Mortalidad por lesiones de tránsito en adultos mayores en la República de Ecuador entre los años 1990 y 2018: estudio descriptivo

The present study aimed to estimate the trend in road traffic injury mortality in older adults (60 years of age or older) and comparison with those <60 years of age in Ecuador (1990-2018). Official death records and population projections were used to calculate mortality rates per 100,000 population, rate ratios, years of potential life lost (YPLL), and trends. Those under 60 years of age had mortality rates of 16.7 (per 100,000) compared to 36.2 (per 100,000) for older adults, with an increasing trend in YPLL. Older adults recorded fewer deaths than the younger population. However, it is necessary to develop road safety strategies oriented to the progressive aging of the Ecuadorian population. Keywords: older adults, traffic accidents, mortality, trends, Ecuador. References [1]World Health Organization (2018, May 17). Global Status Report on Road Safety 2018 [Online]. Available: https://www.who.int/violence_injury_prevention/road_safety_status/2018/en/ [2]A. F. Algora-Buenafé, M. Russo-Puga, P. R. Suasnavas-Bermúdez, P. Merino-Salazar and A. R. Gómez-García,"Tendencias de los accidentes de tránsito en Ecuador: 2000-2015", Gerencia y Políticas de Salud, vol. 16, n.º 33, pp. 52–58, noviembre de 2017. [Online]. Available: https://doi.org/10.11144/javeriana.rgps16-33.tate. [Last Access: September 2nd, 2021 ]. [3]Pan American Health Organization (2019, June 22). Status of Road Safety in the Region of the Americas [Online]. Available: http://iris.paho.org/xmlui/handle/123456789/51088. [4]S. J. Eun, "Trends in mortality from road traffic injuries in South Korea, 1983–2017: Joinpoint regression and age-period-cohort analyses", Accident Analysis &Prevention, vol. 134, p. 105325, January 2020. [Online]. Available: https://doi.org/10.1016/j.aap.2019.105325. [Last Access: September 2nd, 2021 ]. [5]S. Azami-Aghdash, M. H. Aghaei, and H. Sadeghi-Bazarghani, "Epidemiology of Road Traffic Injuries among Elderly People; A Systematic Review and Meta-Analysis", Bulletin of Emergency and Trauma, vol. 6, n.º 4, pp. 279–291, October 2018. [Online]. Available: https://doi.org/10.29252/beat-060403. [Last Access: September 7th, 2021 ]. [6]Y. Abolfathi Momtaz, R. Kargar, R. Hosseiny, and R. Sahaf, "Rate and pattern of road traffic accidents among older and younger drivers", Healthy Aging Research, vol. 7, n.º 2, June 2018, art. n.º e18. [Online]. Available: https://doi.org/10.1097/hxr.0000000000000018. [Last Access: October 13th, 2021 ]. [7]P. Martínez, D. Contreras and M. Moreno, "Safe mobility, socioeconomic inequalities, and aging: A 12-year multilevel interrupted time-series analysis of road traffic death rates in a Latin American country", PLOS ONE, vol. 15, n.º 1, enero de 2020, art. n.º e0224545. [Online]. Available: https://doi.org/10.1371/journal.pone.0224545. [Last Access: October 10th, 2021 ]. [8]G. Bergen et al., "How do older adult drivers self-regulate? Characteristics of self-regulation classes defined by latent class analysis", Journal of Safety Research, vol. 61, pp. 205–210, June 2017. [Online]. Available: https://doi.org/10.1016/j.jsr.2017.01.002. [Last Access: October 9th, 2021 ] [9]Instituto Nacional de Estadística y Censos (2018, February 2). Registros Estadísticos de Nacidos Vivos, Defunciones Fetales y Defunciones Generales [Online]. Available: https://www.ecuadorencifras.gob.ec/nacimientos_y_defunciones. [10]Instituto Nacional de Estadística y Censos (2017, August 2). Proyecciones Demográficas, 2010 – 2020. [Online]. Available: https://sni.gob.ec/proyecciones-y-estudios-demograficos. [11]W. Y. Yee, "Road traffic injuries in the elderly", Emergency Medicine Journal, vol. 23, n.º 1, pp. 42–46, January 2006. [Online]. Available: https://doi.org/10.1136/emj.2005.023754. [Last Access: October 21st, 2021] [12]L. McElroy, J. Juern, A. Bertleson, Q. Xiang, A. Szabo and J. Weigelt, "A single urban center experience with adult pedestrians struck by motor vehicles", WMJ:official publication of the State Medical Society of Wisconsin, vol. 112(3), pp. 117-122, 2013. [13]K. Bhalla, M. Naghavi, S. Shahraz, D. Bartels and C. J. L. Murray, "Building national estimates of the burden of road traffic injuries in developing countries from all available data sources: Iran", Injury Prevention, vol. 15, n.