Health Care Access and COVID-19 Vaccination in the United States: A Cross-Sectional Analysis.

BACKGROUND: Although federal legislation made COVID-19 vaccines free, inequities in access to medical care may affect vaccine uptake. OBJECTIVE: To assess whether health care access was associated with uptake and timeliness of COVID-19 vaccination in the United States. DESIGN: A cross-sectional study. SETTING: 2021 National Health Interview Survey (Q2-Q4). SUBJECTS: In all, 21,532 adults aged≥18 were included in the study. MEASURES: Exposures included 4 metrics of health care access: health insurance, having an established place for medical care, having a physician visit within the past year, and medical care affordability. Outcomes included receipt of 1 or more COVID-19 vaccines and receipt of a first vaccine within 6 months of vaccine availability. We examined the association between each health care access metric and outcome using logistic regression, unadjusted and adjusted for demographic, geographic, and socioeconomic covariates. RESULTS: In unadjusted analyses, each metric of health care access was associated with the uptake of COVID-19 vaccination and (among those vaccinated) early vaccination. In adjusted analyses, having health coverage (adjusted odds ratio [AOR] 1.60; 95% CI: 1.39, 1.84), a usual place of care (AOR 1.58; 95% CI: 1.42, 1.75), and a doctor visit within the past year (AOR 1.45, 95% CI: 1.31, 1.62) remained associated with higher rates of COVID-19 vaccination. Only having a usual place of care was associated with early vaccine uptake in adjusted analyses. LIMITATIONS: Receipt of COVID-19 vaccination was self-reported. CONCLUSIONS: Several metrics of health care access are associated with the uptake of COVID-19 vaccines. Policies that achieve universal coverage, and facilitate long-term relationships with trusted providers, may be an important component of pandemic responses.

Short-term hyperoxia-induced functional and morphological changes in rat hippocampus.

Excess oxygen (O2) levels may have a stimulating effect, but in the long term, and at high concentrations of O2, it is harmful to the nervous system. The hippocampus is very sensitive to pathophysiological changes and altered O2 concentrations can interfere with hippocampus-dependent learning and memory functions. In this study, we investigated the hyperoxia-induced changes in the rat hippocampus to evaluate the short-term effect of mild and severe hyperoxia. Wistar male rats were randomly divided into control (21% O2), mild hyperoxia (30% O2), and severe hyperoxia groups (100% O2). The O2 exposure lasted for 60 min. Multi-channel silicon probes were used to study network oscillations and firing properties of hippocampal putative inhibitory and excitatory neurons. Neural damage was assessed using the Gallyas silver impregnation method. Mild hyperoxia (30% O2) led to the formation of moderate numbers of silver-impregnated "dark" neurons in the hippocampus. On the other hand, exposure to 100% O2 was associated with a significant increase in the number of "dark" neurons located mostly in the hilus. The peak frequency of the delta oscillation decreased significantly in both mild and severe hyperoxia in urethane anesthetized rats. Compared to normoxia, the firing activity of pyramidal neurons under hyperoxia increased while it was more heterogeneous in putative interneurons in the cornu ammonis area 1 (CA1) and area 3 (CA3). These results indicate that short-term hyperoxia can change the firing properties of hippocampal neurons and network oscillations and damage neurons. Therefore, the use of elevated O2 concentration inhalation in hospitals (i.e., COVID treatment and surgery) and in various non-medical scenarios (i.e., airplane emergency O2 masks, fire-fighters, and high altitude trekkers) must be used with extreme caution.

The feasibility and acceptability of an app-based intervention with brief behavioural support (APPROACH) to promote brisk walking in people diagnosed with breast, prostate and colorectal cancer in the UK.

