ORCID Profile
0000-0002-6437-3792
Current Organisation
Monash University
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Publisher: Elsevier BV
Date: 09-2015
Publisher: Wiley
Date: 09-07-2014
Abstract: The association between glucose lowering in diabetes mellitus and major cardiovascular (CV) outcomes is weak indeed, some oral hypoglycemic agents are associated with increased CV events. Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) are a new class of oral hypoglycemic agent that may have beneficial CV effects. We undertook a systematic review and meta-analysis to appraise the CV safety and efficacy of DPP-4 inhibitors. Comprehensive search for prospective trials involving DPP-4 inhibitors. Trials included reported at least one of the outcomes examined, recruited minimum 100 patients and minimum follow-up 24 weeks. The risk ratio (RR) was calculated using the Mantel-Haenszel random-effects model for mortality and major cardiovascular (CV) outcomes. Fifty trials enrolling 55,141 participants were included. Mean follow-up 45.3 weeks. DPP-4 inhibitors compared with all comparators (placebo and active) showed no difference in all-cause mortality (n = 50,982, RR = 1.01, 95% CI 0.91-1.13, P = 0.83), CV mortality (n = 48,151, RR = 0.97, 95% CI 0.85-1.11, P = 0.70), acute coronary syndrome (ACS) (n = 53,034 RR = 0.97, 95% CI 0.87-1.08, P = 0.59), or stroke (n = 42,737, RR = 0.98, 95% CI 0.81-1.18, P = 0.80), and a statistically significant increase in heart failure outcomes (n = 39,953, RR = 1.16, 95% CI 1.01-1.33, P = 0.04). Treatment with DPP-4 inhibitors compared with placebo shows no increase in risk with regards to all-cause mortality, CV mortality, ACS, or stroke, but a statistically significant trend toward increased risk of HF outcomes. These findings suggest no cardiovascular harm (or benefit) with DPP-4 inhibitors further large-scale CV outcome studies will resolve the issue of excess HF risk.
Publisher: Elsevier BV
Date: 07-2016
Publisher: Oxford University Press (OUP)
Date: 08-04-2021
Abstract: Does the application of reference ranges for sex steroids and the modified Ferriman-Gallwey (mFG) scale established in the community from which the study s le was drawn, combined with the most conservative polycystic ovary morphology (PCOM) criteria to the recognised diagnostic criteria for polycystic ovary syndrome (PCOS) improve the certainty of diagnosis of PCOS in non-healthcare-seeking women? Despite application of the stringent definitions of the elements used to diagnose PCOS in a non-healthcare seeking community-based s le, the risk of diagnostic uncertainty remains. There is heterogeneity in prevalence estimates for PCOS due, in part, to lack of standardisation of the elements comprising the recognised National Institutes of Health (NIH), Rotterdam and Androgen Excess Society (AE-PCOS) diagnostic criteria. The AE-PCOS Society proposed refinements to the definitions of biochemical androgen excess and PCOM that can now be incorporated into these sets of diagnostic criteria to estimate PCOS prevalence. An Australian cross-sectional study of 168 non-healthcare-seeking women. The 168 included women were aged 18–39 years, euthyroid and normoprolactinemic, not recently pregnant, breast feeding or using systemic hormones. Each provided menstrual history and assessment of the mFG, had measurement of sex steroids by liquid chromatography, tandem mass spectrometry, and a pelvic ultrasound. The presence of PCOS was determined using modified (m) NIH, Rotterdam, and AE-PCOS criteria according to AE-PCOS Society recommendations. Overall, 10.1% of the included participants met the mNIH PCOS criteria, which requires the presence of menstrual dysfunction, while 18.5% met the mRotterdam and 17.5% the AE-PCOS criteria, with the latter requiring hyperandrogenism. Eight of the 27 participants with menstrual dysfunction, 10 of 31 women with PCOM, and 39 of 68 women with hyperandrogenism had no other feature of PCOS. Of the 19 participants with hyperandrogenaemia, 10 met the mNIH criteria (52.5%) and 14 met both the mRotterdam and AE-PCOS criteria (78.9%). Women who had the combination of hyperandrogenism and PCOM explained the greatest discrepancy between the mNIH and the other criteria. Clinical androgenisation relied on participant self-assessment, which has been shown to be valid when compared with clinician assessment. The s le size was a function of both the strict inclusion criteria and the requirements of non-healthcare-seeking women having a blood draw and pelvic ultrasound which may have introduced a selection bias. Despite applying stringent cut-offs for serum androgens, the mFG scale and the ovarian follicle count, these criteria remain arbitrary. Accordingly, healthy women may be captured by these criteria, and misidentified as having PCOS, while women with the condition may be missed. Consequently, PCOS remains a diagnosis to be made with care. The study was supported by the Grollo-Ruzzene Foundation. Dr S.R.D. is an NHMRC Senior Principal Research Fellow (Grant no. 1135843). S.R.D. has been paid for developing and delivering educational presentations for Besins Healthcare, BioFemme and Pfizer Australia, has been on Advisory Boards for Theramex, Abbott Laboratories, Mayne Pharmaceuticals and Roche and a consultant to Lawley Pharmaceuticals and Que Oncology and has received has received institutional grant funding for Que Oncology research there are no other relationships or activities that could appear to have influenced the submitted work. N/A