º 3, pp. 150–156, June 2009. [Online]. Available: https://doi.org/10.1136/ip.2008.020826. [Last Access: October 1st, 2021]. [14]D. Bartels, K. Bhalla, S. Shahraz, J. Abraham, R. Lozano and C. J. L. Murray, "Incidence of road injuries in Mexico: country report", International Journal of Injury Control and Safety Promotion, vol. 17, n.º 3, pp. 169–176, September 2010. [Online]. Available: https://doi.org/10.1080/17457300903564553. [Last Access: November 16th, 2021]. [15]W. R. Boot, C. Stothart and N. Charness, "Improving the Safety of Aging Road Users: A Mini-Review", Gerontology, vol. 60, n.º 1, pp. 90–96, 2014. [Online]. Available: https://doi.org/10.1159/000354212.  [Last Access: November 6th, 2021] [16]Y. L. Michael, E. P. Whitlock, J. S. Lin, R. Fu, E. A. O'Connor and R. Gold, "Primary Care–Relevant Interventions to Prevent Falling in Older Adults: A Systematic Evidence Review for the U.S. Preventive Services Task Force", Annals of Internal Medicine, vol. 153, n.º 12, p. 815, December 2010. [Online]. Available: https://doi.org/10.7326/0003-4819-153-12-201012210-00008.[Last Access: November 29th, 2021] [17]H. Etehad, S. Yousefzadeh-Chabok, A. Davoudi-Kiakalaye, D. A. Moghadam, H. Hemati and Z. Mohtasham-Amiri, "Impact of road traffic accidents on the elderly", Archives of Gerontology and Geriatrics, vol. 61, n.º 3, pp. 489–493, November de 2015. [Online]. Available: https://doi.org/10.1016/j.archger.2015.08.008. [Last Access: November 3th, 2021]. [18]B. H. Ang, W. S. Chen and S. W. H. Lee, "Global burden of road traffic accidents in older adults: A systematic review and meta-regression analysis", Archives of Gerontology and Geriatrics, vol. 72, pp. 32–38, September 2017. [Online]. Available: https://doi.org/10.1016/j.archger.2017.05.004. [Last Access: December 19th, 2021] [19]J. P. Thompson, M. R. J. Baldock and J. K. Dutschke, "Trends in the crash involvement of older drivers in Australia", Accident Analysis & Prevention, vol. 117, pp. 262–269, August 2018. [Online]. Available: https://doi.org/10.1016/j.aap.2018.04.027. [Last Access: December 16th, 2021].El presente estudio tuvo como objetivo estimar la tendencia de mortalidad por lesiones de tránsito en adultos mayores (igual o mayor a 60 años edad) y la comparación con los menores a 60 años edad en el Ecuador (1990-2018). Se emplearon los registros de defunción y proyecciones demográficas oficiales para el cálculo de tasas de mortalidad por 100 mil habitantes, razón de tasas, años de vida potencialmente perdidos (AVPP) y tendencias. Los menores a 60 años edad registraron tasas de mortalidad de 16,7 (por 100 mil) frente a 36,2 (por 100 mil) en los adultos mayores, con tendencia al aumento en los AVPP. Los adultos mayores registraron menor número de casos de fallecimientos con relación a la población más joven. Sin embargo, es necesario elaborar estrategias en seguridad vial orientadas al progresivo envejecimiento de la población ecuatoriana. Palabras Clave: Anciano, accidentes de tránsito, mortalidad, tendencias, Ecuador. Referencias [1]World Health Organization (2018, May 17). Global Status Report on Road Safety 2018 [Online]. Available: https://www.who.int/violence_injury_prevention/road_safety_status/2018/en/ [2]A. F. Algora-Buenafé, M. Russo-Puga, P. R. Suasnavas-Bermúdez, P. Merino-Salazar y A. R. Gómez-García,"Tendencias de los accidentes de tránsito en Ecuador: 2000-2015", Gerencia y Políticas de Salud, vol. 16, n.º 33, pp. 52–58, noviembre de 2017. Accedido el 2 deseptiembre de 2021. [En línea]. Disponible: https://doi.org/10.11144/javeriana.rgps16-33.tate [3]Pan American Health Organization (2019, June 22). Status of Road Safety in the Region of the Americas [Online]. Available: http://iris.paho.org/xmlui/handle/123456789/51088. [4]S. J. Eun, "Trends in mortality from road traffic injuries in South Korea, 1983–2017: Joinpoint regression and age-period-cohort analyses", Accident Analysis &Prevention, vol. 134, p. 105325, enero de 2020. Accedido el 2 de septiembre de 2021. [En línea]. Disponible: https://doi.org/10.1016/j.aap.2019.105325. [5]S. Azami-Aghdash, M. H. Aghaei y H. Sadeghi-Bazarghani, "Epidemiology of Road Traffic Injuries among Elderly People; A Systematic Review and Meta-Analysis", Bulletin of Emergency and Trauma, vol. 6, n.