Simulation-driven optimization of insulin therapy profiles in a commercial hybrid closed-loop system.

BACKGROUND: Automated insulin delivery (AID) has represented a breakthrough in managing type 1 diabetes (T1D), showing safe and effective glucose control extensively across the board. However, metabolic variability still poses a challenge to commercial hybrid closed-loop (HCL) solutions, whose performance depends on customizable insulin therapy profiles. In this work, we propose an Identification-Replay-Optimization (IRO) approach to optimize gradually and safely such profiles for the Control-IQ AID algorithm. METHODS: Closed-loop data are generated using the full adult cohort of the UVA/Padova T1D simulation platform in diverse glycemic scenarios. For each subject, daily records are processed and used to estimate a personalized model of the underlying insulin-glucose dynamics. Every two weeks, all identified models are integrated into an optimization procedure where daily basal and bolus profiles are adjusted so as to minimize the risks for hypo- and hyperglycemia. The proposed strategy is tested under different scenarios of metabolic and behavioral variability in order to evaluate the efficacy and convergence of the proposed strategy. Finally, glycemic metrics between cycles are compared using paired t-tests with p<0.05 as the significance threshold. RESULTS: Simulations reveal that the proposed IRO approach was able to improve glucose control over time by safely mitigating the risks for both hypo- and hyperglycemia. Furthermore, smaller changes were recommended at each cycle, indicating convergence when simulation conditions were maintained. CONCLUSIONS: The use of reliable simulation-driven tools capable of accurately reproducing field-collected data and predicting changes can substantially shorten the process of optimizing insulin therapy, adjusting it to metabolic changes and leading to improved glucose control.

Performance Effect of Adjusting Insulin Sensitivity for Model-Based Automated Insulin Delivery Systems.

BACKGROUND: Model predictive control (MPC) has become one of the most popular control strategies for automated insulin delivery (AID) in type 1 diabetes (T1D). These algorithms rely on a prediction model to determine the best insulin dosing every sampling time. Although these algorithms have been shown to be safe and effective for glucose management through clinical trials, managing the ever-fluctuating relationship between insulin delivery and resulting glucose uptake (aka insulin sensitivity, IS) remains a challenge. We aim to evaluate the effect of informing an AID system with IS on the performance of the system. METHOD: The University of Virginia (UVA) MPC control-based hybrid closed-loop (HCL) and fully closed-loop (FCL) system was used. One-day simulations at varying levels of IS were run with the UVA/Padova T1D Simulator. The AID system was informed with an estimated value of IS obtained through a mixed meal glucose tolerance test. Relevant controller parameters are updated to inform insulin dosing of IS. Performance of the HCL/FCL system with and without information of the changing IS was assessed using a novel performance metric penalizing the time outside the target glucose range. RESULTS: Feedback in AID systems provides a certain degree tolerance to changes in IS. However, IS-informed bolus and basal dosing improve glycemic outcomes, providing increased protection against hyperglycemia and hypoglycemia according to the individual's physiological state. CONCLUSIONS: The proof-of-concept analysis presented here shows the potentially beneficial effects on system performance of informing the AID system with accurate estimates of IS. In particular, when considering reduced IS, the informed controller provides increased protection against hyperglycemia compared with the naïve controller. Similarly, reduced hypoglycemia is obtained for situations with increased IS. Further tailoring of the adaptation schemes proposed in this work is needed to overcome the increased hypoglycemia observed in the more resistant cases and to optimize the performance of the adaptation method.

First Outpatient Clinical Trial of a Full Closed-Loop Artificial Pancreas System in South America.

