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1.
ESMO Open ; 7(2): 100445, 2022 04.
Article in English | MEDLINE | ID: mdl-35398717

ABSTRACT

INTRODUCTION: Pembrolizumab is an established first-line option for patients with advanced non-small-cell lung cancer (NSCLC) expressing programmed death-ligand 1 ≥50%. Durable responses are seen in a subset of patients; however, many derive little clinical benefit. Biomarkers of the systemic inflammatory response predict survival in NSCLC. We evaluated their prognostic significance in patients receiving first-line pembrolizumab for advanced NSCLC. METHODS: Patients treated with first-line pembrolizumab for advanced NSCLC with programmed death-ligand 1 expression ≥50% at two regional Scottish cancer centres were identified. Pretreatment inflammatory biomarkers (white cell count, neutrophil count, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, albumin, prognostic nutritional index) were recorded. The relationship between these and progression-free survival (PFS) and overall survival (OS) were examined. RESULTS: Data were available for 219 patients. On multivariate analysis, albumin and neutrophil count were independently associated with PFS (P < 0.001, P = 0.002, respectively) and OS (both P < 0.001). A simple score combining these biomarkers was explored. The Scottish Inflammatory Prognostic Score (SIPS) assigned 1 point each for albumin <35 g/l and neutrophil count >7.5 × 109/l to give a three-tier categorical score. SIPS predicted PFS [hazard ratio 2.06, 95% confidence interval (CI) 1.68-2.52 (P < 0.001)] and OS [hazard ratio 2.33, 95% CI 1.86-2.92 (P < 0.001)]. It stratified PFS from 2.5 (SIPS2), to 8.7 (SIPS1) to 17.9 months (SIPS0) (P < 0.001) and OS from 5.1 (SIPS2), to 12.4 (SIPS1) to 28.7 months (SIPS0) (P < 0.001). The relative risk of death before 6 months was 2.96 (95% CI 1.98-4.42) in patients with SIPS2 compared with those with SIPS0-1 (P < 0.001). CONCLUSIONS: SIPS, a simple score combining albumin and neutrophil count, predicts survival in patients with NSCLC receiving first-line pembrolizumab. Unlike many proposed prognostic scores, SIPS uses only routinely collected pretreatment test results and provides a categorical score. It stratifies survival across clinically meaningful time periods that may assist clinicians and patients with treatment decisions. We advocate validation of the prognostic utility of SIPS in this and other immune checkpoint inhibitor treatment settings.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Albumins/therapeutic use , Biomarkers , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Immune Checkpoint Inhibitors , Inflammation/drug therapy , Lung Neoplasms/drug therapy
2.
JDR Clin Trans Res ; 7(1): 16-24, 2022 Jan.
Article in English | MEDLINE | ID: mdl-33323035

ABSTRACT

BACKGROUND: For health care services to address the health care needs of populations and respond to changes in needs over time, workforces must be planned. This requires quantitative models to estimate future workforce requirements that take account of population size, oral health needs, evidence-based approaches to addressing needs, and methods of service provision that maximize productivity. The aim of this scoping review was to assess whether and how these 4 elements contribute to existing models of oral health workforce planning. METHODS: A scoping review was conducted. MEDLINE, Embase, HMIC, and EconLit were searched, all via OVID. Additionally, gray literature databases were searched and key bodies and policy makers contacted. Workforce planning models were included if they projected workforce numbers and were specific to oral health. No limits were placed on country. A single reviewer completed initial screening of abstracts; 2 independent reviewers completed secondary screening and data extraction. A narrative synthesis was conducted. RESULTS: A total of 4,009 records were screened, resulting in 42 included articles detailing 47 models. The workforce planning models varied significantly in their use of data on oral health needs, evidence-based services, and provider productivity, with most models relying on observed levels of service utilization and demand. CONCLUSIONS: This review has identified quantitative workforce planning models that aim to estimate future workforce requirements. Approaches to planning the oral health workforce are not always based on deriving workforce requirements from population oral health needs. In many cases, requirements are not linked to population needs, while in models where needs are included, they are constrained by the existence and availability of the required data. It is critical that information systems be developed to effectively capture data necessary to plan future oral health care workforces in ways that relate directly to the needs of the populations being served. KNOWLEDGE TRANSFER STATEMENT: Policy makers can use the results of this study when making decisions about the planning of oral health care workforces and about the data to routinely collect within health services. Collection of suitable data will allow for the continual improvement of workforce planning, leading to a responsive health service and likely future cost savings.


