ORCID Profile
0000-0001-9038-8050
Current Organisation
UNSW Sydney
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Publisher: Wiley
Date: 26-12-2018
DOI: 10.1111/DMCN.13651
Abstract: To identify a cohort of children with cerebral palsy ( CP ) from hospital data determine the proportion that participated in standardized educational testing and attained a score within the normal range and describe the relationship between test results and motor symptoms. This population‐based retrospective cohort study used data from New South Wales, Australia. We linked hospital data for children younger than 16 years of age admitted between 1st July 2000 and 31st March 2014 to education data from 2009 to 2014. Hospital diagnosis codes were used to identify a cohort of children with CP ( n =3944) and describe their motor symptoms. Educational outcomes in the CP cohort were compared with those among children without CP . Of those with educational data ( n =1770), 46% were exempt from reading assessment because of intellectual or functional disability, 7% were absent or withdrawn from testing and 47% participated in testing. About 30% of all children with educational data had test scores in the normal range. The proportion was greatest among those with hemiplegia ( %) and lowest among those with tetraplegia ( %). One‐third of children with CP participated in standardized testing and achieved a result in the normal range. The proportions were lower in children with more severe motor symptoms. From 2009 to 2014, most Australian children with cerebral palsy (CP) attended a mainstream school. The rate of disability‐related exemption from standardized educational testing was almost 50%. Thirty per cent of children with CP achieved educational scores in the normal range.
Publisher: BMJ
Date: 18-09-2014
Publisher: Elsevier BV
Date: 11-2022
DOI: 10.1016/J.JPSYCHIRES.2022.09.050
Abstract: Research has posited that machine learning could improve suicide risk prediction models, which have traditionally performed poorly. This systematic review and meta-analysis evaluated the performance of machine learning models in predicting longitudinal outcomes of suicide-related outcomes of ideation, attempt, and death and examines outcome, data, and model types as potential covariates of model performance. Studies were extracted from PubMed, Web of Science, Embase, and PsycINFO. A bivariate mixed effects meta-analysis and meta-regression analyses were performed for studies using machine learning to predict future events of suicidal ideation, attempts, and/or deaths. Risk of bias was assessed for each study using an adaptation of the Prediction model Risk Of Bias Assessment Tool. Narrative review included 56 studies, and analyses examined 54 models from 35 studies. The models achieved a very good pooled AUC of 0.86, sensitivity of 0.66 (95% CI [0.60, 0.72)], and specificity of 0.87 (95% CI [0.84, 0.90]). Pooled AUCs for ideation, attempt, and death were similar at 0.88, 0.87, and 0.84 respectively. Model performance was highly varied however, meta-regressions did not provide evidence that performance varied by outcome, data, or model types. Findings suggest that machine learning has the potential to improve suicide risk detection, with pooled estimates of machine learning performance comparing favourably to performance of traditional suicide prediction models. However, more studies with lower risk of bias are necessary to improve the application of machine learning in suicidology.
Publisher: Cold Spring Harbor Laboratory
Date: 26-11-2021
DOI: 10.1101/2021.11.24.21266837
Abstract: Depression and anxiety affect 4% to 14% of Australians every year symptoms may have been exacerbated during the COVID-19 pandemic. We examined recent patterns of antidepressant use in Australia in the period 2015 to 2021, which includes the first year of the pandemic. We used national dispensing claims for people aged ≥10 years to investigate annual trends in prevalent and new antidepressant use (no antidepressants dispensed in the year prior). We conducted stratified analyses by sex, age group and antidepressant class. We report outcomes from 2015 to 2019 and used time series analysis to quantify changes during the first year of the COVID-19 pandemic (March 2020 to February 2021). In 2019 the annual prevalence of antidepressant use was 170.4 per 1,000 women and 101.8 per 1,000 men, an increase of 7.0% and 9.2% from 2015, respectively. New antidepressant use also increased for both sexes (3.0% for women and 4.9% for men) and across most age groups, particularly among adolescents (aged 10-17 years 46%-57%). During the first year of the COVID-19 pandemic, we observed higher than expected prevalent use (+2.2%, 95%CI 0.3%, 4.2%) among females, corresponding to a predicted excess of 45,217 (95%CI 5,819, 84,614) females dispensed antidepressants. The largest increases during the first year of the pandemic occurred among female adolescents for both prevalent (+11.7%, 95%CI 4.1%, 20.5%) and new antidepressant use (+15.6%, 95%CI 8.5%, 23.7%). Antidepressant use continues to increase in Australia overall and especially among young people. We found a differential impact of the COVID-19 pandemic in treated depression and anxiety, greater among females than males, and greater among young females than other age groups, suggesting an increased mental health burden in populations already on a trajectory of increased use of antidepressants prior to the pandemic. Reasons for these differences require further investigation.