BACKGROUND: The first two studies of an artificial pancreas (AP) system carried out in Latin America took place in 2016 (phase 1) and 2017 (phase 2). They evaluated a hybrid algorithm from the University of Virginia (UVA) and the automatic regulation of glucose (ARG) algorithm in an inpatient setting using an AP platform developed by the UVA. The ARG algorithm does not require carbohydrate (CHO) counting and does not deliver meal priming insulin boluses. Here, the first outpatient trial of the ARG algorithm using an own AP platform and doubling the duration of previous phases is presented. METHOD: Phase 3 involved the evaluation of the ARG algorithm in five adult participants (n = 5) during 72 hours of closed-loop (CL) and 72 hours of open-loop (OL) control in an outpatient setting. This trial was performed with an own AP and remote monitoring platform developed from open-source resources, called InsuMate. The meals tested ranged its CHO content from 38 to 120 g and included challenging meals like pasta. Also, the participants performed mild exercise (3-5 km walks) daily. The clinical trial is registered in ClinicalTrials.gov with identifier: NCT04793165. RESULTS: The ARG algorithm showed an improvement in the time in hyperglycemia (52.2% [16.3%] OL vs 48.0% [15.4%] CL), time in range (46.9% [15.6%] OL vs 50.9% [14.4%] CL), and mean glucose (188.9 [25.5] mg/dl OL vs 186.2 [24.7] mg/dl CL) compared with the OL therapy. No severe hyperglycemia or hypoglycemia episodes occurred during the trial. The InsuMate platform achieved an average of more than 95% of the time in CL. CONCLUSION: The results obtained demonstrated the feasibility of outpatient full CL regulation of glucose levels involving the ARG algorithm and the InsuMate platform.

Non-pharmaceutical intervention to reduce COVID-19 impact in Argentina.

This work is focused on the multilevel control of the population confinement in the city of Buenos Aires and its surroundings due to the pandemic generated by the COVID-19 outbreak. The model used here is known as SEIRD and two objectives are sought: a time-varying identification of the infection rate and the inclusion of a controller. A control differential equation has been added to regulate the transitions between confinement and normal life, according to five different levels. The plasma treatment from recovered patients has also been considered in the control algorithm. Using the proposed strategy the ICU occupancy is reduced, and as a consequence, the number of deaths is also decreased.

Cuantificación del desperdicio de alimentos en servicios de alimentación de la Universidad de Costa Rica / Quantification of Food Waste in Food Services of the Universidad de Costa Rica

Resumen Antecedentes: los alimentos desperdiciados en ventas al detalle en Latinoamérica (15 %) podrían suplir las necesidades alimenticias del 64 % de quienes sufren hambre en la región. Objetivo: determinar los desperdicios de alimentos en tres servicios de alimentación de la sede Rodrigo Facio de la Universidad de Costa Rica a partir de la guía de medición de la Red Costarricense para Disminuir la Pérdida y el Desperdicio de Alimentos. Materiales y métodos: los desperdicios en los servicios de alimentación N1 y N2 fueron medidos en 2018 y 2019 y en el N3 en 2019; se realizaron 15 mediciones siguiendo la metodología de la guía y se reportaron como porcentaje del total de producción de sólidos. Resultados: los desperdicios en la producción total fueron 15,0-16,6 % en 2018 y 6,4-11,5 % en 2019. No se encontraron diferencias entre los servicios de alimentación en la producción promedio (p=0,1467), en el desperdicio del área de almacenamiento (p=0,1293) ni en la producción de alimentos (p=0,7718). Se encontraron diferencias en el desperdicio entre los servicios de alimentación en el área de servicio: desperdicios en barra (p=0,0197), en plato/ desayuno (p=0,0075) y en plato/almuerzo (p=0,0362). Conclusiones: la cantidad de desperdicios encontrados son menores a los reportados en otros estudios.

Abstract Background: Food wasted in retail in Latinamerica (15%) could supply the nutritional needs of 64% of the hungry in the region. Objective: To determine food waste in three food services of the Rodrigo Facio campus of the Universidad de Costa Rica, using the measurement guide of the Costa Rican Network to reduce food loss and waste. Materials and Methods: Waste in food services N1 and N2 were measured in 2018 and 2019, and in the N3 in 2019. In total 15 measurements were made following the methodology of the guide and they were reported as a percentage of total solids production. Results: Waste in total production was 15.0-16.6% in 2018 and 6.4-11.5% in 2019. No differences were found between food services in average production (p=0.1467), in the waste storage area (p=0.1293), nor food production (p = 0.7718). Differences in waste were found between food services in the service area: Waste in the service bar (p=0.0197), in plate/breakfast (p=0.0075), and in plate/lunch (p=0.0362). Conclusions: The amount of waste found is lower than that reported in other studies.

