Achieve Target Levels Research Articles

THE ROLE OF SEMANTICS IN LINGUISTIC COMPETENCE

In second language acquisition, semantics assumes a heightened position of importance in regards to achieving target levels of competence. Assuming that the target competence is equal to a native-speaker's, a non-native speaker will never fully reach a native level of semantic competence. The ways that L1 semantics can affect L2 semantics is an area of interest in both cognitive and generative linguistics. Research from both perspectives is valuable to evaluate semantics at the lexical and syntactic level.

Population pharmacokinetic simulation of varied Immune Globulin Subcutaneous (Human), 20% solution (Ig20Gly) loading and maintenance dosing regimens in immunoglobulin-naïve patients with primary immunodeficiency diseases

BackgroundThe pharmacokinetics of Ig20Gly, a 20% subcutaneous immunoglobulin (IG) therapy, is well characterized in IG-experienced patients with primary immunodeficiency diseases (PID). Data from IG-naïve patients are limited. ObjectiveSimulate serum total immunoglobulin G (IgG) pharmacokinetic profiles in IG-naïve patients with PID for different Ig20Gly initiation and maintenance dosing regimens. MethodsA population pharmacokinetic model developed with data from pivotal phase 2/3 trials of weekly Ig20Gly in PID (NCT01412385, NCT01218438) was used to simulate pharmacokinetic profiles of IgG in various scenarios with 400- or 800-mg/kg total loading doses (administered as split doses over 1–2 weeks) and corresponding 100- or 200-mg/kg weekly maintenance doses, respectively. Endogenous baseline IgG levels (1.5, 2.0, 4.0, 6.0 g/L) were evaluated for each scenario; time to putative therapeutic target IgG trough level (7 g/L) was determined. ResultsSerum IgG levels reached steady-state by approximately Week 12 for all scenarios and baseline endogenous IgG levels. Time to target trough level generally occurred sooner with 1-week versus 2-week loading schemes. Endogenous baseline IgG levels <4 g/L required a 1-week 800-mg/kg total loading dose to achieve target levels within 2 weeks. Both maintenance regimens sustained serum IgG above target level. ConclusionsSimulations indicated IG-naïve patients with PID can achieve protective serum IgG levels within 1–3 weeks using appropriate Ig20Gly loading regimens. Patients with low endogenous IgG may benefit most from an 800-mg/kg/month loading dose. 400- or 800-mg/kg/month Ig20Gly maintenance regimens appeared adequate to maintain stable IgG levels. Serum IgG monitoring and clinical status can guide dosing parameters.

Assessment of the functional state of the heart in children born to mothers with type I diabetes mellitus

Maternal diabetes mellitus (DM) is a chronic disease that carries significant risks for the fetus and newborn. Hyperglycemia during pregnancy contributes to the development of structural heart defects, myocardial hypertrophy, and impaired cardiac function in newborns. The objective of the study was to evaluate the echocardiographic parameters of the cardiac function in children born to mothers with type 1 diabetes mellitus (DM1).A prospective study of 163 newborns was conducted on the basis of the Republican Scientific and Practical Center “Mother and Child”. The children were divided into 2 groups. The main group consisted of 107 children born to mothers with DM1 (Gr1), the control group – 56 healthy infants born to women with normoglycemia during pregnancy (Gr2).It was found that a newborn in Gr1 has a larger thickness of the interventricular septum (IVS) (p &lt; 0.001), the posterior wall of the left ventricle (p &lt; 0.001), and the size of the right ventricle (p &lt; 0.001). It was revealed that in Gr1 the frequency of myocardial hypertrophy with an interventricular septum thickness of 5 mm or more is 30.8 %, which is statistically significantly higher in comparison with Gr2 (1.8 %, F = 0.115, p &lt; 0.001). When assessing the blood flow using a pulse-wave Doppler study, the manifestations of the diastolic dysfunction in Gr1 were revealed. The E/A ratio for the flow through the mitral valve in Gr1 was 0.9 (0.8–1.1), in Gr2 – 1.2 (1.0–1.4), p = 0.043. The study confirmed a lower frequency of registration of myocardial hypertrophy with good glycemic control during pregnancy (p &lt; 0.05). Direct correlations between the average level of glycated hemoglobin in mothers and the IVS thickness (r = 0.374, p &lt; 0.05) and the posterior wall of the left ventricle (r = 0.293, p &lt; 0.05) of their newborns were observed in infants in Gr1.The use of pump insulin therapy in pregnant women with type 1 diabetes allowed a statistically significant reduction in the frequency of hypertrophy of the left ventricle in infants in the neonatal period.Diabetes mellitus type 1 in the mother determines not only the risk of congenital heart defects, but also hypertrophic changes in the myocardium, contributes to the diastolic dysfunction in this group of children. The achievement of target levels of glycated hemoglobin during pregnancy, using pump insulin therapy, provides a lower frequency of registration of ventricular septal hypertrophy. The revealed statistically significant differences in the IVS thickness and the posterior wall of the left ventricle in infants born to mothers with type 1 diabetes should be taken into account by doctors in the system of organizing medical care in inpatient settings and at the stage of dispensary observation.

