Publications by authors named "Allan Xu"

17 Publications

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Medical training in acute specialties: the acute care common stem training pathway.

Br J Hosp Med (Lond) 2021 Feb 3;82(2):1-5. Epub 2021 Feb 3.

Department of Intensive Care Medicine, National Hospital for Neurology and Neurosurgery, London, UK.

In 2007, the acute care common stem pathway changed the delivery of acute specialty training. Acute care common stem is the core training programme for all emergency medicine trainees, 46% of anaesthetic trainees and a cohort of acute medicine trainees with more than 630 places nationally, the third highest of any core training programme. In their first 2 years of core training (CT1-2), trainees rotate through 6-month rotations in emergency medicine, acute medicine, anaesthetics and intensive care to gain core competencies in the assessment and management of acutely unwell patients, before completing 1 year (CT3) in their parent specialty. Acute care common stem trainees benefit from undertaking rotations in allied acute specialties, which is invaluable when treating complex and comorbid patients in an ageing population. Acute care common stem gives trainees core skills in management of acutely unwell patients, which can be built upon in higher specialty training.
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http://dx.doi.org/10.12968/hmed.2020.0634DOI Listing
February 2021

Use of a proforma to improve documentation of the post-take ward round and encourage initiation of the comprehensive geriatric assessment in the care of the older people's service.

Br J Hosp Med (Lond) 2021 Jan 28;82(1):1-6. Epub 2021 Jan 28.

Care of the Older People's Service, Royal London Hospital, Bart's Health NHS Trust, London, UK.

Aims/background: The post-take ward round is often the first time that a senior clinician reviews a patient on the acute medical take. Despite this, there is no official guidance regarding structure or documentation of the post-take ward round. The aim of this quality improve project was to develop a ward round proforma specifically tailored to the care of the older people's service to improve quality of documentation and to encourage initiation of the comprehensive geriatric assessment.

Methods: An initial audit was carried out assessing the documentation of key information and the initiation of the comprehensive geriatric assessment during the post-take ward round. A proforma was subsequently designed and implemented with the aims of improving the quality of documentation and increasing the number of patients for whom the comprehensive geriatric assessment was started. A repeat audit was conducted to assess the effectiveness of the proforma.

Results: The results demonstrated an improvement in documentation of all key information criteria and an increase in the initiation of the comprehensive geriatric assessment.

Conclusions: Use of a specifically tailored post-take ward round proforma improves the quality and consistency of documentation and encourages the initiation of the comprehensive geriatric assessment.
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http://dx.doi.org/10.12968/hmed.2020.0604DOI Listing
January 2021

Intravenous Compatibility of Ceftazidime-Avibactam and Aztreonam Using Simulated and Actual Y-site Administration.

Clin Ther 2020 08 16;42(8):1580-1586.e2. Epub 2020 Jul 16.

Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, Albany, NY, USA.

Purpose: The objective of this communication was to determine the intravenous compatibility of ceftazidime/avibactam and aztreonam using simulated and actual Y-site administration.

Methods: Ceftazidime-avibactam was reconstituted and diluted to concentrations of 8, 25, and 50 mg/mL in 0.9% sodium chloride. Aztreonam was reconstituted and diluted to concentrations of 10 and 20 mg/mL. Each combination of concentrations was tested for compatibility using visual, Tyndall beam, microscopy, turbidity, and pH assessments. Microscopy results were compared to those from sodium chloride 0.9% in water, pH was compared to that at time 0, and turbidity of combinations was compared to that of individual agents. Actual Y-site mixing was conducted over 2-h infusions with samples collected at 0, 1, and 2 h. Test results were evaluated at 0, 1, 2, 4, 8, and 12 h after mixing. All experiments were completed in triplicate.

Findings: Across simulated and actual Y-site experiments, no evidence of incompatibility between combinations of ceftazidime-avibactam + aztreonam was observed. Visual and microscopic tests revealed no particulate matter, color changes, or turbidity. Tyndall beam tests were negative with all combinations. No evidence of incompatibility was observed in turbidity testing. The pH values were consistent across each of the 6 combinations, from immediately after mixing until 12 h after mixing. When the addition of agents was reversed in simulated Y-site experiments, no differences in compatibility were observed. No differences in compatibility between actual and simulated Y-site administration were observed, and there was minimal variability across all replicate experiments.