INTRODUCTION: Increased moderate to vigorous physical activity (MVPA) can improve clinical and psychosocial outcomes for people living with and beyond cancer (LWBC). This study aimed to assess the feasibility and acceptability of trial procedures in a pilot randomised controlled trial (RCT) of a theory-driven app-based intervention with behavioural support focused on promoting brisk walking (a form of MVPA) in people LWBC (APPROACH). METHODS: Participants diagnosed with breast, prostate or colorectal cancer were recruited from a single UK hospital site. Assessments at baseline and 3 months included online questionnaires, device-measured brisk walking (activPAL accelerometer) and self-reported weight and height. Participants were randomised to intervention or control (care as usual). The intervention comprised a non-cancer-specific app to promote brisk walking (National Health Service 'Active 10') augmented with print information about habit formation, a walking planner and two behavioural support telephone calls. Feasibility and acceptability of trial procedures were explored. Initial estimates for physical activity informed a power calculation for a phase III RCT. A preliminary health economics analysis was conducted. RESULTS: Of those medically eligible, 369/577 (64%) were willing to answer further eligibility questions and 90/148 (61%) of those eligible were enrolled. Feasibility outcomes, including retention (97%), assessment completion rates (>86%) and app download rates in the intervention group (96%), suggest that the trial procedures are acceptable and that the intervention is feasible. The phase III RCT will require 472 participants to be randomised. As expected, the preliminary health economic analyses indicate a high level of uncertainty around the cost-effectiveness of the intervention. CONCLUSIONS: This pilot study demonstrates that a large trial of the brisk walking intervention with behavioural support is both feasible and acceptable to people LWBC. The results support progression onto a confirmatory phase III trial to determine the efficacy and cost-effectiveness of the intervention.

Cross-model validation of public health microsimulation models; comparing two models on estimated effects of a weight management intervention.

BACKGROUND: Health economic modelling indicates that referral to a behavioural weight management programme is cost saving and generates QALY gains compared with a brief intervention. The aim of this study was to conduct a cross-model validation comparing outcomes from this cost-effectiveness analysis to those of a comparator model, to understand how differences in model structure contribute to outcomes. METHODS: The outcomes produced by two models, the School for Public Health Research diabetes prevention (SPHR) and Health Checks (HC) models, were compared for three weight-management programme strategies; Weight Watchers (WW) for 12 weeks, WW for 52 weeks, and a brief intervention, and a simulated no intervention scenario. Model inputs were standardised, and iterative adjustments were made to each model to identify drivers of differences in key outcomes. RESULTS: The total QALYs estimated by the HC model were higher in all treatment groups than those estimated by the SPHR model, and there was a large difference in incremental QALYs between the models. SPHR simulated greater QALY gains for 12-week WW and 52-week WW relative to the Brief Intervention. Comparisons across socioeconomic groups found a stronger socioeconomic gradient in the SPHR model. Removing the impact of treatment on HbA1c from the SPHR model, running both models only with the conditions that the models have in common and, to a lesser extent, changing the data used to estimate risk factor trajectories, resulted in more consistent model outcomes. CONCLUSIONS: The key driver of difference between the models was the inclusion of extra evidence-based detail in SPHR on the impacts of treatments on HbA1c. The conclusions were less sensitive to the dataset used to inform the risk factor trajectories. These findings strengthen the original cost-effectiveness analyses of the weight management interventions and provide an increased understanding of what is structurally important in the models.

The role of real-world evidence for regulatory and public health decision-making for Accelerated Vaccine Deployment- a meeting report.

The COVID-19 pandemic underscored the need for rapid evidence generation to inform public health decisions beyond the limitations of conventional clinical trials. This report summarises presentations and discussions from a conference on the role of Real-World Evidence (RWE) in expediting vaccine deployment. Attended by regulatory bodies, public health entities, and industry experts, the gathering was a collaborative exchange of experiences and recommendations for leveraging RWE for vaccine deployment. RWE proved instrumental in refining decision-making processes to optimise dosing regimens, enhance guidance on target populations, and steer vaccination strategies against emerging variants. Participants felt that RWE was successfully integrated into lifecycle management, encompassing boosters and safety considerations. However, challenges emerged, prompting a call for improvements in data quality, standardisation, and availability, acknowledging the variability and potential inaccuracies in data across diverse healthcare systems. Regulatory transparency should also be prioritised to foster public trust, and improved collaborations with governments are needed to streamline data collection and navigate data privacy regulations. Moreover, building and sustaining resources, expertise, and infrastructure in LMICs emerged as imperative for RWE-generating capabilities. Continued stakeholder collaboration and securing adequate funding emerged as vital pillars for advancing the use of RWE in shaping responsive and effective public health strategies.

Sociodemographic and socioeconomic disparities in COVID-19 vaccine uptake in Belgium: a nationwide record linkage study.