º 4, pp. 279–291, octubre de 2018. Accedido el 7 deseptiembre de 2021. [En línea]. Disponible: https://doi.org/10.29252/beat-060403 [6]Y. Abolfathi Momtaz, R. Kargar, R. Hosseiny y R. Sahaf, "Rate and pattern of road traffic accidents among older and younger drivers", Healthy Aging Research, vol. 7, n.º 2, junio de 2018, art. n.º e18. Accedido el 13 de octubre de 2021. [En línea]. Disponible: https://doi.org/10.1097/hxr.0000000000000018. [7]P. Martínez, D. Contreras y M. Moreno, "Safe mobility, socioeconomic inequalities, and aging: A 12-year multilevel interrupted time-series analysis of road traffic death rates in a Latin American country", PLOS ONE, vol. 15, n.º 1, enero de 2020, art. n.º e0224545. Accedido el 10 de octubre de 2021. [En línea]. Disponible: https://doi.org/10.1371/journal.pone.0224545 [8]G. Bergen et al., "How do older adult drivers self-regulate? Characteristics of self-regulation classes defined by latent class analysis", Journal of Safety Research, vol. 61, pp. 205–210, junio de 2017. Accedido el 9 de octubre de 2021. [En línea]. Disponible: https://doi.org/10.1016/j.jsr.2017.01.002. [9]Instituto Nacional de Estadística y Censos (2018, February 2). Registros Estadísticos de Nacidos Vivos, Defunciones Fetales y Defunciones Generales [Online].Available: https://www.ecuadorencifras.gob.ec/nacimientos_y_defunciones. [10]Instituto Nacional de Estadística y Censos (2017, August 2). Proyecciones Demográficas, 2010 – 2020. [Online]. Available: https://sni.gob.ec/proyecciones-y-estudios-demograficos. [11]W. Y. Yee, "Road traffic injuries in the elderly", Emergency Medicine Journal, vol. 23, n.º 1, pp. 42–46, enero de 2006. Accedido el 21 de octubre de2021. [En línea]. Disponible: https://doi.org/10.1136/emj.2005.023754. [12]L. McElroy, J. Juern, A. Bertleson, Q. Xiang, A. Szabo and J. Weigelt, "A single urban center experience with adult pedestrians struck by motor vehicles", WMJ:official publication of the State Medical Society of Wisconsin, vol. 112(3), pp. 117-122, 2013. [13]K. Bhalla, M. Naghavi, S. Shahraz, D. Bartels y C. J. L. Murray, "Building national estimates of the burden of road traffic injuries in developing countries from all available data sources: Iran", Injury Prevention, vol. 15, n.º 3, pp. 150–156, junio de 2009. Accedido el 1 de octubre de 2021. [En línea]. Disponible: https://doi.org/10.1136/ip.2008.020826. [14]D. Bartels, K. Bhalla, S. Shahraz, J. Abraham, R. Lozano y C. J. L. Murray, "Incidence of road injuries in Mexico: country report", International Journal of Injury Control and Safety Promotion, vol. 17, n.º 3, pp. 169–176, septiembre de 2010. Accedido el 16 de noviembre de 2021. [En línea]. Disponible: https://doi.org/10.1080/17457300903564553. [15]W. R. Boot, C. Stothart y N. Charness, "Improving the Safety of Aging Road Users: A Mini-Review", Gerontology, vol. 60, n.º 1, pp. 90–96, 2014. Accedido el 6 de noviembre de 2021. [En línea]. Disponible: https://doi.org/10.1159/000354212. [16]Y. L. Michael, E. P. Whitlock, J. S. Lin, R. Fu, E. A. O'Connor y R. Gold, "Primary Care–Relevant Interventions to Prevent Falling in Older Adults: A Systematic Evidence Review for the U.S. Preventive Services Task Force", Annals of Internal Medicine, vol. 153, n.º 12, p. 815, diciembre de 2010. Accedido el 29 de noviembre de 2021. [En línea]. Disponible: https://doi.org/10.7326/0003-4819-153-12-201012210-00008. [17]H. Etehad, S. Yousefzadeh-Chabok, A. Davoudi-Kiakalaye, D. A. Moghadam, H. Hemati y Z. Mohtasham-Amiri, "Impact of road traffic accidents on the elderly", Archives of Gerontology and Geriatrics, vol. 61, n.º 3, pp. 489–493, noviembre de 2015. Accedido el 3 de noviembre de 2021. [En línea]. Disponible: https://doi.org/10.1016/j.archger.2015.08.008. [18]B. H. Ang, W. S. Chen y S. W. H. Lee, "Global burden of road traffic accidents in older adults: A systematic review and meta-regression analysis", Archives of Gerontology and Geriatrics, vol. 72, pp. 32–38, septiembre de 2017. Accedido el 19 de diciembre de 2021. [En línea]. Disponible: https://doi.org/10.1016/j.archger.2017.05.004. [19]J. P. Thompson, M. R. J. Baldock y J. K. Dutschke, "Trends in the crash involvement of older drivers in Australia", Accident Analysis & Prevention, vol. 117, pp. 262–269, agosto de 2018. Accedido el 16 de diciembre de 2021. [En línea]. Disponible: https://doi.org/10.1016/j.aap.2018.04.027

