Publications by authors named "Anna McLean"

27 Publications

  • Page 1 of 1

Improving systems of prenatal and postpartum care for hyperglycemia in pregnancy: A process evaluation.

Int J Gynaecol Obstet 2021 Jul 31. Epub 2021 Jul 31.

Division of Wellbeing and Preventable Chronic Disease, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia.

Objective: To identify successes to date and opportunities for improvement in the implementation of a complex health systems intervention aiming to improve prenatal and postpartum care and health outcomes for women with hyperglycemia in pregnancy in regional and remote Australia.

Methods: A qualitative evaluation, underpinned by the RE-AIM framework (reach, effectiveness, adoption, implementation, maintenance), was conducted mid-intervention. Semi-structured interviews were conducted with the participants, who included clinicians, regional policymakers and managers, and study implementation staff.

Results: Interviewees (n = 45) reported that the early phase of the intervention had resulted in the establishment of a clinician network, increased clinician awareness of hyperglycemia in pregnancy, and improvements in management, including earlier referral for specialist care and a focus on improving communication with women. Enablers of implementation included existing relationships with stakeholders and alignment of the intervention with health service priorities. Challenges included engaging remote clinicians and the labor-intensive nature of maintaining a clinical register of women with hyperglycemia in pregnancy.

Conclusion: The early phase of this health systems intervention has had a positive perceived impact on systems of care for women with hyperglycemia in pregnancy. Findings have informed modifications to the intervention, including the development of a communication and engagement strategy.
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http://dx.doi.org/10.1002/ijgo.13850DOI Listing
July 2021

Rethinking third trimester ultrasound measurements and risk of adverse neonatal outcomes in pregnancies complicated by hyperglycaemia: A retrospective study.

Aust N Z J Obstet Gynaecol 2021 06 3;61(3):366-372. Epub 2021 Jan 3.

Wellbeing and Chronic Preventable Diseases Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.

Background: Antenatal ultrasound is used frequently in pregnancies complicated by hyperglycaemia; however, it is unclear which measurements have the greatest association with adverse neonatal outcomes.

Aim: To assess the association between third trimester ultrasound parameters with adverse neonatal outcomes in pregnancies complicated by hyperglycaemia.

Method: All pregnant women with gestational or type 2 diabetes who birthed in a regional hospital over 12 months were included. A composite adverse neonatal outcome was defined by one or more: admission to special care nursery, acidosis, hypoglycaemia, jaundice, shoulder dystocia, respiratory distress syndrome or 5-minute Apgar score < 5. Logistic regression was used to determine odds ratios (OR) for an adverse neonatal outcome, according to pre-specified cut points in both lower and upper percentiles of abdominal circumference (AC) and estimated fetal weight (EFW).

Results: Of 275 births an adverse outcome occurred in 122 (44%). Unadjusted OR (95% CI) for AC ≤30 was 3.2 (1.1-8.8) and >95 percentile was 3.1 (1.5-6.0) compared with the reference group of 31-70 percentile. Unadjusted OR for EFW ≤30 was 1.5 (0.7-3.1) and >95 percentile was 3.0 (1.4-6.3). After adjusting for maternal age, body mass index, diabetes type, ethnicity, gravidity, mode of delivery and gestation at birth the OR (95% CI) were as follows: AC ≤30 percentile, 3.7 (1.1-12.4); AC >95 , 2.2 (1.1-4.8); EFW ≤30 , 2.6 (1.1-6.1); EFW >95 , 2.5 (1.1-6.1).

Conclusion: An AC and EFW up to the 30 percentile may pose just as great a risk to the fetus as an AC or EFW >95 percentile in pregnancies complicated by hyperglycaemia.
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http://dx.doi.org/10.1111/ajo.13281DOI Listing
June 2021

Blowing Away Fatty Liver: Mission Impossible?

Am J Respir Crit Care Med 2021 02;203(4):412-413

Department of Respiratory and Sleep Medicine Royal Prince Alfred Hospital Sydney, New South Wales, Australia.

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http://dx.doi.org/10.1164/rccm.202009-3578EDDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885836PMC
February 2021

Priorities and expectations of patients attending a multidisciplinary interstitial lung disease clinic.

Respirology 2021 01 17;26(1):80-86. Epub 2020 Aug 17.

Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.

Background And Objective: The significant and progressive morbidity associated with ILD mean that patients often struggle with the impact of this disease on their QOL and independence. To date, no studies have investigated the importance of multidisciplinary care on patient experience in ILD. We aimed to determine the expectations and priorities of patients attending a tertiary referral centre multidisciplinary ILD clinic. In particular, we sought to learn how important the multidisciplinary element of the clinic was to patients and which aspects of the clinic were most valued.

Methods: An 18-item patient questionnaire was developed in conjunction with expert physicians and specialist nurses involved in the ILD clinic and sent to all patients on the centre's ILD registry at the time of the study (n = 240). Patients rated the importance of different aspects of their experience of attending the clinic. Data collected were analysed using descriptive statistics. Comparisons across disease severity were made using two-sided Z-tests for independent proportions.

Results: A total of 100 respondents comprised the study group. Almost all respondents valued the multidisciplinary aspect of the clinic. Obtaining an accurate diagnosis and improving their disease understanding was most important to respondents. The importance of the ILD specialist nurse for both education and support increased with worsening disease severity.

