scholarly journals 1090. Does calculation method matter for targeting vancomycin AUC?

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S636-S636
Author(s):  
Jack Chang ◽  
Dhara Patel ◽  
Kimberly C Claeys ◽  
Marc H Scheetz ◽  
Emily Heil
Keyword(s):  
Bayesian Model ◽  
Bayesian Method ◽  
Drug Exposure ◽  
Area Under The Curve ◽  
First Order ◽  
Bayesian Estimates ◽  
Actual Patient ◽  
Spearman's Rho ◽  
Spearman’S Rho ◽  
Population Pk

Abstract Background Recent vancomycin (VAN) guidelines recommend targeting an area under the curve (AUC) concentration of 400-600 for treatment of methicillin resistant Staphylococcus aureus infections. Multiple strategies for calculating AUC exist, including first order pharmacokinetic (foPK) equations and Bayesian models. Most clinical applications of foPK assume unchanged patient status and project ideal administration times to estimate exposure. Bayesian modeling provides the best estimate of true drug exposure and can incorporate changing patient covariates and exact doses. We compared two commonly used foPK methods to Bayesian estimates of VAN AUC. Graphs depict calculated AUCs using the three different methods: 1) Population PK estimated (foPOPPK) 2) Two-level first dose estimated (foFDPK) 3) Bayesian estimated. Methods First order equations were performed using population PK estimates (foPOPPK) to estimate steady state (SS) AUC and initial doses. Two concentrations after first dose were used to estimate SS AUC (foFDPK). A 2-compartment Bayesian model allometrically scaled for weight and adjusted for creatinine clearance was used to determine 24-48 hour AUCs. Differences between AUCs were compared using a mixed-effects analysis, and correlation of foPK equations to Bayesian estimates was described using Spearman’s correlation. Patient results from each method were classified as below (< 400), within (400-600), or above ( >600) targets. Results 65 adult patients were included. The median and IQR for calculated AUCs using foPOPPK, foFDPK, and Bayesian methods were 495.6 (IQR: 76.6), 498.2 (IQR: 107.4), and 472.1 (IQR: 177.9), respectively with p >0.65 for both foPK methods vs. the Bayesian method. AUCs predicted by foPK equations were poorly correlated with Bayesian AUCs (Spearman’s rho= -0.08, p=0.55), while AUCs from foFDPK better correlated with Bayesian AUCs (Spearman’s rho= 0.48, p=0.00). AUCs were within, above, and below target for 54%, 20%, and 26% for the Bayesian model; 95%, 5% and 0% for foPOPPK; and 74%, 12%, and 14% for foFDPK. foPK AUC estimates concurred with Bayesian estimates only 52% of the time. Conclusion AUCs calculated by the three methods did not differ on average, but dosing recommendations for foPK at the patient level varied substantially compared to the Bayesian method. This difference is because Bayesian estimation incorporates actual patient exposures while foPK equations rely on idealized dose timing to predict AUCs. Disclosures Kimberly C. Claeys, PharmD, GenMark (Speaker’s Bureau) Marc H. Scheetz, PharmD, MSc, Nevakar (Grant/Research Support)SuperTrans Medical (Consultant)US Patent #10688195B2 (Other Financial or Material Support, Patent holder)

Alterations of serum levels of plasminogen, TNF-α, and IDO in granulomatosis with polyangiitis patients

Vascular ◽  
2021 ◽  
pp. 170853812098630
Author(s):  
Dobroslav Kyurkchiev ◽  
Tsvetelina Yoneva ◽  
Adelina Yordanova ◽  
Ekaterina Kurteva ◽  
Georgi Vasilev ◽  
...  
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Renal Involvement ◽  
Clinical Manifestations ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Necrosis Factor Alpha ◽  
Cross Sectional ◽  
Spearman's Rho ◽  
Tnf Α ◽  
Spearman’S Rho