Publisher: Elsevier BV
Date: 02-2020
Publisher: Wiley
Date: 04-2020
DOI: 10.1111/IMJ.14397
Abstract: Although serum ferritin is considered a reliable indicator of iron stores, there are few data documenting the prevalence of low ferritin in representative s les of young women. To estimate the prevalence of low ferritin and to identify factors associated with low ferritin in young Australian women. Women, aged 18-39 years, living in the eastern states of Australia were recruited by email to a cross-sectional, online questionnaire-based study between November 2016 and July 2017. Participants not pregnant, breast feeding, taking hormonal contraception, using assisted reproduction or postmenopausal were invited to provide a blood s le. Of the 3689 invited participants, 761 (23.1%) provided a s le and 736 women, mean (SD) age 31.7 (±5.6) years, were included in the analyses. The overall prevalence of serum ferritin <30 μg/L was 34.8% (95% confidence interval (CI) 31.4-38.3%), with 41.4% (35.1-48.0%) in NSW, 31.5% (26.4-37.1%) in Victoria and 32.6% (26.8-39.0%) in Queensland. Serum ferritin 2 days of heavy menstrual bleeding (adjusted odds ratio (AOR) 1.73, 95% CI 1.15-2.59), living in New South Wales (AOR 1.57, 95% CI 1.07-2.30), not working outside home (AOR 1.58, 95% CI 1.01-2.49), and inversely associated with never experiencing heavy menses (AOR 0.46, 95% CI 0.23-0.93) and obesity (AOR 0.32, 95% CI 0.21-0.50). This study demonstrates that serum ferritin below 30 μg/L is common amongst young Australian women. Healthcare professionals should note the association between low ferritin and heavy bleeding.
Publisher: Wiley
Date: 2013
Abstract: Heart failure (HF) is a prothrombotic state, but current evidence does not support the routine use of aspirin, antiplatelet agents, or anticoagulation in these patients in sinus rhythm (SR). We conducted an updated meta-analysis comparing these medications on outcomes in HF. All randomized trials in patients with chronic HF and reduced ejection fraction (HFREF) in sinus rhythm (SR n >100), in which the effect of aspirin, antiplatelet agents, or anticoagulants was determined, were prospectively evaluated. Four trials met the entry criteria. Intervention time was 28 months. No difference in all-cause mortality was seen when aspirin was compared with warfarin [n = 3701, relative risk (RR) 1.00, 95% confidence interval (CI) 0.88-1.13, P = 0.94]. Compared with aspirin, significantly fewer strokes were seen with warfarin (n = 3701, RR 0.59, 95% CI 0.41-0.85, P = 0.004), and fewer fatal and non-fatal ischaemic strokes (n = 3368, RR 0.48, 95% CI 0.32-0.73, P = 0.0006). Warfarin doubled the risk of major haemorrhage compared with aspirin (n = 3701, RR 2.02, 95% CI 1.45-2.80, P < 0.0001) however, intracranial haemorrhage was rare. There was no significant difference in HF hospitalizations with aspirin vs. warfarin (n = 3701, RR 1.16, 95% CI 0.79-1.71, P = 0.45). With warfarin compared with aspirin in HFREF in SR, significant reductions in stroke risk were observed but no mortality benefit was seen. Major haemorrhage doubled but intracranial haemorrhage was rare. These findings suggest that overall the benefit of warfarin in HFREF in SR outweighs the risk. Aspirin use did not increase HF hospitalization as has been previously suggested.
Publisher: Springer Science and Business Media LLC
Date: 09-01-2018
DOI: 10.1007/S10557-017-6768-4
Abstract: Previous studies on the 'treatment gap' in patients with heart failure (HF) have focused either on prescribing or patients' adherence to prescribed treatment. This study sought to determine whether or not recent initiatives to close the gap have also minimised any mismatches between physicians' expectation of their patients' medications, medications in the patients' possession and their actual medication use. A cross-sectional observational survey was conducted from December 2015 to June 2016 in The Alfred Hospital HF clinic in Melbourne, Australia. Patients were invited to participate if they had chronic HF (NYHA class II to IV), were aged ≥ 60 years, had no history of HF related hospitalisation within the past 6 months and were prescribed at least two HF medications. Of 123 eligible patients, 102 were recruited into the study. Beta-blockers, mineralocorticoid receptor antagonists, loop diuretics and statins were associated with the highest rates of mismatches of drugs and doses, ranging from 10 to 17%. Discrepancy of total daily doses was the most common type of mismatch. Overall, only 23.5% of the patients were taking the right drugs at the right doses as expected by their cardiologists/HF specialists. Despite improved prescribers' adherence to guideline-directed medical therapy, there remain considerable mismatches between prescribers' expectation of patients' HF medications, medications in patients' possession and their actual medication use. Initiatives to improve this situation are urgently needed.