Conclusion: Our results suggest that a multidisciplinary approach to the management of ILD with additional focus on patient education, as well as tailoring care to disease severity, is a plausible pathway to improving the patient experience with ILD.
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http://dx.doi.org/10.1111/resp.13913DOI Listing
January 2021

The Neurofibromatoses.

Dtsch Arztebl Int 2020 May;117(20):354-360

Neurofibromatosis Center, Department of Neurosurgery, Helios Hospital Erfurt

Background: Neurofibromatosis of types 1 and 2 (NF1, NF2) and schwannomatosis are the diseases that make up the neurofibromatosis spectrum. With respective incidences of 1 in 3000, 1 in 33 000, and 1 in 60 000 births, they form part of the group of rare tumor-suppressor syndromes. They give rise to a greater tumor burden for the nervous system than any other type of neoplastic disease. New approaches to symptomatic treatment are emerging.

Methods: This review is based on articles retrieved by a selective literature search on the pathogenesis, diagnosis, and treatment of the neurofibromatoses.

Results: NF1 and NF2 are monogenic diseases, while the genetics of schwannomatosis is complex. The three entities are clinically and pathophysiologically distinct. An important aspect of their tumor biology is the alternation of growth phases and growth pauses. Correlations between genotypes and phenotypes are variable, while new mutations and genetic mosaics are common. Ninety-nine percent of patients with NF1 have six or more café-au-lait spots by the age of 12 months; 90-95% of patients with NF2 develop bilateral vestibular schwannomas. In schwannomatosis, pain is the most prominent symptom; two-thirds of those affected develop spinal schwannomas. The severity and prognosis of these disorders are not closely correlated with the radiological findings; rather, neurologic deficits, malignant transformation, and psychosocial stress are of greater clinical importance. Advances in knowledge of pathophysiology have led to the development of targeted treatment approaches. Examples include the off-label treatment of vestibular schwannomas with bevacizumab and of plexiform neurofibromas with MEK inhibitors.

Conclusion: Patients with neurofibromatoses need individualized care. They should be treated in centers of expertise where interdisciplinary consultation is available and new types of pharmacotherapy can be provided.
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http://dx.doi.org/10.3238/arztebl.2020.0354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373809PMC
May 2020

Improving Models of Care for Diabetes in Pregnancy: Experience of Current Practice in Far North Queensland, Australia.

Front Public Health 2019 19;7:192. Epub 2019 Jul 19.

Wellbeing and Preventable Chronic Disease Division, Menzies School of Health Research, University Drive North, Casuarina, NT, Australia.

To map health practitioners' experiences and describe knowledge regarding screening and management of Diabetes in Pregnancy (DIP) in Far North Queensland, Australia. Mixed methods including a cross-sectional survey (101 respondents) and 8 focus groups with 61 health practitioners. All participants provided clinical care for women with DIP. A wide range of healthcare professionals participated; 96% worked with Indigenous women, and 63% were from regional or remote work settings. Universal screening for gestational diabetes at 24-28 weeks gestation was reported as routine with 87% using a 75 g Oral Glucose Tolerance Test. Early screening for DIP was reported by 61% although there was large variation in screening methods and who should be screened <24 weeks. Health practitioners were confident providing lifestyle advice (88%), dietary, and blood glucose monitoring education (67%, 81%) but only 50% were confident giving insulin education. Electronic medical records were used by 80% but 55% also used paper records. Dissatisfaction with information from hospitals was reported by 40%. In the focus groups improving communication and information technology systems were identified as key areas. Other barriers described were difficulties in care coordination and access for remote women. Communication, information technology systems, coordination of care, and education for health professionals are key areas that will be addressed by a complex health systems intervention being undertaken by the DIP Partnership in North Queensland.
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http://dx.doi.org/10.3389/fpubh.2019.00192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659099PMC
July 2019

Diagnosis and management of type 2 diabetes in youth in North Queensland and the Northern Territory: A health professional survey.

Aust J Rural Health 2019 Feb 29;27(1):42-48. Epub 2019 Jan 29.

Department Diabetes and Endocrinology, Cairns Hospital, Cairns, Queensland, Australia.

Objective: To describe clinician practice regarding diagnosis, management and perceived barriers to the optimal management of youth-onset type 2 diabetes mellitus in North Queensland and the Northern Territory and to compare self-reported practice to guideline recommendations.

Design: A mailed questionnaire distributed between July and October 2017.

Setting: Clinicians practising in three tertiary hospitals and two primary care organisations in North Queensland and the Northern Territory.

Participants: Of the 72 participants, 42 (58%) who responded were endocrinologists, diabetes educators, GPs and paediatricians.

Results: Of the 42 clinicians, 23 referred to the guidelines. A diabetes educator, GP, endocrinologist and dietitian were the most commonly included clinicians in the multidisciplinary team. Half of the clinicians' screen the children if additional risk factors are present. The HbA1c is the most common test used for screening and diagnosis. At diagnosis, the clinicians' recommended lifestyle change in 86% of the patients, treatment with metformin in 48%, and, when indicated, treatment with insulin in up to 45%. All clinicians believe that non-adherence is a major factor limiting optimal care. Most commonly cited barriers to optimal care were poor patient or family health literacy and limited patient or family understanding of the condition.

