ORCID Profile
0000-0001-8730-8910
Current Organisation
University of South Australia
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Publisher: BMJ
Date: 10-06-2020
DOI: 10.1136/BJOPHTHALMOL-2020-316373
Abstract: To identify the association between ranibizumab and risk of stroke and acute myocardial infarction (AMI) in patients with exudative age-related macular degeneration (AMD). We identified patients aged ≥45 years who received ranibizumab for exudative AMD from the Korean National Health Insurance database. Of these, we selected patients suffering stroke or AMI for the self-controlled case series. We estimated incidence rate ratios (IRR) for stroke or AMI by comparing incidence rates of ranibizumab-exposed periods to that of baseline using conditional Poisson regression. The risks of haemorrhagic and ischaemic strokes were also calculated separately. Among 33 134 patients receiving ranibizumab, 2397 patients had stroke or AMI. The risk of stroke (IRR=0.83, 95% CI 0.75 to 0.91) was not increased during the overall exposed period however, there was a marginally elevated risk in ≥57 days exposed period (IRR=1.14, 95% CI 1.001 to 1.31). When analysing by the types of stroke, no increased risks of haemorrhagic (IRR=1.01, 95% CI 0.80 to 1.26) and ischaemic stroke (IRR=0.78, 95% CI 0.71 to 0.86) were observed during the exposed period, although the risks of ischaemic and haemorrhagic stroke were slightly elevated during ≥57 days exposed period. We could not find an association between ranibizumab and AMI. Ranibizumab intravitreal injections did not increase the overall risk of stroke or AMI. Although the cardiovascular risk in patient receiving ranibizumab seems to be low, continuous monthly use of ranibizumab for high-risk patients should be judged carefully.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-05-2019
DOI: 10.1097/CORR.0000000000000673
Abstract: Mortality after THA and TKA is lower than expected for several years after surgery when compared with age- and sex-adjusted population data. With long-term followup (beyond approximately 10 years), some evidence has suggested that this trend reverses, such that postsurgical mortality is higher than expected as more time passes. However, the degree to which this may be the case has not been clearly established. In this large-registry study, we asked: What is the long-term mortality after THA and TKA compared with the expected mortality, adjusted for age, sex, and calendar year. Using data on 243,057 THAs and 363,355 TKAs performed for osteoarthritis from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) from 2003 to 2016, and life tables from the Australian Bureau of Statistics the Standardised Mortality Ratio (SMR), relative mortality and excess mortality (relative to the expected mortality for people of the same sex and age in the same country) was calculated separately for hips and knees. The AOANJRR contains near-complete (98%-100%) data from all hospitals in Australia performing arthroplasty but does not include followup data on people who have left the country. Followup was from the date of surgery to 13 years, mean 5.8 years. We found a lower-than-expected mortality for THA and TKA in the early years after surgery. This association diminished over time and the mortality became higher than expected after 12 years for both THA and TKA. For THA, the excess mortality (per thousand people) increased from 11 fewer deaths (95% CI, 10–11 fewer) after 1 year to four more deaths (95% CI, 0–9 more) in the 13th year, and the SMR increased from 0.50 (95% CI, 0.48–0.52) after 1 year to 1.07 (95% CI, 0.99–1.14) in the 13th year. For TKA, the excess mortality (per thousand people) increased from 12 fewer deaths (95% CI, 12–13 fewer) after 1 year to five more deaths (95% CI 2–9 more) in the 13th year, and the SMR increased from 0.39 (95% CI, 0.37–0.40) after 1 year to 1.09 (95% CI, 1.03–1.15) in the 13th year. Mortality after hip and knee arthroplasty is lower than expected (based on population norms) in the first 8 years to 9 years but gradually increases over time, becoming higher than expected after 12 years. The lower-than-expected mortality in the early years after surgery is likely the result of patient selection with patients undergoing primary arthroplasty having better health at the time of surgery than that of the age- and sex-matched population. The increasing mortality over time cannot be regression to the mean, as late mortality is higher than expected, moving beyond the mean. It is important to understand if there are modifiable factors associated with this increased mortality. The reasons for the change are uncertain. Factors to consider in future research include determining the effect of different patient factors on late mortality. Some of these included higher obesity rates for joint replacement patients and the association or causal impact of osteoarthritis and/or its treatment to increase late mortality in a similar manner to other forms of arthritis. There is also a possibility that the arthroplasty device itself may affect late mortality. Level III, therapeutic study.
Publisher: JMIR Publications Inc.
Date: 10-01-2022
DOI: 10.2196/33873
Abstract: Digital technologies can enable rapid targeted delivery of audit and feedback interventions at scale. Few studies have evaluated how mode of delivery affects clinical professional behavior change and none have assessed the feasibility of such an initiative at a national scale. The aim of this study was to develop and evaluate the effect of audit and feedback by digital versus postal (letter) mode of delivery on primary care physician behavior. This study was developed as part of the Veterans’ Medicines Advice and Therapeutics Education Services (MATES) program, an intervention funded by the Australian Government Department of Veterans’ Affairs that provides targeted education and patient-specific audit with feedback to Australian general practitioners, as well as educational material to veterans and other health professionals. We performed a cluster randomized controlled trial of a multifaceted intervention to reduce inappropriate gabapentinoid prescription, comparing digital and postal mode of delivery. All veteran patients targeted also received an educational intervention (postal delivery). Efficacy was measured using a linear mixed-effects model as the average number of gabapentinoid prescriptions standardized by defined daily dose (in idual level), and number of veterans visiting a psychologist in the 6 and 12 months following the intervention. The trial involved 2552 general practitioners in Australia and took place in March 2020. Both intervention groups had a significant reduction in total gabapentinoid prescription by the end of the study period (digital: mean reduction of 11.2%, P=.004 postal: mean reduction of 11.2%, P=.001). We found no difference between digital and postal mode of delivery in reduction of gabapentinoid prescriptions at 12 months (digital: –0.058, postal: –0.058, P=.98). Digital delivery increased initiations to psychologists at 12 months (digital: 3.8%, postal: 2.0%, P=.02). Our digitally delivered professional behavior change intervention was feasible, had comparable effectiveness to the postal intervention with regard to changes in medicine use, and had increased effectiveness with regard to referrals to a psychologist. Given the logistical benefits of digital delivery in nationwide programs, the results encourage exploration of this mode in future interventions.
Publisher: Elsevier BV
Date: 11-2023
Publisher: MDPI AG
Date: 06-06-2019
Abstract: Background: Multiple studies have assessed the appropriateness of the use of medicines for nursing home residents however, few have included duration of use in their assessment. The aim of this study was to assess the level and duration of use of medications recommended for short-term use in residents of aged care facilities in Australia. Methods: Australian Government Department of Veterans’ Affairs (DVA) administrative claims data were used for this study. Veterans eligible for all health services subsidised by DVA were followed for one year from 1 July 2015 to 30 June 2016. The number of days covered for each medicine was calculated by multiplying the number of prescriptions dispensed during the year by the pack duration for the medicine. The pack duration was calculated by iding the quantity supplied at each dispensing by the usual number of doses per day in older people according to Australian prescribing guidelines. The proportion of patients using each medicine and the number of days covered during the study period were determined. Results: 14, 237 residents met the inclusion criteria. One in five participants were dispensed antipsychotics, and the median duration of use was 180 days in the one-year period. More than one-third were dispensed a benzodiazepine, and the median duration of use was 240 days in the year. Half were dispensed an opioid analgesic with a median duration of use of 225 days in the year. Fifty-two percent were dispensed proton pump inhibitors with a median duration of use of 360 days in the year. A quarter received an antibiotic recommended for the management of urinary tract infection, with a median duration of use of 14 days in the year. Conclusion: Long-term use of antipsychotics, benzodiazepines, opioid analgesics and proton pump inhibitors is common in aged care residents. Ensuring appropriate duration of use for these medicines is necessary to reduce risk of harm.
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.IJMEDINF.2018.09.002
Abstract: Adverse drug events (ADEs) are among the top causes of hospitalization and death. Social media is a promising open data source for the timely detection of potential ADEs. In this paper, we study the problem of detecting signals of ADEs from social media. Detecting ADEs whose drug and AE may be reported in different posts of a user leads to major concerns regarding the content authenticity and user credibility, which have not been addressed in previous studies. Content authenticity concerns whether a post mentions drugs or adverse events that are actually consumed or experienced by the writer. User credibility indicates the degree to which chronological evidence from a user's sequence of posts should be trusted in the ADE detection. We propose AC-SPASM, a Bayesian model for the authenticity and credibility aware detection of ADEs from social media. The model exploits the interaction between content authenticity, user credibility and ADE signal quality. In particular, we argue that the credibility of a user correlates with the user's consistency in reporting authentic content. We conduct experiments on a real-world Twitter dataset containing 1.2 million posts from 13,178 users. Our benchmark set contains 22 drugs and 8089 AEs. AC-SPASM recognizes authentic posts with F Our study demonstrates that taking into account the content authenticity and user credibility improves the detection of ADEs from social media. Our work generates hypotheses to reduce experts' guesswork in identifying unknown potential ADEs.
Publisher: Oxford University Press (OUP)
Date: 24-02-2023
Abstract: Observational studies can impact patient care but must be robust and reproducible. Nonreproducibility is primarily caused by unclear reporting of design choices and analytic procedures. This study aimed to: (1) assess how the study logic described in an observational study could be interpreted by independent researchers and (2) quantify the impact of interpretations’ variability on patient characteristics. Nine teams of highly qualified researchers reproduced a cohort from a study by Albogami et al. The teams were provided the clinical codes and access to the tools to create cohort definitions such that the only variable part was their logic choices. We executed teams’ cohort definitions against the database and compared the number of subjects, patient overlap, and patient characteristics. On average, the teams’ interpretations fully aligned with the master implementation in 4 out of 10 inclusion criteria with at least 4 deviations per team. Cohorts’ size varied from one-third of the master cohort size to 10 times the cohort size (2159–63 619 subjects compared to 6196 subjects). Median agreement was 9.4% (interquartile range 15.3–16.2%). The teams’ cohorts significantly differed from the master implementation by at least 2 baseline characteristics, and most of the teams differed by at least 5. Independent research teams attempting to reproduce the study based on its free-text description alone produce different implementations that vary in the population size and composition. Sharing analytical code supported by a common data model and open-source tools allows reproducing a study unambiguously thereby preserving initial design choices.
Publisher: Hindawi Limited
Date: 04-07-2016
DOI: 10.1111/JCPT.12418
Abstract: Although several studies have identified factors which increase the risk of heat-related illness, few have assessed the contribution of medicines. To address this knowledge gap, our study aimed to assess the risk of hospital admission for dehydration or other heat-related illness following initiation of medicines. We conducted a retrospective analysis using prescription event symmetry analysis (PESA) of 6700 veterans with incident hospital admission for dehydration or heat-related illness (ICD-10-AM codes E86, X30, T67), between 1 January 2001 and 30 June 2013. The main outcome measure was first ever hospital admission for dehydration or heat-related illness following initiation of commonly used medicines. A significantly higher risk of incident hospital admission for dehydration or heat-related illness was observed following initiation of anticoagulants, cardiovascular medicines, NSAIDs, antipsychotics, antidepressants and anticholinergic agents. The risk of hospital admission for dehydration or heat-related illness ranged from 1·17 (SSRIs) to 2·79 (ACEI plus diuretic combination product). No significant association was observed between initiation of anticonvulsants, anti-Parkinson's agents, hypnotics, anxiolytics or antihistamines and hospital admission for dehydration or heat-related illness. Many commonly used medicines were found to be associated with increased risk of hospitalization for dehydration or heat-related illness. Initiation of ACE inhibitors in combination with diuretics had the highest risk. Prescribers and patients should be aware of the potential for medicines to be associated with increased risk of dehydration and heat-related illness.
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.ARTH.2016.09.040
Abstract: Opioids are commonly used for the management of preoperative and postoperative pain among patients undergoing total knee arthroplasty (TKA). There is limited literature on the chronic use of opioids pre-TKA and post-TKA. The aim of this study was to characterize the use of opioids in TKA patients before and after surgery and identify risk factors of chronic opioid use. Opioid use among 15,020 patients undergoing TKA (01/01/2001-31/12/2012) was examined. Generalized estimating equations assessed change in total oral morphine equivalents pre-TKA and post-TKA, and logistic regression estimated risk factors of chronic opioid use. Of the total s le, 7782 (52.0%) patients had at least 1 opioid (38.6% pre-TKA and 34.4% post-TKA). The most commonly prescribed opioids were oxycodone, codeine + acetaminophen, and tramadol. Pre-TKA, 720 (4.8%) patients were chronic opioid users, of which 241 (33.5%) stopped being chronic users after surgery and 479 (66.5%) continued but had a 16% reduction (incidence rate ratio = 0.84 95% confidence interval, 0.78-0.90) in total oral morphine equivalents. Of the 5077 (33.8%) occasional opioid user pre-TKA, 2407 (47.4%) stopped after surgery. Compared to nonopioid users, chronic users were younger, were female, had more comorbidity, and had longer hospital stays. Older age was associated with ceasing chronic opioid use post-TKA. There was a reduction in opioid use following TKA. Almost 50% of occasional users and more than 30% of chronic users pre-TKA ceased opioids postoperatively. There was a reduction in use for those chronic users who continued to take opioids postsurgery.
Publisher: Springer Science and Business Media LLC
Date: 12-2013
Abstract: The Australian Government Department of Veterans’ Affairs (DVA) funds an ongoing health promotion based program to improve use of medicines and related health services, which implements interventions that include audit and feedback in the form of patient-specific feedback generated from administrative claims records. We aimed to determine changes in medicine use as a result of the program. The program provides targeted patient-specific feedback to medical practitioners. The feedback is supported with educational material developed by a clinical panel, subject to peer review and overseen by a national editorial committee. Veterans who meet target criteria also receive educational brochures. The program is supported by a national call centre and ongoing national consultation. Segmented regression analyses (interrupted time series) were undertaken to assess changes in medication use in targeted veterans pre and post each intervention. 12 interventions were included three to increase medicine use, seven which aimed to reduce use, and two which had combination of messages to change use. All programs that aimed to increase medicine use were effective, with relative effect sizes at the time of the intervention ranging from 1% to 8%. Mixed results were seen with programs aiming to reduce inappropriate medicine use. Highly specific programs were effective, with relative effect sizes at the time of the intervention of 10% decline in use of NSAIDs in high risk groups and 14% decline in use of antipsychotics in dementia. Interventions targeting combinations of medicines, including medicine interactions and potentially inappropriate medicines in the elderly did not change practice significantly. Interventions with combinations of messages targeting multiple components of practice had an impact on one component, but not all components targeted. The Veterans’ MATES program showed positive practice change over time, with interventions increasing use of appropriate medicines where under-use was evident and reduced use of inappropriate medicines when single medicines were targeted. Combinations of messages were less effective, suggesting specific messages focusing on single medicines are required to maximise effect. The program provides a model that could be replicated in other settings.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-07-2021
DOI: 10.1097/CORR.0000000000001895
Abstract: When analyzing the outcomes of joint arthroplasty, an important factor to consider is patient comorbidities. The presence of multiple comorbidities has been associated with longer hospital stays, more postoperative complications, and increased mortality. The American Society of Anesthesiologists (ASA) physical status classification system score is a measure of a patient’s overall health and has been shown to be associated with complications and mortality after joint arthroplasty. The Rx-Risk score is another measure for determining the number of different health conditions for which an in idual is treated, with a possible score ranging from 0 to 47. For patients undergoing THA or TKA, we asked: (1) Which metric, the Rx-Risk score or the ASA score, correlates more closely with 30- and 90-day mortality after TKA or THA? (2) Is the Rx-Risk score correlated with the ASA score? This was a retrospective analysis of the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) database linked to two other national databases, the National Death Index (NDI) database and the Pharmaceutical Benefits Scheme (PBS), a dispensing database. Linkage to the NDI provided outcome information on patient death, including the fact of and date of death. Linkage to the PBS was performed to obtain records of all medicines dispensed to patients undergoing a joint replacement procedure. Patients were included if they had undergone either a THA (119,076 patients, 131,336 procedures) or TKA (182,445 patients, 215,712 procedures) with a primary diagnosis of osteoarthritis, performed between 2013 and 2017. We excluded patients with missing ASA information (THA: 3% [3055 of 119,076] TKA: 2% [4095 of 182,445]). This left 127,761 primary THA procedures performed in 116,021 patients (53% [68,037 of 127,761] were women, mean age 68 ± 11 years) and 210,501 TKA procedures performed in 178,350 patients (56% [117,337 of 210,501] were women, mean age 68 ± 9 years) included in this study. Logistic regression models were used to determine the concordance of the ASA and Rx-Risk scores and 30-day and 90-day postoperative mortality. The Spearman correlation coefficient (r) was used to estimate the correlation between the ASA score and Rx-Risk score. All analyses were performed separately for THAs and TKAs. We found both the ASA and Rx-Risk scores had high concordance with 30-day mortality after THA (ASA: c-statistic 0.83 [95% CI 0.79 to 0.86] Rx-Risk: c-statistic 0.82 [95% CI 0.79 to 0.86]) and TKA (ASA: c-statistic 0.73 [95% CI 0.69 to 0.78] Rx-Risk: c-statistic 0.74 [95% CI 0.70 to 0.79]). Although both scores were strongly associated with death, their correlation was moderate for patients undergoing THA (r = 0.45) and weak for TKA (r = 0.38). However, the median Rx-Risk score did increase with increasing ASA score. For ex le, for THAs, the median Rx-Risk score was 1, 3, 5, and 7 for ASA scores 1, 2, 3, and 4, respectively. For TKAs, the median Rx-Risk score was 2, 4, 5, and 7 for ASA scores 1, 2, 3, and 4, respectively. The ASA physical status and RxRisk were associated with 30-day and 90-day mortality however, the scores were only weakly to moderately correlated with each other. This suggests that although both scores capture a similar level of patient illness, each score may be capturing different aspects of health. The Rx-Risk may be used as a complementary measure to the ASA score. Level III, therapeutic study.
Publisher: BMJ
Date: 10-2020
DOI: 10.1136/BMJOPEN-2020-039579
Abstract: To evaluate the impact of a patient-specific national programme targeting older Australians and health professionals that aimed to increase use of emollient moisturisers to reduce to the risk of skin tears. A prospective cohort intervention. The intervention targeted 52 778 Australian Government’s Department of Veterans’ Affairs patients aged over 64 years who had risk factors for wound development, and their general practitioners (GPs) (n=14 178). An interrupted time series model compared the rate of dispensing of emollients in the targeted cohort before and up to 23 months after the intervention. Commitment questions were included in self-report forms. In the first month after the intervention, the rate of claims increased 6.3-fold (95% CI: 5.2 to 7.6, p .001) to 10 emollient dispensings per 1000 patients in the first month after the intervention. Overall, the intervention resulted in 10 905 additional patient-months of treatment. The increased rate of dispensing among patients who committed to talking to their GP about using an emollient was six times higher (rate ratio: 6.2, 95% CI: 4.4 to 8.7) than comparison groups. The intervention had a sustained effect over 23 months. Veterans who responded positively to commitment questions had higher uptake of emollients than those who did not.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.JOCA.2017.11.016
Abstract: To evaluate the prevalence and change in analgesic medications use prior to joint replacement in older patients between 2001 and 2012. A population based epidemiological study was conducted. Opioids, non-steroidal anti-inflammatories (NSAIDs), paracetamol, corticosteroid injections, medications for neuropathic pain, hypnotics, and muscle relaxants supplied 1 year prior to total knee replacement (TKR, n = 15,517) and hip replacement (THR, n = 10,018) were assessed. Patient characteristics and surgical indication adjusted prevalence ratios (PRs) and 95% confidence intervals (CI) are provided. From 2001 to 2012, in the TKR cohort (median age 78.9) the prevalence of opioid use prior to surgery increased from 37% to 49% (PR = 1.01, 95% CI 1.00-1.01, P = 0.01), while in the THR cohort (median age 81.1) it increased from 44% to 54% (PR = 1.01, 95% CI 1.01-1.02, P < 0.001). Paracetamol use increased from 52% to 61% (PR = 1.0, 95% CI 1.0-1.0, P = 0.913) in the TKR cohort and from 55% to 67% (PR = 1.01, 95% CI 1.00-1.01, P = 0.005) in the THR cohort. Neuropathic pain medication use increased from 5% to 11% in the TKR cohort (PR = 1.04, 95% CI 1.02-1.06, P < 0.0001) and from 6% to 12% in the THR cohort (PR = 1.06, 95% CI 1.04-1.09, P < 0.0001). NSAID use decreased from 76% to 50% in the TKR cohort (PR = 0.96, 95% CI 0.95-0.96, P < 0.0001), and from 81% to 47% in THR cohort (PR = 0.95, 95% CI 0.94-0.95, P < 0.0001). Corticosteroid injections prevalence also decreased (TKR: 21-18%, PR = 0.97, 95% CI 0.96-0.97, P < 0.001, THR: 18-17%, PR = 0.97, 95% CI 0.96-0.98, P < 0.001). Pain medication utilization prior to joint replacement surgery changed significantly in this national older cohort of patients during the 2000s.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2015
Publisher: Frontiers Media SA
Date: 22-03-2022
DOI: 10.3389/FPHAR.2022.837632
Abstract: Post-marketing vaccine safety surveillance aims to detect adverse events following immunization in a population. Whether certain methods of surveillance are more precise and unbiased in generating safety signals is unclear. Here, we synthesized information from existing literature to provide an overview of the strengths, weaknesses, and clinical applications of epidemiologic and analytical methods used in vaccine monitoring, focusing on cohort, case-control and self-controlled designs. These designs are proposed to be evaluated in the EUMAEUS (Evaluating Use of Methods for Adverse Event Under Surveillance–for vaccines) study because of their widespread use and potential utility. Over the past decades, there have been an increasing number of epidemiological study designs used for vaccine safety surveillance. While traditional cohort and case-control study designs remain widely used, newer, novel designs such as the self-controlled case series and self-controlled risk intervals have been developed. Each study design comes with its strengths and limitations, and the most appropriate study design will depend on availability of resources, access to records, number and distribution of cases, and availability of population coverage data. Several assumptions have to be made while using the various study designs, and while the goal is to mitigate any biases, violations of these assumptions are often still present to varying degrees. In our review, we discussed some of the potential biases (i.e., selection bias, misclassification bias and confounding bias), and ways to mitigate them. While the types of epidemiological study designs are well established, a comprehensive comparison of the analytical aspects (including method evaluation and performance metrics) of these study designs are relatively less well studied. We summarized the literature, reporting on two simulation studies, which compared the detection time, empirical power, error rate and risk estimate bias across the above-mentioned study designs. While these simulation studies provided insights on the analytic performance of each of the study designs, its applicability to real-world data remains unclear. To bridge that gap, we provided the rationale of the EUMAEUS study, with a brief description of the study design and how the use of real-world multi-database networks can provide insights into better methods evaluation and vaccine safety surveillance.
