ORCID Profile
0000-0002-3701-4997
Current Organisation
University of Oxford
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Publisher: Springer Science and Business Media LLC
Date: 22-02-2021
Publisher: Elsevier BV
Date: 08-2014
DOI: 10.1016/J.CANEP.2014.05.004
Abstract: Cancer of unknown primary (CUP) is a common cancer yet little is known about the reliability of incidence data. We audited 574 CUP (C80.9) diagnoses (median age 81 years) registered by the New South Wales (NSW) Central Cancer Registry (2004-2007) in a cohort of Australian Government Department of Veterans' Affairs clients. The registry did not clarify diagnoses with notifiers during this period due to interpretation of privacy legislation. For the audit, current registry practice was applied by seeking additional information from CUP notifiers and reclassifying diagnoses as necessary. In addition, clinicopathological characteristics were extracted from notifications. Fisher's exact test and Student's t-test were used to compare the demographic and clinicopathological characteristics of the CUP subgroups. Age/sex-standardised CUP incidence rates and 95% confidence intervals were calculated, standardised to the 2001 Australian population. 172 (30.0%) cases were reclassified to a known primary site, mostly cutaneous, and nine (1.6%) were found to be non-malignant diagnoses. After the audit the age/sex-standardised CUP incidence rates decreased from 26.0 (95% CI 21.2-30.8) to 15.9 (95% CI 12.5-19.3) per 100,000 person-years. Of the 393 remaining CUP cases, 202 (51%) were registered on the basis of a clinical diagnosis (46 by death certificate only) and 191 (49%) by pathological diagnosis (79 by cytology alone). Compared to cases with a pathological diagnosis, cases with a clinical diagnosis were older (85.6 vs. 82.0 years, p<0.001), and the reported number and location of metastases differed (p<0.001) metastatic sites were more likely to be unspecified for clinical diagnoses (36.1% vs. 4.2%). Cancer registry processes can markedly influence CUP incidence. Future population-based CUP research should take this into account, and consider stratification by basis of diagnosis due to differences in patient and tumour characteristics.
Publisher: Cold Spring Harbor Laboratory
Date: 31-07-2023
DOI: 10.1101/2023.07.31.23293419
Abstract: The COVID-19 pandemic caused significant disruption to routine activity in primary care. Medication reviews are an important primary care activity to ensure safety and appropriateness of ongoing prescribing and a disruption could have significant negative implications for patient care. Using routinely collected data, our aim was to i) describe the SNOMED CT codes used to report medication review activity ii) report the impact of COVID-19 on the volume and variation of medication reviews. With the approval of NHS England, we conducted a cohort study of 20 million adult patient records in general practice, in-situ using the OpenSAFELY platform. For each month between April 2019 - March 2022, we report the percentage of patients with a medication review coded monthly and in the previous 12 months. These measures were broken down by regional, clinical and demographic subgroups and amongst those prescribed high risk medications. In April 2019, 32.3% of patients had a medication review coded in the previous 12 months. During the first COVID-19 lockdown, monthly activity substantially decreased (−21.1% April 2020), but the rate of patients with a medication review coded in the previous 12 months was not substantially impacted according to our classification (−10.5% March 2021). There was regional and ethnic variation (March 2022 - London 21.9% vs North West 33.6% Chinese 16.8% vs British 33.0%). Following the introduction of “structured medication reviews”, the rate of structured medication review in the last 12 months reached 2.9% by March 2022, with higher percentages in high risk groups (March 2022 - care home residents 34.1%, 90+ years 13.1%, high risk medications 10.2%). The most used SNOMED CT medication review code across the study period was Medication review done - 314530002 (59.5%). We have reported a substantial reduction in the monthly rate of medication reviews during the pandemic but rates recovered by the end of the study period.
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.CANEP.2019.04.004
Abstract: Little is known about the risk factors for cancer of unknown primary site (CUP). We examined the demographic, social and lifestyle risk factors for CUP in a prospective cohort of 266,724 people aged 45 years and over in New South Wales, Australia. Baseline questionnaire data were linked to cancer registration, hospitalisation, emergency department admission, and mortality data. We compared in iduals with incident cancer registry-notified CUP (n = 327) to two sets of controls randomly selected (3:1) using incidence density s ling with replacement: (i) incident cancer registry-notified metastatic cancer of known primary site (n = 977) and (ii) general cohort population (n = 981). We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). In a fully adjusted model incorporating self-rated overall health and comorbidity, people diagnosed with CUP were more likely to be older (OR 1.05, 95% CI 1.04-1.07 per year) and more likely to have low educational attainment (OR 1.77, 95% CI 1.24-2.53) than those diagnosed with metastatic cancer of known primary. Similarly, compared to general cohort population controls, people diagnosed with CUP were older (OR 1.10, 95% CI 1.08-1.12 per year), of low educational attainment (OR 1.69, 95% CI 1.08-2.64), and current (OR 3.42, 95% CI 1.81-6.47) or former (OR 1.95, 95% CI 1.33-2.86) smokers. The consistent association with educational attainment suggests low health literacy may play a role in CUP diagnosis. These findings highlight the need to develop strategies to achieve earlier identification of diagnostically challenging malignancies in people with low health literacy.
Publisher: Elsevier BV
Date: 11-2023
Publisher: Springer Science and Business Media LLC
Date: 24-01-2012
Publisher: Wiley
Date: 25-05-2023
DOI: 10.5694/MJA2.51985
Abstract: To determine the numbers and types of medicines dispensed around the time of death to people who die by suicide to compare the medicines recently dispensed and those recorded in post mortem toxicology reports. Analysis of linked National Coronial Information System (NCIS) and Pharmaceutical Benefits Scheme (PBS) data from the Australian Suicide Prevention using Health Linked Data (ASHLi) study, a population‐based case series study of closed coronial cases for deaths of people in Australia aged ten years or more during 1 July 2013 – 10 October 2019 deemed by coroners to be the result of intentional self‐harm. Proportions of people to whom medicines were dispensed around the time of death, by medicine group, class, and specific medicine comparison of medicines recently dispensed and those detected by post mortem toxicology. Toxicology reports were available for 13 541 of 14 206 people who died by suicide (95.3% 10 246 men, 75.7%) poisoning with medicines contributed to 1163 deaths (8.6%). At least one PBS‐subsidised medicine had been dispensed around the time of death to 7998 people (59.1%). For three medicine classes, the proportions of people in whom the medicines were detected post mortem and their death was deemed medicine‐related were larger for those without records of recent dispensing than for people for whom they had been dispensed around the time of death: antidepressants (17.7% v 12.0%), anxiolytics (16.3% v 14.8%), and sedatives/hypnotics (24.3% v 16.5%). At least one recently dispensed medicine not detected post mortem was identified for 6208 people (45.8%). A considerable proportion of people who died by suicide were not taking psychotropic medicines recently dispensed to them, suggesting non‐adherence to pharmacotherapy, and a smaller than expected proportion were using antidepressants. Conversely, medicines that had not recently been dispensed were detected post mortem in many people for whom poisoning with medicines was a contributing factor, suggesting medicine stockpiling.
Publisher: CMA Joule Inc.
Date: 25-03-2018
DOI: 10.1503/CMAJ.170666
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-07-2023
Abstract: The burden of cardiovascular disease is increasing, with many people treated for multiple cardiovascular conditions. We examined persistence and adherence to medicines for cardiovascular disease treatment or prevention in Australia. Using national dispensing claims for a 10% random s le of people, we identified adults (≥18 years) initiating antihypertensives, statins, oral anticoagulants, or antiplatelets in 2018. We measured persistence to therapy using a 60‐day permissible gap, and adherence using the proportion of days covered up to 3 years from initiation, and from first to last dispensing. We reported outcomes by age, sex, and cardiovascular multimedicine use. We identified 83 687 people initiating antihypertensives (n=37 941), statins (n=34 582), oral anticoagulants (n=15 435), or antiplatelets (n=7726). Around one‐fifth of people discontinued therapy within 90 days, with 50% discontinuing within the first year. Although many people achieved high adherence (proportion of days covered ≥80%) within the first year, these rates were higher when measured from first to last dispensing (40.5% and 53.2% for statins 55.6% and 80.5% for antiplatelets, respectively). Persistence was low at 3 years (17.5% antiplatelets to 37.3% anticoagulants). Persistence and adherence increased with age, with minor differences by sex. Over one‐third of people had cardiovascular multimedicine use (reaching 92% among antiplatelet users): they had higher persistence and adherence than people using medicines from only 1 cardiovascular group. Persistence to cardiovascular medicines decreases substantially following initiation, but adherence remains high while people are using therapy. Cardiovascular multimedicine use is common, and people using multiple cardiovascular medicines have higher rates of persistence and adherence.
Publisher: Wiley
Date: 19-02-2021
DOI: 10.1111/AJCO.13554
Publisher: Wiley
Date: 28-07-2016
DOI: 10.1111/BCP.13043
Publisher: Springer Science and Business Media LLC
Date: 02-11-2015
Publisher: Wiley
Date: 02-2023
DOI: 10.1111/BCP.15668
Abstract: Dose‐prediction software is recommended to enable area under the curve over 24 h (AUC 24 )‐guided dosing of the antibiotic vancomycin. However, uncertainty remains about how best to implement software in the clinic. We describe the activity, over 18 months, of a consultative therapeutic drug monitoring Advisory Service (the Service) for vancomycin that used dose‐prediction software alongside clinical expertise, identifying factors that influence attainment of therapeutic targets. Of the 408 vancomycin dose reports provided for 182 courses of therapy, most (57%) recommended a dose change. The majority (82.8%, 193/233) of recommended dose adjustments were accepted by treating teams. A dose report was not published for 125 courses of therapy, with reasons including patient in intensive care unit or service error. An estimated 26.6 h of staff time was allocated to Service activities each month. Publication of a dose report facilitated attainment of therapeutic targets ( P = .002). Software integration could improve Service outcomes, avoiding errors and reducing staff workload.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Wiley
Date: 03-06-2020
DOI: 10.1002/PDS.5035
Publisher: Wiley
Date: 25-10-2017
DOI: 10.1002/PDS.4342
Abstract: We compared statin adherence in in iduals initiating combined amlodipine/atorvastatin therapy as a fixed-dose (FDC) or free combination and identified subgroups benefiting most from FDCs. We used a 10% s le of Australian Pharmaceutical Benefits Scheme dispensing data (2005-2015) to identify in iduals initiating amlodipine and atorvastatin as an FDC (n = 3996) or free combination (n = 5434), with or without prior statin dispensing. We measured the proportion of days covered in each 30-day period over 24 months and classified patterns of statin adherence using group-based trajectory models. We identified predictors of adherence trajectories using logistic regression. The median age was 71 years, and 53% were female. We identified 4 patterns of statin adherence: near-perfect adherence (n = 5383), good adherence (n = 1893), declining adherence (n = 1247), and early nonadherence (n = 907). Compared with the free combination, FDC initiators were more likely to have near-perfect adherence if they were previously statin adherent irrespective of amlodipine dose (amlodipine 5 mg: OR = 1.61, 95% CI 1.38-1.87 amlodipine 10 mg: OR = 2.39, 95% CI 1.63-3.51) or they were previously statin nonadherent and initiated on the 5 mg amlodipine dose (OR = 1.87, 95% CI 1.50-2.32). Statin-naïve in iduals initiating on the FDC with 10 mg amlodipine were less likely to have near-perfect adherence (OR = 0.60, 95% CI 0.41-0.88) and more likely to have early nonadherence (OR = 1.73, 95% CI 1.17-2.55). The amlodipine/atorvastatin FDC was associated with greater statin adherence among prevalent statin users, and in iduals who initiated on lower amlodipine doses. The FDCs did not improve adherence in statin-naïve in iduals and in some cases resulted in poorer adherence.
