Defining Target Engagement Required for Efficacy In Vivo at the Retinoic Acid Receptor-Related Orphan Receptor C2 (RORγt).

The Th17 pathway has been implicated in autoimmune diseases. The retinoic acid receptor-related orphan receptor C2 (RORγt) is a master regulator of Th17 cells and controls the expression of IL-17A. RORγt is expressed primarily in IL-17A-producing lymphoid cells. Here we describe a virtual screen of the ligand-binding pocket and subsequent screen in a binding assay that identified the 1-benzyl-4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran]-2'-carboxamide scaffold as a starting point for optimization of binding affinity and functional activity guided by structure-based design. Compound 12 demonstrated activity in a mouse PK/PD model and efficacy in an inflammatory arthritis mouse model that were used to define the level and duration of target engagement required for efficacy in vivo. Further optimization to improve ADME and physicochemical properties with guidance from simulations and modeling provided compound 22, which is projected to achieve the level and duration of target engagement required for efficacy in the clinic.

Improving the normalization of complex interventions: part 2 - validation of the NoMAD instrument for assessing implementation work based on normalization process theory (NPT).

INTRODUCTION: Successful implementation and embedding of new health care practices relies on co-ordinated, collective behaviour of individuals working within the constraints of health care settings. Normalization Process Theory (NPT) provides a theory of implementation that emphasises collective action in explaining, and shaping, the embedding of new practices. To extend the practical utility of NPT for improving implementation success, an instrument (NoMAD) was developed and validated. METHODS: Descriptive analysis and psychometric testing of an instrument developed by the authors, through an iterative process that included item generation, consensus methods, item appraisal, and cognitive testing. A 46 item questionnaire was tested in 6 sites implementing health related interventions, using paper and online completion. Participants were staff directly involved in working with the interventions. Descriptive analysis and consensus methods were used to remove redundancy, reducing the final tool to 23 items. Data were subject to confirmatory factor analysis which sought to confirm the theoretical structure within the sample. RESULTS: We obtained 831 completed questionnaires, an average response rate of 39% (range: 22-77%). Full completion of items was 50% (n = 413). The confirmatory factor analysis showed the model achieved acceptable fit (CFI = 0.95, TLI = 0.93, RMSEA = 0.08, SRMR = 0.03). Construct validity of the four theoretical constructs of NPT was supported, and internal consistency (Cronbach's alpha) were as follows: Coherence (4 items, α = 0.71); Collective Action (7 items, α = 0.78); Cognitive Participation (4 items, α = 0.81); Reflexive Monitoring (5 items, α = 0.65). The normalisation scale overall, was highly reliable (20 items, α = 0.89). CONCLUSIONS: The NoMAD instrument has good face validity, construct validity and internal consistency, for assessing staff perceptions of factors relevant to embedding interventions that change their work practices. Uses in evaluating and guiding implementation are proposed.

Presenting information on dental risk: PREFER study protocol for a randomised controlled trial involving patients receiving a dental check-up.

INTRODUCTION: A new dental contract being tested in England places patients into traffic light categories according to risk (Red = High risk). This reflects health policy which emphasises patients' shared responsibility for their health, and a growing expectation that clinicians discuss health risk in consultations. Alongside this, there are technological developments such as scans and photographs which have generated new, vivid imagery which may be used to communicate risk information to patients. However, there is little evidence as to whether the form in which risk information is given is important. METHODS: The PREFER study is a pragmatic, multi-centre, three-arm, patient-level randomised controlled trial, based in four NHS dental practices, from which 400 high/medium risk patients will be recruited. The study compares three ways of communicating risk information at dental check-ups: 1) verbal only (usual care); 2) a Traffic Light graphic with verbal explanation; 3) a Quantitative Light-Induced Fluorescence (QLF) photograph showing, for example, patches of red fluorescence where dental plaque has been present for two days or more (with a verbal explanation). The study assesses patient preferences using the economic preference-based valuation methodology Willingness-to-Pay (WTP). Any changes in oral self-care (for example in tooth-brushing), will be measured by self-report, and clinical outcome data collected by clinicians and extracted from QLF photographs. Predictors and moderators of any behaviour change will be explored using demographic characteristics and psychological variables from the Extended Parallel Process Model. A cost-benefit framework will explore the financial implications for NHS dentistry of the three risk presentation methods.