Publisher: Elsevier BV
Date: 04-2007
DOI: 10.1016/J.IJCARD.2006.05.043
Abstract: Many cardiovascular disease states are associated with autonomic dysfunction, specifically sympathetic activation and parasympathetic withdrawal. Both these autonomic derangements are independently associated with adverse prognostic outcomes. HMG CoA reductase inhibitors (statins) reduce cardiovascular mortality and morbidity when compared to placebo in subjects with proven coronary artery disease (CAD), including sudden presumed arrhythmic death. As autonomic dysfunction is associated with arrhythmogenesis, statins may be having a beneficial effect on autonomic function in these subjects. We conducted a randomised, double-blind, placebo-controlled, cross-over study examining the effect of rapid short-term lipid lowering with a statin on autonomic function in CAD patients. Ten subjects with proven CAD (8 male, 2 female mean age 63.4 years) were randomised to receive either 80 mg atorvastatin or placebo over a 4 week period followed by a 4 week washout, then the alternative treatment for a further 4 weeks. Autonomic parameters assessed were plasma noradrenaline levels on recumbency and 80 degrees head-up tilt, cold pressor testing, and heart rate variability (HRV) analysis. Plasma noradrenaline levels were significantly reduced (p=0.050) after 20 min rest in the recumbent position, with atorvastatin compared to placebo. A nonsignificant reduction in plasma noradrenaline with atorvastatin compared to placebo was observed in the prolonged 80 degrees head-up position (p=0.207). In addition, sympathovagal balance was shifted to greater vagal predominance with atorvastatin (low-frequency/high-frequency ratio in the HRV frequency domain) when compared to placebo, p=0.06. We found that rapid lipid lowering with atorvastatin reduces sympathetic nervous system in this pilot study of CAD patients. Larger trials are required to definitively address the effects of statins on autonomic activity in these patients.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Mary Ann Liebert Inc
Date: 07-2021
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.IJCARD.2008.10.022
Abstract: We conducted a prospective, randomised, open-label, blinded end point (PROBE) study examining the relative efficacy of irbesartan 300 mg/day versus maximising dose of ACE inhibitor, additional to background conventional heart failure therapy. Patients with CHF, NYHA Class II-III and a left ventricular ejection fraction 0.05). This PROBE study has demonstrated similar clinical responses with increased dose of ACE inhibitor compared to addition of ARB in patients with systolic CHF. These findings suggest that either approach to increasing renin-angiotensin blockade in patients taking low doses of background ACE inhibitor results in similar clinical outcomes.
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.HLC.2012.12.017
Abstract: Multiple agents have been investigated to prevent atrial fibrillation (AF) after cardiac surgery. Several studies have investigated the use of β-blockers such as metoprolol or amiodarone with promising results. We aimed to investigate perioperative pharmacologic prophylaxis against AF using metoprolol, and amiodarone in combination with metoprolol. We conducted a prospective, randomised, single-blind, controlled pilot study in patients undergoing elective cardiac surgery. Subjects were randomised pre-operatively to one of three treatment groups: standard therapy (control) or metoprolol (5 mg IV over 5 min on commencement of bypass then 5 mg IV qid for 24h then 25-50 mg tds orally until discharge) or amiodarone (300 mg over 1h starting shortly after the commencement of bypass, then 900 mg over 24h then 400 mg orally tds until discharge) plus metoprolol as above. Patients had ECG monitoring for the occurrence of AF for six days or until discharge. Two hundred and fifteen patients were enrolled. Between-group differences in AF in an intention-to-treat analysis were not significant: control 34% (23-45%), metoprolol 35% (24-46%), combined 22% (12-33%) (p = 0.21). However 87 patients (40%) did not receive the assigned treatment mainly due to side effects, especially bradycardia. The remaining 128 patients were analysed on a per-protocol basis with the overall difference between the three groups bordering on significance: control 34% (23-45%), metoprolol 26% (9-43%), combined 11% (0-23%) (p = 0.06). Logistic regression analysis, correcting for age and gender, was used to separate the in idual effects of metoprolol and amiodarone in the presence of metoprolol which showed that compared to control there was a significant effect of metroprolol on AF incidence (O.R. 0.31 (0.10-0.99), p = 0.048) but not of amiodarone (O.R. 0.97 (0.19-5.02), p = 0.97). (1) Perioperative metoprolol but not amiodarone itself in combination with metoprolol is associated with a significant reduction in postoperative AF. (2) Perioperative administration of metoprolol and combination of metoprolol with amiodarone is associated with a high incidence of side effects, especially bradycardia. (3) Further studies are indicated to confirm these preliminary findings but in the meantime it would not be unreasonable to implement the use of perioperative metoprolol for routine prophylaxis of AF.
Publisher: Elsevier BV
Date: 04-2019
Abstract: To describe the challenges in recruitment of a national s le of young Australian women for a study of their physical and psychological wellbeing. Women, aged 18 to 39 years, were invited by email to complete an online questionnaire and, if not using systemic hormones, pregnant or breast feeding, to provide a blood s le. A total of 94,546 email invitations were sent. Follow-up of 1,000 randomly selected non-responders by text message recruited 15 additional women. Direct telephoning resulted in another 516 completed questionnaires from a further 3,614 randomly selected non-responders. In all, 6,986 women completed the questionnaire and blood s les were provided by 761 (20.6%) of 3,689 eligible participants. The study s le is similar to women within the target age range captured by the Australian Census for their state of residence in terms of age distribution, education, relationship status, employment and occupation. Recruitment, by predominantly electronic means, has achieved a large, representative study s le of young women recruited from the eastern states of Australia. Implications for public health: Recruitment of a representative study s le can be achieved in the absence of a high response rate.
Publisher: Informa UK Limited
Date: 1994
DOI: 10.3109/08037059409102294
Abstract: In this study, which was primarily designed to determine the lipid-lowering efficacy of pravastatin in the setting of background antihypertensive therapy with ACE inhibitors and calcium antagonists, we took the opportunity to examine whether pravastatin interacts with antihypertensive therapy to produce additional falls in blood pressure. This may help clarify the mechanism of action of pravastatin's rapid beneficial effects on cardiovascular morbidity. We treated 25 hypertensive hypercholesterolaemic patients with 12 weeks of either pravastatin or placebo in this double blind, placebo controlled parallel group study. Placebo treatment did not alter plasma lipids, whereas 12 weeks' treatment with pravastatin reduced total cholesterol by 27% (from 7.1 +/- 0.27 to 5.2 +/- 0.18, p < 0.001 compared with placebo) and low density lipoprotein cholesterol by 35% (from 4.9 +/- 0.36 to 3.2 +/- 0.17, p < 0.001). There were no changes in systolic or diastolic blood pressure either following 12 weeks' treatment or 3 weeks' withdrawal of pravastatin. Thus, pravastatin remains efficacious as a lipid lowering agent in the presence of antihypertensive therapy but does not enhance the blood pressure lowering action of these drugs. Therefore it is unlikely that blood pressure reduction is the mechanism by which pravastatin mediates its reported short term effects on cardiovascular morbidity.
Publisher: The Endocrine Society
Date: 07-08-2019
Abstract: Whether serum androgen levels can identify women with “androgen insufficiency” or “androgen excess” is unresolved thus, what constitutes “normal” remains uncertain. We sought to determine whether androgens, including 11-oxygenated C19 steroids, vary with age, menstrual cycle, or body mass index (BMI), during the reproductive years. Cross-sectional study recruited from eastern Australian states. A total of 588 women, aged 18 to 39 years, who were not pregnant, lactating, or using systemic hormone therapy, with regular menstrual cycles and no previous diagnosis of polycystic ovarian syndrome. Sex steroids measured using liquid chromatography-tandem mass spectrometry. Testosterone and androstenedione concentrations were significantly higher during the menstrual cycle mid- and luteal phases than in the early follicular phase, with median values across the cycle of 0.34 nmol/L (range, 0.04 to 1.01) and 1.97 nmol/L (range, 0.53 to 7.89), respectively. No cyclical variations were found in dehydroepiandrosterone (DHEA 4.91 nmol/L range, 0.08 to 23.51), 11-ketoandrostenedione (11KA 7.99 nmol/L range, 0.07 to 31.67), or 11-ketotestosterone (11KT 1.27 nmol/L range, 0.03 to 7.61). Overweight women had lower median testosterone (P 0.05), DHEA (P 0.05), and 11KA (P 0.01) levels than normal-weight women. All C19 steroids were significantly lower (P 0.01) in those aged 35 to 39 years than in those aged 18 to 25 years. The median 11KA/androstenedione (4.3:1) and 11KT/testosterone (3.9:1) ratios did not change with age, after adjustment for BMI and cycle stage. We have demonstrated that 11KA and 11KT are stable across the menstrual cycle and make major quantitative contributions to the circulating androgen pool. All C19 androgens declined with age before menopause hence, age-specific reference ranges are required for the interpretation of androgen levels in premenopausal women.
Publisher: Wiley
Date: 27-06-2019
DOI: 10.1111/AJO.13021
Abstract: In Australia many hormonal contraceptives are not Pharmaceutical Benefits Scheme ( PBS ) supported, hence the use of different formulations have not been quantified. To document the use of hormonal contraceptives and factors associated with their use. Cross‐sectional, online questionnaire‐based study of 6986 Australian women, aged 18–39 years, recruited by email invitation from two large, representative databases. Main outcome measures were the prevalence of use of hormonal contraceptives and associated socio‐demographic characteristics. Of the 6600 potential hormone contraceptive users, 43.2% were current users. Most (63.6%) reported using a combined oral contraceptive ( COC ) of which 30.9% were non‐ PBS ‐supported anti‐androgenic progestin‐containing COC s. Use of long‐acting reversible contraceptives ( LARC ) or an injectable contraceptive was reported by 26.8%. Education beyond secondary school, being Australian born, rural residency, normal body mass index, age years and nulliparity were significantly associated with hormonal contraceptive use. Women who reported polycystic ovary syndrome or acne were more likely to be taking a third or fourth generation COC ( P 0.0001) and endometriosis was significantly associated with intrauterine system ( IUS ) use. Third or fourth generation COC use was reported by 12.1% of obese, current smokers. An estimated one‐third of Australian women aged 18–39 are taking a non‐PBS‐supported anti‐androgenic progestin COC , highlighting inequity in access to COC options. That hormonal contraceptive use is higher in rural areas is a novel finding and the proportion of LARC or injectable use suggests that uptake in Australia is higher than previously reported.