Conclusion: This study demonstrates several aspects of diagnosis and management of type 2 diabetes mellitus in youth that deviate from the guidelines. Patients need improved access to social workers, psychologists and Indigenous health workers. Other key areas to address are evaluation of risk-based screening, supporting appropriate and early use of insulin and the management of youth with type 2 diabetes mellitus inclusive of their family through contextualised health care delivery.
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http://dx.doi.org/10.1111/ajr.12458DOI Listing
February 2019

Diagnosing Lung Cancer: The Complexities of Obtaining a Tissue Diagnosis in the Era of Minimally Invasive and Personalised Medicine.

J Clin Med 2018 Jun 29;7(7). Epub 2018 Jun 29.

Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2050, Australia.

The role of the respiratory physician in diagnosing lung cancer has increased in complexity over the last 20 years. Adenocarcinoma is now the prevailing histopathological sub-type of non-small cell lung cancer (NSCLC) resulting in more peripheral cancers. Conventional bronchoscopy is often not sufficient to obtain adequate tissue samples for diagnosis. Radiologically guided transthoracic biopsy is a sensitive alternative, but carries significant risks. These limitations have driven the development of complimentary bronchoscopic navigation techniques for peripheral tumour localisation and sampling. Furthermore, linear endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) is increasingly being chosen as the initial diagnostic procedure for those with central lesions and/or radiological evidence of node-positive disease. This technique can diagnose and stage patients in a single, minimally invasive procedure with a diagnostic yield equivalent to that of surgical mediastinoscopy. The success of molecular targeted therapies and immune checkpoint inhibitors in NSCLC has led to the increasing challenge of obtaining adequate specimens for accurate tumour subtyping through minimally invasive procedures. This review discusses the changing epidemiology and treatment landscape of lung cancer and explores the utility of current diagnostic options in obtaining a tissue diagnosis in this new era of precision medicine.
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http://dx.doi.org/10.3390/jcm7070163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068581PMC
June 2018

Vitamin D supplementation in pregnant women with diabetes in Far North Queensland.

Aust J Rural Health 2018 Dec 30;26(6):451-452. Epub 2018 May 30.

University of New England School of Health, Armidale, New South Wales, Australia.

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http://dx.doi.org/10.1111/ajr.12437DOI Listing
December 2018

Decreases in Mixed Venous Blood O Saturation in Cardiac Surgery Patients Following Extubation.

J Intensive Care Med 2020 Mar 15;35(3):264-269. Epub 2017 Nov 15.

Division of Pulmonary and Critical Care Medicine, The George Washington University Medical Center, Washington, DC, USA.

Background: Decreases in mixed venous O saturation (SO) have been reported to occur in postcardiac surgery patients during weaning from mechanical ventilation. Our aim was to establish whether the physiological mechanism responsible for this phenomenon was a decrease in systemic O delivery (DO) or an increase in global O consumption ( O ).

Methods: We studied 21 mechanically ventilated, postoperative cardiac patients for 30 minutes before and 60 minutes after extubation. We monitored continuously arterial O saturation by pulse oximetry (SO) and central venous O saturation (SO) with an oximetry catheter. Mixed venous O saturation (SO) and cardiac output were also measured continuously with an oximetry pulmonary artery catheter. Systemic O delivery and O were calculated according to accepted formulae.

Results: Immediately following extubation, SO and SO decreased rapidly ( < .01). Systemic O consumption increased from 65 (57) mL·min to 194 (66) mL·min ( < .05) with no changes in DO. Consequently, systemic O extraction rose from 38% (8%) to 45% (9%; < .01). Preoperative left ventricular ejection fraction correlated with the decline in SO postextubation. All patients weaned successfully.

Conclusions: Decreases in SO after discontinuation of ventilatory support in postcardiac surgery patients occur as O increases in response to greater energy requirements by muscles of ventilation that are not initially matched by increases in DO.
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http://dx.doi.org/10.1177/0885066617741435DOI Listing
March 2020

Ultrasound-guided versus computed tomography-scan guided biopsy of pleural-based lung lesions.

Lung India 2016 Sep-Oct;33(5):487-92

Department of Pulmonary and Critical Care, Veterans Affairs Medical Center, George Washington University, Washington, DC, USA.

Background: Computed tomography (CT) guided biopsies have long been the standard technique to obtain tissue from the thoracic cavity and is traditionally performed by interventional radiologists. Ultrasound (US) guided biopsy of pleural-based lesions, performed by pulmonologists is gaining popularity and has the advantage of multi-planar imaging, real-time technique, and the absence of radiation exposure to patients. In this study, we aim to determine the diagnostic accuracy, the time to diagnosis after the initial consult placement, and the complications rates between the two different modalities.

Methods: A retrospective study of electronic medical records was done of patients who underwent CT-guided biopsies and US-guided biopsies for pleural-based lesions between 2005 and 2014 and the data collected were analyzed for comparing the two groups.

Results: A total of 158 patients underwent 162 procedures during the study period. 86 patients underwent 89 procedures in the US group, and 72 patients underwent 73 procedures in the CT group. The overall yield in the US group was 82/89 (92.1%) versus 67/73 (91.8%) in the CT group (P = 1.0). Average days to the procedure was 7.2 versus 17.5 (P = 0.00001) in the US and CT group, respectively. Complication rate was higher in CT group 17/73 (23.3%) versus 1/89 (1.1%) in the US group (P < 0.0001).

