ORCID Profile
0000-0002-5299-8656
Current Organisation
University of Liverpool
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Springer Science and Business Media LLC
Date: 09-08-2019
Publisher: Elsevier BV
Date: 03-2009
Publisher: Springer Science and Business Media LLC
Date: 12-2017
Publisher: Elsevier BV
Date: 03-2019
Publisher: Oxford University Press (OUP)
Date: 10-01-2016
DOI: 10.1093/JAC/DKV451
Publisher: American Society for Microbiology
Date: 10-2017
DOI: 10.1128/AAC.00707-17
Abstract: The aim of this study was to develop a population pharmacokinetic (PK) model for teicoplanin across childhood age ranges to be used as Bayesian prior information in the software constructed for in idualized therapy. We developed a nonparametric population model fitted to PK data from neonates, infants, and older children. We then implemented this model in the BestDose multiple-model Bayesian adaptive control algorithm to show its clinical utility. It was used to predict the dosages required to achieve optimal teicoplanin predose targets (15 mg/liter) from day 3 of therapy. We performed in idual simulations for an infant and a child from the original population, who provided early first dosing interval concentration-time data. An allometric model that used weight as a measure of size and that also incorporated renal function using the estimated glomerular filtration rate (eGFR), or the ratio of postnatal age (PNA) to serum creatinine concentration (SCr) for infants months old, best described the data. The median population PK parameters were as follows: elimination rate constant (Ke) = 0.03 · (wt/70) −0.25 · Renal (h −1 ) V = 19.5 · (wt/70) (liters) Renal = eGFR 0.07 (ml/min/1.73 m 2 ), or Renal = PNA/SCr (μmol/liter). Increased teicoplanin dosages and alternative administration techniques (extended infusions and fractionated multiple dosing) were required in order to achieve the targets safely by day 3 in simulated cases. The software was able to predict in idual measured concentrations and the dosages and administration techniques required to achieve the desired target concentrations early in therapy. Prospective evaluation is now needed in order to ensure that this in idualized teicoplanin therapy approach is applicable in the clinical setting. (This study has been registered in the European Union Clinical Trials Register under EudraCT no. 2012-005738-12.)
Publisher: Oxford University Press (OUP)
Date: 19-08-2016
DOI: 10.1093/JAC/DKW295
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.EJOGRB.2019.08.007
Abstract: Severe early-onset fetal growth restriction (FGR) predisposes to fetal death, neonatal death, neonatal morbidity and neurodisability. The use of placental biomarkers has been proposed for risk stratification in pre-ecl sia, but they could be equally useful in fetal growth restriction in aiding management. To determine the efficacy of angiogenic biomarkers at predicting adverse pregnancy outcome in severe early-onset fetal growth restriction. This is a secondary analysis of the multicentre, placebo-controlled STRIDER UK randomised controlled trial of singleton pregnancies with severe early-onset fetal growth restriction. Women with FGR pregnancies between 22 A complete data set was available for 105 of 135 randomised women. Multivariate regression analysis identified estimated fetal weight (EFW) and sFlt-1:PlGF as independent predictors of livebirth (EFW OR: 1.01 (1.008, 1.021) p < 0.001 and lower sFlt-1:PlGF ratio OR: 0.53 (0.284, 0.994) p = 0.048) and overall survival (EFW OR: 1.01 (1.006, 1.015) p < 0.001 and lower sFlt-1/PlGF ratio OR: 0.51 (0.286, 0.904) p = 0.021). EFW was a consistent predictor for all outcomes other than gestation at delivery. sFlt-1:PlGF ratio was a consistent predictor for all outcomes other than neonatal morbidity. In severe early-onset FGR pregnancies livebirth and overall survival can be predicted using a model involving EFW and sFlt-1:PlGF ratio. This model require validation in a larger cohort but may allow informed decision making about pregnancy management, especially in previable cases.
Publisher: American Academy of Pediatrics (AAP)
Date: 06-2012
Publisher: Oxford University Press (OUP)
Date: 24-02-2005
DOI: 10.1111/J.1365-2249.2005.02743.X
Abstract: The increasing prevalence of atopic diseases over the last few decades is thought to be due to reduced exposure to environmental microbes that normally down-regulate allergic responses (hygiene hypothesis). We have shown previously that administration of the environmental microbe Mycobacterium vaccae ameliorates atopic dermatitis in school-age children at 3 months post-treatment. The present study tested the hypothesis that M. vaccae suppresses Th2-type cytokine activity and increases transforming growth factor (TGF)-β1 immunomodulatory activity in these children. Interleukin (IL)-4, IL-5, TGF-β1 and interferon (IFN)-γ activity were assessed in resting and stimulated peripheral blood mononuclear cells (PBMC) isolated from 12 of the children who received M. vaccae in our original clinical trial. A cDNA expression array was used to examine a broader range of cytokine pathway transcripts. There were no significant changes in either Th2-type or TGF-β1 activity. A 5- to 10-fold increase in Th1-type activity was found at 1 month post-M. vaccae administration (P & 0·05), but it had returned to baseline by 3 months. The results do not support the hypothesis that M. vaccae reduces Th2-type or increases TGF-β1 activity of PBMC isolated from children with atopic dermatitis. The transient surge in IFN-γ at 1 month is unlikely to explain any improvement in eczema score at 3 months.
