Effect of fluoridated water on invasive NHS dental treatments for adults: the LOTUS retrospective cohort study and economic evaluation.

Background: Most water fluoridation studies were conducted on children before the widespread introduction of fluoride toothpastes. There is a lack of evidence that can be applied to contemporary populations, particularly adolescents and adults. Objective: To pragmatically assess the clinical and cost effectiveness of water fluoridation for preventing dental treatment and improving oral health in a contemporary population of adults, using a natural experiment design. Design: Retrospective cohort study using routinely collected National Health Service dental claims (FP17) data. Setting: National Health Service primary dental care: general dental practices, prisons, community dental services, domiciliary settings, urgent/out-of-hours and specialised referral-only services. Participants: Dental patients aged 12 years and over living in England (n = 6,370,280). Intervention and comparison: Individuals exposed to drinking water with a fluoride concentration ≥ 0.7 mg F/l between 2010 and 2020 were matched to non-exposed individuals on key characteristics using propensity scores. Outcome measures: Primary: number of National Health Service invasive dental treatments (restorations/'fillings' and extractions) received per person between 2010 and 2020. Secondary: decayed, missing and filled teeth, missing teeth, inequalities, cost effectiveness and return on investment. Data sources: National Health Service Business Services Authority dental claims data. Water quality monitoring data. Primary outcome: Predicted mean number of invasive dental treatments was 3% lower in the optimally fluoridated group than in the sub/non-optimally fluoridated group (incidence rate ratio 0.969, 95% CI 0.967 to 0.971), a difference of -0.173 invasive dental treatments (95% CI -0.185 to -0.161). This magnitude of effect is smaller than what most stakeholders we engaged with (n = 50/54) considered meaningful. Secondary outcomes: Mean decayed, missing and filled teeth were 2% lower in the optimally fluoridated group, with a difference of -0.212 decayed, missing and filled teeth (95% CI -0.229 to -0.194). There was no statistically significant difference in the mean number of missing teeth per person (0.006, 95% CI -0.008 to 0.021). There was no compelling evidence that water fluoridation reduced social inequalities in treatments received or missing teeth; however, decayed, missing and filled teeth data did not demonstrate a typical inequalities gradient. Optimal water fluoridation in England in 2010-20 was estimated to cost £10.30 per person (excluding original setup costs). Mean National Health Service treatment costs for fluoridated patients 2010-20 were 5.5% lower per person, by £22.26 (95% CI -£23.09 to -£21.43), and patients paid £7.64 less in National Health Service dental charges per person (2020 prices). Limitations: Pragmatic, observational study with potential for non-differential errors of misclassification in fluoridation assignment and outcome measurement and residual and/or unmeasured confounding. Decayed, missing and filled teeth data have not been validated. Water fluoridation cost estimates are based on existing programmes between 2010 and 2020, and therefore do not include the potentially significant capital investment required for new programmes. Conclusions: Receipt of optimal water fluoridation between 2010 and 2020 resulted in very small health effects, which may not be meaningful for individuals, and we could find no evidence of a reduction in social inequalities. Existing water fluoridation programmes in England produced a positive return on investment between 2010 and 2020 due to slightly lower National Health Service treatment costs. These relatively small savings should be evaluated against the projected costs and lifespan of any proposed capital investment in water fluoridation, including new programmes. Future work: National Health Service dental data are a valuable resource for research. Further validation and measures to improve quality and completeness are warranted. Trial registrations: This trial is registered as ISRCTN96479279, CAG: 20/CAG/0072, IRAS: 20/NE/0144. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: NIHR128533) and is published in full in Public Health Research; Vol. 12, No. 5. See the NIHR Funding and Awards website for further award information.

Fluoride is a natural mineral that prevents tooth decay. It is added to some drinking water and toothpastes to improve dental health. Water with fluoride added is known as 'optimally fluoridated'. Most research on water fluoridation was carried out before fluoride was added to toothpastes in the 1970s and only included children. We wanted to know if water fluoridation still produced large reductions in tooth decay, now that decay levels are much lower because of fluoride in toothpaste. We also wanted to look at its effect on adults and teenagers. Dental patients we spoke to told us they worried about needing treatment with the 'drill', or 'injection', losing their teeth and paying for their dental care. To see if water fluoridation helped with these concerns, we compared the National Health Service dental records of 6.4 million adults and teenagers who received optimally fluoridated or non-optimally fluoridated water in England between 2010 and 2020. We found water fluoridation made a very small difference to each person. Between 2010 and 2020, the number of NHS fillings and extractions was 3% lower per person for those who received optimally fluoridated water. We found no difference in the number of teeth lost per person and no strong sign that fluoridation reduced differences in dental health between rich and poor areas. Between 2010 and 2020, the cost of optimal water fluoridation was £10.30 per person (not including setup costs). National Health Service dental patients who received optimally fluoridated water cost the National Health Service £22.26 (5.5%) less and paid £7.64 (2%) less per person in National Health Service dental charges over the 10 years. The benefits we found are much smaller than in the past, when toothpastes did not contain fluoride. The cost to set up a new water fluoridation programme can be high. Communities may need to consider if these smaller benefits would still outweigh the costs.

