ORCID Profile
0000-0002-4124-4971
Current Organisations
E O Lawrence Berkeley National Laboratory
,
Canberra Hospital
,
University of California, Berkeley
,
Australian National University
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Publisher: American Astronomical Society
Date: 28-12-2011
Publisher: American Astronomical Society
Date: 28-12-2011
Publisher: Wiley
Date: 08-10-2019
DOI: 10.1002/PRP2.526
Abstract: Dichloroacetate (DCA) is an investigational drug targeting the glycolytic hallmark of cancer by inhibiting pyruvate dehydrogenase kinases (PDK). It is metabolized by GSTZ1, which has common polymorphisms altering enzyme or promoter activity. GSTZ1 is also irreversibly inactivated by DCA. In the first clinical trial of DCA in a hematological malignancy, DiCAM (DiChloroAcetate in Myeloma), we have examined the relationship between DCA concentrations, GSTZ1 genotype, side effects, and patient response. DiCAM recruited seven myeloma patients in partial remission. DCA was administered orally for 3 months with a loading dose. Pharmacokinetics were performed on day 1 and 8. Trough and peak concentrations of DCA were measured monthly. GSTZ1 genotypes were correlated with drug concentrations, tolerability, and disease outcomes. One patient responded and two patients showed a partial response after one month of DCA treatment, which included the loading dose. The initial half‐life of DCA was shorter in two patients, correlating with heterozygosity for GSTZ1*A genotype, a high enzyme activity variant. Over 3 months, one patient maintained DCA trough concentrations approximately threefold higher than other patients, which correlated with a low activity promoter genotype (−1002A, rs7160195) for GSTZ1 . This patient displayed the strongest response, but also the strongest neuropathy. Overall, serum concentrations of DCA were sufficient to inhibit the constitutive target PDK2, but unlikely to inhibit targets induced in cancer. Promoter GSTZ1 polymorphisms may be important determinants of DCA concentrations and neuropathy during chronic treatment. Novel dosing regimens may be necessary to achieve effective DCA concentrations in most cancer patients while avoiding neuropathy.
Publisher: Wiley
Date: 10-2016
DOI: 10.1111/IMJ.13205
Abstract: Prior randomised studies of immunoglobulin replacement therapy have studied mixed populations with or without a history of infections. Immunoglobulin therapy is expensive and in limited supply suggesting that optimising patient selection is of value. In this retrospective study, infection history identified high-risk groups benefiting from treatment. A group of patients without any infection history had a low risk of infection without immunoglobulin.
Publisher: Elsevier BV
Date: 10-2017
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1111/JTH.15721
Publisher: Wiley
Date: 2010
Publisher: Wiley
Date: 31-10-2019
DOI: 10.1111/TRF.15578
Abstract: Hemolytic disease of the fetus and newborn (HDFN) is due to passively transferred maternal antibodies directed against fetal red blood cell (RBC) antigens and can lead to severe morbidity and mortality. Anti-M is usually a naturally occurring antibody of low clinical significance, although occasionally severe cases of HDFN are seen. Two M+ sisters are presented, each developing hemolysis during the first 2 weeks of life due to maternal anti-M, resulting in severe anemia and requiring blood transfusion. RBC agglutination was observed in peripheral blood s les of both infants at room temperature with dissociation at 37°C. Maternal anti-M detected by column indirect agglutination technique, was of low titer (1:16) and demonstrated low thermal litude, reacting in saline at 4°C but was not detectable in saline at 37°C. Anti-M of low thermal litude may cause hemolytic disease of the newborn with laboratory features resembling cold agglutinin disease.