Proteinuria en habitantes de una aldea costera de Santa Rosa, Guatemala / Proteinuria in inhabitants of a coastal village of Santa Rosa, Guatemala

Objetivo: determinar la presencia de proteinuria en habitantes de una aldea de la región costera de Santa Rosa, Guatemala, julio del año 2019. Material y métodos: estudio descriptivo y transversal, en una muestra de 575 habitantes de la aldea Casas Viejas, captada por durante cuatro jornadas médicas. Las muestras de orina fueron analizadas con tiras reactivas. Resultados: de los habitantes que participaron, 55.48 % (319) fueron de sexo femenino, la mediana de edad fue de 24 años, el 39.820% (229) estudiante y el 85.2 % (490) sin antecedentes patológicos. De los factores predisponentes de enfermedad renal, el 56.170% (323) consume antiinflamatorios no esteroideo -AINES-, el 82.26 % (473) bebidas carbonatadas, el 13.570% (78) bebidas alcohólicas; la mediana de consumo de agua fue de 6 vasos diarios y 13.22 % (76) han estado expuestos a agroquímicos. Proteinuria se documentó en 8.87 % (51) de los habitantes. Conclusiones: más de la mitad de los sujeto de estudio son de sexo femenino y sin antecedentes patológicos; de los factores predisponentes a enfermedad renal los más frecuentes son el consumo de -AINES-, bebidas carbonatadas y la hidratación inadecuada. Nueve de cada cien sujetos de estudio presentan proteinuria.

Objetive: to establish urine protein presence in inhabitants of a small village of the coastal region in Santa Rosa, Guatemala. July 2019. Material y methods: Descriptive and transversal study performed on 575 persons from Casas Viejas village, using a nonprobabilistic sampling. Proteinuria was determined by urine test strips. Results: Of the persons studied, 55.48% (319) were female, mean age was 24 years old, 39.82% (229) were students and 85.25% had no pathological background. Predisposing factors of kidney disease were noted, 56.17% (323) consumed Non-steroidal Anti-inflammatory Drugs (NSAIDs), 82.26% (473) consumed carbonated drinks, 13.57% (78) alcoholic beverages, the mean water consumption was 6 glasses per day, and 13.22% (76), were exposed to agrochemical pesticides. Proteinuria was found in 8.87% (51) of the sample. Conclutions: more than half of population were female and didn´t showed pathological signs. Predisposing factors to kidney disease were, frequent NSAIDs use, carbonated drinks consumption a no adequate hydration. Nine of each one hundred people studied presented urine protein.

Control-Oriented Model With Intra-Patient Variations for an Artificial Pancreas.

In this work, a low-order model designed for glucose regulation in Type 1 Diabetes Mellitus (T1DM) is obtained from the UVA/Padova metabolic simulator. It captures not only the nonlinear behavior of the glucose-insulin system, but also intra-patient variations related to daily insulin sensitivity ( SI) changes. To overcome the large inter-subject variability, the model can also be personalized based on a priori patient information. The structure is amenable for linear parameter varying (LPV) controller design, and represents the dynamics from the subcutaneous insulin input to the subcutaneous glucose output. The efficacy of this model is evaluated in comparison with a previous control-oriented model which in turn is an improvement of previous models. Both models are compared in terms of their open- and closed-loop differences with respect to the UVA/Padova model. The proposed model outperforms previous T1DM control-oriented models, which could potentially lead to more robust and reliable controllers for glycemia regulation.

Artificial Pancreas: Clinical Study in Latin America Without Premeal Insulin Boluses.

BACKGROUND: Emerging therapies such as closed-loop (CL) glucose control, also known as artificial pancreas (AP) systems, have shown significant improvement in type 1 diabetes mellitus (T1DM) management. However, demanding patient intervention is still required, particularly at meal times. To reduce treatment burden, the automatic regulation of glucose (ARG) algorithm mitigates postprandial glucose excursions without feedforward insulin boluses. This work assesses feasibility of this new strategy in a clinical trial. METHODS: A 36-hour pilot study was performed on five T1DM subjects to validate the ARG algorithm. Subjects wore a subcutaneous continuous glucose monitor (CGM) and an insulin pump. Insulin delivery was solely commanded by the ARG algorithm, without premeal insulin boluses. This was the first clinical trial in Latin America to validate an AP controller. RESULTS: For the total 36-hour period, results were as follows: average time of CGM readings in range 70-250 mg/dl: 88.6%, in range 70-180 mg/dl: 74.7%, <70 mg/dl: 5.8%, and <50 mg/dl: 0.8%. Results improved analyzing the final 15-hour period of this trial. In that case, the time spent in range was 70-250 mg/dl: 94.7%, in range 70-180 mg/dl: 82.6%, <70 mg/dl: 4.1%, and <50 mg/dl: 0.2%. During the last night the time spent in range was 70-250 mg/dl: 95%, in range 70-180 mg/dl: 87.7%, <70 mg/dl: 5.0%, and <50 mg/dl: 0.0%. No severe hypoglycemia occurred. No serious adverse events were reported. CONCLUSIONS: The ARG algorithm was successfully validated in a pilot clinical trial, encouraging further tests with a larger number of patients and in outpatient settings.