A survey of experts to identify methods to detect problematic studies: Stage 1 of the INSPECT-SR Project.

Background: Randomised controlled trials (RCTs) inform healthcare decisions. Unfortunately, some published RCTs contain false data, and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs which have been conducted on a given topic. This means that any of these 'problematic studies' are likely to be included, but there are no agreed methods for identifying them. The INSPECT-SR project is developing a tool to identify problematic RCTs in systematic reviews of healthcare-related interventions. The tool will guide the user through a series of 'checks' to determine a study's authenticity. The first objective in the development process is to assemble a comprehensive list of checks to consider for inclusion. Methods: We assembled an initial list of checks for assessing the authenticity of research studies, with no restriction to RCTs, and categorised these into five domains: Inspecting results in the paper; Inspecting the research team; Inspecting conduct, governance, and transparency; Inspecting text and publication details; Inspecting the individual participant data. We implemented this list as an online survey, and invited people with expertise and experience of assessing potentially problematic studies to participate through professional networks and online forums. Participants were invited to provide feedback on the checks on the list, and were asked to describe any additional checks they knew of, which were not featured in the list. Results: Extensive feedback on an initial list of 102 checks was provided by 71 participants based in 16 countries across five continents. Fourteen new checks were proposed across the five domains, and suggestions were made to reword checks on the initial list. An updated list of checks was constructed, comprising 116 checks. Many participants expressed a lack of familiarity with statistical checks, and emphasized the importance of feasibility of the tool. Conclusions: A comprehensive list of trustworthiness checks has been produced. The checks will be evaluated to determine which should be included in the INSPECT-SR tool.

Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions.

INTRODUCTION: Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INveStigating ProblEmatic Clinical Trials in Systematic Reviews (INSPECT-SR) project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare-related interventions. METHODS AND ANALYSIS: The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: (1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, (2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, (3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in, (4) a consensus meeting to select checks to be included in a draft tool and to determine its format and (5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies and will help patients by protecting them from the influence of false data on their healthcare. ETHICS AND DISSEMINATION: The University of Manchester ethics decision tool was used, and this returned the result that ethical approval was not required for this project (30 September 2022), which incorporates secondary research and surveys of professionals about subjects relating to their expertise. Informed consent will be obtained from all survey participants. All results will be published as open-access articles. The final tool will be made freely available.

Longitudinal adherence to surveillance for late effects of cancer treatment: a population-based study of adult survivors of childhood cancer.

BACKGROUND: Adult survivors of childhood cancer are at elevated risk of morbidity and mortality compared to the general population, but their adherence to lifelong periodic surveillance is suboptimal. We aimed to examine adherence to surveillance guidelines for high-yield tests and identify risk factors for nonadherence in adult survivors of childhood cancer. METHODS: In this retrospective, population-based cohort study, we used health care administrative data from Ontario, Canada, to identify adult survivors of childhood cancer diagnosed between 1986 and 2014 who were at elevated risk of therapy-related colorectal cancer, breast cancer, or cardiomyopathy. Using a Poisson regression framework, we assessed longitudinal adherence and predictors of adherence to the Children's Oncology Group surveillance guideline. RESULTS: Among 3241 survivors, 327 (10%), 234 (7%), and 3205 (99%) were at elevated risk for colorectal cancer, breast cancer, and cardiomyopathy, respectively. Within these cohorts, only 13%, 6%, and 53% were adherent to recommended surveillance as of February 2020. During a median follow-up of 7.8 years, the proportion of time spent adherent was 14% among survivors at elevated risk for colorectal cancer, 10% for breast cancer, and 43% for cardiomyopathy. Significant predictors of adherence varied across the risk groups, but higher comorbidity was associated with adherence to recommended surveillance. INTERPRETATION: Survivors of childhood cancer in Ontario are rarely up to date for recommended surveillance tests. Tailored interventions beyond specialized clinics are needed to improve surveillance adherence.

Study protocol for a Randomised controlled trial of EArly transjugular intrahepatiC porTosystemic stent-shunt in Acute Variceal Bleeding (REACT-AVB trial).