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.TRANSCI.2018.02.023
Abstract: Although manufacturers recommend varying infusion rates for differing intravenous immunoglobulin products (IVIg), there may be improved efficiency and reduced potential for error with the application of a single infusion policy for all IVIg products. During the transition from a 6% to a 10% IVIg, we prospectively evaluated patient reported adverse reactions to IVIg with the 10% product (Intragam 10) given at a rate faster than recommended by the manufacturer. While there was a significant increase in the rate of immediate infusion reactions when compared with the previous IVIg preparation (Intragam P), there was no increase in the rate of reactions post infusion. The rate of reactions was within previously reported expectations for other IVIg products. All reactions were minor, requiring no or minimal intervention and few impacted significantly on the quality of life. Despite an active haemovigilance program, minor adverse reactions were generally not reported. Our results suggest that a fast single rate of IVIg infusion is safe, and may minimise patient attendance and hospital resources with acceptable safety. In implementing a strategy to increase IVIg infusion rates an active process to monitor safety is preferred over standard haemovigiliance or pharmacovigilance processes.
Publisher: American Astronomical Society
Date: 27-01-2012
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.TRANSCI.2014.12.008
Abstract: For hospitals providing services to regional populations, difficulties are associated with transferred patients with poorly communicated medical history and a risk of alloimmunisation. Identification of patients at risk would assist in treatment planning. A retrospective study of alloimmunised patients was undertaken, comparing the demographics and diagnoses of this population with a control patient population. A preponderance of diagnoses of Sepsis, Haematological Malignancy, GIT Bleeds and Renal Failure was demonstrated in the alloimmunised population. Consistent with prior studies, RhD negative patients and female patients were over-represented in the study group, which was also on average significantly older.
Publisher: American Astronomical Society
Date: 21-05-2010
Publisher: Wiley
Date: 05-09-2019
DOI: 10.1111/AJO.12889
Abstract: The Serious Transfusion Incident Reporting program (STIR) commenced haemovigilance in relation to RhD immunoglobulin (Ig) administration in 2015. During two years of reporting, 21 reports relating to RhD Ig administration were received. Thirty-three percent (7/21) were related to omission of RhD Ig, putting women at risk of RhD alloimmunisation and adverse consequences in future pregnancies. A recent case reported to STIR highlights poor communication and misinterpretation of pathology results leading to significant morbidity from haemolysis in the fetus. STIR makes recommendations related to education of staff and communication between clinical and laboratory staff to improve the safety of patient care.
Publisher: American Astronomical Society
Date: 20-10-2008
DOI: 10.1086/589937
Publisher: Wiley
Date: 25-07-2023
DOI: 10.1111/IMJ.16183
Abstract: Adverse transfusion events create a direct cost burden on the healthcare system through increased morbidity, mortality, extra investigations for diagnosis, patient treatment and increased use of hospital resources. Understanding the costs and impact minor transfusion reactions have on the healthcare system presents an opportunity for potential cost savings and improved clinical practice. To determine the cost associated with investigating minor transfusion reactions, to identify opportunities to improve the management of blood transfusion reactions and potential cost savings through the application of current national guidelines. A retrospective review of all suspected transfusion reactions reported to the laboratory over a 6‐year period was performed. Reports were assessed for appropriateness of clinical management and associated investigations. Cost of inappropriate investigations and associated blood product discard was calculated using current national tariffs. Of the 274 reports, febrile non‐haemolytic transfusion reactions were the most common reactions, with 96 (35%) cases. One hundred forty‐eight patients were unnecessarily investigated for suspected transfusion reactions totalling AU$ 32 427.00. The initial total value of partially discarded blood products was AU$ 55 656.00. The study demonstrated that unnecessary investigation of minor transfusion reactions adds a significant financial burden to the healthcare system.
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.TRANSCI.2018.11.009
Abstract: To determine the optimum approach and timing to screen for iron deficiency in pregnancy. There is a lack of consensus on identifying and treating iron deficiency during pregnancy. Patient blood management programs may be refined by evaluating outcomes. Retrospective data collection on women delivering prior to and following implementation of patient blood management interventions. Ferritin, transferrin saturation and haemoglobin levels were evaluated in first and second trimesters as predictors of pre-delivery anaemia. The optimum time to screen was determined. Comparison with results following a quality improvement intervention was undertaken. A separate retrospective study was performed to validate the predictive value of ferritin using data extracted from the laboratory information system. Ferritin and transferrin saturation in first trimester detected women who subsequently had anaemia pre-delivery, with ferritin being most discriminatory. Both were superior to haemoglobin concentration. Iron studies in second trimester did not predict pre-delivery anaemia and haemoglobin remained poorly discriminatory. Iron studies lost predictive value when a systematic program ensured treatment of iron depletion during pregnancy. The ability of ferritin to predict pre-delivery anaemia in the first, but not the second, trimester was confirmed on the validation cohort. First trimester serum ferritin may identify candidates for iron therapy during pregnancy. This strategy may be preferable to haemoglobin screening alone or universal replacement in centres at low risk of anaemia.