Publisher: Springer Science and Business Media LLC
Date: 12-10-2012
Publisher: Cold Spring Harbor Laboratory
Date: 05-08-2023
DOI: 10.1101/2023.07.28.23293269
Abstract: Fit notes (“sick notes”) are issued by general practitioners (GPs) when a person can’t work for health reasons and is an indication of the public health and economic burden for people recovering from COVID-19. With NHS England approval, we used routine clinical data from million patients to compare fit note incidence in people 18-64 years with and without evidence of COVID-19 in 2020, 2021 and 2022. We fit Cox regression models to estimate adjusted hazard ratios, overall and by time post-diagnosis and within demographic subgroups. We identified 365,421, 1,206,555 and 1,321,313 people with evidence of COVID-19 in 2020, 2021 and 2022. The fit note rate was 4.88 per 100 person-months (95%CI 4.83-4.93) in 2020, 2.66 (95%CI 2.64-2.67) in 2021, and 1.73 (95%CI 1.72-1.73) in 2022. Compared with the age, sex and region matched general population, the hazard ratio (HR) adjusted for demographics and clinical characteristics over the follow-up period was 4.07 (95%CI 4.02-4.12) in 2020 decreasing to 1.57 (95%CI 1.56-1.58) in 2022. The HR was highest in the first 30 days post-diagnosis in all years. Despite likely underestimation of the fit note rate, we identified a considerable increase among people with COVID-19, even in an era when most people are vaccinated. Most fit notes are associated with the acute phase of the disease, but the increased risk several months post-diagnosis provides further evidence of the long-term impact. We searched Pubmed from 1 March 2020 to 30 June 2023 using the following search terms: (“COVID-19” OR “SARS-CoV-2” OR “coronavirus”) AND (“United Kingdom” OR “England” OR “Britain” OR “Scotland” OR “Wales”) AND (“fit note” OR “sick note” OR “sick leave” OR “sickness absence”). We also searched the reference list of relevant articles. We included both peer-reviewed research studies and grey literature that quantified receipt of fit notes or sick leave during the COVID-19 pandemic. We found two peer-reviewed studies and one briefing by an independent think tank. A study of 959,356 National Health Service (NHS) employees in England quantified receipt of non-COVID-19 related fit notes during the first wave of the pandemic. They found that the overall fit note rate was lower in 2020 compared with 2019. However, increases in the number of people receiving fit notes were observed for respiratory, infectious disease, and mental health conditions. The second study of 15,931 domiciliary care workers in Wales between Mar 2020 and Nov 2021 found that 15% had been issued a fit note over the study period. Fit notes were more common among women, people ≥45 years, and those with comorbidities. The briefing found that the percentage of sickness absence days taken by NHS employees was higher in 2022 (5.6%) compared with 2019 (4.3%), with a particular increase in absences due to mental health and infectious diseases. In 2022, 18% of sickness absence days were attributable to COVID-19. This study is the first to quantify changes in fit note rate since the start of the COVID-19 pandemic among people with a reported SARS-CoV-2 infection and how this compares with the general population in the UK. We found that people with evidence of SARS-CoV-2 infection had a higher fit note rate than the general population, even after adjusting for demographics and clinical characteristics. While this increased risk was greatest in 2020 (hazard ratio [HR] = 4.07, 95%CI 4.02-4.12), it continued to a lesser extent even into 2022 (HR = 1.57, 95%CI 1.56-1.58). The fit note rate was greatest in the first 30 days post-diagnosis, suggesting that most sick leave is associated with the acute phase. In subgroup analyses, the groups with the greatest relative increased risk changed over the years. People aged 18-24 years had a larger relative increased risk of fit notes (as measured by HR) in 2022 than 2021, when compared with the general population in each year. Additionally, while in 2020 and 2021 the HR increased along with lessening deprivation, this effect dissipated in 2022. In contrast, people hospitalised with COVID-19 were less likely to be issued a fit note than the pneumonia cohort, suggesting the long-term effects may be similar to comparable severe respiratory infections cases resulting in hospitalisation. While we have likely underestimated the fit note rate due to overcounting of people in the workforce and misclassification of COVID-19 status, we still identified a substantial increased risk of receiving a fit note in people with COVID-19 compared with the general population over all years, even after adjusting for demographics and a wide range of clinical characteristics. The increased risk persisted into 2022, in an era where most people are vaccinated and the severity of COVID-19 illness is lessened. Given the high infection rates still occurring, these findings provide evidence for a substantial impact of COVID-19 on productivity and further evidence of the long-term impacts of COVID-19.
Publisher: Wiley
Date: 17-06-2022
DOI: 10.1111/ADD.15970
Publisher: Wiley
Date: 21-12-2021
DOI: 10.1002/PDS.5395
Abstract: In May 2019, Australia's Pharmaceutical Benefits Scheme (PBS) tightened the prescribing restrictions for publicly subsidized high and standard strength proton‐pump inhibitors (PPIs). We aimed to determine the impacts on PPI use in Australia. Population‐based interrupted time series analysis of PBS dispensing claims for a 10% s le of PBS‐eligible Australian residents from January 2017 to December 2020 and national prescription and over‐the‐counter sales to pharmacies from January 2017 to October 2020. We examined trends in monthly PPI dispensings, switches from higher to lower strength formulations, and volume (kg) dispensed and sold. From May 2019, we observed a small, immediate decrease (−7830 [95%CI: −8818 to −6842]) in standard strength PPI dispensings/month, which rebounded to exceed pre‐intervention levels by December 2020. High strength dispensings decreased until the end of the study period to less than half their pre‐intervention average/month low strength dispensings/month increased until the end of the study period to more than double their pre‐intervention average/month. We observed transient increases in switches to lower strength formulations post‐intervention. The kilograms of PPIs sold/month followed a similar pattern to PBS kilograms dispensed/month with the exception of standard strength formulations where PBS dispensings decreased by −74 (95%CI: −93 to −55) but total sales remained unchanged (comprising PBS and private prescriptions, and over‐the‐counter sales). Tightened prescribing restrictions had an immediate and sustained impact on PPI use in Australia, with decreased high strength use and increased low strength use. Some patients likely switched to private market prescriptions for standard strength PPI, given the observed patterns in total volume sold/dispensed.
Publisher: Public Library of Science (PLoS)
Date: 19-03-2020
Publisher: SAGE Publications
Date: 15-05-2019
Abstract: To identify distinct trajectories of antipsychotic use prior to and during pregnancy and describe the associated maternal and birth characteristics. We conducted a population-based cohort study of births (2005–2012) using linked administrative data in New South Wales, Australia. We used group-based trajectory modelling to classify trajectories of antipsychotic use in the 450 days prior to pregnancy and during pregnancy. We characterised women with different trajectories according to maternal sociodemographic characteristics, mental health diagnoses and hospitalisations, use of psychotropic medicines and birth outcomes. Of 137,993 women who gave birth, 2741 (2.0%) were exposed to antipsychotics prior to or during pregnancy. We identified six trajectories of antipsychotic use: two involved short-term use of low daily doses prior to pregnancy (51.1%), while three involved long-term use of low (20.9%), moderate (11.0%) and high (2.0%) daily doses throughout pregnancy. One trajectory (15.0%) involved increasing use during pregnancy. Women with long-term use were more likely to have a schizophrenia or bipolar disorder diagnosis, to have used multiple psychotropics and to have a mental health hospitalisation during pregnancy. Overall, women using antipsychotics had elevated rates of adverse birth outcomes compared to unexposed women. Women with the greatest antipsychotic exposure had the highest rates of gestational diabetes and gestational hypertension. Women using antipsychotics around pregnancy are heterogeneous, with varying patterns of use and associated birth outcomes, reflecting underlying differences in the indications for treatment and/or severity of illness. This ersity should be considered when developing clinical guidelines and designing safety studies.
Publisher: BMJ
Date: 05-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-08-2022
DOI: 10.1097/J.PAIN.0000000000002433
Abstract: Concomitant use of pregabalin with opioids and/or benzodiazepines is common, despite the increased risks. However, clinical trials suggest pregabalin can have an opioid-sparing effect when treating acute postoperative pain. We explored how opioid and benzodiazepine use changed over time in people initiating pregabalin, using dispensing claims data for a 10% s le of Australians (2013-19). Among 142,776 people initiating pregabalin (median age = 61 years, 57% female), we used group-based trajectory modelling to identify 6 pregabalin dose trajectories in the first year postinitiation. Two trajectories involved discontinuation: after one dispensing (49%), and after 6 months of treatment (14%). Four trajectories involved persistent use with variable estimated median daily doses of 39 mg (16%), 127 mg (14%), 276 mg (5%), and 541 mg (2%). We quantified opioid and benzodiazepine use in the year before and after pregabalin initiation using generalised linear models. Over the study period, 71% were dispensed opioids and 34% benzodiazepines, with people on the highest pregabalin dose having highest rates of use. Opioid use increased postpregabalin initiation. Among people using both opioids and pregabalin, the geometric mean daily dose in oral morphine equivalents increased after pregabalin initiation in all trajectories, ranging from +5.9% (99% confidence interval 4.8%-7.0%) to +39.8% (99% confidence interval 38.3%-41.5%) in people on the highest daily pregabalin dose. Among people using both pregabalin and benzodiazepines, the dose remained constant over time for people in all trajectories. Notwithstanding its reputation as opioid-sparing, in this outpatient setting, we observed that people using opioids tended to use higher opioid daily doses after pregabalin initiation, especially those on high pregabalin doses.