Avian Influenza in wild birds from Chile, 2007-2009.

Aquatic and migratory birds, the main reservoir hosts of avian influenza viruses including those with high pathogenic potential, are the wildlife species with the highest risk for viral dissemination across countries and continents. In 2002, the Chilean poultry industry was affected with a highly pathogenic avian influenza strain, which created economic loss and triggered the establishment of a surveillance program in wild birds. This effort consisted of periodic samplings of sick or suspicious animals found along the coast and analyses with standardized techniques for detection of influenza A virus. The aim of this work is to report the detection of three avian influenza strains (H13N2, H5N9, H13N9) in gulls from Chile between 2007-2009, which nucleotide sequences showed highest similitudes to viruses detected in wild birds from North America. These results suggest a dissemination route for influenza viruses along the coasts of Americas. Migratory and synanthropic behaviors of birds included in this study support continued monitoring of avian influenza viruses isolated from wild birds in The Americas and the establishment of biosecurity practices in farms.

High levels of hsCRP are associated with carbohydrate metabolism disorder.

AIM: To determine risk parameters associated with high values of high sensitive C-reactive protein (hsCRP) in subjects with different glucose fasting levels. METHODS: Anthropometric parameters, arterial pressure, glycemia, lipid profile, uric acid, and hsCRP were studied in a population of 513 individuals between 40 and 65 years. RESULTS: In total, 349 (68.0%) were normoglycemic (NG); 113 (22.0%) had impaired fasting glucose (IFG); and 51 (9.9%) were diabetic subjects. A multivariate linear regression analysis showed that the natural logarithm of hsCRP was associated significantly with glycemia levels (P = 0.009), uric acid (P = 0.001), diastolic blood pressure (P = 0.011), smoking habit (P = 0.021), BMI (P<0.001), and sex (P<0.001). One-third of the NG subjects had high hsCRP levels. A multiple logistic regression analysis showed that sex and BMI were variables related to high levels of hsCRP in subjects with IFG and NG. In NG subjects, uric acid levels were associated with risk of presenting high hsCRP levels and were higher in women than men. In NG women, ROC curves analysis identified a uric acid level of 3.9 mg/dl as a cut-off point to predict a high value of hsCRP. Those individuals with uric acid values higher than 3.9 mg/dl and normal glycemia had 3.5-fold more risk of having hsCRP levels over 3.0 mg/l. CONCLUSIONS: We sustain that high levels of hsCRP are associated with disturbance in carbohydrate metabolism. In addition, we believe that in low cardiovascular risk population, such as NG women, uric acid levels above 3.9 mg/dl might represent a signal of possible pro-inflammatory state and cardiovascular risk.

Patrón de comportamiento tipo A, ira y enfermedades cardiovasculares (ECV) en población urbana chilena / Type A Behavior Pattern, Anger and Cardiovascular Disease (CVD) in Chilean Urban Population

