Comparison of participants and non-participants to the ORISCAV-LUX population-based study on cardiovascular risk factors in Luxembourg

BACKGROUND: Poor response is a major concern in public health surveys. In a population-based ORISCAV-LUX study carried out in Grand-Duchy of Luxembourg to assess the cardiovascular risk factors, the non-response rate was not negligible. The aims of the present work were: 1) to investigate the representativeness of study sample to the general population, and 2) to compare the known demographic and cardiovascular health-related profiles of participants and non-participants. METHODS: For sample representativeness, the participants were compared to the source population according to stratification criteria (age, sex and district of residence). Based on complementary information from the "medical administrative database", further analysis was carried out to assess whether the health status affected the response rate. Several demographic and morbidity indicators were used in the univariate comparison between participants and non-participants. RESULTS: Among the 4452 potentially eligible subjects contacted for the study, there were finally 1432 (32.2%) participants. Compared to the source population, no differences were found for gender and district distribution. By contrast, the youngest age group was under-represented while adults and elderly were over-represented in the sample, for both genders. Globally, the investigated clinical profile of the non-participants was similar to that of participants. Hospital admission and cardiovascular health-related medical measures were comparable in both groups even after controlling for age. The participation rate was lower in Portuguese residents as compared to Luxembourgish (OR = 0.58, 95% CI: 0.48-0.69). It was also significantly associated with the professional status (P < 0.0001). Subjects from the working class were less receptive to the study than those from other professional categories. CONCLUSION: The 32.2% participation rate obtained in the ORISCAV-LUX survey represents the realistic achievable rate for this type of multiple-stage, nationwide, population-based surveys. It corresponds to the expected rate upon which the sample size was calculated. Given the absence of discriminating health profiles between participants and non-participants, it can be concluded that the response rate does not invalidate the results and allows generalizing the findings for the population

First nationwide survey on cardiovascular risk factors in Grand-Duchy of Luxembourg (ORISCAV-LUX)

BACKGROUND: The ORISCAV-LUX study is the first baseline survey of an on-going cardiovascular health monitoring programme in Grand-Duchy of Luxembourg. The main objectives of the present manuscript were 1) to describe the study design and conduct, and 2) to present the salient outcomes of the study, in particular the prevalence of the potentially modifiable and treatable cardiovascular disease risk factors in the adult population residing in Luxembourg. METHOD: ORISCAV-LUX is a cross-sectional study based on a random sample of 4496 subjects, stratified by gender, age categories and district, drawn from the national insurance registry of 18-69 years aged Luxembourg residents, assuming a response rate of 30% and a proportion of 5% of institutionalized subjects in each stratum. The cardiovascular health status was assessed by means of a self-administered questionnaire, clinical and anthropometric measures, as well as by blood, urine and hair examinations. The potentially modifiable and treatable risk factors studied included smoking, hypertension, dyslipidemia, diabetes mellitus, and obesity. Both univariate and multivariate statistical analyses used weighted methods to account for the stratified sampling scheme. RESULTS: A total of 1432 subjects took part in the survey, yielding a participation rate of 32.2%. This figure is higher than the minimal sample size of 1285 subjects as estimated by power calculation. The most predominant cardiovascular risk factors were dyslipidemia (69.9%), hypertension (34.5%), smoking (22.3%), and obesity (20.9%), while diabetes amounted 4.4%. All prevalence rates increased with age (except smoking) with marked gender differences (except diabetes). There was a significant difference in the prevalence of hypertension and of lipid disorders by geographic region of birth. The proportion of subjects cumulating two or more cardiovascular risk factors increased remarkably with age and was more predominant in men than in women (P<0.0001). Only 14.7% of men and 23.1% of women were free of any cardiovascular risk factor. High prevalence of non-treated CVRF, notably for hypertension and dyslipidemia, were observed in the study population. CONCLUSION: The population-based ORISCAV-LUX survey revealed a high prevalence of potentially modifiable and treatable cardiovascular risk factors among apparently healthy subjects; significant gender and age-specific differences were seen not only for single but also for combined risk factors. From a public health perspective, these preliminary findings stress the urgent need for early routine health examinations, preventive interventions and lifestyle behavioural changes, even in young asymptomatic adults, to decrease cardiovascular morbidity and mortality in Luxembourg

The epidemiology of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) in community-living seniors: protocol of the MemoVie cohort study, Luxembourg