Childhood socioeconomic conditions and teeth in older adulthood: Evidence from SHARE wave 5.

OBJECTIVES: Dental diseases are the most common chronic diseases worldwide. Healthy teeth are vital for quality of life, particularly diet and nutrition. However, little information exists to inform health policymakers about potentially long-lasting influences of early-life conditions. The purpose of this study was to investigate the relation between early-life socioeconomic conditions and number of natural teeth at age 50 and above. METHODS: Analyses were conducted on cross-sectional data from the Survey of Health, Ageing and Retirement in Europe (SHARE wave 5), which includes information on 41 560 respondents aged 50 years or older from 14 European countries and Israel. Using SHARE life history information, a series of regression models (OLS, Tobit) were estimated to analyse the relationship between socioeconomic conditions in earlier life and the number of teeth at age 50+. RESULTS: Childhood socioeconomic background was associated with the number of natural teeth at age 50 and above, even after controlling for current determinants of oral health. Respondents who had had more than 25 books in their childhood household had a mean 1.4 (95% CI: 1.2-1.5) more teeth than respondents with fewer books. Respondents who reported poor financial conditions during childhood had a mean 0.6 (95% CI: 0.3-0.9) fewer teeth than respondents who reported better financial conditions in childhood. CONCLUSION: These findings substantiate the association between socioeconomic conditions in the early years of life and tooth retention to older adulthood and highlight the long-lasting relation between childhood living conditions and oral health through the lifecourse.

Explaining time changes in oral health-related quality of life in England: a decomposition analysis.

BACKGROUND: Oral diseases are highly prevalent and impact on oral health-related quality of life (OHRQoL). However, time changes in OHRQoL have been scarcely investigated in the current context of general improvement in clinical oral health. This study aims to examine changes in OHRQoL between 1998 and 2009 among adults in England, and to analyse the contribution of demographics, socioeconomic characteristics and clinical oral health measures. METHODS: Using data from two nationally representative surveys in England, we assessed changes in the Oral Health Impact Profile-14 (OHIP-14), in both the sample overall (n=12 027) and by quasi-cohorts. We calculated the prevalence and extent of oral impacts and summary OHIP-14 scores. An Oaxaca-Blinder type decomposition analysis was used to assess the contribution of demographics (age, gender, marital status), socioeconomic position (education, occupation) and clinical measures (presence of decay, number of missing teeth, having advanced periodontitis). RESULTS: There were significant improvements in OHRQoL, predominantly among those that experienced oral impacts occasionally, but no difference in the proportion with frequent oral impacts. The decomposition model showed that 43% (-4.07/-9.47) of the decrease in prevalence of oral impacts reported occasionally or more often was accounted by the model explanatory variables. Improvements in clinical oral health and the effect of ageing itself accounted for most of the explained change in OHRQoL, but the effect of these factors varied substantially across the lifecourse and quasi-cohorts. CONCLUSIONS: These decomposition findings indicate that broader determinants could be primarily targeted to influence OHRQoL in different age groups or across different adult cohorts.

Factors affecting patient valuations of caries prevention: Using and validating the willingness to pay method.

OBJECTIVES: Determining the value of, or strength of preference for health care interventions is useful for policy makers in planning health care services. Willingness to pay (WTP) is an established economic technique to determine the strength of preferences for interventions by eliciting monetary valuations from individuals in hypothetical situations. The objective of this study was to elicit WTP values for a dental preventive intervention and to analyze the factors affecting these as well as investigating the validity of the WTP method. METHODS: Patients aged 40 years plus attending dental practices in the UK and Germany were recruited on a consecutive basis over one month. Participants received information about a novel root caries prevention intervention. They then completed a questionnaire including a WTP task. Where the coating was indicated, patients were offered this for a payment and acceptance was recorded. Analysis included econometric modelling and comparison of expected (based on stated WTP) versus actual behaviour. RESULTS: The mean WTP for the coating was £96.41 (standard deviation 60.61). Econometric models showed that no demographic or dental history factors were significant predictors of WTP. 63% of the sample behaved as expected when using stated WTP to predict whether they would buy the coating. The remainder were split almost equally between those expected to pay but who did not and those who were expected to refuse but paid. CONCLUSIONS: Values for a caries preventive intervention had a large and unpredictable variance. In comparing hypothetical versus real preferences both under- and over-valuation occurs. CLINICAL SIGNIFICANCE: Wide and unpredictable variation in valuations for prevention may mean that there are difficult policy questions around what resource should be allocated to dental prevention and how to target this resource.

