scholarly journals Prediction of Unbound Ceftriaxone Concentration in Children: Simple Bioanalysis Method and Basic Mathematical Equation

2020 ◽  
Vol 65 (1) ◽  
pp. e00779-20
Author(s):  
Min Kan ◽  
Hai-Yan Shi ◽  
Bing Han ◽  
Yue-E Wu ◽  
Qian Li ◽  
...  

ABSTRACTThe pharmacological activity of ceftriaxone depends on the unbound concentration. However, direct measurement of unbound concentrations is obstructive, and high individual variability of the unbound fraction of ceftriaxone was shown in children. We aim to evaluate and validate a method to predict unbound ceftriaxone concentrations in pediatric patients. Ninety-five pairs of concentrations (total and unbound) from 92 patients were measured by the bioanalysis method that we developed. The predictive performance of the three equations (empirical in vivo equation, disease-adapted equation, and multiple linear regression equation) was assessed by the mean absolute prediction error (MAPE), the mean prediction error (MPE), the proportions of the prediction error within ±30% (P30) and ±50% (P50), and linear regression of predicted versus actual unbound levels (R2). The average total and unbound ceftriaxone concentrations were 126.18 ± 81.46 μg/ml and 18.82 ± 21.75 μg/ml, and the unbound fraction varied greatly from 4.75% to 39.97%. The MPE, MAPE, P30, P50, and R2 of the empirical in vivo equation, disease equation, and multiple linear equation were 0.17 versus 0.00 versus 0.06, 0.24 versus 0.15 versus 0.27, 63.2% versus 89.5% versus 74.7%, 96.8% versus 97.9% versus 86.3%, and 0.8730 versus 0.9342 versus 0.9315, respectively. The disease-adapted equation showed the best predictive performance. We have developed and validated a bioanalysis method with one-step extraction pretreatment for the determination of total ceftriaxone concentrations, and a prediction equation of the unbound concentration is recommended. The proposed method can facilitate clinical practice and research on unbound ceftriaxone in children. (This study has been registered at ClinicalTrials.gov under identifier NCT03113344.)

1977 ◽  
Vol 232 (5) ◽  
pp. H537-H544
Author(s):  
H. V. Allen ◽  
M. F. Anderson ◽  
J. D. Meindl

A totally implantable pulsed Doppler ultrasonic blood flowmeter has recently been developed to provide information on the velocity-flow profile in a vessel as well as its diameter. Volume flow can be indirectly obtained according to the formula: Q = (phi/4)(diam)2-v. In order to determine the accuracy of this estimate, in vivo direct bleedout measurements were performed on the abdominal aorta of six dogs with an overall accuracy in 77 trials of +2.0 +/- 8.7% (mean +/- 1 SD). The best-fit mean linear regression line was found to be: flowmeter output = 1.013-true flow + 5.1 ml/min. The scatter in the flowmeter's accuracy is thought to be due to small variations in the angle of the transducer. The source of the 2% overestimation in the mean accuracy could not be directly attributed to any one condition; the error is sufficiently small that in many cases it can be neglected.


2019 ◽  
Vol 104 (6) ◽  
pp. e64.2-e64
Author(s):  
H-Y Shi ◽  
X Huang ◽  
Q Li ◽  
Wu Y-E ◽  
MW Khan ◽  
...  

BackgroundTo evaluate the predictive ability of the existing formula to measure free ceftriaxone levels in children, and optimize the formula by adding disease and maturation factors.MethodsFifty children receiving ceftriaxone were evaluated, and the predictive performance of the different equations were assessed by mean absolute error (MAE), mean prediction error (MPE) and linear regression of predicted vs. actual free levels.ResultsThe average free ceftriaxone concentration was 2.11 ± 9.51µg/ml. The predicted free concentration was 1.15 ± 4.39µg/ml with the in vivo binding equation, which increased to 1.58 ± 7.73µg/ml and 2.01 ± 9.53µg/ml when adjusted for age (disease adapted equation), and age and albumin (disease-maturation equation) respectively. The average MAE values were 0.48 (in vivo banding equation), 0.34 (disease adapted equation) and 0.41 (disease maturation equation). The average MPE values were -0.41 (in vivo binding equation), 0.14 (disease adapted equation) and 0.09 (disease maturation equation). The respective linear regression equations and coefficients were y=1.8647x+1.0731(R2=0.7398), y=1.1455x+0.8414(R2=0.8674), and y=0.9664x(R2=0.8641) for the in vivo binding, disease adapted and disease maturation equations respectively.ConclusionCompared to the in vivo binding equation, the disease adapted and disease maturation equations showed lower MAE and MPE values, and the latter showed the lowest MPE value. In addition, the slope of the disease maturation equation was closer to 1 compared to the other two. Therefore, the optimized disease maturation equation should be used to measure free ceftriaxone levels in children.Disclosure(s)Nothing to disclose.