Publisher: Elsevier BV
Date: 03-2020
DOI: 10.1016/J.IDH.2019.11.001
Abstract: Despite the availability of several rapid Influenza tests (RIT), the literature on its impact on antimicrobial stewardship programs (AMS) is minimal. Studies utilising rapid point of care tests (POCT) have shown benefit in terms of shortening antimicrobial therapy and prescriptions of antivirals. We designed this study to assess whether RIT had an impact on antibiotic cessation. Xpert Flu/RSV (Cepheid, CA) was performed on all patients who presented with influenza-like illness (ILI) in 2017. Clinical data was collected from electronic medical records (eMR). Patients with RSV were not included. Turnaround time (TAT) for the test was time from specimen collection until when the result was either notified or appeared on eMR. Standard univariate analysis and multivariable regression analysis (MVRA) were done. A total of 665 patients tested positive-Influenza A (63%) and B (37%). After positive results, antimicrobials were ceased in 34% (226/665) or not given in 10% (71/665) cases. Median TAT was 7 h, with 50% of tests completed in less than 6 h 56% (368/665) of patients had their antibiotics continued. On MVRA, results of RIT within 6-12 h resulted in most antibiotic cessation (73%, OR 1.55, p = 0.01). It was found that antibiotics are continued in immunosuppressed patients (OR 2.88, p < 0.01), patients with pneumonia (OR 18.8, p < 0.01) and with underlying COPD (OR 2.43, p = 0.03). Influenza patients are more likely to have their antibiotics continued with underlying COPD, pneumonia, or immunosuppression. Results of RIT within 6-12 h can help clinicians in deciding on cessation of antibiotics in patients.
Publisher: Springer Science and Business Media LLC
Date: 27-07-2016
DOI: 10.1007/S10741-016-9575-2
Abstract: The extent and impact of under-prescribing of evidence-based pharmacological therapies among heart failure patients with reduced ejection fraction (HFREF) in contemporary practice is unclear. We sought to examine the prescribing patterns of angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), β-blockers (BBs) and mineralocorticoid receptor antagonists (MRAs), and to quantify the estimated 'treatment gap' among HFREF patients in the 'real-world' setting. The MEDLINE, PubMed, EMBASE, CINAHL and CENTRAL databases were searched for registry- or survey-based studies which examined the prescribing rates of ACE inhibitors, ARBs, BBs and MRAs among HFREF patients. Searches were limited to those published in the years 2000-2015. A total of 23 reports, including 83,605 patients, were evaluated. Overall, ACE inhibitors/ARBs, BBs and MRAs were prescribed to 79.8, 81.4 and 36.4 % of patients, respectively. The estimated treatment gaps in the overall population were 13.1 % for ACE inhibitors/ARBs, 3.9 % for BBs and 16.8 % for MRAs. The proportion of patients who received ≥50 % of the guideline-recommended target doses was 72 % for ACE inhibitors, 51 % for ARBs, 49 % for BBs, 53 % for the combination of ACE inhibitors/ARBs and BBs and 83 % for MRAs. Prescribing these drugs according to contemporary guidelines was associated with lower mortality risk. Patients who were elderly, female and with comorbidities were less likely to receive optimal treatment as recommended by the guidelines. ACE inhibitors, ARBs, BBs and MRAs are under-prescribed in eligible HFREF patients. Efforts should be made to improve approaches to closing the treatment gap at both systems of care and in idual levels.
Publisher: Elsevier BV
Date: 09-2009
DOI: 10.1016/J.HEALUN.2009.05.015
Abstract: Cyclosporine in the form of a microemulsion (Neoral) has been the cornerstone of the majority of immunosuppression regimes in thoracic organ transplantation. Cysporin, an alternative form of cyclosporine, is now available. Although bioavailability has been studied in healthy volunteers and stable renal transplant recipients, there are no bioequivalence data currently available for the population of thoracic organ transplant recipients. This randomized, 2-arm, crossover, open-label study compares the pharmacokinetic profiles of two formulations of cyclosporine (Neoral and Cysporin) in stable heart transplant patients. The pharmacokinetics of Neoral and Cysporin were assessed on 2 study days in 16 stable heart transplant recipients already receiving Neoral, who were at least 15 months post-transplant and had not undergone dose adjustments of Neoral for the previous 3 months. Participants were randomized to receive one study drug for at least 2 weeks with crossover to the other arm for a further 2 weeks. Drug levels were measured from blood s les obtained on the study day at the end of each phase at baseline (pre-dose) and 1, 1.5, 2, 2.5, 3, 4, 6 and 8 hours post-dose. The two formulations of cyclosporine were not found to be bioequivalent for C(max). There was less cyclosporine absorbed with Cysporin than with Neoral (ratio 1.31, 90% confidence intervals 1.20 to 1.42) and, although statistically bioequivalent for area under the curve (AUC), a reduction was observed with the new formulation (ratio 1.17, 90% confidence intervals 1.1 to 1.23). The best fit with AUC was observed at 6 hours post-dose for Neoral and 1.5 hours for Cysporin, not the 2 hours post-dose used clinically. This study suggests that Cysporin may not be clinically bioequivalent to Neoral in heart transplant recipients. The clinical implications of this observation require further exploration in a larger patient cohort.