Publisher: BMJ
Date: 02-2004
Abstract: To update the analysis of the cohort mortality and cancer incidence study of employees in the Australian petroleum industry. Employees from 1981 to 1996 were traced through the Australian National Death Index and the National Cancer Statistics Clearing House. Cause specific mortality and cancer incidence were compared with those of the Australian population by means of standardised mortality ratios (SMRs) and standardised incidence ratios (SIRs). Associations between increased incidence of specific cancers and employment in the petroleum industry were tested by trends according to period of first employment, duration of employment, latency, and hydrocarbon exposure, adjusting for personal smoking history where appropriate. Total follow up time was 176 598 person-years for males and 10 253 person-years for females. A total of 692 of the 15 957 male subjects, and 16 of the 1206 female subjects had died by the cut off date, 31 December 1996. In males, the all-cause SMR and the SMRs for all major disease categories were significantly below unity. There was a non-significant increase of the all-cancer SIR (1.04, 95% CI 0.97 to 1.11). There was a significant increase of the incidence of melanoma (SIR 1.54, 95% CI 1.30 to 1.81), bladder cancer (SIR 1.37, 95% CI 1.00 to 1.83), and prostate cancer (SIR 1.19, 95% CI 1.00 to 1.40), and a marginally significant excess of pleural mesothelioma (SIR 1.80, 95% CI 0.90 to 3.22), leukaemia (SIR 1.39, 95%CI 0.91 to 2.02), and multiple myeloma (SIR 1.72, 95% CI 0.96 to 2.84). Most cases of mesothelioma are probably related to past exposure to asbestos in refineries. The melanoma excess may be the result of early diagnosis. The excess bladder cancer has not been observed previously in this industry and is not readily explained. The ergence between cancer incidence and cancer mortality suggests that the "healthy worker effect" may be related to early reporting of curable cancers, leading to increased likelihood of cure and prolonged mean survival time.
Publisher: Wiley
Date: 13-06-2023
DOI: 10.1111/JOIM.13681
Abstract: This study aimed to compare the cardiovascular safety of interleukin‐6 inhibitors (IL‐6i) and Janus Kinase inhibitors (JAKi) to tumour necrosis factor inhibitors (TNFi). We conducted a retrospective cohort study using population‐based electronic databases from Hong Kong, Taiwan and Korea. We identified newly diagnosed patients with rheumatoid arthritis (RA) who received b/tsDMARDs first time. We followed patients from b/tsDMARD initiation to the earliest outcome (acute coronary heart disease, stroke, heart failure, venous thromboembolism and systemic embolism) or censoring events (death, transformation of b/tsDMARDs on different targets, discontinuation and study end). Using TNFi as reference, we applied generalized linear regression for the incidence rate ratio estimation adjusted by age, sex, disease duration and comorbidities. Random effects meta‐analysis was used for pooled analysis. We identified 8689 participants for this study. Median (interquartile range) follow‐up years were 1.45 (2.77) in Hong Kong, 1.72 (2.39) in Taiwan and 1.45 (2.46) in Korea. Compared to TNFi, the adjusted incidence rate ratios (aIRRs) (95% confidence interval [CI]) of IL‐6i in Hong Kong, Taiwan and Korea are 0.99 (0.25, 3.95), 1.06 (0.57, 1.98) and 1.05 (0.59, 1.86) and corresponding aIRR of JAKi are 1.50 (0.42, 5.41), 0.60 (0.26, 1.41), and 0.81 (0.38, 1.74), respectively. Pooled aIRRs showed no significant risk of cardiovascular events (CVEs) associated with IL‐6i (1.05 [0.70, 1.57]) nor JAKi (0.80 [0.48, 1.35]) compared to TNFi. There was no difference in the risk of CVE among RA patients initiated with IL‐6i, or JAKi compared to TNFi. The finding is consistent in Hong Kong, Taiwan and Korea.
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.IJMEDINF.2018.10.003
Abstract: Adverse drug events (ADEs) are among the top causes of hospitalization and death. Social media is a promising open data source for the timely detection of potential ADEs. In this paper, we study the problem of detecting signals of ADEs from social media. Detecting ADEs whose drug and AE may be reported in different posts of a user leads to major concerns regarding the content authenticity and user credibility, which have not been addressed in previous studies. Content authenticity concerns whether a post mentions drugs or adverse events that are actually consumed or experienced by the writer. User credibility indicates the degree to which chronological evidence from a user's sequence of posts should be trusted in the ADE detection. We propose AC-SPASM, a Bayesian model for the authenticity and credibility aware detection of ADEs from social media. The model exploits the interaction between content authenticity, user credibility and ADE signal quality. In particular, we argue that the credibility of a user correlates with the user's consistency in reporting authentic content. We conduct experiments on a real-world Twitter dataset containing 1.2 million posts from 13,178 users. Our benchmark set contains 22 drugs and 8089 AEs. AC-SPASM recognizes authentic posts with F Our study demonstrates that taking into account the content authenticity and user credibility improves the detection of ADEs from social media. Our work generates hypotheses to reduce experts' guesswork in identifying unknown potential ADEs.
Publisher: Wiley
Date: 21-06-2019
DOI: 10.1111/AJO.12838
Abstract: Pelvic organ prolapse (POP) and stress urinary incontinence (SUI) are common conditions. The use of mesh in the surgical treatment of these conditions in Australia is unclear. To examine the use of mesh in POP and SUI procedures in an Australian national cohort of older women. We conducted a population-based cohort study using data from the Australian Government Department of Veterans' Affairs (DVA) database. The cohort consisted of older women who had POP and SUI procedures between 1 July, 2005 and 31 December, 2016. Women who received mesh were identified by matching device billing codes with the Australian Government's Prosthesis List. In total, 3129 women experienced 3472 hospitalisations for POP and SUI procedures, with 74% of the women aged 75 years and older. There were 2276 (66%) hospitalisations with single POP repairs, 608 (18%) with single SUI procedures and 588 (17%) with concomitant POP and SUI procedures. Mesh was used in 23% of single procedures for POP, in 89% of single procedures for SUI and in 90% of concomitant POP and SUI procedures. The use of mesh in POP procedures decreased from a peak of 33% in 2008 down to 8% by 2016, whereas the use of mesh in SUI procedures increased from 77% in 2006 to 91% by 2016. Mesh was commonly used in SUI procedures, whereas use of mesh in POP repair was less common and the use decreased rapidly after 2011, when warnings about use of mesh in POP were first issued.
Publisher: Springer Science and Business Media LLC
Date: 12-05-2023
DOI: 10.1007/S11095-023-03516-X
Abstract: Chronic Obstructive Pulmonary Disease is characterised by declining lung function and a greater oxidative stress burden due to reduced activity of antioxidant enzymes such as Glutathione Peroxidase 1. The extent to which drugs may contribute to this compromised activity is largely unknown. An integrative drug safety model explores inhibition of Glutathione Peroxidase 1 by drugs and their association with chronic obstructive pulmonary disease adverse drug events. In silico molecular modelling approaches were utilised to predict the interactions that drugs have within the active site of Glutathione Peroxidase 1 in both human and bovine models. Similarities of chemical features between approved drugs and the known inhibitor tiopronin were also investigated. Subsequently the Food and Drug Administration Adverse Event System was searched to uncover adverse drug event signals associated with chronic obstructive pulmonary disease. Statistical and molecular modelling analyses confirmed that the use of several registered drugs, including acetylsalicylic acid and atenolol may be associated with inhibition of Glutathione Peroxidase 1 and chronic obstructive pulmonary disease. The integration of molecular modelling and pharmacoepidemological data has the potential to advance drug safety science. Ongoing review of medication use and further pharmacoepidemiological and biological analyses are warranted to ensure appropriate use is recommended.
Publisher: Wiley
Date: 23-09-2018
DOI: 10.1002/JPPR.1407
Publisher: Dustri-Verlgag Dr. Karl Feistle
Date: 10-2021
DOI: 10.5414/CP203964
Publisher: Wiley
Date: 17-03-2017
DOI: 10.1111/JGS.14837
Abstract: To examine the risk of dementia associated with posttraumatic stress disorder (PTSD) and the contribution of antipsychotic use to this risk. Retrospective cohort study SETTING: Australia. Administrative claims data from the Australian Government Department of Veterans' Affairs were used. Male Vietnam veterans aged 55 to 65 at baseline (2001-02) with no preexisting dementia diagnosis (N = 15,612). The association between PTSD and dementia was assessed over 12 years of follow-up. Dementia was identified as a hospital diagnosis, dementia record in service disability data, or dispensing of medicines for dementia. Cox-proportional hazards models were used, with age as the time-scale. Results were stratified according to baseline antipsychotic use. No greater risk of dementia was observed with PTSD. In veterans who received antipsychotics, dementia risk was significantly higher than in those who did not (hazard ratio (HR) = 2.1, 95% confidence interval (CI) = 1.4-3.3). Dementia risk was significantly greater in veterans hospitalized for PTSD who received antipsychotics (HR = 2.2, 95% CI = 1.1-4.6) and veterans without PTSD who received antipsychotics (HR = 4.3, 95% CI = 2.1-8.6) than in those without PTSD with no antipsychotic use. Antipsychotic use may be a contributor to dementia risk. These findings should be interpreted with caution because the study design was observational. Further research using prospective study designs in settings where diagnostic data, cognitive function, and disease severity are available are required.
Publisher: British Editorial Society of Bone & Joint Surgery
Date: 09-2022
DOI: 10.1302/0301-620X.104B9.BJJ-2022-0116.R1
Abstract: The aim of this study was to estimate the 90-day periprosthetic joint infection (PJI) rates following total knee arthroplasty (TKA) and total hip arthroplasty (THA) for osteoarthritis (OA). This was a data linkage study using the New South Wales (NSW) Admitted Patient Data Collection (APDC) and the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR), which collect data from all public and private hospitals in NSW, Australia. Patients who underwent a TKA or THA for OA between 1 January 2002 and 31 December 2017 were included. The main outcome measures were 90-day incidence rates of hospital readmission for: revision arthroplasty for PJI as recorded in the AOANJRR conservative definition of PJI, defined by T84.5, the PJI diagnosis code in the APDC and extended definition of PJI, defined by the presence of either T84.5, or combinations of diagnosis and procedure code groups derived from recursive binary partitioning in the APDC. The mean 90-day revision rate for infection was 0.1% (0.1% to 0.2%) for TKA and 0.3% (0.1% to 0.5%) for THA. The mean 90-day PJI rates defined by T84.5 were 1.3% (1.1% to 1.7%) for TKA and 1.1% (0.8% to 1.3%) for THA. The mean 90-day PJI rates using the extended definition were 1.9% (1.5% to 2.2%) and 1.5% (1.3% to 1.7%) following TKA and THA, respectively. When reporting the revision arthroplasty for infection, the AOANJRR substantially underestimates the rate of PJI at 90 days. Using combinations of infection codes and PJI-related surgical procedure codes in linked hospital administrative databases could be an alternative way to monitor PJI rates. Cite this article: Bone Joint J 2022 -B(9):1060–1066.
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.HLC.2017.09.004
Abstract: Magnetic resonance imaging (MRI) is a widely used diagnostic tool with great benefits but has been considered contraindicated in people with cardiac implantable electronic devices (CIED). We investigated the occurrence of MRI in people with CIEDs and associated adverse events in a national cohort. Of 17,848 people included, 56 (0.3%) had at least one MRI 16 of 16,102 (0.1%) with MRI non-compatible CIEDs and 40 of 1746 (2%) with MRI compatible CIEDs. Following MRI exposure, hospitalisations for potential serious adverse events were rare.
Publisher: Springer Science and Business Media LLC
Date: 23-03-2023
Publisher: Springer Science and Business Media LLC
Date: 21-09-2022
Publisher: BMJ
Date: 10-2020
DOI: 10.1136/BMJOPEN-2020-038016
Abstract: Educational, and audit and feedback interventions are effective in promoting health professional behaviour change and evidence adoption. However, we lack evidence to pinpoint which particular features make them most effective. Our objective is to identify determinants of quality in professional behaviour change interventions, as perceived by participants. We performed a comparative observational study using data from the Veterans’ Medicines Advice and Therapeutics Education Services program, a nation-wide Australian Government Department of Veterans’ Affairs funded program that provides medicines advice and promotes physician adoption of best practices by use of a multifaceted intervention (educational material and a feedback document containing in idual patient information). Primary care practices providing care to Australian veterans. General practitioners (GPs) targeted by 51 distinct behaviour change interventions, implemented between November 2004 and June 2018. We extracted features related to presentation (number of images, tables and characters), content (polarity and subjectivity using sentiment analysis, number of external links and medicine mentions) and the use of five behaviour change techniques (prompt/cues, goal setting, discrepancy between current behaviour and goal, information about health consequences, feedback on behaviour). The main outcome was perceived usefulness, extracted from postintervention survey. On average, each intervention was delivered to 9667 GPs. Prompt and goal setting strategies in the audit and feedback were independently correlated to perceived usefulness (p=0.030 and p=0.005, respectively). The number of distinct behaviour change techniques in the audit and feedback was correlated with improved usefulness (Pearson’s coefficient 0.45 (0.19, 0.65), p=0.001). No presentation or content features in the educational material were correlated with perceived usefulness. The finding provides additional evidence encouraging the use of behaviour change techniques, in particular prompt and goal setting, in audit and feedback interventions.
Publisher: Wiley
Date: 17-11-2020
DOI: 10.1002/PDS.4924
Abstract: The purpose of this paper is to provide guidance on the evaluation of data linkage quality through the development of a checklist for reporting key elements of the linkage process. Responding to a call for manuscripts from the International Society for Pharmacoepidemiology (ISPE), a working group including international representation from the academic, industry, and contract research, and regulatory sectors was formed to develop a checklist for evaluation of data linkage performance and reporting data linkage specifically for pharmacoepidemiologic research. This checklist expands on the reporting of studies conducted using observational routinely collected health data specific to pharmacoepidemiology (RECORD-PE) guidelines. A key aspect of data linkage evaluation for pharmacoepidemiology is to articulate how a linkage process was performed and its accuracy in terms of validation and verification of the resulting linked data. This study generates a checklist, which covers domains including data sources, linkage variables, linkage methods, linkage results, and linkage evaluation. For each domain, specific recommendations provide a clear and transparent assessment of the linkage process. Linking data sources can help to enrich analytic databases to more accurately define study populations, enable adjustment for confounding, and improve the capture of health outcomes. Clear and transparent reporting of data linkage processes will help to increase confidence in the evidence generated from these data by allowing researchers and end users to critically assess the potential for bias owing to the data linkage process.
Publisher: Wiley
Date: 23-03-2021
DOI: 10.1002/PDS.5214
Abstract: Information regarding availability of electronic healthcare databases in the Asia‐Pacific region is critical for planning vaccine safety assessments particularly, as COVID‐19 vaccines are introduced. This study aimed to identify data sources in the region, potentially suitable for vaccine safety surveillance. This manuscript is endorsed by the International Society for Pharmacoepidemiology (ISPE). Nineteen countries targeted for database reporting were identified using published country lists and review articles. Surveillance capacity was assessed using two surveys: a 9‐item introductory survey and a 51‐item full survey. Survey questions related to database characteristics, covariate and health outcome variables, vaccine exposure characteristics, access and governance, and dataset linkage capability. Other questions collated research/regulatory applications of the data and local publications detailing database use for research. Eleven databases containing vaccine‐specific information were identified across 8 countries. Databases were largely national in coverage (8/11, 73%), encompassed all ages (9/11, 82%) with population size from 1.4 to 52 million persons. Vaccine exposure information varied particularly for standardized vaccine codes (5/11, 46%), brand (7/11, 64%) and manufacturer (5/11, 46%). Outcome data were integrated with vaccine data in 6 (55%) databases and available via linkage in 5 (46%) databases. Data approval processes varied, impacting on timeliness of data access. Variation in vaccine data availability, complexities in data access including, governance and data release approval procedures, together with requirement for data linkage for outcome information, all contribute to the challenges in building a distributed network for vaccine safety assessment in the Asia‐Pacific and globally. Common data models (CDMs) may help expedite vaccine safety research across the region.
Publisher: Wiley
Date: 20-05-2022
DOI: 10.1002/PDS.5450
Publisher: Informa UK Limited
Date: 24-02-2012
DOI: 10.3109/09286586.2011.638743
Abstract: To identify the extent of use of medicines recommended to be used with caution in glaucoma patients with specified comorbidities and to determine evidence of associated harm. Retrospective cohort analysis from administrative claims data and prescription/event sequence symmetry analysis. Australian Government Department of Veterans' Affairs treatment card holders dispensed glaucoma eye-drops. Proportion of veterans with glaucoma and diabetes, airways disease, heart failure, ischemic heart disease or depression, dispensed glaucoma eye drops which should be used with caution. For harms, outcome measures were hospitalizations for airways disease and heart disease. The cohort analysis included 25,984 veterans. Of these, 88% with airways disease were dispensed glaucoma eye drops with the potential to aggravate airways disease, 43% with heart failure were dispensed topical beta-blockers and 49% with depression received glaucoma eye drops which should be used cautiously in those with depression. We found increased risk of initiation of inhaled beta-agonist following timolol (adjusted sequence ratio (ASR) 1.48, 99% CI 1.22-1.78) and latanoprost (ASR 1.24, 99% CI 1.11-1.38) initiation. We found increased risk of inhaled corticosteroid initiation following initiation of timolol (ASR 1.43, 99% CI 1.13-1.81). There was increased risk of antidepressant initiation following timolol initiation (ASR 1.24, 99% CI 1.07-1.43), and latanoprost (ASR 1.16, 99% CI 1.03-1.31). There was also increased risk of hospitalization for bradycardia following timolol initiation (ASR 2.22,99% CI 1.15-4.31). Use of glaucoma eye drops recommended to be used with caution in co-morbidities is common and was associated with adverse outcomes. Awareness of co-morbidities is required in the selection and prescription of glaucoma eye drops.
Publisher: Springer Science and Business Media LLC
Date: 07-2001
Publisher: Wiley
Date: 12-02-2007
Publisher: Springer Science and Business Media LLC
Date: 06-08-2022
DOI: 10.1007/S40801-022-00322-6
Abstract: Studies have found an increased risk of pyoderma gangrenosum associated with rituximab. The structural properties and pharmacological action of rituximab may affect the risk of pyoderma gangrenosum. Additionally, pyoderma gangrenosum is associated with autoimmune disorders for which rituximab is indicated. We aimed to determine whether rituximab is disproportionally associated with pyoderma gangrenosum using a systems biology-informed approach. Adverse event reports were extracted from the US Food and Drug Administration Adverse Event Reporting System (FAERS, 2013-20). The Bayesian Confidence Propagation Neural Network Information Component was used to test for disproportionality. Comparators used to determine potential causal pathways included all other medicines, all medicines with a similar structure (monoclonal antibodies), all medicines with the same pharmacological target (CD20 antagonists) and all medicines used for the same indication(s) as rituximab. Thirty-two pyoderma gangrenosum cases were identified, 62.5% were female, with a median age of 48 years. There was an increased association of pyoderma gangrenosum with rituximab compared with all other medicines (exponentiated Information Component 6.75, 95% confidence interval (CI) 4.66-9.23). No association was observed when the comparator was either monoclonal antibodies or CD20 antagonists. Conditions for which an association of pyoderma gangrenosum with rituximab was observed were multiple sclerosis (6.68, 95% CI 1.63-15.15), rheumatoid arthritis (2.67, 95% CI 1.14-4.80) and non-Hodgkin's lymphoma (2.94, 95% CI 1.80-3.73). Pyoderma gangrenosum was reported more frequently with rituximab compared with all other medicines. The varying results when restricting medicines for the same condition suggest the potential for confounding by indication. Post-market surveillance of biologic medicines in FAERS should consider a multi-faceted approach, particularly when the outcome of interest is associated with the underlying immune condition being treated by the medicine of interest.
Publisher: Springer Science and Business Media LLC
Date: 11-2010
DOI: 10.2165/11584490-000000000-00000
Abstract: Antipsychotics are commonly used in the elderly despite a lack of safety data from randomized trials, particularly for the typical antipsychotics. Observational studies have investigated the association between antipsychotics and stroke but results vary, which may be due to lack of control for unmeasured confounding. To estimate the risk of hospitalization for stroke in elderly users of antipsychotics. Using the Australian Government Department of Veterans' Affairs administrative claims dataset we utilized a self-controlled case series design to risk-adjust for potential unmeasured confounding. Risk periods prior to antipsychotic initiation were also included to search for evidence of confounding by indication. Unexposed patients were included to adjust for the increasing incidence of hospitalization for stroke with age. There were 10 638 patients aged ≥65 years with at least one hospitalization for stroke identified during the 4-year period from 1 January 2003 to 31 December 2006. Of these, 514 patients were initiated on typical antipsychotics and 564 patients were initiated on atypical antipsychotics. Hospitalization for stroke was increased in the first week after initiation of a typical antipsychotic (incidence rate ratio [IRR] 2.3 95% CI 1.3, 3.8). There was no evidence of an increased risk of hospitalization for stroke after initiation of atypical antipsychotics. The risk of hospitalization for stroke progressively increased in the weeks leading up to first-time antipsychotic treatment. However, while the risk of hospitalization for stroke in the week prior to initiating antipsychotic therapy was significantly increased for patients initiated on typical antipsychotics (IRR 7.2 95% CI 5.3, 9.8), patients initiated on atypical antipsychotics had no excess risk in the same period (IRR 1.2 95% CI 0.7, 2.3). The results of this study are consistent with randomized controlled trial evidence indicating that there is no increased risk of serious cerebrovascular events requiring hospitalization in patients taking atypical antipsychotics. No randomized controlled trial evidence is available on the risk of hospitalization for stroke with use of typical antipsychotics in the elderly. This study found a small but significantly increased risk of hospitalization for stroke immediately following the initiation of typical antipsychotics. Antipsychotics are likely to be initiated after hospitalization for stroke. This practice is likely to reflect the prescribing of antipsychotics during hospital admission for post-stroke complications such as delirium however, the long-term effects of this practice are unknown.
