ORCID Profile
0000-0003-0534-0584
Current Organisation
Nepean Blue Mountains Local Health District
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Publisher: Public Library of Science (PLoS)
Date: 04-11-2014
Publisher: Elsevier BV
Date: 03-2020
Publisher: Public Library of Science (PLoS)
Date: 21-08-2020
Publisher: S. Karger AG
Date: 2016
DOI: 10.1159/000446176
Publisher: Wiley
Date: 16-10-2017
DOI: 10.1002/EAT.22786
Abstract: Anorexia nervosa (AN) is a prevalent, serious mental disorder. We aimed to evaluate the cost-effectiveness of family-based treatment (FBT) compared to adolescent-focused in idual therapy (AFT) or no intervention within the Australian healthcare system. A Markov model was developed to estimate the cost and disability-adjusted life-year (DALY) averted of FBT relative to comparators over 6 years from the health system perspective. The target population was 11-18 year olds with AN of relatively short duration. Uncertainty and sensitivity analyses were conducted to test model assumptions. Results are reported as incremental cost-effectiveness ratios (ICER) in 2013 Australian dollars per DALY averted. FBT was less costly than AFT. Relative to no intervention, the mean ICER of FBT and AFT was $5,089 (95% uncertainty interval (UI): dominant to $16,659) and $51,897 ($21,591 to $1,712,491) per DALY averted. FBT and AFT are 100% and 45% likely to be cost-effective, respectively, at a threshold of AUD$50,000 per DALY averted. Sensitivity analyses indicated that excluding hospital costs led to increases in the ICERs but the conclusion of the study did not change. FBT is the most cost-effective among treatment arms, whereas AFT was not cost-effective compared to no intervention. Further research is required to verify this result.
Publisher: American Diabetes Association
Date: 14-10-2022
DOI: 10.2337/CD21-0142
Publisher: Informa UK Limited
Date: 09-04-2014
DOI: 10.1586/17512433.2014.908703
Abstract: Diabetes and its complications account for a significant healthcare burden. There is increasing prevalence of diabetes and newer drugs are being investigated to improve outcomes. Sodium-glucose cotransporter inhibitors (SGLT2 inhibitors) are a newer class of medications, which prevent renal reabsorption of glucose and hence help in glycaemic control without significant risk of hypoglycaemia. Two drugs, namely dapagliflozin and canagliflozin have gained approval and empagliflozin is one of the advanced agents of this class. Early trials with empagliflozin have shown a stable pharmacokinetic profile and pharmacodynamic effects with significant SGLT2 selectivity. Clinical trials have shown improvement in glycaemic control and other benefits including weight loss and lowering of blood pressure. Ongoing trials and surveillance will provide answers about cardiovascular benefits, risk of osteoporosis and cancer.
Publisher: Public Library of Science (PLoS)
Date: 04-02-2013
Publisher: Elsevier BV
Date: 2016
Publisher: MDPI AG
Date: 16-01-2023
Abstract: Increased numbers of patients with chronic conditions use nutraceuticals or food-based therapeutics. However, to date, there is no global consensus on the regulatory processes for nutraceuticals. With the increased use, issues of quality and safety have also arisen. This review summarises the current regulations held for nutraceuticals in the USA, European and Australian jurisdictions using regulatory authority sites and databases. The efficacy and safety concerns, product development, gaps in regulation and challenges in ensuring product authenticity are also summarised. The data highlight the complexity that the globalisation of nutraceuticals brings with respect to challenges in regulation and associated claims regarding efficacy and safety. The development of an effective system with integrity is needed to increase vertical collaboration between consumers, healthcare practitioners, and government agencies and the development of international risk assessment criteria and botanical compendia. This will help in greater transparency and improved trust in the process and products. Emerging technologies could play a role in improving systems engineering by information sharing and leveraging the strengths of different countries. In conclusion, nutraceuticals have been poorly regulated leading to spurious claims based on little or no real evidence. This makes it difficult to separate meaningful results from poor data. More stringent regulation and an effective system of integrity are required to ensure efficacy and safety and enable the adequate monitoring and increase consumer and healthcare professionals’ confidence.