Publisher: Elsevier BV
Date: 09-2016
Publisher: Wiley
Date: 29-03-2014
DOI: 10.1002/EJHF.90
Publisher: Oxford University Press (OUP)
Date: 27-07-2018
Abstract: Polycystic ovary syndrome (PCOS) prevalence estimates vary when different diagnostic criteria are applied. Lack of standardization of in idual elements within these criteria may contribute to prevalence differences. A systematic review of studies reporting prevalence of PCOS, using at least one of the National Institutes of Health (NIH), Rotterdam or Androgen Excess Society (AE-PCOS) criteria, was conducted. The aim was to investigate the impact on prevalence reporting of different definitions of the clinical elements for PCOS diagnosis. A systematic search of Ovid MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Emcare and BIOSIS was conducted. The search was limited to English language and studies published between January 1990 and January 2018. Included articles needed to define PCOS by at least one of the NIH, Rotterdam or AE-PCOS criteria, be of an unselected population and be published as a full text article. Risk-of-bias was assessed. A total of 21 studies met the inclusion criteria. The random-effects pooled prevalence of PCOS in studies that used the NIH criteria (7% [95% CI: 6-7%]), was significantly different from that identified in studies that used the Rotterdam criteria (12% [95% CI: 10-15%], P < 0.0001) but not studies that used the AE-PCOS criteria (10% [95% CI: 6-13%], P = 0.075). The pooled estimates for Rotterdam and AE-PCOS were not significantly different from each other (P = 0.201). Pooled prevalence estimates were compared between studies separated on the basis of: oligo-amenorrhoea vs oligo-amenorrhoea plus short cycles, clinical androgen excess requiring hirsutism vs any clinical androgen excess, use of different versions and cut-offs for the Ferriman-Gallwey (F-G) score, and inclusion vs non-inclusion of oral contraceptive users. There were no statistically significant differences for any of these comparisons. There was insufficient information to allow subgroup analyses of definitions of polycystic ovaries. Inclusion of ovarian morphology results in statistically significantly higher pooled prevalence estimates for PCOS. Heterogeneity in prevalence estimates for PCOS reflect the broad clinical spectrum of the condition, lack of standardization of the elements within each set of diagnostic criteria and the use of a range of diagnostic cut-offs, as well as potential differences between study populations. The use of different definitions for anovulation and clinical androgen excess did not appear to contribute to differences in the estimated prevalence of PCOS in this study. However, as the number of studies in most of the comparison groups was small, real differences may have been missed. Uncertainty surrounding the diagnosis of PCOS urgently needs to be addressed in order to provide clinicians and their patients with greater diagnostic certainty, and hence reduce inappropriate labelling and the potential psychological harm that may accompany misdiagnosis.
Publisher: Oxford University Press (OUP)
Date: 30-08-2011
Abstract: Background: Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are pre-diabetic states, treatment of which may prevent or delay the onset of overt diabetes and thus potentially reduce major cardiovascular (CV) events. We therefore sought to determine whether interventions (including diet, exercise and pharmacological therapy), altered all-cause and cardiovascular related mortality in such subjects. Methods: We performed a meta-analysis of prospective, randomised controlled trials (RCTs) that were identified in the medical literature and databases. Trials were eligible for inclusion if they reported all-cause mortality rates (at a minimum), recruited approximately 100 patients and had a minimum follow-up of one year. Interventions were ided into pharmacological and non-pharmacological. Results: Ten RCTs that enrolled 23,152 patients met the above entry criteria. Trials ran for an average of 3.75 years. Diabetes was delayed or prevented by these interventions vs control (risk ratio 0.83, 95%CI 0.80–0.86). Non-drug approaches ( n = 3495) were superior to drug-based approaches ( n = 20,872) in diabetes prevention (0.52, 0.46–0.58 vs 0.70, 0.58–0.85, P 0.05). There was no difference in risk of all-cause mortality in the intervention versus control group (0.96, 0.84–1.10) and no difference in CV death (1.04, 0.61–1.78). There was a non-significant trend towards reduction in fatal and non-fatal myocardial infarction (0.59, 0.23–1.50). Fatal and non-fatal stroke was borderline reduced (0.76, 0.58–0.99) with intervention versus control. Conclusions: Despite interventions being mostly successful in retarding progression to overt diabetes, this did not result in reductions in all-cause or cardiovascular mortality, or myocardial infarction, with the possible exception of stroke.