BACKGROUND: Recent studies have identified important social inequalities in SARS-CoV-2 infections and related COVID-19 outcomes in the Belgian population. The aim of our study was to investigate the sociodemographic and socioeconomic characteristics associated with the uptake of COVID-19 vaccine in Belgium. METHODS: We conducted a cross-sectional analysis of the uptake of a first COVID-19 vaccine dose among 5 342 110 adults (≥18 years) in Belgium on 31 August 2021. We integrated data from four national data sources: the Belgian vaccine register (vaccination status), COVID-19 Healthdata (laboratory test results), DEMOBEL (sociodemographic/socioeconomic data) and the Common Base Register for HealthCare Actors (individuals licensed to practice a healthcare profession in Belgium). We used multivariable logistic regression analysis for identifying characteristics associated with not having obtained a first COVID-19 vaccine dose in Belgium and for each of its three regions (Flanders, Brussels and Wallonia). RESULTS: During the study period, 10% (536 716/5 342 110) of the Belgian adult population included in our study sample was not vaccinated with a first COVID-19 vaccine dose. A lower COVID-19 vaccine uptake was found among young individuals, men, migrants, single parents, one-person households and disadvantaged socioeconomic groups (with lower levels of income and education, unemployed). Overall, the sociodemographic and socioeconomic disparities were comparable for all regions. CONCLUSIONS: The identification of sociodemographic and socioeconomic disparities in COVID-19 vaccination uptake is critical to develop strategies guaranteeing a more equitable vaccination coverage of the Belgian adult population.

A discrete choice experiment to understand public preferences and priorities for risk-stratified bowel cancer screening programmes in the UK.

OBJECTIVE: Public acceptability of bowel cancer screening programmes must be maintained, including if risk stratification is introduced. We aimed to describe and quantify preferences for different attributes of risk-stratified screening programmes amongst the UK population, focussing on who to invite for bowel screening. METHODS: We conducted a discrete choice experiment (DCE) including the following attributes: risk factors used to estimate bowel cancer risk (age plus/minus sex, lifestyle factors and genetics); personalisation of risk feedback; risk stratification strategy plus resource implications; default screening in the case of no risk information; number of deaths prevented by screening; and number experiencing physical harm from screening. We used the results of conditional logit regression models to estimate the importance of each attribute, willingness to trade-off between the attributes, and preferences for different programmes using contemporary risk scores and models. RESULTS: 1196 respondents completed the survey, generating 21,528 DCE observations. Deaths prevented was the most influential attribute on respondents' decision-making (contributing to 58.8% of the choice), followed by harms experienced (15.9%). For every three additional deaths prevented, respondents were willing to accept an additional screening harm per 100,000 people. Risk factors and risk stratification strategy contributed to just 11.1% and 3.6% of the choice, respectively. Although the influence on decision-making was small, respondents favoured more personalised feedback. CONCLUSIONS: Bowel cancer screening programmes that improve cancer outcomes, particularly by preventing more deaths amongst those screened, are most preferred by the public. Optimising risk prediction models, developing public communication, and readying infrastructure should be prioritised for implementation.

Mild hypoxia-induced structural and functional changes of the hippocampal network.

Hypoxia causes structural and functional changes in several brain regions, including the oxygen-concentration-sensitive hippocampus. We investigated the consequences of mild short-term hypoxia on rat hippocampus in vivo. The hypoxic group was treated with 16% O2 for 1 h, and the control group with 21% O2. Using a combination of Gallyas silver impregnation histochemistry revealing damaged neurons and interneuron-specific immunohistochemistry, we found that somatostatin-expressing inhibitory neurons in the hilus were injured. We used 32-channel silicon probe arrays to record network oscillations and unit activity from the hippocampal layers under anaesthesia. There were no changes in the frequency power of slow, theta, beta, or gamma bands, but we found a significant increase in the frequency of slow oscillation (2.1-2.2 Hz) at 16% O2 compared to 21% O2. In the hilus region, the firing frequency of unidentified interneurons decreased. In the CA3 region, the firing frequency of some unidentified interneurons decreased while the activity of other interneurons increased. The activity of pyramidal cells increased both in the CA1 and CA3 regions. In addition, the regularity of CA1, CA3 pyramidal cells' and CA3 type II and hilar interneuron activity has significantly changed in hypoxic conditions. In summary, a low O2 environment caused profound changes in the state of hippocampal excitatory and inhibitory neurons and network activity, indicating potential changes in information processing caused by mild short-term hypoxia.

Implementation of risk stratification within bowel cancer screening: a community jury study exploring public acceptability and communication needs.

