Ambient ultraviolet-B radiation, supplements and other factors interact to impact vitamin D status differently depending on ethnicity: A cross-sectional study.

BACKGROUND & AIMS: Many determinants of vitamin D status have been well-described, yet supplementation guidelines largely follow a one-size-for-all model and deficiency remains common. We hypothesised that accounting accurately for ultraviolet-B (UVB) radiation and considering interactions could advance understanding of vitamin D status. METHODS: Asian, Black, and White participants from the UK Biobank cohort were included (N = 438,978). The Tropospheric Emission Monitoring Internet Service provided UVB data which we linked to participants' place of residence. UVB dose over 135 days prior to blood draw was weighted and added, yielding cumulative and weighted UVB (CW-D-UVB). The association between 25(OH)D and selected variables was assessed in multivariable linear regression models with and without interactions, stratified by ethnicity. Predictors were ranked using standardised ß-coefficients. RESULTS: Median 25(OH)D differed by ethnicity (Asian: 25.4 nmol/L (10.2 ng/mL), Black: 30.6 nmol/L (12.2 ng/mL), White: 47.9 nmol/L (19.2 ng/mL), p-value < 0.001). CW-D-UVB was strongly associated with 25(OH)D in all ethnicities. It was the most important predictor in White (ßAsian = 0.15, ßBlack = 0.20, ßWhite = 0.35), whereas supplementation was in Asian and Black participants (ßAsian = 0.30, ßBlack = 0.24, ßWhite = 0.21). We identified statistically significant interactions between BMI:supplementation (all), CW-D-UVB:sex (Asian and White), and CW-D-UVB:age (Black and White), and in White population between CW-D-UVB and supplementation, BMI, and cholesterol. CONCLUSION: Vitamin D deficiency was widespread, particularly among non-White individuals. UVB was a strong predictor of 25(OH)D and the effect was modified by other factors. Findings suggest that accurately measured ambient-UVB radiation and interactions could improve 25(OH)D prediction models, and support personalised approaches to vitamin D optimisation.

Circulating 25-hydroxyvitamin D and survival outcomes of colorectal cancer: evidence from population-based prospective cohorts and Mendelian randomisation.

BACKGROUND: To investigate the association between circulating 25-hydroxyvitamin D (25-OHD) and colorectal cancer (CRC) survival outcomes. METHODS: We conducted analyses among the Study of Colorectal Cancer in Scotland (SOCCS) and the UK Biobank (UKBB). Both cancer-specific survival (CSS) and overall survival (OS) outcomes were examined. The 25-OHD levels were categorised into three groups, and multi-variable Cox-proportional hazard models were applied to estimate hazard ratios (HRs). We performed individual-level Mendelian randomisation (MR) through the generated polygenic risk scores (PRS) of 25-OHD and summary-level MR using the inverse-variance weighted (IVW) method. RESULTS: We observed significantly poorer CSS (HR = 0.65,95%CI = 0.55-0.76,P = 1.03 × 10-7) and OS (HR = 0.66,95%CI = 0.58-0.75,P = 8.15 × 10-11) in patients with the lowest compared to those with the highest 25-OHD after adjusting for covariates. These associations remained across patients with varied tumour sites and stages. However, we found no significant association between 25-OHD PRS and either CSS (HR = 0.98,95%CI = 0.80-1.19,P = 0.83) or OS (HR = 1.07,95%CI = 0.91-1.25,P = 0.42). Furthermore, we found no evidence for causal effects by conducting summary-level MR analysis for either CSS (IVW:HR = 1.04,95%CI = 0.85-1.28,P = 0.70) or OS (IVW:HR = 1.10,95%CI = 0.93-1.31,P = 0.25). CONCLUSION: This study supports the observed association between lower circulating 25-OHD and poorer survival outcomes for CRC patients. Whilst the genotype-specific association between better outcomes and higher 25-OHD is intriguing, we found no support for causality using MR approaches.

Systematic review on gene-sun exposure interactions in skin cancer.