2009 ◽  
Vol 47 (169) ◽  
Author(s):  
Parthasarathi Debray ◽  
B M Shreevatsa ◽  
R B MG ◽  
T K Sen ◽  
S Roy ◽  
...  

Peak expiratory fl ow rate (PEFR) measurement is the easiest and cheapest method to evaluaterespiratory functions. So, the study was carried out to evaluate PEFR of healthy Nepalese adults andcompare their values with healthy Indian counterparts to know whether Indian prediction equationsfor PEFR can be used for Nepalese adult population or not.One hundred twenty-three healthy, young, non smoker adult Indian (64: 28 Males, 36 Females) andNepalese (59: 32 Males, 27 Females) medical students of 18 to 20 years of age participated in the study.The mean PEFR of Indian (male: 490.4 liter/min, female: 386.0 liter/min) and Nepalese (male: 485.9liter/min, Female: 365.2 liter/min) young adults were found to have no signifi cant differences.As there is no signifi cant difference in the mean PEFR of Indian and Nepalese young adults, predictionequations made for Indian adults can be used to predict PEFR of Nepalese subjects. Therefore, anattempt has been made to formulate a regression equation from the combined Indian and Nepalesesubjects. A stepwise, multiple, linear, regression analysis was performed for this purpose. The analysisshowed that height is the best predictor for PEFR in the present study. The regression equation basedon height for the combined Indian and Nepalese young adults is calculated as: PEFR = 5.687 × Height(cm) – 495.787. However, a stepwise, multiple, linear, regression equation with residual analysisfor the best fi t model was performed to formulate prediction equation for PEFR and this showed achange of the earlier regression equation to PEFR = 5.930 × Height (cm) – 536.131.Keywords: Peak expiratory fl ow rate, peak fl ow meter, prediction equation, spirometry, youngadults


2021 ◽  
Vol 6 (1) ◽  
pp. e000900
Author(s):  
Ryo Asaoka ◽  
Akio Oishi ◽  
Yuri Fujino ◽  
Hiroshi Murata ◽  
Keiko Azuma ◽  
...  

PurposeTo evaluate the minimum number of visual fields (VFs) required to precisely predict future VFs in eyes with retinitis pigmentosa (RP).MethodsA series of 12 VFs (Humphrey Field Analyzer 10–2 test (8.9 years in average) were analysed from 102 eyes of 52 patients with RP. The absolute error to predict the 12th VF using the prior 11 VFs was calculated in a pointwise manner, using the linear regression, and the 95% CI range was determined. Then, using 3–10 initial VFs, next VFs (4th to 11th VFs, respectively) were also predicted. The minimum number of VFs required for the mean absolute prediction error to reach the 95% CI was identified. Similar analyses were iterated for the second and third next VF predictions. Similar analyses were conducted using mean deviation (MD).ResultsIn the pointwise analysis, the minimum number of VFs required to reach the 95% CI for the 12th VF was five (first and second next VF predictions) and six (third next VF prediction). For the MD analysis, three (first and second next VF predictions) and four (third next VF prediction) VFs were required to reach 95% CI for the 12th VF.ConclusionsThe minimum number of VFs required to obtain accurate predictions of the future VF was five or six in the pointwise analysis and three or four in the analysis with MD.


2009 ◽  
pp. 79-86 ◽  
Author(s):  
Dragan Palic ◽  
Klaas-Jan Leeuw

In this study, the organic matter digestibility (OMD) of six complete diets for ruminants has been determined in-vivo in trials with sheep and in-vitro using two-stage Tilley and Terry (T&T) method, gas production (GP) technique and multi-enzyme incubation (EDOM) procedures. The mean OMD values obtained in vivo and using T&T, GP and EDOM techniques were 684, 716, 685 and 710 g OM/kgDM respectively and did not differ significantly (P>0.05). The obtained in vitro results were regressed against determined in-vivo values to derive prediction equations. Using the T&T technique, the prediction equation OMD (in_vivo) = -17.36 + 0.98 x OMD (in_vitro_T&T), (R2 = 0.75; RMSE = 37.59) has been obtained. The equation OMD (in_vivo) = 198.98 + 0.71 x OMD (in_vitro_GP), (R2 = 0.21; RMSE = 66.36) has been derived for Gas production procedure, while the equation OMD (in_vivo) = 102 + 0.82 x OMD (in_vitro_EDOM), (R2 = 0.86; RMSE = 27.30) has been generated for multi-enzyme incubation technique. The results of this study showed that the OMD of complete diets for ruminants can be successfully determined, and in-vivo values predicted, using multi-enzyme incubation procedure, which is important because of the fact that rumen liquor, needed for the in-vitro twostage T&T and GP techniques is not always available to analytical laboratories.


