Who acquires infection from whom? A sensitivity analysis of transmission dynamics during the early phase of the COVID-19 pandemic in Belgium.

Age-related heterogeneity in a host population, whether due to how individuals mix and contact each other, the nature of host-pathogen interactions defining epidemiological parameters, or demographics, is crucial in studying infectious disease dynamics. Compartmental models represent a popular approach to address the problem, dividing the population of interest into a discrete and finite number of states depending on, for example, individuals' age and stage of infection. We study the corresponding linearised system whose operator, in the context of a discrete-time model, equates to a square matrix known as the next generation matrix. Performing formal perturbation analysis of the entries of the aforementioned matrix, we derive indices to quantify the age-specific variation of its dominant eigenvalue (i.e., the reproduction number) and explore the relevant epidemiological information we can derive from the eigenstructure of the matrix. The resulting method enables the assessment of the impact of age-related population heterogeneity on virus transmission. In particular, starting from an age-structured SEIR model, we demonstrate the use of this approach for COVID-19 dynamics in Belgium. We analyse the early stages of the SARS-CoV-2 spread, with particular attention to the pre-pandemic framework and the lockdown lifting phase initiated as of May 2020. Our results, influenced by our assumption on age-specific susceptibility and infectiousness, support the hypothesis that transmission was only influenced to a small extent by children in the age group [0,18) and adults over 60 years of age during the early phases of the pandemic and up to the end of July 2020.

The impact of quality-adjusted life years on evaluating COVID-19 mitigation strategies: lessons from age-specific vaccination roll-out and variants of concern in Belgium (2020-2022).

BACKGROUND: When formulating and evaluating COVID-19 vaccination strategies, an emphasis has been placed on preventing severe disease that overburdens healthcare systems and leads to mortality. However, more conventional outcomes such as quality-adjusted life years (QALYs) and inequality indicators are warranted as additional information for policymakers. METHODS: We adopted a mathematical transmission model to describe the infectious disease dynamics of SARS-COV-2, including disease mortality and morbidity, and to evaluate (non)pharmaceutical interventions. Therefore, we considered temporal immunity levels, together with the distinct transmissibility of variants of concern (VOCs) and their corresponding vaccine effectiveness. We included both general and age-specific characteristics related to SARS-CoV-2 vaccination. Our scenario study is informed by data from Belgium, focusing on the period from August 2021 until February 2022, when vaccination for children aged 5-11 years was initially not yet licensed and first booster doses were administered to adults. More specifically, we investigated the potential impact of an earlier vaccination programme for children and increased or reduced historical adult booster dose uptake. RESULTS: Through simulations, we demonstrate that increasing vaccine uptake in children aged 5-11 years in August-September 2021 could have led to reduced disease incidence and ICU occupancy, which was an essential indicator for implementing non-pharmaceutical interventions and maintaining healthcare system functionality. However, an enhanced booster dose regimen for adults from November 2021 onward could have resulted in more substantial cumulative QALY gains, particularly through the prevention of elevated levels of infection and disease incidence associated with the emergence of Omicron VOC. In both scenarios, the need for non-pharmaceutical interventions could have decreased, potentially boosting economic activity and mental well-being. CONCLUSIONS: When calculating the impact of measures to mitigate disease spread in terms of life years lost due to COVID-19 mortality, we highlight the impact of COVID-19 on the health-related quality of life of survivors. Our study underscores that disease-related morbidity could constitute a significant part of the overall health burden. Our quantitative findings depend on the specific setup of the interventions under review, which is open to debate or should be contextualised within future situations.

Estimation of skeletal muscle mass in 4-year-old children using the D3-creatine dilution method.

