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Article: Maternal plasma biomarkers for down syndrome: present and future.

Avent, N D

Drugs of today (Barcelona, Spain : 1998)

2013 Volume 49, Issue 2, Page(s) 145–152

Abstract: Down syndrome is the most common cause of mental retardation and has an incidence of between 1:600 and 1:800 pregnancies. It is the condition for which prenatal diagnosis is requested the most and most developed countries have adopted a screening program ...

Abstract	Down syndrome is the most common cause of mental retardation and has an incidence of between 1:600 and 1:800 pregnancies. It is the condition for which prenatal diagnosis is requested the most and most developed countries have adopted a screening program based around maternal plasma/serum testing and ultrasound. Advances have been made recently to eliminate invasive testing for genetic diagnosis of this condition based on the analysis of free fetal DNA in maternal plasma. But, routine noninvasive prenatal diagnosis for trisomy 21 still appears to be years away. Screening based on assessment of various biomarkers present in maternal plasma represents a front-line test to assess the risk of the mother carrying an aneuploid fetus. Recent comparative proteomics techniques have resulted in studies that have assessed maternal plasma from mothers carrying normal and trisomy 21 fetuses and various gestational ages. Over 100 biomarker candidates have been described, but little consensus has emerged. This may be due to a number of compounded factors, but interesting to note that other neurological disorders have overlapping biomarkers. This article describes these developments and how these biomarkers could contribute to future screening in an emerging era where next-generation sequencing of free fetal DNA will be established in prenatal diagnostics, which appears imminent.
MeSH term(s)	Biomarkers ; DNA/blood ; Down Syndrome/diagnosis ; Female ; Humans ; Pregnancy/blood ; Prenatal Diagnosis
Chemical Substances	Biomarkers ; DNA (9007-49-2)
Language	English
Publishing date	2013-02
Publishing country	Spain
Document type	Journal Article ; Review
ISSN	1699-3993
ISSN	1699-3993
DOI	10.1358/dot.2013.49.2.1888610
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Article: Implementation of a novel antimicrobial stewardship strategy for rural facilities utilising telehealth

Avent, M.L / Walker, D / Yarwood, T / Malacova, E / Brown, C / Kariyawasam, N / Ashley, S / Daveson, K

International journal of antimicrobial agents. 2021 June, v. 57, no. 6

2021

Abstract: A significant portion of healthcare takes place in small hospitals, and many are located in rural and regional areas. Facilities in these regions frequently do not have adequate resources to implement an onsite antimicrobial stewardship programme and ... ...

Abstract	A significant portion of healthcare takes place in small hospitals, and many are located in rural and regional areas. Facilities in these regions frequently do not have adequate resources to implement an onsite antimicrobial stewardship programme and there are limited data relating to their implementation and effectiveness. We present an innovative model of providing a specialist telehealth antimicrobial stewardship service utilising a centralised service (Queensland Statewide Antimicrobial Stewardship Program) to a rural Hospital and Health Service. Results of a 2-year post-implementation follow-up showed an improvement in adherence to guidelines [33.7% (95% CI 27.0–40.4%) vs. 54.1% (95% CI 48.7–59.5%)] and appropriateness of antimicrobial prescribing [49.0% (95% CI 42.2–55.9%) vs. 67.5% (95% CI 62.7–72.4%) (P < 0.001). This finding was sustained after adjustment for hospitals, with improvement occurring sequentially across the years for adherence to guidelines [adjusted odds ratio (aOR) = 2.44, 95% CI 1.70–3.51] and appropriateness of prescribing (aOR = 2.48, 95% CI 1.70–3.61). There was a decrease in mean total antibiotic use (DDDs/1000 patient-days) between the years 2016 (52.82, 95% CI 44.09–61.54) and 2018 (39.74, 95% CI 32.76–46.73), however this did not reach statistical significance. Additionally, there was a decrease in mean hospital length of stay (days) from 2016 (3.74, 95% CI 3.08–4.41) to 2018 (2.55, 95% CI 1.98–3.12), although this was not statistically significant. New telehealth-based models of antimicrobial stewardship can be effective in improving prescribing in rural areas. Programmes similar to ours should be considered for rural facilities.
Keywords	antibiotics ; health services ; hospitals ; models ; odds ratio ; telemedicine ; Queensland
Language	English
Dates of publication	2021-06
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	1093977-5
ISSN	1872-7913 ; 0924-8579
ISSN (online)	1872-7913
ISSN	0924-8579
DOI	10.1016/j.ijantimicag.2021.106346
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Article ; Online: An innovative antimicrobial stewardship programme for children in remote and regional areas in Queensland, Australia: optimising antibiotic use through timely intravenous-to-oral switch.

