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.

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.

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.

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.

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.

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.

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.

Modelling the impact of the coronavirus pandemic on bowel cancer screening outcomes in England: A decision analysis to prepare for future screening disruption.

The English Bowel Cancer Screening Programme invites people between the ages of 60 and 74 to take a Faecal Immunochemical Test every two years. This programme was interrupted during the coronavirus pandemic. The research aimed: (1) to estimate the impact of colorectal cancer (CRC) Faecal Immunochemical Test screening pauses of different lengths and the actual coronavirus-related screening pause in England, and (2) to analyse the most effective and cost-effective strategies to re-start CRC screening to prepare for future disruptions. The analysis used the validated Microsimulation Model in Cancer of the Bowel built in the R programming language. The model simulated the life course of a representative English screening population from 2019, by age, sex, socio-economic deprivation, and prior screening history. The modelling scenarios were based on assumptions and data from screening centres in England. Pausing bowel screening in England due to coronavirus pandemic is predicted to increase CRC deaths by 0.73% within 10 years and 0.13% over the population's lifetime, with excess deaths due to peak in 2023. More deaths are expected in men and people aged over 70. Pausing screening for longer would result in greater additional CRC cases and deaths. Postponing screening for everyone would be the most cost-effective strategy to minimise the impact of screening disruption without any additional endoscopy capacity. If endoscopy capacity can be increased, temporarily raising the Faecal Immunochemical Test threshold to 190 µg/g may help to minimise CRC deaths, particularly if screening programmes start from age 50 in the future.

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.

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.

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.

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.

Using health economic modelling to inform the design and development of an intervention: estimating the justifiable cost of weight loss maintenance in the UK.

BACKGROUND: There is a need to develop cost-effective weight loss maintenance interventions to prolong the positive impact of weight loss on health outcomes. Conducting pre-trial health economic modelling is recommended to inform the design and development of behavioural interventions. We aimed to use health economic modelling to estimate the maximum cost per-person (justifiable cost) of a cost-effective behavioural weight loss maintenance intervention, given an estimated intervention effect for individuals with: i) a Body Mass Index (BMI) of 28 kg/m2 or above without diabetes and ii) a diagnosis of type 2 diabetes prescribed a single non-insulin diabetes medication. METHODS: The School for Public Health Research Diabetes prevention model was used to estimate the lifetime Quality-adjusted life year (QALY) gains, healthcare costs, and maximum justifiable cost associated with a weight loss maintenance intervention. Based on a meta-analysis, the estimated effect of a weight loss maintenance intervention following a 9 kg weight loss, was a regain of 1.33 kg and 4.38 kg in years one and two respectively compared to greater regain of 2.84 kg and 5.6 kg in the control group. Sensitivity analysis was conducted around the rate of regain, duration of effect and initial weight loss. RESULTS: The justifiable cost for a weight loss maintenance intervention at an ICER of £20,000 per QALY was £104.64 for an individual with a BMI of 28 or over and £88.14 for an individual with type 2 diabetes. Within sensitivity analysis, this varied from £36.42 to £203.77 for the former, and between £29.98 and £173.05 for the latter. CONCLUSIONS: Researchers developing a weight loss maintenance intervention should consider these maximum justifiable cost estimates and the potential impact of the duration of effect and initial weight loss when designing intervention content and deciding target populations. Future research should consider using the methods demonstrated in this study to use health economic modelling to inform the design and budgetary decisions in the development of a behavioural interventions.

Outbreak of invasive meningococcal disease caused by a meningococcus serogroup B in a nursery school, Wallonia, Belgium, 2018.

Although most invasive meningococcal disease (IMD) cases are sporadic without identified transmission links, outbreaks can occur. We report three cases caused by meningococcus B (MenB) at a Belgian nursery school over 9 months. The first two cases of IMD occurred in spring and summer 2018 in healthy children (aged 3-5 years) attending the same classroom. Chemoprophylaxis was given to close contacts of both cases following regional guidelines. The third case, a healthy child of similar age in the same class as a sibling of one case, developed disease in late 2018. Microbiological analyses revealed MenB with identical finetype clonal complex 269 for Case 1 and 3 (unavailable for Case 2). Antimicrobial susceptibility testing revealed no antibiotic resistance. Following Case 3, after multidisciplinary discussion, chemoprophylaxis and 4CMenB (Bexsero) vaccination were offered to close contacts. In the 12-month follow-up of Case 3, no additional cases were reported by the school. IMD outbreaks are difficult to manage and generate public anxiety, particularly in the case of an ongoing cluster, despite contact tracing and management. This outbreak resulted in the addition of MenB vaccination to close contacts in Wallonian regional guidelines, highlighting the potential need and added value of vaccination in outbreak management.