BACKGROUND: The risk of skin cancer is determined by environmental factors like ultraviolet radiation (UVR), personal habits like time spent outdoors and genetic factors. This review aimed to survey existing studies in gene-environment (GxE) interaction on skin cancer risk, and report on GxE effect estimates. METHODS: We searched Embase, Medline (Ovid) and Web of Science (Core Collection) and included only primary research that reported on GxE on the risk of the three most common types of skin cancer: basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma. Quality assessment followed the Newcastle-Ottawa Scale. Meta-analysis was not possible because no two studies examined the same interaction. This review was registered on PROSPERO (CRD42021238064). RESULTS: In total 260 records were identified after exclusion of duplicates. Fifteen studies were included in the final synthesis-12 used candidate gene approach. We found some evidence of GxE interactions with sun exposure, notably, with MC1R, CAT and NOS1 genes in melanoma, HAL and IL23A in BCC and HAL and XRCC1 in SCC. CONCLUSION: Sun exposure seems to interact with genes involved in pigmentation, oxidative stress and immunosuppression, indicating that excessive UV exposure might exhaust oxidative defence and repair systems differentially, dependent on genetic make-up. Further research is warranted to better understand skin cancer epidemiology and develop sun exposure recommendations. A genome-wide approach is recommended as it might uncover unknown disease pathways dependent on UV radiation.

Does fluoride exposure impact on the human microbiome?

Fluoride is added to drinking water in some countries to prevent tooth decay (caries). There is no conclusive evidence that community water fluoridation (CWF) at WHO recommended concentrations for caries prevention has any harmful effects. However, research is ongoing regarding potential effects of ingested fluoride on human neurodevelopment and endocrine dysfunction. Simultaneously, research has emerged highlighting the significance of the human microbiome in gastrointestinal and immune health. In this review we evaluate the literature examining the effect of fluoride exposure on the human microbiome. Unfortunately, none of the studies retrieved examined the effects of ingested fluoridated water on the human microbiome. Animal studies generally examined acute fluoride toxicity following ingestion of fluoridated food and water and conclude that fluoride exposure can detrimentally perturb the normal microbiome. These data are difficult to extrapolate to physiologically relevant human exposure dose ranges and the significance to humans living in areas with CWF requires further investigation. Conversely, evidence suggests that the use of fluoride containing oral hygiene products may have beneficial effects on the oral microbiome regarding caries prevention. Overall, while fluoride exposure does appear to impact the human and animal microbiome, the long-term consequences of this requires further study.

Comprehensive Analysis of Seasonal and Geographical Variation in UVB Radiation Relevant for Vitamin D Production in Europe.

Dermal synthesis, following sun exposure, is the main source of vitamin D. This study characterizes ambient UVB radiation relevant for vitamin D production in Europe. A biological weighing function was applied to data from the Tropospheric Emissions Monitoring Internet Service (TEMIS) for 46 capital cities over an 18-year period (2004-2021) to isolate wavelengths relevant for vitamin D production (D-UVB). Cumulative and weighted D-UVB (CW-D-UVB) were calculated to approximate seasonal vitamin D accumulation and diminution. Monthly 25(OH)D concentration measurements were extracted from published reports. All data were analyzed by location and time. Despite a moderate latitudinal range (35-64° N), we observed large-up to five-fold-regional differences: the highest mean diurnal D-UVB dose of 5.57 kJ/m2 (SD = 3.55 kJ/m2) was observed in Nicosia (Cyprus) and the lowest in Reykjavik (Iceland, 1.16 ± 1.29 kJ/m2). Seasonal differences in diurnal D-UVB dose were even more pronounced, with a median 36-fold difference between annual peak and trough depending on a location (range: 10- to 525-fold). The mean duration of "vitamin D winter" was 126 days but varied widely (4 to 215 days). Monthly CW-D-UVB and 25(OH)D changes were very strongly correlated: the changes in 25(OH)D concentration increased by 12.6 nmol/L for every 100 kJ/m2 increment of CW-D-UVB in population-based studies (r2 = 0.79, p-value = 1.16 × 10-37). Understanding the differences in D-UVB radiation can help understand determinants of vitamin D status and guide region- and season-specific safe and effective sunlight exposure recommendations and vitamin D supplementation guidelines.

Gene-Environment Interactions in Vitamin D Status and Sun Exposure: A Systematic Review with Recommendations for Future Research.