Publisher: Elsevier BV
Date: 09-2021
Publisher: Cold Spring Harbor Laboratory
Date: 07-06-2023
DOI: 10.1101/2023.06.06.23290826
Abstract: The COVID-19 pandemic created unprecedented pressure on healthcare services. This study aimed to investigate if disease-modifying anti-rheumatic drug (DMARD) safety monitoring was affected during the COVID-19 pandemic. A population-based cohort study was conducted with the approval of NHS England, using the OpenSAFELY platform to access electronic health record data from 24·2 million patients registered at general practices using TPP’s SystmOne software. Patients were included for further analysis if prescribed azathioprine, leflunomide, or methotrexate between November 2019 and July 2022. Outcomes were assessed as monthly trends and variation between various sociodemographic and clinical groups for adherence with standard safety monitoring recommendations. An acute increase in the rate of missed monitoring occurred across the study population (+12·4 percentage points) when lockdown measures were implemented in March 2020. This increase was more pronounced for some patient groups (70-79 year-olds: +13·7 percentage points females: +12·8 percentage points), regions (North West: +17·0 percentage points), medications (Leflunomide: +20·7 percentage points), and monitoring tests (Blood Pressure: +24·5 percentage points). Missed monitoring rates decreased substantially for all groups by July 2022. Substantial and consistent differences were observed in overall missed monitoring rates between several groups throughout the study. DMARD monitoring rates temporarily deteriorated during the COVID-19 pandemic. Deterioration coincided with the onset of lockdown measures, with monitoring rates recovering rapidly as lockdown measures were eased. Differences observed in monitoring rates between medications, tests, regions, and patient groups, highlight opportunities to tackle potential inequalities in the provision or uptake of monitoring services. Further research should aim to evaluate the causes of the differences identified between groups. None. Disease-modifying anti-rheumatic drugs (DMARDs) are immunosuppressive and/or immunomodulatory drugs, which carry risks of serious adverse effects such as gastrointestinal, renal, hepatic, and pulmonary toxicity myelosuppression and increased susceptibility to infection. To mitigate these safety risks, national safety guidance recommends that patients taking these drugs receive regular monitoring. We searched PubMed, Web of Science and Scopus for studies published between database inception and July 28th, 2022, using the terms ([covid-19] AND [monitoring OR shared care OR dmard OR outcome factors] AND [primary care]), with no language restrictions. Studies that investigated the effect of the COVID-19 pandemic on healthcare services were identified. One key study in England showed disruption to various monitoring services in primary care had occurred during the pandemic. Another English study highlighted a disproportionate impact of the COVID-19 pandemic on health outcomes in certain groups. Prior to this study knowledge of how high-risk drugs, such as DMARDs, were affected by the COVID-19 pandemic was limited. This study reports the impact of COVID-19 on the safety monitoring of DMARDs. Moreover, it reports variation in DMARD monitoring rates between demographic, clinical and regional subgroups, which has not yet been described. This is enabled through use of the OpenSAFELY platform, which provides secure access to pseudonymised primary care patient records in England for the purposes of analysing the COVID-19 pandemic impact. DMARD monitoring rates transiently deteriorated during the COVID-19 pandemic, consistent with previous research on other monitoring tests. Deterioration coincided with the onset of lockdown measures, with performance recovering rapidly as lockdown measures were eased. Differences observed in monitoring rates between demographic, clinical and regional subgroups highlight opportunities to identify and tackle potential inequalities in the provision or uptake of monitoring services. Further research should aim to evaluate the causes of the differences identified between groups, and establish the clinical relevance of missed monitoring. Several studies have demonstrated the capability of the OpenSAFELY platform as a secure and efficient approach for analysing NHS primary care data at scale, generating meaningful insights on service delivery.
Publisher: American Medical Association (AMA)
Date: 26-07-2023
DOI: 10.1001/JAMAPSYCHIATRY.2023.2289
Abstract: Determining the association between drug use and suicide is complicated but can help to inform targeted suicide prevention strategies. To examine the substances prevalent in poisoning- and nonpoisoning-related suicides in Australia. This was a multiple-year, cross-sectional study of suicides from July 2013 to October 2019 in Australia with toxicology data available in a national coronial database. The cause of death was classified as poisoning related if any type of poisoning was determined by the coroner to contribute to the cause of death. Prevalence ratios (PRs) were calculated to compare substance detection in poisoning- vs nonpoisoning-related suicides. Data were analyzed from October 2021 to April 2023. All substances detected in decedents at the time of death according to toxicology reports were recorded. The most common in idual substances and substance classes were identified. From these, blood concentrations of substances of interest were analyzed, and the most commonly occurring combinations of substance classes were listed. Toxicology was performed on 13 664 suicide decedents (median [IQR] age, 44 [31-57] years 10 350 male [76%]). From these, 3397 (25%) were poisoning-related suicides (median [IQR] age, 50 [38-63] years 2124 male [63%]). The remainder were classified as nonpoisoning-related suicides (median [IQR] age, 42 [29-55] years 8226 male [80%]). PRs for common medicine classes being detected in poisoning-related suicides compared with nonpoisoning-related suicides were as follows: antidepressants (PR, 1.63 95% CI, 1.54-1.73), benzodiazepines (PR, 2.01 95% CI, 1.90-2.13), nonopioid analgesics/anti-inflammatory drugs (PR, 1.88 95% CI, 1.78-2.00), and opioids (PR, 2.72 95% CI, 2.58-2.87). Alcohol (as ethanol ≥0.03 g/100 mL) was almost equally prevalent in poisoning- and nonpoisoning-related deaths (PR, 1.07 95% CI, 1.01-1.14), whereas hetamines (PR, 0.68 95% CI, 0.61-0.77) and cannabinoids (PR, 0.67 95% CI, 0.60-0.74) were detected more often in nonpoisoning-related suicides. Combinations of multiple sedative agents in poisoning-related suicides were common. Both poisoning- and nonpoisoning-related suicide deaths featured a high prevalence of psychotropic medicines or potential intoxication, which suggests the association of suicide with poor mental health and substance misuse. Findings suggest that substances with a high involvement in poisoning-related suicides should be prescribed cautiously, including antidepressants that are toxic in overdose, sedatives, opioids, and potentially lethal combinations.
Publisher: Wiley
Date: 16-02-2022
DOI: 10.1111/PPE.12870
Abstract: Medicine prescribing for children is impacted by a lack of paediatric‐specific dosing, efficacy and safety data for many medicines. To estimate the prevalence of medicine use among children and the rate of ‘off‐label’ prescribing according to age at dispensing. We used population‐wide primarily outpatient dispensing claims data for 15% of Australian children (0–17 years), 2013–2017 ( n = 840,190). We estimated prescribed medicine use and ‘off‐label’ medicine use according to the child's age ( year, 1–5 years, 6–11 years, 12–17 years) defined as medicines without age‐appropriate dose recommendations in regulator‐approved product information. Within off‐label medicines, we also identified medicines with and without age‐specific dose recommendations in a national prescribing guide, the Australian Medicines Handbook Children's Dosing Companion (AMH CDC). The overall dispensing rate was 2.0 dispensings per child per year. The medicines with the highest average yearly prevalence were systemic antibiotics (435.3 per 1000 children), greatest in children 1–5 years (546.9 per 1000). Other common medicine classes were systemic corticosteroids (92.7 per 1000), respiratory medicines (91.2 per 1000), acid‐suppressing medicines in children year (47.2 per 1000), antidepressants in children 12–17 years (40.3 per 1000) and psychostimulants in children 6–11 years (27.0 per 1000). We identified 12.2% of dispensings as off‐label based on age, but 66.3% of these had age‐specific dosing recommendations in the AMH CDC. Among children year, off‐label dispensings were commonly acid‐suppressing medicines (35.5%) and topical hydrocortisone (33.1%) in children 6–11 years, off‐label prescribing of clonidine (16.0%) and risperidone (13.1%) was common. Off‐label dispensings were more likely to be prescribed by a specialist (21.7%) than on‐label dispensings (7.5%). Prescribed medicine use is common in children, with off‐label dispensings for medicines without paediatric‐specific dosing guidelines concentrated in classes such as acid‐suppressing medicines and psychotropics. Our findings highlight a need for better evidence to support best‐practice prescribing.
Publisher: Wiley
Date: 20-02-2019
DOI: 10.1002/PDS.4755
Abstract: Countries worldwide are developing a variety of strategies to combat the opioid epidemic, such as restricting access to high-strength opioid formulations. We aimed to examine the dispensing patterns of strong opioids by dose units (DUs), age, and sex. We used Australian population-level dispensing data from January 2003 to December 2015 and categorised strong opioids by DU: very low, low, moderate, and high, corresponding to total daily doses of less than or equal to 25, 26 to 50, 51 to 100, and greater than 100 morphine milligramme equivalents, respectively. We measured trends in strong opioid use as dispensings/1000 population/year and stratified dispensing in 2015 by patient age and sex. From 2003 to 2015, strong opioid dispensing of very low, low, moderate, and high DU increased 6.7-, 6.2-, 2.2-, and 1.8-fold, respectively. The increase in very low and low DU dispensing was driven primarily by oxycodone (5, 10, and 15 mg tablets and capsules) and buprenorphine transdermal patches. In 2015, the number of dispensings/1000 population for very low, low, moderate, and high DU were 180.3, 77.0, 52.7, and 34.8, respectively. Females aged greater than or equal to 85 years had the highest opioid use, ranging from 157.1 dispensings/1000 population for high DU to 2104.5 dispensings/1000 population for very low DU. In contrast, the high DU dispensings in males aged 25 to 64 years exceeded their female counterparts by approximately 1.3-fold. Relative to moderate and high DU strong opioids, dispensing of very low and low DU strong opioids increased dramatically during the study period in Australia. Future studies investigating opioids use and harms in elderly females and males between 25 to 64 years are warranted.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-12-2019
Abstract: Oral anticoagulant ( OAC ) therapy reduces the risk of stroke in people with atrial fibrillation ( AF ), and is considered best practice however, there is little Australian evidence around the uptake of OAC s in this population. We used linked hospital admissions, pharmaceutical dispensing claims, medical services, and mortality data for people in Australia's 2 most populous states (July 2010 to June 2015). Among OAC ‐naïve people hospitalized with AF , we estimated initiation of OAC therapy within 30 days of discharge, and persistence with therapy in the first year. We analyzed both outcomes using multivariable Cox regression. In 71 184 people with AF (median age 78 years, 49% female), 22.7% initiated OAC therapy. Initiation was lowest in July to December 2011 (17.0%) and highest in July to December 2014 (30.1%) after subsidy of the direct OAC s. In adjusted analyses, initiation was most likely in people with a CHA 2 DS 2 ‐ VA score ≥7 (versus 0) (hazard ratio=6.25, 95% CI 5.08–7.69), and a history of venous thromboembolism (hazard ratio=2.65, 95% CI 2.49–2.83). Of the people who initiated OAC therapy, 39.9% discontinued within 1 year a lower risk of discontinuation was associated with a CHA 2 DS 2 ‐ VA score ≥7 (versus 0) (hazard ratio=0.22, 95% CI 0.14–0.35), or initiation on a direct OAC (versus warfarin) (hazard ratio=0.55, 95% CI 0.50–0.60). We found that OAC therapy was severely underutilized in people hospitalized with AF , even among high‐risk in iduals. Reasons for this underuse, whether patient, prescriber, or hospital related, should be identified and addressed to reduce stroke‐related morbidity and mortality in people with AF .