Publisher: Wiley
Date: 2016
DOI: 10.1111/IMJ.12957
Abstract: We report the first published case of aggressive diffuse large B-cell (non-Hodgkin) lymphoma in a 35-year-old pregnant woman who had Crohn disease and was taking long-term thiopurine therapy: the patient developed placental insufficiency, and there was intrauterine fetal death.
Publisher: Wiley
Date: 25-10-2021
DOI: 10.1111/VOX.13199
Publisher: Wiley
Date: 28-01-2022
DOI: 10.1111/VOX.13254
Abstract: Electronic medical records (EMRs) are often composed of multiple interlinking systems, each serving a particular task, including transfusion ordering and administration. Transfusion may not be prioritized when developing or implementing electronic platforms. Uniform guidelines may assist information technology (IT) developers, institutions and healthcare workforces to progress with shared goals. A narrative review of current clinical guidance, benefits and risks of electronic systems for clinical transfusion practice was combined with feedback from experienced transfusion practitioners. There is opportunity to improve the safety, quality and efficiency of transfusion practice, particularly through decision support and better identification procedures, by incorporating transfusion practice into EMRs. However, these benefits should not be assumed, as poorly designed processes within the electronic systems and the critically important electronic–human process interfaces may increase risk while creating the impression of safety. Guidelines should enable healthcare and IT industries to work constructively together so that each implementation provides assurance of safe practice.
Publisher: Wiley
Date: 19-02-2019
DOI: 10.1111/IJLH.12984
Abstract: Bone marrow biopsies are a key diagnostic and monitoring intervention in haematology with manual bone marrow techniques the established method of choice. Powered biopsy devices are now available, but are not widely used in haematology. This study compared the quality of bone marrow trephines obtained with the Jamshidi needle and OnControl powered drill system. Retrospective analysis was undertaken on trephine s les prior to and after implementation of the OnControl drill system. Trephine size and quality were assessed independently by three pathologists and compared between techniques and operators using nonparametric tests. There were 164 s les assessed (Jamshidi n = 69, OnControl, same site as aspirate n = 48, OnControl, separate site from aspirate n = 47). The assessable and total length were similar between the Jamshidi and OnControl techniques, with increased crush artefact observed with the OnControl drill (P < 0.001). Using a separate puncture site for trephine collection and aspirate did not reduce the artefact seen with the OnControl system (P = 0.274). Smaller s les (P < 0.001) and an increase in crushed (P = 0.009) and connective tissue (P = 0.002) were seen in trephines obtained by nonlaboratory-based trainees, regardless of the needle used or their stage of training, compared to laboratory trainees. Trephines obtained by either method had similar assessable areas. The OnControl system was associated with more artefact, a finding in line with previous studies. There was no improvement by s ling the trephine from a separate site to the aspirate. Laboratory-based trainees who reviewed marrow morphology produced trephines with better assessable length than those not based in the laboratory.