Background Granulomatosis with polyangiitis (GPA) is a representative of vasculitides associated with anti-neutrophil cytoplasmic autoantibodies. “Classical” antibodies directed against proteinase 3 are involved in the pathogenesis and are part of the GPA diagnosis at the same time. Along with them, however, antibodies against Lysosomal-Associated Membrane Protein-2 (LAMP-2) and antibodies directed against plasminogen have been described in GPA. Objectives and methodology: We performed a cross-sectional study enrolling 34 patients diagnosed with GPA. Our study was aimed at looking for correlations between serum levels of LAMP-2 and plasminogen and the clinical manifestations of the GPA. Furthermore, we examined serum levels of tumor necrosis factor-alpha (TNF-α) and its associated indoleamine-pyrrole 2,3-dioxygenase (IDO), as well as we looked for a correlation between these cytokines and the clinical manifestations of GPA. Results The results showed that in GPA, serum plasminogen levels were negatively associated with renal involvement (receiver operating characteristic (ROC) area under the curve (AUC) of 0.78) (95% CI 0.53–0.91), p = 0.035, and the extent of proteinuria, Spearman’s Rho = –0.4, p = 0.015. Increased levels of TNF-α and IDO correlated with disease activity, Spearman’s Rho =0.62, p = 0.001 and Spearman’s Rho = 0.4, p = 0.022, respectively, whereas only TNF-α was increased in severe forms of GPA with lung involvement (ROC AUC of 0.8) (95% CI 0.66–0.94), p = 0.005. Conclusions In this study, we demonstrate the alteration of soluble factors, which play an important role in the pathogenesis of GPA and their relationship with the clinical manifestations of the disease. Our main results confirm the associations of increased secretory TNF-α and some clinical manifestations, and we describe for the first time decreased serum plasminogen levels and their association with renal involvement.

scholarly journals Impact of Mucositis on Absorption and Systemic Drug Exposure of Isavuconazole

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Laura L. Kovanda ◽  
Francisco M. Marty ◽  
Johan Maertens ◽  
Amit V. Desai ◽  
Christopher Lademacher ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
Drug Exposure ◽  
Area Under The Curve ◽  
Invasive Fungal Disease ◽  
Oral Formulation ◽  
Water Soluble ◽  
Parameter Estimates ◽  
Two Phase ◽  
Population Pk ◽  
The Impact

ABSTRACT Isavuconazonium sulfate is the water-soluble prodrug of isavuconazole. Population analyses have demonstrated relatively predictable pharmacokinetic (PK) behavior in diverse patient populations. We evaluated the impact of mucositis on the oral isavuconazole exposure using population PK modeling. This study included patients treated in two phase 3 trials of isavuconazole, SECURE for treatment of invasive aspergillosis (IA) and other filamentous fungi and VITAL for patients with mucormycosis, invasive fungal disease (IFD) caused by other rare fungi, or IA and renal impairment. Mucositis was reported by site investigators and its impact on oral bioavailability was assessed. Use of the oral formulation was at the discretion of the investigator. Patients with plasma samples collected during the use of isavuconazonium sulfate were included in the construction of population PK model. Of 250 patients included, 56 patients had mucositis at therapy onset or as an adverse event during oral isavuconazole therapy. Levels of oral bioavailability were comparable, at 98.3% and 99.8%, respectively. The average drug exposures (average area under the curve [AUCave]) calculated from either the mean or median parameter estimates were not different between patients with and without mucositis. Mortality and overall clinical responses were similar between patients receiving oral therapy with and without mucositis. We found that isavuconazole exposures and clinical outcomes in this subset of patients with mucositis who were able to take oral isavuconazonium sulfate were comparable to those in patients without mucositis, despite the difference in oral bioavailability. Therefore, mucositis may not preclude use of the oral formulation of isavuconazonium sulfate.

scholarly journals POS0584 ULTRASONOGRAPHY OF THE MEDIAN NERVE IN PATIENTS WITH RHEUMATOID ARTHRITIS UNDER SUSPICION OF CARPAL TUNNEL SYNDROME