Avent, M L / Lee, X J / Irwin, A D / Graham, N / Brain, D / Fejzic, J / van Driel, M / Clark, J E

Journal of global antimicrobial resistance

2021 Volume 28, Page(s) 53–58

Abstract: Objectives: Little is known about the benefits of timely switch from intravenous (IV) to oral antibiotic therapy in children. We evaluated the appropriateness of IV-to-oral switch of antibiotic therapy in remote and regional areas of Australia following ...

Abstract	Objectives: Little is known about the benefits of timely switch from intravenous (IV) to oral antibiotic therapy in children. We evaluated the appropriateness of IV-to-oral switch of antibiotic therapy in remote and regional areas of Australia following the implementation of a multifaceted package of interventions. Methods: The intervention package, including clinician guidelines, medication review stickers, patient information leaflets and educational resources, was implemented in seven facilities in Queensland, Australia. Children with community-acquired pneumonia and skin and soft-tissue infections were switched to oral therapy if they met the required 'IV-to-oral switch' criteria. Data were collected for a 7-month period from May to November for the baseline (2018) and intervention (2019) phases. Results: A total of 357 patients were enrolled in the study, including 178 in the baseline phase and 179 in the intervention phase. The percentage of patients who switched to oral therapy or stopped IV antibiotics, within 24 h of eligibility, increased from 87.6% (156/178) in the baseline phase to 97.2% (174/179) in the intervention phase (P = 0.003). The average number of extra IV days decreased from 0.45 days in the baseline period to 0.18 days in the intervention period (P < 0.001). The median patient length of stay was 2 days for both phases. The only adverse events recorded were line-associated infiltration, with a decrease from 34.3% (61/178) (baseline) to 17.9% (32/179) (intervention) (P < 0.001). Conclusion: A multifaceted intervention package to enhance timely IV-to-oral switch of antibiotic therapy for children in remote and regional facilities is effective.
MeSH term(s)	Administration, Intravenous ; Anti-Bacterial Agents/therapeutic use ; Antimicrobial Stewardship ; Australia ; Child ; Humans ; Queensland
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2021-12-13
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2710046-7
ISSN	2213-7173 ; 2213-7173
ISSN (online)	2213-7173
ISSN	2213-7173
DOI	10.1016/j.jgar.2021.11.014
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Article ; Online: Implementation of a novel antimicrobial stewardship strategy for rural facilities utilising telehealth.

Avent, M L / Walker, D / Yarwood, T / Malacova, E / Brown, C / Kariyawasam, N / Ashley, S / Daveson, K