BACKGROUND: Given limited experience in applying the creatine-(methyl-D3) (D3Cr) dilution method to measure skeletal muscle mass (SMM) in young children, the feasibility of deployment in a fielding setting and performance of the method was assessed in a cohort of 4-year-old children in Dhaka, Bangladesh. METHODS: Following D3Cr oral dose (10 mg) administration, single fasting urine samples were collected at 2-4 days (n = 100). Twenty-four-hour post-dose collections and serial spot urine samples on days 2, 3 and 4 were obtained in a subset of participants (n = 10). Urinary creatine, creatinine, D3Cr and D3-creatinine enrichment were analyzed by liquid chromatography-tandem mass spectrometry. Appendicular lean mass (ALM) was measured by dual-energy x-ray absorptiometry and grip strength was measured by a hand-held dynamometer. RESULTS: SMM was measured successfully in 91% of participants, and there were no adverse events. Mean ± SD SMM was greater than ALM (4.5 ± 0.4 and 3.2 ± 0.6 kg, respectively). Precision of SMM was low (intraclass correlation = 0.20; 95% CI: 0.02, 0.75; n = 10). Grip strength was not associated with SMM in multivariable analysis (0.004 kg per 100 g of SMM; 95% CI: -0.031, 0.038; n = 91). CONCLUSIONS: The D3Cr dilution method was feasible in a community setting. However, high within-child variability in SMM estimates suggests the need for further optimization of this approach. IMPACT: The D3-creatine (D3Cr) stable isotope dilution method was considered a feasible method for the estimation of skeletal muscle mass (SMM) in young children in a community setting and was well accepted among participants. SMM was weakly associated with both dual-energy x-ray absorptiometry-derived values of appendicular lean mass and grip strength. High within-child variability in estimated values of SMM suggests that further optimization of the D3Cr stable isotope dilution method is required prior to implementation in community research settings.

Inferring age-specific differences in susceptibility to and infectiousness upon SARS-CoV-2 infection based on Belgian social contact data.

Several important aspects related to SARS-CoV-2 transmission are not well known due to a lack of appropriate data. However, mathematical and computational tools can be used to extract part of this information from the available data, like some hidden age-related characteristics. In this paper, we present a method to investigate age-specific differences in transmission parameters related to susceptibility to and infectiousness upon contracting SARS-CoV-2 infection. More specifically, we use panel-based social contact data from diary-based surveys conducted in Belgium combined with the next generation principle to infer the relative incidence and we compare this to real-life incidence data. Comparing these two allows for the estimation of age-specific transmission parameters. Our analysis implies the susceptibility in children to be around half of the susceptibility in adults, and even lower for very young children (preschooler). However, the probability of adults and the elderly to contract the infection is decreasing throughout the vaccination campaign, thereby modifying the picture over time.

Different forms of superspreading lead to different outcomes: Heterogeneity in infectiousness and contact behavior relevant for the case of SARS-CoV-2.

Superspreading events play an important role in the spread of several pathogens, such as SARS-CoV-2. While the basic reproduction number of the original Wuhan SARS-CoV-2 is estimated to be about 3 for Belgium, there is substantial inter-individual variation in the number of secondary cases each infected individual causes-with most infectious individuals generating no or only a few secondary cases, while about 20% of infectious individuals is responsible for 80% of new infections. Multiple factors contribute to the occurrence of superspreading events: heterogeneity in infectiousness, individual variations in susceptibility, differences in contact behavior, and the environment in which transmission takes place. While superspreading has been included in several infectious disease transmission models, research into the effects of different forms of superspreading on the spread of pathogens remains limited. To disentangle the effects of infectiousness-related heterogeneity on the one hand and contact-related heterogeneity on the other, we implemented both forms of superspreading in an individual-based model describing the transmission and spread of SARS-CoV-2 in a synthetic Belgian population. We considered its impact on viral spread as well as on epidemic resurgence after a period of social distancing. We found that the effects of superspreading driven by heterogeneity in infectiousness are different from the effects of superspreading driven by heterogeneity in contact behavior. On the one hand, a higher level of infectiousness-related heterogeneity results in a lower risk of an outbreak persisting following the introduction of one infected individual into the population. Outbreaks that did persist led to fewer total cases and were slower, with a lower peak which occurred at a later point in time, and a lower herd immunity threshold. Finally, the risk of resurgence of an outbreak following a period of lockdown decreased. On the other hand, when contact-related heterogeneity was high, this also led to fewer cases in total during persistent outbreaks, but caused outbreaks to be more explosive in regard to other aspects (such as higher peaks which occurred earlier, and a higher herd immunity threshold). Finally, the risk of resurgence of an outbreak following a period of lockdown increased. We found that these effects were conserved when testing combinations of infectiousness-related and contact-related heterogeneity.

The impact of national and international travel on spatio-temporal transmission of SARS-CoV-2 in Belgium in 2021.