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 525.1-525
Author(s):  
S. Tsiami ◽  
E. Ntasiou ◽  
C. Krogias ◽  
R. Gold ◽  
J. Braun ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Carpal Tunnel Syndrome ◽  
Median Nerve ◽  
Carpal Tunnel ◽  
Nerve Conduction Velocity ◽  
Sectional Area ◽  
Cross Sectional ◽  
Spearman's Rho ◽  
Spearman’S Rho ◽  
Tunnel Syndrome

Background:Carpal tunnel syndrome (CTS) is the most common nerve compression syndrome and a common extra-articular manifestation of rheumatoid arthritis (RA). Different causes of CTS are known, among them inflammatory and non-inflammatory pathologies. Electroneurography (ENG) of the median nerve, the method of choice to diagnose CTS, measures impairment of nerve conduction velocity without explaining its underlying cause. However, because the electrical stimulation is often not well tolerated, ENG results may come out inconclusive. Using greyscale ultrasonography (GS-US) provides anatomic information including a structural representation of the carpal tunnel.Objectives:To investigate the performance of nerve GS-US in the diagnosis of CTS in patients with RA.Methods:Consecutive patients with active RA under suspicion of CTS presenting to a large rheumatologic center were included. Both hands were examined by an experienced neurologist including ENG and a GS-US (ML linear probe with 6-15 Hz) of the median nerve. An established grading system for ENG (1), and an established system for GS-US based on cut-offs for the nerve cross sectional area (CSA) [mild: 0,11-0,13cm2, moderate: 0,14-0,15 cm2, severe: > 0,15 cm2 CTS (2)] were used. In addition, the Boston Carpal Tunnel Syndrome Questionnaire (BCTSQ) was used to assess CTS symptoms (3).Results:Both hands of 58 patients with active RA (n=116) and clinical suspicion of CTS (in 38 cases bilaterally) were included. After clinical examination, CTS was suspicious in 96 hands (82.8%), and 59 of all hands had a final diagnosis of CTS (50.9%). Of the latter, 43 hands (72.9%) had a positive ENG and 16 (27.1%) a positive GS-US finding only, while 30 hands (50.8%) were positive in both examinations.There was a good correlation of the cross-sectional area (CSA) as well as the CSA-ratio to the ENG findings: the larger the CSA, the more severe was the CTS as assessed by ENG (Spearman’s rho=0.554; p<0.001). The more severe the GS-US findings of CTS were, the more definite were the distal motor latency (Spearman’s rho=0.554; p<0.001) and sensible nerve conduction velocity of the median nerve (Spearman’s rho=-0.5411; p<0.001).In the 46 hands positive in GS-US, tenosynovial hypertrophy of the flexor tendons was detected in 19 hands (41.3%), 7 of which (36.8%) also showed an additional cystic mass. In these 19 patients, clinical complains were more severely present than in patients with non-inflammatory CTS, as assessed by the BCTSQ with a total score of 68.8±13.4 vs. 59.3±13.7, respectively (p=0.007).Conclusion:In patients with active RA and clinical complains of CTS, ultrasound examinations provide additional information about inflammation which is helpful for a diagnosis of CTS. Thus, ENG and nerve GS-US should be used complementary for a diagnostic workup of CTS in RA patients with a suspicion of CTS. Power-Doppler may further improve the diagnostic performance of GS-US.References:[1]Padua L et al. Acta Neurol Scand 1997; 96:211–217[2]El Miedany et al., Rheumatology (Oxford). 2004 Jul; 43(7):887-895[3]Levine DW et al. J Bone Joint Surg Am 1993; 75: 1585-1592Figure 1.BCTSQ scores in patients with diagnosis of CTS and absence or presence of RA-related tenosynovial hypertrophyDisclosure of Interests:None declared

Factors affecting thyroid volume in adolescent students attending a rural middle school in East Hangzhou, China

