NT Health Research and Publications Online

Welcome to NT Health Research and Publications Online, an open access digital repository that showcases the research projects and output of researchers working for the Northern Territory Department of Health (NT Health), while also collecting and preserving publications and multimedia produced in an official capacity, that represent the department. This service is maintained by NT Health Library Services
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Projects
61
People
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  • Publication
    Journal Article
    Targeting Molecular Measurable Residual Disease and Low-Blast Relapse in AML With Venetoclax and Low-Dose Cytarabine: A Prospective Phase II Study (VALDAC).
    (2024-06-20)
    Tiong, Ing Soo
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    Hiwase, Devendra K
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    Abro, Emad
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    Bajel, Ashish
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    Beligaswatte, Ashanka
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    Reynolds, John
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    Anstee, Natasha
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    Nguyen, Tamia
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    Loo, Sun
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    Chua, Chong Chyn
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    Ashby, Michael
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    Wiltshire, Kaitlyn M
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    Fleming, Shaun
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    Fong, Chun Y
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    Teh, Tse-Chieh
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    Blombery, Piers
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    Dillon, Richard
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    Ivey, Adam
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    Wei, Andrew H
    A prospective phase II study examined the safety and efficacy of venetoclax combined with low-dose cytarabine (LDAC) in AML at first measurable residual disease (MRD) or oligoblastic relapse.Patients with either MRD (≥1 log rise) or oligoblastic relapse (blasts 5%-15%) received venetoclax 600 mg once daily D1-28 plus LDAC once daily D1-10 in 28-day cycles. The primary objective was MRD response in the MRD relapse cohort or complete remission (CR/CRh/CRi) in the oligoblastic relapse cohort.Forty-eight adults with either MRD (n = 26) or oligoblastic (n = 22) relapse were enrolled. Median age was 67 years (range, 18-80) and 94% had received previous intensive chemotherapy. Patients received a median of four cycles of therapy; 17% completed ≥12 cycles. Patients with oligoblastic relapse had more grade ≥3 anemia (32% 4%; = .02) and infections (36% 8%; = .03), whereas grade 4 neutropenia (32 23%) or thrombocytopenia (27 15%) were comparable with the MRD relapse cohort. Markers of molecular MRD relapse included mutant (77%), (4%), (4%), or (4%). Three patients with a log rise in / (12%) were included. By cycle 2 in the MRD relapse cohort, a log reduction in MRD was observed in 69%; 46% achieved MRD negative remission. In the oligoblastic relapse cohort, 73% achieved CR/CRh/CRi. Overall, 21 (44%) underwent hematopoietic cell transplantation. Median overall survival (OS) was not reached in either cohort. Estimated 2-year OS rate was 67% (95% CI, 50 to 89) in the MRD and 53% (95% CI, 34 to 84) in the oligoblastic relapse cohorts.For AML in first remission and either MRD or oligoblastic relapse, venetoclax plus LDAC is well tolerated and highly effective.
  • Publication
    Journal Article
    Genomic Testing in Patients with Kidney Failure of an Unknown Cause: a National Australian Study.
    (2024-05-03)
    Mallawaarachchi, Amali C
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    Fowles, Lindsay
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    Wardrop, Louise
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    Wood, Alasdair
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    O'Shea, Rosie
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    Biros, Erik
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    Harris, Trudie
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    Alexander, Stephen I
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    Bodek, Simon
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    Boudville, Neil
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    Burke, Jo
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    Burnett, Leslie
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    Casauria, Sarah
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    Chadban, Steve
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    Chakera, Aron
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    Crafter, Sam
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    Dai, Pei
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    De Fazio, Paul
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    Faull, Randall
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    Honda, Andrew
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    Huntley, Vanessa
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    Jahan, Sadia
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    Jayasinghe, Kushani
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    Jose, Matthew
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    Leaver, Anna
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    MacShane, Mandi
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    Madelli, Evanthia Olympia
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    Nicholls, Kathy
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    Pawlowski, Rhonda
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    Rangan, Gopi
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    Snelling, Paul
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    Soraru, Jacqueline
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    Tchan, Michel
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    Valente, Giulia
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    Wallis, Mathew
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    Wedd, Laura
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    Welland, Matthew
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    Whitlam, John
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    Wilkins, Ella J
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    McCarthy, Hugh
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    Simons, Cas
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    Quinlan, Catherine
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    Patel, Chirag
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    Stark, Zornitza
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    Mallett, Andrew
    The cause of kidney failure is unknown in approximately 10% of patients with stage 5 chronic kidney disease (CKD). For those who first present to nephrology care with kidney failure, standard investigations of serology, imaging, urinalysis and kidney biopsy are limited differentiators of etiology. We aimed to determine the diagnostic utility of whole-genome sequencing (WGS) with analysis of a broad kidney gene panel in patients with kidney failure of unknown cause.We prospectively recruited 100 participants who reached CKD stage 5 at 50 years of age and had an unknown cause of kidney failure after standard investigation. Clinically-accredited WGS was performed in this national cohort after genetic counselling. The primary analysis was targeted to 388 kidney-related genes with second-tier genome-wide and mitochondrial analysis.The cohort was 61% male and the average age of participants at stage 5 CKD was 32 years (9 months to 50 years). A genetic diagnosis was made in 25% of participants. Disease-causing variants were identified across autosomal dominant tubulointerstitial kidney disease (6), glomerular disorders (4), ciliopathies (3), tubular disorders (2), Alport syndrome (4) and mitochondrial disease (1). Most diagnoses (80%) were in autosomal dominant, X-linked or mitochondrial conditions (UMOD; COL4A5; INF2; CLCN5; TRPC6; COL4A4; EYA1; HNF1B; WT1; NBEA; m.3243A>G). Patients with a family history of CKD were more likely to have a positive result (OR 3.29, 95% CI 1.10-11.29). Thirteen percent of participants without a CKD family history had a positive result. In those who first presented in stage 5 CKD, WGS with broad analysis of a curated kidney-disease gene panel was diagnostically more informative than kidney biopsy, with biopsy being inconclusive in 24 of 25 participants.In this prospectively ascertained Australian cohort, we identified a genetic diagnosis in 25% of patients with kidney failure of unknown cause.