Publisher: American Chemical Society (ACS)
Date: 18-09-2002
DOI: 10.1021/JO0262107
Abstract: The reaction of stabilized Peterson reagents (alpha-silyl ester enolates) with ketones has been studied theoretically and experimentally. Enolate geometry was studied by trapping experiments and NMR spectroscopy and was found to differ markedly with the nature of the base (LiHMDS vs LDA vs KHMDS). The chelating effect of the lithium counterion was found to be critical for the reaction. For the two ketones studied, the combined weight of experimental and computational data assigns geometrical selectivity to the initial addition transition state, though in general there appears to be a fine balance between three possible choices for the rate-determining step.
Publisher: Elsevier BV
Date: 05-2002
DOI: 10.1016/S0968-0896(01)00407-2
Abstract: The pH dependence of the affinity of a 11-mer phosphotyrosine (pY) peptide (EPQpYEEIPIYL-NH2) for the SH2 domain of the tyrosine kinase p56(lck) was investigated with surface plasmon resonance (SPR). From SPR competition experiments the affinity in solution was obtained. The pH dependence of the affinity in solution can be well described by a proton linkage model with a single pK(a) shift upon binding, from 6.1 to 4.7. This shift is ascribed to the transition from the -2 to the -1 ionisation state of the tyrosine phosphate group. Based on the X-ray structure for the complex with Lck SH2, a pK(a) value of 5.3 for the bound pY peptide was computed, modelling the solvated protein as a system of point charges in a continuum. With the phosphate in the -2 state the binding energy is 1.8 kcal/mol more favourable than for the -1 state, corresponding to a 20-fold higher affinity. A proper charge is relevant in the design of potential therapeutic Lck SH2 ligands with mimics for the metabolically unstable tyrosine phosphate group.
Publisher: American Chemical Society (ACS)
Date: 09-10-2003
DOI: 10.1021/MA0351672
Publisher: Wiley
Date: 12-11-2016
Abstract: Describe the dispensing patterns for guideline-recommended medications during 2008 in people with acute coronary syndrome (ACS) and how dispensing varies by gender and time since last ACS hospitalization. A descriptive cohort spanning 20 years of people alive post-ACS in 2008. We extracted all ACS hospitalizations and deaths in Western Australia (1989-2008), and all person-linked Pharmaceutical Benefits Scheme claims nationally for 2008. Participants were 23 642 men and women (36.8%), alive and aged 65-89 years in mid-2008 who were hospitalized for ACS between 1989 and 2008. Main outcome was the proportion of the study cohort (in 2008) dispensed guideline-recommended cardiovascular medications in that year. Adjusted odds ratios estimating the association between type (and number) of guideline-recommended medications and time since last ACS hospitalization. Medications most commonly dispensed in 2008 were statins (79.6% of study cohort) and then angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (ACEi/ARBs) (71.1%), aspirin or clopidogrel (59.4%), and β-blockers (54.6%). Only 51.8% of the cohort was dispensed three or more of these drug types in 2008. Women with ACS were 18% less likely to be dispensed statins (adjusted odds ratio (OR)=0.82 95% CI 0.76-0.88). Overall, for each incremental year since last ACS admission, there was an 8% increased odds (adjusted OR=1.08 95% CI 1.07-1.08) of being dispensed fewer of the recommended drug regimen in 2008. Longer time since last ACS admission was associated with dispensing fewer medications types and combinations in 2008. Interventions are warranted to improve dispensing long term and any apparent gender inequality in the drug class filled.