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Qiaoyong Liu ◽  
Yiqian Jiang ◽  
Lijun Shen ◽  
Jiming Zhu
Keyword(s):  
Middle School ◽  
Middle School Students ◽  
Growth And Development ◽  
Univariate Analysis ◽  
Thyroid Volume ◽  
Physical Development ◽  
School Students ◽  
Spearman's Rho ◽  
Spearman’S Rho ◽  
Rural Middle School

AbstractObjectiveTo investigate the thyroid volume (Tvol) and to explore factors that affects it among 12 to 15-year-olds attending a rural middle school in east Hangzhou, China.MethodsA cross-sectional survey of middle school students attending a rural middle school in east Hangzhou, China was conducted. Height, weight and other physical development related indicators in middle school students were measured. The thyroid size was measured using ultrasound, and the thyroid volume calculated.ResultsThe median (P25, P75) of the thyroid volume in 596 middle school students from a rural middle school in east Hangzhou, China was 6.69 (5.66, 7.98) mL. Our study enrolled 305 male students (51.2%) and 291 female students (48.8%). The height, weight and thyroid volume of middle school students increased with age. Univariate analysis revealed that height, weight, body mass index (BMI) and body surface area (BSA) were positive correlated with thyroid volume (p<0.01).The correlation between BSA and thyroid volume was significant (Spearman’s rho=0.473, p<0.01). Multiple linear regression analysis revealed that BSA was positive and significantly correlated with the thyroid volume (p<0.05). Regression equation was Y=−2.532 + 6.186×BSA.ConclusionThe thyroid volume is not only affected by age, but it is also affected by growth and development. Goiter cannot only be assessed based on age, gender and thyroid volume. However, this study established that BSA not only presented the strongest correlation with thyroid volume (Spearman’s rho=0.473), but also had a strong correlation with physical development, taking into account the growth and development of middle school students, and showed greater stability. Therefore, we recommend inclusion of BSA as a reference standard in the measurement of the thyroid volume.

Glioblastoma and primary central nervous system lymphoma: differentiation using MRI derived first-order texture analysis – a machine learning study

2021 ◽  
pp. 197140092199897
Author(s):  
Sarv Priya ◽  
Caitlin Ward ◽  
Thomas Locke ◽  
Neetu Soni ◽  
Ravishankar Pillenahalli Maheshwarappa ◽  
...  
Keyword(s):  
Machine Learning ◽  
Central Nervous System ◽  
Nervous System ◽  
Diagnostic Performance ◽  
Model Performance ◽  
Area Under The Curve ◽  
Central Nervous System Lymphoma ◽  
First Order ◽  
Single Slice ◽  
Contrast Enhanced

Objectives To evaluate the diagnostic performance of multiple machine learning classifier models derived from first-order histogram texture parameters extracted from T1-weighted contrast-enhanced images in differentiating glioblastoma and primary central nervous system lymphoma. Methods Retrospective study with 97 glioblastoma and 46 primary central nervous system lymphoma patients. Thirty-six different combinations of classifier models and feature selection techniques were evaluated. Five-fold nested cross-validation was performed. Model performance was assessed for whole tumour and largest single slice using receiver operating characteristic curve. Results The cross-validated model performance was relatively similar for the top performing models for both whole tumour and largest single slice (area under the curve 0.909–0.924). However, there was a considerable difference between the worst performing model (logistic regression with full feature set, area under the curve 0.737) and the highest performing model for whole tumour (least absolute shrinkage and selection operator model with correlation filter, area under the curve 0.924). For single slice, the multilayer perceptron model with correlation filter had the highest performance (area under the curve 0.914). No significant difference was seen between the diagnostic performance of the top performing model for both whole tumour and largest single slice. Conclusions T1 contrast-enhanced derived first-order texture analysis can differentiate between glioblastoma and primary central nervous system lymphoma with good diagnostic performance. The machine learning performance can vary significantly depending on the model and feature selection methods. Largest single slice and whole tumour analysis show comparable diagnostic performance.

scholarly journals Validity and reliability testing of the Toddler and Infant (TANDI) Health Related Quality of Life instrument for very young children

