Estimating averted illnesses from influenza vaccination for children and pregnant women - El Salvador, Panama, and Peru, 2011-2018.

BACKGROUND: Estimating the burden of disease averted by vaccination can assist policymakers to implement, adjust, and communicate the value of vaccination programs. Demonstrating the use of a newly available modeling tool, we estimated the burden of influenza illnesses averted by seasonal influenza vaccination in El Salvador, Panama, and Peru during 2011-2018 among two influenza vaccine target populations: children aged 6-23 months and pregnant women. METHODS: We derived model inputs, including incidence, vaccine coverage, vaccine effectiveness, and multipliers from publicly available country-level influenza surveillance data and cohort studies. We also estimated changes in illnesses averted when countries' vaccine coverage was achieved using four different vaccine deployment strategies. RESULTS: Among children aged 6-23 months, influenza vaccination averted an estimated cumulative 2,161 hospitalizations, 81,907 medically-attended illnesses, and 126,987 overall illnesses during the study period, with a prevented fraction ranging from 0.3 % to 12.5 %. Among pregnant women, influenza vaccination averted an estimated cumulative 173 hospitalizations, 6,122 medically attended illnesses, and 16,412 overall illnesses, with a prevented fraction ranging from 0.2 % to 10.9 %. Compared to an influenza vaccine campaign with equal vaccine distribution during March-June, scenarios in which total cumulative coverage was achieved in March and April consistently resulted in the greatest increase in averted illness (23 %-3,129 % increase among young children and 22 %-3,260 % increase among pregnant women). DISCUSSION: Influenza vaccination campaigns in El Salvador, Panama, and Peru conducted between 2011 and 2018 prevented hundreds to thousands of influenza-associated hospitalizations and illnesses in young children and pregnant women. Existing vaccination programs could prevent additional illnesses, using the same number of vaccines, by achieving the highest possible coverage within the first two months of an influenza vaccine campaign.

A compartment and metapopulation model of Rocky Mountain spotted fever in southwestern United States and northern Mexico.

Rocky Mountain spotted fever (RMSF) is a fatal tick-borne zoonotic disease that has emerged as an epidemic in western North America since the turn of the 21st century. Along the US south-western border and across northern Mexico, the brown dog tick, Rhipicephalus sanguineus, is responsible for spreading the disease between dogs and humans. The widespread nature of the disease and the ongoing epidemics contrast with historically sporadic patterns of the disease. Because dogs are amplifying hosts for the Rickettsia rickettsii bacteria, transmission dynamics between dogs and ticks are critical for understanding the epidemic. In this paper, we developed a compartment metapopulation model and used it to explore the dynamics and drivers of RMSF in dogs and brown dog ticks in a theoretical region in western North America. We discovered that there is an extended lag-as much as two years-between introduction of the pathogen to a naïve population and epidemic-level transmission, suggesting that infected ticks could disseminate extensively before disease is detected. A single large city-size population of dogs was sufficient to maintain the disease over a decade and serve as a source for disease in surrounding smaller towns. This model is a novel tool that can be used to identify high risk areas and key intervention points for epidemic RMSF spread by brown dog ticks.

A non-linear mixed-effects model to describe the effect of acarbose intake on postprandial glycaemia in a single rat / Um modelo não linear de efeitos mistos para descrever o efeito da ingestão de acarbose na glicemia pós-prandial em um único rato

A non-linear mixed-effects model is proposed to assess the impact of acarbose over time on postprandial glycaemia in a single rat. The model is based on two compartments, one representing the entry of glucose in the blood and the other its exit. The rat was submitted to two treatments: ingestion of starch and ingestion of starch plus acarbose. The model showed great suitability, with inferences on the behavior of glucose levels in response to treatments and supplying a richer description than just the area under the curve. The marginal curves for the two treatments are similar during the first moments; however, after reaching the peak of glucose concentration, they progressively became separate due to acarbose treatment and reached the initial levels more quickly. The proposed model, albeit with a single sample unit, showed similar results to those with larger samples; in other words, acarbose significantly attenuates glycaemia after ingestion of starch.

Neste estudo, foi proposto um modelo não linear de efeitos mistos para verificar o impacto da acarbose ao longo do tempo na glicemia pós -prandial de um único rato. Adotou-se um modelo de dois compartimentos: um representando a entrada de glicose no sangue e outro, a saída. O rato foi submetido a dois tratamentos: ingestão de amido e de amido com adição de acarbose. O modelo proposto apresentou um ótimo ajuste, permitindo fazer inferências do comportamento da glicose para os tratamentos e fornecendo uma descrição muito mais rica do que simplesmente a área sob a curva. As curvas marginais para os dois tratamentos foram semelhantes nos primeiros tempos observados, porém, após o pico de concentração de glicose, elas se distanciaram progressivamente com o tratamento da acarbose atingindo os níveis iniciais mais rapidamente. O modelo adotado, com uma única unidade amostral, mostrou resultados similares a outros estudos com maior número de unidades amostrais, isto é, a acarbose pode atenuar consideravelmente a glicemia após ingestão de amido.

Pharmacokinetic properties, in vitro metabolism and plasma protein binding of govaniadine an alkaloid isolated from Corydalis govaniana Wall.