BACKGROUND: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has rapidly spread over the world and caused tremendous impacts on global health. Understanding the mechanism responsible for the spread of this pathogen and the impact of specific factors, such as human mobility, will help authorities to tailor interventions for future SARS-CoV-2 waves or newly emerging airborne infections. In this study, we aim to analyze the spatio-temporal transmission of SARS-CoV-2 in Belgium at municipality level between January and December 2021 and explore the effect of different levels of human travel on disease incidence through the use of counterfactual scenarios. METHODS: We applied the endemic-epidemic modelling framework, in which the disease incidence decomposes into endemic, autoregressive and neighbourhood components. The spatial dependencies among areas are adjusted based on actual connectivity through mobile network data. We also took into account other important factors such as international mobility, vaccination coverage, population size and the stringency of restriction measures. RESULTS: The results demonstrate the aggravating effect of international travel on the incidence, and simulated counterfactual scenarios further stress the alleviating impact of a reduction in national and international travel on epidemic growth. It is also clear that local transmission contributed the most during 2021, and municipalities with a larger population tended to attract a higher number of cases from neighboring areas. CONCLUSIONS: Although transmission between municipalities was observed, local transmission was dominant. We highlight the positive association between the mobility data and the infection spread over time. Our study provides insight to assist health authorities in decision-making, particularly when the disease is airborne and therefore likely influenced by human movement.

Dietary outcomes of community-based CVD preventive interventions: a systematic review and meta-analysis.

OBJECTIVE: We aimed to synthesise available evidence on the effects of community-based interventions in improving various dietary outcome measures. DESIGN: Systematic review and meta-analysis. SETTING: We searched databases including Medline, EMBASE, PSYCINFO, CINAHL and the Cochrane registry for studies reported between January 2000 and June 2022. The methodological quality of the included studies was evaluated using the Cochrane risk of bias tools for each study type. For some of the outcomes, we pooled the effect size using a random-effects meta-analysis. PARTICIPANTS: A total of fifty-one studies, thirty-three randomised and eighteen non-randomised, involving 100 746 participants were included. RESULTS: Overall, thirty-seven studies found a statistically significant difference in at least one dietary outcome measure favouring the intervention group, whereas fourteen studies found no statistically significant difference. Our meta-analyses indicated that, compared with controls, interventions were effective in decreasing daily energy intake (MJ/d) (mean difference (MD): -0·25; 95 % CI: -0·37, -0·14), fat % of energy (MD: -1·01; 95 % CI: -1·76, -0·25) and saturated fat % of energy (MD: -1·54; 95 % CI: -2·01, -1·07). Furthermore, the interventions were effective in improving fibre intake (g/d) (MD: 1·08; 95 % CI: 0·39, 1·77). Effective interventions use various strategies including tailored individual lifestyle coaching, health education, health promotion activities, community engagement activities and/or structural changes. CONCLUSION: This review shows the potential of improving dietary patterns through community-based CVD preventive interventions. Thus, development and implementation of context-specific preventive interventions could help to minimise dietary risk factors, which in turn decrease morbidity and mortality due to CVD and other non-communicable diseases.

The direct disease burden of COVID-19 in Belgium in 2020 and 2021.

BACKGROUND: Burden of disease estimates have become important population health metrics over the past decade to measure losses in health. In Belgium, the disease burden caused by COVID-19 has not yet been estimated, although COVID-19 has emerged as one of the most important diseases. Therefore, the current study aims to estimate the direct COVID-19 burden in Belgium, observed despite policy interventions, during 2020 and 2021, and compare it to the burden from other causes. METHODS: Disability-adjusted life years (DALYs) are the sum of Years Lived with Disability (YLDs) and Years of Life Lost (YLLs) due to disease. DALYs allow comparing the burden of disease between countries, diseases, and over time. We used the European Burden of Disease Network consensus disease model for COVID-19 to estimate DALYs related to COVID-19. Estimates of person-years for (a) acute non-fatal disease states were calculated from a compartmental model, using Belgian seroprevalence, social contact, hospital, and intensive care admission data, (b) deaths were sourced from the national COVID-19 mortality surveillance, and (c) chronic post-acute disease states were derived from a Belgian cohort study. RESULTS: In 2020, the total number of COVID-19 related DALYs was estimated at 253,577 [252,541 - 254,739], which is higher than in 2021, when it was 139,281 [136,704 - 142,306]. The observed COVID-19 burden was largely borne by the elderly, and over 90% of the burden was attributable to premature mortality (i.e., YLLs). In younger people, morbidity (i.e., YLD) contributed relatively more to the DALYs, especially in 2021, when vaccination was rolled out. Morbidity was mainly attributable to long-lasting post-acute symptoms. CONCLUSION: COVID-19 had a substantial impact on population health in Belgium, especially in 2020, when COVID-19 would have been the main cause of disease burden if all other causes had maintained their 2019 level.

Prenatal Weight Change Trajectories and Perinatal Outcomes among Twin Gestations.