Assessment of necroptosis in the retina in a repeated primary ocular blast injury mouse model.

Primary blast injury (caused by the initial rapid increase in pressure following an explosive blast) to the retina and optic nerve (ON) causes progressive visual loss and neurodegeneration. Military personnel are exposed to multiple low-overpressure blast waves, which may be in quick succession, such as during breacher training or in combat. We investigated the necroptotic cell death pathway in the retina in a mouse repeated primary ocular blast injury (rPBI) model using immunohistochemistry. We further evaluated whether intravitreal injections of a potent necroptosis inhibitor, Necrostatin-1s (Nec-1s), protects the retina and ON axons by retinal ganglion cells (RGC) counts, ON axonal counting and optical coherence tomography (OCT) analysis of vitreous haze. Receptor interacting protein kinase (RIPK) 3, increased in the inner plexiform layer 2 days post injury (dpi) and persisted until 14 dpi, whilst RIPK1 protein expression did not change after injury. The number of degenerating ON axons was increased at 28 dpi but there was no evidence of a reduction in the number of intact ON axons or RNA-binding protein with multiple splicing (RBPMS)+ RGC in the retina by 28 dpi in animals not receiving any intravitreal injections. But, when intravitreal injections (vehicle or Nec-1s) were given there was a significant reduction in RBPMS+ RGC numbers, suggesting that rPBI with intraocular injections is damaging to RGC. There were fewer RGC lost after Nec-1s than vehicle injection, but there was no effect of Nec-1s or vehicle treatment on the number of degenerating axons. OCT analysis demonstrated no effect of rPBI on vitreous haze, but intravitreal injection combined with rPBI increased vitreous haze (P = 0.004). Whilst necroptosis may be an active cell death signalling pathway after rPBI, its inhibition did not prevent cell death, and intravitreal injections in combination with rPBI increased vitreous inflammation and reduced RBPMS+ RGC numbers, implying intravitreal injection is not an ideal method for drug delivery after rPBI.

External Validation of a Colorectal Cancer Model Against Screening Trial Long-Term Follow-Up Data.

BACKGROUND: The University of Sheffield School of Health and Related Research (ScHARR) Bowel Cancer Screening Model has been used previously to make decisions about colorectal cancer screening strategies in England. OBJECTIVES: The objective of this study was to perform an external validation of the ScHARR model against long-term follow-up data about colorectal cancer (CRC) incidence and mortality reductions due to screening, from the Nottingham trial of guaiac faecal occult blood testing for CRC, and the UK Flexible Sigmoidoscopy Screening Trial. METHODS: The ScHARR model was adapted prior to validation to reflect the setting of each trial in terms of population characteristics, details of screening and surveillance programs, uptake of screening, and further investigations and study follow-up. The impact of using current versus historical CRC incidence and mortality data in the validation was also examined by carrying out a series of analyses in which historical data from different years was included in the model. RESULTS: The ScHARR model was able to predict CRC incidence and mortality rate/hazard ratios from both trials to well within the 95% confidence intervals in the observed data. While it was less accurate in predicting absolute incidence and mortality rates, modeling historical incidence and mortality data enabled these predictions to be improved considerably. CONCLUSION: The ScHARR model is able to replicate the long-term relative benefit from screening observed in 2 large-scale UK-based screening trials and can therefore be considered to be an appropriate tool to facilitate decision making around the English bowel cancer screening program.

Low hepatitis C prevalence in Belgium: implications for treatment reimbursement and scale up.

BACKGROUND: Prevalence data of chronic hepatitis C virus (HCV) infection are needed to estimate the budgetary impact of reimbursement of direct-acting antivirals (DAAs). In Belgium, the restricted reimbursement criteria are mainly guided by regional seroprevalence estimates of 0.87% from 1993 to 1994. In this first Belgian nationwide HCV prevalence study, we set out to update the seroprevalence and prevalence of chronic HCV infection estimates in the Belgian general population in order to guide decisions on DAA reimbursement. METHODS: Residual sera were collected through clinical laboratories. We collected data on age, sex and district. HCV antibody status was determined with ELISA and confirmed with a line-immunoassay (LIA). In specimens with undetermined or positive LIA result, HCV viral load was measured. Specimens were classified seronegative, seropositive with resolved infection, indicative of chronic infection and with undetermined HCV status according to the test outcomes. Results were standardized for age, sex and population per district, and adjusted for clustered sampling. RESULTS: In total 3209 specimens, collected by 28 laboratories, were tested. HCV seropositivity in the Belgian general population was estimated to be 0.22% (95% CI: 0.09-0.54%), and prevalence of chronic HCV infection 0.12% (95% CI: 0.03-0.41). In individuals of 20 years and older, these estimates were 0.26% (95% CI: 0.10-0.64%) and 0.13% (95% CI: 0.04-0.43), respectively. Of the total estimated number of HCV seropositive individuals in Belgium, 66% were between 50 and 69 years old. CONCLUSIONS: Prevalence of HCV seropositivity and chronic infection in the Belgian general population were low and comparable to many surrounding countries. These adjusted prevalences can help estimate the cost of reimbursement of DAAs and invite Belgian policy makers to accelerate the scaling up of reimbursement, giving all chronically infected HCV patients a more timely access to treatment.