Воглібоз у комбінації трьох цукрознижувальних препаратів при лікуванні цукрового діабету 2-го типу

Мета дослідження — клініко-метаболічне обґрунтування вибору третього цукрознижувального препарату для підвищення ефективності лікування хворих на цукровий діабет (ЦД) 2-го типу, оцінка впливу інтенсифікації терапії за рахунок додавання воглібозу на показники вуглеводного обміну, що не досягли цільових рівнів при комбінованій терапії метформіном з глімепіридом. Матеріали й методи. Під спостереженням перебувало 45 хворих на ЦД 2-го типу, які не досягнули цільових показників вуглеводного обміну під впливом попереднього лікування (метформін і глімепірид). Після початкового клінічного обстеження хворі були розподілені на дві групи. У першій групі (n = 30) до терапії додавали воглібоз (препарат Воксид, виробництво ТОВ «Кусум Фарм», Україна) по 0,2 мг перед сніданком, обідом і вечерею впродовж 12 тижнів. Результати. Через 12 тижнів лікування рівень глікованого гемоглобіну (НbА1с) у першій групі знизився на 1,5 [1,1; 1,9] % (р &lt; 0,05), у другій групі — на 0,1 [0,09; 0,6] % (р &gt; 0,05). У 80 % пацієнтів досягнуті цільові рівні глікемії. У першій групі пацієнтів виявлено вірогідне підвищення індексу HOMA-β на 24,9 %, а також зниження інсулінорезистентності (HOMA-IR) на 31,5 %. Через 12 тижнів терапії відзначалося статистично вірогідне зниження маси тіла на 2,1 кг у пацієнтів першої групи й відсутність динаміки в пацієнтів другої групи. Доведена безпека з боку функціонального стану печінки та нирок при цьому варіанті терапії. Висновки. Додавання воглібозу для інтенсифікації терапії у хворих на ЦД 2-го типу, які отримували до цього метформін і глімепірид, призвело до вірогідного покращання показників вуглеводного обміну (зниження HbA1c на 1,5 %). Покращання контролю вуглеводного обміну при комбінованій терапії метформіном, глімепіридом і воглібозом супроводжується підвищенням функціональної активності β-клітин підшлункової залози, зниженням інсулінорезистентності на тлі зменшення маси тіла.

Abstract P255: Resistance Hypertension And Achievement Of Target Blood Pressure Level By Continuous Positive Airway Pressure Long Therapy In Patients With Obstructive Sleep Apnea

The aim was to assess the arterial stiffness changes in patients with resistant arterial hypertension (AH) and obstructive sleep apnea (OSA) and possibilities of its correction by continuous positive airway pressure (CPAP)-therapy. Design: In 10 month follow-up study were included 46 patients with RAH, who were divided into groups: 1-st - patients with RAH and moderate to severe OSA on CPAP (n=21); 2-nd - patients with RAH and moderate to severe OSA without CPAP (n=25). They underwent somnography by dual-channel portable monitor device, office and ambulatory blood pressure monitoring, echocardiography and applanation tonometry. All patients received similar antihypertensive therapy according to 2013 ESH Guidelines for the management of arterial hypertension. Results: Patients with RAH and OSA (mean apnea-hypopnea index (AHI) 36.5±2.7 event h-1) in comparison with patients with RAH without OSA (mean AHI 3.4±0.2 event h-1) had significantly higher body mass index (34.2±0.7 vs 31.6±0.7 kg m-2, P&lt;0.05), uric acid level (6.7±0.1 vs 5.6±0.4 mg dl-1, P&lt;0,05)). Patients with RAH and OSA in comparison with patients with RAH without OSA had higher carotid-femoral pulse wave velocity (PWVcf) (12.1±0.5 vs 10.2 m s-1, P&lt;0,05) and central systolic blood pressure (CSBP) (143.8±2.7 vs 136.2±3.4 mm Hg, P&lt;0,05). During 10 months follow-up in patients with RAH and moderate and sever OSA on CPAP-therapy there were significantly decrease of PWVcf (from 12.1±0.5 to 10.5±0.5 m s-1, P&lt;0,05), decrease office systolic blood pressure (from 147.8±3.7 to 136.7±2.8 mm Hg; P&lt;0,05) and diastolic blood pressure (from 96.8±3.5 to 87.0±3.3 mm Hg; P&lt;0,05) with achievement of target levels in 67,2% patients. Central systolic BP decreased (from 143.8±2.7 to 137.7±2.8 mm Hg; P&lt;0,05). Conclusion: The combination of therapy continuous positive airway pressure with antihypertensive treatment in patients with resistant arterial hypertension and moderate to severe obstructive sleep apnea improved achievement of target blood pressure, decreased arterial stiffness and decreased central blood pressure.