INTRODUCTION: In liver cirrhosis, acute variceal bleeding (AVB) is associated with a 1-year mortality rate of up to 40%. Data on early or pre-emptive transjugular intrahepatic portosystemic stent-shunt (TIPSS) in AVB is inconclusive and may not reflect current management strategies. Randomised controlled trial of EArly transjugular intrahepatiC porTosystemic stent-shunt in AVB (REACT-AVB) aims to investigate the clinical and cost-effectiveness of early TIPSS in patients with cirrhosis and AVB after initial bleeding control. METHODS AND ANALYSIS: REACT-AVB is a multicentre, randomised controlled, open-label, superiority, two-arm, parallel-group trial with an internal pilot. The two interventions allocated randomly 1:1 are early TIPSS within 4 days of diagnostic endoscopy or secondary prophylaxis with endoscopic therapy in combination with non-selective beta blockers. Patients aged ≥18 years with cirrhosis and Child-Pugh Score 7-13 presenting with AVB with endoscopic haemostasis are eligible for inclusion. The primary outcome is transplant-free survival at 1 year post randomisation. Secondary endpoints include transplant-free survival at 6 weeks, rebleeding, serious adverse events, other complications of cirrhosis, Child-Pugh and Model For End-Stage Liver Disease (MELD) scores at 6 and 12 months, health-related quality of life, use of healthcare resources, cost-effectiveness and use of cross-over therapies. The sample size is 294 patients over a 4-year recruitment period, across 30 hospitals in the UK. ETHICS AND DISSEMINATION: Research ethics committee of National Health Service has approved REACT-AVB (reference number: 23/WM/0085). The results will be submitted for publication in a peer-reviewed journal. A lay summary will also be emailed or posted to participants before publication. TRIAL REGISTRATION NUMBER: ISRCTN85274829; protocol version 3.0, 1 July 2023.

Protocol for the ONLOOP trial: pragmatic randomized trial evaluating a province-wide system of personalized reminders for evidence-based surveillance tests in adult survivors of childhood cancer in Ontario.

BACKGROUND: Childhood cancer treatment while often curative, leads to elevated risks of morbidity and mortality. Survivors require lifelong periodic surveillance for late effects of treatment, yet adherence to guideline-recommended tests is suboptimal. We created ONLOOP to provide adult survivors of childhood cancer with detailed health information, including summaries of their childhood cancer treatment and recommended surveillance tests for early detection of cardiomyopathy, breast cancer, and/or colorectal cancer, with personalized reminders over time. METHODS: This is an individually randomized, registry-based pragmatic trial with an embedded process and economic evaluation to understand ONLOOP's impact and whether it can be readily implemented at scale. All adult survivors of childhood cancer in Ontario overdue for guideline-recommended tests will be randomly assigned to one of two arms: (1) intervention or (2) delayed intervention. A letter of information and invitation will detail the ONLOOP program. Those who sign up will receive a personalized toolkit and a screening reminder 6 months later. With the participants' consent, ONLOOP will also send their primary care clinician a letter detailing the recommended tests and a reminder 6 months later. The primary outcome will be the proportion of survivors who complete one or more of the guideline-recommended cardiac, breast, or colon surveillance tests during the 12 months after randomization. Data will be obtained from administrative databases. The intent-to-treat principle will be followed. Based on our analyses of administrative data, we anticipate allocating at least 862 individuals to each trial arm, providing 90% power to detect an absolute increase of 6% in targeted surveillance tests completed. We will interview childhood cancer survivors and family physicians in an embedded process evaluation to examine why and how ONLOOP achieved success or failed. A cost-effectiveness evaluation will be performed. DISCUSSION: The results of this study will determine if ONLOOP is effective at helping adult survivors of childhood cancer complete their recommended surveillance tests. This study will also inform ongoing provincial programs for this high-risk population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05832138.

How effective and cost-effective is water fluoridation for adults and adolescents? The LOTUS 10-year retrospective cohort study.

OBJECTIVE: To pragmatically assess the clinical and cost-effectiveness of water fluoridation for preventing dental treatment and improving oral health in a contemporary population of adults and adolescents, using a natural experiment design. METHODS: A 10-year retrospective cohort study (2010-2020) using routinely collected NHS dental treatment claims data. Participants were patients aged 12 years and over, attending NHS primary dental care services in England (17.8 million patients). Using recorded residential locations, individuals exposed to drinking water with an optimal fluoride concentration (≥0.7 mg F/L) were matched to non-exposed individuals using propensity scores. Number of NHS invasive dental treatments, DMFT and missing teeth were compared between groups using negative binomial regression. Total NHS dental treatment costs and cost per invasive dental treatment avoided were calculated. RESULTS: Matching resulted in an analytical sample of 6.4 million patients. Predicted mean number of invasive NHS dental treatments (restorations 'fillings'/extractions) was 3% lower in the optimally fluoridated group (5.4) than the non-optimally fluoridated group (5.6) (IRR 0.969, 95% CI 0.967, 0.971). Predicted mean DMFT was 2% lower in the optimally fluoridated group (IRR 0.984, 95% CI 0.983, 0.985). There was no difference in the predicted mean number of missing teeth per person (IRR 1.001, 95% CI 0.999, 1.003) and no compelling evidence that water fluoridation reduced social inequalities in dental health. Optimal water fluoridation in England 2010-2020 was estimated to cost £10.30 per person (excludes initial set-up costs). NHS dental treatment costs for optimally fluoridated patients 2010-2020 were 5.5% lower, by £22.26 per person (95% CI -£21.43, -£23.09). CONCLUSIONS: Receipt of optimal water fluoridation 2010-2020 resulted in very small positive health effects which may not be meaningful for individuals. Existing fluoridation programmes in England produced a positive return on investment between 2010 and 2020 due to slightly lower NHS dental care utilization. This return should be evaluated against the projected costs and lifespan of any proposed capital investment in water fluoridation, including new programmes.