dose optimisation
Recently Published Documents


TOTAL DOCUMENTS

165
(FIVE YEARS 47)

H-INDEX

18
(FIVE YEARS 5)

2021 ◽  
Vol 186 (2) ◽  
pp. 225-240
Author(s):  
Mazlum AYHAN ◽  
Ferhat KIZILGEÇİ ◽  
Muhammad Aamir IQBAL

Climate change, global warming, environmental pollution, greenhouse gas emissions from agricultural fields, stagnant wheat yields and reduced farm economic returns require optimisation of sources and doses of plant nutrients. A field study was conducted to evaluate wheat response to different forms of fertilisers and nitrogen (N) doses under Mediterranean conditions. The field trial was comprised of fertiliser sources, including chemical fertilisers, compost and leonardite, while different nitrogen levels (0, 80, 160, 240 kg ha-1) were also tested. The experimental variables included yield attributes (height of the, length of the spike, spikelets number per spike, thousand-grain weight and grain yield). In addition, nutritional quality attributes like protein and starch contents were studied along with NDVI values of wheat under different fertilisation regimes. The trial was executed using a randomised complete block (factorial) design using four replications. The results revealed that fertiliser forms and N doses remained ineffective for boosting yield attributes of wheat. For nutritional characteristics of wheat grains, a higher N dose remained instrumental in boosting protein, starch and wet gluten contents. Thus, 240 kg ha-1 of N dose might be recommended for general adoption under Mediterranean conditions; however, study findings are limited in scope and further in-depth studies are needed by testing organic manures from plant and animal origins.


2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Aaron J. Heffernan ◽  
Jason A. Roberts
Keyword(s):  

2021 ◽  
Author(s):  
Amanda Pelegrin Candemil ◽  
Benjamin Salmon ◽  
Karla F Vasconcelos ◽  
Anne C Oenning ◽  
Reinhilde Jacobs ◽  
...  

Abstract Dose optimisation has been revisited in the literature due to the high frequency of cone-beam CT (CBCT) scans and, the reduction of the field-of-view (FOV) size has shown to be an effective strategy. However, small FOV scans have negative influences of the truncation effect from the exomass.The aim of this study was to evaluate the diagnostic accuracy of an optimised CBCT protocol for the detection of simulated vertical root fracture (VRF) in the presence of metallic artefacts from the exomass and/or endomass.Twenty teeth were endodontically instrumented and VRF was induced in half of them. All teeth were individually placed in a human mandible, metallic materials were placed in the exomass and/or endomass, and CBCT scans were obtained at two dose protocols: standard and optimised. Three radiologists evaluated the images and indicated the presence of VRF using a 5-point scale. Sensitivity, specificity and area under the ROC curve (AUC) were obtained and compared using ANOVA (α=0.05). Overall, sensitivity, specificity and AUC did not differ significantly (p>0.05) between the dose protocols.In conclusion, optimised protocols should be considered in the detection of simulated VRF irrespective of the occurrence of artefacts from metallic materials in the exomass and/or endomass.


2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S481-S483
Author(s):  
W Kantasiripitak ◽  
R Mathôt ◽  
B Oldenburg ◽  
A Buisson ◽  
M Ferrante ◽  
...  

