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

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

The experience of quarantine among employees of the National Medical Rescue System during the COVID-19 pandemic

Introduction: For healthcare professionals, working during the coronavirus pandemic is a psychological burden. One aspect of the pandemic is the compulsory quarantine or isolation related to suspected or contracting COVID-19. Aim of the study: The aim of this research is to analyze the subjective feelings and experiences of workers in emergency departments and emergency medical teams that were subjected to quarantine or isolation during the first stage of the pandemic. Material and methods: The research was performed from December 2020 to February 2021 using a survey questionnaire among the workers of the Emergency Medical Services, who in the first stage of the pandemic have undergone quarantine as a result of suspected COVID-19 infection. 89 workers were included in this study. Most of the participants worked in the ED. The mean age of the participants was 31.5 ± 8.94 years. The mean value of the entities’ work experience was 8.4 ± 9.6 years. Conclusions: Medical staff undergoing quarantine experience feelings of a different mood, anxiety, irritability, anxiety, and stress. After quarantine, they valued their health and contact with other people. Medical personnel did not use psychological assistance during quarantine. Employee isolation can be a source of both positive and negative experience. The experience of quarantine was influenced by the gender, form of employment, place of work, and age of the respondents. There is a need for further research on the mental well-being of healthcare professionals and coping with stress in crisis situations

Quantitative study of the primary ossification center of the parietal bone in the human fetus

Detailed morphometric data concentrating on the development of primary ossification centers in human fetuses is critical for the early detection of developmental defects. Thus, an understanding of the growth and development of the parietal bone is crucial in assessing both the normal and pathological development of the calvaria. The size of  the parietal primary ossification center in 37 spontaneously aborted human fetuses of both sexes (16 males and 21 females) aged 18–30 weeks was studied by means of CT, digital-image analysis and statistics. The numerical data of the parietal primary ossification center in the human fetus displays neither sex nor laterality differences. With relation to fetal age in weeks, the parietal primary ossification center grew in sagittal diameter according to the quadratic function y = 16.322 + 0.0347 × (age)2 ± 1.323 R2 = 0.96,  in projection surface area according to the cubic function y = 284.1895 + 0.051 × (age)3 ± 0.490, while in both coronal diameter and volume according to the quartic functions: y = 21.746 + 0.000025 × (age)4 ± 1.256 and y = 296.984 + 0.001 × (age)4, respectively. The obtained morphometric data of the parietal primary ossification center may be considered age-specific references, and so may contribute to the estimation of gestational ages and be useful in the diagnostics of congenital cranial defects

Quantitative anatomy of primary ossification centres of the lateral and basilar parts of the occipital bone in the human foetus

Background: Computed tomography (CT)-based quantitative analysis of primary ossification centres in the cranium has not been carried out to date due to the limited availability of the foetal human material. Detailed morphometric data about the development of primary ossification centres in human foetuses may be useful in the early detection of developmental defects. Understanding the growth and development of the occipital bone is crucial in assessing the normal and pathological development of the cranial base, and the cranium as a whole.Materials and methods: The study material comprised 37 human foetuses (16 males and 21 females) aged 18–30 weeks of gestation. Using CT, digital image analysis software, three-dimensional reconstruction and statistical methods, the size of the primary ossification centres of the lateral and basilar parts of the occipital bone was evaluated.Results: The morphometric characteristics of primary ossification centres of the lateral and basilar parts of the occipital bone display neither sex nor laterality differences. These ossification centres grow linearly with respect to their sagittal and transverse diameters, projection surface area and volume.Conclusions: The obtained morphometric data of primary ossification centres in the lateral and basilar parts of the occipital bone may be considered as normative for their respective prenatal weeks and may contribute to the estimation of gestational ages and the diagnostics of congenital defects