International journal of antimicrobial agents

2021 Volume 57, Issue 6, Page(s) 106346

Abstract	A significant portion of healthcare takes place in small hospitals, and many are located in rural and regional areas. Facilities in these regions frequently do not have adequate resources to implement an onsite antimicrobial stewardship programme and there are limited data relating to their implementation and effectiveness. We present an innovative model of providing a specialist telehealth antimicrobial stewardship service utilising a centralised service (Queensland Statewide Antimicrobial Stewardship Program) to a rural Hospital and Health Service. Results of a 2-year post-implementation follow-up showed an improvement in adherence to guidelines [33.7% (95% CI 27.0-40.4%) vs. 54.1% (95% CI 48.7-59.5%)] and appropriateness of antimicrobial prescribing [49.0% (95% CI 42.2-55.9%) vs. 67.5% (95% CI 62.7-72.4%) (P < 0.001). This finding was sustained after adjustment for hospitals, with improvement occurring sequentially across the years for adherence to guidelines [adjusted odds ratio (aOR) = 2.44, 95% CI 1.70-3.51] and appropriateness of prescribing (aOR = 2.48, 95% CI 1.70-3.61). There was a decrease in mean total antibiotic use (DDDs/1000 patient-days) between the years 2016 (52.82, 95% CI 44.09-61.54) and 2018 (39.74, 95% CI 32.76-46.73), however this did not reach statistical significance. Additionally, there was a decrease in mean hospital length of stay (days) from 2016 (3.74, 95% CI 3.08-4.41) to 2018 (2.55, 95% CI 1.98-3.12), although this was not statistically significant. New telehealth-based models of antimicrobial stewardship can be effective in improving prescribing in rural areas. Programmes similar to ours should be considered for rural facilities.
MeSH term(s)	Anti-Bacterial Agents/therapeutic use ; Antimicrobial Stewardship/methods ; Drug Prescriptions ; Drug Utilization ; Guideline Adherence ; Hospitals, Rural ; Humans ; Outcome Assessment, Health Care/methods ; Practice Patterns, Physicians' ; Rural Population ; Telemedicine
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2021-04-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1093977-5
ISSN	1872-7913 ; 0924-8579
ISSN (online)	1872-7913
ISSN	0924-8579
DOI	10.1016/j.ijantimicag.2021.106346
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Article ; Online: Rh Blood Group D Antigen Genotyping Using a Portable Nanopore-based Sequencing Device: Proof of Principle.

Tounsi, Wajnat A / Lenis, Vasileios P / Tammi, Silja M / Sainio, Susanna / Haimila, Katri / Avent, Neil D / Madgett, Tracey E

Clinical chemistry

2022 Volume 68, Issue 9, Page(s) 1196–1201

Abstract: ... Methods: Genomic DNA (gDNA) samples (n = 13) were tested for Rh blood group D antigen (RHD) gene zygosity ...

Abstract	Background: Nanopore sequencing is direct sequencing of a single-stranded DNA molecule using biological pores. A portable nanopore-based sequencing device from Oxford Nanopore Technologies (MinION) depends on driving a DNA molecule through nanopores embedded in a membrane using a voltage. Changes in current are then measured by a sensor, thousands of times per second and translated to nucleobases. Methods: Genomic DNA (gDNA) samples (n = 13) were tested for Rh blood group D antigen (RHD) gene zygosity using droplet digital PCR. The RHD gene was amplified in 6 overlapping amplicons using long-range PCR. Amplicons were purified, and the sequencing library was prepared following the 1D Native barcoding gDNA protocol. Sequencing was carried out with 1D flow cells R9 version. Data analysis included basecalling, aligning to the RHD reference sequence, and calling variants. Variants detected were compared to the results acquired previously by the Ion Personal Genome Machine (Ion PGM). Results: Up to 500× sequence coverage across the RHD gene allowed accurate variant calling. Exonic changes in the RHD gene allowed RHD allele determination for all samples sequenced except 1 RHD homozygous sample, where 2 heterozygous RHD variant alleles are suspected. There were 3 known variant RHD alleles (RHD01W.02, RHD11, and RHD15) and 6 novel RHD variant alleles, as previously seen in Ion PGM sequencing data for these samples. Conclusions:* MinION was effective in blood group genotyping, provided enough sequencing data to achieve high coverage of the RHD gene, and enabled confident calling of variants and RHD allele determination.
MeSH term(s)	Alleles ; Genotype ; Humans ; Nanopore Sequencing ; Nanopores ; Rh-Hr Blood-Group System/genetics
Chemical Substances	Rh-Hr Blood-Group System ; Rho(D) antigen
Language	English
Publishing date	2022-06-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80102-1
ISSN	1530-8561 ; 0009-9147
ISSN (online)	1530-8561
ISSN	0009-9147
DOI	10.1093/clinchem/hvac075
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Article: RHD genotyping from maternal plasma: guidelines and technical challenges.