Publisher: Elsevier BV
Date: 06-2011
Publisher: Elsevier BV
Date: 12-2010
DOI: 10.1016/J.TRANSCI.2010.10.005
Abstract: Contingency plans have been developed to direct appropriate responses to blood shortages. Planning requires an understanding of the potential savings of different conservation strategies. The Australian Capital Territory (ACT) Haemovigilance and ACT Pathology transfusion databases were reviewed from March to September 2003. All transfusion episodes were prioritised in accordance with the Australian National Blood Supply Contingency Plan. The number of red cell transfusions related to various indications, their appropriateness and acuity was determined. The potential reduction in red cell usage was modelled for potential red cell reduction interventions. There were 2305 units of red cells captured during the timeframes of the audits. This accounted for an estimated 70% of all red cell transfusions in the ACT. After correcting for the number of red cells transfused at each hospital, red cells were prioritised as category 1 in 59%, 2 in 27% and 3 in 13%. The remainder had insufficient data for classification. Transfusion for elective surgery accounted for 14.7% of red cells used, with 9.0% rated category 3 under the contingency plan. There were 17.3% of red cells transfused for inappropriate indications, when reviewed against national guidelines. After excluding inappropriate transfusions, cancelling elective surgery could potentially save a further 5.5% and 4.3% of blood utilisation for category 3 and 2 patients, respectively. Significant differences were found between hospitals. Targeting inappropriate transfusions by vetting particularly for inappropriate transfusions not only re-directs blood away from those unlikely to benefit, but is also more effective at preserving the red blood cells than other measures during times of supply limitation. Contingency planning needs to accommodate the variable case-mix in hospitals, allocate resources for transfusion medicine specialists to review every transfusion request and may be better coordinated at a jurisdictional level.
Publisher: Elsevier BV
Date: 08-2021
Publisher: American Astronomical Society
Date: 10-06-2006
DOI: 10.1086/503533
Publisher: Wiley
Date: 11-2014
DOI: 10.1111/IMJ.12545
Abstract: Outcomes for haematology/oncology patients have improved however, determining their suitability for intensive care unit (ICU) admission remains challenging and controversial. Examine outcomes of patients admitted to an Australian tertiary hospital ICU and explore potential prognostic factors. A retrospective review of patients with haematological and solid tumour malignancies non-electively admitted to The Canberra Hospital (TCH) ICU, between January 2008 and December 2012. Patient demographics, cancer details, reasons for ICU admission and Acute Physiologic and Chronic Health Evaluation (APACHE) II scores were collected, and survival rates calculated and correlated with potential prognostic factors. Of 205 patients, 113 (55%) had haematological malignancies, and 92 (45%) had solid tumours: 58% male and mean age 60.3 years (standard deviation (SD) 13.4). Eighty-two per cent of solid tumour patients had metastatic disease and 55% received palliative chemotherapy. Primary reasons for ICU admission included sepsis (59%), respiratory distress (37%) and hypotension/shock (18%). Mean APACHE II score was 20.1(SD 0.55) mean length of stay in ICU, 4 days (SD 5.2) ICU survival was 76% with 62% and 41% alive at 30 days and 6 months respectively. Overall 1-year survival was 36%. High APACHE II scores and ≥2 organs failing were significant risk factors for 30-day mortality. Short-term outcomes were similar to contemporary studies from a general tertiary hospital setting and better than historical data. Sixty-two per cent of patients were alive 30 days post-ICU admission, with a significant minority alive at 12 months, confirming some patients achieved worthwhile outcomes. Further research is needed to ensure appropriate patient selection and to explore quality of life post ICU.