Health inequity in workers of Latin America and the Caribbean

Latin America and the Caribbean (LAC) is the world’s most inequitable region in terms of wealth distribution. The full scale of social inequalities in health has been hidden by the lack of reliable data. This study aimed to measure and compare health inequalities in the working population within and between 15 countries of LAC

Temporal and spatial distribution fatal occupational injuries in Ecuador

Introduction: Ecuador is a country in South America, divided geographically by the Andean Mountain Range.  With the approval of the Resolution No C.D. 333 in 2010, companies are compelled to report all occupational accidents and diseases to the corresponding Occupational Health Public Organisms. Currently, there are no studies on the geographic and temporal distribution of deadly occupational accidents in the country. Objective: The objective of this study was to determine the temporal and geographic distribution of fatal occupational accidents (FOA) in Ecuador. Material-Methods: Ecologic Study of temporal and geographical distribution of FOA in the 24 provinces of Ecuador between 2010 and 2016. Data was obtained thru official secondary information sources. Gross and Adjusted Mortality Rates were calculated for workers affiliated to the General Mandatory Insurance, allowing the space representation in terms of the object of study. Results: During the period analyzed, 1.748 workers have passed due to work related accidents in Ecuador. The Gross Mortality Rate (x100.000-affiliated workers) presents a decreasing tendency from 2010 (13.2) to 2014 (6.3), increasing for 2015 (9.5). The main provinces with a higher Adjusted Mortality Rate (x10.000-affiliated workers) are located in the Amazon Region: Morona Santiago, Napo, Orellana and Sucumbíos. Conclusions: Ecuadorian Geography implies important differences in terms of FOA distribution by provinces and the compliance of legal norms in Safety and Occupational Health thru time. The temporal distribution and geographic representation of this phenomenon will allow the corresponding public control entities to identify provinces with high mortality rates and implement specific actions to prevent. The results of this study will help establish future research lines that will analyze more in depth this issue