OBJECTIVE: Despite an increase in twin pregnancies in recent decades, the Institute of Medicine twin weight gain recommendations remain provisional and provide no guidance for the pattern or timing of weight change. We sought to characterize gestational weight change trajectory patterns and examine associations with birth outcomes in a cohort of twin pregnancies. STUDY DESIGN: Prenatal and delivery records were examined for 320 twin pregnancies from a maternal-fetal medicine practice in Austin, TX 2011-2019. Prenatal weights for those with >1 measured weight in the first trimester and ≥3 prenatal weights were included in analyses. Trajectories were estimated to 32 weeks (mean delivery: 33.7 ± 3.3 weeks) using flexible latent class mixed models with low-rank thin-plate splines. Associations between trajectory classes and infant outcomes were analyzed using multivariable Poisson or linear regression. RESULTS: Weight change from prepregnancy to delivery was 15.4 ± 6.3 kg for people with an underweight body mass index, 15.4 ± 5.8 kg for healthy weight, 14.7 ± 6.9 kg for overweight, and 12.5 ± 6.4 kg for obesity. Three trajectory classes were identified: low (Class 1), moderate (Class 2), or high gain (Class 3). Class 1 (24.7%) maintained weight for 15 weeks and then gained an estimated 6.6 kg at 32 weeks. Class 2 (60.9%) exhibited steady gain with 13.5 kg predicted total gain, and Class 3 (14.4%) showed rapid gain across pregnancy with 21.3 kg predicted gain. Compared to Class 1, Class 3 was associated with higher birth weight z-score (ß = 0.63, 95% confidence interval [CI]: 0.31,0.96), increased risk for large for gestational age (IRR = 5.60, 95% CI: 1.59, 19.67), and birth <32 weeks (IRR = 2.44, 95%CI: 1.10, 5.4) that was attenuated in sensitivity analyses. Class 2 was associated with moderately elevated birth weight z-score (ß = 0.24, 95%CI: 0.00, 0.48, p = 0.050). CONCLUSION: Gestational weight change followed a low, moderate, or high trajectory; both moderate and high gain patterns were associated with increased infant size outcomes. Optimal patterns of weight change that balance risk during the prenatal, perinatal, and neonatal periods require further investigation, particularly in high-risk twin pregnancies. KEY POINTS: · A majority gained weight below IOM twin recommendations.. · Three patterns of GWC across pregnancy were identified.. · Moderate or high GWC was associated with infant size..

Factors affecting inter-individual variability in endoxifen concentrations in patients with breast cancer: results from the prospective TOTAM trial.

INTRODUCTION: Endoxifen-the principal metabolite of tamoxifen-is subject to a high inter-individual variability in serum concentration. Numerous attempts have been made to explain this, but thus far only with limited success. By applying predictive modeling, we aimed to identify factors that determine the inter-individual variability. Our purpose was to develop a prediction model for endoxifen concentrations, as a strategy to individualize tamoxifen treatment by model-informed dosing in order to prevent subtherapeutic exposure (endoxifen < 16 nmol/L) and thus potential failure of therapy. METHODS: Tamoxifen pharmacokinetics with demographic and pharmacogenetic data of 303 participants of the prospective TOTAM study were used. The inter-individual variability in endoxifen was analyzed according to multiple regression techniques in combination with multiple imputations to adjust for missing data and bootstrapping to adjust for the over-optimism of parameter estimates used for internal model validation. RESULTS: Key predictors of endoxifen concentration were CYP2D6 genotype, age and weight, explaining altogether an average-based optimism corrected 57% (95% CI 0.49-0.64) of the inter-individual variability. CYP2D6 genotype explained 54% of the variability. The remaining 3% could be explained by age and weight. Predictors of risk for subtherapeutic endoxifen (< 16 nmol/L) were CYP2D6 genotype and age. The model showed an optimism-corrected discrimination of 90% (95% CI 0.86-0.95) and sensitivity and specificity of 66% and 98%, respectively. Consecutively, there is a high probability of misclassifying patients with subtherapeutic endoxifen concentrations based on the prediction rule. CONCLUSION: The inter-individual variability of endoxifen concentration could largely be explained by CYP2D6 genotype and for a small proportion by age and weight. The model showed a sensitivity and specificity of 66 and 98%, respectively, indicating a high probability of (misclassification) error for the patients with subtherapeutic endoxifen concentrations (< 16 nmol/L). The remaining unexplained inter-individual variability is still high and therefore model-informed tamoxifen dosing should be accompanied by therapeutic drug monitoring.

Daily Intake of a Functional Synbiotic Yogurt Increases Calcium Absorption in Young Adult Women.

