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

Determination of cardiac performance in healthy dogs during maximal inotropic stimulation with dobutamine.

peer reviewe

The effectiveness and cost-effectiveness of an integrated osteoporosis care programme for postmenopausal women in Flanders: study protocol of a quasi-experimental controlled design

Osteoporosis causes high individual and societal burden, due to limited attention to fracture prevention. Integrated care for chronic conditions has shown to facilitate management of these conditions, improving clinical outcomes alongside quality of life and cost-effectiveness. This manuscript describes an integrated osteoporosis care programme that will be implemented in primary care. OBJECTIVE: To provide a comprehensive description of a quasi-experimental study design in which a newly developed integrated osteoporosis care (IOC) programme for the management of postmenopausal osteoporosis (PO) in primary care (PC) is implemented and will be compared with care as usual (CAU). METHODS: A literature research was performed and expert meetings have been taking place, which has led to the development of a complex PC intervention based on framework for integrated people-centred health services (IPCHS). RESULTS: This manuscript describes the developmental process of the preclinical phase of a quasi-experimental real-world design and the interventions as a result of this process that will be implemented during the clinical phase, along with the evaluation that will take place alongside the clinical phase: An integrative approach for the management of PO in primary care was developed and will be implemented in greater region of Ghent (GRG), Belgium. The approach consists of a complex intervention targeting patients and PC stakeholders in osteoporosis care (e.g. general practitioners (GPs), physiotherapists, nurses, pharmacists). A comparison will be made with CAU using medication possession ratios (MPR) of included patients as primary outcome. These data will be obtained from the national health database. Secondary outcomes are physician outcomes, patient-reported outcome measures (PROMs), and patient-reported experience measures (PREMs). A cost-effectiveness evaluation will be performed if the programme appears to be effective in terms of MPR. TRIAL REGISTRATION: ClinicalTrials.gov : NCT03970902.status: publishe

The effectiveness and cost-effectiveness of an integrated osteoporosis care programme for postmenopausal women in Flanders : study protocol of a quasi-experimental controlled design

The Summary Osteoporosis causes high individual and societal burden, due to limited attention to fracture prevention. Integrated care for chronic conditions has shown to facilitate management of these conditions, improving clinical outcomes alongside quality of life and cost-effectiveness. This manuscript describes an integrated osteoporosis care programme that will be implemented in primary care. Objective To provide a comprehensive description of a quasi-experimental study design in which a newly developed integrated osteoporosis care (IOC) programme for the management of postmenopausal osteoporosis (PO) in primary care (PC) is implemented and will be compared with care as usual (CAU). Methods A literature research was performed and expert meetings have been taking place, which has led to the development of a complex PC intervention based on framework for integrated people-centred health services (IPCHS). Results This manuscript describes the developmental process of the preclinical phase of a quasi-experimental real-world design and the interventions as a result of this process that will be implemented during the clinical phase, along with the evaluation that will take place alongside the clinical phase: An integrative approach for the management of PO in primary care was developed and will be implemented in greater region of Ghent (GRG), Belgium. The approach consists of a complex intervention targeting patients and PC stakeholders in osteoporosis care (e.g. general practitioners (GPs), physiotherapists, nurses, pharmacists). A comparison will be made with CAU using medication possession ratios (MPR) of included patients as primary outcome. These data will be obtained from the national health database. Secondary outcomes are physician outcomes, patient-reported outcome measures (PROMs), and patient-reported experience measures (PREMs). A cost-effectiveness evaluation will be performed if the programme appears to be effective in terms of MPR

Prélèvement au sol des glands d’une espèce de chêne exotique (Quercus rubra) par des animaux accumulateurs-disperseurs dans les forêts belges

Description of the subject. Quercus rubra L. is considered an invasive species in several European countries. However, little is known about its dispersal in the introduced range. Objectives. We investigated the significance of animal dispersal of Q. rubra acorns on the ground by vertebrates in its introduced range, and identified the animal species involved. Method. During two consecutive autumns, the removal of acorns from Q. rubra and from a native oak was assessed weekly in forest sites in Belgium. We used automated detection camera traps to identify the animals that removed acorns. Results. Quercus rubra acorns were removed by wood mice (Apodemus sylvaticus L.), red squirrels (Sciurus vulgaris L.), rats (Rattus sp.), and wild boars (Sus scrofa L.). The two former are scatter-hoarding rodents and can be considered potential dispersers. Conclusions. Dispersal of Q. rubra acorns in Western Europe by scatter-hoarding animals may help the species increasingly colonize forest ecosystems. © 2017, FAC UNIV SCIENCES AGRONOMIQUES GEMBLOUX. All rights reserved.ANR-10- IDEX-03-0

Removal of acorns of the alien oak Quercus rubra on the ground by scatter-hoarding animals in Belgian forests

