Predictive model for atrial fibrillation in hypertensive diabetic patients

Diabetes; Hpertension; Prediction modelsDiabetes; Hipertensión; Modelos de predicciónDiabetis; Hipertensió; Models de prediccióBackground Several scores to identify patients at high risk of suffering atrial fibrillation have been developed. Their applicability in hypertensive diabetic patients, however, remains uncertain. Our aim is to develop and validate a diagnostic predictive model to calculate the risk of developing atrial fibrillation at five years in a hypertensive diabetic population. Methods The derivation cohort consisted of patients with both hypertension and diabetes attended in any of the 52 primary healthcare centres of Barcelona; the validation cohort came from the 11 primary healthcare centres of Terres de l’Ebre (Catalonia South) from January 2013 to December 2017. Multivariable Cox regression identified clinical risk factors associated with the development of atrial fibrillation. The overall performance, discrimination and calibration of the model were carried out. Results The derivation data set comprised 54 575 patients. The atrial fibrillation rate incidence was 15.3 per 1000 person/year. A 5-year predictive model included age, male gender, overweight, heart failure, valvular heart disease, peripheral vascular disease, chronic kidney disease, number of antihypertensive drugs, systolic and diastolic blood pressure, heart rate, thromboembolism, stroke and previous history of myocardial infarction. The discrimination of the model was good (c-index = 0.692; 95% confidence interval, 0.684-0.700), and calibration was adequate. In the validation cohort, the discrimination was lower (c-index = 0.670). Conclusions The model accurately predicts future atrial fibrillation in a population with both diabetes and hypertension. Early detection allows the prevention of possible complications arising from this disease

Blood-biomarkers and devices for atrial fibrillation screening: Lessons learned from the AFRICAT (Atrial Fibrillation Research In CATalonia) study

Biomarkers; Electrocardiography; Blood plasmaBiomarcadores; Electrocardiografía; Plasma sanguíneoBiomarcadors; Electrocardiografia; Plasma sanguiniBackground and objective AFRICAT is a prospective cohort study intending to develop an atrial fibrillation (AF) screening program through the combination of blood markers, rhythm detection devices, and long-term monitoring in our community. In particular, we aimed to validate the use of NT-proBNP, and identify new blood biomarkers associated with AF. Also, we aimed to compare AF detection using various wearables and long-term Holter monitoring. Methods 359 subjects aged 65–75 years with hypertension and diabetes were included in two phases: Phase I (n = 100) and Phase II (n = 259). AF diagnosis was performed by baseline 12-lead ECG, 4 weeks of Holter monitoring (NuuboTM), and/or medical history. An aptamer array including 1310 proteins was measured in the blood of 26 patients. Candidates were selected according to p-value, logFC and biological function to be tested in verification and validation phases. Several screening devices were tested and compared: AliveCor, Watch BP, MyDiagnostick and Fibricheck. Results AF was present in 34 subjects (9.47%). The aptamer array revealed 41 proteins with differential expression in AF individuals. TIMP-2 and ST-2 were the most promising candidates in the verification analysis, but none of them was further validated. NT-proBNP (log-transformed) (OR = 1.934; p<0.001) was the only independent biomarker to detect AF in the whole cohort. Compared to an ECG, WatchBP had the highest sensitivity (84.6%) and AUC (0.895 [0.780–1]), while MyDiagnostick showed the highest specificity (97.10%). Conclusion The inclusion and monitoring of a cohort of primary care patients for AF detection, together with the testing of biomarkers and screening devices provided useful lessons about AF screening in our community. An AF screening strategy using rhythm detection devices and short monitoring periods among high-risk patients with high NT-proBNP levels could be feasible.This work was supported by Fundació Marató de TV3 in the research call “La Marató 2014: malalties del cor” [grant number: 201528-30-31-3]. EP received a predoctoral grant from Vall d’Hebron Institute of Research. Neurovascular Research Laboratory also takes part in the Span-ish stroke research network INVICTUS+ [RD16/0019]. This project is supported by AFFECT-EU, receiving funding from the European Union’s Horizon 2020 research and innovation pro-gramme under grant agreement N°847770. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Blood-biomarkers and devices for atrial fibrillation screening : Lessons learned from the AFRICAT (Atrial Fibrillation Research In CATalonia) study