Conclusions: For pleural-based lesions the diagnostic accuracy of US guided biopsy is similar to that of CT-guided biopsy, with a lower complication rate and a significantly reduced time to the procedure.
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http://dx.doi.org/10.4103/0970-2113.188961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006326PMC
September 2016

Respiratory rate variability in sleeping adults without obstructive sleep apnea.

Physiol Rep 2016 09;4(17)

Pulmonary, Critical Care and Sleep Medicine Division, The George Washington University MFA, Washington, District of Columbia.

Characterizing respiratory rate variability (RRV) in humans during sleep is challenging, since it requires the analysis of respiratory signals over a period of several hours. These signals are easily distorted by movement and volitional inputs. We applied the method of spectral analysis to the nasal pressure transducer signal in 38 adults with no obstructive sleep apnea, defined by an apnea-hypopnea index <5, who underwent all-night polysomnography (PSG). Our aim was to detect and quantitate RRV during the various sleep stages, including wakefulness. The nasal pressure transducer signal was acquired at 100 Hz and consecutive frequency spectra were generated for the length of the PSG with the Fast Fourier Transform. For each spectrum, we computed the amplitude ratio of the first harmonic peak to the zero frequency peak (H1/DC), and defined as RRV as (100 - H1/DC) %. RRV was greater during wakefulness compared to any sleep stage, including rapid-eye-movement. Furthermore, RRV correlated with the depth of sleep, being lowest during N3. Patients spent most their sleep time supine, but we found no correlation between RRV and body position. There was a correlation between respiratory rate and sleep stage, being greater in wakefulness than in any sleep stage. We conclude that RRV varies according to sleep stage. Moreover, spectral analysis of nasal pressure signal appears to provide a valid measure of RRV during sleep. It remains to be seen if the method can differentiate normal from pathological sleep patterns.
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http://dx.doi.org/10.14814/phy2.12949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027356PMC
September 2016

Upper extremity deep venous thrombosis and pulmonary embolus after ovarian hyperstimulation.

BMJ Case Rep 2016 Aug 16;2016. Epub 2016 Aug 16.

Department of Pulmonary and Critical Care, George Washington University Hospital, Washington, District of Columbia, USA.

A healthy female presented with upper extremity (UE) swelling of several days duration. Admission laboratories were normal except for an elevated D-dimer. An UE ultrasound with Doppler revealed a thrombus in the right subclavian vein. A subsequent chest CT angiogram further characterised the subclavian vein thrombus and also identified a pulmonary embolus. A thorough history and laboratory evaluation showed that her only risk factors were long-time contraceptive pills and a recent cycle of ovarian hyperstimulation (OH) 7 weeks prior to presentation. Anticoagulation treatment was started and the patient's remaining outpatient work-up was negative for all other hereditary causes. A complete anatomic work-up showed bilateral thoracic outlet syndrome (TOS). A review of the literature on the occurrence of upper extremity deep venous thrombosis suggests that these usually occur in the presence of a predisposing factor, including catheters, indwelling devices and active malignancies. OH has been shown to precipitate venous thromboembolism events; however, the diagnosis of bilateral TOS as a predisposing risk factor has not been described in a patient who had recently undergone recent OH and in one who was not actively pregnant.
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http://dx.doi.org/10.1136/bcr-2016-216719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015131PMC
August 2016

Programmed death ligand 1 expression in triple-negative breast cancer is associated with tumour-infiltrating lymphocytes and improved outcome.

Histopathology 2016 Jul 13;69(1):25-34. Epub 2016 Jan 13.

Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.

Aims: Triple-negative breast cancer (TNBC) patients generally have a poor outcome; there is a pressing need to identify more effective therapeutic strategies. Clinical trials targeting programmed death 1/programmed death ligand 1 (PD1/PDL1) in melanoma and non-small-cell lung cancer have reported high response rates, and tumoral PDL1 expression has been suggested as a potential biomarker to enrich for patient response to these treatments. There are only very limited data to date reporting the expression of PDL1 in TNBC.

Methods And Results: PDL1 immunohistochemistry was performed on 161 primary TNBCs and assessed in the tumour as well as immune cells in the stromal compartment. PDL1 expression was very common in TNBC, expressed in the tumour cell membrane (64%), cytoplasm (80%) and stromal (93%) cellular compartments. Cytoplasmic tumoral expression of PDL1 was associated with a lower risk of breast cancer-specific death [hazard ratio (HR) 0.45, P = 0.035] while stromal PDL1 expression was associated with a lower rate of deaths from all causes (HR 0.305, P = 0.0042). Membranous expression of PDL1 was not associated with outcome. While both PDL1 expression and tumour-infiltrating lymphocytes were associated with a better outcome, only lymphovascular invasion and high tumour-infiltrating lymphocytes were independently prognostic for breast cancer-specific death.

Conclusion: While PDL1 expression is frequent in TNBC, it was not independently prognostic. There were differences in outcome depending on the cellular compartment of PDL1 expression. These data provide further impetus for investigating the utility of immune checkpoint therapies in TNBC, given the clinical significance of tumour-infiltrating lymphocytes (TILs) and PDL1 expression in this cohort.
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http://dx.doi.org/10.1111/his.12904DOI Listing
July 2016

Immunization of HIV-1-Infected Persons With Autologous Dendritic Cells Transfected With mRNA Encoding HIV-1 Gag and Nef: Results of a Randomized, Placebo-Controlled Clinical Trial.