Vitamin D is essential for good health. Dermal vitamin D production is dependent on environmental factors such as season and latitude, and personal factors such as time spent outdoors and genetics. Varying heritability of vitamin D status by season has been reported, suggesting that gene-environment interactions (GxE) may play a key role. Thus, understanding GxE might significantly improve our understanding of determinants of vitamin D status. The objective of this review was to survey the existing methods in GxE on vitamin D studies and report on GxE effect estimates. We searched the Embase, Medline (Ovid), and Web of Science (Core Collection) databases. We included only primary research that reported on GxE effects on vitamin D status using 25-hydroxyvitamin D as a biomarker. Sun exposure was the only environmental exposure identified in these studies. The quality assessment followed the Newcastle-Ottawa Scale for cohort studies. Seven studies were included in the final narrative synthesis. We evaluate the limitations and findings of the available GxE in vitamin D research and provide recommendations for future GxE research. The systematic review was registered on PROSPERO (CRD42021238081).

Statistical power in vitamin D randomized control trials investigating biomarkers as continuous outcomes.

It has long been suspected that mean vitamin D level and differences among individuals in the population might deteriorate power in vitamin D randomised controlled trials (RCTs). However, standard statistical planning tools cannot accommodate these considerations. Here, to accommodate the large within-person and between-people heterogeneity in naturally fluctuating 25-hydroxyvitamin D (25OHD) concentration, a simulation based approach was used to investigate the power and sample size requirements in vitamin D supplementation RCTs looking at the proportion of regulatory T cells, %Tregs, as a continuous outcome. A range of sample sizes, mean increases in 25OHD in the intervention arm, and population 25OHD heterogeneity were tested. We found that in a population with a mean 25OHD of 50▒nmol/L and moderate heterogeneity in 25OHD (defined as inter-quartile range IQR = 20), sample size of approximately 1000 participants per arm is required to achieve 80% power if 25OHD increased by 10▒nmol/L in the intervention arm, compared to 250, < 100 and < 50 participants per arm if this increase was 20▒nmol/L, 40▒nmol/L or 60▒nmol/L, respectively. Thus we conclude that the increase in 25OHD in the intervention arm and population heterogeneity impact the power of vitamin D RCTs substantially. Sample size determination through simulation is a powerful approach for non-standard trials, and the work presented can easily be adopted to other intervention-outcome pairs.

The association between ambient UVB dose and ANCA-associated vasculitis relapse and onset.

BACKGROUND: The aetiology of ANCA-associated vasculitis (AAV) and triggers of relapse are poorly understood. Vitamin D (vitD) is an important immunomodulator, potentially responsible for the observed latitudinal differences between granulomatous and non-granulomatous AAV phenotypes. A narrow ultraviolet B spectrum induces vitD synthesis (vitD-UVB) via the skin. We hypothesised that prolonged periods of low ambient UVB (and by extension vitD deficiency) are associated with the granulomatous form of the disease and an increased risk of AAV relapse. METHODS: Patients with AAV recruited to the Irish Rare Kidney Disease (RKD) (n = 439) and UKIVAS (n = 1961) registries were studied. Exposure variables comprised latitude and measures of ambient vitD-UVB, including cumulative weighted UVB dose (CW-D-UVB), a well-validated vitD proxy. An n-of-1 study design was used to examine the relapse risk using only the RKD dataset. Multi-level models and logistic regression were used to examine the effect of predictors on AAV relapse risk, phenotype and serotype. RESULTS: Residential latitude was positively correlated (OR 1.41, 95% CI 1.14-1.74, p = 0.002) and average vitD-UVB negatively correlated (0.82, 0.70-0.99, p = 0.04) with relapse risk, with a stronger effect when restricting to winter measurements (0.71, 0.57-0.89, p = 0.002). However, these associations were not restricted to granulomatous phenotypes. We observed no clear relationship between latitude, vitD-UVB or CW-D-UVB and AAV phenotype or serotype. CONCLUSION: Our findings suggest that low winter ambient UVB and prolonged vitD status contribute to AAV relapse risk across all phenotypes. However, the development of a granulomatous phenotype does not appear to be directly vitD-mediated. Further research is needed to determine whether sufficient vitD status would reduce relapse propensity in AAV.

Non-adherence to COVID-19 containment behaviours: results from an all-Ireland telephone survey.