Publisher: Wiley
Date: 05-2015
DOI: 10.1111/JGS.13418
Publisher: American Medical Association (AMA)
Date: 04-2020
Publisher: Springer Science and Business Media LLC
Date: 18-09-2015
Publisher: Elsevier BV
Date: 09-2022
Publisher: Frontiers Media SA
Date: 20-05-2022
DOI: 10.3389/FPHAR.2022.834116
Abstract: Purpose: Inhaled Corticosteroids (ICSs) and oral Leukotriene Receptor Antagonists (LTRAs) are commonly prescribed asthma preventers, however, concerns have been raised as to whether montelukast (LTRA) is associated with an increase in occurrences of neuropsychiatric side effects in children. Our study was conducted to observe prescribing patterns of asthma preventers among paediatric patients specifically focusing on ICSs and LTRAs between Australia and South Korea to see intercountry differences in the use of these medicines. Materials and Methods: The Health Insurance Review and Assessment Paediatric Patients S le dataset for South Korea and data provided by Services Australia were used in the study. Paediatric patients aged between 3 and 19 with more than one dispensing of an asthma preventer and at least one reliever between 1 Jan 2018 and 31 December 2018 were selected. Prevalence per 1,00,000 persons and standardised prevalence were estimated. Results: A total of 3,58,470 patients (2,04,270 from South Korea and 1,54,200 from Australia) were included in the study. A higher prevalence of ICS-based inhalers was seen in Australia with 80.1% compared to 13.5% in South Korea. In addition, Australia showed a stronger tendency of prescribing high dose ICS-based inhalers compared to South Korea with 22.9% vs. 4.9%. In contrast, use of LTRAs was more prevalent in South Korea with 57.6% while in Australia, montelukast was the only LTRA dispensed at a proportion of 18.9%. Moreover, 29.9% of xanthines which are orally available preventers, were prescribed more frequently in South Korea compared to Australia (0.1%). Conclusion: Australia showed a tendency of prescribing ICS-based preventers whereas South Korea exhibited a preference towards the oral LTRAs. Given the potential risk of neuropsychiatric side effects among paediatric patients with montelukast, reasons for the high use of montelukast in South Korea should be investigated further.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2021
DOI: 10.1161/HYPERTENSIONAHA.120.16402
Abstract: Evidence for the effectiveness and safety of the third-generation β-blockers other than atenolol in hypertension remains scarce. We assessed the effectiveness and safety of β-blockers as first-line treatment for hypertension using 3 databases in the United States: 2 administrative claims databases and 1 electronic health record–based database from 2001 to 2018. In each database, comparative effectiveness of β-blockers for the risks of acute myocardial infarction, stroke, and hospitalization for heart failure was assessed, using large-scale propensity adjustment and empirical calibration. Estimates were combined across databases using random-effects meta-analyses. Overall, 118 133 and 267 891 patients initiated third-generation β-blockers (carvedilol and nebivolol) or atenolol, respectively. The pooled hazard ratios (HRs) of acute myocardial infarction, stroke, hospitalization for heart failure, and most metabolic complications were not different between the third-generation β-blockers versus atenolol after propensity score matching and empirical calibration (HR, 1.07 [95% CI, 0.74–1.55] for acute myocardial infarction HR, 1.06 [95% CI, 0.87–1.31] for stroke HR, 1.46 [95% CI, 0.99–2.24] for hospitalized heart failure). Third-generation β-blockers were associated with significantly higher risk of stroke than ACE (angiotensin-converting enzyme) inhibitors (HR, 1.29 [95% CI, 1.03–1.72]) and thiazide diuretics (HR, 1.56 [95% CI, 1.17–2.20]). In conclusion, this study found many patients with first-line β-blocker monotherapy for hypertension and no statistically significant differences in the effectiveness and safety comparing atenolol with third-generation β-blockers. Patients on third-generation β-blockers had a higher risk of stroke than those on ACE inhibitors and thiazide diuretics.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2009
DOI: 10.1161/CIRCHEARTFAILURE.109.861013
Abstract: Background— Randomized controlled trials have demonstrated that collaborative medication reviews can improve outcomes for patients with heart failure. We aimed to determine whether these results translated into Australian practice, where collaborative reviews are nationally funded. Methods and Results— This retrospective cohort study using administrative claims data included veterans 65 years and older receiving bisoprolol, carvedilol, or metoprolol succinate for which prescribing physicians indicated treatment was for heart failure. We compared those exposed to a general practitioner–pharmacist collaborative home medication review with those who did not receive the service. The service includes physician referral, a home visit by an accredited pharmacist to identify medication-related problems, and a pharmacist report with follow-up undertaken by the physician. Kaplan-Meier analyses and Cox proportional hazards models were used to compare time until next hospitalization for heart failure between the exposed and unexposed groups. There were 273 veterans exposed to a home medicines review and 5444 unexposed patients. Average age in both groups was 81.6 years (no significant difference). The median number of comorbidities was 8 in the exposed group and 7 in the unexposed ( P .0001). Unadjusted results showed a 37% reduction in rate of hospitalization for heart failure at any time (hazard ratio, 0.63 95% CI, 0.44 to 0.89). Adjusted results showed a 45% reduction (hazard ratio, 0.55 95% CI, 0.39 to 0.77) among those who had received a home medicines review compared with the unexposed patients. Conclusion— Medicines review in the practice setting is effective in delaying time to next hospitalization for heart failure in those treated with heart failure medicines.
Publisher: AMPCo
Date: 03-2017
DOI: 10.5694/MJA16.00671
Abstract: To identify factors that contribute to older Australians admitted to hospital with diabetes being re-hospitalised within 30 days of discharge. A retrospective cohort study of Department of Veterans' Affairs administrative data for all patients hospitalised for diabetes and discharged alive during the period 1 January - 31 December 2012. Causes of re-hospitalisation and prevalence of clinical factors associated with re-hospitalisation within 30 days of discharge. Multivariate logistic regression analysis (backward stepwise) was used to identify characteristics predictive of 30-day re-hospitalisation. 848 people were hospitalised for diabetes their median age was 87 years (interquartile range, 77-89 years) and 60% were men. 209 patients (24.6%) were re-hospitalised within 30 days of discharge, of whom 77.5% were re-admitted within 14 days of discharge. 51 re-hospitalisations (24%) were for diabetes-related conditions 41% of those re-admitted within 14 days had not seen their general practitioner between discharge and re-admission. Factors predictive of re-hospitalisation included comorbid heart failure (adjusted odds ratio [aOR], 1.49 95% confidence interval [CI], 1.03-2.17 P = 0.036), numbers of prescribers in previous year (aOR [for each additional prescriber], 1.06 95% CI, 1.01-1.08 P = 0.031), and two or more hospitalisations in the 6 months before the index admission (aOR, 1.79 95% CI 1.15-2.78 P = 0.009). Older people hospitalised for diabetes who have comorbid heart failure, multiple recent hospitalisations, and multiple prescribers involved in their care are at greatest risk of being re-admitted to hospital within 30 days. Targeted follow-up during the initial 14 days after discharge may facilitate appropriate interventions that avert re-admission of these at-risk patients.
Publisher: Springer Science and Business Media LLC
Date: 29-05-2014
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.MSARD.2021.103412
Abstract: There is minimal information on the utilisation of Disease Modifying Treatment (DMTs) for multiple sclerosis. The appropriate and safe use of medicines is informed by utilisation studies. Outcomes can inform health interventions to improve appropriate use of medicines and post marketing surveillance activities to improve safety. To evaluate utilisation and treatment patterns of disease modifying treatments (DMTs) for relapsing remitting multiple sclerosis (RRMS). A representative s le of the Australian pharmaceutical benefits scheme data were analysed (2006-2016). Demographics of incident users and trends in incident and prevalent users were determined. In idual patient treatment pathways were determined by sequential initiation of medicines in two different periods (2006-2013 and 2014-2019). There were 20,660 patients with at least one dispensing of a DMT for RRMS during the study period (median age 41 years, 75% female). Incident and prevalent use increased by 20% and 88%, respectively. The market was responsive to 13 new listings of DMTs over the study period. Sequential treatment was found for 66% of initiators in 2006-2013 and 28.5% of initiators in 2014-2019. Diverse treatment pathways were found, with 278 and 93 unique sequences in 2006-2013 and 2014-2019, respectively. The availability of new DMTs has influenced both initial treatment choice and prevalence of users. In idualised treatment patterns and exposure to multiple medicines over time will challenge traditional pharmacovigilance systems.
Publisher: Springer Science and Business Media LLC
Date: 03-02-2018
DOI: 10.1007/S40264-018-0638-2
Abstract: Studies have found an association between the use of proton pump inhibitors (PPIs) and dementia, but these findings may have been confounded by selection biases. We used prescription sequence symmetry analysis (PSSA) to estimate the sequence ratio (SR) between PPI use and dementia compared with an active comparator, the use of histamine-2 receptor antagonists (H2RAs). We conducted a PSSA on a nationwide South Korean database between 2002 and 2013. Exposure was defined as new PPI users, and outcome was defined as a new dementia diagnosis (International Statistical Classification of Diseases and Related Health Problems, 10th revision [ICD-10] codes F00-03, F05.1, G30, G31.1, G31.9, G31.82). In this study, we applied the 3-year time window. So the patients who initiated PPIs 3 years before or after their first diagnosis of dementia were included. The pairs with the time window < 6 months were excluded to minimize the potential protopathic bias. The SR was calculated as the number of patients first diagnosed with dementia after initiating PPI (causal group) ided by the number of patients first diagnosed with dementia before the initiation of PPI (non-causal group). The SR was adjusted (aSR) to avoid the distortion of results due to underlying trends in PPI use and dementia diagnosis over time. We calculated 95% confidence intervals (CIs) for the aSR. The analysis was repeated for initiators of H2RAs. Sensitivity analyses were conducted using 1-, 2-, and 6-year time windows and using the initiation of medication for dementia treatment (Anatomical Therapeutic Chemical code: N06D). Our results showed that the aSR of dementia and PPIs (7342 pairs, aSR 1.21 [95% CI 1.16-1.27]) was not higher than that for dementia and H2RAs (6170 pairs, aSR 1.91 [95% CI 1.80-2.02]). When we used various time windows and restricted the findings to the use of medication for treating dementia, the results were consistent with the main results. The risk of PPIs being associated with dementia may be overestimated. Further pharmacoepidemiological studies are needed to identify the risk of dementia with PPI use.
Publisher: Springer Science and Business Media LLC
Date: 02-2010
Publisher: Springer Science and Business Media LLC
Date: 08-02-2018
DOI: 10.1007/S40266-018-0526-6
Abstract: Medicines are potentially modifiable risk factors for postoperative delirium. However, the extent to which preoperative medicines are included in risk prediction models (RPMs) is unknown. This systematic review aimed to assess the extent of inclusion of preoperative medications in RPMs for postoperative delirium. Articles were systematically searched from MEDLINE, EMBASE and CINAHL using Medical Subject Headings (MeSH) where possible and keywords for postoperative delirium and prediction model. Studies published until May 2017 with a primary outcome of postoperative delirium that developed an RPM containing preoperative patient information were considered. Where a study had two cohorts, a derivation and a validation cohort, findings from the derivation cohort were extracted and reported. Eighteen prospective and one retrospective cohort studies were included for review. Of the 19 studies, only nine considered preoperative medication data, with medications appearing as predictor variables in five models. There was wide variability in the factors included in the final models, with the most frequent predictors being age and cognitive impairment, appearing in 13 (68%) and 11 (58%) RPMs, respectively. While medications are commonly cited risk factors for delirium, they are not adequately considered when developing RPMs. Future studies aiming to develop an RPM for postoperative delirium should include preoperative medication data as a potential predictor variable because of the modifiable nature of medication use and its impact on other factors commonly in models, such as cognition.
Publisher: Therapeutic Guidelines Limited
Date: 04-06-2019
Publisher: Springer Science and Business Media LLC
Date: 06-09-2015
Publisher: Elsevier BV
Date: 11-2019
Publisher: Wiley
Date: 27-06-2018
DOI: 10.1002/PDS.4582
Abstract: Standard Kaplan-Meier (KM) survival analysis is often used to study treatment persistence estimating the proportion of patients who have not yet experienced a treatment break by a given day after treatment initiation. This method only allows patients to be studied until their first treatment break. The "proportion of patients covered" (PPC) method is another approach to study treatment persistence. It measures the proportion of live patients currently covered by treatment. We aimed to describe the PPC method, show how the KM survival analysis and the PPC method can describe treatment persistence, and discuss the interpretation/application of the methods. We identified new users of statins, selective serotonin reuptake inhibitors, hormone replacement therapy, and ibuprofen. We used KM estimates and the PPC to describe persistence in the 3 years post treatment initiation, using a grace period of 90 days to define a treatment break. Three years after statin initiation, approximately 40% of patients were still in continuous treatment (KM survival) and 60% of patients still alive were in current treatment (PPC). Corresponding numbers were 12% and 25% for selective serotonin reuptake inhibitors and 9% and 29% for hormone replacement therapy. At 1 year, numbers were 5% and 10% for ibuprofen. The PPC showed markedly less variability than the KM survival analysis with different choices of grace periods. The KM survival analysis and the PPC method can be used to study different aspects of treatment persistence. Together, they provide a more complete picture of treatment persistence and drug use patterns.
Publisher: Springer Science and Business Media LLC
Date: 09-07-2019
Publisher: American Medical Association (AMA)
Date: 24-03-2022
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.ARTH.2015.06.009
Abstract: This study evaluated the ability of a pharmacy based co-morbidity measure (RxRisk-V) to predict odds of one and five years revision in total hip arthroplasty (THA) and total knee arthroplasty (TKA) and compared its performance to the more commonly used co-morbidity measures in orthopaedics (Charlson and Elixhauser). 11,848 patients with THAs and 18,972 with TKAs performed between 2001 and 2012 were evaluated. Using a combination of conditions, identified by both the pharmacy and diagnoses based coding algorithms, models with acceptable predictive ability of THA and TKA revision were developed. These findings suggest prescription based co-morbidity measures can positively contribute to case-mix adjustment and outcome prediction in this patient population.
Publisher: Oxford University Press (OUP)
Date: 26-10-2015
Publisher: Springer Science and Business Media LLC
Date: 25-10-2019
DOI: 10.1007/S40258-018-0440-4
Abstract: To describe how post-market utilisation analysis in Australia informs cost-effectiveness assessment and pricing decisions, using aflibercept and ranibizumab as case studies. Pharmaceutical claims were used to identify initiators of aflibercept and ranibizumab in the year after aflibercept-listing (December 2012), and ranibizumab initiators in the year before aflibercept listing. The dispensing rates for each cohort were calculated, and their demographic and clinical characteristics compared using Kruskal-Wallis tests. Aflibercept and ranibizumab each accounted for half the age-related macular degeneration market following aflibercept listing. Aflibercept initiators had similar dispensing rates to ranibizumab initiators in the pre- and post-aflibercept era (~ three scripts during the first 90 days, and eight to nine scripts during the following 12 months). All cohorts were similar in terms of their age, sex, residential aged-care status and geographic remoteness, and no differences were observed in their overall co-morbidity scores and history of thromboembolic events. Contrary to clinical trial protocols, post-market utilisation research for ranibizumab and aflibercept demonstrates equivalent use in practice in terms of dose frequency, and the demographic and clinical characteristics of initiators. This supports Australia's decision to pay the same price for each rather than giving a premium to aflibercept. Many other countries are likely overpaying for aflibercept if their utilization patterns are similar to Australia's, and could benefit from incorporating routine utilisation assessment.
Publisher: Springer Science and Business Media LLC
Date: 17-10-2021
DOI: 10.1186/S12874-021-01408-5
Abstract: Case-crossover studies have been widely used in various fields including pharmacoepidemiology. Vines and Farrington indicated in 2001 that when within-subject exposure dependency exists, conditional logistic regression can be biased. However, this bias has not been well studied. We have extended findings by Vines and Farrington to develop a weighting method for the case-crossover study which removes bias from within-subject exposure dependency. Our method calculates the exposure probability at the case period in the case-crossover study which is used to weight the likelihood formulae presented by Greenland in 1999. We simulated data for the population with a disease where most patients receive a cyclic treatment pattern with within-subject exposure dependency but no time trends while some patients stop and start treatment. Finally, the method was applied to real-world data from Japan to study the association between celecoxib and peripheral edema and to study the association between selective serotonin reuptake inhibitor (SSRI) and hip fracture in Australia. When the simulated rate ratio of the outcome was 4.0 in a case-crossover study with no time-varying confounder, the proposed weighting method and the Mantel-Haenszel odds ratio reproduced the true rate ratio. When a time-varying confounder existed, the Mantel-Haenszel method was biased but the weighting method was not. When more than one control period was used, standard conditional logistic regression was biased either with or without time-varying confounding and the bias increased (up to 8.7) when the study period was extended. In real-world analysis with a binary exposure variable in Japan and Australia, the point estimate of the odds ratio (around 2.5 for the association between celecoxib and peripheral edema and around 1.6 between SSRI and hip fracture) by our weighting method was equal to the Mantel-Haenszel odds ratio and stable compared with standard conditional logistic regression. Case-crossover studies may be biased from within-subject exposure dependency, even without exposure time trends. This bias can be identified by comparing the odds ratio by the Mantel-Haenszel method and that by standard conditional logistic regression. We recommend using our proposed method which removes bias from within-subject exposure dependency and can account for time-varying confounders.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Springer Science and Business Media LLC
Date: 08-11-2022
DOI: 10.1007/S40264-021-01136-1
Abstract: Medicines acting on the central nervous system can increase the risk of postoperative delirium, but the specific medicines associated with greatest risk remain unclear. We aimed to examine the risk of in idual central nervous system-acting medicines used preoperatively on delirium after hip or knee surgery. A matched case-control study was conducted using data from the Australian Government Department of Veterans' Affairs. We included people aged 65 years or older who had knee or hip surgery between 2000 and 2019. People with hip or knee surgery who developed postoperative delirium were cases and controls were people with hip or knee surgery but who did not develop postoperative delirium. Use of medicines including anxiolytics, sedatives, and hypnotics, opioid analgesics and antidepressants prior to surgery was compared between cases and controls. A total of 2614 patient cases with postoperative delirium were matched by same sex, age (±2 years), and year of admission (±2 years) with 7842 controls without postoperative delirium. Cases were more likely to be exposed to nitrazepam (odds ratio [OR] = 1.81, 95% confidence interval [CI] 1.24-2.64), sertraline (OR = 1.50, 95% CI 1.20-1.87), mirtazapine (OR = 1.38, 95% CI 1.11-1.74), venlafaxine (OR = 1.42, 95% CI 1.02-1.98), citalopram (OR = 1.54, 95% CI 1.19-1.99), escitalopram (OR = 1.42, 95% CI 1.06-1.89) or fluvoxamine (OR = 5.01, 95% CI 2.15-11.68) prior to surgery than controls. At the class level, exposure to benzodiazepines (OR = 1.20, 95% CI 1.05-1.37) and antidepressants (OR = 1.64, 95% CI 1.47-1.83) prior to surgery was significantly higher in cases than in controls. The numbers needed to treat to harm for one additional delirium case were 43 for sertraline, 40 for citalopram, 57 for mirtazapine and 26 for nitrazepam. Whereas, the numbers needed to treat to harm were found to be 20 for sertraline, 17 for citalopram, 19 for mirtazapine and 10 for nitrazepam in the 85 years or older age group, indicating that the harmful effect of these medicines is pronounced as age advances. People who developed delirium following hip or knee surgery were more likely to be exposed to nitrazepam, sertraline, mirtazapine, venlafaxine, citalopram, escitalopram or fluvoxamine at the time of admission for surgery. Planning to reduce use of these medicines well prior to surgery may decrease the risk of postoperative delirium.
Publisher: Springer Science and Business Media LLC
Date: 27-09-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2021
DOI: 10.1161/HYPERTENSIONAHA.120.16667
Abstract: ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers (ARBs) are equally guideline-recommended first-line treatments for hypertension, yet few head-to-head studies exist. We compared the real-world effectiveness and safety of ACE inhibitors versus ARBs in the first-line treatment of hypertension. We implemented a retrospective, new-user comparative cohort design to estimate hazard ratios using techniques to minimize residual confounding and bias, specifically large-scale propensity score adjustment, empirical calibration, and full transparency. We included all patients with hypertension initiating monotherapy with an ACE inhibitor or ARB between 1996 and 2018 across 8 databases from the United States, Germany, and South Korea. The primary outcomes were acute myocardial infarction, heart failure, stroke, and composite cardiovascular events. We also studied 51 secondary and safety outcomes including angioedema, cough, syncope, and electrolyte abnormalities. Across 8 databases, we identified 2 297 881 patients initiating treatment with ACE inhibitors and 673 938 patients with ARBs. We found no statistically significant difference in the primary outcomes of acute myocardial infarction (hazard ratio, 1.11 for ACE versus ARB [95% CI, 0.95–1.32]), heart failure (hazard ratio, 1.03 [0.87–1.24]), stroke (hazard ratio, 1.07 [0.91–1.27]), or composite cardiovascular events (hazard ratio, 1.06 [0.90–1.25]). Across secondary and safety outcomes, patients on ARBs had significantly lower risk of angioedema, cough, pancreatitis, and GI bleeding. In our large-scale, observational network study, ARBs do not differ statistically significantly in effectiveness at the class level compared with ACE inhibitors as first-line treatment for hypertension but present a better safety profile. These findings support preferentially prescribing ARBs over ACE inhibitors when initiating treatment for hypertension.