BACKGROUND: Population-based cancer screening programmes are shifting away from age and/or sex-based screening criteria towards a risk-stratified approach. Any such changes must be acceptable to the public and communicated effectively. We aimed to explore the social and ethical considerations of implementing risk stratification at three different stages of the bowel cancer screening programme and to understand public requirements for communication. METHODS: We conducted two pairs of community juries, addressing risk stratification for screening eligibility or thresholds for referral to colonoscopy and screening interval. Using screening test results (where applicable), and lifestyle and genetic risk scores were suggested as potential stratification strategies. After being informed about the topic through a series of presentations and discussions including screening principles, ethical considerations and how risk stratification could be incorporated, participants deliberated over the research questions. They then reported their final verdicts on the acceptability of risk-stratified screening and what information should be shared about their preferred screening strategy. Transcripts were analysed using codebook thematic analysis. RESULTS: Risk stratification of bowel cancer screening was acceptable to the informed public. Using data within the current system (age, sex and screening results) was considered an obvious next step and collecting additional data for lifestyle and/or genetic risk assessment was also preferable to age-based screening. Participants acknowledged benefits to individuals and health services, as well as articulating concerns for people with low cancer risk, potential public misconceptions and additional complexity for the system. The need for clear and effective communication about changes to the screening programme and individual risk feedback was highlighted, including making a distinction between information that should be shared with everyone by default and additional details that are available elsewhere. CONCLUSIONS: From the perspective of public acceptability, risk stratification using current data could be implemented immediately, ahead of more complex strategies. Collecting additional data for lifestyle and/or genetic risk assessment was also considered acceptable but the practicalities of collecting such data and how the programme would be communicated require careful consideration.

Protection against COVID-19 hospitalisation conferred by primary-series vaccination with AZD1222 in non-boosted individuals: first vaccine effectiveness results of the European COVIDRIVE study and meta-regression analysis.

Background: Vaccine effectiveness (VE) studies with long-term follow-up are needed to understand durability of protection against severe COVID-19 outcomes conferred by primary-series vaccination in individuals not receiving boosters. COVIDRIVE is a European public-private partnership evaluating brand-specific vaccine effectiveness (VE). We report a prespecified interim analysis of primary-series AZD1222 (ChAdOx1 nCoV-19) VE. Methods: Seven Study Contributors in Europe collected data on individuals aged ≥18 years who were hospitalised with severe acute respiratory infection (June 1st, 2021-September 5th, 2022) and eligible for COVID-19 vaccination prior to hospitalisation. In this test-negative case-control study, individuals were defined as test-positive cases or test-negative controls (SARS-CoV-2 RT-PCR) and were either fully vaccinated (two AZD1222 doses, 4-12 weeks apart, completed ≥14 days prior to symptom onset; no booster doses) or unvaccinated (no COVID-19 vaccine prior to hospitalisation). The primary objective was to estimate AZD1222 VE against COVID-19 hospitalisation. A literature review and meta-regression were conducted to contextualise findings on durability of protection. Findings: 761 individuals were included during the 15-month analysis period. Overall AZD1222 VE estimate was 72.8% (95% CI, 53.4-84.1). VE was 93.8% (48.6-99.3) in participants who received second AZD1222 doses ≤8 weeks prior to hospitalisation, with spline-based VE estimates demonstrating protection (VE ≥ 50%) 30 weeks post-second dose. Meta-regression analysis (data from seven publications) showed consistent results, with ≥80% protection against COVID-19 hospitalisation through ∼43 weeks post-second dose, with some degree of waning. Interpretation: Primary-series AZD1222 vaccination confers protection against COVID-19 hospitalisation with enduring levels of VE through ≥6 months. Funding: AstraZeneca.

COVID-19 vaccine effectiveness against symptomatic infection and hospitalisation in Belgium, July 2021 to May 2022.

