Streptococcus pneumoniae: evolución de los serotipos y los patrones de susceptibilidad antimicrobiana en aislamientos invasores en 11 años de vigilancia en colombia (1994 -2004).

Background. Streptococcus pneumoniae is an important cause of morbidity and mortality in children and adults in the world.Objective. Analysis of data from laboratory surveillance of S. pneumoniae, invasive isolates recovered from 1994 to 2004.Materials And Methods. Database of invasive isolates of S. pneumoniae, sent to the Microbiology Group through the national surveillance laboratory network of acute bacterial meningitis and acute respiratory infections, from 1994 to 2004. The isolates had epidemiological data, serotyping, antimicrobial susceptibility patterns and some of them molecular typing.Results. The data of 2,022 isolates from 120 hospitals of different regions of the country were analyzed. The isolates were recovered mainly from blood cultures (50.7%) and cerebrospinal fluid (42%). The most important serotypes were 14, 6B, 23F, 1, 5, 6A, 19F, 18C y 9V, which account for 83.6% of isolates obtained from children under 6 years of age, 74% from the 6 -14 year age group and 61.4% from children over 14 years of age. Overall, 29.8% of isolates presented diminished susceptibility to penicillin (DSP), 44.3% to trimethoprim-sulphamethoxazole, 32.4% to tetracycline, 8.2% to chloramphenicol and 3.8% to erythromycin. All isolates were susceptible to vancomycin and 13% were multiresistant. Six hundred two DSP isolates were molecularly typed, 27 (4.5%), were related with the Spain23F-1 clone, 38 (6.3%) with the Spain6B-2, 301 (50%) with the Spain9V-3 and 75 (12.5%) with the Colombia23F-26 clone. Moreover, all 138 isolates with capsular type 5 were related to the Colombia5-19 clone.Conclusion. The results provide basic information necessary to design and implement strategies for prevention of pneumococcal disease.Introducción. Streptococcus pneumoniae es una las principales causas de morbilidad y mortalidad en niños y adultos en el mundo. Objetivo. Realizar un análisis de los datos de la vigilancia por el laboratorio de los aislamientos invasores de S. pneumoniae recuperados entre 1994 y 2004. Materiales y métodos. Se empleó la información de los aislamientos invasores de S. pneumoniae recibidos en el Grupo de Microbiología del Instituto Nacional de Salud durante la vigilancia de meningitis bacteriana aguda e infección respiratoria aguda entre 1994 y 2004. Los aislamientos contaban con datos epidemiológicos, serotipo, patrones de susceptibilidad antimicrobiana y algunos con tipificación molecular. Resultados. Se analizaron los datos de 2.022 aislamientos procedentes de 120 hospitales de diferentes regiones del país, recuperados principalmente de hemocultivos (50,7%) y líquido cefalorraquídeo (42%). Los serotipos más importantes fueron el 14, 6B, 23F, 1, 5, 6A, 19F, 18C y 9V, los cuales corresponden al 83,6% en niños menores de 6 años, al 74,0% en el grupo de 6 a 14 años y al 61,4% en mayores de 14 años. El 29,8% de los aislamientos presentó susceptibilidad disminuida a la penicilina (SDP), 44,3% a trimetoprim-sulfametoxazol, 32,4% a tetraciclina, 8,2% a cloranfenicol, 3,8% a eritromicina; todos fueron sensibles a vancomicina y el 13% fue multirresistente. Se tipificaron 602 aislamientos con SDP, de los cuales 27 (4,5%) se relacionaron con el clon 1-España23F, 38 (6,3%) con el clon 2-España6B, 301 (50%) con el 3- España9V y 75 (12,5%) con el clon 26-Colombia23F, además, los 138 aislamientos con tipo capsular 5 se relacionaron con el clon 19-Colombia5. Conclusiones. Los resultados proporcionan información básica necesaria para el diseño e implementación de estrategias para la prevención de la enfermedad neumocócica en nuestro país

Stress echo 2020 : the international stress echo study in ischemic and non-ischemic heart disease

