Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05–6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50–75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron

Measurement of J/ψ -pair production in pp collisions at √s = 13 TeV and study of gluon transverse-momentum dependent PDFs

The production cross-section of J/ψ pairs in proton-proton collisions at a centre-of-mass energy of √s = 13 TeV is measured using a data sample corresponding to an integrated luminosity of 4.2 fb−1 collected by the LHCb experiment. The measurement is performed with both J/ψ mesons in the transverse momentum range 0 < pT< 14 GeV/c and rapidity range 2.0 < y < 4.5. The cross-section of this process is measured to be 16.36 ± 0.28 (stat) ± 0.88 (syst) nb. The contributions from single-parton scattering and double-parton scattering are separated based on the dependence of the cross-section on the absolute rapidity difference ∆y between the two J/ψ mesons. The effective cross-section of double-parton scattering is measured to be σeff = 13.1 ± 1.8 (stat) ± 2.3 (syst) mb. The distribution of the azimuthal angle ϕCS of one of the J/ψ mesons in the Collins-Soper frame and the pT-spectrum of the J/ψ pairs are also measured for the study of the gluon transverse-momentum dependent distributions inside protons. The extracted values of ⟨cos 2ϕCS⟩ and ⟨cos 4ϕCS⟩ are consistent with zero, but the presence of azimuthal asymmetry at a few percent level is allowed

Health effects of air pollution exposure on children and adolescents in São Paulo, Brazil

Children and adolescents have been considered more susceptible to the effects of air pollution than adults. in order to investigate the responses of children of different ages to air pollution exposure, daily records or hospital admissions for children in five age groups (equal or less than 2 years of age, 3-5, 6-13, 14-19, and all ages together, i.e., from 0-19 years of age) were obtained from January 1993 to November 1997 in São Paulo, Brazil, and were compared to daily records of PM10, O-3, SO2, CO and NO2 concentrations in ambient air. for each age group a generalized additive Poisson regression was fitted controlling for smooth functions of time, temperature, humidity, and days of the week, with an additional indicator for holidays. Polynomial distributed lag models were used to estimate the 7-day cumulative effect of each pollutant.Children 2 years or less were the most susceptible to the effects of all five pollutants with an increase of 9.4% (95% CI: 7.9,10.9) in respiratory admissions associated with each interquartile range increase in PM10. the oldest group was the second most susceptible to air pollutants, with each interquartile range increase in PM10 associated with a 5.1% (95% CI: 0.3,9.8) increase in respiratory admissions. An interquartile range increase in CO was associated with an 11.3% (95% CI: 5.9,16.8) increase in respiratory hospitalizations. When a multipollutant model was used, the effect of PM10 on respiratory admissions for all ages together was unchanged, while the SOP and the other pollutants effect was substantially reduced.This study showed that daily respiratory hospital admissions for children and adolescents in São Paulo increased with air pollution, and that the largest effects were found for the youngest (2 years or less) and oldest (14-19 years) age groups. Pediatr Pulmonol. 2001; 31:106-113. (C) 2001 Wiley-Liss, Inc.Harvard Univ, Sch Publ Hlth, Environm Epidemiol Program, Dept Environm Hlth, Boston, MA 02115 USAUniv Santo Amaro, Sch Med, Dept Pediat, Environm Pediat Program, São Paulo, BrazilUniv Santo Amaro, Sch Med, Dept Pathol, Lab Expt Air Pollut, São Paulo, BrazilHarvard Univ, Sch Publ Hlth, Physiol Program, Dept Environm Hlth, Boston, MA 02115 USAWeb of Scienc