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

Use of Ultrasound to Verify the Impact of Telemedicine Myofunctional Therapy on Sleep Apnea Syndrome: Study Protocol Proposal

The anatomy of the upper airways influences the risk of obstructive sleep apnea (OSA). The size of soft tissue structures, such as the tongue, soft palate, and lateral walls of the pharynx, contributes to the pathogenesis of OSA. New lines of treatment for sleep apnea, such as myofunctional therapy (MT), aim to strengthen the oropharyngeal musculature to improve the defining parameters of apnea. The present protocol uses ultrasound imaging to measure the size of the lingual musculature non-invasively and cost-effectively and evaluates the changes in its morphology. Eligible patients include those with OSA who have undergone submental cervical ultrasound and drug-induced sleep endoscopy before starting MT with the AirwayGym app. Follow-up evaluations are conducted at 3 months after beginning treatment. Patients diagnosed with OSA via questionnaires and polysomnography or respiratory polygraphy are evaluated anatomically and functionally using the Iowa Oral Performance Instrument, a tongue digital spoon, somnoscopy, and submental cervical ultrasound to assess their responses to the AirwayGym app. The lingual thickness (mm) and volume (cm3) and the distance between both lingual arteries (mm) are measured. The AirwayGym app helps users and therapists monitor the patient performance of MT. Incorporating submental ultrasound can be a useful non-invasive tool to evaluate OSA and MT

Le Paraguay à l'Ombre de ses Guerres. : Mémoires des guerres II.

Corpus "Colloques AAR"Le Paraguay a été le théâtre des deux guerres les plus importantes et meurtrières de l'Amérique post-coloniale. La Guerre de la Triple Alliance (1865-1870 : Brésil, Argentine, Uruguay/Paraguay) et la Guerre du Chaco (1932-1935 : Bolivie / Paraguay). Ces deux guerres constituent des clés de lecture incontournables pour comprendre les dynamiques en cours dans les pays de la région. Elles ne peuvent être cernées dans toute leurs densité et complexité qu'à la condition de les réinscrire dans une dynamique régionale de longue durée, en tant que dénouement historique des tensions, des fractures et des forces qui assaillent et traversent cet espace tout le long de son histoire pré-coloniale, coloniale et indépendante. Le Colloque International convoque des savoirs divers –anthropologie, littérature, histoire- pour multiplier les angles d'analyse : nations indigènes et guerres étatiques, imaginaires et littératures sur le front de bataille, histoire connectée des guerres, mémoire des guerres. Un colloque organisé avec le soutien de : - ITAIPU, CNRS, CECIEC, MInisterio de Relaciones Exteriores (Paraguay), Ministère des Affaires Etrangères (France), Ambassade du Paraguay en France, Ambassade de France au Paraguay, MInisterio de Educación y Cultura (Paraguay), Université Paris X Nanterre

Muscular Assessment in Patients With Severe Obstructive Sleep Apnea Syndrome: Protocol for a Case-Control Study.

Myofunctional therapy is currently a reasonable therapeutic option to treat obstructive sleep apnea-hypopnea syndrome (OSAHS). This therapy is based on performing regular exercises of the upper airway muscles to increase their tone and prevent their collapse. Over the past decade, there has been an increasing number of publications in this area; however, to our knowledge, there are no studies focused on patients who can most benefit from this therapy. This protocol describes a case-control clinical trial aimed at determining the muscular features of patients recently diagnosed with severe OSAHS compared with those of healthy controls. Patients meeting set criteria will be sequentially enrolled up to a sample size of 40. Twenty patients who meet the inclusion criteria for controls will also be evaluated. Patients will be examined by a qualified phonoaudiologist who will take biometric measurements and administer the Expanded Protocol of Orofacial Myofunctional Evaluation with Scores (OMES), Friedman Staging System, Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index questionnaires. Measures of upper airway muscle tone will also be performed using the Iowa Oral Performance Instrument and tongue digital spoon devices. Evaluation will be recorded and reevaluated by a second specialist to determine concordance between observers. A total of 60 patients will be enrolled. Both the group with severe OSAHS (40 patients) and the control group (20 subjects) will be assessed for differences between upper airway muscle tone and OMES questionnaire responses. This study will help to determine muscle patterns in patients with severe OSAHS and can be used to fill the gap currently present in the assessment of patients suitable to be treated with myofunctional therapy. ISRCTN Registry ISRCTN12596010; https://www.isrctn.com/ISRCTN12596010. PRR1-10.2196/30500

Improving Adherence to Myofunctional Therapy in the Treatment of Sleep-Disordered Breathing

Myofunctional therapy (MT) is used to treat sleep-disordered breathing. However, MT has low adherence—only ~10% in most studies. We describe our experiences with MT delivered through a mobile health app named Airway Gym®, which is used by patients who have rejected continuous positive airway pressure and other therapies. We compared ear, nose, and throat examination findings, Friedman stage, tongue-tie presence, tongue strength measured using the Iowa oral performance instrument (IOPI), and full polysomnography before and after the 3 months of therapy. Participants were taught how to perform the exercises using the app at the start. Telemedicine allowed physicians to record adherence to and accuracy of the exercise performance. Fifty-four patients were enrolled; 35 (64.8%) were adherent and performed exercises for 15 min/day on five days/week. We found significant changes (p 2 saturation (80.91% ± 6.1% to 85.09% ± 5.3%). IOPI scores correlated significantly with AHI after the therapy (Pearson r = 0.4; p = 0.01). The 19 patients who did not adhere to the protocol showed no changes. MT based on telemedicine had good adherence, and its effect on AHI correlated with IOPI and improvement in tongue-tie

Non-acid reflux and sleep apnea: the importance of drug induced sleep endoscopy.