J Acquir Immune Defic Syndr 2016 Mar;71(3):246-53

*Massachusetts General Hospital, Division of Infectious Diseases, Boston, MA; †Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA; ‡Biostatistics Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA; §Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) and University of Montreal, Montréal, QC, Canada; ‖Howard Hughes Medical Institute, Chevy Chase, MD; ¶Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY; and #Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.

Background: HIV-1 eradication may require reactivation of latent virus along with stimulation of HIV-1-specific immune responses to clear infected cells. Immunization with autologous dendritic cells (DCs) transfected with viral mRNA is a promising strategy for eliciting HIV-1-specific immune responses. We performed a randomized controlled clinical trial to evaluate the immunogenicity of this approach in HIV-1-infected persons on antiretroviral therapy.

Methods: Fifteen participants were randomized 2:1 to receive intradermal immunization with HIV-1 Gag- and Nef-transfected DCs (vaccine) or mock-transfected DCs (placebo) at weeks 0, 2, 6, and 10. All participants also received DCs pulsed with keyhole limpet hemocyanin (KLH) to assess whether responses to a neo-antigen could be induced.

Results: After immunization, there were no differences in interferon-gamma enzyme-linked immunospot responses to HIV-1 Gag or Nef in the vaccine or placebo group. CD4 proliferative responses to KLH increased 2.4-fold (P = 0.026) and CD8 proliferative responses to KLH increased 2.5-fold (P = 0.053) after vaccination. There were increases in CD4 proliferative responses to HIV-1 Gag (2.5-fold vs. baseline, 3.4-fold vs. placebo, P = 0.054) and HIV-1 Nef (2.3-fold vs. baseline, 6.3-fold vs. placebo, P = 0.009) among vaccine recipients, but these responses were short-lived.

Conclusion: Immunization with DCs transfected with mRNA encoding HIV-1 Gag and Nef did not induce significant interferon-gamma enzyme-linked immunospot responses. There were increases in proliferative responses to HIV-1 antigens and to a neo-antigen, KLH, but the effects were transient. Dendritic cell vaccination should be optimized to elicit stronger and long-lasting immune responses for this strategy to be effective as an HIV-1 therapeutic vaccine.
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http://dx.doi.org/10.1097/QAI.0000000000000852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752409PMC
March 2016

Rodent models and imaging techniques to study liver regeneration.

Eur Surg Res 2015 12;54(3-4):97-113. Epub 2014 Nov 12.

Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany.

The liver has the unique capability of regeneration from various injuries. Different animal models and in vitro methods are used for studying the processes and mechanisms of liver regeneration. Animal models were established either by administration of hepatotoxic chemicals or by surgical approach. The administration of hepatotoxic chemicals results in the death of liver cells and in subsequent hepatic regeneration and tissue repair. Surgery includes partial hepatectomy and portal vein occlusion or diversion: hepatectomy leads to compensatory regeneration of the remnant liver lobe, whereas portal vein occlusion leads to atrophy of the ipsilateral lobe and to compensatory regeneration of the contralateral lobe. Adaptation of modern radiological imaging technologies to the small size of rodents made the visualization of rodent intrahepatic vascular anatomy possible. Advanced knowledge of the detailed intrahepatic 3D anatomy enabled the establishment of refined surgical techniques. The same technology allows the visualization of hepatic vascular regeneration. The development of modern histological image analysis tools improved the quantitative assessment of hepatic regeneration. Novel image analysis tools enable us to quantify reliably and reproducibly the proliferative rate of hepatocytes using whole-slide scans, thus reducing the sampling error. In this review, the refined rodent models and the newly developed imaging technology to study liver regeneration are summarized. This summary helps to integrate the current knowledge of liver regeneration and promises an enormous increase in hepatological knowledge in the near future.
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http://dx.doi.org/10.1159/000368573DOI Listing
November 2015

Associations with low rates of postpartum glucose screening after gestational diabetes among Indigenous and non-Indigenous Australian women.

Aust N Z J Public Health 2015 Feb 6;39(1):69-76. Epub 2014 Nov 6.

Department of Epidemiology and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria; Onemda VicHealth Koori Health Unit, School of Population and Global Health, University of Melbourne, Victoria.

Objectives: To explore factors associated with postpartum glucose screening among women with Gestational Diabetes Mellitus (GDM).

Methods: A retrospective study using linked records from women with GDM who gave birth at Cairns Hospital in Far North Queensland, Australia, from 1 January 2004 to 31 December 2010.

Results: The rates of postpartum Oral Glucose Tolerance Test (OGTT) screening, while having increased significantly among both Indigenous* and non-Indigenous women from 2004 to 2010 (HR 1.15 per year, 95%CI 1.08-1.22, p<0.0001), remain low, particularly among Indigenous women (10% versus 27%, respectively at six months postpartum). Indigenous women in Cairns had a longer time to postpartum OGTT than Indigenous women in remote areas (HR 0.58, 0.38-0.71, p=0.01). Non-Indigenous women had a longer time to postpartum OGTT if they: were born in Australia (HR 0.76, 0.59-1.00, 0.05); were aged <25 years (HR 0.45, 0.23-0.89, p=0.02); had parity >5 (HR 0.33, 0.12-0.90, p=0.03); smoked (HR 0.48, 0.31-0.76, p=0.001); and did not breastfeed (HR 0.09, 0.01-0.64, p=0.02).