1996 ◽  
Vol 76 (01) ◽  
pp. 111-117 ◽  
Author(s):  
Yasuto Sasaki ◽  
Junji Seki ◽  
John C Giddings ◽  
Junichiro Yamamoto

SummarySodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), are known to liberate nitric oxide (NO). In this study the effects of SNP and SIN-1 on thrombus formation in rat cerebral arterioles and venules in vivo were assessed using a helium-neon (He-Ne) laser. SNP infused at doses from 10 Μg/kg/h significantly inhibited thrombus formation in a dose dependent manner. This inhibition of thrombus formation was suppressed by methylene blue. SIN-1 at a dose of 100 Μg/kg/h also demonstrated a significant antithrombotic effect. Moreover, treatment with SNP increased vessel diameter in a dose dependent manner and enhanced the mean red cell velocity measured with a fiber-optic laser-Doppler anemometer microscope (FLDAM). Blood flow, calculated from the mean red cell velocity and vessel diameters was increased significantly during infusion. In contrast, mean wall shear rates in the arterioles and venules were not changed by SNP infusion. The results indicated that SNP and SIN-1 possessed potent antithrombotic activities, whilst SNP increased cerebral blood flow without changing wall shear rate. The findings suggest that the NO released by SNP and SIN-1 may be beneficial for the treatment and protection of cerebral infarction


1993 ◽  
Vol 70 (04) ◽  
pp. 676-680 ◽  
Author(s):  
H F Kotzé ◽  
V van Wyk ◽  
P N Badenhorst ◽  
A du P Heyns ◽  
J P Roodt ◽  
...  

SummaryPlatelets were isolated from blood of baboons and treated with neuraminidase to remove platelet membrane sialic acid, a process which artificially ages the platelets. The platelets were then labelled with 111In and their mean life span, in vivo distribution and sites of Sequestration were measured. The effect of removal of sialic acid on the attachment of immunoglobulin to platelets were investigated and related to the Sequestration of the platelets by the spleen, liver, and bone marrow. Removal of sialic acid by neuraminidase did not affect the aggregation of platelets by agonists in vitro, nor their sites of Sequestration. The removal of 0.51 (median, range 0.01 to 2.10) nmol sialic acid/108 platelets shortened their life span by 75 h (median, range 0 to 132) h (n = 19, p <0.001), and there was an exponential correlation between the shortening of the mean platelet life span and the amount of sialic acid removed. The increase in platelet-associated IgG was 0.112 (median, range 0.007 to 0.309) fg/platelet (n = 25, p <0.001) after 0.79 (median, range 0.00 to 6.70) nmol sialic acid/108 platelets was removed (p <0.001). There was an exponential correlation between the shortening of mean platelet life span after the removal of sialic acid and the increase in platelet-associated IgG. The results suggest that platelet membrane sialic acid influences ageing of circulating platelets, and that the loss of sialic acid may have exposed a senescent cell antigen that binds IgG on the platelet membrane. The antibody-antigen complex may then provide a signal to the macrophages that the platelet is old, and can be phagocytosed and destroyed.


2020 ◽  
pp. bjophthalmol-2020-316401
Author(s):  
Qian Yang ◽  
Xiaohong Zhou ◽  
Yingqin Ni ◽  
Haidong Shan ◽  
Wenjing Shi ◽  
...  

PurposesTo develop an optimised retinopathy of prematurity (ROP) screening guideline by adjusting the screening schedule and thresholds of gestational age (GA) and birth weight (BW).MethodsA multicentre retrospective cohort study was conducted based on data from four tertiary neonatal intensive care units in Shanghai, China. The medical records of enrolled infants, born from 2012 to 2016 who underwent ROP examinations, were collected and analysed. The incidence and risk factors for ROP were analysed in all infants. Postnatal age (PNA) and postmenstrual age (PMA) of infants, detected to diagnose ROP for the first time, were compared with the present examination schedule. The predictive performance of screening models was evaluated by internally validating sensitivity and specificity.ResultsOf the 5606 eligible infants, ROP was diagnosed in 892 (15.9%) infants; 63 (1.1%) of them received treatment. The mean GA of ROP patients was 29.4±2.4 weeks, and the mean BW was 1260±330 g. Greater prematurity was associated with an older PNA at which ROP developed. The minimum PMA and PNA at which diagnosis of treatable ROP occurred were 32.43 and 3 weeks, respectively. The optimised criteria (GA <32 weeks or BW <1600 g) correctly predicted 98.4% type 1 ROP infants, reducing the infants requiring examinations by 43.2% when internally validated.ConclusionsThe incidence of type 1 ROP and the mean GA and BW of ROP infants have decreased in China. The suggested screening threshold and schedule may be reliably used to guide the modification of ROP screening guideline and decrease medical costs.


Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Sheilla Achieng ◽  
John A Reynolds ◽  
Ian N Bruce ◽  
Marwan Bukhari

Abstract Background/Aims  We aimed to establish the validity of the SLE-key® rule-out test and analyse its utility in distinguishing systemic lupus erythematosus (SLE) from other autoimmune rheumatic connective tissue diseases. Methods  We used data from the Lupus Extended Autoimmune Phenotype (LEAP) study, which included a representative cross-sectional sample of patients with a variety of rheumatic connective tissue diseases, including SLE, mixed connective tissue disease (MCTD), inflammatory myositis, systemic sclerosis, primary Sjögren’s syndrome and undifferentiated connective tissue disease (UCTD). The modified 1997 ACR criteria were used to classify patients with SLE. Banked serum samples were sent to Immune-Array’s CLIA- certified laboratory Veracis (Richmond, VA) for testing. Patients were assigned test scores between 0 and 1 where a score of 0 was considered a negative rule-out test (i.e. SLE cannot be excluded) whilst a score of 1 was assigned for a positive rule-out test (i.e. SLE excluded). Performance measures were used to assess the test’s validity and measures of association determined using linear regression and Spearman’s correlation. Results  Our study included a total of 155 patients of whom 66 had SLE. The mean age in the SLE group was 44.2 years (SD 13.04). 146 patients (94.1%) were female. 84 (54.2%) patients from the entire cohort had ACR SLE scores of ≤ 3 whilst 71 (45.8%) had ACR SLE scores ≥ 4. The mean ACR SLE total score for the SLE patients was 4.85 (SD 1.67), ranging from 2 to 8, with mean disease duration of 12.9 years. The Sensitivity of the SLE-Key® Rule-Out test in diagnosing SLE from other connective tissue diseases was 54.5%, specificity was 44.9%, PPV 42.4% and NPV 57.1 %. 45% of the SLE patients had a positive rule-out test. SLE could not be ruled out in 73% of the MCTD patients whilst 51% of the UCTD patients had a positive Rule-Out test and &gt;85% of the inflammatory myositis patients had a negative rule-out test. ROC analysis generated an AUC of 0.525 illustrating weak class separation capacity. Linear regression established a negative correlation between the SLE-key Rule-Out score and ACR SLE total scores. Spearman’s correlation was run to determine the relationship between ACR SLE total scores and SLE-key rule-out score and showed very weak negative correlation (rs = -0.0815, n = 155, p = 0.313). Conclusion  Our findings demonstrate that when applied in clinical practice in a rheumatology CTD clinic setting, the SLE-key® rule-out test does not accurately distinguish SLE from other CTDs. The development of a robust test that could achieve this would be pivotal. It is however important to highlight that the test was designed to distinguish healthy subjects from SLE patients and not for the purpose of differentiating SLE from other connective tissue diseases. Disclosure  S. Achieng: None. J.A. Reynolds: None. I.N. Bruce: Other; I.N.B is a National Institute for Health Research (NIHR) Senior Investigator and is funded by the NIHR Manchester Biomedical Research Centre. M. Bukhari: None.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lena Dalal ◽  
Abdul Wahab Allaf ◽  
Hind El-Zein

AbstractSelf-nanoemulsifying drug delivery systems (SNEDDS) were used to enhance the dissolution rate of furosemide as a model for class IV drugs and the system was solidified into liquisolid tablets. SNEDDS of furosemide contained 10% Castor oil, 60% Cremophor EL, and 30% PEG 400. The mean droplets size was 17.9 ± 4.5 nm. The theoretical model was used to calculate the amounts of the carrier (Avicel PH101) and coating materials (Aerosil 200) to prepare liquisolid powder. Carrier/coating materials ratio of 5/1 was used and Ludipress was added to the solid system, thus tablets with hardness of 45 ± 2 N were obtained. Liquisolid tablets showed 2-folds increase in drug release as compared to the generic tablets after 60 min in HCl 0.1 N using USP apparatus-II. Furosemide loaded SNEDDS tablets have great prospects for further in vivo studies, and the theoretical model is useful for calculating the adequate amounts of adsorbents required to solidify these systems.


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