Implications: Ceftazidime-avibactam, at concentrations of 8, 25, and 50 mg/mL, appeared compatible with aztreonam at concentrations of 10 and 20 mg/mL.
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http://dx.doi.org/10.1016/j.clinthera.2020.06.005DOI Listing
August 2020

Single-Center Investigation of the Pharmacokinetics of WCK 4282 (Cefepime-Tazobactam Combination) in Renal Impairment.

Antimicrob Agents Chemother 2019 10 23;63(10). Epub 2019 Sep 23.

Wockhardt Limited, Mumbai, India.

WCK 4282 is a combination product of cefepime (FEP) and tazobactam (TAZ) in a 1:1 ratio currently under development for the treatment of multidrug-resistant Gram-negative bacterial infections. We investigated the effect of renal impairment on the pharmacokinetics (PK) and safety of WCK 4282 in 48 subjects with various degrees of renal function. Subjects were categorized on the basis of their Cockcroft-Gault equation-estimated creatinine clearance (CL). We enrolled 6 subjects each into those with mild (CL, 60 to <90 ml/min), moderate (CL, 30 to <60 ml/min), or severe (CL, <30 ml/min) renal impairment and those with end-stage renal disease (ESRD) requiring hemodialysis and 24 healthy control subjects (CL, ≥90 ml/min). Healthy subjects and subjects with mild and moderate renal impairment received a single 90-min infusion of 4 g of WCK 4282 (2 g FEP and 2 g TAZ). Subjects with severe renal impairment and ESRD received 2 g of WCK 4282 (1 g FEP and 1 g TAZ) over 90 min. The plasma exposure of FEP-TAZ increased as renal function decreased. In subjects with mild, moderate, and severe renal impairment and ESRD, the mean exposure (area under the plasma concentration versus time curve from time zero extrapolated to infinity) of FEP and TAZ increased by 1.3- and 1.2-fold, 2.3- and 2.3-fold, 4.7- and 4.0-fold, and 8.5- and 11.6-fold, respectively. The urinary recovery of FEP and TAZ decreased with increasing renal impairment. There were no adverse events reported during the study. The findings suggest that dose adjustments for WCK 4282 will be required according to the degree of renal impairment. A single infusion of WCK 4282 was found to be safe and well tolerated in subjects with normal and impaired renal function. (This study has been registered at ClinicalTrials.gov under identifier NCT02709382.).
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http://dx.doi.org/10.1128/AAC.00873-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761517PMC
October 2019

12th GCC Closed Forum: critical reagents; oligonucleotides; CoA; method transfer; HRMS; flow cytometry; regulatory findings; stability and immunogenicity.

Bioanalysis 2019 Jun 19;11(12):1129-1138. Epub 2019 Jul 19.

WuXi Apptec, Plainsboro, NJ 08536, USA.

The 12th GCC Closed Forum was held in Philadelphia, PA, USA, on 9 April 2018. Representatives from international bioanalytical Contract Research Organizations were in attendance in order to discuss scientific and regulatory issues specific to bioanalysis. The issues discussed at the meeting included: critical reagents; oligonucleotides; certificates of analysis; method transfer; high resolution mass spectrometry; flow cytometry; recent regulatory findings and case studies involving stability and nonclinical immunogenicity. Conclusions and consensus from discussions of these topics are included in this article.
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http://dx.doi.org/10.4155/bio-2019-0131DOI Listing
June 2019

Recommendations for classification of commercial LBA kits for biomarkers in drug development from the GCC for bioanalysis.

Bioanalysis 2019 Apr 17;11(7):645-653. Epub 2019 Apr 17.

WuXi Apptec, Plainsboro, NJ, USA.