Lipids and Lipoproteins in Health and Disease: Focus on Targeting Atherosclerosis.

Despite advances in pharmacotherapy, intervention devices and techniques, residual cardiovascular risks still cause a large burden on public health. Whilst most guidelines encourage achieving target levels of specific lipids and lipoproteins to reduce these risks, increasing evidence has shown that molecular modification of these lipoproteins also has a critical impact on their atherogenicity. Modification of low-density lipoprotein (LDL) by oxidation, glycation, peroxidation, apolipoprotein C-III adhesion, and the small dense subtype largely augment its atherogenicity. Post-translational modification by oxidation, carbamylation, glycation, and imbalance of molecular components can reduce the capacity of high-density lipoprotein (HDL) for reverse cholesterol transport. Elevated levels of triglycerides (TGs), apolipoprotein C-III and lipoprotein(a), and a decreased level of apolipoprotein A-I are closely associated with atherosclerotic cardiovascular disease. Pharmacotherapies aimed at reducing TGs, lipoprotein(a), and apolipoprotein C-III, and enhancing apolipoprotein A-1 are undergoing trials, and promising preliminary results have been reported. In this review, we aim to update the evidence on modifications of major lipid and lipoprotein components, including LDL, HDL, TG, apolipoprotein, and lipoprotein(a). We also discuss examples of translating findings from basic research to potential therapeutic targets for drug development.

Target level achievement of low-density lipoprotein cholesterol in patients with peripheral artery disease: Improvement potential despite increased statin use

Background and Aims: Lowering low-density lipoprotein cholesterol (LDL-C) is a key secondary therapeutic measure in patients with peripheral arterial disease (PAD). The 2019 ESC/EAS (European Society of Cardiology/European Atherosclerosis Society) guidelines for the management of dyslipidaemia recommend LDL-C levels of<55 mg/dl for a very high risk subset such as PAD patients. We aimed to assess the trend of statin use over time and the fraction achieving the recommended target level in PAD patients.

Impact of different statins on low-density lipoprotein cholesterol levels in patients with peripheral artery disease

Background and Aims: Patients with peripheral arterial disease (PAD) are at high risk of cardiovascular events and limb threatening complications. According to the 2019 ESC/EAS (European Society of Cardiology/European Atherosclerosis Society) guidelines for the management of dyslipidaemia high intensity statins and ezetimibe are recommended for low-density lipoprotein cholesterol control (LDL-C). We assessed the impact of different types of statins on the lipid profile of patients with PAD and its effect on LDL-C target level achievement.