Un aumento de las enfermedades cardiovasculares (ECV) mundialmente, la existencia de un porcentaje más alto que el promedio nacional de éstas para la región de Maule (Chile), y una atención incrementada en el análisis de factores psicológicos, motivan el análisis del Patrón de Comportamiento Tipo A (PCTA) y la ira respecto de las ECV. Se trabajó con 1007 participantes de 18 a 74 años (ciudadanos de Talca, Chile), mayoritariamente mujeres, quienes respondieron un cuestionario (información socio demográfica, hábitos alimentarios y de estilo de vida), la Escala Retiro de Patrón de Conducta tipo A (ERCTAa), y el Inventario de Ira de Novaco. Se les midió peso, masa corporal, presión arterial y sangre, como factores de riesgo cardiovascular. Los participantes son altamente sedentarios (79.9%), tabáquicos (53.6%), hipercolesterolémicos (44.5%), con sobrepeso (40.7%) y obesidad (32.6%), un cuarto de los cuales presenta hiperglicemia e hipertensión y con PCTA equirepartido según sexo. Es la ausencia de PCTA (ó presencia de PCTB) la que aparece asociada a factores tradicionales de riesgo cardiovascular (FRCV). La ira alta se presenta más en mujeres que en hombres (2.1% vs. 0.3%; c²(3) = 27.99, p<.0001), disminuyendo para ambos sexos con la edad, pero los infartos acaecen igualmente según sexo.

A worldwide raise in the number of cardiovascular disease (CVD) and the existence of a higher percentage in Maule (Chile) than the national media, and increased attention in the analysis of psychological factors motivate to analyze the Type A Behavior Pattern (TABP) and anger in relation to CVD. The sample was 1007 adults between 18 and 74 years old (citizens of Talca, Chile), mostly women. They provided information about their demographic details, eating habits and lifestyle, answered the Novaco's Anger Inventory and the Retiro Scale of Type A Behavior (RSTAB), and also were taken measurements like weight, body mass index and blood pressure and blood tests related to risk factors to traditional cardiovascular diseases. The results show Overall, that the participants appear highly sedentary (79.9%) with relatively high levels of tabaquism (53.6%), and hypercholesterolemia (44.5%), overweight (40.7%) and obesity (32.6%). A quarter of the sample also presents hyperglycemic indexes, hypertension and TABP unequally distributed by sex. The absence of PCTA (or PCTB presence) appeared mostly associated with traditional cardiovascular risk factors (CRF). Regarding anger, women present more high than men (2.1% against 0.3%; c²(3) = 27.99, p<.0001), decreasing for both sexes with age, while also befall stroke by sex.

[Blood supply during disasters: the experience of Chile in 2010]. / Abastecimiento de sangre durante desastres: la experiencia de Chile en 2010.

A review of the management of blood supply and its administration during disasters was conducted based on the experience of several events that occurred primarily from 2000-2010, particularly the earthquake that measured 8.8 on the Richter scale that struck central and southern Chile on 27 February 2010. The objective was to provide information that could be useful in improving response plans and strategies during potential future disasters. The descriptive information on response procedures was obtained from interviews, internal reports, and the computer database from the Maule regional blood production center. The results lead to the conclusion that to respond efficiently and effectively to the need for blood in the immediate wake of a disaster it is essential to have both a centralized management system that facilitates the supply and administration of blood and volunteers with competence in health that are willing to swiftly arrive during these events. A change in the profile of blood donors during such emergencies was also observed. In Chile, for example, during the two weeks after the earthquake, the ratio of male/female donors was reversed. There was 61.1% participation by women, whereas in the week before the event women accounted for only 37%.

Abastecimiento de sangre durante desastres: la experiencia de Chile en 2010 / Blood supply during disasters: the experience of Chile in 2010

Se realizó una revisión de la gestión del abastecimiento y suministro de sangre durante desastres a partir de las experiencias de diversos eventos ocurridos principalmente en la primera década de este siglo, y en particular el terremoto grado 8,8 en la escala de Richter que afectó la zona centro sur de Chile el 27 de febrero de 2010. El objetivo fue proporcionar información que pueda ser útil para mejorar las estrategias y planes de respuesta durante potenciales desastres futuros. La información descriptiva sobre los procedimientos de respuesta se obtuvo mediante entre-vistas, reportes internos y la base de datos del sistema informático del Centro Productivo Regional de Sangre del Maule. Los resultados permiten concluir que para responder de manera eficiente y efectiva a las necesidades de sangre inmediatamente después de un desastre es de importancia clave tener un sistema centralizado de gestión que facilite el abastecimiento y el suministro de sangre y con-tar con personal voluntario competente en salud que esté dispuesto a acudir con celeridad durante estos eventos. Asimismo, se ha observado que durante dichas emergencias se produce un cambio en el perfil de quienes donan sangre. En Chile, por ejemplo, durante las dos semanas siguientes al terremoto la razón hombre/mujer en los donantes se invirtió, con 61,1 por ciento de participación por parte de las mujeres, quienes en la semana previa al evento representaban a solo 37 por ciento.