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Janine Verstraete ◽  
Lebogang Ramma ◽  
Jennifer Jelsma
Keyword(s):  
Quality Of Life ◽  
Health Related Quality ◽  
Validity And Reliability ◽  
Spearman's Rho ◽  
Spearman’S Rho ◽  
Related Quality ◽  
Health Related ◽  
Six Dimensions ◽  
The Impact

Abstract Background Despite the high burden of disease in younger children there are few tools specifically designed to estimate Health Related Quality of Life (HRQoL) in children younger than 3 years of age. A previous paper described the process of identifying a pool of items which might be suitable for measuring HRQoL of children aged 0–3 years. The current paper describes how the items were pruned and the final draft of the measure, Toddler and Infant (TANDI) Health Related Quality of Life, was tested for validity and reliability. Methods A sample of 187 caregivers of children 1–36 months of age were recruited which included children who were either acutely ill (AI), chronically ill (CI) or from the general school going population (GP). The TANDI, an experimental version of the EQ-5D-Y proxy, included six dimensions with three levels of report and general health measured on a Visual Analogue Scale (VAS) from 0 to 100. The content validity had been established during the development of the instrument. The TANDI, Ages and Stages Questionnaire (ASQ), Faces, Leg, Activity, Cry, Consolabilty (FLACC) or Neonatal Infant Pain Scale (NIPS) and a self-designed dietary information questionnaire were administered at baseline. The TANDI was administered 1 week later in GP children to establish test-retest reliability. The distribution of dimension scores, Cronbach’s alpha, rotated varimax factor analysis, Spearman’s Rho Correlation, the intraclass correlation coefficient, Pearson’s correlation, analysis of variance and regression analysis were used to explore the reliability, and validity of the TANDI. Results Concurrent validity of the different dimensions was tested between the TANDI and other instruments. The Spearman’s Rho coefficients were significant and moderate to strong for dimensions of activity and participation and significant and weak for items of body functions. Known groups were compared and children with acute illness had the lowest ranked VAS (median 60, range 0–100), indicating worse HRQoL. The six dimensions of the TANDI were tested for internal consistency and reliability and the Cronbach’s α as 0.83. Test-retest results showed no variance for dimension scores of movement and play, and high agreement for pain (83%), relationships (87%), communication (83%) and eating (74%). The scores were highly correlated for the VAS (ICC = 0.76; p < 0.001). Conclusion The TANDI was found to be valid and reliable for use with children aged 1–36 months in South Africa. It is recommended that the TANDI be included in future research to further investigate HRQoL and the impact of interventions in this vulnerable age group. It is further recommended that future testing be done to assess the feasibility, clinical utility, and cross-cultural validity of the measure and to include international input in further development.

HUBUNGAN PERILAKU MAHASISWA POLTEKKES YANG MENGGUNAKAN FIXED APLIANCE TENTANG MENYIKAT GIGI DENGAN NILAI OHI-S DI POLTEKKES KEMENKES MEDAN TAHUN 2013

2019 ◽  
Vol 8 (3) ◽  
pp. 211-217
Author(s):  
Herlinawati Herlinawati ◽  
Ngena Ria ◽  
Zuraidah Nasution
Keyword(s):  
Chi Square ◽  
Cross Sectional ◽  
Fixed Appliance ◽  
Spearman's Rho ◽  
Spearman’S Rho