BackgroundThe Belgian COVID-19 vaccination campaign aimed to reduce disease spread and severity.AimWe estimated SARS-CoV-2 variant-specific vaccine effectiveness against symptomatic infection (VEi) and hospitalisation (VEh), given time since vaccination and prior infection.MethodsNationwide healthcare records from July 2021 to May 2022 on testing and vaccination were combined with a clinical hospital survey. We used a test-negative design and proportional hazard regression to estimate VEi and VEh, controlling for prior infection, time since vaccination, age, sex, residence and calendar week of sampling.ResultsWe included 1,932,546 symptomatic individuals, of whom 734,115 tested positive. VEi against Delta waned from an initial estimate of 80% (95% confidence interval (CI): 80-81) to 55% (95% CI: 54-55) 100-150 days after the primary vaccination course. Booster vaccination increased initial VEi to 85% (95% CI: 84-85). Against Omicron, an initial VEi of 33% (95% CI: 30-36) waned to 17% (95% CI: 15-18), while booster vaccination increased VEi to 50% (95% CI: 49-50), which waned to 20% (95% CI: 19-21) 100-150 days after vaccination. Initial VEh for booster vaccination decreased from 96% (95% CI: 95-96) against Delta to 87% (95% CI: 86-89) against Omicron. VEh against Omicron waned to 73% (95% CI: 71-75) 100-150 days after booster vaccination. While recent prior infections conferred higher protection, infections occurring before 2021 remained associated with significant risk reduction against symptomatic infection. Vaccination and prior infection outperformed vaccination or prior infection only.ConclusionWe report waning and a significant decrease in VEi and VEh from Delta to Omicron-dominant periods. Booster vaccination and prior infection attenuated these effects.

Dietary Approaches to the Management Of type 2 Diabetes (DIAMOND) in primary care: A protocol for a cluster randomised trial.

INTRODUCTION: There is strong evidence that type 2 diabetes (T2D) remission can be achieved by adopting a low-energy diet achieved through total dietary replacement products. There is promising evidence that low-carbohydrate diets can achieve remission of T2D. The Dietary Approaches to the Management of type 2 Diabetes (DIAMOND) programme combines both approaches in a behaviourally informed low-energy, low-carbohydrate diet for people with T2D, delivered by nurses in primary care. This trial compares the effectiveness of the DIAMOND programme to usual care in inducing remission of T2D and in reducing risk of cardiovascular disease. METHODS AND ANALYSIS: We aim to recruit 508 people in 56 practices with T2D diagnosed within 6 years, who are demographically representative of the UK population. We will allocate general practices, based on ethnicity and socioeconomic status, to provide usual care for diabetes or offer the DIAMOND programme. Participants in practices offering DIAMOND will see the nurse seven times over 6 months. At baseline, 6 months, and 1 year we will measure weight, blood pressure, HbA1c, lipid profile and risk of fatty liver disease. The primary outcome is diabetes remission at 1 year, defined as HbA1c < 48 mmol/mol and off glucose-lowering medication for at least 6 months. Thereafter, we will assess whether people resume treatment for diabetes and the incidence of microvascular and macrovascular disease through the National Diabetes Audit. Data will be analysed using mixed-effects generalised linear models. This study has been approved by the National Health Service Health Research Authority Research Ethics Committee (Ref: 22/EM/0074). TRIAL REGISTRATION NUMBER: ISRCTN46961767.

Vaccine effectiveness against transmission of alpha, delta and omicron SARS-COV-2-infection, Belgian contact tracing, 2021-2022.

OBJECTIVES: Vaccine effectiveness against transmission (VET) of SARS-CoV-2-infection can be estimated from secondary attack rates observed during contact tracing. We estimated VET, the vaccine-effect on infectiousness of the index case and susceptibility of the high-risk exposure contact (HREC). METHODS: We fitted RT-PCR-test results from HREC to immunity status (vaccine schedule, prior infection, time since last immunity-conferring event), age, sex, calendar week of sampling, household, background positivity rate and dominant VOC using a multilevel Bayesian regression-model. We included Belgian data collected between January 2021 and January 2022. RESULTS: For primary BNT162b2-vaccination we estimated initial VET at 96% (95%CI 95-97) against Alpha, 87% (95%CI 84-88) against Delta and 31% (95%CI 25-37) against Omicron. Initial VET of booster-vaccination (mRNA primary and booster-vaccination) was 87% (95%CI 86-89) against Delta and 68% (95%CI 65-70) against Omicron. The VET-estimate against Delta and Omicron decreased to 71% (95%CI 64-78) and 55% (95%CI 46-62) respectively, 150-200 days after booster-vaccination. Hybrid immunity, defined as vaccination and documented prior infection, was associated with durable and higher or comparable (by number of antigen exposures) protection against transmission. CONCLUSIONS: While we observed VOC-specific immune-escape, especially by Omicron, and waning over time since immunization, vaccination remained associated with a reduced risk of SARS-CoV-2-transmission.