BACKGROUND: Foods containing both prebiotics and probiotics (synbiotics) might enhance calcium bioavailability. OBJECTIVES: We investigated the acute effect in young adult women on calcium absorption of consuming (185 mL) a synbiotic yogurt (SYN) containing inulin (4 g) and Lactobacillus rhamnosus GG (>1 × 107 CFU/mL) compared with a control yogurt (CON). METHODS: Adult normal-weight women (25.0 ± 3.5 y, n = 30) participated in a 3-wk crossover study testing daily consumption of SYN compared with CON. Habitual dietary intake, bone mineral density (BMD), calcium biomarkers, and serum 25-hydroxyvitamin D were measured at baseline. Calcium absorption was tested after each phase of the study using a 42Ca oral tracer. Cumulative tracer recovery was measured in 0-4-h,  0-24-h, and 0-36-h urine pools collected postdosing. The SYN/CON tracer ratio from the timed urine pools was the primary outcome. A beneficial response to SYN was defined as 0-36-h SYN/CON tracer ratio >1. RESULTS: Net 42Ca recovered increased over time in each of the SYN and CON urine pools postdosing (Friedman, P < 0.001), with a trend for higher 42Ca recovery in the 0-36-h urine pool postdosing in the SYN (1.14%) compared with the CON (0.90%) study (Wilcoxon, P = 0.07). For CON, the majority of total tracer was recovered in the 0-24-h pool (86%), whereas for SYN only 50% of total tracer was recovered in the 0-24-h pool (Friedman, P = 0.001). The SYN/CON tracer ratio in the 0-36-h pool (1.24) was >1 (Wilcoxon, P = 0.015). About two-thirds (n = 19) of women studied responded to the SYN treatment. Responders had higher vegetable intake (P = 0.03), tended to have higher potassium and calcium intakes (P ≤ 0.08), and had higher total body BMD (P = 0.09), than nonresponders. CONCLUSIONS: Short-term daily consumption of a synbiotic yogurt enhanced calcium absorption relative to a control yogurt in adult women. Given the observed time delays in tracer recovery, enhancement of calcium absorption likely occurred in the large intestine.The study was registered at clinicaltrials.gov (study registration ID: NCT03420716).

Seroconversion rate after primary vaccination with two doses of BNT162b2 versus mRNA-1273 in solid organ transplant recipients: a systematic review and meta-analysis.

BACKGROUND: In the general population, the seroconversion rate after primary vaccination with two doses of an anti-severe acute respiratory syndrome coronavirus 2 messenger RNA (mRNA) vaccine reaches nearly 100%, with significantly higher antibody titers after mRNA-1273 vaccination compared to BNT162b2 vaccination. Here we performed a systematic review and meta-analysis to compare the antibody response after two-dose mRNA-1273 versus BNT162b2 vaccination in solid organ transplant (SOT) recipients. METHODS: A systematic literature review was performed using PubMed, Web of Science and the Cochrane Library and original research papers were included for a meta-analysis to calculate vaccine-specific seroconversion rates for each of the mRNA vaccines. Next, the pooled relative seroconversion rate was estimated. RESULTS: Eight studies that described the development of antibodies against receptor-binding domain (RBD) and/or spike protein were eligible for meta-analysis. Two of these studies also reported antibody titers. The meta-analysis revealed lower seroconversion rates in SOT recipients vaccinated with two doses of BNT162b2 {44.3% [95% confidence interval (CI) 34.1-54.7]} as compared with patients vaccinated with two doses of mRNA-1273 [58.4% (95% CI 47.2-69.2)]. The relative seroconversion rate was 0.795 (95% CI 0.732-0.864). CONCLUSIONS: This systematic review and meta-analysis indicates that in SOT recipients, higher seroconversion rates were observed after vaccination with mRNA-1273 compared with BNT162b2.

Modelling longitudinal binary outcomes with outcome dependent observation times: an application to a malaria cohort study.