Subject(s)
Health Workforce , Oral Health , Delivery of Health Care , Health Planning , Workforce
3.
Leukemia ; 34(7): 1775-1786, 2020 07.
Article in English | MEDLINE | ID: mdl-31925317

ABSTRACT

In chronic-phase chronic myeloid leukaemia (CP-CML), residual BCR-ABL1+ leukaemia stem cells are responsible for disease persistence despite TKI. Based on in vitro data, CHOICES (CHlorOquine and Imatinib Combination to Eliminate Stem cells) was an international, randomised phase II trial designed to study the safety and efficacy of imatinib (IM) and hydroxychloroquine (HCQ) compared with IM alone in CP-CML patients in major cytogenetic remission with residual disease detectable by qPCR. Sixty-two patients were randomly assigned to either arm. Treatment 'successes' was the primary end point, defined as ≥0.5 log reduction in 12-month qPCR level from trial entry. Selected secondary study end points were 24-month treatment 'successes', molecular response and progression at 12 and 24 months, comparison of IM levels, and achievement of blood HCQ levels >2000 ng/ml. At 12 months, there was no difference in 'success' rate (p = 0.58); MMR was achieved in 80% (IM) vs 92% (IM/HCQ) (p = 0.21). At 24 months, the 'success' rate was 20.8% higher with IM/HCQ (p = 0.059). No patients progressed. Seventeen serious adverse events, including four serious adverse reactions, were reported; diarrhoea occurred more frequently with combination. IM/HCQ is tolerable in CP-CML, with modest improvement in qPCR levels at 12 and 24 months, suggesting autophagy inhibition maybe of clinical value in CP-CML.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cytogenetic Analysis/methods , Fusion Proteins, bcr-abl/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Aged , Female , Follow-Up Studies , Humans , Hydroxychloroquine/administration & dosage , Imatinib Mesylate/administration & dosage , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate
4.
Eur Arch Paediatr Dent ; 21(3): 329-337, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31728914

ABSTRACT

INTRODUCTION: Inflammatory collateral cysts are uncommon cysts primarily affecting first permanent molars during their eruption. There are diagnostic challenges that can be overcome with CBCT imaging. However, given the paediatric age group for this condition, there are patient cooperation and radiation dose factors to consider when justifying the scan. The aim of this case series study is to illustrate the value of CBCT in imaging and diagnosing inflammatory collateral cysts in paediatric patients, to highlight the need for a multidisciplinary approach for this uncommon pathological condition and to review the relevant literature. CASE SERIES DESCRIPTION AND RESULTS: We present three patients aged between 6 and 11 years of age with inflammatory collateral cysts affecting their first or second permanent molars for which CBCT imaging was utilised. All patients underwent cyst enucleation with preservation or extraction of affected teeth under general anaesthesia. DISCUSSION: Inflammatory collateral cysts are likely to be under reported given their indistinct clinical features and radiological signs. Conventional planar radiographs may not reveal this lesions size and full extent. CBCT overcomes these limitations; however, careful assessment of patient cooperation is needed and a low-dose protocol should be used. CONCLUSIONS: CBCT can provide useful imaging information which is difficult to obtain using conventional radiography, especially in cases where an inflammatory collateral cyst is suspected.


Subject(s)
Cysts , Spiral Cone-Beam Computed Tomography , Child , Cone-Beam Computed Tomography , Humans , Molar , Retrospective Studies
5.
Ann R Coll Surg Engl ; 100(3): 209-215, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29364010