Effectiveness and cost-effectiveness of referral to a commercial open group behavioural weight management programme in adults with overweight and obesity: 5-year follow-up of the WRAP randomised controlled trial.

BACKGROUND: There is evidence that commercially available behavioural weight management programmes can lead to short-term weight loss and reductions in glycaemia. Here, we aimed to provide the 5-year impact and cost-effectiveness of these interventions compared with a brief intervention. METHODS: WRAP was a non-blinded, parallel-group randomised controlled trial (RCT). We recruited from primary care practices in England and randomly assigned participants to one of three interventions (brief intervention, 12-week open-group behavioural programme [WW, formerly Weight Watchers], or a 52-week open-group WW behavioural programme) in an uneven (2:5:5) allocation. Participants were followed up 5 years after randomisation using data from measurement visits at primary care practices or a research centre, review of primary care electronic medical notes, and self-report questionnaires. The primary outcome was change in weight at 5 years follow-up, assessed using analysis of covariance. We also estimated cost-effectiveness of the intervention. This study is registered at Current Controlled Trials, ISRCTN64986150. FINDINGS: Between Oct 18, 2012, and Feb 10, 2014, we recruited 1269 eligible participants (two participants were randomly assigned but not eligible and therefore excluded) and 1040 (82%) consented to be approached about additional follow-up and to have their medical notes reviewed at 5 years. The primary outcome (weight) was ascertained for 871 (69%) of 1267 eligible participants. Mean duration of follow-up was 5·1 (SD 0·3) years. Mean weight change from baseline to 5 years was -0·46 (SD 8·31) kg in the brief intervention group, -1·95 (9·55) kg in the 12-week programme group, and -2·67 (9·81) kg in the 52-week programme. The adjusted difference in weight change was -1·76 (95% CI -3·68 to 0·17) kg between the 52-week programme and the brief intervention; -0·80 (-2·13 to 0·54) kg between the 52-week and the 12-week programme; and -0·96 (-2·90 to 0·97) kg between the 12-week programme and the brief intervention. During the trial, the 12-week programme incurred the lowest cost and produced the highest quality-adjusted life-years (QALY). Simulations beyond 5 years suggested that the 52-week programme would deliver the highest QALYs at the lowest cost and would be the most cost-effective. No participants reported adverse events related to the intervention. INTERPRETATION: Although the difference in weight change between groups was not statistically significant, some weight loss was maintained at 5 years after an open-group behavioural weight management programme. Health economic modelling suggests that this could have important implications to reduce the incidence of weight-related disease and these interventions might be cost-saving. FUNDING: The UK National Institute for Health and Care Research Programme Grants for Applied Research and the Medical Research Council.

Triazole-derivatized near-infrared cyanine dyes enable local functional fluorescent imaging of ocular inflammation.

Near-infrared (NIR) chemical fluorophores are promising tools for in-vivo imaging in real time but often succumb to rapid photodegradation. Indocyanine green (ICG) is the only NIR dye with regulatory approval for ocular imaging in humans; however, ICG, when employed for applications such as labelling immune cells, has limited sensitivity and does not allow precise detection of specific inflammatory events, for example leukocyte recruitment during uveitic flare-ups. We investigated the potential use of photostable novel triazole NIR cyanine (TNC) dyes for detecting and characterising activated T-cell activity within the eye. Three TNC dyes were evaluated for ocular cytotoxicity in-vitro using a MTT assay and optimised concentrations for intraocular detection within ex-vivo porcine eyes after topical application or intracameral injections of the dyes. TNC labelled T-cell tracking experiments and mechanistic studies were also performed in-vitro. TNC-1 and TNC-2 dyes exhibited greater fluorescence intensity than ICG at 10 µM, whereas TNC-3 was only detectable at 100 µM within the porcine eye. TNC dyes did not demonstrate any ocular cell toxicity at working concentrations of 10 µM. CD4+T-cells labelled with TNC-1 or TNC-2 were detected within the porcine eye, with TNC-1 being brighter than TNC-2. Detection of TNC-1 and TNC-2 into CD4+T-cells was prevented by prior incubation with dynole 34-2 (50 µM), suggesting active uptake of these dyes via dynamin-dependent processes. The present study provides evidence that TNC dyes are suitable to detect activated CD4+T-cells within the eye with potential as a diagnostic marker for ocular inflammatory diseases.

