PubMed | University of Cologne, Vilnius University, Institute of Human Genetics, Erasmus Medical Center and 110 more.
Type: Journal Article | Journal: PLoS genetics | Year: 2014
Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
Farhadieh R.D.,St Vincents Hospital |
Farhadieh R.D.,Prince of Wales Hospital |
Salardini A.,Yale University |
Yang J.L.,Prince of Wales Hospital Sydney |
And 3 more authors.
Journal of Surgical Oncology | Year: 2010
Objectives: Second primary tumors (SPTs) have been implicated in poor overall survival (OS) of head and neck squamous cell carcinomas (HNSCCs). Confusion remains regarding their actual incidence and prognostic impact. This study assessed the incidence of SPTs; the SPT diagnostic time lag; the impact on OS; and the mean annual risk. Methods: Nine hundred eighty seven consecutive patients treated for primary larynx SCC (1967-2004) were analyzed in this study. 96.3% and 91.4% of patients reached a minimum follow-up period of 3 and 5 years. Results: Two hundred eight (21.1%) patients were diagnosed with SPTs. One hundred forty three (14.5%) patients developed upper aerodigestive tract (UAD)-SPTs, 83 (8.4%) were HNSCCs, 56 (5.7%) were lung, and 4 (0.41%) were esophageal-SPTs. Survival analysis demonstrated clear superior OS rates for the UAD-SPT (P<0.008) and HNSCC-SPT (P<0.001) groups. A comparison of survival of subgroups showed lung/esophagus to have a poorer survival when compared to all other subgroups. OS after diagnosis of an SPTwas poorer when compared with no-SPT group (P<0.001). The mean annual risk of developing UAD-SPTs was 2.4%. Conclusion: These results suggest that HNSCC-SPT should not be viewed as an adverse prognostic factor. Reclassifications of UAD-SPTs into HNSCC-SPT and non-HNSCC-SPT better reflects their clinical behavior and prognosis. © 2009 Wiley-Liss, Inc.
Indraratna P.,St George Hospital |
Indraratna P.,University of New South Wales |
Indraratna P.,Collaborative Research CORE group |
Cao C.,University of New South Wales |
And 2 more authors.
Australian Prescriber | Year: 2014
Ticagrelor and prasugrel are antiplatelet drugs that are alternatives to clopidogrel in acute coronary syndrome. Their advantages include reduced rates of ischaemia and stent thrombosis.The risk of major bleeding is likely to be higher with prasugrel compared to clopidogrel. Intracranial haemorrhage appears to be slightly more common with ticagrelor than with clopidogrel, and it can also cause dyspnoea and ventricular pauses early in treatment.When patients taking prasugrel or ticagrelor require surgery, perioperative management is challenging. The treating cardiologist should be consulted whenever treatment cessation is considered. © 2014 Australian Government Publishing Service. All rights reserved.
Iozzino L.,Psychiatric Epidemiology and Evaluation Unit |
Iozzino L.,University of Verona |
Ferrari C.,Psychiatric Epidemiology and Evaluation Unit |
Large M.,Prince of Wales Hospital Sydney |
And 4 more authors.
PLoS ONE | Year: 2015
Background: Violence in acute psychiatric wards affects the safety of other patients and the effectiveness of treatment. However, there is a wide variation in reported rates of violence in acute psychiatric wards. Objectives: To use meta-analysis to estimate the pooled rate of violence in published studies, and examine the characteristics of the participants, and aspects of the studies themselves that might explain the variation in the reported rates of violence (moderators). Method: Systematic meta-analysis of studies published between January 1995 and December 2014, which reported rates of violence in acute psychiatric wards of general or psychiatric hospitals in high-income countries. Results: Of the 23,972 inpatients described in 35 studies, the pooled proportion of patients who committed at least one act of violence was 17% (95% confidence interval (CI) 14-20%). Studies with higher proportions of male patients, involuntary patients, patients with schizophrenia and patients with alcohol use disorder reported higher rates of inpatient violence. Conclusion: The findings of this study suggest that almost 1 in 5 patients admitted to acute psychiatric units may commit an act of violence. Factors associated with levels of violence in psychiatric units are similar to factors that are associated with violence among individual patients (male gender, diagnosis of schizophrenia, substance use and lifetime history of violence). © 2015 Iozzino et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Javed F.,University of New South Wales |
Savkin A.V.,University of New South Wales |
Chan G.S.H.,University of New South Wales |
Middleton P.M.,Prince of Wales Hospital Sydney |
And 4 more authors.
Medical and Biological Engineering and Computing | Year: 2010
To maintain the hemodynamic stability of patient undergoing hemodialysis, this article proposes a novel model-based control methodology to regulate the changes in relative blood volume (RBV) and percentage change in heart rate (DHR(%)) during hemodialysis by adjusting the ultrafiltration rate (UFR). The control algorithm uses model predictive control (MPC) to account for system variability and to explicitly handle the constraints on UFR. Linear state-space system with time-varying parameters is introduced to model the RBV and DHR. MPC was used to track the change in RBV and DHR to pre-defined reference trajectories. At each sampling instant, the system parameters are updated to get the best fitting into the parameterized model. Simulation results demonstrate that the system is able to regulate RBV and DHR to the reference by adjusting UFR while keeping it within practically realizable bounds. The results show that adjusting UFR may improve the stability of patient during dialysis when compared to conventional hemodialysis with constant UFR. © International Federation for Medical and Biological Engineering 2010.