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

Novel method of music to architecture transposition

Muzyka i architektura posiadają wiele cech wspólnych, szczególnie gdy będziemy je porównywać pod względem zasad kompozycyjnych, a zwłaszcza przy wprowadzeniu wspólnego czasu percepcji tych kompozycji. Podstawowe zasady kompozycyjne mające odniesienie do muzyki, sztuk wizualnych i architektury można pokazać za pomocą pewnych modeli i symulacji. Są nimi między innymi: grafiki muzyczne, wizualizacje malarskie, graficzne i przestrzenne, impresje i barwne kolaże, oraz transpozycje. Autorska metoda transpozycji muzyki na architekturę polega na czasowej analizie wybranej muzyki w formie trzech kroków, poprzedzonych krokiem „0”, poprzez sporządzenie: 1. wykresu wrażeń, 2. zapisu graficznego, który jest krokiem pośrednim ukazującym w sposób graficzny struktury dźwiękowe na osi czasu. Zapisy graficzne dotyczące melodii, rytmu, czy dynamiki słuchanego utworu mogą tu stanowić wytyczne do transpozycji kształtu, światła i koloru dla kompozycji architektonicznej. 3. transpozycji przestrzennej. Decydującym narzędziem badania praw percepcji i budowy kompozycji jest tu zastosowanie wykresu wrażeń. Jest on nośnikiem wrażeniowej gry percepcyjnej z jej dominantami, wstępem i zakończeniem.. Sedno metody transpozycji muzyki na architekturę polega na wprowadzeniu odpowiedniej konfiguracji bodźców przestrzennych, tak aby odwzorować wykres wrażeń sporządzony podczas słuchania muzyki.Music and architecture possess many common features, especially when compared in terms of the composition rules, especially when the common perception time of these compositions is included. Basic composition rules relating to music, visual arts and architecture may be shown using certain models and simulations. These include musical graphic, painted, graphical and spatial visualizations, impression and colorful collages, and transpositions. Novel method of music to architecture transposition is based on the temporal analysis of the selected music in the form of the following three steps preceded by the "0" step: 1. chart of impressions, 2. graphical transposition which is an intermediate step showing graphically the structure of the sound on the time axis. Graphic recording of the melody, rhythm, and dynamics of current musical piece may provide guidance to transpose shape, light and color into architectural composition. The third step is spatial transposition with creation of the chart of sensations as the tool to study the perception rights and the construction of a composition. It is a medium for the perception game with dominants, introduction and ending. The essence of the transposition of the music into the architecture is the introduction of appropriate configuration of the spatial stimuli to reproduce the chart of impressions drawn while listening to music

Validation of the CREST model and comparison with SCAI shock classification for the prediction of circulatory death in resuscitated out-of-hospital cardiac arrest

Aims We validated the CREST model, a 5 variable score for stratifying the risk of circulatory aetiology death (CED) following out-of-hospital cardiac arrest (OHCA) and compared its discrimination with the SCAI shock classification. Circulatory aetiology death occurs in approximately a third of patients admitted after resuscitated OHCA. There is an urgent need for improved stratification of the patient with OHCA on arrival to a cardiac arrest centre to improve patient selection for invasive interventions. Methods and results The CREST model and SCAI shock classification were applied to a dual-centre registry of 723 patients with cardiac aetiology OHCA, both with and without ST-elevation myocardial infarction (STEMI), between May 2012 and December 2020. The primary endpoint was a 30-day CED. Of 509 patients included (62.3 years, 75.4% male), 125 patients had CREST = 0 (24.5%), 162 had CREST = 1 (31.8%), 140 had CREST = 2 (27.5%), 75 had CREST = 3 (14.7%), 7 had a CREST of 4 (1.4%), and no patients had CREST = 5. Circulatory aetiology death was observed in 91 (17.9%) patients at 30 days [STEMI: 51/289 (17.6%); non-STEMI (NSTEMI): 40/220 (18.2%)]. For the total population, and both NSTEMI and STEMI subpopulations, an increasing CREST score was associated with increasing CED (all P &lt; 0.001). The CREST score and SCAI classification had similar discrimination for the total population [area under the receiver operating curve (AUC) = 0.72/calibration slope = 0.95], NSTEMI cohort (AUC = 0.75/calibration slope = 0.940), and STEMI cohort (AUC = 0.69 and calibration slope = 0.925). Area under the receiver operating curve meta-analyses demonstrated no significant differences between the two classifications. Conclusion The CREST model and SCAI shock classification show similar prediction results for the development of CED after OHCA.</p

Paradigms lost and gained: stakeholder experiences of crisis distance learning during the Covid-19 pandemic

The physical distancing requirements designed to slow the contagion of COVID-19 instigated sweeping changes to the education sector. School closures in 193 countries brought significant disruption to education and to the lives of children, parents, and teachers. This study explored the experiences of school stakeholders during this period of crisis distance learning (DL). The perspectives of participants in six discrete focus groups of pupils, parents, and teachers at a private school in Dubai, United Arab Emirates, were subject to thematic analysis. Researchers identified three key themes, including ‘a need for stakeholder support’, ‘curriculum delivery implications’, and ‘educational outcomes of crisis distance learning’. Conclusions and recommendations will be of interest to researchers, teachers, school leaders, and teacher education providers

Overview of the current status of familial hypercholesterolaemia care in over 60 countries - The EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

Background and aims: Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries. Methods: Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management. Results: 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in 3c2/3 countries. Lipoprotein-apheresis is offered in 3c60% countries, although access is limited. Conclusions: FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed

Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

Background: The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally. Methods: Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Data were assessed overall and by WHO regions, sex, and index versus non-index cases. Findings: Of the 61 612 individuals in the registry, 42 167 adults (21 999 [53·6%] women) from 56 countries were included in the study. Of these, 31 798 (75·4%) were diagnosed with the Dutch Lipid Clinic Network criteria, and 35 490 (84·2%) were from the WHO region of Europe. Median age of participants at entry in the registry was 46·2 years (IQR 34·3–58·0); median age at diagnosis of familial hypercholesterolaemia was 44·4 years (32·5–56·5), with 40·2% of participants younger than 40 years when diagnosed. Prevalence of cardiovascular risk factors increased progressively with age and varied by WHO region. Prevalence of coronary disease was 17·4% (2·1% for stroke and 5·2% for peripheral artery disease), increasing with concentrations of untreated LDL cholesterol, and was about two times lower in women than in men. Among patients receiving lipid-lowering medications, 16 803 (81·1%) were receiving statins and 3691 (21·2%) were on combination therapy, with greater use of more potent lipid-lowering medication in men than in women. Median LDL cholesterol was 5·43 mmol/L (IQR 4·32–6·72) among patients not taking lipid-lowering medications and 4·23 mmol/L (3·20–5·66) among those taking them. Among patients taking lipid-lowering medications, 2·7% had LDL cholesterol lower than 1·8 mmol/L; the use of combination therapy, particularly with three drugs and with proprotein convertase subtilisin–kexin type 9 inhibitors, was associated with a higher proportion and greater odds of having LDL cholesterol lower than 1·8 mmol/L. Compared with index cases, patients who were non-index cases were younger, with lower LDL cholesterol and lower prevalence of cardiovascular risk factors and cardiovascular diseases (all p<0·001). Interpretation: Familial hypercholesterolaemia is diagnosed late. Guideline-recommended LDL cholesterol concentrations are infrequently achieved with single-drug therapy. Cardiovascular risk factors and presence of coronary disease were lower among non-index cases, who were diagnosed earlier. Earlier detection and greater use of combination therapies are required to reduce the global burden of familial hypercholesterolaemia. Funding: Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron