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1.  Spatial Characterization of Electrogram Morphology from Transmural Recordings in the Intact Normal Heart 
PLoS ONE  2014;9(10):e110399.
Unipolar (UE) and bipolar electrograms (BE) are utilized to identify arrhythmogenic substrate. We quantified the effect of increasing distance from the source of propagation on local electrogram amplitude; and determined if transmural electrophysiological gradients exist with respect to propagation and stimulation depth.
Mapping was performed on 5 sheep. Deployment of >50 quadripolar transmural needles in the LV were located in Cartesian space using Ensite. Contact electrograms from all needles were recorded during multisite bipolar pacing from epicardial then endocardial electrodes. Analysis was performed to determine stimulus distance to local activation time, peak negative amplitude (V-P), and peak-peak amplitude (VP-P) for (1) unfiltered UE, and (2) unfiltered and 30 Hz high-pass filtered BEs. Each sheep was analysed using repeated ANOVA.
Increasing distance from the pacing sites led to significant (p<0.01) attenuation of UEs (V-P = 7.0±0.5%; VP-P = 5.4±0.3% per cm). Attenuation of BE with distance was insignificant (Vp-p unfiltered  = 2.2±0.5%; filtered  = 1.7±1.4% per cm). Independent of pacing depth, significant (p<0.01) transmural electrophysiological gradients were observed, with highest amplitude occurring at epicardial layers for UE and endocardial layers for BE. Furthermore, during pacing, propagation was earlier at the epicardium than endocardial layer by 1.6±2.0 ms (UE) and 1.4±2.8 ms (BE) (all p>0.01) during endocardial stimulation, and 2.3±2.4 ms (UE) and 1.8±3.7 ms (BE) during epicardal stimulation (all p<0.01).
Electrogram amplitude is inversely proportional to propagation distance for unipolar modalities only, which affected V-P>VP-P. Conduction propagates preferentially via the epicardium during stimulation and is believed to contribute to a transmural amplitude gradient.
PMCID: PMC4215922  PMID: 25361049
3.  Full myocardial revascularization with bilateral internal mammary artery Y grafts 
Annals of Cardiothoracic Surgery  2013;2(4):444-452.
Bilateral internal mammary artery (BIMA) grafting in coronary artery surgery provides better long term outcomes than single internal mammary artery and saphenous vein grafting but the optimum configuration of BIMAs has not been established. This study analyzed perioperative and late outcomes of patients who underwent BIMA grafting with a composite Y configuration.
Patients (n=922) who underwent BIMA Y grafting were identified from a cardiac surgical database and then cross matched against hospital and cardiology databases and the state death register to identify episodes of repeat coronary angiography, cardiac surgical re-intervention and death. Analysis of repeat angiography was performed after retrieval of the angiogram reports.
In 95% of patients, full myocardial revascularization was achieved with BIMAs alone, using a composite Y configuration with an average of 4.1 IMA to coronary artery anastomoses per patient. The perioperative mortality was 1.5% and the 5-, 10- and 15-year survival estimates were 95%, 87% and 77% respectively. Analysis of 166 symptom-driven post-discharge coronary angiograms showed grafts to the left anterior descending artery and increasing severity of coronary artery stenosis at preoperative angiography as predictors of anastomotic patency.
Full myocardial revascularization can be achieved with reasonable safety in most patients with triple vessel disease and good left ventricular function, and provides good late survival.
PMCID: PMC3741876  PMID: 23977621
Coronary artery bypass; internal mammary artery (IMA); myocardial revascularization
4.  Australian tertiary care outcomes of entecavir monotherapy in treatment naive patients with chronic hepatitis B 
AIM: To evaluate the long-term treatment outcomes of entecavir monotherapy in treatment naive patients in an Australian tertiary care setting.
METHODS: A retrospective analysis of treatment naive patients receiving entecavir monotherapy through Westmead Hospital was performed. Patients were excluded if they had received previous treatment with another nucleoside or nucleotide analogue, were pregnant or less than 18 years old.
RESULTS: Out of 336 patients, 163 patients fulfilled the selection criteria. Range of follow up was 3-46 mo (mean 26 mo). 134 patients (82.2%) had pre-treatment biopsies, with 26 patients (16.0 %) demonstrating F3-4 fibrosis. In total, 153 patients (93.9%) achieved at least Partial Virological Suppression (PVS), with 134 patients (82.2%) achieving complete virological suppression. The cumulative CVS and PVS rates at 36 mo were 82.1% and 96.4%, respectively. 3 patients (1.8%) failed to achieve PVS, while 5 patients (3.0%) developed virological rebound. 128 patients (78.5%) maintained CVS throughout follow up. Predictors of CVS included lower baseline DNA level (P = 0.001), hepatitis B virus e antigen negative status (P = 0.001) and increasing age at treatment (log rank 0.001). No significant adverse effects were reported necessitating cessation of entecavir.
CONCLUSION: Entecavir monotherapy is efficacious and safe in an Australian tertiary care setting. Resistance and rebound rates are very low. This is similar to data from controlled and uncontrolled trials around the world.
PMCID: PMC3574598  PMID: 23430314
Chronic hepatitis B; Entecavir; Australia; Asia-Pacific; Monotherapy; Hepatitis B virus; Antivirals
5.  Iodine Intake and Thyroid Function in Pregnant Women in a Private Clinical Practice in Northwestern Sydney before Mandatory Fortification of Bread with Iodised Salt 
Journal of Thyroid Research  2012;2012:798963.
Aim. The primary objective of the study was to assess the iodine nutritional status, and its effect on thyroid function, of pregnant women in a private obstetrical practice in Sydney. Methods. It was a cross-sectional study undertaken between November 2007 and March 2009. Blood samples were taken from 367 women at their first antenatal visit between 7 and 11 weeks gestation for measurement of thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels and spot urine samples for urinary iodine excretion were taken at the same time as blood collection. Results. The median urinary iodine concentration (UIC) for all women was 81 μg/l (interquartile range 41–169 μg/l). 71.9% of the women exhibited a UIC of <150 μg/l. 26% of the women had a UIC <50 μg/l, and 12% had a UIC <20 μg/l. The only detectable influences on UIC were daily milk intake and pregnancy supplements. There was no statistically significant association between UIC and thyroid function and no evidence for an effect of iodine intake on thyroid function. Conclusions. There is a high prevalence of mild to moderate iodine deficiency in women in Western Sydney but no evidence for a significant adverse effect on thyroid function. The 6.5% prevalence of subclinical hypothyroidism is unlikely to be due to iodine deficiency.
PMCID: PMC3503401  PMID: 23209946
6.  Analysis of Oxygen Saturations Recorded During Dental Intravenous Sedations: A Retrospective Quality Assurance of 3500 Cases 
Anesthesia Progress  2011;58(3):113-120.
The death of a patient under sedation in New South Wales, Australia, in 2002 has again raised the question of the safety of dental sedation. This study sought answers to 2 questions: Can safe oxygen saturation levels (≥94%) be consistently maintained by a single operator/sedationist? Does the additional use of propofol, in subanesthetic doses, increase the risk of exposure to hypoxemia? Three thousand five hundred cases generated between 1996 and 2006 were randomly examined and divided into 2 subcohorts: 1750 patients were sedated with midazolam and fentanyl, and 1750 patients received propofol, in subanesthetic increments, in addition to midazolam and fentanyl. Initial sedation was established using midazolam and fentanyl in both subcohorts. The second subcohort received propofol during times of noxious stimulation. Patient exposure to 2 or more oxygen desaturations below 94% was uncommon. The variables that were significantly associated with low saturations were age, gender, and weight. Neither the dose of midazolam nor the additional use of propofol was a significant risk factor. ASA classification (I or II) was not a determinant of risk. The data, within the limitations of the study, showed that a single operator/sedationist, supported by a well-trained team of nurses, can consistently maintain safe oxygen saturation levels. The additional use of propofol did not increase exposure to hypoxemia.
PMCID: PMC3167154  PMID: 21882986
Dental sedation; Safe oxygen saturation levels; Propofol
7.  The compression type of coronary artery motion in patients with ST-segment elevation acute myocardial infarction and normal controls: a case-control study 
BMC Research Notes  2011;4:51.
Prediction of the location of culprit lesions responsible for ST-segment elevation myocardial infarctions may allow for prevention of these events. A retrospective analysis of coronary artery motion (CAM) was performed on coronary angiograms of 20 patients who subsequently had ST-segment elevation myocardial infarction treated by primary or rescue angioplasty and an equal number of age and sex matched controls with normal angiograms.
There was no statistically significant difference between the frequency of CAM types of the ST-segment elevation acute myocardial infarction and control patients (p = 0.97). The compression type of CAM is more frequent in the proximal and mid segments of all three coronary arteries. No statistically significant difference was found when the frequency of the compression type of CAM was compared between the ST-segment elevation acute myocardial infarction and control patients for the individual coronary artery segments (p = 0.59).
The proportion of the compression type of coronary artery motion for individual artery segments is not different between patients who have subsequent ST-segment elevation myocardial infarctions and normal controls.
PMCID: PMC3063224  PMID: 21385385
8.  Correction: A Novel Method to Adjust Efficacy Estimates for Uptake of Other Active Treatments in Long-Term Clinical Trials 
PLoS ONE  2010;5(1):10.1371/annotation/54433693-04e0-4f30-9a99-38fe3c5bb16b.
PMCID: PMC2811202
9.  A Novel Method to Adjust Efficacy Estimates for Uptake of Other Active Treatments in Long-Term Clinical Trials 
PLoS ONE  2010;5(1):e8580.
When rates of uptake of other drugs differ between treatment arms in long-term trials, the true benefit or harm of the treatment may be underestimated. Methods to allow for such contamination have often been limited by failing to preserve the randomization comparisons. In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, patients were randomized to fenofibrate or placebo, but during the trial many started additional drugs, particularly statins, more so in the placebo group. The effects of fenofibrate estimated by intention-to-treat were likely to have been attenuated. We aimed to quantify this effect and to develop a method for use in other long-term trials.
Methodology/Principal Findings
We applied efficacies of statins and other cardiovascular drugs from meta-analyses of randomized trials to adjust the effect of fenofibrate in a penalized Cox model. We assumed that future cardiovascular disease events were reduced by an average of 24% by statins, and 20% by a first other major cardiovascular drug. We applied these estimates to each patient who took these drugs for the period they were on them. We also adjusted the analysis by the rate of discontinuing fenofibrate. Among 4,900 placebo patients, average statin use was 16% over five years. Among 4,895 assigned fenofibrate, statin use was 8% and nonuse of fenofibrate was 10%. In placebo patients, use of cardiovascular drugs was 1% to 3% higher. Before adjustment, fenofibrate was associated with an 11% reduction in coronary events (coronary heart disease death or myocardial infarction) (P = 0.16) and an 11% reduction in cardiovascular disease events (P = 0.04). After adjustment, the effects of fenofibrate on coronary events and cardiovascular disease events were 16% (P = 0.06) and 15% (P = 0.008), respectively.
This novel application of a penalized Cox model for adjustment of a trial estimate of treatment efficacy incorporates evidence-based estimates for other therapies, preserves comparisons between the randomized groups, and is applicable to other long-term trials. In the FIELD study example, the effects of fenofibrate on the risks of coronary heart disease and cardiovascular disease events were underestimated by up to one-third in the original analysis.
Trial Registration ISRCTN64783481
PMCID: PMC2798963  PMID: 20072614

Results 1-9 (9)