Avent, Neil D

Methods in molecular biology (Clifton, N.J.)

2008 Volume 444, Page(s) 185–201

Abstract: Rhesus D (RhD) blood group incompatibility between mother and fetus can occasionally result ... in maternal alloimmunization where the resultant anti-D can cross the placenta and attack the fetal red cells ... generation" RHD genotyping tests were based on the incorrect concept that all D-negative phenotypes were ...

Abstract	Rhesus D (RhD) blood group incompatibility between mother and fetus can occasionally result in maternal alloimmunization where the resultant anti-D can cross the placenta and attack the fetal red cells, which in worse case scenarios can cause fetal anemia and ultimately death. Fetal RHD genotyping was introduced in the mid-1990s after the molecular characterization of the RH genes as an aid to the clinical management of these cases. Initially, these tests used fetal DNA extracted invasively from chorionic villus and amniocyte samples. RHD genotyping of fetuses carried by RhD-negative women has become the first large-scale application of noninvasive prenatal diagnosis (NIPD). Initially the real-time polymerase chain reaction (PCR)-based tests were devised to characterize free fetal DNA in maternal plasma and serum, and RHD genotyping was a convenient assay to develop this exciting new technology, because the accuracy of tests could easily be confirmed after the simple RhD phenotyping of fetal cord blood cells after birth. "First generation" RHD genotyping tests were based on the incorrect concept that all D-negative phenotypes were caused by a complete RHD gene deletion. Thus, it was a relatively simple task to develop diagnostic PCR strategies based on the detection of RHD where D-negative genomes will completely lack RHD. Subsequent research into the molecular basis of D-negative phenotypes revealed that a significant number of D-negative genomes possess fragments of, or mutated RHD genes, the most notable of which is the RHD pseudogene found in Africans. Thus, more comprehensive RHD genotyping tests have evolved to differentiate these alleles, and are more appropriate in the diagnosis of multi-ethnic population groups such as those found in Europe and North America. Many European Union countries have suggested the mass application of RHD NIPD for all fetuses carried by D-negative women. This is of clear benefit, because most RhD prophylaxis programs have switched to antenatal administration. This will help conserve anti-D stocks and it will prevent unnecessary administration of a human-derived blood product to a vulnerable patient group. Although anti-D stocks are inherently safe, there is a moral obligation to eliminate unnecessary administration of it because there have been instances of hepatitis C infection due to contamination. Furthermore, as yet undescribed viruses may be contaminants of blood products. Mass-scale RHD NIPD will shortly be implemented in several countries in the European Community as a consequence.
MeSH term(s)	DNA/blood ; Female ; Gene Expression Regulation, Developmental ; Genetic Testing ; Genotype ; Humans ; Polymerase Chain Reaction ; Practice Guidelines as Topic ; Predictive Value of Tests ; Pregnancy ; Prenatal Diagnosis/methods ; Reproducibility of Results ; Rh Isoimmunization/blood ; Rh Isoimmunization/diagnosis ; Rh Isoimmunization/ethnology ; Rh Isoimmunization/prevention & control ; Rh-Hr Blood-Group System/blood ; Rh-Hr Blood-Group System/genetics
Chemical Substances	Rh-Hr Blood-Group System ; Rho(D) antigen ; DNA (9007-49-2)
Language	English
Publishing date	2008
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1064-3745
ISSN	1064-3745
DOI	10.1007/978-1-59745-066-9_14
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Article: A new chapter in Rh research: Rh proteins are ammonium transporters.

Avent, N D

Trends in molecular medicine

2001 Volume 7, Issue 3, Page(s) 94–96

Abstract: Occasionally, an original research paper has an unusually significant impact on a particular research field. Such a paper, published recently in Nature Genetics, describes the uncovering of the functional role of the Rh protein family--the proteins that ... ...