Publisher: SAGE Publications
Date: 25-04-2023
Publisher: Oxford University Press (OUP)
Date: 25-11-2010
Publisher: Wiley
Date: 17-08-2022
DOI: 10.1111/BCP.15000
Abstract: Public health responses to reduce SARS‐CoV‐2 transmission have profoundly affected the epidemiology and management of other infections. We examined the impact of COVID‐19 restrictions on antibiotic dispensing in Australia. We used national claims data to investigate antibiotic dispensing trends from November 2015 to October 2020 and whether changes reflected reductions in primary care consultations. We used interrupted time series analysis to quantify changes in monthly antibiotic dispensing and face‐to‐face and telehealth GP consultations and examined changes by recipient age, pharmacy State and prescriber specialty. Over the study period, an estimated 19 921 370 people had 125 495 137 antibiotic dispensings, 71% prescribed by GPs. Following COVID‐19 restrictions, we observed a sustained 36% (95% CI: 33–40%) reduction in antibiotic dispensings from April 2020. Antibiotics recommended for managing respiratory tract infections showed large reductions (range 51–69%), whereas those recommended for non‐respiratory infections were unchanged. Dispensings prescribed by GPs decreased from 63.5 per 1000 population for April–October 2019 to 37.0 per 1000 for April–October 2020. Total GP consultation rates remained stable, but from April 2020, 31% of consultations were telehealth. In a setting with a low COVID‐19 incidence, restrictions were associated with a substantial reduction in community dispensings of antibiotics primarily used to treat respiratory infections, coincident with reported reductions in respiratory viral infections. Our findings are informative for post‐pandemic antimicrobial stewardship and highlight the potential to reduce inappropriate prescribing by GPs and specialists for respiratory viral infections.
Publisher: CMA Joule Inc.
Date: 17-11-2015
DOI: 10.1503/CMAJ.140848
Publisher: Wiley
Date: 15-10-2022
DOI: 10.1111/BCP.15074
Abstract: To examine trends in the prevalence and incidence of prescription opioid analgesic use in Australian women of reproductive age and to estimate the number of calendar months each year that women were dispensed opioids. We conducted a retrospective cross‐sectional study involving women aged 15–44 years using pharmaceutical dispensing claims for a 10% random s le of Australians. For the period 2013–2020, we calculated the annual prevalence and incidence of opioid analgesic dispensing per 100 (%) population by opioid type and age group. We also estimated the total number of calendar months that women were dispensed at least 1 opioid each year. The prevalence of opioid use decreased from 12.8% in 2013 to 11.3% in 2020, representing a relative decrease of 11.6% (95% confidence interval 10.7, 12.6%). The incidence of opioid use decreased from 10.3% in 2014 to 8.3% in 2020, representing a relative decrease of 18.6% (95% confidence interval 17.6, 19.6%). Codeine in combination products, followed by oxycodone and tramadol, were the most prevalent opioids. Prevalence and incidence of opioid use were lowest in women aged 15–19 years and the highest in women 30 years and above. Among all women dispensed opioids, 72.7% were dispensed an opioid in only 1 month each year. Prescription opioid use remains common, although decreasing, among women of reproductive age in Australia. However, it is reassuring that the majority of opioid use in this population is short term.