A review of the management of blood supply and its administration during disasters was conducted based on the experience of several events that occurred primarily from 2000-2010, particularly the earthquake that measured 8.8 on the Richter scale that struck central and southern Chile on 27 February 2010. The objective was to provide information that could be useful in improving response plans and strategies during potential future disasters. The descriptive information on response procedures was obtained from interviews, internal reports, and the computer database from the Maule regional blood production center. The results lead to the conclusion that to respond efficiently and effectively to the need for blood in the immediate wake of a disaster it is essential to have both a centralized management system that facilitates the supply and administration of blood and volunteers with competence in health that are willing to swiftly arrive during these events. A change in the profile of blood donors during such emergencies was also observed. In Chile, for example, during the two weeks after the earthquake, the ratio of male/female donors was reversed. There was 61.1 percent participation by women, whereas in the week before the event women accounted for only 37 percent.

Intervention with education and exercise reverses the metabolic syndrome in adults.

About 29% of the adult population of Talca, Chile, suffers from the metabolic syndrome (MS), a value higher than the national prevalence. Evidence indicates that exercise and nutritional changes reduce the predominance of this syndrome. The goal of this study was to evaluate the effects of a structured interventional program of physical activity and nutritional counseling in adults with MS. Fifty-one subjects were studied: 27 were included in the interventional program (I-MS). The control group was formed by 24 individuals who did not participate in the program (NI-MS). We assessed body weight, corporal composition, arterial pressure, glycemia, and lipid profile at baseline and after 18 weeks of treatment. After this period, the I-SM group showed a significant decrease in triglycerides (geometric mean 202.2 to 110.5 mg/dL, P < .001), diastolic blood pressure (mean 85.4 to 79.6 mm Hg, P = .001), waist circumference (mean men 101.5 to 94.1 cm, P < .001; mean women 107.2 to 96.2 cm, P < .001), weight (mean 81.1 to 77.2 kg, P < .001), and body mass index (mean 31.8 to 30.2 kg/m(2), P < .001). In the NI-MS group, the individual parameters did not change significantly. Our results show that a non-pharmacological treatment based on exercise exerts an important beneficial effect in patients with MS, mainly on the waist circumference, blood pressure, and triglycerides.

Pandemic (H1N1) 2009 in breeding turkeys, Valparaiso, Chile.

Pandemic (H1N1) 2009 virus was detected in breeding turkeys on 2 farms in Valparaiso, Chile. Infection was associated with measurable declines in egg production and shell quality. Although the source of infection is not yet known, the outbreak was controlled, and the virus was eliminated from the birds.

Evaluation of metabolic syndrome in adults of Talca city, Chile.

OBJECTIVE: Insulin resistance (IR) is an important risk factor for type 2 Diabetes Mellitus (DM2) and cardiovascular disease (CVD). Metabolic Syndrome (MS) is a clustering of metabolic alterations associated to IR; however, there is no international consensus for defining its diagnosis. Our objective was to evaluate the prevalence and characteristics of MS identified by the ATP III and IDF criteria in adults from Talca city. RESEARCH AND METHODS: We studied 1007 individuals, aged 18-74, and residents from Talca. MS subjects were defined according to ATP III (three altered factors) and IDF criteria (patients with waist circumference >80/90 cm (W/M) and two others altered factors). RESULTS: The prevalence of metabolic syndrome according to the IDF and ATP III criteria was 36.4% and 29.5%, respectively after adjustment for age and sex. The agreement for both criteria was 89%. The prevalence in men was higher than in women for both MS definitions, although not significant. MS probability increased with age, and the highest risk was in the 57-68 age group (ATP-MS) and 53-72 age group (IDF-MS). Hypertension, high triglycerides and abdominal obesity are the most frequent alterations in MS. CONCLUSION: MS prevalence in adults was higher when diagnosed with IDF than with ATP criterion; in both, age is directly related with the MS presence. The MS subjects showed higher levels of blood pressure, waist circumference and plasma triglycerides. Considering our results, it is worrisome that one third of our population has a high risk of developing DM2 and CVD in the future.