Conclusions: Postpartum diabetes screening rates following GDM in Far North Queensland are low, particularly among Indigenous women, with lower rates seen in the regional centre; and among non-Indigenous women with indicators of low socioeconomic status.

Implications: Strategies are urgently needed to improve postpartum diabetes screening after GDM that reach women most at risk.
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http://dx.doi.org/10.1111/1753-6405.12285DOI Listing
February 2015

Lower treatment targets for gestational diabetes: is lower really better?

Med J Aust 2014 Aug;201(4):204-7

Cairns Hospital and Cairns Diabetes Centre, Cairns, QLD, Australia.

Proposed lower diagnostic thresholds and lower treatment targets for gestational diabetes have been controversial internationally. Intervention trials for the recently revised lower Australian treatment targets are currently lacking. While there may be benefits, lowering treatment targets may cause a number of harms including increased risk of hypoglycaemia in pregnant women, greater medicolegal risk for health practitioners, and heavier economic costs for the health system. Regional and remote care providers in particular will have greater costs, and may be overwhelmed in attempts to implement new treatment targets. An excessively glucose-centric focus may divert attention and resources from identifying and addressing other important and growing contributors to adverse pregnancy outcomes, such as obesity. Important groups such as Aboriginal and Torres Strait Islander Australians may not gain overall benefit from lowering treatment targets for gestational diabetes because of current low birthweights and the effect of social costs. It has not yet been established whether implementing lower treatment targets for gestational diabetes will create more benefit than harm. Implementation at this stage is premature.
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http://dx.doi.org/10.5694/mja14.00099DOI Listing
August 2014

Low rates of postpartum glucose screening among indigenous and non-indigenous women in Australia with gestational diabetes.

Matern Child Health J 2015 Mar;19(3):651-63

Global Health and Society Unit, Faculty of Medicine, Nursing and Health Sciences, Monash University, L3/89 Commercial Rd, Prahran, VIC, 3181, Australia,

Women with gestational diabetes have a high risk of type 2 diabetes postpartum, with Indigenous women particularly affected. This study reports postpartum diabetes screening rates among Indigenous and non-Indigenous women with gestational diabetes, in Far North Queensland, Australia. Retrospective study including 1,012 women with gestational diabetes giving birth at a regional hospital from 1/1/2004 to 31/12/2010. Data were linked between hospital records, midwives perinatal data, and laboratory results, then analysed using survival analysis and logistic regression. Indigenous women had significantly longer times to first oral glucose tolerance test (OGTT) [hazards ratio (HR) 0.62, 95 % confidence interval (CI) 0.48-0.79, p < 0.0001) and 'any' postpartum glucose test (HR 0.81, 95 % CI 0.67-0.98, p = 0.03], compared to non-Indigenous women. Postpartum screening rates among all women were low. However, early OGTT screening rates (<6 months) were significantly lower among Indigenous women (13.6 vs. 28.3 %, p < 0.0001), leading to a persistent gap in cumulative postpartum screening rates. By 3 years postpartum, cumulative rates of receiving an OGTT, were 24.6 % (95 % CI 19.9-30.2 %) and 34.1 % (95 % CI 30.6-38.0 %) among Indigenous and non-Indigenous women, respectively. Excluding OGTTs in previous periods, few women received OGTTs at 6-24 months (7.8 vs. 6.7 %) or 2-4 years (5.2 vs. 6.5 %), among Indigenous and non-Indigenous women, respectively. Low rates of postpartum diabetes screening demonstrate that essential 'ongoing management' and 'equity' criteria for population-based screening for gestational diabetes are not being met; particularly among Indigenous women, for whom recent guideline changes have specific implications. Strategies to improve postpartum screening after gestational diabetes are urgently needed.
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http://dx.doi.org/10.1007/s10995-014-1555-3DOI Listing
March 2015

Gestational diabetes mellitus in Far North Queensland, Australia, 2004 to 2010: midwives' perinatal data most accurate source.

Aust N Z J Public Health 2013 Dec;37(6):556-61

Objectives: This study examines the accuracy of Gestational Diabetes Mellitus (GDM) case-ascertainment in routinely collected data.

Methods: Retrospective cohort study analysed routinely collected data from all births at Cairns Base Hospital, Australia, from 1 January 2004 to 31 December 2010 in the Cairns Base Hospital Clinical Coding system (CBHCC) and the Queensland Perinatal Data Collection (QPDC). GDM case ascertainment in the National Diabetes Services Scheme (NDSS) and Cairns Diabetes Centre (CDC) data were compared.

Results: From 2004 to 2010, the specificity of GDM case-ascertainment in the QPDC was 99%. In 2010, only 2 of 225 additional cases were identified from the CDC and CBHCC, suggesting QPDC sensitivity is also over 99%. In comparison, the sensitivity of the CBHCC data was 80% during 2004-2010. The sensitivity of CDC data was 74% in 2010. During 2010, 223 births were coded as GDM in the QPDC, and the NDSS registered 247 women with GDM from the same postcodes, suggesting reasonable uptake on the NDSS register. However, the proportion of Aboriginal and Torres Strait Islander women was lower than expected.

Conclusion: The accuracy of GDM case-ascertainment in the QPDC appears high, with lower accuracy in routinely collected hospital and local health service data. This limits capacity of local data for planning and evaluation, and developing structured systems to improve post-pregnancy care, and may underestimate resources required.