Masked uncontrolled hypertension: risk factors and ways of influence

According to the current Guidelines, the effectiveness of antihypertensive therapy is assessed mainly by achieving target levels of office blood pressure (BP). However, masked uncontrolled hypertension (MUCH) increases the risk of cardiovascular events, therefore deserves timely diagnosis and correction.&#x0D; Objective — to establish the prevalence and risk factors of MUCH and to clarify how the use of fixed combinations can affect the control of office and out‑of‑office BP.&#x0D; Materials and methods. We examined 70 patients with arterial hypertension (AH) of 1 — 2 degrees. The initial assessment of the effectiveness of antihypertensive therapy was carried out 3 months after its appointment. Of the 70 patients initially enrolled in the study, 63 were able to reach essential office BP reduction point (&lt; 140/90 mm Hg, according to 2020 ISH Guidelines). Patients who reached essential point of office BP reduction were additionally provided 24 hour ambulatory BP monitoring (ABPM) to detect possible MUCH.&#x0D; Results. It was found that among 63 patients in whom AH was controlled according to office BP data, 37 patients (58.7 %) had insufficient hypertension control according to ABPM data (they had MUCH). An assessment of possible factors for the development of MUCH showed that elderly age occurred in 29 (78.4 %) patients with MUCH, male sex — in 22 (59.5 %) patients, smoking — in 26 (70.3 %) patients, stress — in 29 (78.4 %) patients, various sleep disorders — in 17 (45.9 %) patients, diabetes mellitus (DM) — in 21 (56.8 %) patients, obesity — in 25 (67.6 %) patients, insulin resistance (IR) — in 27 (73 %) patients, chronic kidney disease (CKD) — in 13 (35.1 %) patients. Analysis of patient therapy showed that out of 37 patients with MUCH, 7 patients received monotherapy, 9 patients received free dual combinations (ACE inhibitor/sartan + calcium antagonist/diuretic), and 21 patients received fixed dual combinations. In accordance with 2018 ESC/ESH Guidelines, antihypertensive therapy was strengthened for patients with MUCH: those patients who had previously received monotherapy or free combinations were transferred to double fixed combinations (ACE inhibitors/sartans + calcium antagonist/diuretic), in which both drugs acted for 24 hours, and those patients with MUCH who received double fixed combinations were transferred to triple fixed combinations. Evaluation of antihypertensive therapy after 3 months showed that of 37 patients with initially established MUCH, complete BP control was achieved in 32 (86.5 %) patients (in the remaining 5 patients, despite sufficient control of office BP, MUCH was maintained according to ABPM data).&#x0D; Conclusions. In inadequate control of out‑of‑office BP, various disturbances of the circadian rhythm (with a predominance of the non‑dipper rhythm) are more common than with complete BP control. MUCH is associated with such risk factors as elderly age, male gender, smoking, stress, sleep disturbances, DM, obesity, IR, and CKD. Strengthening antihypertensive therapy contributed to the achievement of both office and out‑of‑office BP in 86.5 % of patients with previously established MUCH.&#x0D;

Patterns of clinical management of hypothyroidism in adults: An electronic survey of physicians from the Middle East and Africa

Background: Hypothyroidism is a common endocrine disorder that is managed by a wide range of physicians. There are no data on the pattern of clinical management of hypothyroidism in the Middle East and Africa (MEA) region. Objectives: We sought to document current practices in the management of primary hypothyroidism in the MEA region and compare these with international recommendations and practices elsewhere. Materials and Methods: A convenience sample of physicians practicing in the MEA in relevant disciplines were invited to take a web-based survey consisting of previously validated multiple-choice questions dealing with investigation and treatment of an index case of overt primary hypothyroidism in general and in three special situations. Results: Out of complete 397 responses, 368 were eligible for inclusion in the analysis. The majority were endocrinologists and internal medicine specialists; 82.2% of them have been in clinical practice for 10 years or more. Overt hypothyroidism would be treated using L-T4 alone by 97.2% of respondents; 1.7% would use a combination of L-T4 and liothyronine (L-T3) therapy. The rate of replacement would be gradual (66.5%), an empiric dose, adjusted to achieve target levels (14.7%); or a calculated full replacement dose (18.5%). A target thyroid-stimulating hormone (TSH) of 2.0–2.9 mU/L was favored in the index case of overt hypothyroidism (by 34.4%) followed by a target of 3.0–3.9 mU/L (by 26.0%) of respondents. However, a target of 4.0–4.9 mU/L was the most commonly selected TSH target for an octogenarian (by 33.5% of respondents). Persistent hypothyroid symptoms despite achieving a target TSH would prompt testing for other causes by 86.9% of respondents, a change to L-T4 plus L-T3 therapy by 5.8%, and an increase in the thyroid hormone dose by 4.6%. Evaluation of persistent symptoms would include measurements of complete blood count (82.4%), complete metabolic panel (68.7%), morning cortisol (65.3%), Vitamin B12 levels (54.5%), and serum T3 levels (27.9%). Subclinical disease with a TSH 7.8 mU/L would be treated without further justification by 9.0% of respondents, or in the presence of positive thyroid peroxidase antibodies (65.3%), hypothyroid symptoms (65.0%), high low-density lipoprotein (51.7%), or a goiter (36.7%). The TSH target for a newly pregnant patient was 2.0–2.4 mU/L for 28.5% of respondents, with 15.8% preferring a TSH target of 1.5–1.9 mU/L. Thyroid hormone levels would be checked every 4 weeks during pregnancy by 62.9% and every 8 weeks by an additional 17.6%. A hypothyroid patient with a TSH of 0.5 mU/L who becomes pregnant would receive an immediate L-T4 dose increase by only 28.5% of respondents. Conclusions: The survey revealed that (1) nearly exclusive preference for L-T4 alone for therapy, (2) use of age-specific TSH targets for replacement therapy, (3) a low threshold for treating mild thyroid failure, (4) complacent and variable attention to TSH targets in the pregnant and prepregnant woman, and (5) a highly variable approach to both the rate and means of restoring euthyroid status for overt disease. Both alignments with and divergence from guidelines were detected. The results should help in directing focused educational activities in the region, providing a baseline for future monitoring of practices.