Estimating the impact of changes in weight and BMI on EQ-5D-3L: a longitudinal analysis of a behavioural group-based weight loss intervention.

PURPOSE: To estimate the association between changes in BMI and changes in Health-Related Quality of Life (EQ-5D-3L). METHODS: The WRAP trial was a multicentre, randomised controlled trial with parallel design and recruited 1267 adults (BMI ≥ 28 kg/m2). Participants were allocated to Brief Intervention, a Commercial weight management Programme (WW, formerly Weight Watchers) for 12 weeks, or the same Programme for 52 weeks. Participants were assessed at 0, 3, 12, 24, and 60 months. We analysed the relationship between BMI and EQ-5D-3L, adjusting for age and comorbidities, using a fixed effects model. Test for attrition, model specification and missing data were conducted. Secondary analyses investigated a non-symmetric gradient for weight loss vs. regain. RESULTS: A unit increase in BMI was associated with a - 0.011 (95% CI - 0.01546, - 0.00877) change in EQ-5D-3L. A unit change in BMI between periods of observation was associated with - 0.016 017 (95% CI - 0.0077009, - 0.025086) change in EQ-5D-3L. The negative association was reduced during weight loss, as opposed to weight gain, but the difference was not statistically significant. CONCLUSIONS: We have identified a strong and statistically significant negative relationship between BMI changes and HRQoL. These estimates could be used in economic evaluations of weight loss interventions to inform policymaking. CLINICAL TRIAL REGISTRATION: This trial was registered with Current Controlled Trials, number ISRCTN82857232.

Modelling cost-effective strategies for minimising socioeconomic inequalities in colorectal cancer screening outcomes in England.

Colorectal cancer (CRC) incidence and mortality is higher in socioeconomically deprived groups for a variety of reasons, but is exacerbated by poorer screening uptake. However, many strategies for improving screening participation exist. This analysis aimed to model the impact of screening on CRC inequalities in England and then compare different strategies for increasing participation, to determine the most cost-effective methods for reducing screening-induced inequalities. An existing health economic model, Microsimulation Model in Cancer of the Bowel was adapted. Screening-eligible individuals were simulated to investigate the impact of screening on CRC inequalities. Following this, four strategies for promoting screening participation were compared: 1) annual re-invitation of screening non-participants; 2) a national media advertising campaign; 3) text message reminders for non-participants; 4) health promotion in deprived populations. Cost-effectiveness, CRC outcomes, resource impacts and effects on CRC inequalities were assessed. Inequalities analysis was based on age-standardised CRC mortality by socioeconomic group. Screening was found to be highly cost-effective but CRC inequalities increased as screening effectiveness improved. Annual re-invitation of non-participants was most cost-effective for promoting particiption (incremental cost-effectiveness ratio = £4404 per quality-adjusted life-year), reducing CRC mortality (11,129 deaths averted), and reducing screening-induced inequality (slope of inequalities reduced from 20.80 to 19.38), although it required 42% more screening kits to be sent out. Other strategies were cost-effective compared with screening alone, and improved CRC outcomes, but had varying impacts on inequalities. Whilst bowel cancer screening increases socioeconomic inequalities in CRC mortality, effective and cost-effective strategies are available for mitigating screening-induced inequalities.

The health, cost and equity impacts of restrictions on the advertisement of high fat, salt and sugar products across the transport for London network: a health economic modelling study.