BACKGROUND: COVID-19 public health measures like handwashing and social distancing can help stem the spread of the virus. Adherence to guidelines varies between individuals. This study aims to identify predictors of non-adherence to social distancing and handwashing guidelines. METHODS: A cross-sectional weekly telephone survey was conducted over eight weeks (11/06/2020-05/08/2020). The sample included adults resident on the island of Ireland (75:25 split between ROI and NI). Data were collected on demographics, threat perceptions, fear of COVID-19, response efficacy and self-efficacy, response cost and social norms, COVID-19 behaviours, mood, loneliness, and self-reported health. RESULTS: 3011 participants were surveyed. Handwashing non-adherers were more likely to be male (OR: 5.2, 95% CI: 2.4 - 11.3), to have higher levels of loneliness (OR: 1.86, 95% CI: 1.1 - 3.1), and higher perceptions of handwashing costs (OR: 3.4, 95% CI: 2.2 - 5.2). Those reporting rarely engaging in social distancing were more likely to be members of lower socioeconomic groups, to be younger (OR: 0.97, 95% CI: 0.96 - 0.98), male (OR: 1.67, 95% CI: 1.1 - 2.5), healthcare workers (OR: 1.98, 95% CI: 1.1 - 3.4), to report lower mood (OR: 1.72, 95% CI: 1.3 - 2.2), were less likely to live in households with people aged under-18 (OR: 0.75, 95% CI: 0.6 - 0.9), and to have lower fear of COVID-19 (OR: 0.79, 95% CI: 0.6 - 0.9). CONCLUSIONS: Non-adherers to handwashing differ to social distancing non-adherers. Public health messages should target specific demographic groups and different messages are necessary to improve adherence to each behaviour.

An observational and Mendelian randomisation study on vitamin D and COVID-19 risk in UK Biobank.

A growing body of evidence suggests that vitamin D deficiency has been associated with an increased susceptibility to viral and bacterial respiratory infections. In this study, we aimed to examine the association between vitamin D and COVID-19 risk and outcomes. We used logistic regression to identify associations between vitamin D variables and COVID-19 (risk of infection, hospitalisation and death) in 417,342 participants from UK Biobank. We subsequently performed a Mendelian Randomisation (MR) study to look for evidence of a causal effect. In total, 1746 COVID-19 cases (399 deaths) were registered between March and June 2020. We found no significant associations between COVID-19 infection risk and measured 25-OHD levels after adjusted for covariates, but this finding is limited by the fact that the vitamin D levels were measured on average 11 years before the pandemic. Ambient UVB was strongly and inversely associated with COVID-19 hospitalization and death overall and consistently after stratification by BMI and ethnicity. We also observed an interaction that suggested greater protective effect of genetically-predicted vitamin D levels when ambient UVB radiation is stronger. The main MR analysis did not show that genetically-predicted vitamin D levels are causally associated with COVID-19 risk (OR = 0.77, 95% CI 0.55-1.11, P = 0.160), but MR sensitivity analyses indicated a potential causal effect (weighted mode MR: OR = 0.72, 95% CI 0.55-0.95, P = 0.021; weighted median MR: OR = 0.61, 95% CI 0.42-0.92, P = 0.016). Analysis of MR-PRESSO did not find outliers for any instrumental variables and suggested a potential causal effect (OR = 0.80, 95% CI 0.66-0.98, p-val = 0.030). In conclusion, the effect of vitamin D levels on the risk or severity of COVID-19 remains controversial, further studies are needed to validate vitamin D supplementation as a means of protecting against worsened COVID-19.

Media Representations of Science during the First Wave of the COVID-19 Pandemic: A Qualitative Analysis of News and Social Media on the Island of Ireland.

COVID-19 is arguably the most critical science communication challenge of a generation, yet comes in the wake of a purported populist turn against scientific expertise in western societies. This study advances understanding of science-society relations during the COVID-19 pandemic by analysing how science was represented in news and social media coverage of COVID-19 on the island of Ireland. Thematic analysis was performed on a dataset comprising 952 news articles and 603 tweets published between 1 January and 31 May 2020. Three themes characterised the range of meanings attached to science: 'Defining science: Its subjects, practice and process', 'Relating to science: Between veneration and suspicion' and 'Using science: As solution, policy and rhetoric'. The analysis suggested that the COVID-19 pandemic represented a platform to highlight the value, philosophy, process and day-to-day activity of scientific research. However, the study also identified risks the pandemic might pose to science communication, including feeding public alienation by disparaging lay understandings, reinforcing stereotypical images of scientists, and amplifying the politicisation of scientific statements.