ABSTRACT

Introduction The National Institute for Health and Care Excellence guidance Improving Supportive and Palliative Care for Adults with Cancer (2004) and the Cancer Reform Strategy (2007) support the premise that assessment and discussion of patients' needs for physical, social, psychological, and spiritual wellbeing should be undertaken during oncology follow-up. We report the use of the Patient Concerns Inventory in a routine head and neck cancer clinic setting over a seven-year period, summarising the number of available clinics, the number of patients completing the inventory within a clinic, the range of clinical characteristics and the concerns they wanted to discuss. Methods The data were analysed from oncology follow-up clinics between 1 August 2007 and 10 December 2014. Audit approval was given by the Clinical Audit Department, University Hospital Aintree. Results There were 386 patients with 1198 inventories completed at 220 clinics, median 6 (range 4-7) per clinic. The most common concerns raised by patients across all the clinic consultations were dry mouth (34%), fear of recurrence (33%), sore mouth (26%), dental health (25%), chewing (22%) and fatigue/tiredness (21%). Conclusions The incorporation of the Patient Concerns Inventory as part of routine oncology clinics allows for a more patient initiated and focused consultation available to the majority of patients throughout their follow-up. The inventory allows for greater opportunity to provide holistic targeted multiprofessional intervention and support.


Subject(s)
Aftercare/methods , Mouth Neoplasms/therapy , Oropharyngeal Neoplasms/therapy , Patient Reported Outcome Measures , Adult , Aged , Attitude to Health , Clinical Audit , Diagnosis-Related Groups , Female , Holistic Health , Humans , Male , Middle Aged , Mouth Neoplasms/complications , Mouth Neoplasms/psychology , Needs Assessment , Oropharyngeal Neoplasms/complications , Oropharyngeal Neoplasms/psychology , Professional-Patient Relations , Quality of Life
6.
Australas Phys Eng Sci Med ; 40(3): 491-543, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28914430

ABSTRACT

In 2001 the ACPSEM published a position paper on quality assurance in screen film mammography which was subsequently adopted as a basis for the quality assurance programs of both the Royal Australian and New Zealand College of Radiologists (RANZCR) and of BreastScreen Australia. Since then the clinical implementation of digital mammography has been realised and it has become evident that existing screen-film protocols were not appropriate to assure the required image quality needed for reliable diagnosis or to address the new dose implications resulting from digital technology. In addition, the advantages and responsibilities inherent in teleradiology are most critical in mammography and also need to be addressed. The current document is the result of a review of current overseas practice and local experience in these areas. At this time the technology of digital imaging is undergoing significant development and there is still a lack of full international consensus about some of the detailed quality control (QC) tests that should be included in quality assurance (QA) programs. This document describes the current status in digital mammography QA and recommends test procedures that may be suitable in the Australasian environment. For completeness, this document also includes a review of the QA programs required for the various types of digital biopsy units used in mammography. In the future, international harmonisation of digital quality assurance in mammography and changes in the technology may require a review of this document. Version 2.0 represented the first of these updates and key changes related to image quality evaluation, ghost image evaluation and interpretation of signal to noise ratio measurements. In Version 3.0 some significant changes, made in light of further experience gained in testing digital mammography equipment were introduced. In Version 4.0, further changes have been made, most notably digital breast tomosynthesis (DBT) testing and QC have been addressed. Some additional testing for conventional projection imaging has been added in order that sites may have the capability to undertake dose surveys to confirm compliance with diagnostic reference levels (DRLs) that may be established at the National or State level. A key recommendation is that dosimetry calculations are now to be undertaken using the methodology of Dance et al. Some minor changes to existing facility QC tests have been made to ensure the suggested procedures align with those most recently adopted by the Royal Australian and New Zealand College of Radiologists and BreastScreen Australia. Future updates of this document may be provided as deemed necessary in electronic format on the ACPSEM's website ( https://www.acpsem.org.au/whatacpsemdoes/standards-position-papers and see also http://www.ranzcr.edu.au/quality-a-safety/radiology/practice-quality-activities/mqap ).