Fixed appliance atau disebut juga pesawat orthodonti cekat merupakan alat orthodonti yang dilengketkanlangsung pada gigi. Dewasa ini pemakaian fixed appliance semakin banyak diminati kawula muda untukmemperbaiki dan mengoptimalkan fungsi gigi sebagai alat kunyah dan untuk mengoptimalkan fungsiestetika gigi. Piranti fixed appliance memiliki bentuk yang rumit sehingga mempermudah lengketnya plaklebih lama dan dapat meningkatkan resiko terjadinya karies, gingivitis dan penyakit periodontal. Adanyapiranti fixed appliance yang menempel pada gigi-gigi akan menyulitkan untuk membersihkan gigi sehinggacenderung terjadi penumpukan plak pada gigi disekitar bracket dan mahkota gigi pada tepi gingival.Penelitian ini bertujuan untuk mengetahui hubungan perilaku mahasiswa yang memakai fixed appliancetentang menyikat gigi dengan nilai OHI-S di Poltekkes Kemenkes Medan. Jenis penelitian yang digunakanadalah survei analitik dengan desain cross sectional . Populasi dalam penelitian ini berjumlah 122 orang dansampel adalah seluruh populasi yaitu 122 orang (total populasi). instrumen yang dipakai yaitu kaca mulut,pinset, sonde, nier bekken, handuk bersih kuesioner dan formulir pemeriksaan. Analisis data bivariatdengan menggunakan uji chi-square dan Spearman’s rho dengan derajat kepercayaan 95% (α = 0,05).Berdasarkan hasil penelitian, diperoleh kategori pengetahuan mahasiswa tidak berhubungan dengan kriteriaOHI-S (p > 0,05) sedangkan kategori sikap dan tindakan mempunyai hubungan dengan kriteria OHI-S (p <0,05). Nilai OHI-S rata-rata adalah 2,68. Dianjurkan kepada mahasiswa yang menggunakan fixed applianceagar lebih meningkatkan kebersihan gigi dan mulutnya, mengiku

Επίδραση δύο στατινών στην 24ωρη διακύμανση της αρτηριακής σκληρίας και της κεντρικής αορτικής πίεσης σε ασθενείς με δυσλιπιδαιμία

2019 ◽  
Author(s):  
Ανδρομάχη Ρέκλου
Keyword(s):  
Spearman's Rho ◽  
Spearman’S Rho