Publisher: Wiley
Date: 21-03-2021
DOI: 10.1111/CEN.14458
Abstract: To compare the performance of two anti‐Mullerian (AMH) assays over a range of concentrations, in s les collected from young women. A cross‐sectional method‐comparison study of 168 non‐healthcare‐seeking women. Included women were aged 18–39 years, not recently pregnant, breast feeding or using systemic hormones. Serum AMH levels were analysed with the Beckman Coulter Access 2 assay from fresh s les and the Ansh picoAMH assay using s les stored at −80°C, in a parallel setting. Comparisons between the two assays were examined using Bland‐Altman plots. Participants had a mean ± SD age of 32.6 ± 5.4 years and body mass index of 28.1 ± 7.9 kg/m 2 , and 60.1% were parous. Although the assay results were highly correlated (Spearman correlation .982, P .001), the relationship between the assays was nonlinear. Serum AMH values below 4 pmol/L were lower with the picoAMH assay compared with the Access AMH assay (mean difference in this range was −0.49 pmol/L), but for s les with a mean value above 10 pmol/L, the picoAMH assay consistently measured higher than the Access AMH assay (mean difference in this range was +8.2 pmol/L). As AMH concentrations increased the absolute discrepancy between the assays also increased. This study demonstrates that despite the high correlation between two commercially available AMH assays, the assays performed in a discordant manner at high and low concentrations. Hence, the results of these assays are not interchangeable, highlighting the need to establish specific reference limits for in idual assays to guide clinical decision‐making and the challenge of establishing future universal cut‐offs for the application of AMH levels in clinical practice.
Publisher: The Endocrine Society
Date: 06-02-2020
Abstract: An important element of the diagnosis of polycystic ovary syndrome is hyperandrogenism. To determine the distribution of modified Ferriman-Gallwey (mF-G) scores, as a measure of facial and body hair growth, and associations between the mF-G scores and serum androgen concentrations, including 11-oxygenated androgens. Cross-sectional study of non-health-care-seeking women, aged 18 to 39 years, recruited from the eastern states of Australia from November 2016 to July 2017. Participants provided an mF-G self-assessment that corresponded to their appearance when not using treatment for excess hair. Androgens were measured in 710 women by liquid chromatography and tandem mass spectrometry. The distribution of the mF-G scores was right-skewed. The median (range) mF-G score of all participants (73.1% Caucasian) was 5 (0–36). The mF-G scores were negatively associated with age (rs = 0.124 P & 0.0001) and positively associated with body mass index (BMI) (rs = 0.073 P & 0.0001). Only androstenedione remained significantly associated with mF-G scores when controlling for age and BMI. Cluster analysis identified 2 groups with mF-G score of & 10 and ≥ 10. Repeating the cluster analysis using the combined vector of mF-G score and androstenedione returned a similar cluster structure, and again separated the 2 groups at a mF-G score & 10 versus ≥ 10. A self-assessed mF-G score ≥ 10 is indicative of excess body hair. Androstenedione, as well as testosterone, should be measured when hyperandrogenism is being evaluated. The lack of association between mF-G scores and the 11-oxygenated androgens highlights the need for a better understanding of these steroids.
Publisher: Springer Science and Business Media LLC
Date: 03-12-2021
DOI: 10.1007/S10096-019-03752-3
Abstract: Influenza is a major cause of presentations to the emergency departments. Introduction of the Rapid Influenza tests has assisted with diagnosis and facilitated patient discharges. We designed this study to identify factors affecting hospital discharge and to understand the role of Rapid Influenza testing. A retrospective observational study of patients was done during influenza season in 2017. Clinical data was obtained from electronic medical records. Rapid Influenza testing was performed using Xpert Flu/RSV (Cepheid, USA). Univariate and multivariate analysis was done using SPSS Version 26 (IBM, NY). A total of 665 patients presented with laboratory-confirmed influenza. Patients discharged from the hospital were younger (median age 62 vs 68, p = 0.031). Patients with immunosuppression, chronic obstructive pulmonary disease (COPD) and pneumonia were more likely to be admitted to hospital. Rapid testing done with a turnaround (TAT) of 2 h (27.8% vs 17.8%, p = 0.002) and with a TAT of 6 h (55% vs 46.3%, p = 0.026) of the patient presentation was associated with a higher rate of hospital discharge. Median TAT of the RIT was 6 h (IQR 1-40 h). On multivariable analysis, RIT TAT of ≤ 2 h (OR 1.62, p = 0.013) was associated with higher likelihood of patients being discharged, whereas immunosuppressed patients (OR 2.25, p = 0.011), COPD (OR 2.42, p = 0.001) and pneumonia on presentation (OR 8.10, p < 0.001) were more likely to get admitted. Patients with COPD, pneumonia on presentation and those with immunosuppression are more likely to be admitted. Rapid Influenza tests can facilitate the discharge of patients from hospital.