Subject(s)
Mammography/standards , Quality Assurance, Health Care , Biopsy , Humans , Quality Control
7.
J R Coll Physicians Edinb ; 47(2): 164-167, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28675192

ABSTRACT

Background Tablet computers have emerged as a tool to capture, process and store data in examinations, yet evidence relating to their acceptability and usefulness in assessment is limited. Methods We performed an observational study to explore opinions and attitudes relating to tablet computer use in recording performance in a final year objective structured clinical examination at a single UK medical school. Examiners completed a short questionnaire encompassing background, forced-choice and open questions. Forced choice questions were analysed using descriptive statistics and open questions by framework analysis. Results Ninety-two (97% response rate) examiners completed the questionnaire of whom 85% had previous use of tablet computers. Ninety per cent felt checklist mark allocation was 'very/quite easy', while approximately half considered recording 'free-type' comments was 'easy/very easy'. Greater overall efficiency of marking and resource savings were considered the main advantages of tablet computers, while concerns relating to technological failure and ability to record free type comments were raised. Discussion In a context where examiners were familiar with tablet computers, they were preferred to paper checklists, although concerns were raised. This study adds to the limited literature underpinning the use of electronic devices as acceptable tools in objective structured clinical examinations.


Subject(s)
Attitude to Computers , Computers, Handheld , Education, Medical/methods , Educational Measurement/methods , Faculty, Medical/psychology , Students, Medical/psychology , Adult , Aged , Female , Humans , Male , Middle Aged , Surveys and Questionnaires , United Kingdom
8.
Heredity (Edinb) ; 118(3): 284-292, 2017 03.
Article in English | MEDLINE | ID: mdl-27731327

ABSTRACT

Theory predicts unified sex ratios for most organisms, yet biases may be engendered by selfish genetic elements such as endosymbionts that kill or feminize individuals with male genotypes. Although rare, feminization is established for Wolbachia-infected Eurema butterflies. This paradigm is presently confined to islands in the southern Japanese archipelago, where feminized phenotypes produce viable all-daughter broods. Here, we characterize sex bias for E. hecabe in continental Australia. Starting with 186 wild-caught females, we reared >6000 F1-F3 progeny in pedigree designs that incorporated selective antibiotic treatments. F1 generations expressed a consistent bias across 2 years and populations that was driven by an ~5% incidence of broods comprising ⩾80% daughters. Females from biased lineages continued to overproduce daughters over two generations of outcrossing to wild males. Treatment with antibiotics of differential strength influenced sex ratio only in biased lineages by inducing an equivalent incomplete degree of son overproduction. Brood sex ratios were nevertheless highly variable within lineages and across generations. Intriguingly, the cytogenetic signature of female karyotype was uniformly absent, even among phenotypic females in unbiased lineages. Molecular evidence supported the existence of a single Wolbachia strain at high prevalence, yet this was not clearly linked to brood sex bias. In sum, we establish an inherited, experimentally reversible tendency for incomplete offspring bias. Key features of our findings clearly depart from the Japanese feminization paradigm and highlight the potential for more subtle degrees of sex distortion in arthropods.


Subject(s)
Butterflies/genetics , Sex Ratio , Animals , Australia , Butterflies/microbiology , Female , Male , Pedigree , Wolbachia
9.
Frontline Gastroenterol ; 6(3): 156-160, 2015 Jul.
Article in English | MEDLINE | ID: mdl-28839805

ABSTRACT

OBJECTIVE: Faecal calprotectin (FC) is a non-invasive marker used to differentiate irritable bowel syndrome from inflammatory bowel disease (IBD). However, false positives are common. We sought to determine the diagnostic yield of investigation in patients presenting with new lower gastrointestinal (GI) symptoms and a mildly elevated FC (100-200 µg/g). DESIGN: Retrospective study of electronic patient records. PATIENTS: Patients aged 16-50 years with new lower GI symptoms and an FC 100-200 µg/g were identified from our biochemistry laboratory database between September 2009 and 2011. Patients were excluded if they had a previous FC >200 µg/g, were taking non-steroidal anti-inflammatory drugs (NSAIDs), had IBD, positive stool cultures or 'alarm' symptoms. SETTING: Secondary care gastroenterology clinics. RESULTS: 161 patients (103 female patients) were identified. Mean age was 37.3 years with a mean FC of 147 µg/g. 398 endoscopic, radiological and histological investigations were undertaken in 141 patients (an average of 2.8 investigations per patient). 131 colonoscopies were performed with abnormalities in only 24 (18.3%). In patients with a macroscopically normal upper GI endoscopy and colonoscopy, the diagnostic yield of any further investigation was only 7.3%. The negative predictive value (NPV) of an FC 100-200 µg/g was 86.7% for any pathology and 97.5% for significant luminal pathology (IBD, advanced adenoma or colorectal carcinoma). After a mean follow-up of 172.4 weeks, IBD was the final diagnosis in only 4 (2.5%) of patients. CONCLUSIONS: In adult patients under 50 years old presenting with new lower GI symptoms, the NPV of an FC between 100 and 200 µg/g in excluding significant organic GI disease is high.