Abstract	Occasionally, an original research paper has an unusually significant impact on a particular research field. Such a paper, published recently in Nature Genetics, describes the uncovering of the functional role of the Rh protein family--the proteins that express the Rh blood group antigens. Marini et al. (1) demonstrate how two human Rh glycoproteins can correct ammonium transport deficiency in mutant yeast cells. Rh proteins are therefore ammonium transporters--a role that, in vertebrates, has remained previously uncharacterized. These data herald a new era in Rh protein research, beyond their role as blood group antigens, and into the characterization of ammonium transport mechanisms, notably in the kidney.
MeSH term(s)	Amino Acid Sequence ; Animals ; Biological Transport ; Carrier Proteins ; Genetic Complementation Test ; Humans ; Ion Transport ; Kidney/metabolism ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/physiology ; Molecular Sequence Data ; Organ Specificity ; Quaternary Ammonium Compounds/metabolism ; Rh-Hr Blood-Group System/chemistry ; Rh-Hr Blood-Group System/genetics ; Rh-Hr Blood-Group System/physiology ; Saccharomyces cerevisiae/drug effects ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Species Specificity
Chemical Substances	Carrier Proteins ; Membrane Glycoproteins ; Quaternary Ammonium Compounds ; Rh-Hr Blood-Group System
Language	English
Publishing date	2001-03-21
Publishing country	England
Document type	News
ZDB-ID	2036490-8
ISSN	1471-499X ; 1471-4914
ISSN (online)	1471-499X
ISSN	1471-4914
DOI	10.1016/s1471-4914(01)01949-9
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Article ; Online: The QIAGEN 140-locus single-nucleotide polymorphism (SNP) panel for forensic identification using massively parallel sequencing (MPS): an evaluation and a direct-to-PCR trial.

Avent, I / Kinnane, A G / Jones, N / Petermann, I / Daniel, R / Gahan, M E / McNevin, D

International journal of legal medicine

2018 Volume 133, Issue 3, Page(s) 677–688

Abstract: Massively parallel sequencing (MPS) of identity informative single-nucleotide polymorphisms (IISNPs) enables hundreds of forensically relevant markers to be analysed simultaneously. Generating DNA sequence data enables more detailed analysis including ... ...

Abstract	Massively parallel sequencing (MPS) of identity informative single-nucleotide polymorphisms (IISNPs) enables hundreds of forensically relevant markers to be analysed simultaneously. Generating DNA sequence data enables more detailed analysis including identification of sequence variations between individuals. The GeneRead DNAseq 140 IISNP MPS panel (QIAGEN) has been evaluated on both the MiSeq (Illumina) and Ion PGM™ (Applied Biosystems) MPS platforms using the GeneRead DNAseq Targeted Panels V2 library preparation workflow (QIAGEN). The aims of this study were to (1) determine if the GeneRead DNAseq panel is effective for identity testing by assessing deviation from Hardy-Weinberg (HWE) and pairwise linkage equilibrium (LE); (2) sequence samples with the GeneRead DNAseq panel on the Ion PGM™ using the QIAGEN workflow and assess specificity, sensitivity and accuracy; (3) assess the efficacy of adding biological samples directly to the GeneRead DNAseq PCR, without prior DNA extraction; and (4) assess the effect of varying coverage and allele frequency thresholds on genotype concordance. Analyses of the 140 SNPs for HWE and LE using Fisher's exact tests and the sequential Bonferroni correction revealed that one SNP was out of HWE in the Japanese population and five SNP combinations were commonly out of LE in 13 of 14 populations. The panel was sensitive down to 0.3125 ng of DNA input. A direct-to-PCR approach (without DNA extraction) produced highly concordant genotypes. The setting of appropriate allele frequency thresholds is more effective for reducing erroneous genotypes than coverage thresholds.
MeSH term(s)	Animals ; Continental Population Groups/genetics ; Ethnic Groups/genetics ; Gene Frequency ; Genotype ; High-Throughput Nucleotide Sequencing/instrumentation ; Humans ; Linkage Disequilibrium ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Sensitivity and Specificity ; Sequence Analysis, DNA ; Species Specificity
Language	English
Publishing date	2018-12-05
Publishing country	Germany
Document type	Evaluation Study ; Journal Article
ZDB-ID	1055109-8
ISSN	1437-1596 ; 0937-9827
ISSN (online)	1437-1596
ISSN	0937-9827
DOI	10.1007/s00414-018-1975-5
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Article: Molecular biology of the Rh blood group system.