Publisher: BMJ
Date: 2020
DOI: 10.1136/BMJOPEN-2019-032426
Abstract: To measure the paediatric user and prescription prevalence in inpatient and ambulatory settings in South Korea, Hong Kong, Taiwan, Japan and Australia by age and gender. A further objective was to list the most commonly used drugs per drug class, per country. Hospital inpatient and insurance paediatric healthcare data from the following databases were used to conduct this descriptive drug utilisation study: (i) the South Korean Ajou University School of Medicine database (ii) the Hong Kong Clinical Data Analysis and Reporting System (iii) the Japan Medical Data Center (iv) Taiwan’s National Health Insurance Research Database and (v) the Australian Pharmaceutical Benefits Scheme. Country-specific data were transformed into the Observational Medical Outcomes Partnership Common Data Model. Children (≤18 years) with at least 1 day of observation in any of the respective databases from January 2009 until December 2013 were included. For each drug class, we assessed the per-protocol overall user and prescription prevalence rates (per 1000 persons) per country and setting. Our study population comprised 1 574 524 children (52.9% male). The highest proportion of dispensings was recorded in the youngest age category ( years) for inpatients (45.1%) with a relatively high user prevalence of analgesics and antibiotics. Adrenergics, antihistamines, mucolytics and corticosteroids were used in 10%–15% of patients. For ambulatory patients, the highest proportion of dispensings was recorded in the middle age category (2–11 years, 67.1%) with antibiotics the most dispensed drug overall. Country-specific paediatric drug utilisation patterns were described, ranked and compared between four East Asian countries and Australia. The widespread use of mucolytics in East Asia warrants further investigation.
Publisher: Elsevier BV
Date: 10-2018
Publisher: Springer Science and Business Media LLC
Date: 2010
DOI: 10.2165/11531250-000000000-00000
Abstract: Many observational studies in the general population have demonstrated an increased risk of adverse events associated with NSAIDs, including gastrointestinal bleeds, congestive heart failure, acute renal failure, hypertension and acute myocardial infarction. Few studies, however, have explored outcomes in populations considered to be more vulnerable to their effects. To determine the rate of adverse events requiring hospitalization that are associated with NSAIDs in two high-risk veteran populations and the general veteran population. In this retrospective cohort study, we identified veterans being dispensed medicines for diabetes mellitus (diabetes cohort), those receiving renin-angiotensin system medicines and frusemide (furosemide) concurrently (ACE inhibitors/angiotensin II type 1 receptor antagonists [angiotensin receptor blockers ARBs] and frusemide cohort), or at least one other medicine (general population/reference cohort). The primary endpoint was hospitalization with a primary diagnosis of congestive heart failure, gastrointestinal ulcer, acute renal failure, acute myocardial infarction or hypertension. Hospitalization rates during the period of non-exposure and the 30-day period after a subject was first dispensed an NSAID were compared using Poisson regression. There was a significant increase in risk of all hospitalizations of interest in the exposed period compared with the unexposed period in the diabetes cohort (incidence rate ratio [IRR] 1.31 95% CI 1.08, 1.60), ACE inhibitor/ARB and frusemide cohort (IRR 1.34 95% CI 1.13, 1.58) and reference cohort (IRR 1.47 95% CI 1.30, 1.66). The incidence rates demonstrate that for every 10,000 veterans treated for 30 days with NSAIDs, there were 20 extra hospitalizations in the diabetes population, 30 additional hospitalizations in the ACE inhibitor/ARB and frusemide cohort and 6 extra hospitalizations in the reference population compared with those not treated with NSAIDs. NSAID use is associated with an increased risk of hospitalization in all groups, with similar risk ratio estimates. However, the clinical implications were greater in the high-risk populations, in which more hospitalizations were observed. Consideration may need to be given to differential presentation of risk information to clinicians.
Publisher: Springer Science and Business Media LLC
Date: 10-03-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2017
Publisher: Wiley
Date: 08-05-2019
DOI: 10.1002/SIM.8191
Abstract: Girardeau, Ravaud and Donner in 2008 presented a formula for s le size calculations for cluster randomised crossover trials, when the intracluster correlation coefficient, interperiod correlation coefficient and mean cluster size are specified in advance. However, in many randomised trials, the number of clusters is constrained in some way, but the mean cluster size is not. We present a version of the Girardeau formula for s le size calculations for cluster randomised crossover trials when the number of clusters is fixed. Formulae are given for the minimum number of clusters, the maximum cluster size and the relationship between the correlation coefficients when there are constraints on both the number of clusters and the cluster size. Our version of the formula may aid the efficient planning and design of cluster randomised crossover trials.
Publisher: Springer Science and Business Media LLC
Date: 12-2017
Publisher: Frontiers Media SA
Date: 14-09-2022
DOI: 10.3389/FPHAR.2022.945592
Abstract: Purpose: Alpha-1 blockers, often used to treat benign prostatic hyperplasia (BPH), have been hypothesized to prevent COVID-19 complications by minimising cytokine storm release. The proposed treatment based on this hypothesis currently lacks support from reliable real-world evidence, however. We leverage an international network of large-scale healthcare databases to generate comprehensive evidence in a transparent and reproducible manner. Methods: In this international cohort study, we deployed electronic health records from Spain (SIDIAP) and the United States (Department of Veterans Affairs, Columbia University Irving Medical Center, IQVIA OpenClaims, Optum DOD, Optum EHR). We assessed association between alpha-1 blocker use and risks of three COVID-19 outcomes—diagnosis, hospitalization, and hospitalization requiring intensive services—using a prevalent-user active-comparator design. We estimated hazard ratios using state-of-the-art techniques to minimize potential confounding, including large-scale propensity score matching/stratification and negative control calibration. We pooled database-specific estimates through random effects meta-analysis. Results: Our study overall included 2.6 and 0.46 million users of alpha-1 blockers and of alternative BPH medications. We observed no significant difference in their risks for any of the COVID-19 outcomes, with our meta-analytic HR estimates being 1.02 (95% CI: 0.92–1.13) for diagnosis, 1.00 (95% CI: 0.89–1.13) for hospitalization, and 1.15 (95% CI: 0.71–1.88) for hospitalization requiring intensive services. Conclusion: We found no evidence of the hypothesized reduction in risks of the COVID-19 outcomes from the prevalent-use of alpha-1 blockers—further research is needed to identify effective therapies for this novel disease.
Publisher: OMICS Publishing Group
Date: 2013
Publisher: Springer Science and Business Media LLC
Date: 09-08-2018
Publisher: BMJ
Date: 31-05-2016
DOI: 10.1136/BMJ.I2550
Abstract: To determine whether treatment with methylphenidate in children and young people with attention-deficit/hyperactivity disorder (ADHD) was associated with cardiovascular events. Self controlled case series analysis. Nationwide health insurance database, 1 January 2008 to 31 December 2011, in South Korea. 1224 patients aged ≤17 who had experienced an incident cardiovascular event and had had at least one incident prescription for methylphenidate. A recorded diagnosis (either a primary or secondary cause) of any of the following cardiovascular adverse events: arrhythmias (ICD-10 (international classification of diseases, 10th revision) codes I44, I45, I47, I48, I49), hypertension (codes I10-I15), myocardial infarction (code I21), ischemic stroke (code I63), or heart failure (code I50). Incidence rate ratios were calculated with conditional Poisson regression and adjusted for time varying comorbidity and comedication. Increased risk of arrhythmia was observed in all exposed time periods-that is, periods of treatment with methylphenidate-(incidence rate ratio 1.61, 95% confidence interval 1.48 to 1.74), and the risk was highest in the children who had congenital heart disease. No significant risk of myocardial infarction was observed for all exposed time periods (1.33, 0.90 to 1.98), though risk was higher in the early risk periods between eight and 56 days after the start of treatment with methylphenidate. No significant increased risk was observed for hypertension, ischemic stroke, or heart failure. The relative risk of myocardial infarction and arrhythmias is increased in the early period after the start of methylphenidate treatment for ADHD in children and young people. Though the absolute risk is likely to be low, the risk-benefit balance of methylphenidate should be carefully considered, particularly in children with mild ADHD.
Publisher: Wiley
Date: 09-03-2020
DOI: 10.1111/ADJ.12750
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.CMPB.2018.03.021
Abstract: Adverse drug reactions (ADRs) are one of the leading causes of morbidity and mortality and thus should be detected early to reduce consequences on health outcomes. Medication dispensing data are comprehensive sources of information about medicine uses that can be utilized for the signal detection of ADRs. Sequence symmetry analysis (SSA) has been employed in previous studies to detect signals of ADRs from medication dispensing data, but it has a moderate sensitivity and tends to miss some ADR signals. With successful applications in various areas, supervised machine learning (SML) methods are promising in detecting ADR signals. Gold standards of known ADRs and non- ADRs from previous studies create opportunities to take into account additional domain knowledge to improve ADR signal detection with SML. We assess the utility of SML as a signal detection tool for ADRs in medication dispensing data with the consideration of domain knowledge from DrugBank and MedDRA. We compare the best performing SML method with SSA. We model the ADR signal detection problem as a supervised machine learning problem by linking medication dispensing data with domain knowledge bases. Suspected ADR signals are extracted from the Australian Pharmaceutical Benefit Scheme (PBS) medication dispensing data from 2013 to 2016. We construct predictive features for each signal candidate based on its occurrences in medication dispensing data as well as its pharmacological properties. Pharmaceutical knowledge bases including DrugBank and MedDRA are employed to provide pharmacological features for a signal candidate. Given a gold standard of known ADRs and non-ADRs, SML learns to differentiate between known ADRs and non-ADRs based on their combined predictive features from linked sources, and then predicts whether a new case is a potential ADR signal. We evaluate the performance of six widely used SML methods with two gold standards of known ADRs and non-ADRs from previous studies. On average, gradient boosting classifier achieves the sensitivity of 77%, specificity of 81%, positive predictive value of 76%, negative predictive value of 82%, area under precision-recall curve of 81%, and area under receiver operating characteristic curve of 82%, most of which are higher than in other SML methods. In particular, gradient boosting classifier has 21% higher sensitivity than and comparable specificity with SSA. Furthermore, gradient boosting classifier detects 10% more unknown potential ADR signals than SSA. Our study demonstrates that gradient boosting classifier is a promising supervised signal detection tool for ADRs in medication dispensing data to complement SSA.
Publisher: Medical Journals Sweden AB
Date: 11-05-2011
Publisher: Oxford University Press (OUP)
Date: 04-2022
Abstract: To assess the effectiveness of a pharmacist-led intervention using validated tools to reduce medicine-induced deterioration and adverse reactions. Multicenter, open-label parallel randomised controlled trial involving 39 Australian aged-care facilities. Residents on ≥4 medicines or ≥1 anticholinergic or sedative medicine. Pharmacist-led intervention using validated tools to detect signs and symptoms of medicine-induced deterioration which occurred every 8 weeks over 12 months. Usual care (Residential Medication Management Review) provided by accredited pharmacists. Primary outcome was change in Frailty Index at 12 months. Secondary outcomes included changes in cognition, 24-hour movement behaviour by accelerometry, grip strength, weight, adverse events and quality of life. 248 persons (median age 87 years) completed the study 120 in the interventionand, 128 in control arms. In total 575 pharmacist, sessions were undertaken in the intervention arm. There was no statistically significant difference for change in frailty between groups (mean difference: 0.009, 95% CI: −0.028, 0.009, P = 0.320). A significant difference for cognition was observed, with a mean difference of 1.36 point change at 12 months (95% CI: 0.01, 2.72, P = 0.048). Changes in 24-hour movement behaviour, grip strength, adverse events and quality of life were not significantly different between groups. Point estimates favoured the intervention arm at 12 months for frailty, 24-hour movement behaviour and grip strength. The use of validated tools by pharmacists to detect signs of medicine-induced deterioration is a model of practice that requires further research, with promising results from this trial, particularly with regards to improved cognition.
Publisher: Springer Science and Business Media LLC
Date: 19-04-2023
Publisher: JMIR Publications Inc.
Date: 27-09-2021
Abstract: igital technologies can enable rapid targeted delivery of audit and feedback interventions at scale. Few studies have evaluated how mode of delivery affects clinical professional behavior change and none have assessed the feasibility of such an initiative at a national scale. he aim of this study was to develop and evaluate the effect of audit and feedback by digital versus postal (letter) mode of delivery on primary care physician behavior. his study was developed as part of the Veterans’ Medicines Advice and Therapeutics Education Services (MATES) program, an intervention funded by the Australian Government Department of Veterans’ Affairs that provides targeted education and patient-specific audit with feedback to Australian general practitioners, as well as educational material to veterans and other health professionals. We performed a cluster randomized controlled trial of a multifaceted intervention to reduce inappropriate gabapentinoid prescription, comparing digital and postal mode of delivery. All veteran patients targeted also received an educational intervention (postal delivery). Efficacy was measured using a linear mixed-effects model as the average number of gabapentinoid prescriptions standardized by defined daily dose (in idual level), and number of veterans visiting a psychologist in the 6 and 12 months following the intervention. he trial involved 2552 general practitioners in Australia and took place in March 2020. Both intervention groups had a significant reduction in total gabapentinoid prescription by the end of the study period (digital: mean reduction of 11.2%, i P /i =.004 postal: mean reduction of 11.2%, i P /i =.001). We found no difference between digital and postal mode of delivery in reduction of gabapentinoid prescriptions at 12 months (digital: –0.058, postal: –0.058, i P /i =.98). Digital delivery increased initiations to psychologists at 12 months (digital: 3.8%, postal: 2.0%, i P /i =.02). ur digitally delivered professional behavior change intervention was feasible, had comparable effectiveness to the postal intervention with regard to changes in medicine use, and had increased effectiveness with regard to referrals to a psychologist. Given the logistical benefits of digital delivery in nationwide programs, the results encourage exploration of this mode in future interventions.
Publisher: American Medical Association (AMA)
Date: 19-09-2023
Publisher: Springer Science and Business Media LLC
Date: 31-03-2018
DOI: 10.1007/S10654-018-0386-8
Abstract: Active surveillance for unknown or unsuspected adverse drug effects may be carried out by applying epidemiological techniques to large administrative databases. Self-controlled designs, like the symmetry design, have the advantage over conventional design of adjusting for confounders that are stable over time. The aim of this paper was to describe the output of a comprehensive open-ended symmetry analysis of a large dataset. All drug dispensings and all secondary care contacts in Denmark during the period 1995-2012 for persons born before 1950 were analyzed by a symmetry design. We analyzed all drug-drug sequences and all drug-disease sequences occurring during the study period. The identified associations were ranked according to the number of outcomes that potentially could be attributed to the exposure. In the main analysis, 29,891,212 incident drug therapies, and 21,300,000 incident diagnoses were included. Out of 186,758 associations tested in the main analysis, 43,575 (23.3%) showed meaningful effect size. For the top 200 drug-drug associations, 47% represented unknown associations, 24% represented known adverse drug reactions, 30% were explained by mutual indication or reverse causation. For the top 200 drug-disease associations the proportions were 31, 15, and 55%, respectively. Screening by symmetry analysis can be a useful starting point for systematic pharmacovigilance activities if coupled with a systematic post-hoc review of signals.
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.ARTH.2017.09.001
Abstract: Prolonged opioid use following total knee arthroplasty (TKA) has not been extensively studied. A cohort study of primary TKA for osteoarthritis using an integrated healthcare system and Total Joint Replacement Registry (January 2008-December 2011) was conducted. Opioid use during the first year after TKA was the exposure of interest and cumulative daily oral morphine equivalent (OME) amounts were calculated. Total postsurgical OME per 90-day exposure periods were categorized into quartiles. The end point was aseptic revision surgery. Survival analyses were conducted and hazard ratios (HRs) were adjusted for age, gender, prior analgesic use, opioid-related comorbidities, and chronic pain diagnoses. A total of 24,105 patients were studied. After the initial 90-day postoperative period, 41.5% (N = 9914) continued to use opioids. Also, 155 (0.6%) revisions occurred within 1 year and 377 (1.6%) within 5 years. Compared to patients not taking any opioids, patients using medium-low to high OME after the initial 90-day period had a higher adjusted risk of 1-year revision, ranging from HR = 2.4 (95% confidence interval, 1.3-4.5) to HR = 33 (95% confidence interval, 10-110) depending on the OME and time period. Patients who require opioids beyond 90 days after TKA warrant close follow-up.
Publisher: Wiley
Date: 22-11-2005
DOI: 10.1111/J.1471-0528.2005.00753.X
Abstract: Few strategies aimed at addressing rising rates of caesarean section have explicitly involved information-based approaches for pregnant women. This study describes the development and evaluation of such an intervention for pregnant women, encompassing p hlets and a peer support network (PSN). Process evaluation. The study was undertaken at a metropolitan teaching hospital in Adelaide, South Australia. A consecutive s le of pregnant women attending the ultrasound clinic over a two-month period, recruited at 18 weeks of gestation. Participants received two p hlets at 18 weeks of gestation and information on a PSN at around 28 weeks of gestation. A questionnaire was sent to women at seven weeks postnatal, asking them to evaluate the intervention. The extent to which the intervention resources were used and participants were satisfied with the resources they received. Ninety-two women returned questionnaires (response rate of 62%). Women generally resisted engaging with the informational resources, citing irrelevance to their situation, for ex le, 53% (49/92) read all of the p hlets. None of the women used the PSN. Women who had experienced childbirth previously and those of higher education were significantly more likely to read the p hlets. While generally satisfied with p hlet content, one in five women reported feeling distressed by some of the information. This exploratory study casts doubt on the notion of information provision for pregnant women as a panacea for addressing rising rates of caesarean section.
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.HLC.2021.08.027
Abstract: The use of cardiac implantable electronic devices (CIED), which includes pacemakers, implantable cardioverter-defibrillators (ICD), cardiac resynchronisation therapy pacemakers (CRT-P) and cardiac resynchronisation therapy defibrillators (CRT-D) has increased over the past 20 years, but there is a lack of real world evidence on the longevity of these devices in the older population which is essential to inform health care delivery and support clinical decisions. We conducted a retrospective cohort study using data from the Australian Government Department of Veterans' Affairs database. The cohort consisted of people who had a CIED procedure between 2005 and 2015. The cumulative risk of generator replacement/reoperations was estimated accounting for the competing risk of death. A total of 16,662 patients were included. In pacemaker recipients with an average age of 85 years, the 5-year risk of reoperation ranged from 2.8% in single chamber, 3.6% in dual chamber to 7.6% in CRT-P recipients, while the 5-year risk of dying with the index pacemaker in situ was 63% in single chamber, 46% in dual chamber and 56% in CRT-P recipients. In defibrillator recipients with an average age of 80 years, the 5-year risk of reoperation ranged from 11% in single chamber, 13% in dual chamber to 24% in CRT-D recipients, while the 5-year risk of dying with the index defibrillator in situ was 46% in single chamber, 40% in dual chamber and 41% in CRT-D recipients. In this cohort of older patients the 5-year risk of generator reoperation was low in pacemaker recipients whereas up to one in four CRT-D recipients would have a reoperation within 5 years.
Publisher: American Medical Association (AMA)
Date: 23-08-2022
Abstract: There remains a lack of randomized trials investigating aspirin monotherapy for symptomatic venous thromboembolism (VTE) prophylaxis following total hip arthroplasty (THA) or total knee arthroplasty (TKA). To determine whether aspirin was noninferior to enoxaparin in preventing symptomatic VTE after THA or TKA. Cluster-randomized, crossover, registry-nested trial across 31 hospitals in Australia. Clusters were hospitals performing greater than 250 THA or TKA procedures annually. Patients (aged ≥18 years) undergoing hip or knee arthroplasty procedures were enrolled at each hospital. Patients receiving preoperative anticoagulation or who had a medical contraindication to either study drug were excluded. A total of 9711 eligible patients were enrolled (5675 in the aspirin group and 4036 in the enoxaparin group) between April 20, 2019, and December 18, 2020. Final follow-up occurred on August 14, 2021. Hospitals were randomized to administer aspirin (100 mg/d) or enoxaparin (40 mg/d) for 35 days after THA and for 14 days after TKA. Crossover occurred after the patient enrollment target had been met for the first group. All 31 hospitals were initially randomized and 16 crossed over prior to trial cessation. The primary outcome was symptomatic VTE within 90 days, including pulmonary embolism and deep venous thrombosis (DVT) (above or below the knee). The noninferiority margin was 1%. Six secondary outcomes are reported, including death and major bleeding within 90 days. Analyses were performed by randomization group. Enrollment was stopped after an interim analysis determined the stopping rule was met, with 9711 patients (median age, 68 years 56.8% female) of the prespecified 15 562 enrolled (62%). Of these, 9203 (95%) completed the trial. Within 90 days of surgery, symptomatic VTE occurred in 256 patients, including pulmonary embolism (79 cases), above-knee DVT (18 cases), and below-knee DVT (174 cases). The symptomatic VTE rate in the aspirin group was 3.45% and in the enoxaparin group was 1.82% (estimated difference, 1.97% 95% CI, 0.54%-3.41%). This failed to meet the criterion for noninferiority for aspirin and was significantly superior for enoxaparin ( P = .007). Of 6 secondary outcomes, none were significantly better in the enoxaparin group compared with the aspirin group. Among patients undergoing hip or knee arthroplasty for osteoarthritis, aspirin compared with enoxaparin resulted in a significantly higher rate of symptomatic VTE within 90 days, defined as below- or above-knee DVT or pulmonary embolism. These findings may be informed by a cost-effectiveness analysis. ANZCTR Identifier: ACTRN12618001879257
Publisher: Proceedings of the National Academy of Sciences
Date: 06-06-2016
Abstract: Observational research promises to complement experimental research by providing large, erse populations that would be infeasible for an experiment. Observational research can test its own clinical hypotheses, and observational studies also can contribute to the design of experiments and inform the generalizability of experimental research. Understanding the ersity of populations and the variance in care is one component. In this study, the Observational Health Data Sciences and Informatics (OHDSI) collaboration created an international data network with 11 data sources from four countries, including electronic health records and administrative claims data on 250 million patients. All data were mapped to common data standards, patient privacy was maintained by using a distributed model, and results were aggregated centrally. Treatment pathways were elucidated for type 2 diabetes mellitus, hypertension, and depression. The pathways revealed that the world is moving toward more consistent therapy over time across diseases and across locations, but significant heterogeneity remains among sources, pointing to challenges in generalizing clinical trial results. Diabetes favored a single first-line medication, metformin, to a much greater extent than hypertension or depression. About 10% of diabetes and depression patients and almost 25% of hypertension patients followed a treatment pathway that was unique within the cohort. Aside from factors such as s le size and underlying population (academic medical center versus general population), electronic health records data and administrative claims data revealed similar results. Large-scale international observational research is feasible.