Publisher: Wiley
Date: 19-11-2019
DOI: 10.1111/ADD.14798
Abstract: Globally, codeine is the most-used opioid. In December 2016, Australia announced that low-strength codeine (≤ 15 mg) would be re-scheduled and no longer available for purchase over-the-counter this was implemented in February 2018. We aimed to evaluate the effect of this scheduling change on codeine misuse and use and misuse of other opioids. Interrupted time-series analysis of monthly opioid exposure calls to New South Wales Poisons Information Centre (NSWPIC, captures 50% of Australia's poisoning calls), January 2015- January 2019 and monthly national codeine sales, March 2015-March 2019. We incorporated a washout period (January 2017 - January 2018) between the announcement and implementation, when prescriber/consumer behaviour may have been influenced. Intentional opioid overdoses resulting in a call to NSWPIC. We used linear segmented regression to identify abrupt changes in level and slope of fitted lines. Codeine poisonings and sales were stratified into high strength (> 15 mg per dose unit) and low strength (≤ 15 mg). Only low-strength formulations were re-scheduled. We observed an abrupt -50.8 percentage [95% confidence interval (CI) = -79.0 to -22.6%] level change in monthly codeine-related poisonings and no change in slope in the 12 months after February 2018. There was no increase in calls to the NSWPIC for high-strength products, level change: -37.2% (95% CI = -82.3 to 8%) or non-codeine opioids, level change: -4.4% (95% CI = -33.3 to 24.4%). Overall, the re-scheduling resulted in a level change in opioid calls of -35.8% calls/month (95% CI = -51.2 to -20.4%). Low-strength codeine sales decreased by 87.3% (95% CI = -88.5 to -85.9%), with no increase in high-strength codeine sales in the 14 months following re-scheduling, -4.0% (95% CI = -19.6 to 14.6%). Codeine re-scheduling in Australia appears to have reduced codeine misuse and sales.
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: Wiley
Date: 12-12-2023
DOI: 10.1111/BCP.15614
Abstract: We quantified concomitant medicine use and occurrence of potential drug–drug interactions in people living with HIV in Australia who are treated with antiretroviral therapy (ART). In this cohort study using dispensing claims of a 10% random s le of Australians, we identified 2230 people dispensed ART between January 2018 and December 2019 (mean age 49.0 years, standard deviation 12.0 years, 88% male). We examined concomitant medicine use by identifying nontopical medicines dispensed within 90‐days of any antiretroviral medicine dispensing during a 12‐month follow‐up period. For every antiretroviral and nonantiretroviral pair, we identified and classified possible drug–drug interactions using the University of Liverpool HIV drug interactions database. A total of 1728 (78%) people were dispensed at least 1 and 633 (28%) 5 or more unique medicines in addition to ART in a 12‐month period systemic anti‐infectives and medicines acting on the nervous system were the most common (68% and 56%, respectively). Among comedicated people, 1637 (95%) had at least 1 medicine combination classified as weak interactions, 558 (32%) interactions requiring close monitoring/dose adjustment and 94 (5%) that should not be coadministered. Contraindication or interactions requiring close monitoring/dose adjustment were more common among people receiving protease inhibitors (50–73% across different antiretrovirals), non‐nucleoside reverse transcriptase inhibitors (35–64%), people using single‐tablet combinations containing elvitegravir (30–46%) and those using tenofovir disoproxil (26–30%). Concomitant medicine use is widespread among people living with HIV in Australia. Despite a relatively low prevalence of contraindicated medicines, almost a third received medicines that require close monitoring or dose adjustment.
Publisher: Springer Science and Business Media LLC
Date: 11-2019
DOI: 10.1038/S41416-019-0612-5
Abstract: Randomised clinical trials (RCTs) demonstrate that trastuzumab improves survival in patients with human epidermal growth factor 2-positive early breast cancer (HER2 + EBC), but real-world patients and clinical practice often differ from RCTs. We examine real-world treatment patterns and outcomes associated with trastuzumab for HER2 + EBC. We identified all Australians dispensed trastuzumab for HER2 + EBC between 1/1/2007 and 30/6/2016. We estimated the proportion of patients completing 12 months of treatment (defined as ≥350 days of exposure within 540 days of initiation). We estimated overall survival (OS) and recurrence-free survival (RFS) by using trastuzumab dispensing for metastatic breast cancer as a surrogate for recurrence. Our study included 14,644 patients. Among patients with ≥540 days of follow-up ( n = 11,903), 67.4% completed 12 months of trastuzumab. OS rates at 5 and 9 years were 92.7 and 87.9%, and RFS rates at 5 and 9 years were 86.8 and 81.4%, respectively. Patients who completed 12 months of trastuzumab had a 9-year OS rate of 90.2% compared with 86.2% among patients receiving months of therapy (adjusted HR 0.71, 95% CI 0.62–0.81). Real-world HER2 + EBC patients are less likely to complete 12 months of trastuzumab than some clinical trial counterparts but have survival outcomes comparable to those reported in landmark RCTs.
Publisher: Cold Spring Harbor Laboratory
Date: 28-09-2021
DOI: 10.1101/2021.09.26.21264150
Abstract: We quantified changes in dispensing of common medicines proposed for “re-purposing” due to their perceived benefits as therapeutic or preventive for COVID-19 in Australia, a country with relatively low COVID-19 incidence in the first year of the pandemic. We performed an interrupted time series analysis and cross-sectional study using nationwide dispensing claims data (January 2017-November 2020). We focused on six subsidised medicines proposed for re-purposing: hydroxychloroquine, azithromycin, ivermectin, colchicine, corticosteroids, and calcitriol (Vitamin D analogue). We quantified changes in monthly dispensing and initiation trends during COVID-19 (March-November 2020) using autoregressive integrated moving average models (ARIMA) and compared characteristics of initiators in 2020 and 2019. In March 2020, we observed a 99% (95%CI 96%-103%) increase in hydroxychloroquine dispensing (of which approximately 22% attributable to new use), and a 199% increase (95%CI 184%-213%) in initiation, with a shift towards prescribing by general practitioners (42% in 2020 vs 25% in 2019) rather than specialists. These increases subsided following regulatory restrictions on prescribing to relevant specialties. There was a small but sustained increase in ivermectin dispensing over multiple months, with a 80% (95%CI 42%-118%) increase in initiation in May 2020 following its first identification as potentially disease-modifying in April. Other than increases in March related to stockpiling, we observed no increases in initiation of calcitriol or colchicine during COVID-19. Dispensing of corticosteroids and azithromycin remained lower than expected in April through November 2020. While most increases in dispensing observed early on during COVID-19 were temporary and appear to be related to stockpiling among existing users, we did observed increases in initiation of hydroxychloroquine and ivermectin and a shift in prescribing patterns which may be related to media hype around these medicines. A quick response by regulators can help limit inappropriate repurposing to lessen the impact on medicine supply and patient harms.
Publisher: Public Library of Science (PLoS)
Date: 15-06-2022
DOI: 10.1371/JOURNAL.PONE.0269482
Abstract: Since COVID-19 was first recognised, there has been ever-changing evidence and misinformation around effective use of medicines. Understanding how pandemics impact on medicine use can help policymakers act quickly to prevent harm. We quantified changes in dispensing of common medicines proposed for “re-purposing” due to their perceived benefits as therapeutic or preventive for COVID-19 in Australia. We performed an interrupted time series analysis and cross-sectional study using nationwide dispensing claims data (January 2017-November 2020). We focused on six subsidized medicines proposed for re-purposing: hydroxychloroquine, azithromycin, ivermectin, colchicine, corticosteroids, and calcitriol (Vitamin D analog). We quantified changes in monthly dispensing and initiation trends during COVID-19 (March-November 2020) using autoregressive integrated moving average models and compared characteristics of initiators in 2020 and 2019. In March 2020, we observed a 99% (95%CI: 96%-103%) increase in hydroxychloroquine dispensing (approximately 22% attributable to new users), and a 199% increase (95%CI: 184%-213%) in initiation, with an increase in prescribing by general practitioners (42% in 2020 vs 25% in 2019) rather than specialists. These increases subsided following regulatory restrictions on prescribing. There was a small but sustained increase in ivermectin dispensing over multiple months, with an 80% (95%CI 42%-118%) increase in initiation in May 2020 following its first identification as potentially disease-modifying in April. Other than increases in March related to stockpiling, we observed no change in the initiation of calcitriol or colchicine during COVID-19. Dispensing of corticosteroids and azithromycin was lower than expected from April through November 2020. While most increases in dispensing observed early on during COVID-19 were temporary and appear to be related to stockpiling among existing users, we observed increases in the initiation of hydroxychloroquine and ivermectin and a shift in prescribing patterns which may be related to the media hype around these medicines. A quick response by regulators can help limit inappropriate repurposing to lessen the impact on medicine supply and patient harm.
Publisher: Oxford University Press (OUP)
Date: 22-09-2022
DOI: 10.1093/IJE/DYAC180
Abstract: Conflicting evidence suggests a possible association between use of prescribed psychostimulants during pregnancy and adverse perinatal outcomes. We conducted population-based cohort studies including pregnancies conceived between April 2002 and March 2017 (Ontario, Canada N = 554 272) and January 2003 to April 2011 [New South Wales (NSW), Australia N = 139 229]. We evaluated the association between exposure to prescription hetamine, methylphenidate, dextro hetamine or lisdexamfetamine during pregnancy and pre-ecl sia, placental abruption, preterm birth, low birthweight, small for gestational age and neonatal intensive care unit admission. We used inverse probability of treatment weighting based on propensity scores to balance measured confounders between exposed and unexposed pregnancies. Additionally, we restricted the Ontario cohort to social security beneficiaries where supplementary confounder information was available. In Ontario and NSW respectively, 1360 (0.25%) and 146 (0.10%) pregnancies were exposed to psychostimulants. Crude analyses indicated associations between exposure and nearly all outcomes [OR range 1.15–2.16 (Ontario) 0.97–2.20 (NSW)]. Nearly all associations were attenuated after weighting. Pre-ecl sia was the exception: odds remained elevated in the weighted analysis of the Ontario cohort (OR 2.02, 95% CI 1.42–2.88), although some attenuation occurred in NSW (weighted OR 1.50, 95% CI 0.77–2.94) and upon restriction to social security beneficiaries (weighted OR 1.24, 95% CI 0.64–2.40), and confidence intervals were wide. We observed higher rates of outcomes among exposed pregnancies, but the attenuation of associations after adjustment and likelihood of residual confounding suggests psychostimulant exposure is not a major causal factor for most measured outcomes. Our findings for pre-ecl sia were inconclusive exposed pregnancies may benefit from closer monitoring.
Publisher: AMPCo
Date: 06-2015
DOI: 10.5694/MJA15.00103
Abstract: To examine the impact of a two-part special edition of the Australian Broadcasting Corporation's science journalism program Catalyst (titled Heart of the matter), aired in October 2013, that was critical of HMG-CoA reductase inhibitors ("statins"). Population-based interrupted time-series analysis of a 10% s le of Australian long-term concessional beneficiaries who were dispensed statins under the Pharmaceutical Benefits Scheme (about 51% of all people who were dispensed a statin between 1 July 2009 and 30 June 2014) dispensing of proton pump inhibitors (PPIs) was used as a comparator. Change in weekly dispensings and discontinuation of use of statins and PPIs, adjusting for seasonal and long-term trends, overall and (for statins only) stratified by the use of cardiovascular and diabetes medicines. In our s le, 191 833 people were dispensed an average of 26 946 statins weekly. Following the Catalyst program, there was a 2.60% (95% CI, 1.40%-3.77% P < 0.001) reduction in statin dispensing, equivalent to 14 005 fewer dispensings Australia-wide every week. Dispensing decreased by 6.03% (95% CI, 3.73%-8.28% P < 0.001) for people not dispensed other cardiovascular and diabetes medicines and 1.94% (0.42%-3.45% P = 0.01) for those dispensed diabetes medicines. In the week the Catalyst program aired, there was a 28.8% (95% CI, 15.4%-43.7% P < 0.001) increase in discontinuation of statin use, which decayed by 9% per week. An estimated 28 784 additional Australians ceased statin treatment. Discontinuation occurred regardless of the use of other cardiovascular and diabetes medicines. There were no significant changes in PPI use after the Catalyst program. Following airing of the Catalyst program, there was a temporary increase in discontinuation and a sustained decrease in overall statin dispensing. Up until 30 June 2014, there were 504 180 fewer dispensings of statins, and we estimate this to have affected 60 897 people.