Avent, N D

Journal of pediatric hematology/oncology

2000 Volume 23, Issue 6, Page(s) 394–402

Abstract: ... summarizes the current knowledge concerning the molecular basis of Rh antigenicity, D-epitope expression, and ... testing of all D-negative pregnant women and eventually, perhaps, to all patient and donor blood. ...

Abstract	Rh molecular biology has made many advances since the first Rh cDNA was cloned in 1990. This review summarizes the current knowledge concerning the molecular basis of Rh antigenicity, D-epitope expression, and the structures of the Rh genes and proteins. Although many recent reviews have appeared regarding these subjects, advances in Rh protein function that have been published within the last 12 months have had a fundamental impact on the future direction of Rh research. In November 2000, an article described the role of Rh proteins in ammonium transport, which has remained undescribed in vertebrates, except for non-specific transport via K+ channels. The recent identification of nonerythroid Rh proteins, their expression in diverse tissues, and notably polarized epithelial and endothelial cells will be of broad functional significance and will greatly increase our understanding of the role of Rh in ammonium transport and the biology of ammonium metabolism as a whole. The advances in Rh molecular genetics have enabled the development of diagnostic tests in the clinic. At present, this is largely confined to the prenatal diagnosis of fetal blood group status in alloimmunized pregnancies, but could be extended to the noninvasive prenatal testing of all D-negative pregnant women and eventually, perhaps, to all patient and donor blood.
MeSH term(s)	Animals ; Female ; Humans ; Infant, Newborn ; Pregnancy ; Rh-Hr Blood-Group System/genetics ; Rh-Hr Blood-Group System/physiology
Chemical Substances	Rh-Hr Blood-Group System
Language	English
Publishing date	2000-11-16
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1231152-2
ISSN	1536-3678 ; 1077-4114 ; 0192-8562
ISSN (online)	1536-3678
ISSN	1077-4114 ; 0192-8562
DOI	10.1097/00043426-200108000-00018
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Article: Recombinant technology in transfusion medicine.

Avent, N D

Current pharmaceutical biotechnology

2000 Volume 1, Issue 2, Page(s) 117–135

Abstract: Recombinant technology in transfusion medicine has really only just begun to have large-scale impact. The preparation of blood products, determination of blood group phenotype, detection of blood group specific antibodies does not currently employ DNA- ... ...

Abstract	Recombinant technology in transfusion medicine has really only just begun to have large-scale impact. The preparation of blood products, determination of blood group phenotype, detection of blood group specific antibodies does not currently employ DNA-based methods for their preparation or detection. The detection of bloodborne viruses, production of blood grouping reagents and diagnosis of HLA polymorphism all include recombinant DNA-based technologies and are beginning to impact on routine laboratory life in Transfusion medicine. This review analyses the current use of recombinant technology in transfusion medicine, and indicates where there is likely to be significant development of this methodology (particularly in molecular diagnostics) oven the next decade or so. The impact of molecular medicine in the field of transfusion has already begun. Recent licensing of thrombopoietin for clinical use may have a profound effect on the very high current demand for platelet transfusions. Gene therapy protocols for the treatment of haemophilias and other coagulation disorders, and the production of recombinant blood products may reshape the demand for clotting factors from human plasma. I also consider the potential impact of the exciting technologies of DNA arraying and nucleic acid therapeutics in the fields of molecular diagnostics and the possible treatment of leukemia respectively.
MeSH term(s)	Animals ; Blood Grouping and Crossmatching ; Blood Transfusion ; Humans ; Protein Engineering ; Recombinant Proteins/pharmacology ; Recombinant Proteins/therapeutic use
Chemical Substances	Recombinant Proteins
Language	English
Publishing date	2000-11-16
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2132197-8
ISSN	1873-4316 ; 1389-2010
ISSN (online)	1873-4316
ISSN	1389-2010
DOI	10.2174/1389201003378951
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