Publisher: Wiley
Date: 07-2003
DOI: 10.1046/J.1468-1293.2003.00155.X
Abstract: To examine the relationship between depressive disorders and unprotected anal intercourse with casual partners, among homosexually active men attending for primary care. The first 460 homosexually active men enrolling in an Australian integrated primary care programme were screened for current depressive disorders using the Primary Care Evaluation of Mental Disorders (PRIME-MD) and completed questionnaires on their sexual behaviour in the prior 6 months. One hundred and sixty-two (35%) were HIV positive, 283 (62%) were HIV negative and 15 (3%) were untested. The prevalence of major depressive episode (MDE), as measured by the PRIME-MD, on enrollment was 28% (129/460), while the prevalence of dysthymic disorder (DD) was 26% (121/460). These include 84 men (18%) who met the criteria for both disorders ('double depression'). Neither disorder was associated with HIV status. Men with MDE were less likely to have been sexually active than the remainder of the cohort (90/129 [70%] vs. 291/331 [88%] OR: 0.32 [95% CI: 0.19-0.52] P<0.0001). Men with DD alone, however, were significantly more likely than men with neither disorder to report having had unprotected anal intercourse with a casual partner (11/38 [29%] vs. 43/292 [15%] OR: 2.36 [95%CI: 1.09-5.10] P=0.035). Depressive disorders were highly prevalent in this cohort and independent of HIV status. MDE was associated with reduced sexual activity. Among men without MDE, the presence of DD was independently associated with an increased likelihood of reporting unsafe anal sex with a casual partner in the prior 6 months.
Publisher: Cambridge University Press (CUP)
Date: 10-11-2018
DOI: 10.1017/S1041610217001934
Abstract: Antipsychotics are commonly used, and the rate of use is highest, among those aged 65 years or over, where the risk of adverse events is also high. Up to 20% of younger adults use more than one antipsychotic concurrently however there are few studies on the prevalence of antipsychotic polypharmacy in older people. We aimed to analyze antipsychotic use in elderly Australians, focusing on the prevalence of antipsychotic polypharmacy and the use of medicines to manage adverse events associated with antipsychotics. A cross-sectional study was conducted using Australian Department of Veterans’ Affairs (DVA) administrative claims data for the period 1 March 2014 to 30 June 2014. Veterans dispensed at least one antipsychotic medicine during the study period was included. We determined the number of participants dispensed antipsychotic polypharmacy and the number of participants dispensed medicines to manage antipsychotic side effects. There were 7,412 participants with a median age of 86 years. Fifty-one percent ( n =3,784) were women and 48% ( n =3,569) lived in residential aged-care. Fifty one participants (0.7%) were dispensed anticholinergic medicines indicated for the management of antipsychotic-associated extrapyramidal movement disorders and eight (0.1%) were dispensed medicines for the management of hyperprolactinemia. Five percent of participants ( n =365) received dual antipsychotics. Dual antipsychotic users were more likely to be under the care of a psychiatrist or to have had a mental health hospitalization than those using a single antipsychotic. Antipsychotic polypharmacy occurred in one in 20 elderly persons, indicating that there is room for improvement in antipsychotic use in elderly patients.
Publisher: Elsevier BV
Date: 04-2020
Publisher: Springer Science and Business Media LLC
Date: 28-07-2015
Publisher: Oxford University Press (OUP)
Date: 05-12-2017
Abstract: To evaluate the impact of national multifaceted initiatives to improve use of proton pump inhibitors (PPIs) on the use of PPIs among older Australians. Interrupted time series analysis using administrative health claims data from the Australian Government Department of Veterans' Affairs (DVA). Australia. All veterans and dependents who received PPIs between January 2003 and December 2013. National, multifaceted interventions to improve PPI use were conducted by the Australian Government Department of Veterans' Affairs Veterans' MATES programme and Australia's NPS MedicineWise in April 2004, June 2006, May 2009 and August 2012. Trends in monthly rate of use of any PPI among the veteran population, and the monthly rate of use of low strength PPIs among all veterans dispensed a PPI. Interventions in 2004, 2006, 2009 and 2012 slowed the rate of increase in PPI use significantly, with the 2012 intervention resulting in a sustained 0.04% decrease in PPI use each month. The combined effect of all four interventions was a 20.9% (95% CI 7.8-33.9%) relative decrease in PPI use 12 months after the final intervention. The four interventions also resulted in a 42.2% (95% CI 19.9-64.5%) relative increase in low strength PPI use 12 months after the final intervention. National multifaceted programmes targeting clinicians and consumers were effective in reducing overall PPI use and increasing use of low strength PPIs. Interventions to improve PPI use should incorporate regular repetition of key messages to sustain practice change.
Publisher: Springer Science and Business Media LLC
Date: 17-05-2017
Publisher: Oxford University Press (OUP)
Date: 2002
DOI: 10.1086/338232
Abstract: This study examined whether a significant change in antibiotic use caused by an Australian government directive targeted at amoxicillin with clavulanic acid (AC) was associated with changes in prescription share, health care costs, and patient outcomes. We used an integrated database of computerized general practice medical records, which included data regarding 34,242 patients and 318,234 recorded patient visits. There were 15,303 antibiotic prescriptions provided to 9921 patients during a 4-year period, with AC prescribed for 1453 (14.6%) of these patients. A total of 5125 patient outcomes were identified. There was a shift away from best-practice antibiotic prescribing, and a significant association was identified between the rate and cost of process-of-care and patient outcomes and the decrease in AC-prescription share. This policy initiative created unintended changes in prescribing behavior, increased costs to the government, and a trend toward poorer patient outcomes. Detailed analyses are required before instigating initiatives aimed at changing clinicians' prescribing behavior.
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.DIABRES.2017.06.018
Abstract: To explore the feasibility of MedicineInsight data to support risk management plan evaluation, focusing on sodium glucose co-transporter 2 (SGLT2) inhibitors for type 2 diabetes. A retrospective study using de-identified electronic general practitioner records. Patients who initiated SGLT2 inhibitor between 1 Jan 2012 to 1 Sep 2015 were compared to patients who initiated dipeptidyl peptidase 4 (DPP-4) inhibitors. The two cohorts were followed-up for six months. Risk of urinary-tract (UT) and genital infections was evaluated. The indication for use of SGLT2 inhibitors, recommended prior diabetes therapies and recommended monitoring were investigates. There were 1977 people in the SGLT2 cohort (with 93% initiated on dapagliflozin) and 1964 people in the DPP-4 cohort. Of the SGLT2 initiators, 54% had a documented indication for use as type 2 diabetes 86% had used metformin and/or a sulfonylurea in the prior 12months. Renal function monitoring was documented for only 25% in the 6months initiation. The frequency of UTI in the 6months post SGLT2 initiation was not significantly increased compared to the DPP-4 cohort (3.6%vs 4.9% aHR=0.90, 95% CI 0.66-1.24). Genital infection were more frequent in the SGLT2 than in the DPP-4 cohort (2.9% vs 0.9%, aHR=3.50, 95% CI 1.95-5.89). Similar to existing evidence, we found a higher risk of genital infection associated with SGLT2 inhibitors (primarily dapagliflozin) but no increased risk of UTIs compared to DPP-4 use.
Publisher: Springer Science and Business Media LLC
Date: 30-01-2022
DOI: 10.1186/S12874-022-01505-Z
Abstract: We investigated whether we could use influenza data to develop prediction models for COVID-19 to increase the speed at which prediction models can reliably be developed and validated early in a pandemic. We developed COVID-19 Estimated Risk (COVER) scores that quantify a patient’s risk of hospital admission with pneumonia (COVER-H), hospitalization with pneumonia requiring intensive services or death (COVER-I), or fatality (COVER-F) in the 30-days following COVID-19 diagnosis using historical data from patients with influenza or flu-like symptoms and tested this in COVID-19 patients. We analyzed a federated network of electronic medical records and administrative claims data from 14 data sources and 6 countries containing data collected on or before 4/27/2020. We used a 2-step process to develop 3 scores using historical data from patients with influenza or flu-like symptoms any time prior to 2020. The first step was to create a data-driven model using LASSO regularized logistic regression, the covariates of which were used to develop aggregate covariates for the second step where the COVER scores were developed using a smaller set of features. These 3 COVER scores were then externally validated on patients with 1) influenza or flu-like symptoms and 2) confirmed or suspected COVID-19 diagnosis across 5 databases from South Korea, Spain, and the United States. Outcomes included i) hospitalization with pneumonia, ii) hospitalization with pneumonia requiring intensive services or death, and iii) death in the 30 days after index date. Overall, 44,507 COVID-19 patients were included for model validation. We identified 7 predictors (history of cancer, chronic obstructive pulmonary disease, diabetes, heart disease, hypertension, hyperlipidemia, kidney disease) which combined with age and sex discriminated which patients would experience any of our three outcomes. The models achieved good performance in influenza and COVID-19 cohorts. For COVID-19 the AUC ranges were, COVER-H: 0.69–0.81, COVER-I: 0.73–0.91, and COVER-F: 0.72–0.90. Calibration varied across the validations with some of the COVID-19 validations being less well calibrated than the influenza validations. This research demonstrated the utility of using a proxy disease to develop a prediction model. The 3 COVER models with 9-predictors that were developed using influenza data perform well for COVID-19 patients for predicting hospitalization, intensive services, and fatality. The scores showed good discriminatory performance which transferred well to the COVID-19 population. There was some miscalibration in the COVID-19 validations, which is potentially due to the difference in symptom severity between the two diseases. A possible solution for this is to recalibrate the models in each location before use.
Publisher: Springer Science and Business Media LLC
Date: 18-07-2011
Publisher: Wiley
Date: 06-2018
DOI: 10.1002/JPPR.1379
Publisher: Elsevier BV
Date: 12-2020
Publisher: Wiley
Date: 20-05-2020
DOI: 10.1111/AJAG.12801
Abstract: To determine the access to and use of health‐care services by people with dementia in the community. A retrospective cross‐sectional analysis of the Australian Government Department of Veterans' Affairs (DVA) administrative claims data was conducted. Veterans and their spouses with one or more dementia claims between 1 January 2000 and 30 June 2016, who were aged ≥45 years at the time of the claim and who were still alive and living in the community on 30 June 2017, were included. We assessed the proportions of people with dementia who received medical, pharmacy and medicines, allied health services, and home care supports from 1 July 2016 to 30 June 2017. A total of 10 171 people with dementia were included. They had a median age of 89 years, 60% were female, and 63% lived in a major city. Over the one‐year study period, 98% visited the GP and 99% had medicines dispensed at a pharmacy. Eighty‐two per cent saw a specialist, and 19% saw a geriatrician. Thirty‐one per cent received a DVA‐funded dose administration aid to support medication administration, and 19% received a home medicines review. Less than half had claims for occupational therapist services (48%), community nursing (48%), physiotherapists (41%) or dentist visits (33%). Fifty‐eight per cent received home care supports, for ex le domestic assistance. Many people living with dementia in the community do not access all of the health‐care or support services available to them. Ensuring that people with dementia and their carers are supported to access the services available to assist them live in the community setting for as long as possible is important.
Publisher: Springer Science and Business Media LLC
Date: 06-09-2021
DOI: 10.1007/S40266-021-00892-0
Abstract: Renal function testing should be performed prior to initiating medicines that require dose adjustment in renal impairment, with ongoing monitoring in continued use, particularly in older people. There is little evidence regarding the extent to which renal function monitoring is performed in older Australians dispensed medicines requiring renal function monitoring. The aim of this study was to determine the extent of renal function testing in older people dispensed medicines requiring renal function monitoring. A retrospective analysis of administrative claims data from the Australian Government Department of Veterans' Affairs was conducted for people aged 65 years or older who were dispensed one or more medicines requiring renal function monitoring, from 1 June 2019 to 30 September 2019, to investigate the proportion of people with a claim for a pathology test that included creatinine levels in the 6-12 months before or after dispensing of a medicine requiring renal function monitoring. There were 100,113 people who were dispensed at least one medicine requiring renal function monitoring during the study period, of whom 15% had a history of renal impairment and 16% had diabetes mellitus. Sixty-one percent had a claim for a test in the prior 6 months this increased to 80% of participants with a claim for a test in the prior 12 months. The rate of claims for testing was lower in aged care facility residents compared with people living in the community (54% vs 62% in the previous 6 months p < 0.001), and was higher in people with diabetes (75% vs 58% p < 0.001), history of renal impairment (91% vs 59% p < 0.001) or heart failure (77% vs 60% p < 0.001) compared with those without these conditions. Medicines that require renal function monitoring are commonly used in older Australians, and while the majority have claims for tests that include renal function, some are missing out.
Publisher: Springer Science and Business Media LLC
Date: 27-02-2021
DOI: 10.1186/S12874-021-01230-Z
Abstract: The case-crossover design is suited to medication safety studies but is vulnerable to exposure misclassification. Using the ex le of tricyclic antidepressants and the risk of hip fracture, we present a data visualisation tool for observing exposure misclassification in case-crossover studies. A case-crossover study was conducted using Australian Government Department of Veterans’ Affairs claims data. Beneficiaries aged over 65 years who were hospitalised for hip fracture between 2009 and 2012 were included. The case window was defined as 1–50 days pre fracture. Control window one and control window two were defined as 101–150 and 151–200 days pre fracture, respectively. Patients were stratified by whether exposure status changed when control window two was specified instead of control window one. To visualise potential misclassification, each subject’s tricyclic antidepressant dispensings were plotted over the 200 days pre fracture. The study population comprised 8828 patients with a median age of 88 years. Of these subjects, 348 contributed data to the analyses with either control window. The data visualisation suggested that 14% of subjects were potentially misclassified with control window one while 45% were misclassified with control window two. The odds ratio for the association between tricyclic antidepressants and hip fracture was 1.18 (95% confidence interval = 0.91–1.52) using control window one, whereas risk was significantly increased (odds ratio = 1.43, 95% confidence interval = 1.11–1.83) using control window two. Exposure misclassification was less likely to be present with control window one than with an earlier control window, control window two. When specifying different control windows in a case-crossover study, data visualisation can help to assess the extent to which exposure misclassification may contribute to variable results.
Publisher: Wiley
Date: 07-07-2010
DOI: 10.1002/PDS.2009
Abstract: To examine the prescribing of prochlorperazine secondary to the prescribing of a medicine which could lead to symptoms for which prochlorperazine is indicated and commonly used. Given the range of potential hypotensive, sedative, dystonic and other extra-pyramidal side effects associated with prochlorperazine, its association with hip fracture was also examined. Prescription/event sequence symmetry analyses were undertaken from 1st January 2003 to 31st December 2006, using administrative claims data from the Department of Veterans' Affairs, Australia. This method assesses asymmetry in the distribution of an incident event (either prescription of another medicine or hospitalization) before and after the initiation of prochlorperazine. Crude and adjusted sequence ratios (ASR) with 95% confidence intervals (CI) were calculated. A total of 34 235 persons with incident use of prochlorperazine were identified during the study period. Statistically significant positive associations were found for a number of commonly used medicines, including cardiovascular medicines, NSAIDs, opioids and sedatives and the subsequent initiation of prochlorperazine that ranged from 1.07 (95%CI 1.01-1.14) for diuretics to 1.50 (95%CI 1.40-1.61) for statins. Prescription event analysis showed a 49% (95%CI 1.19-1.86) increased risk of hospitalisation for hip fracture following dispensing of prochlorperazine. Prescribers should consider the possible contributing role of newly initiated medicines with the potential to cause of dizziness, and where possible address this through dose reduction or cessation of the medicine, rather than prescribing prochlorperazine.
Publisher: Hindawi Limited
Date: 04-01-2011
DOI: 10.1111/J.1365-2710.2009.01149.X
Abstract: Unintended bleeds are a common complication of warfarin therapy. We aimed to determine the impact of general practitioner-pharmacist collaborative medication reviews in the practice setting on hospitalization-associated bleeds in patients on warfarin. We undertook a retrospective cohort study using administrative claims data for the ambulatory veteran and war widow population, Australia. Participants were veterans, war widows and their dependents aged 65 years and over dispensed warfarin. The exposed groups were those exposed to a general practitioner (GP)-pharmacist collaborative home medication review. The service includes GP referral, a home visit by an accredited pharmacist to identify medication-related problems, a pharmacist report with follow-up undertaken by the GP. The outcome measure was time to next hospitalization for bleeding. There were 816 veterans exposed to a home medicines review and 16,320 unexposed patients, with an average age of 81.5 years, and six to seven co-morbidities. Adjusted results showed a 79% reduction in likelihood of hospitalization for bleeding between 2 and 6 months (HR, 0.21 95% CI, 0.05-0.87) amongst those who had received a home medicines reviewed compared to the unexposed patients. No effect was seen in the time period from review to 2 months, nor in the time period 6 to 12 months post a review. Medicines review in the practice setting delays time to next hospitalization for bleeding in those treated with warfarin in the period 2 to 6 months after the review, but is not sustained over time. Six monthly medication reviews may be required for patients on warfarin who are considered at high risk of bleeding.
Publisher: Elsevier BV
Date: 06-2023
Publisher: Wiley
Date: 29-09-2017
DOI: 10.1111/BCP.13088
Publisher: BMJ
Date: 09-2019
DOI: 10.1136/BMJOPEN-2019-029221
Abstract: To test the association between use of medicines with anticholinergic or sedative properties and physical function, cognitive function, appetite and frailty. This cross-sectional study analysed baseline data collected as part of the Australian Longitudinal Study of Ageing, a population-based cohort of 2087 participants aged 65 years or over living in South Australia. Physical function was measured at baseline using measures including hand grip strength, walking speed, chair stands, activities of daily living and instrumental activities of daily living (IADL). Cognitive function was measured using Mini-Mental State Examination. Appetite was measured using Center for Epidemiologic Studies Depression question 2. Frailty was measured using frailty index. The association between use of anticholinergics or sedatives and physical or cognitive function, appetite, or frailty was assessed using analysis of covariance and ordinal or binary logistic regression. Almost half of the population were using anticholinergics or sedatives (n=954, 45.7%). Use of anticholinergics was significantly associated with poorer grip strength, slower walking speed, poorer IADL and poorer appetite. Use of sedatives was significantly associated with poorer grip strength, slower walking speed and poorer IADL. We found no significant association between medicine use and cognitive function. Users of anticholinergics or sedatives were significantly more likely to be frail compared with non-users. Use of medicines with anticholinergic or sedative properties is significantly associated with poorer physical function, poorer appetite and increased frailty. Early identification of signs and symptoms of deterioration associated with medicine use is particularly important in older people so that worsening frailty and subsequent adverse events are prevented.
Publisher: Wiley
Date: 26-10-2001
DOI: 10.1002/PDS.629
Abstract: Observational databases are increasingly acknowledged for their value in clinical investigation. Australian general practice in particular presents an exciting opportunity to examine treatment in a natural setting. The paper explores issues such as privacy and confidentiality--foremost considerations when conducting this form of pharmacoepidemiological research. Australian legislation is currently addressing these exact issues in order to establish clear directives regarding ethical concerns. The development of a pharmacoepidemiological database arising from the integration of computerized Australian general practice records is described in addition, to the challenges associated with creating a database which considers patient privacy. The database known as 'Medic-GP', presently contains more than 950,000 clinical notes (including consultations, pathology, diagnostic imaging and adverse reactions) over a 5-year time period and relates to 55,000 patients. The paper then details a retrospective study which utilized the database to examine the interaction between antibiotic prescribing and patient outcomes from a community perspective, following a policy intervention. This study illustrates the application of computerized general practice records in research.
Publisher: Wiley
Date: 19-09-2018
DOI: 10.1002/PDS.4663
Abstract: The safety of nonsteroidal anti-inflammatory drugs (NSAIDs) commonly used in Asia-Pacific countries has had limited study. We assessed the risk of hospitalization for gastrointestinal events with loxoprofen and mefenamic acid compared with other NSAIDs in Asia-Pacific populations. We conducted a cohort study using a distributed network with a common data model in Australia, Hong Kong, Japan, Korea, and Taiwan. We included patients who initiated diclofenac, loxoprofen, mefenamic acid, or celecoxib and followed them until their first gastrointestinal hospitalization, switch or discontinuation of medication, disenrollment, or end of database coverage. We used Cox proportional hazards models to assess hospitalization risk. We identified 9879 patients in Japan, 70 492 in Taiwan, 263 741 in Korea, and 246 in Hong Kong who initiated an NSAID, and 44 013 patients in Australia, a predominantly Caucasian population. The incidence of gastrointestinal hospitalization was 25.6 per 1000 person-years in Japan, 32.8 in Taiwan, 11.5 in Korea, 484.5 in Hong Kong, and 35.6 in Australia. Compared with diclofenac, the risk of gastrointestinal events with loxoprofen was significantly lower in Korea (hazards ratio, 0.37 95% CI, 0.25-0.54) but not in Japan (1.65 95% CI, 0.47-5.78). The risk of gastrointestinal events with mefenamic acid was significantly lower in Taiwan (0.45 95% CI, 0.26-0.78) and Korea (0.11 95% CI, 0.05-0.27) but not Hong Kong (2.16 95% CI, 0.28-16.87), compared with diclofenac. Compared with diclofenac, loxoprofen was associated with a lower risk of gastrointestinal hospitalizations in Korea and mefenamic acid with a lower risk in Taiwan and Korea.
Publisher: Wiley
Date: 2007
DOI: 10.1002/PDS.1393
Abstract: To determine if patient-specific prescriber feedback for general medical practitioners (GPs), supported by educational material mailed to their patients, would increase home medicines review (HMR) rates. An observational study was conducted using the Repatriation Pharmaceutical Benefits Scheme (RPBS) Pharmacy Claims Database. The intervention group (n = 40 270) included all veterans aged >/=65 years, dispensed >/=5 unique medicines each month over a 4 month period. Comparison group veterans (n = 49,227) were those who did not have >/=5 or more unique medicines dispensed each month, but did have at least one prescription each month and >/=20 prescriptions over 4 months, of which five were unique medicines, Intervention GPs (n = 11,384) were sub ided into 2 groups: GPs with intervention veterans (n = 2097) and GPs with both intervention and comparison group veterans (n = 9287). The comparison group of GPs (n = 3630) were primary prescribers to the comparison veterans only. Rates of HMRs pre and post-intervention and the number of new GPs participating in HMR services were examined. There was a significant increase in HMR rates in intervention group, from 2.2 per 1000 in the pre-period to 4.6 per 1000 per month in the post-intervention period (Rate Ratio (RR) 2.06, 95% Confidence Interval (CI) (1.90, 2.22), p < 0.0001). HMR rates increased in the intervention group compared with the comparison group (p < 0.0001). HMR rates increased in the intervention group GPs compared with the comparison group (RR 1.79, 95% CI (1.58, 2.02), p < 0.0001). Patient-specific feedback provided to GPs, supported by educational material mailed directly to their patients increased HMR rates for targeted veterans and increased GP participation in the delivery of HMRs.