Publisher: Cambridge University Press (CUP)
Date: 11-08-2017
DOI: 10.1017/S2045796016000469
Abstract: School-based psychological interventions encompass: universal interventions targeting youth in the general population and indicated interventions targeting youth with subthreshold depression. This study aimed to: (1) examine the population cost-effectiveness of delivering universal and indicated prevention interventions to youth in the population aged 11–17 years via primary and secondary schools in Australia and (2) compare the comparative cost-effectiveness of delivering these interventions using face-to-face and internet-based delivery mechanisms. We reviewed literature on the prevention of depression to identify all interventions targeting youth that would be suitable for implementation in Australia and had evidence of efficacy to support analysis. From this, we found evidence of effectiveness for the following intervention types: universal prevention involving group-based psychological interventions delivered to all participating school students and indicated prevention involving group-based psychological interventions delivered to students with subthreshold depression. We constructed a Markov model to assess the cost-effectiveness of delivering universal and indicated interventions in the population relative to a ‘no intervention’ comparator over a 10-year time horizon. A disease model was used to simulate epidemiological transitions between three health states (i.e., healthy, diseased and dead). Intervention effect sizes were based on meta-analyses of randomised control trial data identified in the aforementioned review while health benefits were measured as Disability-adjusted Life Years (DALYs) averted attributable to reductions in depression incidence. Net costs of delivering interventions were calculated using relevant Australian data. Uncertainty and sensitivity analyses were conducted to test model assumptions. Incremental cost-effectiveness ratios (ICERs) were measured in 2013 Australian dollars per DALY averted with costs and benefits discounted at 3%. Universal and indicated psychological interventions delivered through face-to-face modalities had ICERs below a threshold of $50 000 per DALY averted. That is, $7350 per DALY averted (95% uncertainty interval (UI): dominates – 23 070) for universal prevention, and $19 550 per DALY averted (95% UI: 3081–56 713) for indicated prevention. Baseline ICERs were generally robust to changes in model assumptions. We conducted a sensitivity analysis which found that internet-delivered prevention interventions were highly cost-effective when assuming intervention effect sizes of 100 and 50% relative to effect sizes observed for face-to-face delivered interventions. These results should, however, be interpreted with caution due to the paucity of data. School-based psychological interventions appear to be cost-effective. However, realising efficiency gains in the population is ultimately dependent on ensuring successful system-level implementation.
Publisher: Public Library of Science (PLoS)
Date: 28-10-2015
Publisher: MDPI AG
Date: 20-09-2021
DOI: 10.3390/NU13093284
Abstract: Background: Sarcopenia is associated with significant morbidity and mortality in patients with chronic kidney disease. The prevalence of sarcopenia in the dialysis population varies from 4% to 63%. However, the prevalence and risk factors of sarcopenia in the Australian dialysis population remain uncertain. Aim: To study the prevalence of sarcopenia in patients on maintenance dialysis by using the European Working Group on Sarcopenia in Older People (EWGSOP) diagnostic criteria of sarcopenia and to identify associated risk factors. Methods: We evaluated adult patients on maintenance haemodialysis and peritoneal dialysis in this single-centre cross-sectional study in Australia. Patient’s clinical (age, gender, dialysis modality and diabetic status) and laboratory parameters (serum albumin, calcium, phosphate, 25-hydroxy-vitamin D and parathyroid hormone levels) were investigated. We employed bioimpedance spectroscopy, hand grip dynamometer and the timed up and go test (TUG) to evaluate muscle mass, strength and function, respectively. Results: We evaluated 39 dialysis patients with a median age of 69 years old. The prevalence of sarcopenia was 18%. Sarcopenia was associated with low serum albumin (p = 0.02) and low serum phosphate level (p = 0.04). Increasing age and female sex were potential risk factors for sarcopenia (p = 0.05 and 0.08, respectively). Low lean muscle mass, reduced hand grip strength and prolonged TUG were present in 23.1%, 41% and 40.5%, respectively, of the cohort. The hand grip test had good correlation with lean muscle evaluation and the TUG. Conclusions: Sarcopenia was prevalent in 18% of maintenance haemodialysis patients from an Australian single-centre cohort, with low serum albumin and phosphate as significant risk factors.
Publisher: Wiley
Date: 22-04-2016
DOI: 10.1111/NEP.12618
Abstract: In addition to lowering blood glucose in patients with type 2 diabetes mellitus, dipeptidyl peptidase 4 (DPP4) inhibitors have been shown to be antifibrotic and anti-inflammatory. We have previously shown that DPP4 inhibition in human kidney proximal tubular cells exposed to high glucose reduced fibrotic and inflammatory markers. Hence, we wanted to demonstrate renoprotection in an in vivo model. We used a type 1 diabetic animal model to explore the renoprotective potential of saxagliptin independent of glucose lowering. We induced diabetes in enos -/- mice using streptozotocin and matched glucose levels using insulin. Diabetic mice were treated with saxagliptin and outcomes compared with untreated diabetic mice. We provide novel data that saxagliptin limits renal hypertrophy, transforming growth factor beta-related fibrosis and NF-κBp65-mediated macrophage infiltration. Overall, there was a reduction in histological markers of tubulointerstitial fibrosis. There was no reduction in albuminuria or glomerulosclerosis. Our findings highlight the potential of DPP4 inhibition as additional therapy in addressing the multiple pathways to achieve renoprotection in diabetic nephropathy.