10.
J Fish Biol ; 82(4): 1211-25, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23557300

ABSTRACT

Sagittal otoliths were used to age the samples of Tilapia mariae collected from a coastal river and an impoundment. Validation of sagittae checks was achieved using both quantitative marginal increment analysis and by tetracycline marking of the otoliths of fish kept in tanks and in a farm dam. The annulus pattern on the otoliths was generally clear and their formation appeared to be temperature related and largely completed in the Austral spring around September and October. Male T. mariae grow faster and larger than females and the maximum ages of fish from the coastal river and impoundment was 9+ and 4+ years, respectively. Past fish surveys and the absence of older age classes in the impoundment population would suggest that this population was only very recently established.


Subject(s)
Otolithic Membrane/growth & development , Tilapia/growth & development , Animals , Body Size , Female , Introduced Species , Male , Population Dynamics , Queensland , Rivers
11.
Neuropsychopharmacology ; 38(6): 1060-7, 2013 May.
Article in English | MEDLINE | ID: mdl-23303071

ABSTRACT

Xanthurenic acid (XA), an endogenous kynurenine, is a known vesicular glutamate transport (VGLUT) inhibitor and has also been proposed as an mGlu2/3 receptor agonist. Changes in these systems have been implicated in the pathophysiology of schizophrenia and other psychiatric disorders; however, little is known of how XA affects synaptic transmission. We therefore investigated the effects of XA on synaptic transmission at two hippocampal glutamatergic pathways and evaluated the ability of XA to bind to mGlu2/3 receptors. Field excitatory postsynaptic potentials (fEPSPs) were recorded from either the dentate gyrus (DG) or CA1 region of mouse hippocampal slices in vitro. Addition of XA to the bathing medium (1-10 mM) resulted in a dose-related reduction of fEPSP amplitudes (up to 52% reduction) in both hippocampal regions. In the DG, the VGLUT inhibitors Congo Red and Rose Bengal, and the mGlu2/3 agonist LY354740, also reduced fEPSPs (up to 80% reduction). The mGlu2/3 antagonist LY341495 reversed the LY354740 effect, but not the XA effect. LY354740, but not XA, also reduced DG paired-pulse depression. XA had no effect on specific binding of 1 nM [(3)H]LY341495 to membranes with human mGlu2 receptors. We conclude that XA can modulate synaptic transmission via a mechanism that may involve VGLUT inhibition rather than activation of mGlu2/3 receptors. This could be important in the pathophysiology of nervous system disorders including schizophrenia and might represent a target for developing novel pharmacological therapies.


Subject(s)
Hippocampus/metabolism , Kynurenine/physiology , Synaptic Transmission/physiology , Vesicular Glutamate Transport Proteins/antagonists & inhibitors , Vesicular Glutamate Transport Proteins/physiology , Xanthurenates/pharmacology , Animals , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , Hippocampus/drug effects , Humans , Mice , Mice, Inbred C57BL , Organ Culture Techniques , Signal Transduction/drug effects , Signal Transduction/physiology , Synaptic Transmission/drug effects
12.
J Fish Biol ; 80(6): 2176-97, 2012 May.
Article in English | MEDLINE | ID: mdl-22551176

