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

Plant diversity patterns in neotropical dry forests and their conservation implications

This is the author accepted manuscript. The final version is available from American Association for the Advancement of Science via the DOI in this record.Seasonally dry tropical forests are distributed across Latin America and the Caribbean and are highly threatened, with less than 10% of their original extent remaining in many countries. Using 835 inventories covering 4660 species of woody plants, we show marked floristic turnover among inventories and regions, which may be higher than in other neotropical biomes, such as savanna. Such high floristic turnover indicates that numerous conservation areas across many countries will be needed to protect the full diversity of tropical dry forests. Our results provide a scientific framework within which national decision-makers can contextualize the floristic significance of their dry forest at a regional and continental scale.This paper is the result of the Latin American and Caribbean Seasonally Dry Tropical Forest Floristic Network (DRYFLOR), which has been supported at the Royal Botanic Garden Edinburgh by a Leverhulme Trust International Network Grant (IN-074). This work was also supported by the U.K. Natural Environment Research Council grant NE/I028122/1; Colciencias Ph.D. scholarship 529; Synthesys Programme GBTAF-2824; the NSF (NSF 1118340 and 1118369); the Instituto Humboldt (IAvH)–Red colombiana de investigación y monitoreo en bosque seco; the Inter-American Institute for Global Change Research (IAI; Tropi-Dry, CRN2-021, funded by NSF GEO 0452325); Universidad Nacional de Rosario (UNR); and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). The data reported in this paper are available at www.dryflor.info. R.T.P. conceived the study. M.P., A.O.-F., K.B.-R., R.T.P., and J.W. designed the DRYFLOR database system. K.B.-R. and K.G.D. carried out most analyses. K.B.-R. R.T.P., and K.G.D. wrote the manuscript with substantial input from A.D.-S., R.L.-P., A.O.-F., D.P., C.Q., and R.R. All the authors contributed data, discussed further analyses, and commented on various versions of the manuscript. K.B.-R. thanks G. Galeano who introduced her to dry forest research. We thank J. L. Marcelo, I. Huamantupa, C. Reynel, S. Palacios, and A. Daza for help with fieldwork and data entry in Peru

Operations research applications in health systems in Colombia

Sin duda, ver los sistemas de salud desde la perspectiva de la investigación de operaciones impone nuevos retos que no son insalvables. Hay en los sistemas de salud desafíos y dilemas a los que quizás antes no nos veíamos enfrentados al trabajar en otras industrias o servicios. Desde dilemas éticos, causados por la naturaleza del servicio de salud como un derecho fundamental, bien sea porque en las decisiones que se modelan muchas veces están involucradas las vidas y el bienestar de los pacientes, o porque los objetivos de los sistemas de salud van más allá de la rentabilidad o la disminución de costos a los que estamos comúnmente acostumbrados (v. g., mejorar la cobertura o lograr equidad). Por otro lado, entender los sistemas de salud y las decisiones que en ellos se toman (para el tratamiento de los pacientes, para la planeación de las operaciones de los servicios o para la definición de políticas públicas) exige apropiarse de conocimientos que son ajenos a la formación tradicional en investigación de operaciones. Por fortuna, esto último exige la conformación de equipos multidisciplinarios, con personal asistencial (médicos, enfermeras, instrumentadores, terapeutas, etc.), con epidemiólogos, con funcionarios del Estado, con expertos en sistemas de información, calidad y acreditación en salud, entre otros. En estos equipos es también importante la investigación de operaciones, pues los complementa aportando una visión cuantitativa, analítica e ingenieril que algunas veces no tienen.Certainly, viewing health systems from the perspective of operations research poses new challenges that are not insurmountable. There are challenges and dilemmas in health systems that we may not have faced before when working in other industries or services. From ethical dilemmas, caused by the nature of the health service as a fundamental right, either because the decisions that are modeled often involve the lives and well-being of patients, or because the objectives of the health systems are more beyond the profitability or cost reduction that we are commonly used to (eg, improving coverage or achieving equity). On the other hand, understanding the health systems and the decisions made in them (for the treatment of patients, for the planning of the operations of the services or for the definition of public policies) requires the appropriation of knowledge that is foreign to traditional training in operations research. Fortunately, the latter requires the formation of multidisciplinary teams, with healthcare personnel (doctors, nurses, instructors, therapists, etc.), with epidemiologists, with State officials, with experts in information systems, quality and health accreditation, among others. Operations research is also important in these teams, as it complements them by providing a quantitative, analytical and engineering vision that sometimes they do not have.Bogot

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research