Publisher: SAGE Publications
Date: 23-08-2023
DOI: 10.1177/00048674221114782
Abstract: New therapeutic options such as lisdexamfetamine and guanfacine have recently become available for the treatment of attention deficit hyperactivity disorder. We described contemporary patterns of attention deficit hyperactivity disorder medicine use among children, adolescents and adults in Australia. This population-based study used dispensing data for a 10% random s le of Australian residents between July 2012 and December 2020. We estimated the annual prevalence and incidence of attention deficit hyperactivity disorder medicines, second-line guanfacine use and examined concurrent medicine use of both stimulants and non-stimulants. We followed incident users for up to 5 years and analysed treatment persistence using a novel proportion of people covered method. Analyses were stratified by attention deficit hyperactivity disorder medicine, sex and age group young children (0–5 years), children (6–12 years), adolescents (13–17 years), young adults (18–24 years) and adults (⩾25 years). We observed a twofold increase in the overall prevalence of attention deficit hyperactivity disorder medicine use between 2013 and 2020, from 4.9 to 9.7 per 1000 persons. Incident use also increased across all age groups and both sexes, with the most pronounced increases among adolescent females (from 1.4 to 5.3 per 1000 persons). Stimulant treatment persistence after 5 years was highest among those initiating treatment as young children (64%) and children (69%) and lowest among those initiating treatment in adolescence (19%). Concurrent use of stimulants and non-stimulants was more common among males and younger age groups. Most children (87%) initiating guanfacine had prior dispensings of attention deficit hyperactivity disorder medicines. We observed increasing attention deficit hyperactivity disorder medicine use in Australia, especially among young females. Nevertheless, treatment rates remain lower than the estimated prevalence of attention deficit hyperactivity disorder across all subpopulations. Poor long-term treatment persistence in adolescence may warrant improved clinical monitoring of attention deficit hyperactivity disorder in patients transitioning from paediatric to adult care. Reassuringly, use of newly approved guanfacine appeared to be in accordance with guidelines among children.
Publisher: Springer Science and Business Media LLC
Date: 03-2005
DOI: 10.1007/S10822-005-3693-6
Abstract: R67 dihydrofolate reductase (DHFR), a bacterial plasmid-encoded enzyme associated with resistance to the drug trimethoprim, shows neither sequence nor structural homology with the chromosomal DHFR. It presents a highly symmetrical toroidal structure, where four identical monomers contribute to the unique central active-site pore. Two reactants (dihydrofolate, DHF), two cofactors (NADPH) or one of each (R67*DHF*NADPH) can be found simultaneously within the active site, the last one being the reactive ternary complex. As the positioning of the ligands has proven elusive to empirical determination, we addressed the problem from a theoretical perspective. Several potential structures of the ternary complex were generated using the docking programs AutoDock and FlexX. The variability among the final poses, many of which conformed to experimental data, prompted us to perform a comparative scoring analysis and molecular dynamics simulations to assess the stability of the complexes. Analysis of ligand-ligand and ligand-protein interactions along the 4 ns trajectories of eight different structures allowed us to identify important inter-ligand contacts and key protein residues. Our results, combined with published empirical data, clearly suggest that multipe binding modes of the ligands are possible within R67 DHFR. While the pterin ring of DHF and the nicotinamide ring of NADPH assume a stacked endo-conformation at the centre of the pore, probably assisted by V66, Q67 and I68, the tails of the molecules extend towards opposite ends of the cavity, adopting multiple configurations in a solvent rich-environment where hydrogen-bond interactions with K32 and Y69 may play important roles.
Publisher: Wiley
Date: 09-12-2021
DOI: 10.1111/ADD.15755
Abstract: Many nations have provisions for involuntary treatment of alcohol dependence where the person is at serious risk of harm to themselves. To date, there has been little thorough evaluation of its effectiveness. This study aimed to determine if there were differences between involuntary and voluntary treatment for alcohol dependence on subsequent emergency and hospital care. A retrospective cohort design using linked routinely collected administrative data on health‐care utilization. Hospital and community‐based alcohol treatment, New South Wales, Australia. A total of 231 patients who were involuntarily treated for alcohol dependence and 231 matched controls who received treatment as usual within the period May 2012 to April 2018. Involuntary treatment comprised a 28‐day mandated hospital admission which included supervised withdrawal, comprehensive assessment, rehabilitation and support followed by voluntary aftercare support for up to 6 months. Treatment as usual comprised three not mutually exclusive forms of intensive voluntary alcohol treatment: withdrawal management, rehabilitation and pharmacotherapies for alcohol dependence. Outcome measures: changes in the number of emergency department (ED) visits and number of unplanned hospital admissions 12 months before and 12 months after completion of index treatment. Both groups showed a reduction in ED visits (incidence rate ratio (IRR) = 0.56, 95% credible intervals (CrI) = 0.39–0.78) and unplanned hospital admissions (IRR = 0.49, 95% CrI = 0.37–0.65). There was no statistically significant difference between the two groups (IRR = 0.77, 95% CrI = 0.58–1.03 for ED visits and IRR = 0.79, 95% CrI = 0.62–1.01 for hospital admissions). The Bayes factors were 0.925 and 0.936 for ED visits and unplanned hospital admissions, respectively, interpreted as weak evidence in support of the null hypothesis of no difference between the interventions. Involuntary treatment of alcohol dependence was associated with reduced health service utilization in the year following treatment, and the outcomes did not differ from those of a matched control group.