Publisher: Elsevier BV
Date: 10-2019
Abstract: To provide insights into complexities of seeking access to state and federal cross-jurisdictional data for linkage with the Australian Childhood Immunisation Register (ACIR). We provide recommendations for improving access and receipt of linked datasets involving Australian Government-administered data. We describe requirements for linking eleven federal and state data sources to establish a national linked dataset for safety evaluation of vaccines. The required data linkage methodology for integrating cross-jurisdictional data sources is also described. Extensive negotiation was required with 18 different agencies for 21 separate authorisations and 12 ethics approvals. Three variations of the 'best practice' linkage model were implemented. Australian Government approval requests spanned nearly four years from initial request for data, with a further year before ACIR data transfer to the linkage agency. Integration of immunisation registers with other data collections is achievable in Australia but infeasible for routine and rapid identification of vaccine safety concerns. Lengthy authorisation requirements, convoluted disparate application processes and inconsistencies in data supplied all contribute to delayed data availability. Implications for public health: Delayed data access for safety surveillance prevents timely epidemiological reviews. Poor responsiveness to safety concerns may erode public confidence, compromising effectiveness of vaccination programs through reduced participation.
Publisher: Elsevier BV
Date: 09-2008
DOI: 10.1016/J.ARTH.2007.07.009
Abstract: Risk factors were investigated for revision for dislocation in primary total hip arthroplasties (THAs) between September 1, 1999, and December 31, 2004, as reported by the Australian Orthopaedic Association National Joint Replacement Registry. For 65992 primary THAs, the only initial diagnoses with significantly increased relative risk (RR) of revision for dislocation compared to osteoarthritis were fractured neck of femur (RR, 2.03 P < .001), rheumatoid arthritis (RR, 2.01 P < .01), and avascular necrosis (RR, 1.57 P < .05). A total of 58109 primary THAs for osteoarthritis were investigated for effect of age group, sex, and fixation method. There were 428 (0.7%) revisions for dislocation, 369 (0.8%) with a cementless acetabulum, and 59 (0.6%) with cemented acetabulum (RR, 1.59 P < .01). There is a significantly increasing risk of revision for dislocation as head size decreases (P < .001). Cementless acetabula, particularly with smaller heads, have a higher rate of revision for dislocation.
Publisher: SAGE Publications
Date: 03-2005
DOI: 10.2190/9AP6-DGY9-EY2Y-Q4M8
Abstract: Assisting patients to deal with loss is a major, yet unrecognized, role of general practitioners. Although instruments exist for measuring grief resulting from a given loss, such as bereavement, none exists that detects and measures grief from any loss. This study describes the development of the Grief Diagnostic Instrument for this purpose in general practice patients. Evaluation showed it to be a concise, valid, reliable and sensitive measure, and acceptable to general practice patients. The instrument investigates and measures grief from multiple losses rather than a single loss compared to other grief scales. Suggestions have been made for further validation studies. Its use in future grief research and clinical practice are described.
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.VACCINE.2018.11.025
Abstract: To determine whether differences in combination DTaP vaccine types at 2, 4 and 6 months of age were associated with mortality (all-cause or non-specific), within 30 days of vaccination. Observational nationwide cohort study. Linked population data from the Australian Childhood Immunisation Register and National Death Index. Australian infants administered a combination trivalent, quadrivalent or hexavalent DTaP vaccine (DTaP types) between January 1999 and December 2010 at 2, 4 and 6 months as part of the primary vaccination series. The study population included 2.9, 2.6, & 2.3 million children in the 2, 4 and 6 month vaccine cohorts, respectively. Infants were evaluated for the primary outcome of all-cause mortality within 30 days. A secondary outcome was non-specific mortality (unknown cause of death) within 30 days of vaccination. Non-specific mortality was defined as underlying or other cause of death codes, R95 'Sudden infant death syndrome', R96 'Other sudden death, cause unknown', R98 'Unattended death', R99 'Other ill-defined and unspecified cause of mortality' or where no cause of death was recorded. The rate of 30 day all-cause mortality was low and declined from 127.4 to 59.3 deaths per 100,000 person-years between 2 and 6 month cohorts. When compared with trivalent DTaP vaccines, no elevated risk in all-cause or non-specific mortality was seen with any quadrivalent or hexavalent DTaP vaccines, for any cohort. Use of routine DTaP combination vaccines with differing disease antigens administered during the first six months of life is not associated with infant mortality.
Publisher: Springer Science and Business Media LLC
Date: 24-08-2021
DOI: 10.1186/S13063-021-05486-0
Abstract: This a priori statistical analysis plan describes the analysis for CRISTAL. CRISTAL (cluster-randomised, crossover, non-inferiority trial of aspirin compared to low molecular weight heparin for venous thromboembolism prophylaxis in hip or knee arthroplasty, a registry nested study) aims to determine whether aspirin is non-inferior to low molecular weight heparin (LMWH) in preventing symptomatic venous thromboembolism (VTE) following hip arthroplasty (HA) or knee arthroplasty (KA). The study is nested within the Australian Orthopaedic Association National Joint Replacement Registry. The trial was commenced in April 2019 and after an unplanned interim analysis, recruitment was stopped (December 2020), as the stopping rule was met for the primary outcome. The clusters comprised hospitals performing 250 HA and/or KA procedures per annum, whereby all adults ( 18 years) undergoing HA or KA were recruited. Each hospital was randomised to commence with aspirin, orally, 85–150 mg daily or LMWH (enoxaparin), 40 mg, subcutaneously, daily within 24 h postoperatively, for 35 days after HA and 14 days after KA. Crossover was planned once the registration target was met for the first arm. The primary end point is symptomatic VTE within 90 days. Secondary outcomes include readmission, reoperation, major bleeding and death within 90 days, and reoperation and patient-reported pain, function and health status at 6 months. The main analyses will focus on the primary and secondary outcomes for patients undergoing elective primary total HA and KA for osteoarthritis. The analysis will use an intention-to-treat approach with cluster summary methods to compare treatment arms. As the trial stopped early, analyses will account for incomplete cluster crossover and unequal cluster sizes. This paper provides a detailed statistical analysis plan for CRISTAL. Australian and New Zealand Clinical Trials Registry ACTRN12618001879257 . Registered on 19/11/2018.
Publisher: SAGE Publications
Date: 11-04-2018
Abstract: This study examined the use of potentially inappropriate medicines that may affect cognition (PIMcog) in people with dementia and its associated factors. Medical records of all outpatients with dementia attending a tertiary hospital in Vietnam between January 1, 2015, and December 31, 2016, were examined. Medicine use was assessed against a list of PIMcog. Variables associated with having a PIMcog were assessed using a multiple logistic regression. Of the 128 patients, 41% used a PIMcog, 39.1% used cholinesterase inhibitors (CEIs) concomitantly with anticholinergics, and 18% used antipsychotics. The number of hospital visits (adjusted odds ratio [OR]: 1.08 95% confidence interval [CI]: 1.02-1.16) and number of treating specialists (adjusted OR: 0.61 95% CI: 0.45-0.83) were associated with PIMcog use. This study highlights a high-level use of medicines that can further impair cognition or reduce the effectiveness of CEIs in people with dementia. Efforts to improve quality use of medicines for this population are warranted.
Publisher: Springer Science and Business Media LLC
Date: 21-01-2016
DOI: 10.1007/S40264-015-0391-8
Abstract: The potential for routine sequence symmetry analysis (SSA) signal detection in health claims databases to detect new safety signals of medicines is unknown. Our objective was to assess the potential utility of SSA as a signal detection tool in health claims data for detecting medicines with potential heart failure (HF) adverse event signals. We applied the SSA method to all subsidized single-ingredient medicines in Australia. The source of data was the Australian Government Department of Veterans' Affairs (DVA) administrative claims database using data collected between 2002 and 2011. We used first ever HF hospitalization and frusemide initiation as indicators for HF. A signal was considered to be present if the lower limit of the 95 % confidence interval for the adjusted sequence ratio was greater than one. To identify potential new signals of HF, we excluded medicines where HF or edema was listed in the product information (PI) of that medicine or for any other medicine in the same class. We also excluded medicines that were used in HF treatment and medicines indicated for diseases that may contribute to the development of HF. We tested 691 medicines. HF signals were detected for 12 % (80/691) using the hospitalization event and 22 % (153/691) using frusemide initiation. Among medicines that did not have HF listed in the PI, SSA found 11 % (44/397) associated with HF hospitalization and 15 % (60/397) associated with frusemide initiation. Of the medicines tested in which no other medicine in the same class had HF or edema in the PI, and where the medicine was not indicated for a disease that is a risk factor for HF, potential new signals were generated for 2-3 % of these medicines tested (12 of 397 medicines using HF hospitalization and 9 of 397 medicines using frusemide initiation). SSA generated potential new signals of HF for some anti-glaucoma and anti-dyspepsia medicines. For some of the potential signals, the event is biologically plausible and some have pre-marketing and post-marketing case reports to support the finding. Confirmation of these signals using cohort studies is required.
Publisher: BMJ
Date: 11-2019
DOI: 10.1136/BMJOPEN-2019-031657
Abstract: Venous thromboembolism (VTE) is a serious complication following hip arthroplasty (HA) and knee arthroplasty (KA). This study aims to determine whether aspirin is non-inferior to low molecular weight heparin (LMWH) in preventing symptomatic VTE following HA and KA. This is a cluster randomised, crossover, non-inferiority, trial nested within the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR). The clusters will consist of Australian hospitals performing at least 250 HA and/or KA procedures per annum. All adult patients undergoing HA or KA will be included. The intervention will be aspirin, orally, 85–150 mg daily. The comparator will be LMWH (enoxaparin) 40 mg, subcutaneously, daily. Both drugs will commence within 24 hours postoperatively and continue for 35 days after HA and 14 days after KA. Each hospital will be randomised to commence with aspirin or LMWH and then crossover to the alternative treatment after meeting the recruitment target. Data will be collected through the AOANJRR via patient-reported surveys. The primary outcome is symptomatic VTE within 90 days post surgery, verified by AOANJRR staff. The primary analysis will include only patients undergoing elective primary total hip arthroplasty and total knee arthroplasty for osteoarthritis. Secondary outcomes will include symptomatic VTE for all HA and KA (including partial and revision) within 90 days, readmission, reoperation, major bleeding and death within 90 days and reoperation, death and patient-reported pain, function and health status at 6 months. If aspirin is found to be inferior, a cost-effectiveness analysis will be conducted. The study will aim to recruit 15 562 patients from 31 hospitals. Ethics approval has been granted. Trial results will be submitted for publication. The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12618001879257, pre-results) and is endorsed by the Australia and New Zealand Musculoskeletal Clinical Trials Network.
Publisher: Springer Science and Business Media LLC
Date: 16-11-2014
DOI: 10.1007/S40264-013-0124-9
Abstract: The objective of post-marketing surveillance of medicines is to rapidly detect adverse drug reactions (ADRs). Early ADR detection will enable policy makers and health professionals to recognise adverse events that may not have been identified in pre-marketing clinical trials. Multiple methods exist for ADR signal detection. Traditional quantitative methods employed in spontaneous reports data have include reporting odds ratio (ROR), proportional reporting ratio (PRR) and Bayesian techniques. With the development of administrative health claims databases, additional methods such as sequence symmetry analysis (SSA) may be able to be employed routinely to confirm ADR signals. We tested the time to signal detection of quantitative ADR signalling methods in a health claims database (SSA) and in a spontaneous reporting database (ROR, PRR, Bayesian confidence propagation neural network) for rofecoxib-induced myocardial infarction and rosiglitazone-induced heart failure. This study demonstrated that all four signalling methods detected safety signals within 1-3 years of market entry or subsidisation of the medicines, and for both cases the signals were detected before post-marketing clinical trial results. By contrast, the trial results and subsequent warning or withdrawal were published 5-7 years after first marketing of these medicines. This case study highlights that a post-marketing quantitative method utilising administrative claims data can be a complementary tool to traditional quantitative methods employed in spontaneous reports that may help to verify safety signals detected in spontaneous reporting data.
Publisher: MDPI AG
Date: 18-12-2021
Abstract: Australia spends more than $20 billion annually on medicines, delivering significant health benefits for the population. However, inappropriate prescribing and medicine use also result in harm to in iduals and populations, and waste of precious health resources. Medication data linked with other routine collections enable evidence generation in pharmacoepidemiology the science of quantifying the use, effectiveness and safety of medicines in real-world clinical practice. This review details the history of medicines policy and data access in Australia, the strengths of existing data sources, and the infrastructure and governance enabling and impeding evidence generation in the field. Currently, substantial gaps persist with respect to cohesive, contemporary linked data sources supporting quality use of medicines, effectiveness and safety research exemplified by Australia’s limited capacity to contribute to the global effort in real-world studies of vaccine and disease-modifying treatments for COVID-19. We propose a roadmap to bolster the discipline, and population health more broadly, underpinned by a distinct capability governing and streamlining access to linked data assets for accredited researchers. Robust real-world evidence generation requires current data roadblocks to be remedied as a matter of urgency to deliver efficient and equitable health care and improve the health and well-being of all Australians.
Publisher: BMJ
Date: 05-2019
DOI: 10.1136/BMJOPEN-2018-026486
Abstract: The aim of this study was to compare effectiveness and safety of low-strength and high-strength direct oral anticoagulants (DOACs) with warfarin in the Australian Veteran population. Sequential cohort study using inverse probability of treatment weighting (IPTW) and propensity score matching. Initiators of high-strength (apixaban 5 mg, dabigatran 150 mg, rivaroxaban 20 mg) and low-strength DOACS (apixaban 2.5 mg, dabigatran 110 mg, rivaroxaban 15 mg) were compared with warfarin initiators. Australian Government Department of Veterans’ Affairs claims database. 4836 patients who initiated oral anticoagulants (45.8%, 26.0% and 28.2% on low-strength, high-strength DOACs and warfarin, respectively) between August 2013 and March 2015. Mean age was 85, 75 and 83 years for low-strength, high-strength DOACs and warfarin initiators, respectively. One-year risk of hospitalisation for ischaemic stroke, any bleeding event or haemorrhagic stroke. Secondary outcomes were 1-year risk of hospitalisation for myocardial infarction and death. Using the IPTW method, no difference in risk of ischaemic stroke or bleeding was found with low-strength DOACs compared with warfarin. As a class, no increased risk of myocardial infarction was found for low-strength DOACs, however, risk was elevated for apixaban (HR 2.25, 95% CI 1.23 to 4.13). For high-strength DOACs, no difference was found for ischaemic stroke compared with warfarin, however, there was a significant reduction in risk of bleeding events (HR 0.63, 95% CI 0.44 to 0.89) and death (HR 0.40, 95% CI 0.28 to 0.58). Propensity score matching showed no difference in risk of ischaemic stroke or bleeding. We found that in the practice setting both DOAC formulations were similar to warfarin with regard to effectiveness and had no increased risk of bleeding.
Publisher: Wiley
Date: 05-2016
DOI: 10.1111/IMJ.6_13112
Publisher: Springer Science and Business Media LLC
Date: 08-06-2012
Publisher: Wiley
Date: 07-09-2023
DOI: 10.1002/PDS.5522
Abstract: Infection is a major complication following joint replacement (JR) surgery. However, little data exist regarding antibiotic utilisation following primary JR and how use changes with subsequent revision surgery. This study aimed to examine variation in antibiotic utilisation rates before and after hip replacement surgery in those revised for infection, revised for other reasons and those without revision. This retrospective cohort analysis used linked data from the Australian Orthopaedic Association National Joint Replacement Registry and Australian Government Pharmaceutical Benefits Scheme. Patients were included if undergoing total hip replacement (THR) for osteoarthritis in private hospitals between 2002 and 2017. Three groups were examined: primary THR with no subsequent revision (n = 102 577), primary THR with a subsequent revision for reasons other than periprosthetic joint infection (PJI) (n = 3156) and primary THR with a subsequent revision for PJI (n = 520). Monthly antibiotic utilisation rates and prevalence rate ratios (PRRs) with 95% confidence intervals (CIs) were calculated in the 2 years pre- and post-THR. Prior to primary THR antibiotic utilisation was 9%-10%. After primary THR, antibiotic utilisation rates were higher among patients revised for PJI (PRR 1.69, 95% CI 1.60-1.79) compared to non-revised patients, while the utilisation rate was lower in patients revised for reasons other than infection (PRR 0.96, 95% CI 0.93-0.98). For those revised for infection, antibiotic utilisation post-revision surgery was two times higher than those revised for other reasons (PRR 2.16, 95% CI 2.08-2.23). Utilisation of injectable antibiotics including, vancomycin, flucloxacillin and cephazolin was higher in those revised for PJI patients 0-2 weeks following surgery but not in those revised for other reasons compared to the non-revised group. Ongoing antibiotic utilisation after primary surgery may be an early signal of problems with the THR and should be a prompt for primary care physicians to refer patients to specialists for further appropriate investigations and management.
Publisher: Bentham Science Publishers Ltd.
Date: 07-2013
DOI: 10.2174/15748863113089990030
Abstract: While it is well known that randomized controlled trials (RCTs) are usually designed with sufficient s le size and power to detect the efficacy but not safety of a medicine, the extent to which RCTs quantify safety has not been well ascertained. The aim of this study was to assess the safety data available for five commonly prescribed medicines at the time of marketing. Published RCTs for five medicines risperidone, sertraline, donepezil, strontium ranelate and tramadol extended release were identified. All adverse events (AEs) in the trials were independently extracted by two clinical researchers. Using the s le size in the trials, the power to detect the observed difference in AEs rates between the treatment and placebo groups was calculated. A power of 80% or more was deemed adequate to detect AEs studies with power of < 80% were deemed insufficiently powered to detect AEs. 12 RCTs were identified. Six trials were insufficiently powered to detect any of the potential AEs reported. Of the 150 evaluated AEs, the trials were insufficiently powered to detect 81% (122/150) of the AEs reported. For the adverse events that were detected with adequate powered clinical trials, only 53% (10/19) of potentially very common AEs (≥10%) and 17% (18/106) of potentially common AEs (1%-<10%) were identified. Trials are insufficiently powered to detect the majority of adverse events that are reported in clinical trials, even for common adverse events. Observations other than primary efficacy endpoints such as AEs that are not prespecified with adequate power should be treated as hypothesis generating only and not justification of evidence. Claims of safety based on trial evidence not designed for the safety endpoint are often premature.
Publisher: Springer Science and Business Media LLC
Date: 2008
DOI: 10.2165/00002018-200831110-00004
Abstract: Cyclo-oxygenase (COX)-2 inhibitors were introduced to world markets with claims of improved gastrointestinal safety compared with traditional NSAIDs. Randomized clinical trials had demonstrated fewer adverse gastrointestinal events with COX-2 inhibitors, but no difference with other adverse events, including adverse renal events. There was a rapid uptake of these medicines. To compare uptake rates of NSAIDs, including COX-2 inhibitors, in a reference population with those in two high-risk populations: a population taking medicines affecting the renin-angiotensin system and loop diuretics, and a population taking medicines for diabetes mellitus. An observational study was undertaken in which the Department of Veterans' Affairs claims dataset was used to identify: veterans dispensed ACE inhibitors (ACEIs) or angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) and furosemide (ACEI-ARB/furosemide cohort) veterans dispensed medicines for diabetes (diabetes cohort) and all other veterans (reference cohort) from July 1999 to July 2007. Concurrent dispensing of NSAIDs was assessed. Prior to celecoxib becoming subsidized in Australia, the baseline level of NSAID use was 19.5% in the reference cohort, 15.3% in the diabetes cohort and 15.6% in the ACEI-ARB/furosemide cohort. After the listing of celecoxib, utilization of NSAIDs increased by 42.2% in the reference cohort, with similar increases in the diabetes cohort (40.8% p = 0.88 compared with the reference cohort) and the ACEI-ARB/furosemide cohort (49.6% p = 0.09 compared with the reference cohort). With the withdrawal of rofecoxib, utilization of NSAIDs in the reference cohort fell by 25.3%, with similar falls in the diabetes cohort (24% p = 0.28 compared with the reference cohort) and the ACEI-ARB/furosemide cohort (26.1% p = 0.43 compared with the reference cohort). Despite the increased vulnerability of veterans receiving ACEI-ARB/furosemide or diabetes medicines to adverse events of NSAIDs, uptake rates of COX inhibitors were equivalent to the rest of the veteran population. This suggests the gastrointestinal safety messages were interpreted broadly by prescribers and the adverse renal effects were not considered.
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.JBI.2018.07.013
Abstract: Drug safety issues such as Adverse Drug Events (ADEs) can cause serious consequences for the public. The clinical trials that are undertaken to assess medicine efficacy and safety prior to marketing, generally, may provide sufficient s les for discovering common ADEs. However, more s les are needed to detect infrequent and rare events. Additionally, clinical trials may not include all subgroups of patients. For these reasons, post-marketing surveillance of medicines is necessary for identifying drug safety issues. Most regulatory agencies use the Spontaneous Reporting Systems to identify associations between medicines and suspected ADEs. Data mining with effective analytical frameworks and large-scale medical data is potentially an alternative method to discover and monitor ADEs. In the present paper, we aim to detect potential ADEs from prescription data by discovering ADE associated prescription sequences. In an ADE associated prescription sequence 〈D
Publisher: Royal College of General Practitioners
Date: 30-09-2023
Abstract: Health emergencies disproportionally affect vulnerable populations. Digital tools can help primary care providers find, and reach, the right patients. To evaluate whether digital interventions delivered directly to GPs’ clinical software were more effective at promoting primary care appointments during the COVID-19 pandemic than interventions delivered by post. Real-world, non-randomised, interventional study involving GP practices in all Australian states. Intervention material was developed to promote care coordination for vulnerable older veterans during the COVID-19 pandemic, and sent to GPs either digitally to the clinical practice software system or in the post. The intervention material included patient-specific information sent to GPs to support care coordination, and education material sent via post to veterans identified in the administrative claims database. To evaluate the impact of intervention delivery modalities on outcomes, the time to first appointment with the primary GP was measured a Cox proportional hazards model was used, adjusting for differences and accounting for pre-intervention appointment numbers. The intervention took place in April 2020, during the first weeks of COVID-19 social distancing restrictions in Australia. GPs received digital messaging for 51 052 veterans and postal messaging for 26 859 veterans. The digital group was associated with earlier appointments (adjusted hazard ratio 1.38 [1.34 to 1.41]). Data-driven digital solutions can promote care coordination at scale during national emergencies, opening up new perspectives for precision public-health initiatives.