OHIP-TMDs: a patient-reported outcome measure for temporomandibular disorders.

OBJECTIVES: This research aims to assess the test-retest reliability, the face, content and known groups validity, and responsiveness to change, of OHIP-TMDs, a 22-item TMDs-specific version of the Oral Health Impact Profile (OHIP). METHODS: Test-retest reliability - A group of patients with TMDs (n = 20) was administered OHIP-TMDs twice before initial consultation with a 2-week interval. Face and content validity - Content validity index assessments were undertaken with professionals and patients. Known groups validity - Participants (n = 76) with confirmed Axis 1 RDC/TMD diagnoses completed OHIP-TMDs prior to TMDs treatment. Their responses were compared, using inferential statistics, with those of age- and gender-matched controls. Responsiveness to change - Using the same 76 participants, a comparison was made of OHIP-TMDs with OHIP-49 (order of administration randomized) both at baseline and 3 months after starting treatment. RESULTS: OHIP-TMDs showed good test-retest reliability ICC [2,1] 0.805 (95% CI: 0.565, 0.918); good face and content validity; significant differences (P < 0.001) between controls and participants demonstrating known groups validity. Its responsiveness to change was similar to OHIP-49. CONCLUSIONS: OHIP-TMDs is an appropriate biopsychosocial, patient-centred, outcome measure for assessing QOL in patients with TMDs. It is less than half the length of OHIP-49 and contains proportionately more items relevant to TMDs.

Learning from contract change in primary care dentistry: A qualitative study of stakeholders in the north of England.

The aim of this research was to explore and synthesise learning from stakeholders (NHS dentists, commissioners and patients) approximately five years on from the introduction of a new NHS dental contract in England. The case study involved a purposive sample of stakeholders associated with a former NHS Primary Care Trust (PCT) in the north of England. Semi-structured interviews were conducted with 8 commissioners of NHS dental services and 5 NHS general dental practitioners. Three focus group meetings were held with 14 NHS dental patients. All focus groups and interviews were audio recorded and transcribed verbatim. The data were analysed using a framework approach. Four themes were identified: 'commissioners' views of managing local NHS dental services'; 'the risks of commissioning for patient access'; 'costs, contract currency and commissioning constraints'; and 'local decision-making and future priorities'. Commissioners reported that much of their time was spent managing existing contracts rather than commissioning services. Patients were unclear about the NHS dental charge bands and dentists strongly criticised the contract's target-driven approach which was centred upon them generating 'units of dental activity'. NHS commissioners remained relatively constrained in their abilities to reallocate dental resources amongst contracts. The national focus upon practitioners achieving their units of dental activity appeared to outweigh interest in the quality of dental care provided.

Introducing high-cost health care to patients: dentists' accounts of offering dental implant treatment.

OBJECTIVES: The decision-making process within health care has been widely researched, with shared decision-making, where both patients and clinicians share technical and personal information, often being cited as the ideal model. To date, much of this research has focused on systems where patients receive their care and treatment free at the point of contact (either in government-funded schemes or in insurance-based schemes). Oral health care often involves patients making direct payments for their care and treatment, and less is known about how this payment affects the decision-making process. It is clear that patient characteristics influence decision-making, but previous evidence suggests that clinicians may assume characteristics rather than eliciting them directly. The aim was to explore the influences on how dentists' engaged in the decision-making process surrounding a high-cost item of health care, dental implant treatments (DITs). METHODS: A qualitative study using semi-structured interviews was undertaken using a purposive sample of primary care dentists (n = 25). Thematic analysis was undertaken to reveal emerging key themes. RESULTS: There were differences in how dentists discussed and offered implants. Dentists made decisions about whether to offer implants based on business factors, professional and legal obligations and whether they perceived the patient to be motivated to have treatment and their ability to pay. There was evidence that assessment of these characteristics was often based on assumptions derived from elements such as the appearance of the patient, the state of the patient's mouth and demographic details. The data suggest that there is a conflict between three elements of acting as a healthcare professional: minimizing provision of unneeded treatment, trying to fully involve patients in shared decisions and acting as a business person with the potential for financial gain. CONCLUSIONS: It might be expected that in the context of a high-cost healthcare intervention for which patients pay the bill themselves, that decision-making would be closer to an informed than a paternalistic model. Our research suggests that paternalistic decision-making is still practised and is influenced by assumptions about patient characteristics. Better tools and training may be required to support clinicians in this area of practice.