Publisher: Wiley
Date: 12-11-2020
DOI: 10.1111/TRF.15588
Abstract: Objective measures to assess the need for transfusion in chronic anemia are lacking. Near-infrared spectroscopy may be used, but there is wide variability. Assessment of muscle oxygen saturation (SmO Hematology patients and controls were recruited to undertake a 6-minute walk test (6MWT) and a 20-second isometric handgrip exercise. Muscle oxygen saturation in the exercising muscles was measured before and during exercise. Changes in saturation during exercise were described. Correlations between identified variables, hemoglobin concentration, and 6MWT distance were undertaken. The effect of transfusion was assessed on a transfused subset. There were 95 sets of exercises conducted in 74 participants. Baseline SmO While baseline SmO
Publisher: American Astronomical Society
Date: 14-07-2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2020
Publisher: Wiley
Date: 04-05-2021
DOI: 10.1111/VOX.12934
Abstract: Fresh blood product transfusion requires patient education for fully informed consent, and written consumer information is frequently used. Few studies have examined consumer preferences regarding written and verbal transfusion information provided. As a qualitative study, this research was designed to explore participant understanding and by analysing and integrating themes, generate a model to understand how transfusion information should be developed and used in practice. Semi‐structured interviews were conducted with healthcare consumers of transfusion information from various hospital clinical departments. Transcripts were coded to qualitatively compare nature/extent of content and opinions regarding transfusion information through thematic analysis. Analysis identified themes relating to healthcare engagement, purpose of information, mode of delivery and content delivered. Differences were identified between perceived purpose of information provided to consumers between 13 transfusion prescribers and consumers. Prescribers viewed information as a tool for obtaining informed consent, whereas consumers desired reassurance and knowledge. Consumers described both the specialized nature and volume of information as limiting their ability to question professionals on whom they were dependent. Information provided should be tailored to consumers and utilize simple, succinct explanations. Both groups were satisfied with written information adjunctive to verbal information. These findings will be used to redesign transfusion information and may be employed at the bedside when discussing transfusion. They may have implications for consumer information in other settings.
Publisher: American Astronomical Society
Date: 31-03-2009
Publisher: Wiley
Date: 12-10-2022
DOI: 10.5694/MJA2.51748
Publisher: Wiley
Date: 06-08-2019
DOI: 10.1111/BJH.16148
Publisher: Wiley
Date: 30-03-2018
DOI: 10.1111/EJH.13050
Abstract: To evaluate the dilute Russell viper venom time (DRVVT) for the detection of direct-acting oral anticoagulants (DOACs) and to investigate the effect of DOACS on coagulation assays. Patients with DOACs and controls had plasma levels determined by an anti-Xa assay and dilute thrombin clotting time (TCT). Levels were correlated with the DRVVT as well as TCT, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, protein C, protein S and antithrombin levels. The utility of the DRVVT for detecting clinically significant levels of DOACs was evaluated. There were 44 s les from patients taking dabigatran, 83 with rivaroxaban, 18 with apixaban and 55 controls. The PT and APTT failed to detect clinically significant doses of anticoagulants adequately. The TCT was increased in patients taking dabigatran and normal in controls and patients on FXa inhibitors. There was a linear correlation with all DOAC levels and the DRVVT, with moderate precision, but it showed high sensitivity (95%) and specificity (90%) for clinically significant DOAC levels. The DRVVT detects clinically significant levels of DOACs and, in conjunction with the TCT, may be used as a screen for the presence and type of DOAC.
Publisher: Wiley
Date: 08-12-2021
DOI: 10.1002/JHA2.358
Abstract: Platelet transfusions are not always available for bleeding in severe thrombocytopenia, as storage outside of major centers is limited by their short shelf‐life. Data are lacking to support alternative available blood products however, additional fibrinogen has been shown to enhance clot formation in vitro. To test the hypothesis that cryoprecipitate supplementation could improve clot formation in severe thrombocytopenia, eight hematological malignancy patients with platelet counts under 10 × 10 9 /L each had 10 units of apheresis cryoprecipitate transfused prior to planned prophylactic platelet transfusions. The primary endpoint of thromboelastometry litude at 20 min increased by a mean of 5.1 mm ( p 0.01) following cryoprecipitate transfusion despite persisting thrombocytopenia. Thromboelastometry clotting times reduced by a mean of 7.8 s ( p 0.05) and alpha angle increased by a mean of 10.6⁰ ( p 0.01). These results are consistent with cryoprecipitate enhancing the strength of the fibrin latelet meshwork within the forming thrombus. While platelet transfusion remains the standard of care, where platelet supplies are limited, these data provide a rationale for the use of cryoprecipitate to obtain hemostasis in bleeding thrombocytopenic patients.