Abstract Background The endoscopic healing index (EHI) is a novel multi-protein serum biomarker test developed and validated to assess endoscopic disease activity in patients with Crohn’s disease (CD). Evidence for the use of EHI to guide decision-making during infliximab (IFX) treatment remains scarce. Therefore, we aimed to characterise the relationships between IFX dose, serum IFX concentrations, EHI, and endoscopic remission (ER). Methods Data were obtained from 118 biologic naïve adult patients with CD enrolled in the phase 4 TAILORIX trial (EudraCT 2011 003038 14). All patients had confirmed active CD at baseline based on clinical, biological, and endoscopic criteria. IFX and EHI (scores ranging from 0–100) were measured using a homogenous mobility shift assay (HMSA) and immunoassay, respectively (Prometheus Laboratories). First, the previously published population pharmacokinetic (popPK) model of the TAILORIX study population was revisited to describe the HMSA data. The effect of EHI, faecal calprotectin (FC), C-reactive protein (CRP), and serum albumin (ALB) on IFX clearance was evaluated. Next, a minimal continuous-time Markov model was developed to describe the time course of EHI within patients. EHI was considered as a three-stage ordinal variable (scores 0–19, 20–49, and 50–100) with the lowest score stage (0–19) indicative of ER. The course-modifying effect of IFX on EHI was assessed. Finally, a generalised linear model was used to describe the relationship between EHI and the probability of attaining ER (Simple Endoscopic Score for CD [SES-CD] ≤2). The predictive ability of EHI for ER was compared with that of FC, CRP, ALB, and IFX using a receiver operating characteristic (ROC) curve analysis. Results The revisited two-compartment popPK model described the IFX data with adequate descriptive and predictive accuracies. EHI, FC, CRP, and ALB at week (w)0 were not found to explain interpatient variability in IFX clearance. In contrast, higher IFX at w14 was associated with a higher probability of achieving EHI <20 at w14 (Figure 1). The probability of attaining EHI <20 at w14 was predicted to increase more than four-fold when IFX at w14 was targeted at 10 mg/L instead of 5 mg/L (Table 1). EHI and FC equally well predicted the probability of attaining ER at the same time point (Figure 2, Table 2). Conclusion EHI, FC, ALB, and CRP at w0 should not be considered for a priori IFX dose optimisation. Nevertheless, a posteriori IFX dose optimisation (based on IFX concentrations measurements) towards a predefined IFX concentration at w14 may lead to lower post-induction EHI scores and thus improved ER rates. An IFX target of 10 mg/L at w14 is associated with four-fold higher normalisation of EHI as compared to the commonly used target of 5 mg/L.


2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S335-S336
Author(s):  
Z Wang ◽  
B Verstockt ◽  
S Vermeire ◽  
J Sabino ◽  
M Ferrante ◽  
...  

Abstract Background In the UNITI endoscopy sub-study, only 17.4% of patients with Crohn’s disease (CD) on ustekinumab achieved endoscopic response and 10.9% achieved endoscopic remission at week (w)44. We aimed to investigate if improved endoscopic outcomes can be achieved through dose optimisation based on a population pharmacokinetic-pharmacodynamic (popPK-PD) modelling and simulation analysis. Methods Real-world data were obtained from 83 patients with moderate-to-severe CD (94% multi-refractory) enrolled in a prospective cohort study receiving ustekinumab 6 mg/kg induction and every eight-week (q8w) 90 mg maintenance therapy. Ustekinumab serum concentrations were measured at mid-dose (w4) and trough (w8, w16, w24). Faecal calprotectin (fCal) was measured at baseline and at w4, w8, w16, w24. Endoscopic response (≥50% decrease in simple endoscopic score for CD [SES-CD]) and endoscopic remission (SES-CD ≤2) were assessed at w24. Modelling and simulation were performed using NONMEM 7.4. Results Three sequential models were developed: a two-compartment popPK model linking ustekinumab dose to ustekinumab exposure, an indirect response popPK-PD model describing the effect of ustekinumab exposure on fCal, and a logistic regression popPD model linking fCal at w8 to endoscopic outcomes at w24 (Figure 1). Ustekinumab clearance increased with decreasing serum albumin and increasing bodyweight. The terminal half-life of ustekinumab in a median patient (bodyweight 65 kg, serum albumin 42.7 g/L) was 20.4 days. fCal decreased with increasing ustekinumab exposure. The probability of endoscopic response at w24 increased from 10.0% to 17.9% with fCal at w8 decreasing from 1,800 μg/g to 694 μg/g (Figure 2a) The probability of endoscopic remission at w24 increased from 2.1% to 10.0% with fCal at w8 decreasing from 1,800 μg/g to 214 μg/g (Figure 2b).The results from the simulation-based comparison of q8w and q4w maintenance dosing are shown in Table 1. Dose doubling (180 mg q8w), as opposed to interval halving (90 mg q4w), was predicted to result in a ustekinumab trough concentration of 2.4 μg/mL instead of 4.8 μg/mL. Conclusion The developed model can guide clinical trial design and support model-informed dose optimisation to improve endoscopic outcome rates. Although our analyses showed that q4w dosing resulted in higher ustekinumab and lower fCal concentrations, the proportion of patients achieving endoscopic remission was limited.


Sign in / Sign up

Export Citation Format

Share Document