Cost-effectiveness Analysis of the Dental RECUR Pragmatic Randomized Controlled Trial: Evaluating a Goal-oriented Talking Intervention to Prevent Reoccurrence of Dental Caries in Children

BACKGROUND: The formation of dental caries is the most common chronic disease in children, and is preventable. The oral health-related quality of life has an immense impact on an individual’s daily functioning, well-being or overall quality of life. OBJECTIVES: This study aims to investigate the cost effectiveness of the Dental RECUR Brief Negotiated Interview for Oral Health (DR-BNI). This 30-minute therapeutic “talk” by a dental nurse with a parent/guardian was compared with a placebo-controlled intervention in preventing reoccurrence of dental caries in children who have had a primary tooth extracted. METHODS: An economic model was developed to simulate the clinical progression of dental caries among children who have previously had a primary tooth extracted. The analysis was conducted using the UK NHS perspective. The main outcome was the incremental cost-effectiveness ratio (ICER) based on the quality-adjusted life years (QALYs). Estimates of costs and probabilities were obtained from the DR-BNI multicentre randomised controlled trial (RCT), while QALY values were obtained from published literature. Univariate and probabilistic sensitivity analyses were conducted to assess the uncertainty of the result and robustness of the model. Affordability and risk-aversion of the intervention were investigated to help decision makers make the best possible choices. RESULTS: With an intervention cost of £6.47, the results from the RCT showed the healthcare cost for the DR-BNI intervention was £115.90 per child while the control had a healthcare cost of £119.46 per child. The QALYs gained for the prevention of reoccurrence of dental caries was higher in the DR-BNI intervention arm by 0.023 QALYs; thus, the DR-BNI was the dominant intervention. At willingness to pay threshold of £3500/QALY gained, a maximum probability of being cost effectiveness is achieved at 86%. The secondary analysis showed a cost-savings of £20.94 per participant for the prevention of at least one filling or extraction. Affordability results showed that the DR-BNI programme is affordable to the UK health system at a moderately low budget. CONCLUSIONS: This study shows the proactive talking intervention to have a very moderate cost and to be effective in providing better health related quality-of-life gains. The intervention is cost savings with a dominant ICER even with a 200% increase in the cost of intervention. The NHS will be providing better oral health for children at a better net monetary benefit-to-risk ratio by adopting the DR-BNI intervention in preventing the reoccurrence of dental fillings and extractions for each participant. Trial Registration: This trial was registered prospectively on 27th September 2013 with the trial registration number ISRCTN 24958829. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40258-022-00720-5

A new primary dental care service compared with standard care for child and family to reduce the re-occurrence of childhood dental caries (Dental RECUR): study protocol for a randomised controlled trial

Background: In England and Scotland, dental extraction is the single highest cause of planned admission to the hospital for children under 11 years. Traditional dental services have had limited success in reducing this disease burden. Interventions based on motivational interviewing have been shown to impact positively dental health behaviours and could facilitate the prevention of re-occurrence of dental caries in this high-risk population. The objective of the study is to evaluate whether a new, dental nurse-led service, delivered using a brief negotiated interview based on motivational interviewing, is a more cost-effective service than treatment as usual, in reducing the re-occurrence of dental decay in young children with previous dental extractions. Methods/Design: This 2-year, two-arm, multicentre, randomised controlled trial will include 224 child participants, initially aged 5 to 7 years, who are scheduled to have one or more primary teeth extracted for dental caries under general anaesthesia (GA), relative analgesia (RA: inhalation sedation) or local anaesthesia (LA). The trial will be conducted in University Dental Hospitals, Secondary Care Centres or other providers of dental extraction services across the United Kingdom. The intervention will include a brief negotiated interview (based on the principles of motivational interviewing) delivered between enrolment and 6 weeks post-extraction, followed by directed prevention in primary dental care. Participants will be followed up for 2 years. The main outcome measure will be the dental caries experienced by 2 years post-enrolment at the level of dentine involvement on any tooth in either dentition, which had been caries-free at the baseline assessment. Discussion: The participants are a hard-to-reach group in which secondary prevention is a challenge. Lack of engagement with dental care makes the children and their families scheduled for extraction particularly difficult to recruit to an RCT. Variations in service delivery between sites have also added to the challenges in implementing the Dental RECUR protocol during the recruitment phase. Trial registration: ISRCTN24958829 (date of registration: 27 September 2013), Current protocol version: 5.0

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

Identifying the participant characteristics that predict recruitment and retention of participants to randomised controlled trials involving children : a systematic review