Socioeconomic position and subjective oral health: findings for the adult population in England, Wales and Northern Ireland.

BACKGROUND: The objective of this study was to assess socioeconomic inequalities in subjective measures of oral health in a national sample of adults in England, Wales and Northern Ireland. METHODS: We analysed data from the 2009 Adult Dental Health Survey for 8,765 adults aged 21 years and over. We examined inequalities in three oral health measures: self-rated oral health, Oral Health Impact Profile (OHIP-14), and Oral Impacts on Daily Performance (OIDP). Educational attainment, occupational social class and household income were included as socioeconomic position (SEP) indicators. Multivariable logistic regression models were fitted and from the regression coefficients, predictive margins and conditional marginal effects were estimated to compare predicted probabilities of the outcome across different SEP levels. We also assessed the effect of missing data on our results by re-estimating the regression models after imputing missing data. RESULTS: There were significant differences in predicted probabilities of the outcomes by SEP level among dentate, but not among edentate, participants. For example, persons with no qualifications showed a higher predicted probability of reporting bad oral health (9.1 percentage points higher, 95% CI: 6.54, 11.68) compared to those with a degree or equivalent. Similarly, predicted probabilities of bad oral health and oral impacts were significantly higher for participants in lower income quintiles compared to those in the highest income level (p < 0.001). Marginal effects for all outcomes were weaker for occupational social class compared to education or income. Educational and income-related inequalities were larger among young people and non-significant among 65+ year-olds. Using imputed data confirmed the aforementioned results. CONCLUSIONS: There were clear socio-economic inequalities in subjective oral health among adults in England, Wales and Northern Ireland with stronger gradients for those at younger ages.

'Your whole life is lived through your teeth': biographical disruption and experiences of tooth loss and replacement.

The experience and meaning of tooth loss and replacement has varied historically and culturally but has received relatively little attention from social scientists. Our study set out to understand these experiences in the context of the arrival of newer, dental implant treatments. Semi-structured qualitative interviews were carried out with 39 men and women who had experienced tooth loss and replacement. A thematic analysis was sensitised by previous sociological work on chronic illness, particularly Bury's notion of biographical disruption. We found that while for some individuals the loss of a tooth was relatively insignificant, for others it was devastating and disruptive. In seeking to understand this difference, the concept of biographical disruption was a helpful analytical tool. Our analysis identified two forms of disruption. The first related to the meanings of tooth loss (the neglected mouth) and denture wearing (a marker of old age). The second, embodied, disruption concerned the relationship between the self and mouth in those wearing dentures (the invaded, unreliable mouth) and could occur even where tooth loss and denture wearing had been biographically anticipated.

Developing Effective and Efficient care pathways in chronic Pain: DEEP study protocol.

BACKGROUND: Pain affecting the face or mouth and lasting longer than three months ("chronic orofacial pain", COFP) is relatively common in the UK. This study aims to describe and model current care pathways for COFP patients, identify areas where current pathways could be modified, and model whether these changes would improve outcomes for patients and use resources more efficiently. METHODS/DESIGN: The study takes a prospective operations research approach. A cohort of primary and secondary care COFP patients (n = 240) will be recruited at differing stages of their care in order to follow and analyse their journey through care. The cohort will be followed for two years with data collected at baseline 6, 12, 18, and 24 months on: 1) experiences of the care pathway and its impacts; 2) quality of life; 3) pain; 4) use of health services and costs incurred; 5) illness perceptions. Qualitative in-depth interviews will be used to collect data on patient experiences from a purposive sub-sample of the total cohort (n = 30) at baseline, 12 and 24 months. Four separate appraisal groups (public, patient, clincian, service manager/commissioning) will then be given data from the pathway analysis and asked to determine their priority areas for change. The proposals from appraisal groups will inform an economic modelling exercise. Findings from the economic modelling will be presented as incremental costs, Quality Adjusted Life Years (QALYs), and the incremental cost per QALY gained. At the end of the modelling a series of recommendations for service change will be available for implementation or further trial if necessary. DISCUSSION: The recent white paper on health and the report from the NHS Forum identified chronic conditions as priority areas and whilst technology can improve outcomes, so can simple, appropriate and well-defined clinical care pathways. Understanding the opportunity cost related to care pathways benefits the wider NHS. This research develops a method to help design efficient systems built around one condition (COFP), but the principles should be applicable to a wide range of other chronic and long-term conditions.