Implications: Data linkage should be considered to improve accuracy of routinely collected local health service data. The accuracy of the NDSS for Aboriginal and Torres Strait Islander women requires further evaluation.
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http://dx.doi.org/10.1111/1753-6405.12148DOI Listing
December 2013

Vitamin D concentrations in pregnant women with diabetes attending for antenatal care in Far North Queensland.

Aust N Z J Obstet Gynaecol 2014 Jun 8;54(3):275-8. Epub 2014 Feb 8.

SMD James Cook University, Cairns, Queensland, Australia.

Serum concentrations of vitamin D were measured in 101 pregnant women with diabetes, both pre-existing and gestational, who attended for antenatal care in Cairns Base Hospital. Eighty-two (81.2%) had sufficient concentrations of vitamin D, 12 (11.9%) had levels indicating insufficiency and 7 (6.9%) were deficient. These findings contrast with those in the general population of pregnant women in the region, among whom 93.1% have been shown to have sufficient levels. The study contributes to the ongoing debate around the need for universal antenatal vitamin D screening in Australia.
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http://dx.doi.org/10.1111/ajo.12176DOI Listing
June 2014

Simultaneous TCR and CD244 signals induce dynamic downmodulation of CD244 on human antiviral T cells.

J Immunol 2013 Sep 2;191(5):2072-81. Epub 2013 Aug 2.

Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Cambridge, MA 02139, USA.

Various cosignaling molecules on T cells can contribute to activation, inhibition, or exhaustion, depending on context. The surface receptor signaling lymphocytic activation molecule (SLAM) family receptor CD244 (2B4/SLAMf4) has been shown to be capable of either inhibitory or enhancing effects upon engagement of its ligand CD48 (SLAMf2). We examined phenotypes of CD8 T cells from HIV(+) and HIV(neg) human donors, specific for HIV and/or respiratory syncytial virus. Cultured and ex vivo CD8 T cells expressed PD-1, CD244, and TIM-3. We found that ex vivo CD8 T cells downregulated CD244 in response to superantigen. Furthermore, cognate peptide induced rapid downregulation of both CD244 and TIM-3, but not PD-1, on CD8 T cell clones. CD244 downmodulation required simultaneous signaling via both TCR and CD244 itself. Using a pH-sensitive fluorophore conjugated to avidin-Ab tetramers, we found that CD244 crosslinking in the presence of TCR signaling resulted in rapid transport of CD244 to an acidic intracellular compartment. Downregulation was not induced by PMA-ionomycin, or prevented by PI3K inhibition, implicating a TCR-proximal signaling mechanism. CD244 internalization occurred within hours of TCR stimulation and required less peptide than was required to induce IFN-γ production. The degree of CD244 internalization varied among cultured CD8 T cell lines of different specificities, and correlated with the enhancement of IFN-γ production in response to CD48 blockade in HIV(+), but not HIV(neg), subjects. Our results indicate that rapid CD244 internalization is induced by a two-signal mechanism and plays a role in modulation of antiviral CD8 T cell responses by CD48-CD244 signaling.
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http://dx.doi.org/10.4049/jimmunol.1300435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777852PMC
September 2013

A threefold increase in gestational diabetes over two years: review of screening practices and pregnancy outcomes in Indigenous women of Cape York, Australia.

Aust N Z J Obstet Gynaecol 2013 Aug 8;53(4):363-8. Epub 2013 Mar 8.

Cairns Diabetes Centre, Cairns Base Hospital, Cairns, Queensland, Australia.

Background: Australian Aboriginal women have a high prevalence of type 2 diabetes (T2DM) in pregnancy and gestational diabetes (GDM).

Aims: To review how screening practice affects the pregnancy data of all Indigenous women and their newborns living in Cape York, Queensland.

Methods: All medical charts of mothers and their neonates delivered in the regional hospital over two-one-year periods (2006 and 2008) were reviewed. Universal testing with an oral glucose tolerance test (OGTT) was introduced in 2007.

Results: Gestational diabetes (GDM) increased from 4.7 to 14.2%, and T2DM was similar (2.4 and 2.3%). There were 127 deliveries in 2006 and 134 in 2008. Testing rates with OGTT improved from 31.4% in 2006 to 65.6% in 2008. Mothers with diabetes in pregnancy (DIP) were older and heavier than non-DIP mothers. Caesarean section rates were significantly higher in the DIP group compared with the non-DIP group (66 vs 25%) in both time periods. The booking weight of DIP mothers decreased 16 kg, their babies normalised their weight, length and head circumference; respiratory distress and Apgar scores improved comparing the two periods. In DIP, infants >40% had hypoglycaemia; however, rates of serious complications were low. Rates of breastfeeding were similar between groups. Follow-up rates for GDM improved from 16.6% in 2006 to 31.6% in 2008. Of those tested one-third were diagnosed with T2DM.

Conclusion: The rate of GDM tripled after implementation of universal testing. Outcomes improved. There is still need for improvement in testing and follow-up practices in relation to DIP.
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http://dx.doi.org/10.1111/ajo.12042DOI Listing
August 2013

Therapeutic targets in triple negative breast cancer.

J Clin Pathol 2013 Jun 22;66(6):530-42. Epub 2013 Feb 22.

Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.