BACKGROUND : In spite of the global reduction of 21% in malaria incidence between 2010 and 2015, the disease still threatens many lives of children and pregnant mothers in African countries. A correct assessment and evaluation of the impact of malaria control strategies still remains quintessential in order to eliminate the disease and its burden. Malaria follow-up studies typically involve routine visits at pre-scheduled time points and/or clinical visits whenever individuals experience malaria-like symptoms. In the latter case, infection triggers outcome assessment, thereby leading to outcome-dependent sampling (ODS). Commonly used methods to analyze such longitudinal data ignore ODS and potentially lead to biased estimates of malaria-specific transmission parameters, hence, inducing an incorrect assessment and evaluation of malaria control strategies. METHODS : In this paper, a new method is proposed to handle ODS by use of a joint model for the longitudinal binary outcome measured at routine visits and the clinical event times. The methodology is applied to malaria parasitaemia data from a cohort of [Formula: see text] Ugandan children aged 0.5-10 years from 3 regions (Walukuba-300 children, Kihihi-355 children and Nagongera-333 children) with varying transmission intensities (entomological inoculation rate equal to 2.8, 32 and 310 infectious bites per unit year, respectively) collected between 2011-2014. RESULTS : The results indicate that malaria parasite prevalence and force of infection (FOI) increase with age in the region of high malaria intensity with highest FOI in age group 5-10 years. For the region of medium intensity, the prevalence slightly increases with age and the FOI for the routine process is highest in age group 5-10 years, yet for the clinical infections, the FOI gradually decreases with increasing age. For the region with low intensity, both the prevalence and FOI peak at the age of 1 year after which the former remains constant with age yet the latter suddenly decreases with age for the clinically observed infections. CONCLUSION : Malaria parasite prevalence and FOI increase with age in the region of high malaria intensity. In all study sites, both the prevalence and FOI are highest among previously asymptomatic children and lowest among their symptomatic counterparts. Using a simulation study inspired by the malaria data at hand, the proposed methodology shows to have the smallest bias, especially when consecutive positive malaria parasitaemia presence results within a time period of 35 days were considered to be due to the same infection.

Predicting mortality in intensive care unit patients infected with Klebsiella pneumoniae: A retrospective cohort study.

INTRODUCTION: Although several models to predict intensive care unit (ICU) mortality are available, their performance decreases in certain subpopulations because specific factors are not included. Moreover, these models often involve complex techniques and are not applicable in low-resource settings. We developed a prediction model and simplified risk score to predict 14-day mortality in ICU patients infected with Klebsiella pneumoniae. METHODOLOGY: A retrospective cohort study was conducted using data of ICU patients infected with Klebsiella pneumoniae at the largest tertiary hospital in Northern Vietnam during 2016-2018. Logistic regression was used to develop our prediction model. Model performance was assessed by calibration (area under the receiver operating characteristic curve-AUC) and discrimination (Hosmer-Lemeshow goodness-of-fit test). A simplified risk score was also constructed. RESULTS: Two hundred forty-nine patients were included, with an overall 14-day mortality of 28.9%. The final prediction model comprised six predictors: age, referral route, SOFA score, central venous catheter, intracerebral haemorrhage surgery and absence of adjunctive therapy. The model showed high predictive accuracy (AUC = 0.83; p-value Hosmer-Lemeshow test = 0.92). The risk score has a range of 0-12 corresponding to mortality risk 0-100%, which produced similar predictive performance as the original model. CONCLUSIONS: The developed prediction model and risk score provide an objective quantitative estimation of individual 14-day mortality in ICU patients infected with Klebsiella pneumoniae. The tool is highly applicable in practice to help facilitate patient stratification and management, evaluation of further interventions and allocation of resources and care, especially in low-resource settings where electronic systems to support complex models are missing.

Level of cardiovascular disease knowledge, risk perception and intention towards healthy lifestyle and socioeconomic disparities among adults in vulnerable communities of Belgium and England.