Publisher: Wiley
Date: 12-10-2021
DOI: 10.1002/PDS.5081
Publisher: Elsevier BV
Date: 06-2020
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.LUNGCAN.2022.01.024
Abstract: Based on data from randomized controlled trials (RCTs), immune checkpoint inhibitors (ICI) are standard-of-care in advanced non-small cell lung cancer (aNSCLC). However, trial eligibility criteria are restrictive, and participants and outcomes may not represent the wider population. We aim to assess the generalizability of key phase III RCTs to real-world patients. Among aNSCLC patients enrolled in the Embedding Research (and Evidence) in Cancer Healthcare (EnRICH) program between 26/6/17-18/2/21, we assessed the proportion of patients who fulfilled key trial eligibility criteria: performance status (PS) 0-1, normal laboratory results, no EGFR/ALK mutations, no exclusionary comorbidities (previous cancer, conditions necessitating steroid use, autoimmune diseases, HIV, hepatitis B/C, tuberculosis, interstitial lung disease, organ transplantation). We defined patients who met all assessed criteria as trial-typical and describe ICI uptake and overall survival (OS). Of 454 patients (median age 71 years, 42.1% female), 30% were trial-typical. Less than half received ICI (47.6%), with trial-typical patients more likely to receive ICI (69.1% vs 38.4%, adjusted odds ratio 3.77, 95% CI 2.40-5.91). Median OS was 10.2 and 5.4 months in patients receiving first- and second-line ICI, respectively. Rationalizing trial criteria to include patients with PS ≤ 2 and exclude those with targetable mutations, steroid use, autoimmune diseases, interstitial lung disease, tuberculosis or organ transplantation increased the proportion of trial-typical patients to 57.3%. Landmark phase III RCTs in aNSCLC have limited generalizability. OS of real-world patients receiving ICI is shorter than reported in trials. Novel ICI trials should consider broader eligibility criteria to improve their generalizability.
Publisher: Wiley
Date: 11-05-2020
DOI: 10.1111/DAR.13086
Publisher: Wiley
Date: 06-08-2007
Publisher: AMPCo
Date: 22-03-2020
DOI: 10.5694/MJA2.50552
Publisher: American Medical Association (AMA)
Date: 08-2016
Publisher: Wiley
Date: 28-02-2018
DOI: 10.1002/PDS.4408
Abstract: To evaluate the impact of 2 policy changes on quetiapine dispensing in Australia: removal of prior authorisation for prescribing (policy 1: July 2007) and removal of repeat prescriptions for 25-mg quetiapine (policy 2: January 2014). We performed an interrupted time series analysis using Pharmaceutical Benefits Scheme claims data (July 2005 to December 2015). We assessed the impact of both policies on monthly quetiapine dispensing (25 mg and >25 mg) and the impact of policy change 2 on monthly rates of 25-mg discontinuation and switching from 25 mg to other quetiapine strengths. We also estimated the impact of both policies on the proportion of people with potentially inappropriate therapy (no evidence of dose escalation) following 25-mg initiation. Following removal of prior authorisation, 25-mg and >25-mg quetiapine dispensing in the Pharmaceutical Benefits Scheme 10% s le increased by 11/month (95% CI: 2-21) and 14/month (95% CI: 8-20), respectively. After removing 25-mg repeats, there was a permanent decrease of 1072 (95% CI 773-1371) dispensings and an increase in discontinuation of this strength 48% of people dispensed the 25-mg strength that discontinued, discontinued quetiapine completely the remainder continued to use higher quetiapine strengths. We observed minimal switching to other quetiapine strengths. There was no change in inappropriate 25-mg therapy following policy change 1 and a small decrease (79% to 76%, P = 0.05) following policy change 2. More nuanced policies are needed to ensure the appropriate access to 25-mg quetiapine for dose escalation while discouraging use for indications where the evidence of risk and benefit is unclear.
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: American Association for Cancer Research (AACR)
Date: 04-2007
DOI: 10.1158/1055-9965.EPI-06-0924
Abstract: Insulin-like growth factors (IGF) and their binding proteins (IGFBP) have been implicated in the risk of several epithelial or glandular tumors, including prostate cancer, breast cancer, and colon cancer. Cervical cancer, which is also of epithelial origin, has been shown to overexpress receptors for IGF-I, and plasma levels of IGF-I have been positively associated with cervical cancer precursors in one epidemiologic study. In this case-control study, we investigated plasma levels of IGF-I and IGFBP-3 in relation to the risk of histologically confirmed high-grade cervical intraepithelial neoplasia (HGCIN) and the risk of human papillomavirus (HPV) infection. Included in this analysis were 329 cases and 621 controls recruited from clinics affiliated with two Montréal-area hospital centers. We observed a reduced risk of HGCIN for increasing levels of IGF-I, with an adjusted odds ratio (OR) of 0.40 (95% confidence interval, 0.19-0.87) for the highest quartile relative to the lowest quartile of IGF-I. No association was observed between IGFBP-3 levels and HGCIN. Among controls, IGF-I was associated with a decreased risk of being positive for HPV-16 or HPV-18, with an adjusted odds ratio of 0.20 (95% confidence interval, 0.05-0.87) for the highest quartile relative to the lowest quartile of IGF-I. There was no association observed between IGFBP-3 levels and HPV infection status. IGF-I–mediated effects seemed to predominate among women & years of age. In contrast to the previously reported study, our results suggest that levels of IGF-I in young women may be inversely associated with HGCIN, a precursor to cervical cancer. (Cancer Epidemiol Biomarkers Prev 2007 (4):716–22)
Publisher: Wiley
Date: 22-03-2020
DOI: 10.1111/BCP.14276
Publisher: Wiley
Date: 26-09-2017
DOI: 10.1111/AJCO.12602
Abstract: Routine data collections are used increasingly to examine outcomes of real-world cancer drug use. These datasets lack clinical details about important endpoints such as disease progression. To validate a proxy for disease progression in metastatic cancer patients using prescribing and dispensing claims. We used data from a cohort study of patients undergoing chemotherapy who provided informed consent to the collection of cancer-treatment data from medical records and linkage to pharmaceutical claims. We derived proxy decision rules based on changes to drug treatment in prescription histories (n = 36 patients) and validated the proxy in prescribing data (n = 62 patients). We adapted the decision rules and validated the proxy in dispensing data (n = 109). Our gold standard was disease progression ascertained in patient medical records. In idual progression episodes were the unit of analysis for sensitivity and Positive Predictive Value (PPV) calculations and specificity and Negative Predictive Value (NPV) were calculated at the patient level. The sensitivity of our proxy in prescribing data was 74.3% (95% Confidence Interval (CI), 55.6-86.6%) and PPV 61.2% (95% CI, 45.0-75.3%) specificity and NPV were 87.8% (95% CI, 73.8-95.9%) and 100% (95% CI, 90.3-100%), respectively. In dispensing data, the sensitivity of our proxy was 64% (95% CI, 55.0-77.0%) and PPV 56.0% (95% CI, 43.0-69.0%) specificity and NPV were 81% (95% CI, 70.05-89.0%) and 91.0% (95% CI, 82.0-97.0%), respectively. Our proxy overestimated episodes of disease progression. The proxy's performance is likely to improve if the date of prescribing is used instead of date of dispensing in claims data and by incorporating medical service claims (such as imaging prior to drug changes) in the algorithm. Our proxy is not sufficiently robust for use in real world comparative effectiveness research for cancer medicines.
Publisher: The Sax Institute
Date: 03-2015
DOI: 10.17061/PHRP2521518
Abstract: Increasingly, automated methods are being used to code free-text medication data, but evidence on the validity of these methods is limited. To examine the accuracy of automated coding of previously keyed in free-text medication data compared with manual coding of original handwritten free-text responses (the 'gold standard'). A random s le of 500 participants (475 with and 25 without medication data in the free-text box) enrolled in the 45 and Up Study was selected. Manual coding involved medication experts keying in free-text responses and coding using Anatomical Therapeutic Chemical (ATC) codes (i.e. chemical substance 7-digit level chemical subgroup 5-digit pharmacological subgroup 4-digit therapeutic subgroup 3-digit). Using keyed-in free-text responses entered by non-experts, the automated approach coded entries using the Australian Medicines Terminology database and assigned corresponding ATC codes. Based on manual coding, 1377 free-text entries were recorded and, of these, 1282 medications were coded to ATCs manually. The sensitivity of automated coding compared with manual coding was 79% (n = 1014) for entries coded at the exact ATC level, and 81.6% (n = 1046), 83.0% (n = 1064) and 83.8% (n = 1074) at the 5, 4 and 3-digit ATC levels, respectively. The sensitivity of automated coding for blank responses was 100% compared with manual coding. Sensitivity of automated coding was highest for prescription medications and lowest for vitamins and supplements, compared with the manual approach. Positive predictive values for automated coding were above 95% for 34 of the 38 in idual prescription medications examined. Automated coding for free-text prescription medication data shows very high to excellent sensitivity and positive predictive values, indicating that automated methods can potentially be useful for large-scale, medication-related research.
Publisher: Elsevier BV
Date: 07-2021
Publisher: Cold Spring Harbor Laboratory
Date: 08-09-2023
Publisher: Springer Science and Business Media LLC
Date: 21-01-2014
DOI: 10.1007/S00198-013-2610-4
Abstract: Following initiation of oral bisphosphonate therapy through a secondary fracture prevention program, 2-year treatment compliance and persistence remained high and were similar in patients randomised to follow-up by either the program or primary care physician. Thus, community-based and specialist management are equally effective in supporting compliance and persistence with anti-osteoporotic treatments. The purpose of this study was to determine whether management by a secondary fracture prevention (SFP) program (aka "fracture liaison service") results in better compliance and persistence to oral bisphosphonate therapy than follow-up by the primary care physician, after initiation within an SFP program. This prospective RCT included 102 patients with incident osteoporotic fractures referred to a SFP program in Sydney, Australia. Following oral bisphosphonate therapy initiation, patients were randomised to either 6-monthly follow-up with the SFP program (group A) or referral to their primary care physician with a single SFP program visit at 24 months (group B). Compliance and persistence to treatment were measured using pharmaceutical claims data. Predictors of compliance and persistence and associations between compliance and persistence, and changes in bone mineral density (BMD) or bone resorption marker, urinary deoxypyridinoline over 24 months were analysed. The median medication possession ratio at 24 months was 0.78 (IQR, 0.50-0.93) in group A and 0.79 (IQR, 0.48-0.96) in group B (p = 0.68). Persistence at 24 months was also similar in both groups (64 vs. 61%, respectively p = 0.75). After adjusting for confounders, patients in group A were not more likely to be compliant (OR, 1.06 95% CI, 0.46-2.47) or persistent (HR, 0.83 95% CI, 0.27-1.67) than those randomised to group B. Time-based changes in BMD or bone turnover were not associated with compliance or persistence. Compliance and persistence to oral bisphosphonate therapy remain high amongst patients initiated within an SFP program, with community-based and SFP program management being equally effective in maintaining therapeutic compliance and persistence over 2 years. These results indicate that one of the main functions of an SFP program may be the initiation of therapy rather than continuous patient monitoring.