Bordering on crisis: A qualitative analysis of focus group, social media, and news media perspectives on the Republic of Ireland-Northern Ireland border during the 'first wave' of the COVID-19 pandemic.

RATIONALE: International border controls were among the earliest and most effective of measures to constrain transmission of COVID-19. However, such measures are complex when established borders are open yet politically contested, as for the border that divides the Republic of Ireland (ROI) from Northern Ireland (NI). Understanding how this border affected the everyday lives of both populations during the pandemic is important for informing the continued development of effective responses to COVID-19 and future health crises. OBJECTIVE: This multi-methods study aimed to explore public perspectives on how the ROI-NI border affected experiences of and responses to the 'first wave' of the pandemic. METHOD: The study collated data from focus groups (n = 8), news articles (n = 967), and Twitter posts (n = 356) on the island of Ireland, which mentioned the ROI-NI border in relation to COVID-19. Thematic analysis was used to explore the range of perspectives on the role played by the border during the early months of the pandemic. RESULTS: Analysis identified three themes: Cross-Border Interdependencies illustrated the complexity and challenges of living near the border; Interpretations of Cross-Border Policy Disparities showed that lay publics perceived NI and ROI policy approaches as discordant and politicised; and Responses to Cross-Border Policy Disparities revealed alternating calls to either strengthen border controls, or pursue a unified all-island approach. CONCLUSIONS: Results reveal clear public appetite for greater synchronisation of cross-border pandemic responses, emphasise the specific vulnerability of communities living near the border, and highlight the risk of long-term socio-political repercussions of border management decisions taken during the pandemic. Findings will inform implementation of pandemic responses and public health policies in jurisdictions that share a porous land border.

Differential genetic influences over colorectal cancer risk and gene expression in large bowel mucosa.

Site-specific variation in colorectal cancer (CRC) incidence, biology and prognosis are poorly understood. We sought to determine whether common genetic variants influencing CRC risk might exhibit topographical differences on CRC risk through regional differences in effects on gene expression in the large bowel mucosa. We conducted a site-specific genetic association study (10 630 cases, 31 331 controls) to identify whether established risk variants exert differential effects on risk of proximal, compared to distal CRC. We collected normal colorectal mucosa and blood from 481 subjects and assessed mucosal gene expression using Illumina HumanHT-12v4 arrays in relation to germline genotype. Expression quantitative trait loci (eQTLs) were explored by anatomical location of sampling. The rs3087967 genotype (chr11q23.1 risk variant) exhibited significant site-specific effects-risk of distal CRC (odds ratio [OR] = 1.20, P = 8.20 × 10-20 ) with negligible effects on proximal CRC risk (OR = 1.05, P = .10). Expression of 1261 genes differed between proximal and distal colonic mucosa (top hit PRAC gene, fold-difference = 10, P = 3.48 × 10-57 ). In eQTL studies, rs3087967 genotype was associated with expression of 8 cis- and 21 trans-genes. Four of these (AKAP14, ADH5P4, ASGR2, RP11-342M1.7) showed differential effects by site, with strongest trans-eQTL signals in proximal colonic mucosa (eg, AKAP14, beta = 0.61, P = 5.02 × 10-5 ) and opposite signals in distal mucosa (AKAP14, beta = -0.17, P = .04). In summary, genetic variation at the chr11q23.1 risk locus imparts greater risk of distal rather than proximal CRC and exhibits site-specific differences in eQTL effects in normal mucosa. Topographical differences in genomic control over gene expression relevant to CRC risk may underlie site-specific variation in CRC. Results may inform individualised CRC screening programmes.

Power determination in vitamin D randomised control trials and characterising factors affecting it through a novel simulation-based tool.