Background: Stress echocardiography (SE) has an established role in evidence-based guidelines, but recently its breadth and variety of applications have extended well beyond coronary artery disease (CAD). We lack a prospective research study of SE applications, in and beyond CAD, also considering a variety of signs in addition to regional wall motion abnormalities. Methods: In a prospective, multicenter, international, observational study design, > 100 certified high-volume SE labs (initially from Italy, Brazil, Hungary, and Serbia) will be networked with an organized system of clinical, laboratory and imaging data collection at the time of physical or pharmacological SE, with structured follow-up information. The study is endorsed by the Italian Society of Cardiovascular Echography and organized in 10 subprojects focusing on: contractile reserve for prediction of cardiac resynchronization or medical therapy response; stress B-lines in heart failure; hypertrophic cardiomyopathy; heart failure with preserved ejection fraction; mitral regurgitation after either transcatheter or surgical aortic valve replacement; outdoor SE in extreme physiology; right ventricular contractile reserve in repaired Tetralogy of Fallot; suspected or initial pulmonary arterial hypertension; coronary flow velocity, left ventricular elastance reserve and B-lines in known or suspected CAD; identification of subclinical familial disease in genotype-positive, phenotype- negative healthy relatives of inherited disease (such as hypertrophic cardiomyopathy). Results: We expect to recruit about 10,000 patients over a 5-year period (2016-2020), with sample sizes ranging from 5,000 for coronary flow velocity/ left ventricular elastance/ B-lines in CAD to around 250 for hypertrophic cardiomyopathy or repaired Tetralogy of Fallot. This data-base will allow to investigate technical questions such as feasibility and reproducibility of various SE parameters and to assess their prognostic value in different clinical scenarios. Conclusions: The study will create the cultural, informatic and scientific infrastructure connecting high-volume, accredited SE labs, sharing common criteria of indication, execution, reporting and image storage of SE to obtain original safety, feasibility, and outcome data in evidence-poor diagnostic fields, also outside the established core application of SE in CAD based on regional wall motion abnormalities. The study will standardize procedures, validate emerging signs, and integrate the new information with established knowledge, helping to build a next-generation SE lab without inner walls

Quality control of B-lines analysis in stress Echo 2020

Background The effectiveness trial “Stress echo (SE) 2020” evaluates novel applications of SE in and beyond coronary artery disease. The core protocol also includes 4-site simplified scan of B-lines by lung ultrasound, useful to assess pulmonary congestion. Purpose To provide web-based upstream quality control and harmonization of B-lines reading criteria. Methods 60 readers (all previously accredited for regional wall motion, 53 B-lines naive) from 52 centers of 16 countries of SE 2020 network read a set of 20 lung ultrasound video-clips selected by the Pisa lab serving as reference standard, after taking an obligatory web-based learning 2-h module ( http://se2020.altervista.org ). Each test clip was scored for B-lines from 0 (black lung, A-lines, no B-lines) to 10 (white lung, coalescing B-lines). The diagnostic gold standard was the concordant assessment of two experienced readers of the Pisa lab. The answer of the reader was considered correct if concordant with reference standard reading ±1 (for instance, reference standard reading of 5 B-lines; correct answer 4, 5, or 6). The a priori determined pass threshold was 18/20 (≥ 90%) with R value (intra-class correlation coefficient) between reference standard and recruiting center) > 0.90. Inter-observer agreement was assessed with intra-class correlation coefficient statistics. Results All 60 readers were successfully accredited: 26 (43%) on first, 24 (40%) on second, and 10 (17%) on third attempt. The average diagnostic accuracy of the 60 accredited readers was 95%, with R value of 0.95 compared to reference standard reading. The 53 B-lines naive scored similarly to the 7 B-lines expert on first attempt (90 versus 95%, p = NS). Compared to the step-1 of quality control for regional wall motion abnormalities, the mean reading time per attempt was shorter (17 ± 3 vs 29 ± 12 min, p < .01), the first attempt success rate was higher (43 vs 28%, p < 0.01), and the drop-out of readers smaller (0 vs 28%, p < .01). Conclusions Web-based learning is highly effective for teaching and harmonizing B-lines reading. Echocardiographers without previous experience with B-lines learn quickly.info:eu-repo/semantics/publishedVersio

Resistance to non-beta-lactamantibiotics in the clinicalisolates of Streptococcuspneumoniaeof children inLatin America. SIREVA II,2000–2005

