordinality, and these types were applied to the dimensions.\ud \ud This work has empirically developed a descriptive system for the dimensions of HRQoL identified in previous research. Further research is needed to test the descriptive system on a paediatric population and reduce the number of dimensions to be amenable to health state valuation.\ud

This report on the 2007–8 seasons at Tell el-Amarna summarises continued work on the Stone Village, South Tombs Cemetery, the desert GPS survey, and the study of the Christian remains around the tomb of Panehsy (no. 6). As an experiment to complement the surveys, a 3D laser scanner was used for landscape studies at several points. No building repair work was undertaken. Post-excavation work covered charcoal, human bones (involving a larger team from the University of Arkansas), small finds, carved block and statue fragments from the Great Palace, Kom el-Nana, and el-Mangara (many in the SCA magazine at el-Ashmunein), animal bones and pottery from grid 12 and from the cemetery. Experiments were continued into the manufacturing process of faience.

OBJECTIVES: In contrast to the proliferation of studies incorporating health state values from adults of all ages, relatively few studies have reported upon the application of the time trade off (TTO) approach to generate health state values from populations of younger adults. This study sought to employ a conventional TTO approach to obtain values for a selection of Child Health Utility 9D (CHU9D) health states from a sample of young adults aged 18-29 years and to compare with the values generated from application of the original UK adult standard gamble scoring algorithm and the Australian adolescent scoring algorithm. \ud \ud METHODS: A convenience sample of Flinders University undergraduate students aged 18-29 years were invited to participate in an interviewer administered conventional TTO task to value a series of five CHU9D health impairment states using the widely used variant developed by the York EQ-5D team. \ud \ud RESULTS: A total of 152 students within the target age range were approached to participate in the study of whom n = 38 consented to participate, giving an overall participation rate of 25 %. With the exception of one health state, the mean TTO values were consistently lower than those generated from application of the original scoring algorithm for the CHU9D elicited with adults of all ages. A significant proportion of participants (n = 17, 45 %) considered the most severe CHU9D (PITS) state to be worse than death. \ud \ud CONCLUSIONS: This study adds to a growing body of evidence indicating that the values attached to identical health states are typically lower for younger people in comparison with adults of all ages and dependent upon the elicitation method utilised. The values obtained are applicable for re-scaling raw CHU9D health state values obtained from younger adolescent samples using profile case best-worst scaling.

In this paper we report the estimation of conditional logistic regression models for the Health Utilities Index Mark 2 and the SF-6D, using ordinal preference data. The results are compared to the conventional regression models estimated from standard gamble data, and to the observed mean standard gamble health state valuations. For both the HUI2 and the SF-6D, the models estimated using ordinal data are broadly comparable to the models estimated on standard gamble data and the predictive performance of these models is close to that of the standard gamble models. Our research indicates that ordinal data have the potential to provide useful insights into community health state preferences. However, important questions remain.

We examine the relationship between Visual Analogue Scale (VAS) and Standard Gamble (SG) assumed in the development of the multiplicative multi-attribute utility functions (M-MAUFs) for the Health Utilities Index (HUI) Mark 2 and Mark 3, using data from a UK valuation study of the HUI2. A range of functional forms are considered, and are compared on the basis of their explanatory power and predictive ability.A restricted cubic function fits the data better than a power curve with a mean absolute error (MAE) of 0.025 and root mean square error (RMSE) of 0.029 compared to a MAE of 0.135 and RMSE of 0.135 for the power curve. The use of a cubic mapping function instead of a power function leads to different predicted health state values. We question the reliance on the assumption of a power curve relationship between VAS and SG data, in the Health Utilities Index valuation framework. Our results demonstrate that further work is required to examine the appropriateness of the published M-MAUFs for the Health Utilities Indices.

The Health Utilities Index is one of the most widely used generic health status classification systems. The valuation algorithm rests upon a power transformation between visual analog scale (VAS) and standard gamble (SG) data. This transformation has been the subject of much debate. To date, the literature has concentrated upon the mapping functions themselves. We examine whether alternative mapping functions produce more accurate utility predictions.We undertook valuation interviews with 201 members of the UK general population, following the methods of the original Health Utilities Index-2 valuation survey. We estimated a cubic and a power mapping function using the mean VAS and SG data from the survey and calculated 2 alternative Multiplicative Multi Attribute Utility Functions (MAUFs). Using a validation sample, we assessed the predictive precision of the models in terms of accuracy (root mean square error and mean absolute error); clinical importance of the prediction error (% states with prediction error greater than 0.03); bias (t test); and whether the prediction error was related to the health state severity (Ljung Box Q statistic).The power MAUF was an extremely poor predictive model, mean absolute error = 0.18, root mean square error = 0.206. The predictions were biased (t = -12.92). The errors were not related to the severity of the health state, (Liung Box = 10.87). The Cubic MAUF was a better predictive model than the Power MAUF (mean absolute error = 0.084, root mean square error = 0.101). The Cubic MAUF also produced biased predictions (t = -3.57). The prediction errors were not related to the severity of the health state (Liung Box = 5.242).The Power MAUF is considerably worse than the Cubic MAUF. Our results suggest that the problems with the power function can translate into significant problems with predictive performance of the MAUF.

Aim: The purpose of this study was to determine if the in vitro age of endothelial cells alters endothelial response(s) to breast cancer cells. Method: After characterizing lower passage ("young"; passages 10–16) and higher passage ("old"; passages 30–36) bovine pulmonary artery endothelial cells (BPAECs), fluorescently labeled MCF-7 breast cancer cells were added to confluent monolayers of young and old BPAECs. Results: Transient gaps that peaked in size by 12h and closed by 48h occurred between the young BPAECs, while large persistent gaps formed between the old BPAECs. Gap formation did not occur when 184A1 cells, a non-malignant mammary epithelial cell line, were added in place of MCF-7 cells, suggesting that the age-related responses of the endothelial cells to MCF-7 cell addition were specific to the tumor cell addition. Additionally, more MCF-7 cells migrated through old BPAEC monolayers, than young BPAEC monolayers, grown on Matrigel ™ -coated filters. Finally, DNA fragmentation and fluorescent annexin-V binding assays suggested increased MCF-7 cell-induced apoptosis in older BPAECs, though results from a caspase-3 activation assay were equivocal. Conclusions: In sum, our findings support the notion that aged endothelial cells are more susceptible to breast cancer-induced injury, perhaps due to increased apoptosis.