TGF-ß-induced IOP elevations are mediated by RhoA in the early but not the late fibrotic phase of open angle glaucoma.

Purpose: Elevations in intraocular pressure (IOP) are associated with the development of glaucoma and loss of sight. High transforming growth factor-ß (TGF-ß) 1 levels in the eye's anterior chamber can lead to dysfunctional contractions through RhoA signaling in trabecular meshwork (TM) cells and IOP spikes. Sustained high TGF-ß levels leads to TM fibrosis and sustained increases in IOP. We investigated whether inhibiting RhoA, using a siRNA-mediated RhoA (siRhoA), controls IOP by altering TM expression of fibrosis and contractility-related proteins in a rodent model of glaucoma. Methods: TGF-ß was injected intracamerally twice a week into adult Sprague Dawley rats, and IOP was recorded with tonometry. Animals were euthanized on day 7 and 35 with TM expression of fibrosis and contractility-related proteins, as well as survival of retinal ganglion cells (RGCs) assessed with immunohistochemistry. siRNA against RhoA or enhanced green fluorescent protein (EGFP) was also injected intracamerally into select animals. Successful RhoA knockdown was determined with quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry, and the effects of the knockdown on the parameters above analyzed. Results: TGF-ß caused increased TM contractile proteins and IOP spikes by day 7, sustained increases in IOP from day 15, and TM fibrosis at day 35. siRhoA abolished the transient 7 day IOP rise but not the later sustained IOP increase (due to fibrosis). At 35 days, TGF-ß-related RGC loss was not prevented with siRhoA treatment. Conclusions: We conclude that RhoA signaling mediates the early IOP rise induced by TM cellular changes associated with contractility but not the sustained IOP elevation caused by TM fibrosis. Thus, RhoA therapies offer a clinically relevant opportunity for IOP management, likely through the modulation of TM contractility, but appear to be ineffective in the amelioration of fibrosis.

Screening for Chlamydia trachomatis and Neisseria gonorrhoeae Infections in Men Who Have Sex With Men: Diagnostic Accuracy of Nucleic Acid Amplification Test on Pooled Urine, Anorectal, and Pharyngeal Specimens.

Neisseria gonorrhoeae and Chlamydia trachomatis screening was performed in a cohort of 100 men who have sex with men. A nucleic acid amplification test on a pooled sample of first-pass urine, pharyngeal, and anorectal specimens was compared with results on nonpooled samples. Despite an excellent agreement (Cohen κ, 0.932), pooling specimens reduced test sensitivity to 89.5%.

Estimating the cost-effectiveness of brief interventions for heavy drinking in primary health care across Europe.

Background: Screening and Brief Interventions for alcohol are an effective public health measure to tackle alcohol-related harm, however relatively few countries across the European Union (EU) have implemented them widely. This may be due to a lack of understanding of the specific financial implications of such policies within each country. Methods: A novel 'meta-modelling' approach was developed based on previous SBI cost-effectiveness models for four EU countries. Data were collected on the key factors which drive cost-effectiveness for all 28 EU countries (mean per capita alcohol consumption, proportion of the population to be screened over a 10-year SBI programme; per capita alcohol-attributable mortality; per capita alcohol-attributable morbidity; mean cost of an alcohol-related hospitalisation and mean SBI-delivery staff cost). Regression analysis was used to fit two meta-models estimating net programme costs and Quality-Adjusted Life Years (QALYs) gained, to calculate cost-effectiveness estimates specific to each EU country. Results: Costs are dependent upon the proportion of the population covered by the screening programme, the country-specific per capita mortality and morbidity rate and the country-specific costs of GP care and hospitalisation. QALYs depend on the proportion of the population screened and per capita alcohol consumption. Despite large inter-country variability in factor values, SBI programmes are likely to be cost-effective in 24 out of 28 EU countries and cost-saving in 50% of countries. Conclusion: Implementing national programmes of SBI in primary health care would be a cost-effective means of reducing alcohol-attributable morbidity and deaths in almost all countries of the EU.