BACKGROUND: Cognitive impairment and Alzheimer’s disease (AD) are increasingly considered a major public health problem. The MemoVie cohort study aims to investigate the living conditions or risk factors under which the normal cognitive capacities of the senior population in Luxembourg (≥ 65 year-old) evolve (1) to mild cognitive impairment (MCI) – transitory non-clinical stage – and (2) to AD. Identifying MCI and AD predictors undeniably constitutes a challenge in public health in that it would allow interventions which could protect or delay the occurrence of cognitive disorders in elderly people. In addition, the MemoVie study sets out to generate hitherto unavailable data, and a comprehensive view of the elderly population in the country. METHODS/DESIGN: The study has been designed with a view to highlighting the prevalence in Luxembourg of MCI and AD in the first step of the survey, conducted among participants selected from a random sample of the general population. A prospective cohort is consequently set up in the second step, and appropriate follow-up of the non-demented participants allows improving the knowledge of the preclinical stage of MCI. Case-control designs are used for cross-sectional or retrospective comparisons between outcomes and biological or clinical factors. To ensure maximal reliability of the information collected, we decided to opt for structured face to face interviews. Besides health status, medical and family history, demographic and socio-cultural information are explored, as well as education, habitat network, social behavior, leisure and physical activities. As multilingualism is expected to challenge the cognitive alterations associated with pathological ageing, it is additionally investigated. Data relative to motor function, including balance, walk, limits of stability, history of falls and accidents are further detailed. Finally, biological examinations, including ApoE genetic polymorphism are carried out. In addition to standard blood parameters, the lipid status of the participants is subsequently determined from the fatty acid profiles in their red blood cells. The study obtained the legal and ethical authorizations. DISCUSSION: By means of the multidisciplinary MemoVie study, new insights into the onset of cognitive impairment during aging should be put forward, much to the benefit of intervention strategies as a whole

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60&nbsp;years old

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Using Robson's Ten‐Group Classification System for comparing caesarean section rates in Europe: an analysis of routine data from the Euro‐Peristat study

Objective Robson's Ten Group Classification System (TGCS) creates clinically relevant sub‐groups for monitoring caesarean birth rates. This study assesses whether this classification can be derived from routine data in Europe and uses it to analyse national caesarean rates. Design Observational study using routine data. Setting Twenty‐seven EU member states plus Iceland, Norway, Switzerland and the UK. Population All births at ≥22 weeks of gestational age in 2015. Methods National statistical offices and medical birth registers derived numbers of caesarean births in TGCS groups. Main outcome measures Overall caesarean rate, prevalence and caesarean rates in each of the TGCS groups. Results Of 31 countries, 18 were able to provide data on the TGCS groups, with UK data available only from Northern Ireland. Caesarean birth rates ranged from 16.1 to 56.9%. Countries providing TGCS data had lower caesarean rates than countries without data (25.8% versus 32.9%, P = 0.04). Countries with higher caesarean rates tended to have higher rates in all TGCS groups. Substantial heterogeneity was observed, however, especially for groups 5 (previous caesarean section), 6, 7 (nulliparous/multiparous breech) and 10 (singleton cephalic preterm). The differences in percentages of abnormal lies, group 9, illustrate potential misclassification arising from unstandardised definitions. Conclusions Although further validation of data quality is needed, using TGCS in Europe provides valuable comparator and baseline data for benchmarking and surveillance. Higher caesarean rates in countries unable to construct the TGCS suggest that effective routine information systems may be an indicator of a country's investment in implementing evidence‐based caesarean policies. Tweetable abstract Many European countries can provide Robson's Ten‐Group Classification to improve caesarean rate comparisons

The downward spiral of mental disorders and educational attainment: a systematic review on early school leaving.

BACKGROUND: Most psychiatric disorders present symptom patterns that cause severe impairment on the emotional, cognitive and social level. Thus, adolescents who suffer from a mental disorder risk finding themselves in a downward spiral caused by the reciprocal association of psychological symptoms and negative school experiences that may culminate in early school leaving. In addition to previous collective work that mainly focused on school refusing behaviour among children and was presented as an expert's opinion, the following systematic review fills the knowledge gap by providing a structured overview of the bidirectional association between mental health and secondary school dropout based on a sound methodology and with a particular focus on mediating factors. METHODS: Four electronic databases were searched from January 1990 until June 2014. Selected references were assessed for study details, main results, mediating factors and methodological limitations. Standardized risk of bias assessment was conducted. RESULTS: Mood and anxiety disorders seemed to have a less consequential direct effect on early school leaving than substance use and disruptive behaviour disorders. The association between externalizing disorders and educational attainment was even stronger when the disorder occurred early in life. On the other hand, internalizing disorders were reported to develop as a consequence of school dropout. Only few studies had addressed gender differences, with discrepant results. Socio-economic background, academic achievement and family support were identified as significant mediating factors of the association between mental disorders and subsequent educational attainment. CONCLUSIONS: Findings suggested a strong association between mental health and education, in both directions. However, most studies focused on mediating factors that could not be targeted by intervention programs