Outcomes have improved significantly for many women diagnosed with breast cancer. For the heterogeneous group of tumours lacking expression of the oestrogen, progesterone and HER2 receptors, 'triple negative' breast cancers (TNBC), the prognosis overall has remained quite poor. When TNBC recurs, there is often little response to chemotherapy, and there are a few treatment options in this setting. Thus, there is an urgent clinical need to identify new therapeutic targets in order to improve the outlook for these patients. This review highlights the most promising therapeutic targets identified through new sequencing technologies, as well as through studies of apoptosis. We also present mounting evidence that the developmental signalling pathways Wnt/β-catenin, NOTCH and Hedgehog play an important role in the pathogenesis and progression of TNBC with new therapeutic approaches inhibiting these pathways in advanced preclinical studies or early clinical trials.
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http://dx.doi.org/10.1136/jclinpath-2012-201361DOI Listing
June 2013

Extreme diabetic lipaemia associated with a novel lipoprotein lipase gene mutation.

Clin Chim Acta 2009 Aug 15;406(1-2):167-9. Epub 2009 May 15.

Southern Adelaide Diabetes and Endocrine Services, Southern Adelaide Health Services, Adelaide, Australia.

Diabetic lipaemia, severe hypertriglyceridaemia associated with diabetic ketoacidosis, is a well recognised, but rare condition. Why this occurs in some patients and not others is unknown. We report a case of extreme lipaemia in a 20-year-old woman with type 1 diabetes who presented to hospital with diabetic ketoacidosis (DKA). At admission the patient's blood was grossly lipaemic and plasma lipid analyses showed triglyceride and cholesterol concentrations of 379 mmol/L and 52 mmol/L, respectively. She had no peripheral stigmata of chronic hyperlipidaemia and 1 year previously her plasma triglyceride and total cholesterol concentrations were 2.5 mmol/L and 4.4 mmol/L respectively. She was treated with insulin and the hypertriglyceridaemia resolved over several days. Because of the marked hypertriglyceridaemia, lipoprotein lipase (LPL) genetic testing was performed. Sequencing of the LPL gene revealed that she was heterozygous for the common S447X LPL variant and heterozygous for a novel missense mutation in exon five (I225N). Ile(225) is highly conserved among species and this mutation is predicted to impair function of the mature LPL protein. We conclude that heterozygosity for LPL mutations may predispose to transient severe hypertriglyceridaemia, when combined with insulin deficiency.
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http://dx.doi.org/10.1016/j.cca.2009.05.003DOI Listing
August 2009

Severe systemic lupus erythematosus induced by antiviral treatment for hepatitis C.

J Clin Rheumatol 2008 Jun;14(3):166-8

School of Medicine, James Cook University, Queensland, Australia.

We report the case of a 43-year-old man who developed systemic lupus erythematosus (SLE) after receiving pegylated alpha-interferon and ribavirin for chronic hepatitis C. He displayed 8 features of the American College of Rheumatology criteria for SLE: glomerulonephritis, arthritis, serositis, a florid discoid rash, lymphopenia, oral ulcers, the development of high titers of antinuclear antibodies, and antidouble stranded DNA antibodies. Furthermore, his admission was complicated by the development of life threatening myopericarditis and vasculitis. This case is notable for the clinical severity and nature of multiorgan lupus involvement from hepatitis C antiviral therapy. Clinical signs of SLE have resolved and anti DS DNA has normalized.
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http://dx.doi.org/10.1097/RHU.0b013e3181775e80DOI Listing
June 2008

Experience with cardiac valve operations in Cape York Peninsula and the Torres Strait Islands, Australia.

Med J Aust 2007 Jun;186(11):560-3

Department of Cardiology, Cairns Base Hospital, Cairns, QLD.

Objective: To describe the outcome of valve surgery, for rheumatic heart disease (RHD) and non-RHD, in residents of Cape York Peninsula and the Torres Strait Islands referred to the Cairns Base Hospital specialist outreach service.

Design And Participants: Retrospective review of medical records on all patients residing in the outreach area who had surgery for valvular heart disease between 1 January 1992 and 31 December 2004.

Main Outcome Measures: Operation type and perioperative characteristics; 5- and 10-year survival rates; reoperation rates; complications.

Results: Forty-seven patients met the selection criteria; the median age was 40 years (range, 4-76 years); and 39 patients were Indigenous. RHD was the predominant cause of valve dysfunction (30/47 patients). Thirty-seven patients had valve replacements, six had valve repair and four had balloon valvotomy as the initial procedure. There were three bleeding complications, two episodes of operated valve endocarditis, and six embolic complications. There were nine valve-related deaths (six in the first 5 years). At 5 years, all seven patients who had had valve repair or balloon valvotomy were alive. Seven of the 47 patients required reoperation. Survival analysis showed freedom from valve-related deaths to be 83% (95% CI, 66%-92%) at 5 years and 61% (95% CI, 33%-80%) at 10 years. Freedom from reoperation at 5 years was 88% (95% CI, 71%-95%). Among the 30 patients with RHD, freedom from valve-related death was 80% (95% CI, 60%-92%) at 5 years and 52% (95% CI, 21%-75%) at 10 years. In patients with RHD, freedom from reoperation at 5 years was 87% (95% CI, 65%-96%).

Conclusion: Valvular heart disease results in substantial morbidity and mortality, despite intervention. Efforts need to focus on prevention of rheumatic fever and closer follow-up.
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http://dx.doi.org/10.5694/j.1326-5377.2007.tb01053.xDOI Listing
June 2007
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