Pharmacokinetics of levetiracetam in neurosurgical ICU patients.

The pharmacokinetics (PK) of drugs is dramatically altered in critical illness. Augmented renal clearance (ARC), a phenomenon characterized by creatinine clearance (CrCl) greater than 130 ml/min/1.73m2, is commonly described in critically ill patients. Levetiracetam, an antiepileptic drug commonly prescribed for seizure prophylaxis in the neurosurgical ICU, undergoes predominant elimination via the kidneys. Hence, we hypothesize that current dosing practice of intravenous (IV) levetiracetam 500 mg twice daily is inadequate for critically ill patients due to enhanced drug elimination. The objectives of our study were to describe the population PK of levetiractam using a nonparametric approach to design an optimal dosing regimen for critically ill neurosurgical patients. This was a prospective, observational, population PK study. Serial blood samples were obtained from neurosurgical ICU patients who received at least one dose of IV levetiracetam. We used uHPLC to analyze these samples and Pmetrics™ software to perform PK analysis. Twenty subjects were included, with a median age of 54 years and CrCl of 104 ml/min. A two-compartmental model with linear elimination adequately described the profile of levetiracetam. Mean clearance (CL) was 3.55 L/h and volume of distribution (V) was 18.8 L. No covariates were included in the final model. Monte Carlo simulations showed a low probability of target attainment (PTA, trough at steady state of ≥6 mg/L) with a standard dose of 500 mg twice daily. A dose of at least 1000 mg twice daily was required to achieve 80% PTA. Two subjects, both with subtherapeutic trough levels, developed early onset seizures. Our study examined the population PK of levetiracetam in a critically ill neurosurgical population. We found that this population displayed higher clearance and required higher doses to achieve target levels.

Mobile application "Aterostop" for a comprehensive assessment of cardiovascular risk in patients in the Russian population

The article provides an overview of an innovative software product for a comprehensive assessment of cardiovascular risk in cardiac patients in the Russian Federation. Based on the new recommendations of the Russian National Atherosclerosis Society (2020), the Aterostop application allows to assess cardiovascular risk, determine the patients achievement of target levels of low-density lipoprotein cholesterol, and also provides recommendations for correcting lipid-lowering therapy. The calculator is implemented as a web browser version, as well as a mobile application for Android and iOS platforms.

Cardiovascular risk profiles and 20-year mortality in older people: gender differences in the Pro.V.A. study

The age- and gender-related cardio-metabolic changes may limit the applicability of guidelines for the prevention of cardiovascular diseases (CVD) in older people. We investigated the association of cardiovascular risk profile with 20-year all-cause and CVD-mortality in older adults, focusing on age- and gender-specific differences. This prospective study involved 2895 community-dwelling individuals aged ≥65 years who participated in the Pro.V.A study. The sum of achieved target levels (smoking, diet, physical activity, body weight, blood pressure, lipids, and diabetes) recommended by the European Society of Cardiology 2016 guidelines was assessed in each participant. From this sum, cardiovascular risk profile was categorised as very high (0–2), high (3), medium (4), low (5), and very low (6–7 target levels achieved). All-cause and CV mortality data over 20 years were obtained from health registers. At Cox regression, lower cardiovascular risk profile was associated with reduced 20-year all-cause mortality in both genders, with stronger results for women (HR = 0.42 [95%CI:0.25–0.69] and HR = 0.61 [95%CI:0.42–0.89] for very low vs. very high cardiovascular risk profile in women and men, respectively). This trend was more marked for CVD mortality. Lower cardiovascular risk profile was associated with reduced all-cause and CVD mortality only in men < 75 years, while the associations persisted in the oldest old women. A lower cardiovascular risk profile, as defined by current guidelines, may reduce all-cause and CVD mortality in older people, with stronger and longer benefits in women. These findings suggest that personalised and life-course approaches considering gender and age differences may improve the delivery of preventive actions in older people.