We present the first case of a patient with obstructive sleep apnea syndrome (OSA), where drug induced sleep endoscopy was helpful to suspect a non-acid reflux disease and showed an improvement in a swollen epiglottis after treatment. Patient ameliorated significantly his disease only with medical therapy. A 54-year-old man without significant anatomical findings with obstructive sleep apnea syndrome and non-acid gastroesophageal reflux disease (GERD) disease whose Apnea- hypopnea index (AHI) was significantly reduced with the intake of 500 mg of sodium alginate twice a day for 6 months. Conventional digestive tests such as esophagoscopy and simple- and double-channel 24-h pH-metry suggested mild GERD. Conventional proton-pump inhibitor treatment with pantoprazole (40 mg daily) was started without any improvement in his sleep. Multichannel intraluminal 24-h impedanciometry indicated the presence of severe pathological GER of gaseous origin. The patient's AHI decreased from 25.3 at baseline to 8 after treatment with sodium alginate. A drug-induced sleep endoscopy study showed the changes before and after this treatment and was helpful for the diagnosis. Thus, medical treatment can be a therapeutic option in some patients with OSA. Multichannel 24-h impedanciometry should be performed when nonacid GERD is suspected

Le Paraguay à l'Ombre de ses Guerres. : Ecrire l'histoire du Mercosur et de l'Europe.

Corpus "Colloques AAR"Le Paraguay a été le théâtre des deux guerres les plus importantes et meurtrières de l'Amérique post-coloniale. La Guerre de la Triple Alliance (1865-1870 : Brésil, Argentine, Uruguay/Paraguay) et la Guerre du Chaco (1932-1935 : Bolivie / Paraguay). Ces deux guerres constituent des clés de lecture incontournables pour comprendre les dynamiques en cours dans les pays de la région. Elles ne peuvent être cernées dans toute leurs densité et complexité qu'à la condition de les réinscrire dans une dynamique régionale de longue durée, en tant que dénouement historique des tensions, des fractures et des forces qui assaillent et traversent cet espace tout le long de son histoire pré-coloniale, coloniale et indépendante. Le Colloque International convoque des savoirs divers –anthropologie, littérature, histoire- pour multiplier les angles d'analyse : nations indigènes et guerres étatiques, imaginaires et littératures sur le front de bataille, histoire connectée des guerres, mémoire des guerres. Un colloque organisé avec le soutien de : - ITAIPU, CNRS, CECIEC, MInisterio de Relaciones Exteriores (Paraguay), Ministère des Affaires Etrangères (France), Ambassade du Paraguay en France, Ambassade de France au Paraguay, MInisterio de Educación y Cultura (Paraguay), Université Paris X Nanterre

Risk of diabetes in patients with sleep apnea: comparison of surgery versus CPAP in a long-term follow-up study

Abstract This study aimed to obtain a comprehensive view of the risk of developing diabetes in patients with obstructive sleep apnea (OSA) and to compare this risk between patients receiving continuous positive airway pressure (CPAP) therapy versus upper airway surgery (UAS). We used local and the global-scale federated data research network TriNetX to obtain access to electronic medical records, including those for patients diagnosed with OSA, from health-care organizations (HCOs) worldwide. Using propensity score matching and the score-matched analyses of data for 5 years of follow-up, we found that patients who had undergone UAS had a lower risk of developing diabetes than those who used CPAP (risk ratio 0.415, 95% confidence interval (CI) 0.349–0.493). The risk for newly diagnosed diabetes patients showed a similar pattern (hazard ratio 0.382; 95% CI 0.317–0.459). Both therapies seem to protect against diabetes (Risk 0.081 after UAS vs. 0.195 after CPAP). Analysis of the large data sets collected from HCOs in Europe and globally lead us to conclude that, in patients with OSA, UAS can prevent the development of diabetes better than CPAP. Graphical Abstrac

Risk of diabetes in patients with sleep apnea: comparison of surgery versus CPAP in a long-term follow-up study

This study aimed to obtain a comprehensive view of the risk of developing diabetes in patients with obstructive sleep apnea (OSA) and to compare this risk between patients receiving continuous positive airway pressure (CPAP) therapy versus upper airway surgery (UAS). We used local and the global-scale federated data research network TriNetX to obtain access to electronic medical records, including those for patients diagnosed with OSA, from health-care organizations (HCOs) worldwide. Using propensity score matching and the score-matched analyses of data for 5 years of follow-up, we found that patients who had undergone UAS had a lower risk of developing diabetes than those who used CPAP (risk ratio 0.415, 95% confidence interval (CI) 0.349-0.493). The risk for newly diagnosed diabetes patients showed a similar pattern (hazard ratio 0.382; 95% CI 0.317-0.459). Both therapies seem to protect against diabetes (Risk 0.081 after UAS vs. 0.195 after CPAP). Analysis of the large data sets collected from HCOs in Europe and globally lead us to conclude that, in patients with OSA, UAS can prevent the development of diabetes better than CPAP