Publisher: Public Library of Science (PLoS)
Date: 06-12-2018
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.CANEP.2015.02.007
Abstract: Little is known about patterns of care after a cancer of unknown primary (CUP) diagnosis. We performed a retrospective cohort study to describe and compare the treatment, health service use and survival of patients with CUP and metastatic cancer of known primary among 143,956 Australian Government Department of Veterans' Affairs clients, 2004-2007. We randomly matched clients with CUP (C809 n=252) with clients with a first diagnosis of metastatic solid cancer of known primary (n=980). We ascertained health services from the month of diagnosis up to 2 months post-diagnosis for consultations, hospitalizations and emergency department visits, and up to 1 year for treatment. We compared cancer treatments using conditional logistic regression consultation rates using negative binomial regression and survival using stratified Cox regression. 30% of CUP patients and 70% of patients with known primary received cancer treatment and the median survival was 37 days and 310 days respectively. CUP patients received fewer cancer medicines (odds ratio (OR)=0.54, 95% confidence interval (CI) 0.33-0.89) and less cancer-related surgery (OR=0.25, 95% CI 0.15-0.41) males with CUP received more radiation therapy (OR=2.88, 95% CI 1.69-4.91). CUP patients had more primary care consultations (incidence rate ratio (IRR)=1.25, 95% CI 1.11-1.41), emergency department visits (IRR=1.86, 95% CI 1.50-2.31) and hospitalizations (IRR=1.18, 95% CI 1.03-1.35), and a higher risk of death within 30 days (hazard ratio=3.30, 95% CI 1.69-6.44). Patients with CUP receive less treatment but use more health services, which may reflect underlying patient and disease characteristics.
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.CANEP.2015.02.006
Abstract: Population-based data on the use of health services and diagnostic investigations for patients with cancer of unknown primary (CUP) is scarce. It is uncertain whether the pathways to diagnosis are different for CUP compared to other cancers. We performed a population-based nested matched case-control study using linked routinely collected records for Australian Government Department of Veterans' Affairs clients, 2004-2007. We compared health care consultations, hospitalisations, emergency department visits, and diagnostic procedures in the three months prior and the month of diagnosis for 281 clients registered with a diagnosis of CUP (C809) and 1102 controls randomly selected from clients registered with a first diagnosis of metastatic cancer of known primary. Overall, the median age at cancer diagnosis was 83 years. CUP patients were slightly older and had significantly more comorbidities prior to diagnosis than those with known primary. Compared to known primary, a diagnosis of CUP was significantly more likely after an emergency department visit, less specialist input, fewer invasive diagnostic procedures such as resection or endoscopy, and more non-invasive procedures such as magnetic resonance imaging. There were no differences in primary care or allied health consultations and hospitalisations. This health care pathway suggests delayed recognition of cancer and scope for improvement in the medical management of high-risk in iduals presenting to primary care. The pattern of diagnostic investigations reveals under-investigation in some CUP patients but this is likely to reflect recognition of limited treatment options and poor prognosis and is consistent with clinical guidelines.
Publisher: BMJ
Date: 22-10-2020
DOI: 10.1136/BMJQS-2019-009897
Abstract: Proton pump inhibitor (PPI) use is widespread. There have been increasing concerns about overuse of high-dose PPIs for durations longer than clinically necessary. To evaluate the impact of national education initiatives on reducing PPI use in Australia. Population-based, controlled interrupted time series analysis of PPI dispensing claims data for Australian adults from July 2012 to June 2018 we used statin dispensing as a control. A year-long educational initiative led by NPS MedicineWise (previously the National Prescribing Service) from April 2015. Simultaneously, Choosing Wisely released recommendations in April 2015 and May 2016. Both promoted review of prolonged PPI use and encouraged stepping down or ceasing treatment, where appropriate. We examined monthly changes in PPI (and statin) dispensing (stratified by high, standard and low tablet strength), rates of switching from higher to lower strength PPIs and rates of PPI (and statin) discontinuation. We observed 12 040 021 PPI dispensings to 579 594 people. We observed a sustained −1.7% (95% CI: −2.7 to −0.7%) decline in monthly dispensing of standard strength PPIs following the initiatives until the end of the study period. There were no significant changes in high or low strength PPI (or statin) dispensings, switching to lower strength PPIs, or PPI (and statin) treatment discontinuation. Our findings suggest that these educational initiatives alone were insufficient in curbing overuse of PPIs on a national level. Concerted efforts with policy levers such as imposing tighter restrictions on subsidised use of PPIs may be more effective. Noting low strength esomeprazole is not publicly subsidised in Australia, availability of these preparations may also facilitate more appropriate practice
Publisher: Wiley
Date: 13-11-2018
DOI: 10.1002/PDS.4683
Publisher: AMPCo
Date: 17-02-2020
DOI: 10.5694/MJA2.50507
Publisher: Elsevier BV
Date: 04-2023
Publisher: BMJ
Date: 08-09-2021
Publisher: Springer Science and Business Media LLC
Date: 29-05-2020
DOI: 10.1038/S41416-020-0908-5
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher: Springer Science and Business Media LLC
Date: 05-09-2015
DOI: 10.1007/S00198-014-2880-5
Abstract: This 7-year prospective observational study determined the predictors of re-fracture amongst 234 patients managed within a Secondary Fracture Prevention programme. Poor compliance, multiple co-morbidities, corticosteroid therapy, low hip bone mineral density (BMD) or low body weight were all significantly associated with re-fracture in patients commenced on long-term anti-resorptive therapy. Risk factors for osteoporotic fracture amongst treatment-naïve patients are well established. In contrast, predictors of re-fracture in patients optimally managed within a Secondary Fracture Prevention (SFP) programme are ill-defined. This prospective observational study included 234 subjects with incident osteoporotic fractures managed long-term by the Concord SFP programme. Using Cox proportional hazards models, predictors of re-fracture were analysed separately for patients commenced on specific pharmacotherapy (group 1, N=171) and subjects receiving calcium and/or vitamin D supplements only (group 2, N=63). Relevant anthropometric, clinical and technical data were documented at each visit. Compliance and persistence were analysed as time-varying covariates. During a mean follow-up of 5.2 (range 3.5-7.3) years, 20.9% of all subjects re-fractured (26.3% in group 1, 6.3% in group 2). Multivariate predictors of re-fracture in group 1 were significant co-morbidity (HR 2.04 if >3, 95% CI 1.10-3.79, p=0.024), corticosteroid use (HR 1.75, 95% CI 1.12-2.73, p=0.013) and total hip BMD (HR 1.36 per 0.1 g/cm2 decrease, 95% CI 1.08-1.70, p=0.008). In contrast, gender, prevalent fractures and lumbar spine BMD were not associated with re-fracture. Amongst patients with complete compliance data, a medication possession ratio of ≤50% (HR 3.36, 95% CI 1.32-8.53, p=0.011) and low body weight (HR 1.04 per 1-kg decrease, 95% CI 1.003-1.08, p=0.032) were significantly associated with re-fracture. Amongst patients managed within a dedicated SFP programme, poor compliance, multiple co-morbidities, corticosteroid therapy, low hip BMD or low body weight are all associated with increased risk of re-fracture. This subgroup of patients therefore require intensive management including strategies to improve compliance.
Publisher: Cold Spring Harbor Laboratory
Date: 16-05-2023
DOI: 10.1101/2023.05.12.23289914
Abstract: The effectiveness of COVID-19 monoclonal antibody and antiviral therapies against severe COVID-19 outcomes is unclear. Initial benefit was shown in unvaccinated patients and before the Omicron variant emerged. We used the OpenSAFELY platform to emulate target trials to estimate the effectiveness of sotrovimab or molnupiravir, versus no treatment. With the approval of NHS England, we derived population-based cohorts of non-hospitalised high-risk in iduals in England testing positive for SARS-CoV-2 during periods of dominance of the BA.1 (16/12/2021-10/02/2022) and BA.2 (11/02/2022-21/05/2022) Omicron sublineages. We used the clone-censor-weight approach to estimate the effect of treatment with sotrovimab or molnupiravir initiated within 5 days after positive test versus no treatment. Hazard ratios (HR) for COVID-19 hospitalisation or death within 28 days were estimated using weighted Cox models. Of the 35,856 [BA.1 period] and 39,192 [BA.2 period] patients, 1,830 [BA.1] and 1,242 [BA.2] were treated with molnupiravir and 2,244 [BA.1] and 4,164 [BA.2] with sotrovimab. The estimated HRs for molnupiravir versus untreated were 1.00 (95%CI: 0.81 .22) [BA.1] and 1.22 (0.96 .56) [BA.2] corresponding HRs for sotrovimab versus untreated were 0.76 (0.66 .89) [BA.1] and 0.92 (0.79 .06) [BA.2]. Compared with no treatment, sotrovimab was associated with reduced risk of adverse outcomes after COVID-19 in the BA.1 period, but there was weaker evidence of benefit in the BA2 period. Molnupiravir was not associated with reduced risk in either period. UKRI, Wellcome Trust, MRC, NIHR and HDRUK.
Publisher: Informa UK Limited
Date: 17-03-2023
DOI: 10.1080/09540121.2022.2050179
Abstract: Pharmacy dispensing data are useful for estimating adherence to therapy. Here, we implement multiple adherence measures to antiretroviral therapy (ART) and provide an online tool for visualising results. We conducted a cohort study for 2,042 people dispensed ART in Australia. We assessed adherence using the Proportion of Days Covered (PDC) within 360 days of follow-up as a continuous measure and dichotomised (PDC ≥80%). We defined a covered day as the 1) exposure to ≥3 antiretrovirals at the same time 2) exposure to any antiretroviral 3) lowest number of days covered per antiretroviral 4) average of days covered over all antiretrovirals 5) highest number of days covered per antiretroviral. For each method, we conducted sensitivity analyses. The median PDC ranged between 93.3%-98.3%. Between 67.0%-87.7% of in iduals were classified as adherent, with higher values for measure 2 (85.5%-89.7%) and lower values for measure 3 (67.0%-70.9%). Censoring loss to follow-up had a higher impact on adherence estimates than considering a grace period. The variation in adherence estimates can be substantial, especially when dichotomising adherence. Researchers should consider operationalising multiple measures to estimate adherence bounds and identify a range of people at risk of non-adherence for targeted interventions.