Publisher: Wiley
Date: 26-10-2010
DOI: 10.1111/J.1440-1754.2010.01888.X
Abstract: Aim: To determine the impact of Rhesus (Rh) D prophylaxis on positive direct antiglobulin test (DAT) results and ability of a DAT grade to predict an infant's need for phototherapy. Methods: Laboratory and infant medical records were reviewed for DAT status, DAT grade, interventions for hyperbilirubinemia including phototherapy, blood transfusion, exchange transfusion and intravenous immunoglobulin. Two epochs of DAT results were reviewed, the first in the era prior to Rh D prophylaxis, the second after introduction of standardised Rh D prophylaxis for Rh negative women. Results: A total of 165 DAT‐positive infants' medical records were reviewed. The number of positive DAT results increased from 1.5% to 2.3% ( P 0.0001) following introduction of anti‐Rh D prophylaxis, the increase related to an increase in anti‐D DATs (7.4% to 32% – P 0.0001). An infant with a DAT grade of 5–8 was 2.6 times more likely to need phototherapy than an infant with a DAT grade of 2–4 (odds ratio (OR), 2.571 95% confidence interval (CI), 1.225–5.393 P = 0.08) and an infant with a DAT grade of 10–12 was 4.7 times more likely to need phototherapy than an infant with a DAT grade of 2–4 (OR, 4.724 95% CI, 1.602–13.926, P = 0.013). Conclusions: Rh D prophylaxis has increased positive DAT results, which may increase the number of unnecessary bilirubin measurements. A low or high DAT grade is strongly predictive of whether an infant does or does not require phototherapy. However, an intermediate DAT requires concomitant bilirubin measurements to determine phototherapy requirements.
Publisher: Wiley
Date: 06-10-2018
DOI: 10.1111/IJLH.12751
Abstract: Marrow granulomas have been commonly associated with mycobacterial infections, prompting extensive investigations in some cases where they are found, but in the setting of changing infectious epidemiology, there is a lack of recent data to guide the search for probable causes. A retrospective case series examining the clinical and pathological findings in all cases where marrow granulomas were reported over a 10-year period at The Canberra Hospital, Australia. Of the 6062 marrow biopsies performed, 73 (1.2%) from 66 in iduals had confirmed granulomas. Some patients had multiple potential causes found. B-cell non-Hodgkin Lymphoma, sarcoidosis and autoimmune disease were the most frequently observed causes. Infections were less common in this cohort than in the previous series, with no tuberculosis seen. The presence of granulomas in the marrow did not signify the presence of active malignancy in the marrow. There were no associations with any specific morphological characteristics of the granulomas and the presumed causes. Marrow granulomas are seen in a variety conditions. Neither their presence nor their morphological features are a guide to further investigations, which should be determined by the clinical presentation as appropriate.
Publisher: Wiley
Date: 25-10-2021
DOI: 10.1111/VOX.13200
Publisher: Wiley
Date: 16-06-2016
DOI: 10.1111/IJLH.12510
Abstract: Low haemoglobin density (LHD%) from Coulter counters has been suggested as a means to detect iron deficiency. Its performance in a broad population group, including pregnancy, has not been evaluated. A retrospective study of adult and paediatric (under 12 years old) patient s les referred for blood counts and iron studies between October 2013 and March 2015. Receiver operator characteristic (ROC) curves were constructed to evaluate the performance of LHD% adults, children, and in the antenatal subgroup. Using a strict definition for iron deficiency, compared with a selected normal cohort, LHD% had a ROC area under the curve (AUC) of 0.90 (0.89-0.91), but in an unselected cohort, the AUC fell to 0.74 (0.73-0.75) with a sensitivity of 74% and specificity of 60% at a cut-off value of 5.9%. In the paediatric cohort, the AUC was 0.79(0.73-0.85), giving a sensitivity and specificity of 75% and 68%, respectively. LHD% did not effectively identify iron deficiency in pregnancy with an AUC of 0.60 (0.54-0.65) and was no better than MCV at detecting iron deficiency. LHD% detects iron deficiency in adult and paediatric populations, but not in the antenatal setting, and does not appear superior to MCV.
Publisher: American Astronomical Society
Date: 02-2008
DOI: 10.1086/524881
Location: United States of America
Location: United States of America
No related grants have been discovered for Philip Crispin.