AFRICAT is a prospective cohort study intending to develop an atrial fibrillation (AF) screening program through the combination of blood markers, rhythm detection devices, and long-term monitoring in our community. In particular, we aimed to validate the use of NT-proBNP, and identify new blood biomarkers associated with AF. Also, we aimed to compare AF detection using various wearables and long-term Holter monitoring. 359 subjects aged 65-75 years with hypertension and diabetes were included in two phases: Phase I (n = 100) and Phase II (n = 259). AF diagnosis was performed by baseline 12-lead ECG, 4 weeks of Holter monitoring (Nuubo TM), and/or medical history. An aptamer array including 1310 proteins was measured in the blood of 26 patients. Candidates were selected according to p-value, logFC and biological function to be tested in verification and validation phases. Several screening devices were tested and compared: AliveCor, Watch BP, MyDiagnostick and Fibricheck. AF was present in 34 subjects (9.47%). The aptamer array revealed 41 proteins with differential expression in AF individuals. TIMP-2 and ST-2 were the most promising candidates in the verification analysis, but none of them was further validated. NT-proBNP (log-transformed) (OR = 1.934; p<0.001) was the only independent biomarker to detect AF in the whole cohort. Compared to an ECG, WatchBP had the highest sensitivity (84.6%) and AUC (0.895 [0.780-1]), while MyDiagnostick showed the highest specificity (97.10%). The inclusion and monitoring of a cohort of primary care patients for AF detection, together with the testing of biomarkers and screening devices provided useful lessons about AF screening in our community. An AF screening strategy using rhythm detection devices and short monitoring periods among high-risk patients with high NT-proBNP levels could be feasible

Top table of the differential expressed proteins between AF and no AF

S1 Table: Top table of the differential expressed proteins between AF and no AF. Results from the discovery study.Results from the discovery study. Proteins selected to be verified in the whole Phase 1 are highlighted in grey. Proteins in bold but not highlighted were already tested in the whole phase 1 as part of a previous published work.Peer reviewe

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Sarcopenia, definición y diagnóstico: ¿Necesitamos valores de referencia para adultos mayores de Latinoamérica?

Sarcopenia is one of the main geriatric syndromes that has been associated with limitation in activities of daily living, disability, and mortality in the elderly population. However, the definition, diagnostic criteria and cut-off points are diverse in the literature, which makes the diagnosis of sarcopenia difficult. The aim of this narrative review was to detect in the literature all the international consensus related to sarcopenia, to compare their definition, diagnostic criteria and cut-off points, in order to identify a definition and criteria that can be used in Latin America. Seven international consensuses were identified that have defined sarcopenia as a syndrome / disease characterized by loss of muscle mass and function associated with the aging process. Despite having a similar definition, there is not a total concordance between the criteria and evaluations. Sarcopenia can be detected using functional assessments of muscle strength, gait speed, and balance, which are frequently used by professionals in the area of rehabilitation. Additionally, the risk of sarcopenia can be assessed using SARC-F and SARC-CaF. Due to its functional impact, sarcopenia should be diagnosed early in older adults by occupational therapists, physical therapists and physiotherapists, to prevent and treat future clinical and functional complications in this population. The creation of reference values is necessary to favor the diagnosis of sarcopenia in the Latin American population.La sarcopenia es uno de los principales síndromes geriátricos que está asociada con limitación en las actividades de la vida diaria, discapacidad y mortalidad en la población adulta mayor. Sin embargo, su definición, criterios diagnósticos y puntos de corte son diversos en la literatura, lo que dificulta el diagnóstico de la sarcopenia. El objetivo de esta revisión narrativa fue detectar en la literatura todos los consensos internacionales relacionados con sarcopenia, comparar su definición, criterios diagnósticos y puntos de corte, con el propósito de identificar una definición y criterios que puedan ser utilizados en Latinoamérica. Fueron identificados 7 consensos internacionales que han definido la sarcopenia como un síndrome/enfermedad caracterizado por la pérdida de la masa y función muscular asociada al proceso de envejecimiento. A pesar de tener una definición similar, no hay una total concordancia entre los criterios y evaluaciones. La sarcopenia puede ser detectada utilizando evaluaciones funcionales de fuerza muscular, velocidad de la marcha y equilibrio, que son frecuentemente utilizados por profesionales del área de la rehabilitación. Adicionalmente, el riesgo de sarcopenia puede ser identificado utilizando los cuestionarios SARC-F y SARC-CalF. Debido a su impacto funcional, la sarcopenia debería ser diagnosticada precozmente en adultos mayores por terapeutas ocupacionales, kinesiólogos y fisioterapeutas, para prevenir y tratar futuras complicaciones clínicas y funcionales en esta población. Es necesario la creación de valores de referencia para favorecer el diagnóstico de la sarcopenia en población latinoamericana