Fil: Agudelo, Clara Inés. Instituto Nacional de Salud; Colombia.Fil: Castañeda, Elizabeth. Instituto Nacional de Salud; Colombia.Fil: Corso, Alejandra. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Regueira, Mabel. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: de Cunto Brandileone, María Cristina. Instituto Adolfo Lutz; Brasil.Fil: Pires Brandão, Angela. Fundação Oswaldo Cruz; Brasil.Fil: Maldonado, Aurora. Instituto de Salud Pública; Chile.Fil: Hormazabal, Juan Carlos. Instituto de Salud Pública; Chile.Fil: Tamargo, Isis. Instituto de Medicina Tropical Pedro Kourí; Cuba.Fil: Echániz-Avilés, Gabriela. Instituto Nacional de Salud Pública; México.Fil: Soto, Araceli. Instituto Nacional de Salud Pública; México.Fil: Viveros, Mónica Guadalupe. Instituto de Diagnóstico y Referencia Epidemiológicos; México.Fil: Hernández, Irma. Instituto de Diagnóstico y Referencia Epidemiológicos; México.Fil: Chamorro, Gustavo. Laboratorio Central de Salud Pública; Paraguay.Fil: Weiler, Natalie. Laboratorio Central de Salud Pública; Paraguay.Fil: Sánchez, Jacqueline. Hospital Infantil Dr. Robert Reid Cabral; República Dominicana.Fil: Feris, Jesús M. Hospital Infantil Dr. Robert Reid Cabral; República Dominicana.Fil: Camou, Teresa. Servicio Nacional de Laboratorios de Salud Pública; Uruguay.Fil: García, Gabriela. Servicio Nacional de Laboratorios de Salud Pública; Uruguay.Fil: Spadola, Enza. Instituto Nacional de Higiene Rafael Rangel; Venezuela.Fil: Payares, Daisy. Instituto Nacional de Higiene Rafael Rangel; Venezuela.Fil: Gabastou, Jean-Marc. Organización Panamericana de la Salud; Estados Unidos.Fil: di Fabio, José Luis. Organización Panamericana de la Salud; Estados Unidos.Fil: Grupo SIREVA II; Argentina.Objetivo. Determinar la evolución de la resistencia a la eritromicina, el cloranfenicol, el trimetoprim-sulfametozaxol (SXT) y la vancomicina de aislamientos invasores de Streptococcus pneumoniaeobtenidos de niños de 10 países de América Latina y del Caribe en seis años de vigilancia. Métodos. Se analizaron 8 993 aislamientos de S. pneumoniaerecuperados entre 2000 y 2005 de niños menores de 6 años con infecciones invasoras, procedentes de Argentina, Brasil, Chile, Colombia, Cuba, México, Paraguay, República Dominicana, Uruguay y Venezuela. La sensibilidad a los antibióticos se determinó mediante los métodos establecidos y estandarizados en el proyecto SIREVA. La resistencia a múltiples antibióticos se definió como la resistencia a tres o más familias de antibióticos, de los no betalactámicos analizados en este estudio o de los betalactámicos evaluados en un estudio previo en el que 37,8% de estos aislamientos presentaron sensibilidad disminuida a la penicilina. Resultados. Se encontró algún grado de resistencia al SXT y la eritromicina (56,4% y 15,4% de los aislamientos estudiados, respectivamente) y 4,6% presentó alta resistencia al cloranfenicol. Todos los aislamientos fueron sensibles a la vancomicina. Se observó la mayor frecuencia de resistencia al SXT en los aislamientos de neumonía y a la eritromicina en los casos de sepsis (61,6% y 25,5%, respectivamente; P< 0,01). La mayor frecuencia de resistencia al SXT se observó en Brasil (71,9%) y a la eritromicina en México (38,2%) y Venezuela (32,9%). Los serotipos 14, 6B, 19F y 23F fueron los que más frecuentemente se asociaron con la resistencia a los antibióticos estudiados. Conclusiones. Se observó una elevada y creciente frecuencia de aislamientos resistentes al SXT y la eritromicina, y una disminución en la proporción de aislamientos resistentes al cloranfenicol. Estas tendencias mostraron diferencias entre los países estudiado

Resistance to non-beta-lactamantibiotics in the clinicalisolates of Streptococcuspneumoniaeof children inLatin America. SIREVA II,2000–2005