Thousands of observational studies have linked vitamin D deficiency with numerous diseases, but randomised controlled trials (RCTs) often fail to show benefit of supplementation. Population characteristics and trial design have long been suspected to undermine power but were not systematically investigated. We propose a flexible generative model to characterise benefit of vitamin D supplementation at the individual level, and use this to quantify power in RCTs. The model can account for seasonality and population heterogeneity. In a simulated 1-year trial with 1000 participants per arm and assuming a 25-hydroxyvitamin D (25OHD) increase of 20 nmol/L due to the intervention, with baseline 25OHD in the population of 15, 35, 50, 60 and 75 nmol/L, the power to detect intervention effect was 77%, 99%, 95%, 68% and 19%, respectively. The number of participants required per arm to achieve 80% power according to baseline 25OHD of 15-60 nmol/L was 1200, 400, 600 and 1400, respectively. As expected, larger increases in 25OHD due to supplementation improved power in certain scenarios. For a population baseline of 50 nmol/L, with 1500 participants in each arm, there was 100% power to detect a 20 nmol/L 25OHD increase while it was 76% for a 10 nmol/L increase. Population characteristics and trial design, including temporal considerations, have a dramatic impact on power and required sample size in vitamin D RCTs.

The effect of vitamin D supplementation on survival in patients with colorectal cancer: systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Low circulating vitamin D levels are associated with poor colorectal cancer (CRC) survival. We assess whether vitamin D supplementation improves CRC survival outcomes. METHODS: PubMed and Web of Science were searched. Randomised controlled trial (RCTs) of vitamin D supplementation reporting CRC mortality were included. RCTs with high risk of bias were excluded from analysis. Random-effects meta-analysis models calculated estimates of survival benefit with supplementation. The review is registered on PROSPERO, registration number: CRD42020173397. RESULTS: Seven RCTs (n = 957 CRC cases) were identified: three trials included patients with CRC at outset, and four population trials reported survival in incident cases. Two RCTs were excluded from meta-analysis (high risk of bias; no hazard ratio (HR)). While trials varied in inclusion criteria, intervention dose and outcomes, meta-analysis found a 30% reduction in adverse CRC outcomes with supplementation (n = 815, HR = 0.70; 95% confidence interval (CI): 0.48-0.93). A beneficial effect was seen in trials of CRC patients (progression-free survival, HR = 0.65; 95% CI: 0.36-0.94), with suggestive effect in incident CRC cases from population trials (CRC-specific survival, HR = 0.76; 95% CI: 0.39-1.13). No heterogeneity or publication bias was noted. CONCLUSIONS: Meta-analysis demonstrates a clinically meaningful benefit of vitamin D supplementation on CRC survival outcomes. Further well-designed, adequately powered RCTs are needed to fully evaluate benefit of supplementation in augmenting 'real-life' follow-up and adjuvant chemotherapy regimens, as well as determining optimal dosing.

Platelet function/reactivity testing and prediction of risk of recurrent vascular events and outcomes after TIA or ischaemic stroke: systematic review and meta-analysis.

BACKGROUND: The prevalence of ex vivo 'high on-treatment platelet reactivity (HTPR)' and its relationship with recurrent vascular events/outcomes in patients with ischaemic cerebrovascular disease (CVD) is unclear. METHODS: A systematic review and meta-analysis was performed in accordance with the PRISMA statement. MEDLINE, EMBASE and Cochrane Library were searched for completed manuscripts until May 2019 on TIA/ischaemic stroke patients, ≥ 18 years, treated with commonly-prescribed antiplatelet therapy, who had platelet function/reactivity testing and prospective follow-up data on recurrent stroke/TIA, myocardial infarction, vascular death or other cerebrovascular outcomes. Data were pooled using random-effects meta-analysis. Primary outcome was the composite risk of recurrent stroke/TIA, myocardial infarction or vascular death. Secondary outcomes were recurrent stroke/TIA, severe stroke (NIHSS > 16) or disability/impairment (modified Rankin scale ≥ 3) during follow-up. RESULTS: Antiplatelet-HTPR prevalence was 3-65% with aspirin, 8-56% with clopidogrel and 1.8-35% with aspirin-clopidogrel therapy. Twenty studies (4989 patients) were included in our meta-analysis. There was a higher risk of the composite primary outcome (OR 2.93, 95% CI 1.90-4.51) and recurrent ischaemic stroke/TIA (OR 2.43, 95% CI 1.51-3.91) in patients with vs. those without 'antiplatelet-HTPR' on any antiplatelet regimen. These risks were also more than twofold higher in patients with vs. those without 'aspirin-HTPR' and 'dual antiplatelet-HTPR', respectively. Clopidogrel-HTPR status did not significantly predict outcomes, but the number of eligible studies was small. The risk of severe stroke was higher in those with vs. without antiplatelet-HTPR (OR 2.65, 95% CI 1.00-7.01). DISCUSSION: Antiplatelet-HTPR may predict risks of recurrent vascular events/outcomes in CVD patients. Given the heterogeneity between studies, further prospective, multi-centre studies are warranted.