Burden of heart failure in primary healthcare

Objectives: To determine the epidemiology of heart failure registered in primary healthcare clinical records in Catalunya, Spain, between 2010 and 2014, focusing on incidence, mortality, and resource utilization. Design: Retrospective observational cohort study. Setting: Study was carried out in primary care setting. Participants and interventions: Patients registered as presenting a new heart failure diagnosis. The inclusion period ran from 1st January 2010 to 31st December 2013, but patients were followed until 31st December 2013 in order to analyze mortality. Main measures: Information came from electronic medical records. Results: A total of 64 441 patients were registered with a new diagnosis of heart failure (2.76 new cases per 1000 persons-year). Among them, 85.8% were ≥65 years. The number of cases/1000 persons-year was higher in men in all age groups. Incidence ranged from 0.04 in women <45 years to 27.61 in the oldest group, and from 0.08 in men <45 years to 28.52 in the oldest group. Mortality occurred in 16 305 (25.3%) patients. Primary healthcare resource utilization increased after the occurrence of heart failure, especially the number of visits made by nurses to the patients’ homes. Conclusion: Heart failure incidence increases with age, is greater in men, and remains stable. Mortality continues to be high in newly diagnosed patients in spite of the current improvements in treatment. Home visits represent the greatest cost for the management of this disease in primary care setting. Resumen: Objetivo: Determinar la epidemiología de la insuficiencia cardíaca registrada en las historias clínicas de atención primaria en Cataluña, España, entre 2010 y 2014, centrándose en la incidencia, la mortalidad y la utilización de recursos sanitarios. Diseño: Estudio de cohorte observacional retrospectivo. Emplazamiento: El estudio se llevó a cabo en atención primaria. Participantes e intervenciones: Pacientes registrados con nuevo diagnóstico de insuficiencia cardíaca en el período de estudio. El período de inclusión fue del 1 de enero de 2010 al 31 de diciembre de 2013, pero los pacientes se siguieron hasta el 31 de diciembre de 2014 para poder determinar la mortalidad. Mediciones principales: La información se obtuvo de la historia clínica electrónica de los participantes. Resultados: Se registraron un total de 64.441 pacientes con nuevo diagnóstico de insuficiencia cardíaca (2,76 nuevos casos/1000 personas-año). De ellos, el 85,8% tenían ≥65 años. El número de casos/1000 personas-año fue mayor en hombres en todos los grupos de edad. La incidencia varió de 0,04 en mujeres <45 años a 27,61 en el grupo de mayor edad, y de 0,08 en hombres <45 años a 28,52 en el grupo de mayor edad. La mortalidad se produjo en 16.305 (25,3%) pacientes. La utilización de los recursos de atención primaria aumentó tras el diagnóstico de insuficiencia cardíaca, especialmente el número de visitas realizadas por las enfermeras a los pacientes en su domicilio. Conclusión: La incidencia de insuficiencia cardíaca aumenta con la edad, es mayor en hombres y se mantiene estable en el tiempo. La mortalidad continúa siendo alta en pacientes recién diagnosticados a pesar de las mejoras actuales en el tratamiento. Las visitas domiciliarias representan el mayor coste para el manejo de esta enfermedad en el ámbito de atención primaria