Over the last decade, the use of biomarker data has become integral to drug development. Biomarkers are not only utilized for internal decision-making by sponsors; they are increasingly utilized to make critical decisions for drug safety and efficacy. As the regulatory agencies are routinely making decisions based on biomarker data, there has been significant scrutiny on the validation of biomarker methods. Contract research organizations regularly use commercially available immunoassay kits to validate biomarker methods. However, adaptation of such kits in a regulated environment presents significant challenges and was one of the key topics discussed during the 12th Global Contract Research Organization Council for Bioanalysis (GCC) meeting. This White Paper reports the GCC members' opinion on the challenges facing the industry and the GCC recommendations on the classification of commercial kits that can be a win-win for commercial kit vendors and end users.
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http://dx.doi.org/10.4155/bio-2019-0072DOI Listing
April 2019

Single-Center Evaluation of the Pharmacokinetics of WCK 5222 (Cefepime-Zidebactam Combination) in Subjects with Renal Impairment.

Antimicrob Agents Chemother 2019 01 21;63(1). Epub 2018 Dec 21.

Wockhardt Limited, Mumbai, India.

WCK 5222 is a novel β-lactam-β-lactam-enhancer combination of cefepime (FEP) and zidebactam (ZID). ZID is a novel β-lactam enhancer with a dual action of binding to Gram-negative penicillin-binding protein 2 (PBP2) and β-lactamase inhibition. WCK 5222 is being developed as a new therapeutic option for the treatment of complicated multidrug-resistant Gram-negative pathogen infections. We investigated the effect of renal impairment on the pharmacokinetics (PK) and safety of WCK 5222 in 48 subjects based on Cockcroft-Gault-estimated creatinine clearance (CL). We enrolled mild ( = 6; CL, 60 to <90 ml/min), moderate ( = 6; CL, 30 to <60 ml/min), and severe ( = 6; CL, <30 ml/min; not on dialysis) impairment, end-stage renal disease (ESRD) on hemodialysis (HD) ( = 6), and matched normal controls ( = 24; CL, ≥90 ml/min). Healthy control subjects and mild and moderate renal impairment subjects received a single 60-min intravenous (i.v.) infusion of 3 g WCK 5222 (2 g FEP/1 g ZID); severe renal impairment and HD subjects received a single 60-min i.v. infusion of 1.5 g WCK 5222 (1 g FEP plus 0.5 g ZID). Body and renal clearance decreased, and plasma half-life () and the area under the concentration-time curve from time zero extrapolated to infinity (AUC [h µg/ml]) increased in a graded relationship with severity of renal impairment for both FEP and ZID. Our findings suggest that dose adjustments for WCK 5222 will be required according to the degree of renal impairment. Overall, WCK 5222 (FEP-ZID) was found to be safe and well tolerated in subjects with normal and impaired renal function. (This study has been registered at ClinicalTrials.gov under identifier NCT02942810.).
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http://dx.doi.org/10.1128/AAC.01484-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325229PMC
January 2019

11th GCC Closed Forum: cumulative stability; matrix stability; immunogenicity assays; laboratory manuals; biosimilars; chiral methods; hybrid LBA/LCMS assays; fit-for-purpose validation; China Food and Drug Administration bioanalytical method validation.

Bioanalysis 2018 Apr 27;10(7):433-444. Epub 2018 Apr 27.

Worldwide Clinical Trials, Austin, TX, USA.

The 11th Global CRO Council Closed Forum was held in Universal City, CA, USA on 3 April 2017. Representatives from international CRO members offering bioanalytical services were in attendance in order to discuss scientific and regulatory issues specific to bioanalysis. The second CRO-Pharma Scientific Interchange Meeting was held on 7 April 2017, which included Pharma representatives' sharing perspectives on the topics discussed earlier in the week with the CRO members. The issues discussed at the meetings included cumulative stability evaluations, matrix stability evaluations, the 2016 US FDA Immunogenicity Guidance and recent and unexpected FDA Form 483s on immunogenicity assays, the bioanalytical laboratory's role in writing PK sample collection instructions, biosimilars, CRO perspectives on the use of chiral versus achiral methods, hybrid LBA/LCMS assays, applications of fit-for-purpose validation and, at the Global CRO Council Closed Forum only, the status and trend of current regulated bioanalytical practice in China under CFDA's new BMV policy. Conclusions from discussions of these topics at both meetings are included in this report.
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http://dx.doi.org/10.4155/bio-2018-0014DOI Listing
April 2018

9th GCC closed forum: CAPA in regulated bioanalysis; method robustness, biosimilars, preclinical method validation, endogenous biomarkers, whole blood stability, regulatory audit experiences and electronic laboratory notebooks.