Govaniadine (GOV) is an alkaloid isolated from Corydalis govaniana Wall. It has been reported to show a different number of biological activities including anti-urease, leishmanicidal and antinociceptive. The present study aims to characterize the GOV in vitro metabolism after incubation with rat and human liver microsomes (RLM and HLM, respectively) and to evaluate its pharmacokinetic properties. The identification of GOV metabolites was conducted by different mass analyzers: a micrOTOF II-ESI-ToF Bruker Daltonics® and an amaZon-SL ion trap (IT) Bruker Daltonics®. For the pharmacokinetic study of GOV in rats after intravenous administration, a LC-MS/MS method was developed and applied to. The analyses were performed using an Acquity UPLC® coupled to an Acquity TQD detector equipped with an ESI interface. The liver microsomal incubation resulted in new O-demethylated, di-hydroxylated and mono-hydroxylated compounds. Regarding the method validation, the calibration curve was linear over the concentration range of 2.5-3150.0ngmL-1, with a lower limit of quantitation (LLOQ) of 2.5ngmL-1. This method was successfully applied to a pharmacokinetic study. The profile was best fitted to a two-compartment model, the first phase with a high distribution rate constant (α) 0.139±0.086min-1, reflected by the short distribution half-life (t1/2α) 9.2±8.9min and the later one, with an elimination half-life (t1/2ß) 55.1±37.9min. The main plasma protein binding was 96.1%. This is a first report in this field and it will be useful for further development of govaniadine as a drug candidate.

Comparison of body fat calculations by sex and puberty status in obese schoolchildren using two and four compartment body composition models.

INTRODUCTION: Determine body composition changes in adiposity can assess an individual. OBJECTIVE: The objective of this study was to evaluate total body fat percentage based on two and four compartment models in obese Chilean school children, adjusting for differences in sex and puberty status. METHODS: Sixty-one obese school children (33 boys and 28 girls) between 8 and 13 years of age were evaluated. Two compartment measurements of body fat percentage considered isotope dilution, plethysmography, radiographic absorptiometry and bioelectrical impedance; using the four compartment model as a benchmark. RESULTS: Each method explained between 43-87% of the variance in body fat percentage in Tanner stage I and II children and between 78-96% in Tanner stage III and V children. In both groups of children methods differed significantly for stage I, with the exception of plethysmography. High R2 values were observed for girls in all Tanner stages. Each method explained between 34-92% of the variance in body fat percentage for girls in stages I and II and between 63-93% for stages III and V. In obese boys, R2 values were high for stages III and V. In girls and boys in Tanner stage III and V, the smallest differences were observed for isotopic dilution, and DXA (dual-energy X-ray absorptiometry) scan for stages I and II. CONCLUSIONS: For obese boys and girls, the two compartment model with isotopic dilution and DXA had the best precision and smallest differences in determining body fat percentage compared to the benchmark.

The four-compartment model of body composition in obese Chilean schoolchildren, by pubertal stage: comparison with simpler models.

OBJECTIVES: We assessed the agreement of body fat and fat-free mass measured by simpler methods against the four-compartment model (4C). METHODS: In 60 obese schoolchildren (body mass index ≥95th percentile) between the ages of 8 and 13 y who were recruited from one school in Chile, multicompartmental body composition was estimated with the use of isotopic dilution, plethysmography (BodPod), radiographic absorptiometry (DEXA), and anthropometric equations. These results were compared to those of the 4C model, which is considered the gold standard. RESULTS: For body fat, the 4C model showed the best agreement with DEXA for boys in Tanner stages I and II (r = 0.971) and with isotopic dilution for boys in Tanner stages III and IV (r = 0.984). The best agreement in girls occurred with isotopic dilution, regardless of pubertal stage (r = 0.948 for Tanner stages I and II; r = 0.978 for Tanner stages III and IV). Both isotopic dilution and the Huang, Ellis, and Deurenberg anthropometric equations underestimated body fat in boys; by contrast, DEXA, BodPod, and the Slaughter equation overestimated body fat in boys. All of the equations underestimated body fat in girls. For fat-free mass in both boys and girls, the 4C model showed the best agreement with isotopic dilution, regardless of pubertal stage. The Huang equation showed the best agreement for boys (r = 0.730 for Tanner stages I and II; r = 0.695 for Tanner stages III and IV) and for girls in Tanner stages I and II (r = 0.884). The Ellis equation had the best agreement for girls in Tanner stages III and IV (r = 0.917). CONCLUSIONS: For obese Chilean children of both sexes, isotopic dilution and DEXA were the two-compartment methods that had the best agreement with the gold-standard 4C model for both body fat and fat-free mass; these were followed by the Huang and Ellis anthropometric equations.

Respiratory system dynamical mechanical properties: modeling in time and frequency domain.

The mechanical properties of the respiratory system are important determinants of its function and can be severely compromised in disease. The assessment of respiratory system mechanical properties is thus essential in the management of some disorders as well as in the evaluation of respiratory system adaptations in response to an acute or chronic process. Most often, lungs and chest wall are treated as a linear dynamic system that can be expressed with differential equations, allowing determination of the system's parameters, which will reflect the mechanical properties. However, different models that encompass nonlinear characteristics and also multicompartments have been used in several approaches and most specifically in mechanically ventilated patients with acute lung injury. Additionally, the input impedance over a range of frequencies can be assessed with a convenient excitation method allowing the identification of the mechanical characteristics of the central and peripheral airways as well as lung periphery impedance. With the evolution of computational power, the airway pressure and flow can be recorded and stored for hours, and hence continuous monitoring of the respiratory system mechanical properties is already available in some mechanical ventilators. This review aims to describe some of the most frequently used models for the assessment of the respiratory system mechanical properties in both time and frequency domain.