BACKGROUND: The burden of cardiovascular diseases (CVDs) greatly varies between and within countries. Low- and middle-income countries (LMICs) and vulnerable communities of high-income countries (HIC) share disproportionately higher burden. Evidence is limited on the level of CVD knowledge and risk perception in vulnerable communities. Hence, in this study, we assessed the level of CVD knowledge, risk perception and change intention towards physical activity and healthy diet among vulnerable communities in Antwerp, Belgium and Nottingham, England. Furthermore, we investigated the socioeconomic disparities particularly in the Antwerp setting. METHOD: A cross-sectional study was performed among 1,424 adults (958 in Antwerp and 466 in Nottingham) aged 18 or older among selected vulnerable communities. Districts or counties were selected based on socioeconomic and multiple deprivation index. A stratified random sampling was used in Antwerp, and purposive sampling in Nottingham. We determined the level of CVD knowledge, risk perception and intention towards a healthy lifestyle in Antwerp and Nottingham using a percentage score out of 100. To identify independent socioeconomic determinants in CVD knowledge, risk perception, intention to PA and healthy diet, we performed multilevel multivariable modeling using the Antwerp dataset. RESULTS: The mean knowledge percent score was 75.4 in Antwerp and 69.4 in Nottingham, and only 36.5% and 21.1% of participants respectively, had good CVD knowledge (scored 80% or above). In the multivariable analysis using the Antwerp dataset, level of education was significantly associated with (1) CVD knowledge score (Adjusted ß = 0.11, 95%CI: 0.03, 0.18), (2) risk perception (0.23, 95%CI: 0.04, 0.41), (3) intention to physical activity (PA) (0.51, 95%CI: 0.35, 0.66), and (4) healthy diet intention (0.54, 95%CI: 0.32, 0.75). Furthermore, those individuals with a higher household income had a better healthy diet intention (0.44, 95%CI: 0.23, 0.65). In contrast, those who were of non-European origin scored lower on intention to have a healthy diet (-1.34, 95%CI:-2.07, -0.62) as compared to their European counterparts. On average, intention to PA was significantly higher among males (-0.43, 95%CI:-0.82, -0.03), whereas females scored better on healthy diet intention (2.02, 95%CI: 1.46, 2.57). CONCLUSIONS: Knowledge towards CVD risks and prevention is low in vulnerable communities. Males have a higher intention towards PA while females towards a healthy diet and it also greatly varies across level of education. Moreover, those born outside Europe and with low household income have lower healthy diet intention than their respective counterparts. Hence, CVD preventive interventions should be participatory and based on a better understanding of the individuals' socioeconomic status and cultural beliefs through active individual and community engagement.

Seroprevalence of IgG antibodies against SARS-CoV-2 - a serial prospective cross-sectional nationwide study of residual samples, Belgium, March to October 2020.

BackgroundTo control epidemic waves, it is important to know the susceptibility to SARS-CoV-2 and its evolution over time in relation to the control measures taken.AimTo assess the evolving SARS-CoV-2 seroprevalence and seroincidence related to the first national lockdown in Belgium, we performed a nationwide seroprevalence study, stratified by age, sex and region using 3,000-4,000 residual samples during seven periods between 30 March and 17 October 2020.MethodsWe analysed residual sera from ambulatory patients for IgG antibodies against the SARS-CoV-2 S1 protein with a semiquantitative commercial ELISA. Weighted seroprevalence (overall and by age category and sex) and seroincidence during seven consecutive periods were estimated for the Belgian population while accommodating test-specific sensitivity and specificity.ResultsThe weighted overall seroprevalence initially increased from 1.8% (95% credible interval (CrI): 1.0-2.6) to 5.3% (95% CrI: 4.2-6.4), implying a seroincidence of 3.4% (95% CrI: 2.4-4.6) between the first and second collection period over a period of 3 weeks during lockdown (start lockdown mid-March 2020). Thereafter, seroprevalence stabilised, however, significant decreases were observed when comparing the third with the fifth, sixth and seventh period, resulting in negative seroincidence estimates after lockdown was lifted. We estimated for the last collection period mid-October 2020 a weighted overall seroprevalence of 4.2% (95% CrI: 3.1-5.2).ConclusionDuring lockdown, an initially small but increasing fraction of the Belgian population showed serologically detectable signs of exposure to SARS-CoV-2, which did not further increase when confinement measures eased and full lockdown was lifted.

COVID-19 mortality, excess mortality, deaths per million and infection fatality ratio, Belgium, 9 March 2020 to 28 June 2020.

BackgroundCOVID-19 mortality, excess mortality, deaths per million population (DPM), infection fatality ratio (IFR) and case fatality ratio (CFR) are reported and compared for many countries globally. These measures may appear objective, however, they should be interpreted with caution.AimWe examined reported COVID-19-related mortality in Belgium from 9 March 2020 to 28 June 2020, placing it against the background of excess mortality and compared the DPM and IFR between countries and within subgroups.MethodsThe relation between COVID-19-related mortality and excess mortality was evaluated by comparing COVID-19 mortality and the difference between observed and weekly average predictions of all-cause mortality. DPM were evaluated using demographic data of the Belgian population. The number of infections was estimated by a stochastic compartmental model. The IFR was estimated using a delay distribution between infection and death.ResultsIn the study period, 9,621 COVID-19-related deaths were reported, which is close to the excess mortality estimated using weekly averages (8,985 deaths). This translates to 837 DPM and an IFR of 1.5% in the general population. Both DPM and IFR increase with age and are substantially larger in the nursing home population.DiscussionDuring the first pandemic wave, Belgium had no discrepancy between COVID-19-related mortality and excess mortality. In light of this close agreement, it is useful to consider the DPM and IFR, which are both age, sex, and nursing home population-dependent. Comparison of COVID-19 mortality between countries should rather be based on excess mortality than on COVID-19-related mortality.