Targeting human milk fortification to improve very preterm infant growth and brain development: study protocol for Nourish, a single-center randomized, controlled clinical trial

BackgroundHuman milk is recommended for very preterm infants, but its variable macronutrient content may contribute to undernutrition during a critical period in development. We hypothesize that individually targeted human milk fortification is more effective in meeting macronutrient requirements than the current standard of care.MethodsWe designed a single-center randomized, controlled trial enrolling 130 infants born < 31 completed weeks’ gestation. Participants will receive fortified maternal and/or pasteurized donor milk but no formula. For participants in the intervention group, milk will be individually fortified with protein and fat modulars to achieve target levels based on daily point-of-care milk analysis with mid-infrared spectroscopy, in addition to standard fortification. The study diet will continue through 36 weeks’ postmenstrual age (PMA). Clinical staff and parents will be masked to study group. Primary outcomes include: 1) body length and lean body mass by air displacement plethysmography at 36 weeks’ PMA; 2) quantitative magnetic resonance imaging-based measures of brain size and microstructure at term equivalent age; and 3) Bayley-IV scales at 2 years’ corrected age.DiscussionWe expect this trial to provide important data regarding the effectiveness of individually targeted human milk fortification in the neonatal intensive care unit (NICU).Trial registrationNCT03977259, registered 6 June, 2019.

Association between H-type arterial hypertension and vascular stiffness (a pilot study)

Increased arterial stiffness is an important determinant of cardiovascular risk. Elevated total homocysteine (HC) levels appeared to be an independent risk factor for cardiovascular disease (CVD). To date, clinical studies on the relationship between HC and pulse wave velocity (PWV) assessment have shown conflicting results. Aim. To estimate the prevalence of hyperhomocystinemia (HHc) among patients with mild to moderate arterial hypertension and the effect of HHc on the vascular wall stiffness. Materials and methods. Our study was carried out as a part of the HYPSTER study in Ukraine. The study included 40 patients with I and II degree of arterial hypertension (AH) (average office systolic blood pressure (SBP)/diastolic (DBP) – 155.88/92.60 ± 1.63/1.43 mm Hg), heart rate – 71.40 ± 1.29 beats/min. The average age of the patients was 55.85 ± 2.09 (26–74) years. Patients with HC levels ≥10 μmol/l were defined as patients with H-type AH (HHc). Arterial stiffness was determined by PWV. Results. We found that at the beginning of the study, 75 % (30 patients with mild and moderate hypertension) had H-type hypertension with an increased level of HC. Patients with H-type AH and AH patients without HHc did not differ in age and AH duration. At the same time, patients with H-type AH had higher body weights and BMI. Office SBP in patients with H-type hypertension was higher compared to patients without HHc (156.45 ± 1.04 mm Hg vs. 152.55 ± 1.41 mm Hg at the beginning (P &lt; 0.05) and 130.65 ± 0.96 mm Hg vs. 126.97 ± 1.08 mm Hg after 6 months (P &lt; 0.05)) of treatment, respectively. BMI in H-type AH was 30.72 ± 0,39 kg/m2 vs. 28.34 ± 0.69 kg/m2 without HHc (P &lt; 0.05) at the beginning of the study. It was difficult to achieve target levels of BP in the patients with H-type hypertension during the treatment and they had high initial blood pressure values. In contrast to the patients without HHc, H-type AH patients had a more pronounced degree of insulin resistance (according to the HOMA index), lower GFR both at the beginning and at the end of the treatment. According to ambulatory BP monitoring, H-type AH patients presented with a significantly higher SBP level before starting the treatment compared to those with AH without HHc. The regression analysis revealed an association between HC and PWVel, regardless of the degree of BP reduction (PWVel (6 months), m/s, β = 0.307, P = 0.001). Conclusions. Hyperhomocystinemia was observed in 75 % of patients with arterial hypertension. Homocysteine levels were associated with vascular stiffness, regardless of the reduction in blood pressure level.