Measuring and decomposing oral health inequalities in an UK population.

OBJECTIVES: With health inequalities high on the policy agenda, this study measures oral health inequalities in the UK. METHODS: We compare an objective clinical measure of oral health (number of natural teeth) with a self-reported measure of the impact of oral health (the Oral Health Impact Profile, OHIP) to establish whether the type of measure affects the scale of inequality measured. Gini coefficients and Concentration Indices (CIs) are calculated with subsequent decompositions using data from the 1998 UK Adult Dental Health Survey. Because the information on OHIP is only available on dentate individuals, analyses on the number of natural teeth are conducted for two samples - the entire sample and the sample with dentate individuals only, the latter to allow direct comparison with OHIP. RESULTS: We find considerable overall pure oral health inequalities (number of teeth: Gini = 0.68 (including edentate), Gini = 0.40 (excluding edentate); OHIP: Gini = 0.33) and income-related inequalities for both measures (number of teeth: CI = 0.35 (including edentate), CI = 0.15 (excluding edentate); OHIP: CI = 0.03), and the CI is generally higher for the number of teeth than for OHIP. There are differences across age groups, with CI increasing with age for the number of teeth (excluding edentate: 16-30 years: CI = 0.01, 65 + years: CI = 0.11; including edentate: 16-30 years: CI = 0.01, 65 + years: CI = 0.19). However, inequalities for OHIP were highest in the youngest age group (CI = 0.05). Number of teeth reflects the accumulation of damage over a lifetime, while OHIP records more immediate concerns. CONCLUSIONS: There are considerable pure oral health inequalities and income-related oral health inequalities in the UK. Using sophisticated methods to measure oral health inequality, we have been able to compare inequality in oral health with inequality in general health. The results provide a benchmark for future comparisons but also indicate that the type of health measure may be of considerable significance in how we think about and measure oral health inequalities.

The future for oral health surveillance.

OBJECTIVES: To take an overview of the history and future of oral health surveillance. METHODS: A brief review of the history and policy context of national surveys and equivalent large surveys of oral health and their objectives followed by an analysis of their fitness for modern purpose. RESULTS AND CONCLUSION: The quality of oral health surveillance has improved immeasurably since the first attempts in the early 1960s, but national and regional surveys are still hampered by a lack of clarity about their purpose. The data they collect and describe are potentially invaluable and have the major advantages of being both robust and relatively straightforward to interpret and explain to policy makers. A greater clarity of purpose both from researchers and those who commission research would allow better use of data and a greater understanding of the limitations of surveillance. The international research community have a role to play in establishing and sharing best practice globally.

Beyond price: individuals' accounts of deciding to pay for private healthcare treatment in the UK.

BACKGROUND: Delivering appropriate and affordable healthcare is a concern across the globe. As countries grapple with the issue of delivering healthcare with finite resources and populations continue to age, more health-related care services or treatments may become an optional 'extra' to be purchased privately. It is timely to consider how, and to what extent, the individual can act as both a 'patient' and a 'consumer'. In the UK the majority of healthcare treatments are free at the point of delivery. However, increasingly some healthcare treatments are being made available via the private healthcare market. Drawing from insights from healthcare policy and social sciences, this paper uses the exemplar of private dental implant treatment provision in the UK to examine what factors people considered when deciding whether or not to pay for a costly healthcare treatment for a non-fatal condition. METHODS: Qualitative interviews with people (n = 27) who considered paying for dental implants treatments in the UK. Data collection and analysis processes followed the principles of the constant comparative methods, and thematic analysis was facilitated through the use of NVivo qualitative data software. RESULTS: Decisions to pay for private healthcare treatments are not simply determined by price. Decisions are mediated by: the perceived 'status' of the healthcare treatment as either functional or aesthetic; how the individual determines and values their 'need' for the treatment; and, the impact the expenditure may have on themselves and others. Choosing a private healthcare provider is sometimes determined simply by personal rapport or extant clinical relationship, or based on the recommendation of others. CONCLUSIONS: As private healthcare markets expand to provide more 'non-essential' services, patients need to develop new skills and to be supported in their new role as consumers.