A Substantial Proportion of 6- to 12-Month-Old Infants Have Calculated Daily Absorbed Iron below Recommendations, Especially Those Who Are Breastfed.

OBJECTIVE: To calculate the amount of bioavailable iron consumed among 6- to 12- month-old infants considering differences in iron bioavailability among dietary iron sources and to compare this with current recommended intakes. STUDY DESIGN: We used the Feeding Infants and Toddlers Study database of dietary intakes from 2016 and the estimated bioavailability of dietary iron sources to evaluate the proportion of infants whose calculated total daily absorbed iron fell below physiologic requirements, that is, the recommended amount needed to fully support growth and erythropoiesis. RESULTS: The calculated daily iron absorption was below the recommended amount in 54.3% of infants evaluated ranging from 19.5% of 448 exclusively formula-fed infants, to 95.8% of 296 exclusively breastfed infants and 72.2% of 102 mixed fed infants. The calculated mean iron absorption of 6- to 9- month-old breastfed infants was 0.27 mg/day, far less than the estimated physiologic requirement of 0.69 mg/day. The most highly bioavailable iron, heme iron, was <12% of the contributor to total iron absorbed in breastfed infants. CONCLUSIONS: These data indicate a need for further education and public health policies to support increased iron intake in 6- to 12- month-old infants, emphasizing those receiving any breast milk. Exclusively formula-fed infants are at lower risk, but rates of low absorbed iron indicate that all infants may need monitoring for clinical evidence of low iron status. Consideration should be given to increasing the proportion of heme iron obtained from animal products in the diet where feasible.

Lessons Learned from Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets Patients on Vitamin D Functions.

We summarize here lessons learned from studies on skeletal and extra-skeletal functions of vitamin D in hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) patients with a mutant, nonfunctioning vitamin D receptor (VDR). During childhood, HVDRR patients are dependent on intestinal VDR, demonstrate low intestinal fraction calcium absorption, and have a bone calcium accretion rate that leads to hypocalcemia and rickets. After puberty, there is recovery in intestinal calcium absorption and in bone calcium accretion and structure. HVDRR monocytes and lymphocytes show impairment in the expression of antimicrobial proteins and demonstrate a proinflammatory cytokine profile. However, HVDRR patients do not exhibit increased rates of infections or inflammatory diseases. Vitamin D deficiency is associated with asthmatic exacerbations. Surprisingly, HVDRR patients do not usually develop asthma. They have normal allergic tests and lung functions and are protected against provoked bronchial hyperactivity. HVDRR patients have decreased IL-5 levels in their exhaled breath condensate. Given that IL-5 is a key cytokine in the development of airway inflammation and hyperactivity and that VDR is important for IL-5 generation, it is plausible that low lung IL-5 protects HVDRR patients from asthma. Vitamin D metabolites have suppressive effects on the renin angiotensin system. However, no HVDRR patient showed hypertension or echocardiographic pathology, and their renin angiotensin metabolites were normal. The VDR is expressed throughout the reproductive system, suggesting a role in reproduction. However, the reproductive history of HVDRR patients is normal despite the lack of a normal VDR. HVDRR patients provide a unique opportunity to study the role of the VDR and the role of vitamin D in various human systems.

Measuring association among censored antibody titer data.

Censoring due to a limit of detection or limit of quantification happens quite often in many medical studies. Conventional approaches to deal with censoring when analyzing these data include, for example, the substitution method and the complete case (CC) analysis. More recently, maximum likelihood estimation (MLE) has been increasingly used. While the CC analysis and the substitution method usually lead to biased estimates, the MLE approach appears to perform well in many situations. This article proposes an MLE approach to estimate the association between two measurements in the presence of censoring in one or both quantities. The central idea is to use a copula function to join the marginal distributions of the two measurements. In various simulation studies, we show that our approach outperforms existing conventional methods (CC and substitution analyses). In addition, rank-based measures of global association such as Kendall's tau or Spearman's rho can be studied, hence, attention is not only confined to Pearson's product-moment correlation coefficient capturing solely linear association. We have shown in our simulations that our approach is robust to misspecification of the copula function or marginal distributions given a small association. Furthermore, we propose a straightforward MLE method to fit a (multiple) linear regression model in the presence of censoring in a covariate or both the covariate and the response. Given the marginal distribution of the censored covariate, our method outperforms conventional approaches. We also compare and discuss the performance of our method with multiple imputation and missing indicator model approaches.