Σκοπός: Η αρτηριακή σκληρία αποτελεί έναν ανεξάρτητο παράγοντα καρδιαγγειακού κινδύνου. Οι στατίνες πέρα από την υπολιπιδαιμική δράση εμφανίζουν πολλαπλές ευεργετικές πλειοτροπικές επιδράσεις στο καρδιαγγειακό σύστημα ενώ υπάρχουν δεδομένα ότι θα μπορούσαν να βελτιώσουν και την αρτηριακή σκληρία άμεσα. Σκοπός της παρούσης μελέτης ήταν η εκτίμηση της επίδρασης στατινών στην 24ωρη διακύμανση της αρτηριακής σκληρίας και της κεντρικής αορτικής πίεσης ασθενών με μεμονωμένη δυσλιπιδαιμία χωρίς συνοδά καρδιαγγειακά νοσήματα που δεν ελάμβαναν κάποια επιπλέον αγωγή.Μέθοδος: Πενήντα δύο αρχικά ασθενείς, τυχαιοποιήθηκαν, ώστε να λάβουν για 6 μήνες είτε μιας ισχυρής δράσης (ροσουβαστατίνη 10 mg) είτε μιας ήπιας δράσης στατίνη (σιμβαστατίνη 20mg) ,με σκοπό την επίτευξη του στόχου LDL-C <115 mg/dl. Εάν ένας ασθενής ,ανεξαρτήτως ομάδας, δε μπορούσε να επιτύχει τον στόχο της LDL-C στο τέλος του 1ου μήνα παρακολούθησης, αποκλειόταν από τη μελέτη. Από το σύνολο των 52 ασθενών, 44 ασθενείς, 22 σε κάθε ομάδα, πέτυχαν τον στόχο της LDL-C στο τέλος του 1ου μήνα και συνέχισαν στη μελέτη. Οι ασθενείς αυτοί εκτιμήθηκαν πριν και μετά την αγωγή ως προς τις παραμέτρους αρτηριακής σκληρίας: κεντρική αορτική πίεση (cBP), κεντρικό αυξητικό δείκτη (ΑIx) και ταχύτητα σφυγμικού κύματος (PWV). Η 24ωρη αρτηριακή σκληρία αξιολογήθηκε με τη βοήθεια της συσκευής Mobil-O-Graph 24h PWA Monitor. Παράλληλα πραγματοποιήθηκε συσχέτιση των παραμέτρων της αρτηριακής σκληρίας της επίσκεψη διαλογής και των δύο ομάδων ως προς τις δύο μεθόδους που χρησιμοποιήθηκαν (24ωρη καταγραφή με Mobil-O-Graph 24h PWA Monitor και με την συσκευή Sphygmocor) με συντελεστή συσχέτισης «spearman’s rho».Αποτελέσματα: Οι δυο ομάδες, παρουσίαζαν παρόμοια κατανομή ως προς τις βασικές παραμέτρους: ηλικία, φύλο, κάπνισμα, ΒΜΙ, ιστορικό υποθυρεοειδισμού αλλά και στη πλειονότητα των άλλων μετρήσεων. Παρατηρήθηκε ωστόσο μια διαφοροποίηση ως προς τα επίπεδα της LDL-C (με p <0.015) και της κεντρικής συστολικής πίεσης (με p <0.020) κατά την έναρξη της μελέτης, η οποία για την περίπτωση της LDL-C εξαλείφθηκε στους 6 μήνες ενώ για την περίπτωση της κεντρικής συστολικής πίεσης παρέμεινε σταθερή. Δεν διαπιστώθηκε, παρά την επιβεβαιωμένη επίτευξη του στόχου της LDL-C σε όλους τους ασθενείς, στατιστικώς σημαντική διαφοροποίηση σε κάποια από τις παραμέτρους της αρτηριακής σκληρίας, σε καμία από τις δύο ομάδες.Όπως ήταν αναμενόμενο, η μείωση της ολικής χοληστερόλης και της LDL-C, ήταν ιδιαίτερα εμφανείς και στις δύο ομάδες. Σε μικρότερο βαθμό και στις δύο ομάδες σημειώθηκε μείωση των τριγλυκεριδίων ενώ σχετικά με την HDL-C, οι τιμές αυξήθηκαν αλλά σε επίπεδα στατιστικώς μη σημαντικά. Επιπροσθέτως, στην ομάδα της ροσουβαστατίνης σημειώθηκε μείωση του ουρικού οξέος η οποία απουσίαζε στην ομάδα της σιμβαστατίνης. Είναι αξιοσημείωτο ότι οι δύο μέθοδοι, Mobil-O-Graph 24h PWA Monitor και Sphygmocor, εμφάνισαν ισχυρή συσχέτιση και στις δύο ομάδες (p<0.001) στις βασικές μετρήσεις για τη σκληριά που πραγματοποιήθηκαν στην επίσκεψη διαλογής: ταχύτητα σφυγμικού (PWV), κεντρικό αυξητικό δείκτη (Aix75), κεντρική συστολική, διαστολική πίεση και πίεση παλμού (cPP, cSBP και cDBP ). Ωστόσο , η συσχέτιση ήταν ασθενής δεδομένου ότι για όλες τις παραμέτρους της σκληρίας οι συντελεστές συσχέτισης ήταν χαμηλοί (R2 Linear <0.5).Συμπεράσματα: Σε ασθενείς χαμηλού καρδιαγγειακού κινδύνου με φυσιολογικές παραμέτρους αρτηριακής σκληρίας, η χορήγηση στατινών δεν ελαττώνει τη σκληρία και ως εκ τούτου θα πρέπει να πραγματοποιείται λόγω της υπολιπιδαιμικής δράσης τους και όχι για τα πλειοτροπικά χαρακτηριστικά τους τα οποία βέβαια, καλό είναι να λαμβάνονται υπόψη σε εξατομικευμένο επίπεδο.