EFFECT OF 24-WEEK ATORVASTATIN THERAPY IN STEMI PATIENTS ON ARTERIAL STIFFNESS

Objective: To study the parameters of regional arterial stiffness in patients after acute myocardial infarction with ST segment elevation (STEMI) depending on the achievement of the target level of low-density lipoprotein cholesterol (LDL-C) during 24-week therapy with atorvastatin 40–80 mg. Design and method: The study included 80 STEMI patients (mean age 51.8 ± 8.2 years) in the first 24–96 hours from the disease onset. The diagnosis was confirmed by biomarkers of myocardial necrosis, electrocardiography, coronary angiography. All patients received treatment for STEMI. On 7th-9th day from the disease onset and after 24 weeks of follow-up, the regional arterial stiffness was assessed by volume sphygmography (VaSera-1000, “Fukuda Denshi”, Japan). The following indicators were determined: the pulse wave velocity in the aorta (PWV), in the arteries of elastic type on the right and left (R/L-PWV), cardio-ankle vascular index - CAVI (CAVI-1 and L-CAVI-1). CAVI-1- reflects the true arterial stiffness between the heart valve and the leg artery, L-CAVI-1 - between the groin area and the leg artery. The patients were divided into two groups depending on the LDL-C level after 24 weeks. Group 1 included 39 patients who did not reach the LDL-C &lt; 1.4 mmol/L and/or decrease by 50% from the initial. The second consisted of 41 people who reached the target LDL-C level. Results: After 24 weeks of therapy in patients of group 1, there was no significant dynamics in all studied parameters. While in the 2nd group, there was a statistically significant decrease in almost all characteristics of vascular rigidity: PWV - from 8.1 ± 1.8 to 7.1 (5.6;7.3) m/s - by 21.7% (p = 0.01); R-PWV - from 13.1 (12.5;14.2) to 12.0 ± 0.84 m/s - by 8.1% (p = 0.03); L-PWV- from 6.8 (12.5;15.1) to 12.2 (11.2; 12.9) m/s - by 6.8% (p = 0.001). No significant changes were observed in CAVI-1. L-CAVI-1 decreased from 7.8 (7.3;8.4) to 7.4 ± 0.9 - by 4.6% (p = 0.03). Conclusions: Achievement of the LDL-C target level in patients after STEMI during 24-week therapy with atorvastatin 40–80 mg was accompanied by a significant improvement in the structural and functional properties of arteries according to volume sphygmography.

29043 Using Milestones to Judge the Progress of Clinical Informatics Fellows Compared with their Personal Goals

ABSTRACT IMPACT: We report a novel metric for assessing clinical informatics fellows relative to their personal goals, using standardized milestones that have been approved for the field by ACGME. OBJECTIVES/GOALS: ACGME has defined 20 milestones that serve as the goals for fellows in clinical informatics. Each fellow is rated from 1 to 5 on the achievement of each milestone, where 1 is entry-level, 4 is the level expected of a graduating fellow, and 5 is aspirational. We assessed fellows’ progress toward the personal goal levels that they set for each milestone. METHODS/STUDY POPULATION: At the start of the fellowship, we asked each fellow to rate the personal target levels that they want to achieve for each milestone. Since the default target level of achievement for a graduating fellow is a 4, we asked fellows to document exceptions from this target. We calculated a metric for each fellow’s achievement of each milestone as their achievement rating (assigned by mentors and rotation leaders during the semi-annual Clinical Competency Committee meeting) divided by the fellow’s desired level of achievement. In summarizing across the milestones, we counted those milestones having achievement metrics &gt;=1.0 as ‘achieved,’ and then for milestones that were not achieved, we calculated an average for the fellow. RESULTS/ANTICIPATED RESULTS: As of June, 2020, our two graduating 2nd-year fellows had fully met 9/20 and 18/20 milestones, respectively. For the unmet milestones they averaged 81% and 85% achievement. The largest shortfalls were 75% achievements in Assessing User Needs for one fellow, and in Recognition of Errors for the other. One of our three 1st-year fellows had fully met 3/20 milestones; the other two had met none at 1st-year’s end. For unmet milestones, the 1st-year fellows’ average achievement metrics were 69%, 67%, and 52%. The greatest shortfalls were in Resource Utilization (creating job descriptions, budgeting etc.) and in Communication with Patients and Families. However, the rotations that would expose them to project management and to patient-facing systems such as MyChart come in our 2nd-year. DISCUSSION/SIGNIFICANCE OF FINDINGS: Assessing milestones met plus the percent achievement for those not yet met provides a useful metric for comparing fellows and identifying areas in need of more training. Although milestones will soon change to reflect the recent practice analysis for clinical informatics, we expect that this approach to assessing fellows will remain equally useful.

Vancomycin pharmacokinetic parameters in patients undergoing hematopoietic stem cell transplantation.