Publisher: Oxford University Press (OUP)
Date: 29-10-2020
Abstract: Artemisinin derivatives are the leading class of antimalarial drugs due to their rapid onset of action and rapid clearance of circulating parasites. The parasite clearance half-life measures the rate of loss of parasites from blood after treatment, and this is currently used to assess antimalarial activity of novel agents and to monitor resistance. However, a number of recent studies have challenged the use of parasite clearance to measure drug activity, arguing that many circulating parasites may be nonviable. Plasmodium falciparum–infected subjects (n = 10) in a malaria volunteer infection study were administered a single dose of artesunate (2 mg/kg). Circulating parasite concentration was assessed by means of quantitative polymerase chain reaction (qPCR). Parasite viability after artesunate administration was estimated by mathematical modeling of the ex vivo growth of parasites collected from subjects. We showed that in artemisinin-sensitive infection, viable parasites declined to & .1% of baseline within 8 hours after artesunate administration, while the total number of circulating parasites measured with quantitative polymerase chain reaction remained unchanged. In artemisinin-resistant infections over the same interval, viable parasites declined to 51.4% (standard error of the mean, 4.6%) of baseline. These results demonstrate that in vivo drug activity of artesunate is faster than is indicated by the parasite clearance half-life.
Publisher: American Physiological Society
Date: 15-07-2013
DOI: 10.1152/AJPRENAL.00398.2012
Abstract: Inflammatory responses are central to the pathogenesis of diabetic nephropathy. Toll-like receptors (TLRs) are ligand-activated membrane-bound receptors which induce inflammatory responses predominantly through the activation of NF-κB. TLR2 and 4 are present in proximal tubular cells and are activated by endogenous ligands upregulated in diabetic nephropathy, including high-mobility group box-1 (HMGB1) and fibronectin. Human proximal tubules were exposed to 5 mM (control), 11.2 mM (approximating the clinical diagnostic threshold for diabetes mellitus), and 30 mM (high) glucose for 72 h or 7 days. Cells were harvested for protein, mRNA, and nuclear extract to assess for TLR2, 4, and inflammatory markers. Glucose (11.2 mM) maximally increased TLR2 and 4 expression, HMGB1 release, and NF-κB activation with increased expression of cytokines. However, only TLR2 expression and subsequent NF-κB binding were sustained at 7 days. Recombinant HMGB1 induced NF-κB activation, which was prevented by both TLR2 silencing [small interfering (si)RNA] and TLR4 inhibition. Peroxisome proliferator-activated receptor-γ (PPAR-γ) transcription was reduced by exposure to 11.2 mM glucose with an increase observed at 30 mM glucose at 24 h. This may reflect a compensatory increase in PPAR-γ induced by exposure to 30 mM glucose, limiting the inflammatory response. Therefore, short-term moderate increases in glucose in vitro increase HMGB1, which mediates NF-κB activation through both TLR2 and 4. Furthermore, in vivo, streptozotocin-induced diabetic mice exhibited an increase in tubular TLR2 and HMGB1 expression. These results collectively suggest that TLR2 is likely to be the predominant long-term mediator of NF-κB activation in transducing inflammation in diabetic nephropathy.