Publisher: Wiley
Date: 21-07-2023
DOI: 10.1111/BCP.15821
Abstract: There are increasing concerns about harms related to suboptimal antipsychotic use. Here we describe recent population‐based trends in antipsychotic use and harms in Australia and identify population groups exhibiting patterns of use likely to contribute to these harms. Using population‐based data from the Australian Pharmaceutical Benefits Scheme (2015‐2020), poisoning calls to the New South Wales (NSW) Poisons Information Centre (2015‐2020) and poisoning deaths in all coronial records (2005‐2018) in Australia, we measured trends in the prevalence of antipsychotic use and related deaths and poisonings. We applied latent class analyses to identify patterns of antipsychotic use that may contribute to harms. Quetiapine and olanzapine had the highest prevalence of use between 2015 and 2020. Noteworthy trends included increases of 9.1% and 30.8% in quetiapine use and poisonings, while olanzapine use decreased by 4.5% but poisonings increased by 32.7%. Quetiapine and olanzapine poisonings and related deaths had the highest rates of co‐ingestion of opioids, benzodiazepines and pregabalin compared to other antipsychotics. We identified six distinct population groups using antipsychotics: (i) ongoing high‐dose use with sedatives (8%), (ii) ongoing use (42%), (iii) ongoing use with analgesics and sedatives (11%), (iv) long‐term low‐dose use (9%), (v) sporadic use (20%) and (vi) sporadic use with analgesics (10%). Ongoing potentially suboptimal antipsychotic use and associated harms highlight the need to monitor such patterns of use, for ex le through prescription monitoring systems.
Publisher: SAGE Publications
Date: 17-02-2023
DOI: 10.1177/00048674221079740
Abstract: Depression and anxiety affect 4–14% of Australians every year symptoms may have been exacerbated during the COVID-19 pandemic. We examined recent patterns of antidepressant use in Australia in the period 2015–2021, which includes the first year of the pandemic. We used national dispensing claims for people aged ⩾10 years to investigate annual trends in prevalent and new antidepressant use (no antidepressants dispensed in the year prior). We conducted stratified analyses by sex, age group and antidepressant class. We report outcomes from 2015 to 2019 and used time series analysis to quantify changes during the first year of the COVID-19 pandemic (March 2020–February 2021). In 2019, the annual prevalence of antidepressant use was 170.4 per 1000 women and 101.8 per 1000 men, an increase of 7.0% and 9.2% from 2015, respectively. New antidepressant use also increased for both sexes (3.0% for women and 4.9% for men) and across most age groups, particularly among adolescents (aged 10–17 years 46–57%). During the first year of the COVID-19 pandemic, we observed higher than expected prevalent use (+2.2%, 95% CI = [0.3%, 4.2%]) among females, corresponding to a predicted excess of 45,217 (95% CI = [5,819, 84,614]) females dispensed antidepressants. The largest increases during the first year of the pandemic occurred among female adolescents for both prevalent (+11.7%, 95% CI = [4.1%, 20.5%]) and new antidepressant use (+15.6%, 95% CI = [8.5%, 23.7%]). Antidepressant use continues to increase in Australia overall and especially among young people. We found a differential impact of the COVID-19 pandemic in treated depression and anxiety, greater among females than males, and greater among young females than other age groups, suggesting an increased mental health burden in populations already on a trajectory of increased use of antidepressants prior to the pandemic. Reasons for these differences require further investigation.
Publisher: BMJ
Date: 17-02-2009
DOI: 10.1136/BMJ.B636
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-06-2023
No related grants have been discovered for Malcolm Gillies.