Current guidelines on vancomycin dosing lack specific recommendations about its dosing in hematopoietic stem cell transplant (HSCT) patients, the objective of the current study was to compare vancomycin pharmacokinetic variables in this population with those of general population. A prospective study was designed and the calculated parameters of vancomycin pharmacokinetic were compared with individualized parameters. Two trough levels before 4th and 5th doses and a peak level after the 4th dose, were taken. All patients received a dose of 15 mg/kg of vancomycin two or three times a day. Pharmacokinetic parameters were calculated using a one compartmental model. The association between different variables and of acute kidney injury (AKI) development and achievement of target levels were also evaluated. A significant difference was observed between population Volume of distribution (Vd) and individualized Vd (mean 57.33 L vs 162.86 L, p value 0.019) and trough and peak levels (p values 0.0001 and 0.001; for mean trough and peak levels respectively). The achievement of the recommended trough levels and area under the concentration time curve per minimum inhibitory concentration (AUC24/MIC) was very low (5/71 and 24/71 patients respectively). No significant differences were observed between population and individualized clearance and rate of elimination of vancomycin (p values of 0.092 and 0.55 respectively). Concomitant receipt of cyclosporine was significantly related with development of AKI (p value 0.046). The dosing methods which use population-based pharmacokinetic variables does not result in desired therapeutic levels in HSCT patients, mainly because of larger vancomycin volume of distribution.

Effect of increasing dietary proportion of plantain on milk production and nitrogen use of grazing dairy cows in late lactation

Abstract Context Plantain has shown promise as a forage that can mitigate nitrogen (N) losses from farm systems, although adoption and regulation requires knowledge of the minimum amount of forage area or diet quantity to observe an effect. Aims A grazing study was conducted to evaluate the effect of offering increasing proportions of spatially adjacent plantain (PL) and perennial ryegrass–white clover (PRGWC) on milk production and N utilisation of dairy cows. Methods Forty-eight late lactating cows blocked into replicated (n = 3) groups of four cows were randomly allocated to one of the following four forage treatments based on percentage area of plantain: 0%, 15%, 30%, or 60%. Cows were allocated 25 kg DM/cow.day of forage above ground level daily on the basis of metabolisable energy requirements. Dry matter intake was estimated from the difference between pre- and post-grazing pasture mass, using a calibrated electronic rising-plate meter. Milk production was measured as yield and milk solids, while N use was estimated from total milk N excretion and spot subsamples of blood, urine and faeces. Key results Offering cows spatially adjacent strips of PL increased apparent dry matter intake compared with PRGWC pasture alone (16.4 vs 15.1 kg DM/cow.day, P = 0.027) and apparent metabolisable energy intake (203 vs 188 MJ/kg.cow.day, P &lt; 0.001). Milk yield (16.1 kg/cow.day), milk solids production (1.6 kg/cow.day) and fat concentration (5.69%) were unaffected by the proportion of plantain in the diet. PL offered at 60% of the area increased milk protein concentration compared with PRGWC (4.65 vs 4.36%, P &lt; 0.01). There was no treatment effect on total apparent N intake (563 g N/cow.day), N excretion in milk (113 g N/cow.day) and N-utilisation efficiency (20 g milk N/100 g N consumed). However, total milk urea, blood urea and urine urea N concentrations declined with increasing plantain in the diet, reflecting an influence on urea metabolism. Conclusions Offering plantain to grazing dairy cows did not improve milk yield or N-use efficiency, but influenced urea metabolism. Implications Sowing plantain in spatially separate strips within perennial ryegrass–white clover pastures is a useful option to achieve target levels of plantain in the diet and, in conjunction with other mitigation strategies, can be used to improve the sustainability of pastoral dairy farming.

The role of sodium-glucose cotransporter 2 inhibitors in the treatment of type 2 diabetes: from clinical research to real practice

In type 2 diabetes mellitus (T2DM), the development and progression of cardiovascular diseases occurs, which allows it to be considered as a cardiorenal metabolic syndrome. This should be taken into account when choosing hypoglycemic drugs. Patients with T2DM receiving insulin therapy often have a long history of diabetes, cardiovascular disease, chronic kidney disease, obesity, and need to be prescribed high doses of insulin and/or complex insulin therapy regimens to maintain glycemic control, which does not always lead to the achievement of target levels of glycemia and glycated hemoglobin (HbA1c). Adding to any insulin therapy regimen drugs from the class of sodium-glucose cotransporter type 2 inhibitors (SGLT-2), which have proven their cardio- and renoprotective properties, seems to be a rational combination in patients with T2DM and may have a number of advantages. The article presents 4 clinical examples of dapagliflozin administration, a drug from the SGLT2 class, to patients who are on insulin therapy, having T2DM with a long history (10–26 years), as well as cardiovascular diseases, chronic kidney disease, and obesity. Dapagliflozin administration allowed to improve glycemic control, to stabilize the insulin dose, as well as reduce body weight without increasing the frequency of serious episodes of hypoglycemia in patients who initially received large doses of insulin. In the long term, we can expect reduction of the progression of cardiovascular risks and the risks of hospitalization due to existing complications of the disease.