Publisher: John Wiley & Sons, Ltd
Date: 12-11-2014
Publisher: Springer Science and Business Media LLC
Date: 16-02-2021
DOI: 10.1186/S12936-021-03627-Z
Abstract: New anti-malarial therapeutics are required to counter the threat of increasing drug resistance. Malaria volunteer infection studies (VIS), particularly the induced blood stage malaria (IBSM) model, play a key role in accelerating anti-malarial drug development. Supply of the reference 3D7-V2 Plasmodium falciparum malaria cell bank (MCB) is limited. This study aimed to develop a new MCB, and compare the safety and infectivity of this MCB with the existing 3D7-V2 MCB, in a VIS. A second bank (3D7-V1) developed in 1995 was also evaluated. The 3D7-V2 MCB was expanded in vitro using a bioreactor to produce a new MCB designated 3D7-MBE-008. This bank and 3D7-V1 were then evaluated using the IBSM model, where healthy participants were intravenously inoculated with blood-stage parasites. Participants were treated with artemether-lumefantrine when parasitaemia or clinical thresholds were reached. Safety, infectivity and parasite growth and clearance were evaluated. The in vitro expansion of 3D7-V2 produced 200 vials of the 3D7-MBE-008 MCB, with a parasitaemia of 4.3%. This compares to 0.1% in the existing 3D7-V2 MCB, and 0.01% in the 3D7-V1 MCB. All four participants (two per MCB) developed detectable P. falciparum infection after inoculation with approximately 2800 parasites. For the 3D7-MBE-008 MCB, the parasite multiplication rate of 48 h (PMR 48 ) using non-linear mixed effects modelling was 34.6 (95% CI 18.5–64.6), similar to the parental 3D7-V2 line parasitaemia in both participants exceeded 10,000/mL by day 8. Growth of the 3D7-V1 was slower (PMR 48 of 11.5 [95% CI 8.5–15.6]), with parasitaemia exceeding 10,000 parasites/mL on days 10 and 8.5. Rapid parasite clearance followed artemether-lumefantrine treatment in all four participants, with clearance half-lives of 4.01 and 4.06 (weighted mean 4.04 [95% CI 3.61–4.57]) hours for 3D7-MBE-008 and 4.11 and 4.52 (weighted mean 4.31 [95% CI 4.16–4.47]) hours for 3D7-V1. A total of 59 adverse events occurred most were of mild severity with three being severe in the 3D7-MBE-008 study. The safety, growth and clearance profiles of the expanded 3D7-MBE-008 MCB closely resemble that of its parent, indicating its suitability for future studies. Trial Registration: Australian New Zealand Clinical Trials registry numbers: P3487 (3D7-V1): ACTRN12619001085167. P3491 (3D7-MBE-008): ACTRN12619001079134
Publisher: Oxford University Press (OUP)
Date: 02-03-2017
DOI: 10.1093/CKJ/SFW132
Publisher: Springer Science and Business Media LLC
Date: 14-01-2021
DOI: 10.1186/S12936-021-03581-W
Abstract: In the absence of a method to culture Plasmodium vivax , the only way to source parasites is ex vivo. This h ers many aspects of P. vivax research. This study aimed to assess the safety of apheresis, a method for selective removal of specific components of blood as a means of extracting and concentrating P. vivax parasites. An iterative approach was employed across four non-immune healthy human subjects in single subject cohorts. All four subjects were inoculated with ~ 564 blood stage P. vivax (HMP013- Pv ) and subjected to apheresis 10 to 11 days later . Blood s les collected during apheresis (haematocrit layers 0.5% to 11%) were tested for the presence and concentration of P. vivax by microscopy, flow cytometry, 18S rDNA qPCR for total parasites, and pvs2 5 qRT-PCR for female gametocyte transcripts. Safety was determined by monitoring adverse events. Malaria transmission to mosquitoes was assessed by membrane feeding assays. There were no serious adverse events and no significant safety concerns. Apheresis concentrated asexual parasites by up to 4.9-fold (range: 0.9–4.9-fold) and gametocytes by up to 1.45-fold (range: 0.38–1.45-fold) compared to pre-apheresis densities. No single haematocrit layer contained 40% of all the recovered P. vivax asexual parasites. Ex vivo concentration of parasites by Percoll gradient centrifugation of whole blood achieved greater concentration of gametocytes than apheresis. Mosquito transmission was enhanced by up to fivefold in a single apheresis s le compared to pre-apheresis. The modest level of parasite concentration suggests that the use of apheresis may not be an ideal method for harvesting P. vivax. Trial Registration Australia New Zealand Clinical Trials Registry (ANZCTR) Trial ID: ACTRN12617001502325 registered on 19th October 2017. www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373812.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 31-03-2023
DOI: 10.2215/CJN.0000000000000160