Publisher: American Society for Microbiology
Date: 11-2014
DOI: 10.1128/AAC.03685-14
Abstract: Teicoplanin is frequently administered to treat Gram-positive infections in pediatric patients. However, not enough is known about the pharmacokinetics (PK) of teicoplanin in children to justify the optimal dosing regimen. The aim of this study was to determine the population PK of teicoplanin in children and evaluate the current dosage regimens. A PK hospital-based study was conducted. Current dosage recommendations were used for children up to 16 years of age. Thirty-nine children were recruited. Serum s les were collected at the first dose interval (1, 3, 6, and 24 h) and at steady state. A standard 2-compartment PK model was developed, followed by structural models that incorporated weight. Weight was allowed to affect clearance (CL) using linear and allometric scaling terms. The linear model best accounted for the observed data and was subsequently chosen for Monte Carlo simulations. The PK parameter medians/means (standard deviation [SD]) were as follows: CL, [0.019/0.023 (0.01)] × weight liters/h/kg of body weight volume, 2.282/4.138 liters (4.14 liters) first-order rate constant from the central to peripheral compartment ( K cp ), 0.474/3.876 h −1 (8.16 h −1 ) and first-order rate constant from peripheral to central compartment ( K pc ), 0.292/3.994 h −1 (8.93 h −1 ). The percentage of patients with a minimum concentration of drug in serum ( C min ) of mg/liter was 53.85%. The median/mean (SD) total population area under the concentration-time curve (AUC) was 619/527.05 mg · h/liter (166.03 mg · h/liter). Based on Monte Carlo simulations, only 30.04% (median AUC, 507.04 mg · h/liter), 44.88% (494.1 mg · h/liter), and 60.54% (452.03 mg · h/liter) of patients weighing 50, 25, and 10 kg, respectively, attained trough concentrations of mg/liter by day 4 of treatment. The teicoplanin population PK is highly variable in children, with a wider AUC distribution spread than for adults. Therapeutic drug monitoring should be a routine requirement to minimize suboptimal concentrations. IMPORTANCE (This trial has been registered in the European Clinical Trials Database Registry [EudraCT] under registration number 2012-005738-12.)
Publisher: Wiley
Date: 02-2020
DOI: 10.1002/UOG.20851
Abstract: Fetal growth restriction (FGR) is associated with maternal cardiovascular changes. Sildenafil, a phosphodiesterase type-5 inhibitor, potentiates the actions of nitric oxide, and it has been suggested that it alters maternal hemodynamics, potentially improving placental perfusion. Recently, the Dutch STRIDER trial was stopped prematurely owing to excess neonatal mortality secondary to pulmonary hypertension. The main aim of this study was to investigate the effect of sildenafil on maternal hemodynamics in pregnancies with severe early-onset FGR. This was a cardiovascular substudy within a UK multicenter, placebo-controlled trial, in which 135 women with a singleton pregnancy and severe early-onset FGR (defined as a combination of estimated fetal weight or abdominal circumference below the 10 Included were 134 women assigned randomly to sildenafil (n = 69) or placebo (n = 65) who had maternal BP and HR recorded at baseline. At 1-2 h post-randomization, compared with baseline values, sildenafil increased maternal HR by 4 bpm more than did placebo (mean difference, 5.00 bpm (95% CI, 1.00-12.00 bpm) vs 1.25 bpm (95% CI, -5.38 to 7.88 bpm) P = 0.004) and reduced systolic BP by 1 mmHg more (mean difference, -4.13 mmHg (95% CI, -9.94 to 1.44 mmHg) vs -2.75 mmHg (95% CI, -7.50 to 5.25 mmHg) P = 0.048). Even after adjusting for maternal mean arterial pressure, sildenafil reduced aortic PWV by 0.60 m/s more than did placebo (mean difference, -0.90 m/s (95% CI, -1.31 to -0.51 m/s) vs -0.26 m/s (95% CI, -0.75 to 0.59 m/s) P = 0.001). Sildenafil was associated with a non-significantly greater decrease in SV index after 1-2 h post-randomization than was placebo (mean difference, -5.50 mL/m Sildenafil in a dose of 25 mg three times daily increases HR, reduces BP and reduces arterial stiffness in pregnancies complicated by severe early-onset FGR. These changes are short term, modest and consistent with the anticipated vasodilatory effect. They have no short- or long-term clinical impact on the mother. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Publisher: Elsevier BV
Date: 02-2018
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Mark Turner.