Publisher: Wiley
Date: 06-2012
Abstract: The impact of cardiac dysfunction on the liver is known as cardiac hepatopathy. In certain instances this can result in significant hepatic fibrosis or cirrhosis. The validity of non-invasive tools to assess hepatic fibrosis, such as FibroScan(®) which measures liver stiffness (LSM), has not been established in this setting. We examined the impact of cardiac dysfunction on LSM using FibroScan(®) and the influence of volume changes on LSM. A prospective, cross-sectional study examined the use of FibroScan(®) in subjects with left-sided heart failure (LHF, n = 32), right-sided heart failure (RHF, n = 9), and acute decompensated heart failure (ADHF, n = 8). The impact of volume changes upon LSM was further examined in the ADHF group (pre- and post-diuresis) and in a haemodialysis group (HD, n = 12), pre- and post-ultrafiltration on dialysis. Compared with healthy controls [n = 55, LSM = median 4.4 (25th percentile 3.6, 75th percentile 5.1) kPa], LSM was increased in all the cardiac dysfunction subgroups [LHF, 4.7 (4.0, 8.7) kPa, P = 0.04 RHF, 9.7 (5.0, 10.8) kPa, P < 0.001 ADHF, 11.2 (6.7, 14.3) kPa, P 0.05] with mean diuresis 5051 ± 1585 mL, or ultrafiltration in HD [6.0 (3.6, 5.1) vs. 5.7 (4.8, 7.0) kPa, P > 0.05] with mean diuresis 1962 ± 233 mL. Our findings support the concept of increased LSM in the cardiac failure population. LSM was not altered to a statistically significant level with acute volume changes.
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1016/J.IJCARD.2009.12.028
Abstract: Statins are often prescribed for prevention of atherosclerotic outcomes in patients who have chronic heart failure (CHF), if this has an ischaemic etiology. These agents may also possess additional properties, independent of effects on blood lipid levels, which may have an effect on cardiac remodeling. However, beneficial effects were not observed in the recent UNIVERSE trial. We prospectively planned a sub-study of UNIVERSE to explore relevant mechanistic effects of rosuvastatin, including effects on collagen turnover and plasma coenzyme Q10 (CoQ) levels. Additionally, CoQ levels in CHF patients receiving chronic statin therapy were measured. CoQ levels were significantly reduced after 26 weeks of rosuvastatin statin therapy (n = 32), compared to placebo (n = 37) in CHF patients in UNIVERSE trial. Patients with CHF (n = 56) matched for age, gender and severity of disease who had been taking statins for 12 months or longer had CoQ levels of 847 ± 344 nmol/L, significantly lower than 1065.4 ± 394 nmol/L in UNIVERSE patients at baseline (p = 0.0001). Serum types I and III N-terminal procollagen peptide (PINP and PIIINP), measures of collagen turnover which can contribute to cardiac fibrosis were significantly increased in the rosuvastatin group compared to baseline in UNIVERSE patients (PINP: p = 0.03, PIIINP: p = 0.001). In conclusion putative beneficial effects of statin therapy on cardiac remodeling in UNIVERSE may have been negated by increases in collagen turnover markers as well as a reduction in plasma CoQ levels in these patients with CHF.
Publisher: Oxford University Press (OUP)
Date: 06-08-2020
DOI: 10.1016/J.JSXM.2020.07.007
Abstract: Although hypoactive sexual desire dysfunction (HSDD low sexual desire with personal distress) negatively impacts well-being, contemporary life-course prevalence data for HSDD are lacking. To document, in an epidemiologic study, the prevalence of low sexual desire with associated distress (epidemiological HSDD [eHSDD]), and associated psychosocial factors in Australian women. A cross-sectional study of 10,554 women, aged 18–79 years, recruited from the community was performed. Low desire was determined by corresponding questions in the Profile of Female Sexual Function and Female Sexual Function Index. HSDD was defined as having a low desire and Female Sexual Distress Scale-Revised score of ≥11. Clinicians need to be aware that young women often experience sexually related distress whereas low desire with associated distress is most common in women at midlife. The majority of the participants were partnered (66.5%) and 38.9% were recently sexually inactive. Low desire prevalence increased from age 18–24 years to 75–79 years (27.4%, 95% CI 25.5–29.3 vs 91.6%, 95% CI 88.3–94.1, P & .001). Just over half of all participants aged 25–39 years had sexually related personal distress, after which the prevalence declined with age (P & .001). 10,259 participants provided sufficient information for eHSDD classification. eHSDD increased from age 18–24 years (12.2%, 95% CI 10.8–13.7) to 40–44 years (33.4%, 95% CI 28.5–38.8), remained constant until 60–64 years (33.1%, 95% CI 28.3–38.4), and progressively declined to 7.3% (95% CI 4.8–10.9) by 75–79 years. HSDD was significantly, positively associated with being partnered (P & .001), sexually inactive (P & .001), more educated (P = .001), and psychotropic medication use (P & .001), and negatively with Asian ethnicity (P & .001). This study involved the assessment of desire using a single question derived from the Profile of Female Sexual Function or the Female Sexual Function Index. eHSDD is most prevalent at midlife. Furthermore, the likelihood of eHSDD is greater for women who are partnered, sexually inactive, more educated, or taking psychotropic medications. Taken together these findings should aid health professionals in identifying women most at risk of eHSDD.
No related grants have been discovered for Marina Skiba.