Bioanalysis 2016 Mar 26;8(6):487-95. Epub 2016 Feb 26.

WuXi/XBL, 107 Morgan Lane, Plainsboro, NJ, USA.

The 9th GCCClosed Forum was held just prior to the 2015 Workshop on Recent Issues in Bioanalysis (WRIB) in Miami, FL, USA on 13 April 2015. In attendance were 58 senior-level participants, from eight countries, representing 38 CRO companies offering bioanalytical services. The objective of this meeting was for CRO bioanalytical representatives to meet and discuss scientific and regulatory issues specific to bioanalysis. The issues selected at this year's closed forum include CAPA, biosimilars, preclinical method validation, endogenous biomarkers, whole blood stability, and ELNs. A summary of the industry's best practices and the conclusions from the discussion of these topics is included in this meeting report.
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http://dx.doi.org/10.4155/bio.16.16DOI Listing
March 2016

Simultaneous determination of buprenorphine, norbuprenorphine and naloxone in human plasma by liquid chromatography/tandem mass spectrometry.

J Pharm Biomed Anal 2016 Feb 17;120:142-52. Epub 2015 Dec 17.

Indivior Inc., Richmond, VA 23235, USA. Electronic address:

A simple, sensitive and rapid liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for simultaneous quantification of naloxone, buprenorphine and its metabolite norbuprenorphine in human plasma. Human plasma samples were extracted using a single step liquid-liquid extraction, and then separated on an Imtakt Unison UK-C18 column (2.1×50mm, 3μm) using alkaline mobile phases with gradient elution. All of the analytes were detected in positive ion mode using multiple reaction monitoring (MRM). The method was validated and the specificity, linearity, lower limit of quantitation, precision, accuracy, recoveries and stability were determined. The linear range was 20-10000pg/mL for buprenorphine and norbuprenorphine; and 1-500pg/mL for naloxone. The correlation coefficient (R(2)) values for all three analytes were ≥0.995. The precision and accuracy for intra-day and inter-day were <11.0%. The recoveries were >63% and matrix effects were tracked by the deuterated internal standards (IS) with the IS-normalized matrix factor ranging from 0.96 to 1.33 for all three analytes. The validated method was successfully applied in a clinical pharmacokinetic study with low dose administration of sublingual buprenorphine and naloxone.
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http://dx.doi.org/10.1016/j.jpba.2015.12.008DOI Listing
February 2016

8th GCC: consolidated feedback to US FDA on the 2013 draft FDA guidance on bioanalytical method validation.

Bioanalysis 2014 ;6(22):2957-63

Covance Laboratories, Chantilly, VA, USA.

The 8th GCC Closed Forum for Bioanalysis was held in Baltimore, MD, USA on 5 December 2013, immediately following the 2013 AAPS Workshop (Crystal City V): Quantitative Bioanalytical Methods Validation and Implementation--The 2013 Revised FDA Guidance. This GCC meeting was organized to discuss the contents of the draft revised FDA Guidance on bioanalytical method validation that was published in September 2013 and consolidate the feedback of the GCC members. In attendance were 63 senior-level participants, from seven countries, representing 46 bioanalytical CRO companies/sites. This event represented a unique opportunity for CRO bioanalytical experts to share their opinions and concerns regarding the draft FDA Guidance, and to build unified comments to be provided to the FDA.
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http://dx.doi.org/10.4155/bio.14.287DOI Listing
July 2015

Recommendations on incurred sample stability (ISS) by GCC.

Bioanalysis 2014 Sep;6(18):2385-90

Quintiles Bioanalytical & ADME Labs, Ithaca, NY, USA.