ABSTRACT

The reproductive biology of two invasive tilapia species, Oreochromis mossambicus and Tilapia mariae, resident in freshwater habitats in north-eastern Australia was investigated. Oreochromis mossambicus exhibited plasticity in some of its life-history characteristics that enhanced its ability to occupy a range of habitats. These included a shallow, weed-choked, freshwater coastal drain that was subject to temperature and dissolved oxygen extremes and water-level fluctuations to cooler, relatively high-altitude impoundments. Adaptations to harsher conditions included a decreased total length (L(T) ) and age (A) at 50% maturity (m50), short somatic growth intervals, early maturation and higher relative fecundities. Potential fecundity in both species was relatively low, but parental care ensured high survival rates of both eggs and larvae. No significant difference in the relative fecundity of T. mariae populations in a large impoundment and a coastal river was found, but there were significant differences in relative fecundities between several of the O. mossambicus populations sampled. Total length (L(T) ) and age at 50% maturity of O. mossambicus populations varied considerably depending on habitat. The L(Tm50) and A(m50) values for male and female O. mossambicus in a large impoundment were considerably greater than for those resident in a small coastal drain. Monthly gonad developmental stages and gonado-somatic indices suggested that in coastal areas, spawning of O. mossambicus and T. mariae occurred throughout most of the year while in cooler, high-altitude impoundments, spawning peaked in the warmer, summer months. The contribution these reproductive characteristics make to the success of both species as colonizers is discussed in the context of future control and management options for tilapia incursions in Australia.


Subject(s)
Reproduction , Tilapia/physiology , Animals , Australia , Body Size , Female , Male , Seasons , Sex Ratio , Sexual Maturation
14.
Arch Dis Child ; 93(4): 307-12, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18356383

ABSTRACT

OBJECTIVES: To compare clinical practice guideline (CPG) recommendations and reported physician management of acute paediatric asthma in the 11 largest paediatric emergency departments, all of which have CPGs, in Australia (n = 9) and New Zealand (n = 2). All 11 sites participate in the Paediatric Research in Emergency Departments International Collaborative (PREDICT) research network. METHODS: (a) A review of CPGs for acute childhood asthma from all PREDICT sites. (b) A standardised anonymous survey of senior emergency doctors at PREDICT sites investigating management of acute childhood asthma. RESULTS: CPGs for mild to moderate asthma were similar across sites and based on salbutamol delivery by metered dose inhaler with spacer and oral prednisolone. In severe to critical asthma, differences between sites were common and related to recommendations for: ipratropium use; metered-dose inhaler versus nebulised delivery of salbutamol in severe asthma; use of intravenous aminophylline, intravenous magnesium and dosing of intravenous salbutamol in critical asthma. The questionnaire (78 of 83 doctors responded) also revealed significant differences between doctors in the treatment of moderate to severe asthma. Ipratropium was used for moderate asthma by 42%. For severe to critical asthma, nebulised delivery of salbutamol was preferred by 79% of doctors over metered dose inhalers. For critical asthma, doctors reported using intravenous aminophylline in 45%, intravenous magnesium in 55%, and intravenous salbutamol in 87% of cases. Thirty-nine different dosing regimens for intravenous salbutamol were reported. CONCLUSIONS: CPG recommendations and reported physician practice for mild to moderate paediatric asthma management were broadly similar across PREDICT sites and consistent with national guidelines. Practice was highly variable for severe to critical asthma and probably reflects limitations of available evidence. Areas of controversy, in particular the comparative efficacy of intravenous bronchodilators, would benefit from multi-centre trials. Collaborative development of CPGs should be considered.


Subject(s)
Anti-Asthmatic Agents/administration & dosage , Asthma/drug therapy , Practice Patterns, Physicians'/statistics & numerical data , Acute Disease , Albuterol/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Australia , Child , Drug Therapy, Combination , Female , Guideline Adherence/statistics & numerical data , Health Care Surveys , Humans , Male , Metered Dose Inhalers , New Zealand , Practice Guidelines as Topic , Prednisolone/administration & dosage , Severity of Illness Index
15.
J Neuroendocrinol ; 19(11): 891-900, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17927667