Background Randomised controlled trials (RCTs) are recommended as the ‘gold standard’ in evaluating health care interventions. The conduct of RCTs is often impacted by difficulties surrounding recruitment and retention of participants in both adult and child populations. Factors influencing recruitment and retention of children to RCTs can be more complex than in adults. There is little synthesised evidence of what influences participation in research involving parents and children. Aim To identify predictors of recruitment and retention in RCTs involving children. Methods A systematic review of RCTs was conducted to synthesise the available evidence. An electronic search strategy was applied to four databases and restricted to English language publications. Quantitative studies reporting participant predictors of recruitment and retention in RCTs involving children aged 0–12 were identified. Data was extracted and synthesised narratively. Quality assessment of articles was conducted using a structured tool developed from two existing quality evaluation checklists. Results Twenty-eight studies were included in the review. Of the 154 participant factors reported, 66 were found to be significant predictors of recruitment and retention in at least one study. These were classified as parent, child, family and neighbourhood characteristics. Parent characteristics (e.g. ethnicity, age, education, socioeconomic status (SES)) were the most commonly reported predictors of participation for both recruitment and retention. Being young, less educated, of an ethnic minority and having low SES appear to be barriers to participation in RCTs although there was little agreement between studies. When analysed according to setting and severity of the child’s illness there appeared to be little variation between groups. The quality of the studies varied. Articles adhered well to reporting guidelines around provision of a scientific rationale for the study and background information as well as displaying good internal consistency of results. However, few studies discussed the external validity of the results or provided recommendations for future research. Conclusion Parent characteristics may predict participation of children and their families to RCTs; however, there was a lack of consensus. Whilst sociodemographic variables may be useful in identifying which groups are least likely to participate they do not provide insight into the processes and barriers to participation for children and families. Further studies that explore variables that can be influenced are warranted. Reporting of studies in this field need greater clarity as well as agreed definitions of what is meant by retention

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

The quality of written information for parents regarding the management of a febrile convulsion:a randomized controlled trial

To identify whether providing a new information leaflet for parents regarding the management of a febrile convulsion was more effective in comparison with standard leaflets.  Although information leaflets are frequently recommended within healthcare, their quality is often poor. Furthermore, the evidence regarding the effectiveness of leaflets is inconsistent. Few studies have evaluated the effects of providing leaflets that have been developed to improve their quality. Within the specialty of paediatrics, parents are often unprepared regarding the management of febrile convulsion at home and the provision of supplementary leaflets is recommended, despite limited evidence regarding the effectiveness of this approach. There is also limited evidence regarding whether improving the quality of these leaflets leads to better outcomes, e.g. increasing parents’ behavioural knowledge. Double-blind randomized controlled trial. One hundred and twenty-six parents of children hospitalized due to benign febrile convulsion were recruited (May 2000–February 2002). Seventy-one parents were randomized to receive the standard care (control leaflet) and 55 parents received the intervention (new leaflet). Data were collected from parents on discharge immediately prior to receiving the intervention and 7–14 days following the intervention via telephone interview. Parents who received the new leaflet found this to be more reassuring and easier to understand than parents who received the control leaflet. No differences between groups were identified regarding the primary outcome, i.e. behavioural knowledge and most of the secondary outcomes, e.g. perceived confidence, state anxiety and satisfaction with the leaflet. Although this study provides modest support for the effectiveness of providing high-quality leaflets, further research is required to determine the best methods for optimizing the effectiveness of leaflets provided at hospital discharge. The quality of leaflets may influence some outcomes, e.g. understanding and reassurance with the written information provided; however, additional strategies to inform parents may be necessary

Cost-effectiveness Analysis of the Dental RECUR Pragmatic Randomized Controlled Trial: Evaluating a Goal-oriented Talking Intervention to Prevent Reoccurrence of Dental Caries in Children

Abstract: Background: The formation of dental caries is the most common chronic disease in children, and is preventable. The oral health-related quality of life has an immense impact on an individual’s daily functioning, well-being or overall quality of life. Objectives: This study aims to investigate the cost effectiveness of the Dental RECUR Brief Negotiated Interview for Oral Health (DR-BNI). This 30-minute therapeutic “talk” by a dental nurse with a parent/guardian was compared with a placebo-controlled intervention in preventing reoccurrence of dental caries in children who have had a primary tooth extracted. Methods: An economic model was developed to simulate the clinical progression of dental caries among children who have previously had a primary tooth extracted. The analysis was conducted using the UK NHS perspective. The main outcome was the incremental cost-effectiveness ratio (ICER) based on the quality-adjusted life years (QALYs). Estimates of costs and probabilities were obtained from the DR-BNI multicentre randomised controlled trial (RCT), while QALY values were obtained from published literature. Univariate and probabilistic sensitivity analyses were conducted to assess the uncertainty of the result and robustness of the model. Affordability and risk-aversion of the intervention were investigated to help decision makers make the best possible choices. Results: With an intervention cost of £6.47, the results from the RCT showed the healthcare cost for the DR-BNI intervention was £115.90 per child while the control had a healthcare cost of £119.46 per child. The QALYs gained for the prevention of reoccurrence of dental caries was higher in the DR-BNI intervention arm by 0.023 QALYs; thus, the DR-BNI was the dominant intervention. At willingness to pay threshold of £3500/QALY gained, a maximum probability of being cost effectiveness is achieved at 86%. The secondary analysis showed a cost-savings of £20.94 per participant for the prevention of at least one filling or extraction. Affordability results showed that the DR-BNI programme is affordable to the UK health system at a moderately low budget. Conclusions: This study shows the proactive talking intervention to have a very moderate cost and to be effective in providing better health related quality-of-life gains. The intervention is cost savings with a dominant ICER even with a 200% increase in the cost of intervention. The NHS will be providing better oral health for children at a better net monetary benefit-to-risk ratio by adopting the DR-BNI intervention in preventing the reoccurrence of dental fillings and extractions for each participant. Trial Registration: This trial was registered prospectively on 27th September 2013 with the trial registration number ISRCTN 24958829