Publisher: AMPCo
Date: 07-2021
DOI: 10.5694/MJA2.51153
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: Royal College of General Practitioners
Date: 10-11-2020
DOI: 10.3399/BJGPOPEN20X101120
Abstract: In 2013 pregabalin was subsidised by Australia’s Pharmaceutical Benefits Scheme (PBS) for neuropathic pain. Since the subsidy, pregabalin prescribing has been increasing in Australia and so has related harm. There are concerns it is being prescribed for indications other than neuropathic pain, which have little evidence of efficacy. To describe pregabalin prescribing in Australian general practice. A cross-sectional study of patients attending 445 general practice sites in the national MedicineInsight database from March 2012–February 2018. The following aspects were calculated: the proportion of prescriptions that were for pregabalin per year the prevalence of pain conditions in patients prescribed pregabalin and same-day prescribing of pregabalin with opioids or benzodiazepines. Prescribing increased from 13 per 10 000 to 104 per 10 000 prescriptions between 2012–2013 and 2017–2018. A total of 1 891 623 patients were identified of whom 114 123 (6.0%) were prescribed pregabalin 49.7% ( n = 56 772) had a recorded diagnosis of neuropathic pain. Among people prescribed pregabalin without a recorded diagnosis of neuropathic pain, 43.5% ( n = 24 927) had a diagnosis of back problems, 8.8% ( n = 5073) chronic pain, and 26.4% ( n = 30 146) had no pain diagnosis. Pregabalin was prescribed the same day as an opioid to 38.1% of patients (95% confidence interval [CI] = 37.1% to 39.1%) and a benzodiazepine to 13.1% of patients (95% CI = 12.5% to 13.7%). Patients with a diagnosis of chronic pain had the highest rate of same-day prescribing of pregabalin with an opioid (70.4%, 95% CI = 68.9% to 71.9%) or a benzodiazepine (25.8%, 95% CI = 24.2% to 27.4%) Substantial increases in pregabalin prescribing were identified in Australian general practice, but only half of patients had a neuropathic pain diagnosis recorded, the only approved indication for subsidy. High rates of same-day prescribing with opioids and benzodiazepines may put patients at increased risk of harm.
Publisher: Wiley
Date: 12-02-2019
DOI: 10.1111/AJCO.13121
Publisher: Portland Press Ltd.
Date: 18-03-2016
DOI: 10.1042/CS20150838
Abstract: Oxidative phosphorylation (OXPHOS) drives ATP production by mitochondria, which are dynamic organelles, constantly fusing and iding to maintain kidney homoeostasis. In diabetic kidney disease (DKD), mitochondria appear dysfunctional, but the temporal development of diabetes-induced adaptations in mitochondrial structure and bioenergetics have not been previously documented. In the present study, we map the changes in mitochondrial dynamics and function in rat kidney mitochondria at 4, 8, 16 and 32 weeks of diabetes. Our data reveal that changes in mitochondrial bioenergetics and dynamics precede the development of albuminuria and renal histological changes. Specifically, in early diabetes (4 weeks), a decrease in ATP content and mitochondrial fragmentation within proximal tubule epithelial cells (PTECs) of diabetic kidneys were clearly apparent, but no changes in urinary albumin excretion or glomerular morphology were evident at this time. By 8 weeks of diabetes, there was increased capacity for mitochondrial permeability transition (mPT) by pore opening, which persisted over time and correlated with mitochondrial hydrogen peroxide (H2O2) generation and glomerular damage. Late in diabetes, by week 16, tubular damage was evident with increased urinary kidney injury molecule-1 (KIM-1) excretion, where an increase in the Complex I-linked oxygen consumption rate (OCR), in the context of a decrease in kidney ATP, indicated mitochondrial uncoupling. Taken together, these data show that changes in mitochondrial bioenergetics and dynamics may precede the development of the renal lesion in diabetes, and this supports the hypothesis that mitochondrial dysfunction is a primary cause of DKD.
Publisher: Wiley
Date: 05-12-2021
DOI: 10.1002/CPT.2113
Abstract: This study evaluated the ability of a pilot therapeutic drug monitoring (TDM) Advisory Service to facilitate vancomycin therapeutic target attainment within a real‐world clinical setting. The Service provided area under the concentration‐time curve (AUC)–guided vancomycin dose recommendations, using Bayesian forecasting software and clinical expertise, to prescribers at an Australian hospital. A retrospective audit of intravenous vancomycin therapy ( 48 hours) in adults (≥ 18 years old) was undertaken over a 54‐month period to evaluate attainment of established vancomycin pharmacokinetic harmacodynamic targets (AUC over 24 hours / minimum inhibitory concentration: 400–600) before (36‐month period) and after (18‐month period) Service implementation. Interrupted time series analysis was employed to evaluate monthly measures of the median proportion of therapy spent within the target range. Indices of time to target attainment were also assessed before and after Service implementation. The final cohort comprised 1,142 courses of vancomycin (816 patients) 835 courses (596 patients) and 307 courses (220 patients) administered before and after Service implementation, respectively. Prior to piloting the Service, the median proportion of time in the target range was 40.1% (95% CI, 34.3–46.0%) this increased by 10.4% (95% CI, 1.2–19.6%, P = 0.03) after the Service, and was sustained throughout the post‐Service evaluation period. Post‐Service target attainment at 48–72 hours after initiation of therapy was increased (7.8%, 95% CI, 1.3–14.3%, P = 0.02). The findings of this study provide evidence that a consultative TDM Service can facilitate attainment of vancomycin therapeutic targets however, optimization of the Service may further improve the use of vancomycin.
Publisher: Mary Ann Liebert Inc
Date: 02-2020
Publisher: Wiley
Date: 02-2022
DOI: 10.1111/IMJ.15036
Abstract: P2Y 12 inhibitor therapy is recommended for 12 months in patients hospitalised for acute myocardial infarction (AMI) unless the bleeding risk is high. To describe real‐world use of P2Y 12 inhibitor therapy following AMI hospitalisation. We used population‐level linked hospital data to identify all patients discharged from a public hospital with a primary diagnosis of AMI between July 2011 and June 2013 in New South Wales and Victoria, Australia. We used dispensing claims to examine dispensing of a P2Y 12 inhibitor (clopidogrel, prasugrel or ticagrelor) within 30 days of discharge and multilevel models to identify predictors of post‐discharge dispensing and persistence of therapy to 1 year. We identified 31 848 patients hospitalised for AMI, of whom 56.8% were dispensed a P2Y 12 inhibitor within 30 days of discharge. The proportion of patients with post‐discharge dispensing varied between hospitals (interquartile range: 25.0–56.5%), and significant between‐hospital variation remained after adjusting for patient characteristics. Patient factors associated with the lowest likelihood of post‐discharge dispensing were: having undergone coronary artery bypass grafting (odds ratio (OR): 0.17 95% confidence intervals (CI): 0.15–0.20) having oral anticoagulants dispensed 180 days before or 30 days after discharge (OR: 0.39, 95% CI: 0.35–0.44) major bleeding (OR: 0.68, 95% CI: 0.61–0.76) or being aged ≥85 years (OR: 0.68, 95% CI: 0.62–0.75). A total of 26.8% of patients who were dispensed a P2Y 12 inhibitor post‐discharge discontinued therapy within 1 year. Post‐hospitalisation use of P2Y 12 inhibitor therapy in AMI patients is low and varies substantially by hospital of discharge. Our findings suggest strategies addressing both health system (hospital and physician) and patient factors are needed to close this evidence‐practice gap.
Publisher: American Medical Association (AMA)
Date: 18-09-2019
Publisher: Wiley
Date: 09-05-2023
DOI: 10.1111/DAR.13675
Abstract: Prescriber behaviour is important for understanding opioid use patterns. We described variations in practitioner‐level opioid prescribing in New South Wales, Australia (2013–2018). We quantified opioid prescribing patterns among medical practitioners using population‐level dispensing claims data, and used partitioning around medoids to identify clusters of practitioners who prescribe opioids based on prescribing patterns and patient characteristics identified from linked dispensing claims, hospitalisations and mortality data. The number of opioid prescribers ranged from 20,179 in 2013 to 23,408 in 2018. The top 1% of practitioners prescribed 15% of all oral morphine equivalent (OME) milligrams dispensed annually, with a median of 1382 OME grams (interquartile range [IQR], 1234–1654) per practitioner the bottom 50% prescribed 1% of OMEs dispensed, with a median of 0.9 OME grams (IQR 0.2–2.6). Based on 63.6% of practitioners with ≥10 patients filling opioid prescriptions in 2018, we identified four distinct practitioner clusters. The largest cluster prescribed multiple analgesic medicines for older patients (23.7% of practitioners) accounted for 76.7% of all OMEs dispensed and comprised 93.0% of the top 1% of practitioners by opioid volume dispensed. The cluster prescribing analgesics for younger patients with high rates of surgery (18.7% of practitioners) prescribed only 1.6% of OMEs. The remaining two clusters comprised 21.2% of prescribers and 20.9% of OMEs dispensed. We observed substantial variation in opioid prescribing among practitioners, clustered around four general patterns. We did not assess appropriateness but some prescribing patterns are concerning. Our findings provide insights for targeted interventions to curb potentially harmful practices.
Publisher: Springer Science and Business Media LLC
Date: 22-03-2021
DOI: 10.1186/S12874-021-01235-8
Abstract: Interrupted time series analysis is increasingly used to evaluate the impact of large-scale health interventions. While segmented regression is a common approach, it is not always adequate, especially in the presence of seasonality and autocorrelation. An Autoregressive Integrated Moving Average (ARIMA) model is an alternative method that can accommodate these issues. We describe the underlying theory behind ARIMA models and how they can be used to evaluate population-level interventions, such as the introduction of health policies. We discuss how to select the shape of the impact, the model selection process, transfer functions, checking model fit, and interpretation of findings. We also provide R and SAS code to replicate our results. We illustrate ARIMA modelling using the ex le of a policy intervention to reduce inappropriate prescribing. In January 2014, the Australian government eliminated prescription refills for the 25 mg tablet strength of quetiapine, an antipsychotic, to deter its prescribing for non-approved indications. We examine the impact of this policy intervention on dispensing of quetiapine using dispensing claims data. ARIMA modelling is a useful tool to evaluate the impact of large-scale interventions when other approaches are not suitable, as it can account for underlying trends, autocorrelation and seasonality and allows for flexible modelling of different types of impacts.
Publisher: BMJ
Date: 05-2020
DOI: 10.1136/BMJOPEN-2020-038181
Abstract: In Australia, suicide is the leading cause of death for people aged 15–44 years. Health professionals deliver most of our key suicide prevention strategies via health services, but other efficacious population-level strategies include means restriction and public awareness c aigns. Currently, we have no population-level data allowing us to determine which in iduals, in what parts of Australia, are likely to use our most promising interventions delivered by health services. The aims of this study are to describe: (1) health service utilisation rates in the year prior to death by suicide, and how this varies by in idual case characteristics (2) prescribed medicines use in the year prior to death by suicide, medicines used in suicide by poisoning and how this varies by in idual case characteristics. This is a population-based case series study of all suicide cases in Australia identified through the National Coronial Information System (NCIS) from 2013 to 2019. Cases will be linked to administrative claims data detailing health service use and medicines dispensed in the year before death. We will also obtain findings from the coronial enquiry, including toxicology. Descriptive statistics will be produced to characterise health service and prescribed medicine use and how utilisation varies by age, sex, method of death and socioeconomic status. We will explore the geographical variability of health service and medicine use, highlighting regions in Australia associated with more limited access. This project involves the use of sensitive and confidential data. Data will be linked using a third-party privacy-preserving protocol meaning that investigators will not have access to identifiable information once the data have been linked. Statistical analyses will be carried out in a secure environment. This study has been approved by the following ethics committees: (1) the Justice Department Human Research Ethics Committee (REF: CF/17/23250), (2) the Western Australian Coroners Court (REF: EC 14/18 M0400), (3) the Australian Institute of Health and Welfare (REF: EO2017/4/366) and (4) NSW Population & Health Services Research Ethics Committee (REF: 2017/HRE1204). Findings will be published in peer-reviewed journals, presented at conferences and communicated to regulatory authorities, clinicians and policy-makers.