Fil: Agudelo, Clara Inés. Instituto Nacional de Salud; Colombia.Fil: Castañeda, Elizabeth. Instituto Nacional de Salud; Colombia.Fil: Corso, Alejandra. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Regueira, Mabel. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: de Cunto Brandileone, María Cristina. Instituto Adolfo Lutz; Brasil.Fil: Pires Brandão, Angela. Fundação Oswaldo Cruz; Brasil.Fil: Maldonado, Aurora. Instituto de Salud Pública; Chile.Fil: Hormazabal, Juan Carlos. Instituto de Salud Pública; Chile.Fil: Tamargo, Isis. Instituto de Medicina Tropical Pedro Kourí; Cuba.Fil: Echániz-Avilés, Gabriela. Instituto Nacional de Salud Pública; México.Fil: Soto, Araceli. Instituto Nacional de Salud Pública; México.Fil: Viveros, Mónica Guadalupe. Instituto de Diagnóstico y Referencia Epidemiológicos; México.Fil: Hernández, Irma. Instituto de Diagnóstico y Referencia Epidemiológicos; México.Fil: Chamorro, Gustavo. Laboratorio Central de Salud Pública; Paraguay.Fil: Weiler, Natalie. Laboratorio Central de Salud Pública; Paraguay.Fil: Sánchez, Jacqueline. Hospital Infantil Dr. Robert Reid Cabral; República Dominicana.Fil: Feris, Jesús M. Hospital Infantil Dr. Robert Reid Cabral; República Dominicana.Fil: Camou, Teresa. Servicio Nacional de Laboratorios de Salud Pública; Uruguay.Fil: García, Gabriela. Servicio Nacional de Laboratorios de Salud Pública; Uruguay.Fil: Spadola, Enza. Instituto Nacional de Higiene Rafael Rangel; Venezuela.Fil: Payares, Daisy. Instituto Nacional de Higiene Rafael Rangel; Venezuela.Fil: Gabastou, Jean-Marc. Organización Panamericana de la Salud; Estados Unidos.Fil: di Fabio, José Luis. Organización Panamericana de la Salud; Estados Unidos.Fil: Grupo SIREVA II; Argentina.Objetivo. Determinar la evolución de la resistencia a la eritromicina, el cloranfenicol, el trimetoprim-sulfametozaxol (SXT) y la vancomicina de aislamientos invasores de Streptococcus pneumoniaeobtenidos de niños de 10 países de América Latina y del Caribe en seis años de vigilancia. Métodos. Se analizaron 8 993 aislamientos de S. pneumoniaerecuperados entre 2000 y 2005 de niños menores de 6 años con infecciones invasoras, procedentes de Argentina, Brasil, Chile, Colombia, Cuba, México, Paraguay, República Dominicana, Uruguay y Venezuela. La sensibilidad a los antibióticos se determinó mediante los métodos establecidos y estandarizados en el proyecto SIREVA. La resistencia a múltiples antibióticos se definió como la resistencia a tres o más familias de antibióticos, de los no betalactámicos analizados en este estudio o de los betalactámicos evaluados en un estudio previo en el que 37,8% de estos aislamientos presentaron sensibilidad disminuida a la penicilina. Resultados. Se encontró algún grado de resistencia al SXT y la eritromicina (56,4% y 15,4% de los aislamientos estudiados, respectivamente) y 4,6% presentó alta resistencia al cloranfenicol. Todos los aislamientos fueron sensibles a la vancomicina. Se observó la mayor frecuencia de resistencia al SXT en los aislamientos de neumonía y a la eritromicina en los casos de sepsis (61,6% y 25,5%, respectivamente; P< 0,01). La mayor frecuencia de resistencia al SXT se observó en Brasil (71,9%) y a la eritromicina en México (38,2%) y Venezuela (32,9%). Los serotipos 14, 6B, 19F y 23F fueron los que más frecuentemente se asociaron con la resistencia a los antibióticos estudiados. Conclusiones. Se observó una elevada y creciente frecuencia de aislamientos resistentes al SXT y la eritromicina, y una disminución en la proporción de aislamientos resistentes al cloranfenicol. Estas tendencias mostraron diferencias entre los países estudiado

A global observational analysis to understand changes in air quality during exceptionally low anthropogenic emission