Description du sujet. Quercus rubra L. est considéré comme une espèce invasive dans plusieurs pays d'Europe. Cependant, sa dispersion dans l'aire d'introduction est peu documentée. Objectifs. Nous avons observé si les glands au sol étaient déplacés par les animaux et identifié les animaux impliqués. Méthode. Durant deux automnes consécutifs, le prélèvement des glands de Q. rubra et d'une espèce de chêne indigène a été évalué chaque semaine dans différents sites en Belgique. Grâce à des pièges photographiques, les animaux prélevant des glands ont été identifiés. Résultats. Les glands de Q. rubra ont été prélevés par le mulot sylvestre (Apodemus sylvaticus L.), l'écureuil roux (Sciurus vulgaris L.), le rat (Rattus sp.) et le sanglier (Sus scrofa L.). Les deux premiers sont des rongeurs accumulateurs-disperseurs, considérés comme disperseurs potentiels. Conclusions. La dispersion des glands de Q. rubra en Europe occidentale par les animaux accumulateurs-disperseurs pourrait aider l'espèce à coloniser progressivement les écosystèmes forestiers.Description of the subject. Quercus rubra L. is considered an invasive species in several European countries. However, little is known about its dispersal in the introduced range. Objectives. We investigated the significance of animal dispersal of Q. rubra acorns on the ground by vertebrates in its introduced range, and identified the animal species involved. Method. During two consecutive autumns, the removal of acorns from Q. rubra and from a native oak was assessed weekly in forest sites in Belgium. We used automated detection camera traps to identify the animals that removed acorns. Results. Quercus rubra acorns were removed by wood mice (Apodemus sylvaticus L.), red squirrels (Sciurus vulgaris L.), rats (Rattus sp.), and wild boars (Sus scrofa L.). The two former are scatter-hoarding rodents and can be considered potential dispersers. Conclusions. Dispersal of Q. rubra acorns in Western Europe by scatter-hoarding animals may help the species increasingly colonize forest ecosystems

Removal of acorns of the alien oak Quercus rubra on the ground by scatter-hoarding animals in Belgian forests

Description du sujet. Quercus rubra L. est considéré comme une espèce invasive dans plusieurs pays d'Europe. Cependant, sa dispersion dans l'aire d'introduction est peu documentée. Objectifs. Nous avons observé si les glands au sol étaient déplacés par les animaux et identifié les animaux impliqués. Méthode. Durant deux automnes consécutifs, le prélèvement des glands de Q. rubra et d'une espèce de chêne indigène a été évalué chaque semaine dans différents sites en Belgique. Grâce à des pièges photographiques, les animaux prélevant des glands ont été identifiés. Résultats. Les glands de Q. rubra ont été prélevés par le mulot sylvestre (Apodemus sylvaticus L.), l'écureuil roux (Sciurus vulgaris L.), le rat (Rattus sp.) et le sanglier (Sus scrofa L.). Les deux premiers sont des rongeurs accumulateurs-disperseurs, considérés comme disperseurs potentiels. Conclusions. La dispersion des glands de Q. rubra en Europe occidentale par les animaux accumulateurs-disperseurs pourrait aider l'espèce à coloniser progressivement les écosystèmes forestiers.Description of the subject. Quercus rubra L. is considered an invasive species in several European countries. However, little is known about its dispersal in the introduced range. Objectives. We investigated the significance of animal dispersal of Q. rubra acorns on the ground by vertebrates in its introduced range, and identified the animal species involved. Method. During two consecutive autumns, the removal of acorns from Q. rubra and from a native oak was assessed weekly in forest sites in Belgium. We used automated detection camera traps to identify the animals that removed acorns. Results. Quercus rubra acorns were removed by wood mice (Apodemus sylvaticus L.), red squirrels (Sciurus vulgaris L.), rats (Rattus sp.), and wild boars (Sus scrofa L.). The two former are scatter-hoarding rodents and can be considered potential dispersers. Conclusions. Dispersal of Q. rubra acorns in Western Europe by scatter-hoarding animals may help the species increasingly colonize forest ecosystems

Single-Unit versus Double-Unit Umbilical Cord Blood Transplantation in Children and Young Adults with Residual Leukemic Disease

International audienc

Single-Unit versus Double-Unit Umbilical Cord Blood Transplantation in Children and Young Adults with Residual Leukemic Disease

International audienceWe previously reported in a French prospective randomized study that transplantation of 2 unrelated cord blood (UCB) units instead of 1 unit does not decrease the risk of transplantation failure but may enhance alloreactivity. Here we evaluated the influence of pretransplantation minimal residual disease (MRD) on leukemia relapse and survival after single- versus double-UCB transplantation (UCBT). Among 137 children and young adults who underwent UCBT in this randomized study, 115 had available data on MRD assessment done immediately before initiation of the pretransplantation conditioning regimen. MRD was considered positive at a level of ≥10-4, which was the case of 43 out of 115 patients. Overall, the mean 3-year survival probability was 69.1 ± 4.4%, and it was not significantly influenced by the MRD level: 70.7 ± 5.4% in MRD-negative (<10-4) patients (n = 72), 71.1 ± 9.4% in MRD-positive patients with 10-4 ≤ MRD <10-3 (n = 26) and 58.8 ± 11.9% in MRD-positive patients with ≥10-3 (n = 17). In the MRD-positive group, the mean risk of relapse was significantly lower in the double-UCBT arm compared with the single-UCBT arm (10.5 ± 7.2% versus 41.7 ± 10.4%; P = .025) leading to a higher mean 3-year survival rate (82.6 ± 9.3% versus 53.6 ± 10.3%; P = .031). This difference was observed only in patients who had not received antithymocyte globulin during their conditioning regimen. In the MRD-negative group, there was no differencebetween the single- and the double-UCBT arms. We conclude that even in cases of positive pretransplantation MRD, UCBT in children and young adults with acute leukemia yields a high cure rate, and that a double-unit strategy may enhance the graft-versus-leukemia effect and survival in these patients