Abstract: The blockade of immune regulatory sites, cytotoxic T-lymphocyte antigen 4, programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1) with immune checkpoint inhibitors has revolutionized survival outcomes in patients with cancer. However, immune checkpoint inhibitors are associated with a range of immune-related adverse events. The aim of this network meta-analysis was to evaluate severe adverse kidney events in patients with oncological or hematological malignancy receiving monotherapy, dual therapy, or combined therapy treatment with immune checkpoint inhibitors when compared with either placebo or standard chemotherapy. Phase 3 randomized control trials reporting severe grade (3–5) adverse kidney events were identified across five electronic databases from inception to May 2022. This was supplemented with hand searching of medical journals and the National Clinical Trials registry. A Bayesian network meta-analysis was performed for AKI, hypertension, CKD, and the composite of all acute kidney adverse events. The results are reported as per the PRISMA guidelines. Ninety-five randomized control trials reported severe grade adverse kidney events. The risk of developing severe AKI is higher among patients who received PD-1 plus chemotherapy (odds ratio [OR], 1.8 95% credible interval [CrI], 1.4 to 2.5) and PD-L1 plus chemotherapy (OR, 1.8 95% CrI, 1.2 to 2.7) compared with standard chemotherapy and placebo (94 studies, 63,357 participants). The risk of developing the composite of all severe acute kidney adverse events is higher among patients who received PD-1 plus chemotherapy (OR, 1.6 95% CrI, 1.1 to 2.3) and PD-L1 plus chemotherapy (OR, 1.7 95% CrI, 1.1 to 2.8) when compared with standard chemotherapy and placebo (95 studies, 63,973 participants). The combined regimen of PD-1 plus chemotherapy and PD-L1 plus chemotherapy was associated with higher incidence of severe AKI and the composite of all severe acute kidney adverse events. This article contains a podcast at edirect.mp3/edia odcast/CJASN/2023_07_10_CJN0000000000000160.mp3
Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.JAD.2014.11.061
Abstract: Depression symptom screening scales are often used to determine a clinical diagnosis of major depressive disorder (MDD) in prevention research. The aim of this review is to systematically examine the reliability, validity and diagnostic utility of commonly used screening scales in depression prevention research among children and adolescents. We conducted a systematic review of the electronic databases PsycINFO, PsycEXTRA and Medline examining the reliability, validity and diagnostic utility of four commonly used depression symptom rating scales among children and adolescents: the Children׳s Depression Inventory (CDI), Beck Depression Inventory (BDI), Center for Epidemiologic Studies - Depression Scale (CES-D) and the Reynolds Adolescent Depression Scale (RADS). We used univariate and bivariate random effects models to pool data and conducted metaregression to identify and explain causes of heterogeneity. We identified 54 studies (66 data points, 34,542 participants). Across the four scales, internal reliability was 'good' (pooled estimate: 0.89, 95% Confidence Interval (CI): 0.86-0.92). Sensitivity and specificity were 'moderate' (sensitivity: 0.80, 95% CI: 0.76-0.84 specificity: 0.78, 95% CI: 0.74-0.83). For studies that used a diagnostic interview to determine a diagnosis of MDD, positive predictive power for identifying true cases was mostly poor. Psychometric properties did not differ on the basis of study quality, s le type (clinical vs. nonclinical) or s le age (child vs. adolescent). Some analyses may have been underpowered to identify conditions in which test performance may vary, due to low numbers of studies with adequate data. Commonly used depression symptom rating scales are reliable measures of depressive symptoms among adolescents however, using cutoff scores to indicate clinical levels of depression may result in many false positives.
Publisher: Wiley
Date: 24-01-2015
DOI: 10.1111/NEP.12347
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2013
Publisher: Cold Spring Harbor Laboratory
Date: 27-10-2020
DOI: 10.1101/2020.10.26.20214619
Abstract: Containing the spread of artemisinin (ART)-resistant Plasmodium falciparum will be assisted by improved understanding of its human-to-mosquito transmission. We compared gametocyte dynamics among field isolates containing K13 mutations conferring ART resistance and K13 wild-type parasites. In Pailin, Cambodia, the male to female gametocyte ratio was higher among K13 mutant infections compared to K13 wild-type infections. We also investigated the effects of artesunate and atovaquone-proguanil on the transmissibility of an ART-resistant K13 mutant strain, Cam3.II R539T , in a volunteer infection study. Gametocyte production was higher after a single dose of artesunate (2 mg/kg) in volunteers infected with ART-resistant compared to ART-sensitive parasites. Despite the presence of gametocytes in volunteers infected with ART-resistant parasites, there was no infection observed in Anopheles stephensi mosquitoes after atovaquone-proguanil treatment. We report transmission determinants of ART-resistant infections that could be advantageous over ART-sensitive infections. Moreover, we show additional benefits of treating ART-resistant infections with atovaquone-proguanil treatment.
Location: India
No related grants have been discovered for Muralikrishna Gangadharan Komala.