Study protocol for the COvid-19 Toolbox for All IslaNd (CONTAIN) project: A cross-border analysis in Ireland to disentangle psychological, behavioural, media and governmental responses to COVID-19.

COVID-19 represents a serious challenge to governments and healthcare systems. In addition to testing/contact tracing, behavioural and social responses such as handwashing and social distancing or cocooning are effective tools for mitigating the spread of the disease. Psychological (e.g., risk perceptions, self-efficacy) and contextual factors (government, public health messaging, etc.) are likely to drive these behaviours. Collated real-time information of these indicators strengthens local, national and international public health advice and messaging. Further, understanding how well public health and government messages and measures are understood, communicated via (social) media and adhered to is vital. There are two governments and public health jurisdictions on the island of Ireland, the Republic of Ireland (ROI) and Northern Ireland (NI). This represents an opportunity to explore implications of differing measures and messaging across these two jurisdictions as they relate to COVID-19 on two similar populations. The expert research team are drawn from a range of disciplines in the two countries. This project has four nested studies: Assessment of key behavioural, social and psychological factors through a large, prospective representative telephone survey of individuals aged over-18 on a weekly basis over eight weeks (n=3072); and conduct qualitative focus groups over the same period.Interrogation of social media messaging and formal media responses in both jurisdictions to investigate the spread of (mis)information.Modelling data from Studies 1 and 2, plotting the psychosocial/behavioural and media messaging information with international, ROI and NI incidence and mortality data. Conducting an assessment of health policy transfer in an attempt to incorporate the most significant public health and political insights from each jurisdiction. The CONTAIN project will develop an evidence-based toolbox for targeting public health messaging and political leadership and will be created for use for the anticipated second wave of COVID-19, and subsequently for future epidemics/pandemics.

Urinary soluble CD163 and monocyte chemoattractant protein-1 in the identification of subtle renal flare in anti-neutrophil cytoplasmic antibody-associated vasculitis.

BACKGROUND: Prior work has shown that urinary soluble CD163 (usCD163) displays excellent biomarker characteristics for detection of active renal vasculitis using samples that included new diagnoses with highly active renal disease. This study focused on the use of usCD163 in the detection of the more clinically relevant state of mild renal flare and compared results of usCD163 testing directly to testing of urinary monocyte chemoattractant protein-1 (uMCP-1). METHODS: Patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV, n = 88) were identified within a serially sampled, longitudinal and multicentre cohort. Creatinine-normalized usCD163 and uMCP-1 levels were measured by enzyme-linked immunosorbent assay and, both alone and in combination, were compared between times of active renal AAV and during remission and/or active non-renal AAV. RESULTS: Samples from 320 study visits included times of active renal vasculitis (n = 39), remission (n = 233) and active extrarenal vasculitis (n = 48). Median creatinine levels were 0.9 mg/dL [interquartile range (IQR) 0.8-1.2] in remission and 1.4 mg/dL (IQR 1.0-1.8) during renal flare. usCD163 levels were higher in patients with active renal vasculitis compared with patients in remission and those with active extrarenal vasculitis, with median values of 162 ng/mmol (IQR 79-337), 44 (17-104) and 38 (7-76), respectively (P < 0.001). uMCP-1 levels were also higher in patients with active renal vasculitis compared with patients in remission and those with active extrarenal vasculitis, with median values of 10.6 pg/mmol (IQR 4.6-23.5), 4.1 (2.5-8.4) and 4.1 (1.9-6.8), respectively (P < 0.001). The proposed diagnostic cut-points for usCD163 and uMCP-1 were 72.9 ng/mmol and 10.0 pg/mmol, respectively. usCD163 and uMCP-1 levels were marginally correlated (r2 = 0.11, P < 0.001). Combining novel and existing biomarkers using recursive tree partitioning indicated that elevated usCD163 plus either elevated uMCP-1 or new/worse proteinuria improved the positive likelihood ratio (PLR) of active renal vasculitis to 19.2. CONCLUSION: A combination of usCD163 and uMCP-1 measurements appears to be useful in identifying the diagnosis of subtle renal vasculitis flare.