Interpreting oral health-related quality of life data.

The most common way of presenting data from studies using quality of life or patient-based outcome (PBO) measures is in terms of mean scores along with testing the statistical significance of differences in means. We argue that this is insufficient in and of itself and call for a more comprehensive and thoughtful approach to the reporting and interpretation of data. PBO scores (and their means for that matter) are intrinsically meaningless, and differences in means between groups mask important and potentially different patterns in response within groups. More importantly, they are difficult to interpret because of the absence of a meaningful benchmark. The minimally important difference (MID) provides that benchmark to assist interpretability. This commentary discusses different approaches (distribution-based and anchor-based) and specific methods for assessing the MID in both longitudinal and cross-sectional studies, and suggests minimum standards for reporting and interpreting PBO measures in an oral health context.

Managing resources in NHS dentistry: using health economics to inform commissioning decisions.

BACKGROUND: The aim of this study is to develop, apply and evaluate an economics-based framework to assist commissioners in their management of finite resources for local dental services. In April 2006, Primary Care Trusts in England were charged with managing finite dental budgets for the first time, yet several independent reports have since criticised the variability in commissioning skills within these organisations. The study will explore the views of stakeholders (dentists, patients and commissioners) regarding priority setting and the criteria used for decision-making and resource allocation. Two inter-related case studies will explore the dental commissioning and resource allocation processes through the application of a pragmatic economics-based framework known as Programme Budgeting and Marginal Analysis. METHODS/DESIGN: The study will adopt an action research approach. Qualitative methods including semi-structured interviews, focus groups, field notes and document analysis will record the views of participants and their involvement in the research process. The first case study will be based within a Primary Care Trust where mixed methods will record the views of dentists, patients and dental commissioners on issues, priorities and processes associated with managing local dental services. A Programme Budgeting and Marginal Analysis framework will be applied to determine the potential value of economic principles to the decision-making process. A further case study will be conducted in a secondary care dental teaching hospital using the same approach. Qualitative data will be analysed using thematic analysis and managed using a framework approach. DISCUSSION: The recent announcement by government regarding the proposed abolition of Primary Care Trusts may pose challenges for the research team regarding their engagement with the research study. However, whichever commissioning organisations are responsible for resource allocation for dental services in the future; resource scarcity is highly likely to remain an issue. Wider understanding of the complexities of priority setting and resource allocation at local levels are important considerations in the development of dental commissioning processes, national oral health policy and the future new dental contract which is expected to be implemented in April 2014.

Temporomandibular disorder patients' journey through care.

UNLABELLED: Temporomandibular disorders (TMDs) are a common group of chronic disorders (illnesses) that health care providers can find difficult to diagnose and explain. Similar difficulties in the diagnosis of other chronic conditions have been shown to have a negative impact on health. An understanding of TMD patients' experiences and journey through care could indicate time points and strategies to help patients. OBJECTIVE: To develop a robust empirically derived map of TMD sufferers' journey through care. METHODS: A qualitative study using semi-structured interviews was undertaken using a purposive sample of patients with TMDs. Analysis followed the principles of the constant comparative method where data collection and thematic analysis occurred concurrently and continued until data saturation (n = 29). RESULTS: The experiences of patients could be grouped into three key stages: genesis of problem, seeking help in primary care and secondary care intervention. A wide variety of negative effects were described throughout these stages. An empirically derived map of the patients' reported journey through care emerged. CONCLUSIONS: The experiences of patients with TMDs mirror experiences of other types of chronic illness. Mapping the journey through care for TMDs highlights the potential for interaction between the stages of the journey and the individual's illness. It may be possible to target interventions at specific stages on the map to help minimize the psychosocial effects of TMDs.