ABSTRACT

The activity of the hypothalamic-pituitary-adrenal (HPA) axis is characterised both by an ultradian pulsatile pattern of glucocorticoid secretion and an endogenous diurnal rhythm. Glucocorticoid feedback plays a major role in regulating HPA axis activity and this mechanism occurs via two different receptors: mineralocorticoid (MR) and glucocorticoid receptors (GR). In the present study, the effects of both acute and subchronic treatment with the GR antagonist Org 34850 on basal and stress-induced HPA axis activity in male rats were evaluated. To investigate the effect of Org 34850 on basal diurnal corticosterone rhythm over the 24-h cycle, an automated blood sampling system collected samples every 10 min. Acute injection of Org 34850 (10 mg/kg, s.c.) did not affect basal or stress-induced corticosterone secretion, but was able to antagonise the inhibitory effect of the glucocorticoid agonist methylprednisolone on stress-induced corticosterone secretion. However, 5 days of treatment with Org 34850 (10 mg/kg, s.c., two times a day), compared to rats treated with vehicle (5% mulgofen in 0.9% saline, 1 ml/kg, s.c.), increased corticosterone secretion over the 24-h cycle and resulted in changes in the pulsatile pattern of hormone release, but had no significant effect on adrenocorticotrophic hormone secretion or on stress-induced corticosterone secretion. Subchronic treatment with Org 34850 did not alter GR mRNA expression in the hippocampus, paraventricular nucleus of the hypothalamus or anterior-pituitary, or MR mRNA expression in the hippocampus. Our data suggest that a prolonged blockade of GRs is required to increase basal HPA axis activity. The changes observed here with ORG 34850 are consistent with inhibition of GR-mediated negative feedback of the HPA axis. In light of the evidence showing an involvement of dysfunctional HPA axis in the pathophysiology of depression, Org 34850 could be a potential treatment for mood disorders.


Subject(s)
Corticosterone/metabolism , Receptors, Glucocorticoid/antagonists & inhibitors , Steroids/metabolism , Stress, Psychological , Sulfones/metabolism , Adrenocorticotropic Hormone/metabolism , Animals , Circadian Rhythm/drug effects , Circadian Rhythm/physiology , Hypothalamo-Hypophyseal System/drug effects , Hypothalamo-Hypophyseal System/physiology , In Situ Hybridization , Male , Pituitary-Adrenal System/drug effects , Pituitary-Adrenal System/physiology , Rats , Rats, Sprague-Dawley , Steroids/pharmacology , Sulfones/pharmacology
16.
Australas Phys Eng Sci Med ; 30(2): 65-100, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17682397

ABSTRACT

In 2001 the ACPSEM published a position paper on quality assurance in screen film mammography which was subsequently adopted as a basis for the quality assurance programs of both the Royal Australian and New Zealand College of Radiologists (RANZCR) and of BreastScreen Australia. Since then the clinical implementation of digital mammography has been realised and it has become evident that existing screen-film protocols were not appropriate to assure the required image quality needed for reliable diagnosis or to address the new dose implications resulting from digital technology. In addition, the advantages and responsibilities inherent in teleradiology are most critical in mammography and also need to be addressed. The current document is the result of a review of current overseas practice and local experience in these areas. At this time the technology of digital imaging is undergoing significant development and there is still a lack of full international consensus about some of the detailed Quality Control tests that should be included in quality assurance (QA) programs. This document describes the current status in digital mammography QA and recommends test procedures that may be suitable in the Australasian environment. For completeness, this document also includes a review of the QA programs required for the various types of digital biopsy units used in mammography. In the future, international harmonisation of digital quality assurance in mammography and changes in the technology may require a review of this document. Accordingly, updates of this document will be provided as deemed necessary in electronic format on the ACPSEM's website (see http://www.acpsem.org.au/au/subgroup/radiology/RadiologySG_index.html).


Subject(s)
Mammography/instrumentation , Mammography/standards , Quality Assurance, Health Care , Australia , Biopsy , Humans , New Zealand
17.
Australas Phys Eng Sci Med ; 29(3): 251-6, 2006 Sep.
Article in English | MEDLINE | ID: mdl-17058586

ABSTRACT

There are obvious differences in the automatic selection of kVp, anode, and filter between a digital mammography system and the equivalent film/screen system for the same thickness of PMMA absorber. To investigate the reason for these changes, a large number of images were acquired using 2, 4, 6, and 8 cm thick PMMA absorbing slabs, and various combinations of kVp, mAs, anode, and filter. The SNR and CNR were calculated using two different contrast test objects and plotted as a function of AGD. The results can be summarized as follows: 1) For any given AGD with 4, 6, and 8 cm thick PMMA absorbers, SNR(Rh/Rh) > SNR(Mo/Rh) > SNR(Mo/Mo), 2) For any given AGD: At 4 cm thickness, CNR(Mo/Mo) > CNR(Mo/Rh) > CNR(Rh/Rh), At 6 cm thickness, CNR(Rh/Rh) approximately CNR(Mo/Rh) > CNR(Mo/Mo), At 8 cm thickness, CNR(Rh/Rh) > CNR(Mo/Rh), 3) For any given absorber thickness and target/filter combination, CNR is approximately proportional to SNR, 4) For any given absorber thickness and target/filter combination, SNR (and hence CNR) is approximately proportional to (AGD)0.3 rather than the expected (AGD)(0.5), 5) CNR measured using 0.1 mm thick aluminium foil as the contrast object is more dependent on choice of kVp than using a 1 mm deep hole in a PMMA slab.