The topic of incurred sample stability (ISS) has generated considerable discussion within the bioanalytical community in recent years. The subject was an integral part of the seventh annual Workshop on Recent Issues in Bioanalysis (WRIB) held in Long Beach, CA, USA, in April 2013, and at the Global CRO Council for Bioanalysis (GCC) meeting preceding it. Discussion at both events focused on the use of incurred samples for ISS purposes in light of results from a recent GCC survey completed by member companies. This paper reports the consensus resulting from these discussions and serves as a useful reference for depicting ISS issues and concerns, summarizing the GCC survey results and providing helpful recommendations on ISS in the context of bioanalytical method development and application.
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http://dx.doi.org/10.4155/bio.14.155DOI Listing
September 2014

Recommendations on bioanalytical method stability implications of co-administered and co-formulated drugs by Global CRO Council for Bioanalysis (GCC).

Bioanalysis 2012 Sep;4(17):2117-26

Advion Bioanalytical Laboratories, Quintiles, NY, USA.

An open letter written by the Global CRO Council for Bioanalysis (GCC) describing the GCC survey results on stability data from co-administered and co-formulated drugs was sent to multiple regulatory authorities on 14 December 2011. This letter and further discussions at different GCC meetings led to subsequent recommendations on this topic of widespread interest within the bioanalytical community over the past 2 years.
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http://dx.doi.org/10.4155/bio.12.192DOI Listing
September 2012

Identification of synthetic cannabinoids in herbal incense blends in the United States.

J Forensic Sci 2012 Sep 26;57(5):1168-80. Epub 2012 Jul 26.

NMS Labs, 2300 Stratford Avenue, Willow Grove, PA 19090, USA.

Synthetic cannabinoid agonists are chemically diverse with multiple analogs gaining popularity as drugs of abuse. We report on the use of thin layer chromatography, gas chromatography mass spectrometry, high-performance liquid chromatography, and liquid chromatography time of flight mass spectrometry for the identification and quantitation of these pharmacologically active chemicals in street drug dosage forms. Using these approaches, we have identified the synthetic cannabinoids JWH-018, JWH-019, JWH-073, JWH-081, JWH-200, JWH-210, JWH-250, CP47,497 (C=8) (cannabicyclohexanol), RCS-4, RCS-8, AM-2201, and AM-694 in various commercially available products. Other noncannabinoid drugs including mitragynine have also been detected. Typical concentrations of drug in the materials are in the range 5-20 mg/g, or 0.5-2% by weight for each compound, although many products contained more than one drug.
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http://dx.doi.org/10.1111/j.1556-4029.2012.02207.xDOI Listing
September 2012

Development and validation of a liquid chromatography-tandem mass spectrometry method for the identification and quantification of JWH-018, JWH-073, JWH-019, and JWH-250 in human whole blood.

J Anal Toxicol 2011 Sep;35(7):386-93

NMS Labs, 3701 Welsh Rd., Willow Grove, Pennsylvania 18901, USA.

A sensitive and specific method for the quantification of JWH-018, JWH-073, and JWH-250 and the qualitative identification of JWH-019 in whole blood was developed and validated. Samples fortified with JWH-018-d₉ and JWH-073-d₉ underwent liquid-liquid extraction and were analyzed by liquid chromatography-positive ion electrospray ionization-tandem mass spectrometry. Two transitions were monitored for all analytes except JWH-250, for which there was only one available transition. JWH-019 did not meet the stringent requirements for quantitative analysis, and thus this method is only appropriate for the qualitative identification of this compound in whole blood. The linear range was 0.1-20 μg/L for all quantitative analytes. The maximum average within and between-run imprecision was 7.9% and 10.2%, respectively, and all controls quantified within 8.2% of target concentrations. Process efficiency, a measurement that takes into effect extraction efficiency and matrix effect, was ≥ 32.0% for all quantitative analytes; similar results were obtained for the deuterated internal standards. All analytes were stable at room, refrigerated, and frozen temperatures for at least 30 days. The method was used to quantify JWH-018 and JWH-073 in a blood specimen collected from a person known to have used an herbal incense blend containing these substances.
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http://dx.doi.org/10.1093/anatox/35.7.386DOI Listing
September 2011