  • Publication
    Journal Article
    Supporting healthy lifestyles for First Nations women and communities through co-design: lessons and early findings from remote Northern Australia.
    (2024-05-28)
    Dias, Tara
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    Canuto, Karla
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    Boyle, Jacqueline A
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    D'Antoine, Heather
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    Hampton, Denella
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    Martin, Kim
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    Phillips, Jessica
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    Bartlett, Norlisha
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    Mcintyre, H David
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    Graham, Sian
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    McCarthy, Leisa
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    Kirkham, Renae
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    The period before, during, and after pregnancy presents an opportunity to reduce diabetes-related risks, which in Australia disproportionately impact Aboriginal and Torres Strait Islander women. Collaboration with Aboriginal and Torres Strait Islander women/communities is essential to ensure acceptability and sustainability of lifestyle modifications. Using a novel co-design approach, we aimed to identify shared priorities and potential lifestyle strategies. We also reflected on learnings from this approach.We conducted 11 workshops and 8 interviews at two sites in Australia's Northern Territory (Central Australia and Top End), using experience-based co-design (EBCD) and incorporating principles of First Nations participatory research. Workshops/interviews explored participant' experiences and understanding of diabetes in pregnancy, contextual issues, and potential lifestyle strategies. Participants included three groups: 1) Aboriginal and Torres Strait Islander women of reproductive age (defined as aged 16-45 years); 2) Aboriginal and Torres Strait Islander community members; and 3) health/community services professionals. The study methodology sought to amplify the voices of Aboriginal women.Participants included 23 women between ages 16-45 years (9 with known lived experience of diabetes in pregnancy), 5 community members and 23 health professionals. Key findings related to identified priority issues, strategies to address priorities, and reflections on use of EBCD methodology. Priorities were largely consistent across study regions: access to healthy foods and physical activity; connection to traditional practices and culture; communication regarding diabetes and related risks; and the difficulty for women of prioritising their health among competing priorities. Strategies included implementation of a holistic women's program in Central Australia, while Top End participants expressed the desire to improve nutrition, peer support and community awareness of diabetes. EBCD provided a useful structure to explore participants' experiences and collectively determine priorities, while allowing for modifications to ensure co-design methods were contextually appropriate. Challenges included the resource-intensive nature of stakeholder engagement, and collaborating effectively with services and communities when researchers were "outsiders".A hybrid methodology using EBCD and First Nations participatory research principles enabled collaboration between Aboriginal women, communities and health services to identify shared priorities and solutions to reduce diabetes-related health risks. Genuine co-design processes support self-determination and enhance acceptability and sustainability of health strategies.
  • Person
    MacKay, Diana
  • Publication
    Journal Article
    Chest computed tomography findings among adult Aboriginal Australians with bronchiectasis in the Top End Northern Territory of Australia.
    (2024-06-12) ;
    Howarth, Timothy
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    Heraganahally, Sanjana
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    Sorger, Lisa
    There is limited evidence in the literature illustrating chest computed tomography (CT) characteristics among adult Aboriginal Australians with bronchiectasis. This retrospective study evaluates the radiological characteristics of bronchiectasis in Aboriginal Australians residing in the Top End, Northern Territory of Australia.Patients aged >18 years with chest CT-confirmed bronchiectasis between 2011 and 2020 were included. Demographics and relevant clinical parameters were collected. Alongside confirming bronchiectasis, chest CT reports were assessed for (i) lobar location (ii) unilateral or bilateral involvement and (iii) bronchiectasis type when available.A total of 459 patients were identified with chest CT-confirmed bronchiectasis, with a median age of 47 years, and 55% were females. Bronchiectasis was predominantly recorded in the left lower lobe (LLL) (73%), followed by the right lower lobe (RLL) (62%) and the left upper lobe (LUL) was least common (22%). Females recorded the right middle lobe (RML) affected significantly more often than males (50 vs. 34%, P = 0.012). Bilateral involvement was common (74%), with the strongest pairwise correlation associated between the right upper lobe (RUL) and LUL (P < 0.001). Cylindrical (50%) and cystic (28%) types were most common. The RML and LLL showed positive correlation with cylindrical and LUL with cystic bronchiectasis. Neither lobar location nor bronchiectasis type showed any significant association with lung function parameters other than RML, Lingula and LUL involvement being associated with better percent predicted values of diffusing capacity for carbon monoxide. There were no significant associations between sputum culture and type or lobar locations of bronchiectasis except for non-Aspergillus fungus culture prevalence was higher with cystic or cylindrical types.The results of this study may be an avenue to develop CT bronchiectasis severity scale in the future specific for Aboriginal Australians.
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