Subject(s)
Mammography/instrumentation , Mammography/methods , Radiographic Image Enhancement/instrumentation , Radiographic Image Enhancement/methods , Radiographic Image Interpretation, Computer-Assisted/methods , Radiometry/methods , Equipment Design , Equipment Failure Analysis , Humans , Phantoms, Imaging , Radiation Dosage , Relative Biological Effectiveness , Reproducibility of Results , Sensitivity and Specificity
18.
Australas Phys Eng Sci Med ; 28(3): 179-83, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16250473

ABSTRACT

The measurement of the FWHM of the slice thickness radiation dose profile of a CT scanner using a prototype low sensitivity CR imaging plate has been investigated, as an alternative to the traditional method using envelope-packed industrial film. Using a standard Agfa clinical CR system to acquire the image, the FWHM of the dose profile can be accurately measured using readily available Public Domain software. An Agfa 18 x 24 cm CR cassette gives a pixel pitch of 113.5 microm, but with interpolation, the measurement accuracy can be less than 1 pixel. For a nominal 10 mm collimation, 15 successive measurements of the FWHM using CR gave an average width of 10.00 mm with a standard deviation of 0.02 mm. This may be compared with 4 successive measurements using film and a dual exposure technique to define the optical density at half peak height, yielding an average width of 9.98 mm with a SD of 0.03 mm. This prototype NDT plate is not a commercial product, but a radiotherapy plate with a similar sensitivity is available commercially and should give similar results.


Subject(s)
Equipment Failure Analysis/instrumentation , Equipment Failure Analysis/methods , Quality Assurance, Health Care/methods , Radiation Protection/instrumentation , Radiology Department, Hospital , Radiometry/instrumentation , Tomography, X-Ray Computed/instrumentation , Australia , Equipment Design , Radiation Dosage , Radiation Protection/methods , Radiometry/methods
19.
J Paediatr Child Health ; 38(6): 578-81, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12410870

ABSTRACT

OBJECTIVE: Children referred for persistent cough were evaluated for the referring and final diagnosis, and the extent of the use of medications prior to referral and the side effects encountered. METHODS: Data on children seen by respiratory paediatricians for persistent cough (> or =4 weeks) in a tertiary respiratory setting were collected prospectively over 12 months. RESULTS: Of the 49 children, 61.2% were diagnosed with asthma at referral, with similar referral rates from general practitioners and paediatricians. Children with isolated cough were just as likely to have been diagnosed with asthma as children with cough and wheeze. Medication use (asthma, gastro-oesophageal reflux and antibiotics) prior to referral was high, asthma medications were most common, and of these 12.9% had significant steroid side effects. The most common abnormality found (46.9%) was a bronchoscopically defined airway lesion, and in 56.5% of these children, another diagnosis (aspiration, achalasia, gastro-oesophageal reflux) existed. No children had a sole final diagnosis of asthma and pre-referral medications were weaned in all children. CONCLUSION: Over diagnosis of asthma and the overuse of asthma treatments with significant side effects is common in children with persistent cough referred to a tertiary respiratory clinic. Children with persistent cough deserve careful evaluation to minimize the use of unnecessary medications and, if medications are used, assessment of response to treatment is important.


Subject(s)
Anti-Asthmatic Agents , Cough/drug therapy , Cough/etiology , Diagnostic Errors , Adolescent , Anti-Asthmatic Agents/adverse effects , Anti-Bacterial Agents , Asthma/diagnosis , Asthma/drug therapy , Child , Child, Preschool , Drug Utilization Review , Female , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/drug therapy , Humans , Infant , Male , Prospective Studies , Queensland , Referral and Consultation , Steroids/adverse effects
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