BACKGROUND: Policies aimed at restricting the marketing of high fat, salt and sugar products have been proposed as one way of improving population diet and reducing obesity. In 2019, Transport for London implemented advertising restrictions on high fat, salt and sugar products. A controlled interrupted time-series analysis comparing London with a north of England control, suggested that the advertising restrictions had resulted in a reduction in household energy purchases. The aim of the study presented here was to estimate the health benefits, cost savings and equity impacts of the Transport for London policy using a health economic modelling approach, from an English National Health Service and personal social services perspective. METHODS: A diabetes prevention microsimulation model was modified to incorporate the London population and Transport for London advertising intervention. Conversion of calorie to body mass index reduction was mediated through an approximation of a mathematical model estimating weight loss. Outcomes gathered included incremental obesity, long-term diabetes and cardiovascular disease events, quality-adjusted life years, healthcare costs saved and net monetary benefit. Slope index of inequality was calculated for proportion of people with obesity across socioeconomic groups to assess equity impacts. RESULTS: The results show that the Transport for London policy was estimated to have resulted in 94,867 (4.8%) fewer individuals with obesity, and to reduce incidence of diabetes and cardiovascular disease by 2,857 and 1,915 cases respectively within three years post intervention. The policy would produce an estimated 16,394 additional quality-adjusted life-years and save £218 m in NHS and social care costs over the lifetime of the current population. Greater benefits (e.g. a 37% higher gain in quality-adjusted life-years) were expected to accrue to individuals from the most socioeconomically deprived groups compared to the least deprived. CONCLUSIONS: This analysis suggests that there are considerable potential health and economic gains from restricting the advertisement of high fat, salt and sugar products. The population health and economic impacts of the Transport for London advertising restrictions are likely to have reduced health inequalities in London.

Optimizing the Design of a Repeated Fecal Immunochemical Test Bowel Cancer Screening Programme With a Limited Endoscopy Capacity From a Health Economic Perspective.

OBJECTIVES: In 2016, it was announced that the fecal immunochemical test (FIT) would replace the guaiac fecal occult blood test in the UK Bowel Cancer Screening Programme. England has limited endoscopy capacity. This study informed decision making by determining the most cost-effective FIT screening strategy (age range, frequency, and FIT threshold) under a constrained endoscopy capacity. METHODS: An economic model with a colorectal cancer natural history component was used to model 60 221 screening strategies with first screening at age 50 to 60 years, screening interval of 1 to 6 years, 3+ screening episodes, and FIT integer threshold of 20 to 180 µg hemoglobin/g feces. Screening strategies requiring the same endoscopy capacity were compared to determine the characteristics of the most cost-effective strategies. RESULTS: With 50 000 annual screening referral colonoscopies, the 20 most cost-effective strategies had a starting age of 50 to 53 years, 2-yearly screening, 7 or 8 rounds of screening, and FIT threshold of 127 to 166. Compared with a 2-yearly screening interval, screening less frequently (3-, 4-, 5-, or 6-yearly) with a more sensitive FIT was less cost-effective. CONCLUSIONS: The UK Bowel Cancer Screening Programme should use a 2-yearly FIT screening interval. When endoscopy capacity increases, the screening starting age should be reduced first followed by reducing the FIT threshold. These findings are relevant for other colorectal cancer screening programs with constrained endoscopy capacity.

A community jury study exploring the public acceptability of using risk stratification to determine eligibility for cancer screening.

INTRODUCTION: Using risk stratification to determine eligibility for cancer screening is likely to improve the efficiency of screening programmes by targeting resources towards those most likely to benefit. We aimed to explore the implications of this approach from a societal perspective by understanding public views on the most acceptable stratification strategies. METHODS: We conducted three online community juries with 9 or 10 participants in each. Participants were purposefully sampled by age (40-79 years), sex, ethnicity, social grade and English region. On the first day, participants were informed of the potential benefits and harms of cancer screening and the implications of different ways of introducing stratification using scenarios based on phenotypic and genetic risk scores. On the second day, participants deliberated to reach a verdict on the research question, 'Which approach(es) to inviting people to screening are acceptable, and under what circumstances?' Deliberations and feedback were recorded and analysed using thematic analysis. RESULTS: Across the juries, the principle of risk stratification was generally considered to be an acceptable approach for determining eligibility for screening. Disregarding increasing capacity, the participants considered it to enable efficient resource allocation to high-risk individuals and could see how it might help to save lives. However, there were concerns regarding fair implementation, particularly how the risk assessment would be performed at scale and how people at low risk would be managed. Some favoured using the most accurate risk prediction model whereas others thought that certain risk factors should be prioritized (particularly factors considered as non-modifiable and relatively stable, such as genetics and family history). Transparently justifying the programme and public education about cancer risk emerged as important contributors to acceptability. CONCLUSION: Using risk stratification to determine eligibility for cancer screening was acceptable to informed members of the public, particularly if it included risk factors they considered fair and when communicated transparently. PATIENT OR PUBLIC CONTRIBUTION: Two patient and public involvement representatives were involved throughout this study. They were not involved in synthesizing the results but contributed to producing study materials, co-facilitated the community juries and commented on the interpretation of the findings and final report.