Publisher: Elsevier BV
Date: 09-2023
Publisher: Wiley
Date: 05-09-2018
DOI: 10.1111/ADD.14412
Abstract: Pregabalin is a gamma-aminobutyric acid (GABA) analogue, used to treat neuropathic pain and epilepsy. Pregabalin was registered in Australia in 2005, and subsidized publically in 2013. We aimed to describe Australian patterns of pregabalin use and intentional poisoning, and identify people potentially at high risk of misuse. Population-based retrospective cohort study of dispensings in the 10% s le of Australian Pharmaceutical Benefits Scheme (July 2012-February 2017) intentional poisoning calls to New South Wales Poisons Information Centre (NSWPIC) (2004-2016) intentional poisonings in two Australian toxicology service databases and poisoning fatalities in NSW coronial records (2005-2016). A total of 122 572 people dispensed pregabalin, people with intentional pregabalin overdoses managed by NSWPIC and the toxicology services and pregabalin-associated deaths referred to the NSW coroner. Trends in dispensing, poisoning, death demographics and patient characteristics, proportion of users at high risk of misuse (latent class analysis, LCA) and characteristics of high-risk users. Pregabalin dispensing increased by 73 424 per year [95% confidence interval (CI) = 61726-85 121 P < 0.001] between 2013 and 2016. NSWPIC received 1158 reports of intentional pregabalin poisonings, with a 53.8% increase per year, 2005-2016 (95% CI = 44.0-64.2%, P < 0.001). We identified 88 pregabalin-associated deaths, 57.8% yearly increase (95% CI = 30.0-91.6%, P < 0.001). Patients overdosing on pregabalin commonly co-ingested opioids, benzodiazepines and illicit drugs, and had high rates of psychiatric and substance use comorbidities 14.7% of pregabalin users were classed by the LCA as at high risk of misuse, and were more likely to be younger, male, co-prescribed benzodiazepines or opioids, have more in idual prescribers and higher pregabalin strengths dispensed. There has been a dramatic increase in pregabalin use, poisonings and deaths in Australia since it became subsidized publicly in 2013. One in seven Australians dispensed pregabalin appears to be at high risk of misuse.
Publisher: Wiley
Date: 27-10-2022
DOI: 10.1002/PHAR.2735
Abstract: Multimorbidity and multimedicine use are common in people with cardiovascular disease and can lead to harms, such as prescribing errors and drug interactions. We quantified multimedicine use in people treated with cardiovascular medicines in a national s le of Australians. Cross‐sectional study. Pharmaceutical dispensing claims for a 10% random s le of Australians. Australian adults dispensed any cardiovascular medicine between June and August 2019. None. We quantified the number and type of cardiovascular and non‐cardiovascular medicines dispensed during the study period, and the number of unique prescribers, by age and sex. We identified 493,081 people dispensed any cardiovascular medicine (median age = 67 years, 50.2% women). The population prevalence of cardiovascular medicine dispensing increased from 1.7% ( n = 10,503) in people 18–34 years to 80.1% ( n = 99,271) in people 75–84 years. Cardiovascular medicine dispensing varied by sex women 18–34 years were more likely to be dispensed any cardiovascular medicine than men (male:female prevalence ratio [PR] = 0.84, 95% confidence interval [CI] = 0.81–0.87), whereas the prevalence of cardiovascular medicine dispensing was higher in men 35–44 years (PR = 1.27, 95% CI 1.24–1.30) and 45–54 years (PR = 1.24, 95% CI 1.22–1.26) and was similar between sexes in people ≥65 years. Overall, both women and men were dispensed a median of 2.0 (interquartile range [IQR] = 1.0–3.0) cardiovascular medicines. Two‐thirds of people ≥65 years (73.5% n = 208,524) were dispensed ≥2 cardiovascular medicines, with 16.6% ( n = 6736) of people ≥85 years dispensed five or more. Women and men were dispensed a median of 2.0 (IQR = 1.0–5.0) and 2.0 (IQR = 0.0–4.0) non‐cardiovascular medicines, respectively, to treat comorbid conditions, commonly gastroesophageal reflux disease medicines (32.2% of women and 26.6% of men), antibiotics (28.7% of women and 22.4% of men), and antidepressants (26.3% of women and 15.9% of men). One quarter of both sexes had multiple prescribers for their cardiovascular medicines alone, whereas 54.5% ( n = 134,939) of women and 49.9% ( n = 122,706) of men had multiple prescribers for all medicines. Multimedicine use is common in people treated with cardiovascular medicines and presents a risk for inappropriate prescribing. Understanding the comorbid conditions commonly treated concurrently with cardiovascular disease can help improve co‐prescribing guidelines and develop a person‐centered approach to multimorbidity treatment.
Publisher: Wiley
Date: 22-01-2019
DOI: 10.1111/ADD.14531
Publisher: Swansea University
Date: 15-04-2021
Abstract: ObjectiveA wealth of data is generated through Australia’s universal health care arrangements. However, use of these data has been h ered by different federal and state legislation, privacy concerns and challenges in linking data across jurisdictions. A series of data reforms have been touted to increase population health research capacity in Australia, including pharmacoepidemiology research. Here we catalogued research leveraging Australia’s Pharmaceutical Benefits Scheme (PBS) data (2014–2018) and discussed these outputs in the context of previously implemented and new data reforms. MethodsWe conducted a systematic review of population-based studies using PBS dispensing claims. Independent reviewers screened abstracts of 4,996 articles and 310 full-text manuscripts. We characterised publications according to study population, analytical approach, data sources used, aims and medicines focus. ResultsWe identified 180 studies 133 used in idual-level data, 70 linked PBS dispensing claims with other health data (66 across jurisdictions). Studies using in idual-level data focussed on Australians receiving government benefits (87 studies) rather than all PBS-eligible persons. 63 studies examined clinician or patient practices and 33 examined exposure-outcome relationships (27 evaluated medicines safety, 6 evaluated effectiveness). Medicines acting on the nervous and cardiovascular system account for the greatest volume of PBS medicines dispensed and were the most commonly studied (67 and 40 studies, respectively). Antineoplastic and immunomodulating agents account for approximately one third of PBS expenditure but represented only 10% of studies in this review. ConclusionsThe studies in this review represent more than a third of all population-based pharmacoepidemiology research published in the last three decades in Australia. Recent data reforms have contributed to this escalating output. However, studies are concentrated among specific subpopulations and medicines classes, and there remains a limited understanding of population benefits and harms derived from medicines use. The current draft Data Availability and Transparency legislation should further bolster efforts in population health research.
Publisher: American Medical Association (AMA)
Date: 10-08-2023
DOI: 10.1001/JAMANETWORKOPEN.2023.28159
Abstract: There are known risks of using opioids for extended periods. However, less is known about the long-term trajectories of opioid use following initiation. To identify 5-year trajectories of prescription opioid use, and to examine the characteristics of each trajectory group. This population-based cohort study conducted in New South Wales, Australia, linked national pharmaceutical claims data to 10 national and state data sets to determine sociodemographic characteristics, clinical characteristics, drug use, and health services use. The cohort included adult residents (aged ≥18 years) of New South Wales who initiated a prescription opioid between July 1, 2003, and December 31, 2018. Statistical analyses were conducted from February to September 2022. Dispensing of a prescription opioid, with no evidence of opioid dispensing in the preceding 365 days, identified from pharmaceutical claims data. The main outcome was the trajectories of monthly opioid use over 60 months from opioid initiation. Group-based trajectory modeling was used to classify these trajectories. Linked health care data sets were used to examine characteristics of in iduals in different trajectory groups. Among 3 474 490 in iduals who initiated a prescription opioid (1 831 230 females [52.7%] mean [SD] age, 49.7 [19.3] years), 5 trajectories of long-term opioid use were identified: very low use (75.4%), low use (16.6%), moderate decreasing to low use (2.6%), low increasing to moderate use (2.6%), and sustained use (2.8%). Compared with in iduals in the very low use trajectory group, those in the sustained use trajectory group were older (age ≥65 years: 22.0% vs 58.4%) had more comorbidities, including cancer (4.1% vs 22.2%) had increased health services contact, including hospital admissions (36.9% vs 51.6%) had higher use of psychotropic (16.4% vs 42.4%) and other analgesic drugs (22.9% vs 47.3%) prior to opioid initiation, and were initiated on stronger opioids (20.0% vs 50.2%). Results of this cohort study suggest that most in iduals commencing treatment with prescription opioids had relatively low and time-limited exposure to opioids over a 5-year period. The small proportion of in iduals with sustained or increasing use was older with more comorbidities and use of psychotropic and other analgesic drugs, likely reflecting a higher prevalence of pain and treatment needs in these in iduals.
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.CANEP.2019.05.001
Abstract: The relationship between comorbid disease and health service use and risk of cancer of unknown primary site (CUP) is uncertain. A prospective cohort of 266,724 people aged 45 years and over in New South Wales, Australia. Baseline questionnaire data were linked to cancer registration, health service records 4-27 months prior to diagnosis, and mortality data. We compared in iduals with incident registry-notified CUP (n = 327 90% C80) to two sets of randomly selected controls (3:1): (i) incident metastatic cancer of known primary site (n = 977) and (ii) general cohort population (n = 981). We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). In fully adjusted models incorporating sociodemographic and lifestyle factors, people with cancer registry-notified CUP were more likely to have fair compared with excellent self-rated overall health (OR 1.78, 95% CI 1.01-3.14) and less likely to self-report anxiety (OR 0.48, 95% CI 0.24-0.97) than those registered with metastatic cancer of known primary. Compared to general cohort population controls, people registered with CUP were more likely to have poor rather than excellent self-rated overall health (OR 6.22, 95% CI 1.35-28.6), less likely to self-report anxiety (OR 0.28, 95% CI 0.12-0.63), and more likely to have a history of diabetes (OR 1.89, 95% CI 1.15-3.10) or cancer (OR 1.62, 95% CI 1.03-2.57). Neither tertiary nor community-based health service use independently predicted CUP risk. Low self-rated health may be a flag for undiagnosed cancer, and an investigation of its clinical utility in primary care appears warranted.
Location: United Kingdom of Great Britain and Northern Ireland
Location: Australia
Start Date: 2019
End Date: 2017
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2019
End Date: 2017
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2019
End Date: 2017
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2019
End Date: 2017
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2014
End Date: 2017
Funder: National Health and Medical Research Council
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