The OTELO survey: A case study of [O III] lambda 4959,5007 emitters at z=0.83

Context. The OSIRIS Tunable Filter Emission Line Object (OTELO) survey is a very deep, blind exploration of a selected region of the Extended Groth Strip and is designed for finding emission-line sources (ELSs). The survey design, observations, data reduction, astrometry, and photometry, as well as the correlation with ancillary data used to obtain a final catalogue, including photo-z estimates and a preliminary selection of ELS, were described in a previous contribution. Aims. Here, we aim to determine the main properties and luminosity function (LF) of the [O III] ELS sample of OTELO as a scientific demonstration of its capabilities, advantages, and complementarity with respect to other surveys. Methods. The selection and analysis procedures of ELS candidates obtained using tunable filter pseudo-spectra are described. We performed simulations in the parameter space of the survey to obtain emission-line detection probabilities. Relevant characteristics of [O III] emitters and the LF ([O III]), including the main selection biases and uncertainties, are presented. Results. From 541 preliminary emission-line source candidates selected around z = 0.8, a total of 184 sources were confirmed as [O III] emitters. Consistent with simulations, the minimum detectable line flux and equivalent width in this ELS sample are ∼5 × 10−19 erg s−1 cm2 and ∼6 Å, respectively. We are able to constrain the faint-end slope (α = −1.03 ± 0.08) of the observed LF ([O III]) at a mean redshift of z = 0.83. This LF reaches values that are approximately ten times lower than those from other surveys. The vast majority (84%) of the morphologically classified [O III] ELSs are disc-like sources, and 87% of this sample is comprised of galaxies with stellar masses of M⋆ <  1010 M⊙

Grupo español de cirugía torácica asistida por videoimagen: método, auditoría y resultados iniciales de una cohorte nacional prospectiva de pacientes tratados con resecciones anatómicas del pulmón

Introduction: our study sought to know the current implementation of video-assisted thoracoscopic surgery (VATS) for anatomical lung resections in Spain. We present our initial results and describe the auditing systems developed by the Spanish VATS Group (GEVATS). Methods: we conducted a prospective multicentre cohort study that included patients receiving anatomical lung resections between 12/20/2016 and 03/20/2018. The main quality controls consisted of determining the recruitment rate of each centre and the accuracy of the perioperative data collected based on six key variables. The implications of a low recruitment rate were analysed for '90-day mortality' and 'Grade IIIb-V complications'. Results: the series was composed of 3533 cases (1917 VATS; 54.3%) across 33 departments. The centres' median recruitment rate was 99% (25-75th:76-100%), with an overall recruitment rate of 83% and a data accuracy of 98%. We were unable to demonstrate a significant association between the recruitment rate and the risk of morbidity/mortality, but a trend was found in the unadjusted analysis for those centres with recruitment rates lower than 80% (centres with 95-100% rates as reference): grade IIIb-V OR=0.61 (p=0.081), 90-day mortality OR=0.46 (p=0.051). Conclusions: more than half of the anatomical lung resections in Spain are performed via VATS. According to our results, the centre's recruitment rate and its potential implications due to selection bias, should deserve further attention by the main voluntary multicentre studies of our speciality. The high representativeness as well as the reliability of the GEVATS data constitute a fundamental point of departure for this nationwide cohort

Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue

Metabolic plasticity is the ability of a biological system to adapt its metabolic phenotype to different environmental stressors. We used a whole-body and tissue-specific phenotypic, functional, proteomic, metabolomic and transcriptomic approach to systematically assess metabolic plasticity in diet-induced obese mice after a combined nutritional and exercise intervention. Although most obesity and overnutrition-related pathological features were successfully reverted, we observed a high degree of metabolic dysfunction in visceral white adipose tissue, characterized by abnormal mitochondrial morphology and functionality. Despite two sequential therapeutic interventions and an apparent global healthy phenotype, obesity triggered a cascade of events in visceral adipose tissue progressing from mitochondrial metabolic and proteostatic alterations to widespread cellular stress, which compromises its biosynthetic and recycling capacity. In humans, weight loss after bariatric surgery showed a transcriptional signature in visceral adipose tissue similar to our mouse model of obesity reversion. Overall, our data indicate that obesity prompts a lasting metabolic fingerprint that leads to a progressive breakdown of metabolic plasticity in visceral adipose tissue

Olive oil's bitter principle reverses acquired autoresistance to trastuzumab (Herceptin™) in HER2-overexpressing breast cancer cells

[Background] A low incidence of breast cancer in the Mediterranean basin suggests that a high consumption of Extra Virgin Olive Oil (EVOO) might confer this benefit. While the anti-HER2 oncogene effects of the main ω-9 fatty acid present in EVOO triacylglycerols (i.e., oleic acid) have been recently described, the anti-breast cancer activities of EVOO non-glyceridic constituents -which consist of at least 30 phenolic compounds-, remained to be evaluated. [Methods] Semi-preparative HPLC was used to isolate EVOO polyphenols (i.e., tyrosol, hydroxytyrosol, oleuropein). Both the anti-proliferative and the pro-apoptotic effects of EVOO phenolics were evaluated by using MTT-based quantification of metabolically viable cells and ELISA-based detection of histone-associated DNA fragments, respectively. The nature of the interaction between oleuropein aglycone and the anti-HER2 monoclonal antibody trastuzumab (Herceptin™) was mathematically evaluated by the dose-oriented isobologram technique. HER2-specific ELISAs were employed to quantitatively assess both the basal cleavage of the HER2 extracellular domain (ECD) and the expression level of total HER2. The activation status of HER2 was evaluated by immunoblotting procedures using a monoclonal antibody specifically recognizing the tyrosine phosphorylated (Phosphor-Tyr1248) form of HER2. [Results] Among EVOO polyphenols tested, oleuropein aglycone was the most potent EVOO phenolic in decreasing breast cancer cell viability. HER2 gene-amplified SKBR3 cells were ~5-times more sensitive to oleuropein aglycone than HER2-negative MCF-7 cells. Retroviral infection of the HER2 oncogene in MCF-7 cells resulted in a "SKBR3-assimilated" phenotype of hypersensitivity to oleuropein aglycone. An up to 50-fold increase in the efficacy of trastuzumab occurred in the presence of oleuropein aglycone. A preclinical model of acquired autoresistance to trastuzumab (SKBR3/Tzb100 cells) completely recovered trastuzumab sensitivity (> 1,000-fold sensitization) when co-cultured in the presence of oleuropein aglycone. Indeed, the nature of the interaction between oleuropein aglycone and trastuzumab was found to be strongly synergistic in Tzb-resistant SKBR3/Tzb100 cells. Mechanistically, oleuropein aglycone treatment significantly reduced HER2 ECD cleavage and subsequent HER2 auto-phosphorylation, while it dramatically enhanced Tzb-induced down-regulation of HER2 expression. [Conclusion] Olive oil's bitter principle (i.e., oleuropein aglycone) is among the first examples of how selected nutrients from an EVOO-rich "Mediterranean diet" directly regulate HER2-driven breast cancer disease.JAM is the recipient of a Basic, Clinical and Translational Research Award (BCTR0600894) from the Susan G. Komen Breast Cancer Foundation (Texas, USA). This work was also supported by the Instituto de Salud Carlos III (Ministerio de Sanidad y Consumo, Fondo de Investigación Sanitaria -FIS-, Spain, Grants CP05-00090 and PI06-0778 to JAM, and Grant RD06-0020-0028 to JAM, RC and JB)

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

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions