Publications by authors named "C Omar Farouk Kamlin"

96 Publications

Comparison of the Pharmacokinetic Profiles of Trientine Tetrahydrochloride and Trientine Dihydrochloride in Healthy Subjects.

Eur J Drug Metab Pharmacokinet 2021 Sep 6;46(5):665-675. Epub 2021 Aug 6.

Orphalan, 226 Boulevard Voltaire, 75011, Paris, France.

Background And Objective: Wilson disease (WD) is an autosomal recessive inherited disorder of copper metabolism. Chelation of excessive copper is recommended but data on the pharmacokinetics of trientine are limited. The aim of this study was to compare the pharmacokinetics of a new trientine tetrahydrochloride formulation (TETA 4HCl) with those of an established trientine dihydrochloride (TETA 2HCl) salt.

Methods: A randomised single-centre crossover study to evaluate the pharmacokinetics, safety and tolerability of two different oral formulations of trientine (TETA 4HCl tablets vs TETA 2HCl capsules) in 23 healthy adult subjects receiving a single dose equivalent to 600 mg of trientine base was performed.

Results: Following oral administration, the median time to reach maximum plasma concentration (T) was 2.00 h (TETA 4HCl) and 3.00 h (TETA 2HCl). The rate (maximum plasma concentration [C]) and extent (area under the plasma concentration-time curve from time zero to infinity [AUC]) of absorption of the active moiety, trientine, were greater (by approximately 68% and 56%, respectively) for TETA 4HCl than for the TETA 2HCl formulation. The two formulations presented a similar terminal elimination rate (λ) and a similar terminal half-life (t) for trientine. Differences between TETA 4HCl and TETA 2HCl in the levels of the two main mono- and diacetylated metabolites were less than seen for trientine. For both tested formulations, healthy male volunteers demonstrated higher trientine plasma levels but lower mono- and diacetylated metabolite levels compared with females, with no sex differences in terminal half-life (t) observed. Single oral doses of both formulations were safe and well tolerated.

Conclusions: Compared with an identical dose of a TETA 2HCl formulation, the TETA 4HCl formulation provided more rapid absorption of trientine and greater systemic exposure in healthy subjects. Clinical Trials Number EudraCT # 2015-002199-25.
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http://dx.doi.org/10.1007/s13318-021-00704-1DOI Listing
September 2021

A multi-centre randomised controlled trial of respiratory function monitoring during stabilisation of very preterm infants at birth.

Resuscitation 2021 Jul 22. Epub 2021 Jul 22.

Division of Neonatology, Department of Paediatrics, Leiden University Medical Centre, Leiden, the Netherlands. Electronic address:

Aim: To determine whether the use of a respiratory function monitor (RFM) during PPV of extremely preterm infants at birth, compared with no RFM, leads to an increase in percentage of inflations with an expiratory tidal volume (Vte) within a predefined target range.

Methods: Unmasked, randomised clinical trial conducted October 2013 - May 2019 in 7 neonatal intensive care units in 6 countries. Very preterm infants (24-27 weeks of gestation) receiving PPV at birth were randomised to have a RFM screen visible or not. The primary outcome was the median proportion of inflations during manual PPV (face mask or intubated) within the target range (Vte 4-8 mL/kg). There were 42 other prespecified monitor measurements and clinical outcomes.

Results: Among 288 infants randomised (median (IQR) gestational age 26 (25-27) weeks), a total number of 51,352 inflations were analysed. The median (IQR) percentage of inflations within the target range in the RFM visible group was 30.0 (18.0-42.2)% vs 30.2 (14.8-43.1)% in the RFM non-visible group (p = 0.721). There were no differences in other respiratory function measurements, oxygen saturation, heart rate or FiO. There were no differences in clinical outcomes, except for the incidence of intraventricular haemorrhage (all grades) and/or cystic periventricular leukomalacia (visible RFM: 26.7% vs non-visible RFM: 39.0%; RR 0.71 (0.68-0.97); p = 0.028).

Conclusion: In very preterm infants receiving PPV at birth, the use of a RFM, compared to no RFM as guidance for tidal volume delivery, did not increase the percentage of inflations in a predefined target range.

Trial Registration: Dutch Trial Register NTR4104, clinicaltrials.gov NCT03256578.
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http://dx.doi.org/10.1016/j.resuscitation.2021.07.012DOI Listing
July 2021

Extubation generates lung volume inhomogeneity in preterm infants.

Arch Dis Child Fetal Neonatal Ed 2021 Jun 23. Epub 2021 Jun 23.

Newborn Research, The Royal Women's Hospital, Parkville, Victoria, Australia.

Objective: To evaluate the feasibility of electrical impedance tomography (EIT) to describe the regional tidal ventilation (V) and change in end-expiratory lung volume (EELV) patterns in preterm infants during the process of extubation from invasive to non-invasive respiratory support.

Design: Prospective observational study.

Setting: Single-centre tertiary neonatal intensive care unit.

Patients: Preterm infants born <32 weeks' gestation who were being extubated to nasal continuous positive airway pressure as per clinician discretion.

Interventions: EIT measurements were taken in supine infants during elective extubation from synchronised positive pressure ventilation (SIPPV) before extubation, during and then at 2 and 20 min after commencing nasal continuous positive applied pressure (nCPAP). Extubation and pressure settings were determined by clinicians.

Main Outcome Measures: Global and regional ΔEELV and ΔV, heart rate, respiratory rate and oxygen saturation were measured throughout.

Results: Thirty infants of median (range) 2 (1, 21) days were extubated to a median (range) CPAP 7 (6, 8) cm HO. SpO/FiO ratio was a mean (95% CI) 50 (35, 65) lower 20 min after nCPAP compared with SIPPV. EELV was lower at all points after extubation compared with SIPPV, and EELV loss was primarily in the ventral lung (p=0.04). V was increased immediately after extubation, especially in the central and ventral regions of the lung, but the application of nCPAP returned V to pre-extubation patterns.

Conclusions: EIT was able to describe the complex lung conditions occurring during extubation to nCPAP, specifically lung volume loss and greater use of the dorsal lung. EIT may have a role in guiding peri-extubation respiratory support.
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http://dx.doi.org/10.1136/archdischild-2021-321788DOI Listing
June 2021

The addition of fetal scalp blood lactate measurement as an adjunct to cardiotocography to reduce caesarean sections during labour: The Flamingo randomised controlled trial.

Aust N Z J Obstet Gynaecol 2021 Mar 23. Epub 2021 Mar 23.

Department of Maternal-Fetal Medicine, Pregnancy Research Centre, Royal Women's Hospital, Melbourne, Victoria, Australia.

Background: Fetal scalp blood sampling for lactate measurement (FBSLM) is sometimes used to assist in identification of the need for expedited birth in the presence of an abnormal cardiotocograph (CTG). However, there is no randomised controlled trial evidence to support this.

Aim: To determine whether adding FBSLM reduces the risk of birth by emergency caesarean section in labours complicated by an abnormal CTG, compared with CTG without FBS.

Material And Methods: Labouring women at a tertiary maternity hospital in Melbourne, Australia with a singleton, cephalic presentation, at ≥37 weeks gestation with an abnormal CTG pattern were randomised to the intervention (n = 61), with intermittent FBSLM in addition to CTG monitoring, or control (CTG without FBS, n = 62). The primary outcome was rate of birth by caesarean section. Secondary outcomes included overall operative birth and fetal and neonatal safety endpoints.

Trial Registration: ACTRN12611000172909.

Results: The smaller than anticipated sample was unable to demonstrate an effect from adding FBSLM to CTG monitoring on birth by caesarean section vs monitoring by CTG without FBS (25/61 and 28/62 respectively, P = 0.64, risk ratio 0.91, 95% confidence intervals 0.60-1.36). One newborn infant in the CTG group met the criteria for the composite neonatal outcome of death or serious outcome, neonatal encephalopathy, five-minute Apgar score < 4, neonatal resuscitation, admission to neonatal intensive care unit for 96 h or more.

Conclusion: We were unable to provide robust evidence of the effectiveness of FBSLM to improve the specificity of the CTG in the assessment of fetal wellbeing.
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http://dx.doi.org/10.1111/ajo.13327DOI Listing
March 2021

Lung ultrasound during newborn resuscitation predicts the need for surfactant therapy in very- and extremely preterm infants.

Resuscitation 2021 05 3;162:227-235. Epub 2021 Feb 3.

The Ritchie Centre, Hudson Institute of Medical Research, 27-31 Wright St, Clayton, VIC 3168, Australia; Monash Newborn, Monash Children's Hospital, 246 Clayton Rd, Clayton, VIC 3168, Australia.

Introduction: Early identification of infants requiring surfactant therapy improves outcomes. We evaluated the accuracy of delivery room lung ultrasound (LUS) to predict surfactant therapy in very- and extremely preterm infants.

Methods: Infants born at <32 weeks were prospectively enrolled at 2 centres. LUS videos of both sides of the chest were obtained 5-10 min, 11-20 min, and 1-3 h after birth. Clinicians were masked to the results of the LUS assessment and surfactant therapy was provided according to local guidelines. LUS videos were graded blinded to clinical data. Presence of unilateral type 1 ('whiteout') LUS or worse was considered test positive. Receiver Operating Characteristic (ROC) analysis compared the accuracy of LUS and an FiO threshold of 0.3 to predict subsequent surfactant therapy.

Results: Fifty-two infants with a median age of 27 weeks (IQR 26-28) were studied. Thirty infants (58%) received surfactant. Area under the ROC curve (AUC) for LUS at 5-10 min, 11-20 min and 1-3 h was 0.78 (95% CI, 0.66-0.90), 0.76 (95% CI, 0.65-0.88) and 0.86 (95% CI, 0.75-0.97) respectively, outperforming FiO at the 5-10 min timepoint (AUC 0.45, 95% CI 0.29-0.62, p = 0.001). At 11-20 min, LUS had a specificity of 95% (95% CI 77-100%) and sensitivity of 59% (95% CI, 39-77%) to predict surfactant therapy. All infants born at 23-27 weeks with LUS test positive received surfactant. Twenty-six infants (50%) had worsening of LUS grades on serial assessment.

Conclusions: LUS in the delivery room and accurately predicts surfactant therapy in infants <32 weeks.
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http://dx.doi.org/10.1016/j.resuscitation.2021.01.025DOI Listing
May 2021
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