Role of glycogen concentration and epinephrine on glucose uptake in rat epitrochlearis muscle

1997 ◽  
Vol 272 (4) ◽  
pp. E649-E655 ◽  
Author(s):  
J. Jensen ◽  
R. Aslesen ◽  
J. L. Ivy ◽  
O. Brors
Keyword(s):  
Glucose Uptake ◽  
Muscle Glycogen ◽  
Similar Treatment ◽  
Glycogen Concentration ◽  
Spearman's Rho ◽  
Spearman’S Rho ◽  
Tracer Amount ◽  
Muscle Glycogen Concentration ◽  
Basal Glucose Uptake

The effects of diet-manipulated variations in muscle glycogen concentration and epinephrine on glucose uptake were studied in epitrochlearis muscles from Wistar rats. Both basal and insulin-stimulated glucose uptake [measured with a tracer amount of 2-[1,2-3H(N)]deoxy-D-glucose] inversely correlated with initial glycogen concentration (glycogen concentration vs. basal glucose uptake: Spearman's rho = -0.76, n = 84, P < 0.000001; glycogen concentration vs. insulin-stimulated glucose uptake: Spearman's rho = -0.67, n = 44, P < 0.00001). Two fasting-refeeding procedures were used that resulted in differences in muscle glycogen concentrations, although with similar treatment for the last 48 h before the experiment. In the rats with the lower glycogen concentration, basal as well as insulin-stimulated glucose uptake was elevated. The muscle glycogen concentration had no effect on epinephrine-stimulated glycogenolysis. Epinephrine, however, was found to reduce basal glucose uptake in all groups. These results suggest that 1) the glycogen concentration participates in the regulation of both basal and insulin-stimulated glucose uptake in skeletal muscle, 2) the magnitude of epinephrine-stimulated glycogen breakdown is independent of the glycogen concentration, and 3) epinephrine inhibits basal glucose uptake at all glycogen concentrations.

scholarly journals Population Pharmacokinetic Analysis of Voriconazole and Anidulafungin in Adult Patients with Invasive Aspergillosis

2014 ◽  
Vol 58 (8) ◽  
pp. 4718-4726 ◽  
Author(s):  
Ping Liu ◽  
Diane R. Mould
Keyword(s):  
Invasive Aspergillosis ◽  
Area Under The Curve ◽  
Compartment Model ◽  
Population Pharmacokinetic Analysis ◽  
Institutional Review Boards ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Parameter Estimates ◽  
First Order ◽  
Two Compartment Model

ABSTRACTTo assess the pharmacokinetics (PK) of voriconazole and anidulafungin in patients with invasive aspergillosis (IA) in comparison with other populations, sparse PK data were obtained for 305 adults from a prospective phase 3 study comparing voriconazole and anidulafungin in combination versus voriconazole monotherapy (voriconazole, 6 mg/kg intravenously [IV] every 12 h [q12h] for 24 h followed by 4 mg/kg IV q12h, switched to 300 mg orally q12h as appropriate; with placebo or anidulafungin IV, a 200-mg loading dose followed by 100 mg q24h). Voriconazole PK was described by a two-compartment model with first-order absorption and mixed linear and time-dependent nonlinear (Michaelis-Menten) elimination; anidulafungin PK was described by a two-compartment model with first-order elimination. For voriconazole, the normal inverse Wishart prior approach was implemented to stabilize the model. Compared to previous models, no new covariates were identified for voriconazole or anidulafungin. PK parameter estimates of voriconazole and anidulafungin are in agreement with those reported previously except for voriconazole clearance (the nonlinear clearance component became minimal). At a 4-mg/kg IV dose, voriconazole exposure tended to increase slightly as age, weight, or body mass index increased, but the difference was not considered clinically relevant. Estimated voriconazole exposures in IA patients at 4 mg/kg IV were higher than those reported for healthy adults (e.g., the average area under the curve over a 12-hour dosing interval [AUC0–12] at steady state was 46% higher); while it is not definitive, age and concomitant medications may impact this difference. Estimated anidulafungin exposures in IA patients were comparable to those reported for the general patient population. This study was approved by the appropriate institutional review boards or ethics committees and registered on ClinicalTrials.gov (NCT00531479).

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