Gestational diabetes mellitus is associated with increased pro-migratory activation of vascular endothelial growth factor receptor 2 and reduced expression of vascular endothelial growth factor receptor 1

<div><p>Placentas from gestational diabetes mellitus (GDM) are often hypervascularized; however, participation of vascular endothelial growth factor (VEGF) and its receptors in this placental adaptation is unclear. We aimed to test whether changes in phosphorylation of tyrosine 951 or tyrosine 1175 (pY951 or pY1175) of the vascular endothelial growth factor receptor 2 (KDR) are associated with the proangiogenic state observed in placentas from GDM. We obtained placental samples from women with normal pregnancies (n = 24) or GDM (n = 18). We measured the relative expression of markers for endothelial cell number (CD31, CD34), VEGF, vascular endothelial growth factor receptor 1 (Flt-1), KDR, pY951 and pY1175 of KDR in placental homogenate. Immunohistochemistry of placental blood vessels were performed using CD34. Proliferation and migration of human umbilical vein endothelial cells (HUVEC) obtained from normal pregnancy and GDM were determined in absence or presence of conditioned medium (CM) harvested from GDM or normoglycemic HUVEC cultures. GDM was associated with more CD31 and CD34 protein compared to normal pregnancy. High number, but reduced area of placental blood vessels was found in GDM. Reduced Flt-1 levels (mRNA and protein) are associated with reduced KDR mRNA, but higher KDR protein levels in placentas from GDM. No significant changes in Y951-or Y1175-phosphorylation of KDR in placentas from GDM were found. GDM did not alter proliferation of HUVECs, but enhanced migration. Conditioned medium harvested from GDM HUVEC cultures enhanced KDR protein amount, tube formation capacity and cell migration in HUVEC isolated from normoglycemic pregnancies. The data indicate that GDM is associated with reduced expression of Flt-1 but high pro-migratory activation of KDR reflecting a proangiogenic state in GDM.</p></div

Placental CD31 and CD34 protein.

<p>Protein levels of CD31 and CD34 in total placental homogenates of normal pregnancy (NP, white bar) and gestational diabetes mellitus (GDM, hatched bar) were determined by western blot. <b>A)</b> Representative western blot for CD31 (55 kDa), CD34 (80 kDa) and β-actin (43 kDa). <b>B)</b> Densitometric analysis of CD31/ β-actin ratio (left Y-axis) and CD34/ β-actin ratio (right Y-axis). <b>C)</b> Representative images of CD34 staining in placentas from Normal and GDM. <b>D)</b> Number of vessels per villi. <b>E)</b> Mean blood vessel area (MVA)/mean chorionic villi area (MCVA) ratio. In B, n = 6–12 in each group. In D and E, n = 4–5 in each group. Magnification 40X. P-value is indicated in each graph.</p

Working model.

<p>Results of this study suggest that placentas from gestational diabetes mellitus are in a proangiogenic state characterized by elevated endothelial cell markers, ie. more endothelial cells, and higher KDR, resulting in enhanced migration in GDM cells than cells from normal control pregnancies. Additional alteration/compensatory mechanisms include reduction in the mRNA and protein levels of Flt-1, reduced mRNA levels of KDR, and no changes in VEGF, or cell proliferation. Changes observed in GDM are shown in red and black arrows.</p