This global study, which has been coordinated by the World Meteorological Organization Global Atmospheric Watch (WMO/GAW) programme, aims to understand the behaviour of key air pollutant species during the COVID-19 pandemic period of exceptionally low emissions across the globe. We investigated the effects of the differences in both emissions and regional and local meteorology in 2020 compared with the period 2015–2019. By adopting a globally consistent approach, this comprehensive observational analysis focuses on changes in air quality in and around cities across the globe for the following air pollutants PM2.5, PM10, PMC (coarse fraction of PM), NO2, SO2, NOx, CO, O3 and the total gaseous oxidant (OX = NO2 + O3) during the pre-lockdown, partial lockdown, full lockdown and two relaxation periods spanning from January to September 2020. The analysis is based on in situ ground-based air quality observations at over 540 traffic, background and rural stations, from 63 cities and covering 25 countries over seven geographical regions of the world. Anomalies in the air pollutant concentrations (increases or decreases during 2020 periods compared to equivalent 2015–2019 periods) were calculated and the possible effects of meteorological conditions were analysed by computing anomalies from ERA5 reanalyses and local observations for these periods. We observed a positive correlation between the reductions in NO2 and NOx concentrations and peoples’ mobility for most cities. A correlation between PMC and mobility changes was also seen for some Asian and South American cities. A clear signal was not observed for other pollutants, suggesting that sources besides vehicular emissions also substantially contributed to the change in air quality. As a global and regional overview of the changes in ambient concentrations of key air quality species, we observed decreases of up to about 70% in mean NO2 and between 30% and 40% in mean PM2.5 concentrations over 2020 full lockdown compared to the same period in 2015–2019. However, PM2.5 exhibited complex signals, even within the same region, with increases in some Spanish cities, attributed mainly to the long-range transport of African dust and/or biomass burning (corroborated with the analysis of NO2/CO ratio). Some Chinese cities showed similar increases in PM2.5 during the lockdown periods, but in this case, it was likely due to secondary PM formation. Changes in O3 concentrations were highly heterogeneous, with no overall change or small increases (as in the case of Europe), and positive anomalies of 25% and 30% in East Asia and South America, respectively, with Colombia showing the largest positive anomaly of ~70%. The SO2 anomalies were negative for 2020 compared to 2015–2019 (between ~25 to 60%) for all regions. For CO, negative anomalies were observed for all regions with the largest decrease for South America of up to ~40%. The NO2/CO ratio indicated that specific sites (such as those in Spanish cities) were affected by biomass burning plumes, which outweighed the NO2 decrease due to the general reduction in mobility (ratio of ~60%). Analysis of the total oxidant (OX = NO2 + O3) showed that primary NO2 emissions at urban locations were greater than the O3 production, whereas at background sites, OX was mostly driven by the regional contributions rather than local NO2 and O3 concentrations. The present study clearly highlights the importance of meteorology and episodic contributions (e.g., from dust, domestic, agricultural biomass burning and crop fertilizing) when analysing air quality in and around cities even during large emissions reductions. There is still the need to better understand how the chemical responses of secondary pollutants to emission change under complex meteorological conditions, along with climate change and socio-economic drivers may affect future air quality. The implications for regional and global policies are also significant, as our study clearly indicates that PM2.5 concentrations would not likely meet the World Health Organization guidelines in many parts of the world, despite the drastic reductions in mobility. Consequently, revisions of air quality regulation (e.g., the Gothenburg Protocol) with more ambitious targets that are specific to the different regions of the world may well be required.Peer reviewedFinal Published versio

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6+/-9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; pPeer reviewe

Nightside condensation of iron in an ultra-hot giant exoplanet

Ultra-hot giant exoplanets receive thousands of times Earth's insolation. Their high-temperature atmospheres (>2,000 K) are ideal laboratories for studying extreme planetary climates and chemistry. Daysides are predicted to be cloud-free, dominated by atomic species and substantially hotter than nightsides. Atoms are expected to recombine into molecules over the nightside, resulting in different day-night chemistry. While metallic elements and a large temperature contrast have been observed, no chemical gradient has been measured across the surface of such an exoplanet. Different atmospheric chemistry between the day-to-night ("evening") and night-to-day ("morning") terminators could, however, be revealed as an asymmetric absorption signature during transit. Here, we report the detection of an asymmetric atmospheric signature in the ultra-hot exoplanet WASP-76b. We spectrally and temporally resolve this signature thanks to the combination of high-dispersion spectroscopy with a large photon-collecting area. The absorption signal, attributed to neutral iron, is blueshifted by -11+/-0.7 km s-1 on the trailing limb, which can be explained by a combination of planetary rotation and wind blowing from the hot dayside. In contrast, no signal arises from the nightside close to the morning terminator, showing that atomic iron is not absorbing starlight there. Iron must thus condense during its journey across the nightside.Comment: Published in Nature (Accepted on 24 January 2020.) 33 pages, 11 figures, 3 table

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

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