Publisher: Springer Science and Business Media LLC
Date: 14-07-2023
DOI: 10.1007/S40520-023-02491-Y
Abstract: Frailty is increasingly recognised as a dynamic syndrome, with multiple causes, dimensions and consequences. There is little understanding of how those frailty assessment metrics interact over time. The aim of this study was to describe the longitudinal correlation between five frailty metrics, namely multimorbidity, muscular strength, mood alterations, cognitive capacity, and functional capacity in a cohort study of aged care (nursing home) residents. 248 aged care residents with Frailty Index at baseline of 0.4 and no dementia were followed for 12 months. A multimorbidity score and an activity of daily living limitation score were created using in idual items of the Frailty Index. Muscular strength was measured by grip strength. Cognitive capacity was measured using the Montreal Cognitive Assessment (MoCA) test. Mood alterations were measured using the anxiety/depression screening question from EQ-5D. We analysed the inter-in idual correlation at baseline, association between baseline and future change, and within-in idual correlation at baseline, 6 and 12 months. Population analysis shows that metrics were not associated at baseline. All of the studied metrics at baseline were associated with change in 12 months, with the exception of anxiety/depression scores. Pairwise within-in idual correlation was strong between MoCA and grip strength (0.13, p = 0.02) and activity of daily living (− 0.48, p 0.001), and between activities of daily living and multimorbidity index (0.28, p 0.001). No within-in idual correlation was found between anxiety depression score and other metrics. The results suggest an interdependence between comorbidities, physical capacity, cognition and activities of daily living in aged care residents. Comprehensive measurement of frailty-related metrics may provide improved understanding of frailty progression at later life stages.
Publisher: Oxford University Press (OUP)
Date: 08-2020
Abstract: To demonstrate the application of the Large-scale Evidence Generation and Evaluation across a Network of Databases (LEGEND) principles described in our companion article to hypertension treatments and assess internal and external validity of the generated evidence. LEGEND defines a process for high-quality observational research based on 10 guiding principles. We demonstrate how this process, here implemented through large-scale propensity score modeling, negative and positive control questions, empirical calibration, and full transparency, can be applied to compare antihypertensive drug therapies. We assess internal validity through covariate balance, confidence-interval coverage, between-database heterogeneity, and transitivity of results. We assess external validity through comparison to direct meta-analyses of randomized controlled trials (RCTs). From 21.6 million unique antihypertensive new users, we generate 6 076 775 effect size estimates for 699 872 research questions on 12 946 treatment comparisons. Through propensity score matching, we achieve balance on all baseline patient characteristics for 75% of estimates, observe 95.7% coverage in our effect-estimate 95% confidence intervals, find high between-database consistency, and achieve transitivity in 84.8% of triplet hypotheses. Compared with meta-analyses of RCTs, our results are consistent with 28 of 30 comparisons while providing narrower confidence intervals. We find that these LEGEND results show high internal validity and are congruent with meta-analyses of RCTs. For these reasons we believe that evidence generated by LEGEND is of high quality and can inform medical decision-making where evidence is currently lacking. Subsequent publications will explore the clinical interpretations of this evidence.
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.ARTH.2015.05.004
Abstract: This study evaluated the association and predictive ability of co-morbidities measured by RxRisk-V, Elixhauser and Charlson measures and post-total hip (THA) and total knee arthroplasties (TKA) infection. THAs and TKAs (2001-2012) were identified using the Australian Department of Veterans' Affairs data. Infections within 90 days post-surgery were the study endpoint. Co-morbidities were identified using pharmacy (RxRisk-V) and hospitalization history (Elixhauser, Charlson). Of the 11,848 THAs, 3.1% (N = 364) had infections and out of 18,972 TKAs 3.4% (N = 648). Comorbidity burden and specific conditions were associated with infection likelihood. RxRisk-V performed better than other measures, but none had high predictive ability and differences were small. The best performing infection prediction models resulted when a combination of conditions identified by all measures was used.
Publisher: American Medical Association (AMA)
Date: 09-06-2023
DOI: 10.1001/JAMANETWORKOPEN.2023.17838
Abstract: Ischemic heart disease remains the leading cause of mortality following hip and knee arthroplasty. Due to its antiplatelet and cardioprotective properties, aspirin has been proposed as an agent that could reduce mortality when used as venous thromboembolism (VTE) prophylaxis following these procedures. To compare aspirin with enoxaparin in reducing 90-day mortality for patients undergoing hip or knee arthroplasty procedures. This study was a planned secondary analysis of the CRISTAL cluster randomized, crossover, registry-nested trial performed across 31 participating hospitals in Australia between April 20, 2019, and December 18, 2020. The aim of the CRISTAL trial was to determine whether aspirin was noninferior to enoxaparin in preventing symptomatic VTE following hip or knee arthroplasty. The primary study restricted the analysis to patients undergoing total hip or knee arthroplasty for a diagnosis of osteoarthritis only. This study includes all adult patients (aged ≥18 years) undergoing any hip or knee arthroplasty procedure at participating sites during the course of the trial. Data were analyzed from June 1 to September 6, 2021. Hospitals were randomized to administer all patients oral aspirin (100 mg daily) or subcutaneous enoxaparin (40 mg daily) for 35 days after hip arthroplasty and 14 days after knee arthroplasty procedures. The primary outcome was mortality within 90 days. The between-group difference in mortality was estimated using cluster summary methods. A total of 23 458 patients from 31 hospitals were included, with 14 156 patients allocated to aspirin (median [IQR] age, 69 [62-77] years 7984 [56.4%] female) and 9302 patients allocated to enoxaparin (median [IQR] age, 70 [62-77] years 5277 [56.7%] female). The mortality rate within 90 days of surgery was 1.67% in the aspirin group and 1.53% in the enoxaparin group (estimated difference, 0.04% 95% CI, −0.05%-0.42%). For the subgroup of 21 148 patients with a nonfracture diagnosis, the mortality rate was 0.49% in the aspirin group and 0.41% in the enoxaparin group (estimated difference, 0.05% 95% CI, −0.67% to 0.76%). In this secondary analysis of a cluster randomized trial comparing aspirin with enoxaparin following hip or knee arthroplasty, there was no significant between-group difference in mortality within 90 days when either drug was used for VTE prophylaxis. anzctr.org.au Identifier: ACTRN12618001879257
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: Frontiers Media SA
Date: 29-08-2022
DOI: 10.3389/FPHAR.2022.978871
Abstract: Aim: To examine the incidence and nature of medicine-related problems over time experienced by nursing home residents. Method: We analyzed records collected in the Reducing Medicine-Induced Deterioration and Adverse Events (ReMInDAR) trial. The trial pharmacists provided services to reduce medicine-induced deterioration and adverse reactions for residents every 8-weeks over a year. The problems identified by the pharmacists were documented in reports and subsequently classified independently by research pharmacists using the D.O.C.U.M.E.N.T system. The number and type of problems at each service and time to develop a new problem post first session were assessed. All analyses were performed using R software (Version 4.1.1). Results: The cohort was 115 nursing home residents who received 575 services. In the 12-months, a total of 673 medicine-related problems or symptom reports were identified in 112 residents. Most residents (75%) experienced a new medicine-related problem by the fourth month post the first assessment. After the first session, the proportion of residents with a new medicine-related problem or symptom report declined at each repeated pharmacy session (59% at visit 2 vs. 28% at visit 6, p & 0.01). Conclusion: Residents living in nursing homes frequently experience medicine-related problems. Our results suggest clinical pharmacist services performed every 4-months may have the potential to reduce the medicine-related problems in nursing homes.
Publisher: Springer Science and Business Media LLC
Date: 25-06-2019
DOI: 10.1007/S11096-019-00866-8
Abstract: Background Internationally, antipsychotics are frequently initiated during hospital admission for older patients and use often continues post-discharge without indication. We located no Australian studies on this topic. Objective to identify the hospital admissions (excluding psychosis) associated with antipsychotic initiation and continuation in older Australians. Setting Australian Government Department of Veterans' Affairs. Method Retrospective analysis of administrative claims data for people admitted to hospital from 1 January 2014 to 31 December 2014, aged ≥ 65 years, who were antipsychotic naïve. Main outcome measure number of admissions associated with antipsychotic initiation, and the major diagnosis groups for these admissions. Where antipsychotics were initiated, we determined the time to cessation of antipsychotics after discharge. Results There were 142,009 hospital admissions for 66,415 people with a median age of 86 years. 921 (0.65%) admissions were associated with antipsychotic initiation, most commonly where the primary diagnoses were for mental and behavioural disorders excluding psychosis (17.8%) and injuries (16%). Fourteen percent of antipsychotic initiations were for primary diagnoses of delirium or dementia. When secondary diagnoses were considered, 55% of antipsychotic initiations were associated with delirium, dementia or both. The median duration of use among people who used antipsychotics was 132 days, and 40% continued use until death or one year follow-up. Conclusion Initiation of antipsychotics during hospital admissions was not frequent in this Australian population. Amongst those who did initiate antipsychotics, for almost half no diagnosis corresponding with an approved indication for use was recorded and long-term use of up to one year was common.
Publisher: Wiley
Date: 08-05-2013
DOI: 10.1002/PDS.3439
Publisher: AMPCo
Date: 11-2011
DOI: 10.5694/MJA11.10055
Abstract: To determine the risk of stroke associated with non-steroidal anti-inflammatory drug (NSAID) use. Retrospective cohort study of 162,065 Australian veterans with incident dispensing of an NSAID between 1 January 2001 and 31 December 2008, using prescription event sequence symmetry analysis. Hospitalisation for stroke, ischaemic stroke or haemorrhagic stroke. The absolute risk of stroke was low: 7.1/1000 people/year. Incident use of NSAIDs was associated with a 1.88 times increased risk (95% CI, 1.70-2.08) of hospitalisation for stroke (ischaemic or haemorrhagic) following first ever dispensing of an NSAID. This equates to an increased absolute risk of 13.4 strokes/1000 people/year. Significant positive associations between starting an NSAID and having a hospitalisation for stroke were found for most NSAIDs, with adjusted sequence ratios ranging from 1.44 (95% CI, 1.16-1.80) for indomethacin to 1.80 (95% CI, 1.59-2.04) for rofecoxib. Incident use of NSAIDs was associated with an increased risk of stroke. Increased awareness of the potential for serious adverse cardiovascular events, together with in idual assessment of cardiovascular risk, careful deliberation of the balance between risk and benefits and appropriate supervision, is required when initiating NSAID therapy.
Publisher: Frontiers Media SA
Date: 03-11-2022
DOI: 10.3389/FMED.2022.1010444
Abstract: Large population-based studies examining frailty trajectory found a linear increase in frailty over time. The pattern in which frailty changes over time for an in idual person is less well-described. We examined the frailty trajectory of older adults living in aged-care in Australia. This secondary study used data from a randomised controlled trial involving 39 aged-care facilities in Australia. The trial intervention was an on-going pharmacist-led intervention occurring every 8 weeks over 12 months aimed at preventing medicine-induced deterioration and adverse reactions. Frailty was assessed using the Frailty Index. Participants were categorised as non-frail, pre-frail and frail. In idual frailty trajectory over 12 months was visualised using the alluvial plot. Case notes were examined to explore reasons for any rapid transitions in frailty status. A total of 248 participants was included. At baseline, 40.3% were non-frail and 59.7% were pre-frail. The proportion of participants who were non-frail and pre-frail decreased over time 15.7% were frail at 6 months and 23.4% were frail at 12 months. Overall, twenty different combinations of frailty transitions were identified over 12 months. Retrospective analysis of case notes suggest that death or transition from non-frail to frail was often preceded by hospitalisation, falls, medication change or clinically significant deterioration in grip strength or cognition. The degree of frailty increased over time, but there were variations in the in idual trajectories. Regular monitoring of events that precede changes in frailty status is needed to identify strategies to prevent further deterioration in residents’ conditions.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2010
DOI: 10.2106/JBJS.H.01882
Publisher: Elsevier BV
Date: 07-2020
Publisher: Wiley
Date: 09-2003
DOI: 10.1046/J.1365-2923.2003.01596.X
Abstract: To determine the association between rural undergraduate training, rural postgraduate training and medical school entry criteria favouring rural students, on likelihood of working in rural Australian general practice. National case-control study of 2414 rural and urban general practitioners (GPs) s led from the Health Insurance Commission database. Participants completed a questionnaire providing information on demographics, current practice location and rural undergraduate and postgraduate experience. Rural GPs were more likely to report having had any rural undergraduate training [odds ratio (OR) 1.61, 95% confidence interval (CI) 1.32-1.95] than were urban GPs. Rural GPs were much more likely to report having had rural postgraduate training (OR 3.14, 95% CI 2.57-3.83). As the duration of rural postgraduate training increased so did the likelihood of working as a rural GP: those reporting that more than half their postgraduate training was rural were most likely to be rural GPs (OR 10.52, 95% CI 5.39-20.51). South Australians whose final high school year was rural were more likely to be rural GPs (OR 3.18, 95% CI 0.99-10.22). Undergraduate rural training, postgraduate training and medical school entry criteria favouring rural students, all are associated with an increased likelihood of being a rural GP. Longer rural postgraduate training is more strongly associated with rural practice. These findings argue for continuation of rural undergraduate training opportunities and rural entry schemes, and an expansion in postgraduate training opportunities for GPs.
Publisher: The Royal Australian College of General Practitioners
Date: 02-2021
Publisher: Informa UK Limited
Date: 05-2018
DOI: 10.2147/PPA.S150142
Publisher: Elsevier BV
Date: 2017
Publisher: Wiley
Date: 16-04-2010
DOI: 10.1002/PDS.1942
Abstract: Observational studies have investigated the comparative safety of antipsychotics with varying results. Instrumental variable analysis has been suggested as a possible alternative to conventional analyses when there is concern about the effect of unmeasured confounding in observational studies. Using the ex le of the risk of death with typical compared to atypical antipsychotics, we aimed to explore the performance of two different instruments. We used the doctor prescribing preference instrument, which has been used in previous studies, to investigate further the assumptions of this instrument in the Australian population. We also propose an alternative instrument, nursing home facility preference. With the Australian Department of Veterans' Affairs administrative claims database, we used an instrumental variable analysis to compare the risk of death after 12 months between the two antipsychotic classes. Using the doctor prescribing preference instrument we estimated that typical antipsychotics were associated with an extra 24 (95% Confidence Interval (CI) 18-30) deaths per 100 patients per year compared to atypical antipsychotics, and an extra 10 (95% CI 7-14) deaths per 100 patients per year among nursing home residents. Facility prescribing preference was a stronger instrument (OR=19.2 95% CI 17.1-21.6) and provided a better balance of covariates than doctor prescribing preference. Our study has shown that valid instruments in one population may not be directly applicable to other health care settings and testing of assumptions is crucial when performing IV analyses. Facility prescribing preference appears to be a potentially valid instrument for further work in this area.
Publisher: Wiley
Date: 10-10-2022
DOI: 10.1002/PDS.5507
Abstract: Ambiguity in communication of key study parameters limits the utility of real‐world evidence (RWE) studies in healthcare decision‐making. Clear communication about data provenance, design, analysis, and implementation is needed. This would facilitate reproducibility, replication in independent data, and assessment of potential sources of bias. The International Society for Pharmacoepidemiology (ISPE) and ISPOR–The Professional Society for Health Economics and Outcomes Research (ISPOR) convened a joint task force, including representation from key international stakeholders, to create a harmonized protocol template for RWE studies that evaluate a treatment effect and are intended to inform decision‐making. The template builds on existing efforts to improve transparency and incorporates recent insights regarding the level of detail needed to enable RWE study reproducibility. The overarching principle was to reach for sufficient clarity regarding data, design, analysis, and implementation to achieve 3 main goals. One, to help investigators thoroughly consider, then document their choices and rationale for key study parameters that define the causal question (e.g., target estimand), two, to facilitate decision‐making by enabling reviewers to readily assess potential for biases related to these choices, and three, to facilitate reproducibility. Recognizing that the impact of this harmonized template relies on uptake, we have outlined a plan to introduce and pilot the template with key international stakeholders over the next 2 years. The HARmonized Protocol Template to Enhance Reproducibility (HARPER) helps to create a shared understanding of intended scientific decisions through a common text, tabular and visual structure. The template provides a set of core recommendations for clear and reproducible RWE study protocols and is intended to be used as a backbone throughout the research process from developing a valid study protocol, to registration, through implementation and reporting on those implementation decisions.
Publisher: BMJ
Date: 04-2019
DOI: 10.1136/BMJOPEN-2018-023990
Abstract: To determine time to opioid cessation post discharge from hospital in persons who had been admitted to hospital for a surgical procedure and were previously naïve to opioids. Retrospective cohort study using administrative health claims database from the Australian Government Department of Veterans’ Affairs (DVA). DVA gold card holders aged between 18 and 100 years who were admitted to hospital for a surgical admission between 1 January 2014 and 30 December 2015 and naïve to opioid therapy prior to admission were included in the study. Gold card holders are eligible for all health services that DVA funds. The outcome of interest was time to cessation of opioids, with follow-up occurring over 12 months. Cessation was defined as a period without an opioid prescription that was equivalent to three times the estimated supply duration. The proportion who became chronic opioid users was defined as those who continued taking opioids for greater than 90 days post discharge. Cumulative incidence function with death as a competing event was used to determine time to cessation of opioids post discharge. In 2014–2015, 24 854 persons were admitted for a surgical admission. In total 3907 (15.7%) were discharged on opioids. In total 3.9% of those discharged on opioids became chronic users of opioids. The opioid that the patients were most frequently discharged with was oxycodone oxycodone alone accounted for 43%, while oxycodone with naloxone accounted for 8%. Opioid initiation post-surgical hospital admission leads to chronic use of opioids in a small percentage of the population. However, given the frequency at which surgical procedures occur, this means that a large number of people in the population may be affected. Post-discharge assessment and follow-up of at-risk patients is important, particularly where psychosocial elements such as anxiety and catastrophising are identified.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Hindawi Limited
Date: 14-02-2015
DOI: 10.1111/JCPT.12249
Abstract: Hospital admissions associated with an adverse drug reaction are often coded to the International Classification of Diseases external cause Y-codes, denoting the medicine class deemed to cause the adverse drug reaction. Matching hospital data with outpatient dispensing data has the potential to identify the specific causative medicines but the ability to identify the causative medicines in this way has not been previously assessed. This study aimed to determine the proportion of Y-coded hospitalizations for drug-induced hepatotoxicity that could be matched with a potential causative medicine from outpatient dispensing data. A retrospective cohort study was undertaken from 1 Jan 2005 to 30 June 2012 using data from the Australian Government Department of Veterans' Affairs of all admissions coded to drug-induced hepatotoxicity. Medicine use in the 6 months prior to hospitalization was examined to identify the probable causative medicines. Thirty five admissions were identified for 31 patients. All admissions were preceded by use of medicines known to cause hepatotoxicity. Twenty four admissions had a Y-code recorded, of which 19 admissions had at least one Y-code specifying the causative medicine class (22 Y-codes). Of the 22 Y-codes, 95% could be successfully matched with a medicine from the same class that had been dispensed in the 6 months prior to admission. Further, 92% were preceded by use of multiple hepatotoxic medicines. Results of our study demonstrate that hospital administrative data can be linked to prescription dispensing data to identify specific medicines suspected of causing the adverse drug reaction.
Publisher: Wiley
Date: 21-05-2013
DOI: 10.1002/PDS.3440
Abstract: To undertake a multi-country study to investigate the risk of acute hyperglycaemia with antipsychotic use. Using a distributed network model with a common minimal data set, we performed a prescription sequence symmetry analysis (PSSA) to investigate the risk of acute hyperglycaemia associated with antipsychotic initiation. Incident insulin prescriptions were used as a proxy indicator of acute hyperglycaemia. Participating countries and population datasets included Australia (300,000 persons), Japan I (300,000 persons), Japan II (200,000 persons), Korea (53 million persons) Taiwan (1 million persons), Sweden (9 million persons), USA-Public (87 million persons) and USA-Private (47 million persons). Olanzapine showed a trend towards increased risk in most databases, with a significant association observed in the USA-Public database (Adjusted sequence ratio (ASR) = 1.14 95% Confidence Interval (CI) 1.10-1.17) and Sweden (ASR = 1.53 95% CI 1.13-2.06). Null or negative associations were observed for haloperidol, quetiapine and risperidone. Acute hyperglycaemia appears to be associated with olanzapine use, however, this effect was only observed in two large databases. Despite different patterns of utilization of both antipsychotics and insulin, PSSA analysis results for in idual antipsychotic medicines were qualitatively similar across most countries. PSSA, used in conjunction with existing methods, may provide a simple and timely method further supporting multi-national drug safety monitoring.
Publisher: Informa UK Limited
Date: 27-09-2016
DOI: 10.1080/14740338.2016.1238071
Abstract: To determine the association between incident proton pump inhibitor (PPI) use and Clostridium difficile infections across multiple countries Method: National data covering the total population in Australia and Korea, the Canadian population over 65 years and a 3 million person random s le data set from Taiwan were assessed, as were data from a worker insurance population and a hospital inpatient/outpatient population in Japan. Sequence symmetry analysis was used to assess the association with oral vancomycin dispensing as the outcome of interest. 54,957 patients were included. Positive associations were observed in Australia adjusted sequence ratio (ASR) 2.48 (95% CI 1.90, 3.12), Korea ASR 2.15 (95%CI 2.11, 2.19), Canada ASR 1.45 (95% CI 1.16, 1.79), Japan hospital dataset ASR 3.21 (95%CI 2.12, 4.55) and Japan worker insurance dataset ASR 5.40 (95% CI 2.73, 8.75). The pooled result was ASR 2.40 (95%CI 1.88, 3.05) and 3.16 (95%CI 1.95, 5.10) when limited to Japan, Korean and Taiwan. Results did not vary by in idual PPI. The temporal analysis showed effects within the first two weeks of PPI initiation. Our study confirms the association between PPI initiation and C. difficile infections across countries in the Asia-Pacific region.
Publisher: Springer Science and Business Media LLC
Date: 07-2011
DOI: 10.2165/11588470-000000000-00000
Abstract: Antipsychotics are commonly used in the elderly to treat the behavioural symptoms of dementia. Randomized controlled trial data on the safety of antipsychotics are limited and little is known about the long-term effects of these medicines. Observational studies have investigated the risk of hip fracture and pneumonia associated with the use of antipsychotics, but varying results may be due to lack of control for unmeasured confounding. The aim of the study was to investigate the risk of hospitalization for hip fracture and pneumonia in elderly subjects exposed to antipsychotic medication using the self-controlled case-series design to control for unmeasured confounding. The source of data for this study was the Australian Government Department of Veterans' Affairs Health Care Claims Database. A self-controlled case-series design was used to measure the excess risk of hospitalization for hip fracture and pneumonia after antipsychotic exposure compared with no-exposure over the 4-year period from 2005 to 2008. There was a significantly increased risk of hip fracture 1 week after exposure to typical antipsychotics, and the risk remained significantly raised with >12 weeks of continuous exposure (incidence rate ratio [IRR] 2.19 95% CI 1.62, 2.95). The risk of hip fracture was highest in the first week after initiation of atypical antipsychotics (IRR 2.17 95% CI 1.54, 3.06). The risk then declined with longer-term treatment however, it remained significantly raised with >12 weeks of continuous exposure (IRR 1.43 95% CI 1.23, 1.66). The risk of hospitalization for pneumonia was raised in all post-exposure periods for both typical and atypical antipsychotics. Antipsychotic use in the elderly is associated with an increased risk of hospitalization for hip fracture and pneumonia. Given the increased risks of morbidity and mortality associated with these outcomes, practitioners should consider these additional risks when prescribing antipsychotics to treat behavioural symptoms of dementia in the elderly.
Publisher: Frontiers Media SA
Date: 06-07-2022
DOI: 10.3389/FPHAR.2022.893484
Abstract: Background: Routinely collected healthcare data such as administrative claims and electronic health records (EHR) can complement clinical trials and spontaneous reports to detect previously unknown risks of vaccines, but uncertainty remains about the behavior of alternative epidemiologic designs to detect and declare a true risk early. Methods: Using three claims and one EHR database, we evaluate several variants of the case-control, comparative cohort, historical comparator, and self-controlled designs against historical vaccinations using real negative control outcomes (outcomes with no evidence to suggest that they could be caused by the vaccines) and simulated positive control outcomes. Results: Most methods show large type 1 error, often identifying false positive signals. The cohort method appears either positively or negatively biased, depending on the choice of comparator index date. Empirical calibration using effect-size estimates for negative control outcomes can bring type 1 error closer to nominal, often at the cost of increasing type 2 error. After calibration, the self-controlled case series (SCCS) design most rapidly detects small true effect sizes, while the historical comparator performs well for strong effects. Conclusion: When applying any method for vaccine safety surveillance we recommend considering the potential for systematic error, especially due to confounding, which for many designs appears to be substantial. Adjusting for age and sex alone is likely not sufficient to address differences between vaccinated and unvaccinated, and for the cohort method the choice of index date is important for the comparability of the groups. Analysis of negative control outcomes allows both quantification of the systematic error and, if desired, subsequent empirical calibration to restore type 1 error to its nominal value. In order to detect weaker signals, one may have to accept a higher type 1 error.
Publisher: Research Square Platform LLC
Date: 27-10-2023
Publisher: Wiley
Date: 08-2018
DOI: 10.1002/PDS.4629
Publisher: Weston Medical Publishing
Date: 18-03-2020
Abstract: Introduction and aims: Mental health disorders and substance abuse are risk factors that both precede and follow chronic opioid use. We predicted that incident opioid users would have lower rates of mental health comorbidities than chronic opioid users, but that incident chronic opioid users would have lower rates of mental health comorbidities than prevalent chronic users.Design and methods: We used administrative health claims data to evaluate differences in lifetime mental health and substance abuse comorbidity profiles of people who were prevalent and incident chronic opioid users, as well as those who used opioids acutely. Results were stratified by age.Results: Over 5,188 people were prevalent chronic opioid users at study entry. Of the 10,079 people who initiated opioids, 10.2 percent had a subsequent chronic episode (incident chronic) and the remainder stopped within 90 days (incident acute). In prevalent chronic users compared to incident chronic users, rates of depression and anxiety were higher across all age groups (odds ratio (OR) across age groups range from = 1.60, 95 percent confidence interval (CI) = 1.35,1.89, to OR = 6.66, 95 percent CI = 3.02, 14.69) and prevalence of alcohol abuse was higher in those aged 55 to 74 years (OR = 5.11, 95 percent CI = 1.83, 14.24, p = 0.002). Acute users were less likely than incident chronic users to have depression and anxiety in those aged over 74 years (depression OR = 0.82, 95 percent CI = 0.70, 0.95 anxiety OR = 0.82, 95% CI 0.70, 0.98).Conclusions: Mental health morbidities commonly associated with chronic opioid use increase in prevalence as chronic use continues.
Publisher: Wiley
Date: 14-02-2013
DOI: 10.1002/PDS.3417
Abstract: To determine the validity of sequence symmetry analysis (SSA) method to detect adverse drug reactions from an administrative claims database. Published randomised controlled trials (RCTs) of 19 medicines were identified through search databases, product information (PI) or the US Food and Drug Administration Web site. All adverse events (AEs) in the RCTs and the PI for the medicines were extracted. AEs were considered 'gold standard positive events' if they were reported as being statistically significant events in adequately powered RCTs. The remaining AEs were considered 'gold standard negative events' if the event was not listed as an AE in the PI for that medicine or any other medicine in its class. Indicators of AEs were identified by consensus from two clinical researchers. SSA was run for each medicine-indicator pair using four different time windows: 3, 6, 9 and 12 months. A total of 120 randomised placebo controlled trials were reviewed for the 19 tested medicines. A total of 165 medicine-indicator pairs (44 positive and 121 negative events) were identified and tested by SSA. At the 12-month time window, the sensitivity, specificity, positive and negative predictive values of SSA were 61% (95%CI 0.46-0.74), 93% (95%CI 0.87-0.96), 77% (95%CI 0.61-0.88) and 87% (95%CI 0.80-0.92), respectively. Using a 3-month time window, the SSA had a lower sensitivity (52%). The SSA technique was found to have moderate sensitivity and high specificity for detecting ADRs. These results suggest that SSA is a potential tool for detecting ADRs using administrative claims data that could complement existing pharmacosurveillance methods.
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.JAMDA.2016.02.008
Abstract: Most studies assessing the effect of central nervous system (CNS)-acting medicines on cognitive disturbances have focused on the use of in idual medicines. The impact on cognitive function when another CNS-acting medicine is added to a patient's treatment regimen is not well known. To determine risk of hospitalization for confusion, delirium, or dementia in older people associated with increasing numbers of CNS-acting medicines taken concurrently, as well as the number of standard doses taken each day (measured as defined daily doses). Retrospective cohort study, from July 2011 to June 2012, using health claims data. Australian veteran population. A total of 74,321 community-dwelling in iduals aged 65 years and over, who were dispensed at least 1 CNS-acting medicine in the year before study entry. Patients with prior hospitalization for confusion or delirium, and those with dementia or receiving palliative care, were excluded. Hospitalization for confusion, delirium, or dementia. Over the 1-year study period, 401 participants were hospitalized with confusion, delirium, or dementia. Adjusted analyses showed the risk of hospitalization was 2.4 times greater with the use of 2 CNS-acting medicines compared with no use [incident rate ratio (IRR) 2.39, 95% confidence interval (CI) 1.79-3.19, P < .001], and more than 19 times greater when 5 or more CNS-acting medicines were taken concurrently (IRR 19.35, 95% CI 11.10-33.72, P < .001). Similarly, the risk of hospitalization was significantly increased among patients taking between 1.0 and 1.9 standard doses per day (IRR 2.64, 95% CI 1.99-3.50, P < .001) and between 2.0 and 2.9 standard doses per day (IRR 3.43, 95% CI 2.07-5.69, P < .001) compared with no use. Use of multiple CNS-acting medicines or higher doses is associated with an increased risk of hospitalization for confusion, delirium, or dementia. Health care professionals need to be alert to the contribution of CNS-acting medicines among patients presenting with confusion or delirium and consider strategies to reduce treatment burden where possible.
Publisher: Springer Science and Business Media LLC
Date: 22-09-2017
Publisher: Elsevier BV
Date: 12-2010
DOI: 10.1111/J.1753-6405.2010.00613.X
Abstract: Antipsychotics are commonly used in the elderly despite limited efficacy and safety data from randomised controlled trials. Observational comparative safety studies of antipsychotics vary, which may be due to confounding. To compare the characteristics of typical and atypical antipsychotic initiators. Using the Australian Government Department of Veterans' Affairs claims dataset, we compared patient and prescribing physician characteristics and health care utilisation between atypical and typical antipsychotic initiators. Significant independent predictors of use were calculated using a multivariate log-binomial model. Compared to patients initiated on typical antipsychotics (n=10,966), patients initiated on atypical antipsychotics (n=9,239) were less likely to be male (Relative Risk (RR)=0.91, 95% CI 0.89-0.94) and have prior dispensing of morphine (RR=0.53, 95% CI 0.49-0.57) and oral corticosteroids (RR=0.86, 95% CI 0.81-0.91) and to have been hospitalised for myocardial infarction or pneumonia. Patients initiated on atypical antipsychotics were more likely to be in aged care (RR=1.08, 95% CI 1.05-1.12), to be prescribed the medicine by their usual doctor (RR=1.12, 95% CI 1.09-1.16) and have prior dispensing of anticholinesterases (RR=1.19, 95% CI 1.15-1.23), antidepressants (RR=1.18 95% CI 1.15-1.22) and anti-parkinson medications (RR=1.30, 95% CI 1.25-1.36). Differences between typical and atypical antipsychotic initiators indicate the potential for confounding in observational studies. Future pharmacoepidemiogical research in Australia, investigating the adverse events of antipsychotics, should consider the variables identified in this study to control for confounding.
Publisher: Wiley
Date: 10-02-2023
DOI: 10.1111/DOM.14982
Abstract: Drug‐induced diabetes is underreported in conventional drug safety monitoring and may contribute to the increasing incidence of type 2 diabetes. Therefore, we used routinely collected prescription data to screen all commonly used drugs for diabetogenic effects. Leveraging the Danish nationwide health registries, we used a case‐only symmetry analysis design to evaluate all possible associations between drug initiation and subsequent diabetes. The study was conducted among in iduals aged ≥40 years with a first‐ever prescription for any antidiabetic drug 1996‐2018 (n = 348 996). Sequence ratios (SRs) and 95% confidence intervals (CIs) were obtained for all possible drug class‐diabetes combinations. A lower bound of the 95% CI .00 was considered a signal. Signals generated in Denmark were replicated using the Services Australia, Pharmaceutical Benefits Scheme 10% data extract. Overall, 386 drug classes were investigated, of which 70 generated a signal. In total, 43 were classified as previously known based on the SIDER database or a literature review, for ex le, glucocorticoids (SR 1.67, 95% CI 1.62‐1.72) and β‐blockers (SR 1.20, 95% CI 1.16‐1.23). Of 27 new signals, three drug classes yielded a signal in both the Danish and Australian data source: digitalis glycosides (SR 2.15, 95% CI 2.04‐2.27, and SR 1.76, 95% CI 1.50‐2.08), macrolides (SR 1.20, 95% CI 1.16‐1.24, and SR 1.11, 95% CI 1.06‐1.16) and inhaled β2‐agonists combined with glucocorticoids (SR 1.35, 95% CI 1.28‐1.42, and SR 1.14, 95% CI 1.06‐1.22). We identified 70 drug‐diabetes associations, of which 27 were classified as hitherto unknown. Further studies evaluating the hypotheses generated by this work are needed, particularly for the signal for digitalis glycosides.
Publisher: Weston Medical Publishing
Date: 2019
Abstract: Objective: Work that has shown a relationship between anxiety and chronic opioid use has not focused on older people specifically, despite the additional risks in older populations. This study aimed to understand whether anxiety prior to opioid initiation increased the likelihood of chronic opioid use over time in persons aged 60 years or older.Design: Administrative claims data were used to calculate time between initiation of opioids and a first chronic episode of opioid use. Patients were classified as having a history of anxiety if they were dispensed medicines in the anxiolytics class or had a hospitalization event for anxiety prior to treatment with an opioid. Proportional hazards models were used to compare the likelihood of experiencing a chronic episode of opioid use between those with and without a history of anxiety.Results: The cohort was 15,000 persons, of which, 5,076 (34 percent) had history of anxiety. Those with anxiety prior to their first opioid dispensing were 30 percent more likely to have an episode of chronic use after adjustment for age, gender, number of comorbidities, and prior surgery (HR = 1.30, 95% CI = 1.16-1.47). The risk of a chronic episode in patients who had surgery prior to initiation of an opioid was 60 percent greater in those with anxiety compared to no anxiety (HR = 1.60, 95% CI = 1.21-2.11) and 24 percent greater in those with anxiety but no prior surgery (HR = 1.24, 95% CI = 1.08-1.42).Conclusions: A significant proportion of older people will have a chronic episode of opioid use. This risk is increased where a history of anxiety is present.
Publisher: Springer Science and Business Media LLC
Date: 15-05-2014
Publisher: AMPCo
Date: 02-2016
DOI: 10.5694/MJA15.01000
Publisher: Frontiers Media SA
Date: 24-11-2021
DOI: 10.3389/FPHAR.2021.773875
Abstract: Using real-world data and past vaccination data, we conducted a large-scale experiment to quantify bias, precision and timeliness of different study designs to estimate historical background (expected) compared to post-vaccination (observed) rates of safety events for several vaccines. We used negative (not causally related) and positive control outcomes. The latter were synthetically generated true safety signals with incident rate ratios ranging from 1.5 to 4. Observed vs. expected analysis using within-database historical background rates is a sensitive but unspecific method for the identification of potential vaccine safety signals. Despite good discrimination, most analyses showed a tendency to overestimate risks, with 20%-100% type 1 error, but low (0% to 20%) type 2 error in the large databases included in our study. Efforts to improve the comparability of background and post-vaccine rates, including age-sex adjustment and anchoring background rates around a visit, reduced type 1 error and improved precision but residual systematic error persisted. Additionally, empirical calibration dramatically reduced type 1 to nominal but came at the cost of increasing type 2 error.
Publisher: Informa UK Limited
Date: 25-10-2018
DOI: 10.1080/03007995.2017.1384375
Abstract: To compare persistence in people who initiate the combination of amlodipine and statin as a fixed-dose combination (FDC) or separate pill combination (SePC), and assess the impact of prior medicine exposure on this outcome. Prescription dispensing data from a national administrative dataset was used to identify patients initiating FDCs or SePCs of amlodipine and statin between April and September 2013. Each cohort was stratified according to dispensing of calcium channel blockers (CCBs) or statins in the prior 12 months. Time to cessation of combination therapy (persistence) was analyzed over 12 months using Kaplan Meyer survival analysis and Cox proportional hazards (PH) models. Patient factors associated with length of treatment were identified using Cox PH modeling. Of 26,000 people who initiated combination amlodipine and statin, the majority initiated SePCs (77%). The unadjusted cessation rates at 12 months were SePC 40% and FDC 44%. Following adjustment for patient factors, the risk of ceasing combination therapy was higher in those taking the SePC versus FDC, hazard ratio (95% CI): 1.15 (1.11, 1.21). Patients naïve to both therapies had double the cessation rate compared to those who had at least one prior dispensing of a statin. Factors positively associated with persistence were prior use of other antihypertensive drugs and reaching the medicine subsidy safety-net: factors that were more common in users of SePC amlodipine and statin. In this study we found a lower risk (15%) of ceasing combination therapy when people initiate amlodipine and statin in the form of a FDC. While this outcome supports findings in other countries that FDCs improve persistence with combination therapy, prior experience with component or similar medicines has a larger impact on persistence regardless of formulation initiated.
Publisher: SERDI
Date: 2016
DOI: 10.14283/JFA.2016.83
Abstract: In iduals identified as frail have been shown to be at an increased risk of adverse health outcomes. However, there is no gold standard frailty measure and frailty status can vary depending on the measure used, suggesting the measures perform differently. Construct validity can be used to assess a measure’s performance. This study aimed to examine the construct validity of four frailty measures in an Australian older population using Rasch analysis. Frailty status among the 2087 participants aged 65 years and above from the Australian Longitudinal Study of Ageing (ALSA) was assessed using: frailty phenotype - FP, simplified frailty phenotype - SFP, frailty index - FI, and prognostic frailty score – PFS. Rasch analysis was used to assess the unidimensionality of the measures, which is the extent to which the underlying characteristic of frailty is assessed. The criteria for unidimensionality from principal component analysis of the residuals was when 50% or more of the raw variance was explained by the measures, and less than 5% was unexplained variance. Only FI meet the unidimensionality criteria with 74% of explained variance and 2.1% of unexplained variance. SFP did not show a unidimensional construct with 13.3% of explained variance and 47.1% of unexplained variance. FP and PFS had 39.6%, 18.1% and 46.5%, 8.7% of explained and unexplained variance, respectively. Our findings showed that FI has better construct validity than the other three measures in assessing frailty among the Australian older population.
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.SOCSCIMED.2015.09.019
Abstract: Interventions asking patients to commit to speaking with their doctor about a health-related issue could be used to improve quality of care. To evaluate the impact of commitment questions targeting patients on the uptake of recommended health services within a national quality improvement program (Veterans' MATES). Patients targeted in the home medicines reviews (HMRs), dose administration aids (DAAs), renal function testing and diabetes interventions were posted educational information and response forms which asked whether they intended to talk to their general practitioner (GP) about the targeted service. Uptake of the service after each intervention was determined using health claims data. Log binomial regression models compared the monthly rate of service use in the nine months post-intervention among patients answering 'yes' to a commitment question with non-responders and patients answering 'no' or 'unsure'. Each intervention targeted up to 58,000 patients. The average response rate was 28%. Positive responses were associated with increased uptake of HMRs (rate ratio (RR) 2.64, 95% CI 2.39-2.92 p < 0.0001), dose administration aids (RR 2.53, 95% CI 2.29-2.79 p < 0.0001), renal function tests (RR 1.18, 95% CI 1.13-1.24 p < 0.0001), GP management plans (RR 1.30, 95% CI 1.14-1.48 p < 0.0001) and diabetes care plans (RR 1.47, 95% CI 1.24-1.75 p < 0.0001) compared to non-responders. Similar increases in uptake were also observed among positive responders when compared to patients responding 'no' or 'unsure' to the commitment question. Positive responses to commitment questions distributed as part of national, multifaceted interventions were consistently associated with increased uptake of targeted services.
Publisher: BMJ
Date: 30-05-2006
Publisher: Springer Science and Business Media LLC
Date: 25-05-2005
Publisher: Springer Science and Business Media LLC
Date: 05-04-2022
DOI: 10.1186/S12931-022-02010-Z
Abstract: In elderly populations, paracetamol may be used regularly for conditions such as osteoarthritis. Paracetamol has been associated with respiratory disease through a proposed mechanism of glutathione depletion and oxidative stress. Given that chronic obstructive pulmonary disease (COPD) is frequently co-morbid with osteoarthritis, this study investigated whether the dose and timing of paracetamol exposure may induce COPD exacerbations. The study population was 3523 Australian Government Department of Veterans’ Affairs full entitlement holders who had existing COPD on 1 January 2011, who were dispensed at least one prescription of paracetamol between 1 January 2011 and 30 September 2015, and had no paracetamol dispensed in the 6 months prior to 1 January 2011. The outcome was time to first hospitalisation for COPD exacerbation after initiation of paracetamol. A weighted cumulative exposure approach was used. The association between paracetamol exposure and COPD exacerbation was protective or harmful depending on the dose, duration, and recency of exposure. Compared to non-use, current use at the maximum dose of 4 g daily for 7 days was associated with a lower risk (HR = 0.78, 95% CI = 0.67–0.92) and a higher risk after 30 days (HR = 1.27, 95% CI = 1.06–1.52). Risk declined to baseline after 2 months. For past use, there was a short-term increase in risk on discontinuation depending of dose, duration and time since stopping. Patients and doctors should be aware of the possible risk of COPD exacerbation with higher dose paracetamol 1 to 6 weeks after initiation or discontinuation, but no increased risk after 2 months.
Publisher: Wiley
Date: 17-03-2014
DOI: 10.1111/JGS.12741
Abstract: To determine whether there is greater risk of initiation of oxybutynin to treat urinary incontinence (UI) after initiation of medicines reported to be associated with UI. Prescription sequence symmetry analysis (PSSA). Administrative claims data from the Australian Government Department of Veterans' Affairs. In iduals who initiated oxybutynin and a medicine reported to be associated with UI in a 12-month period. Between January 1, 2001, and December 31, 2011, the distribution of incident dispensing of medicines reported to be associated with UI (prazosin, diuretics, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), hormone replacement therapy (HRT), opioid analgesics, anticonvulsants, levodopa, antipsychotics, sedatives, selective serotonin reuptake inhibitors (SSRIs), venlafaxine, anticholinesterases) was assessed before and after incident dispensing of oxybutynin (to treat UI). Crude and adjusted sequence ratios (ASRs) with 95% confidence intervals (CIs) were calculated. Significant associations between initiation of CCBs, ACEIs, ARBs, and hypnotic-sedatives and subsequent initiation of oxybutynin were found. ASRs ranged from 1.28 (95% CI = 1.19-1.39) for ACEIs to 1.59 (95% CI = 1.29-1.96) for verapamil. In women, there was greater risk of initiation of oxybutynin after prazosin (ASR = 1.84, 95% CI = 1.29-2.63) and HRT (ASR = 1.54, 95% CI = 1.42-1.67) initiation. PSSA showed no significant association with initiation of opioids, anticonvulsants, levodopa, SSRIs, venlafaxine, or anticholinesterases and subsequent initiation of oxybutynin. This study highlights the potential for initiation of commonly used medicines to be associated with subsequent initiation of oxybutynin to treat UI. Greater awareness of the potential for medicines to contribute to UI is required.
Publisher: Springer Science and Business Media LLC
Date: 10-02-2017
DOI: 10.1007/S11657-017-0309-4
Abstract: Osteoporosis interventions targeting older Australians and clinicians were conducted in 2008 and 2011 as part of a national quality improvement program underpinned by behavioural theory and stakeholder engagement. Uptake of bone mineral density (BMD) tests among targeted men and women increased after both interventions and sustained increases in osteoporosis treatment were observed among men targeted in 2008. Educational interventions incorporating patient-specific prescriber feedback have improved osteoporosis screening and treatment among at-risk patients in clinical trials but have not been evaluated nationally. This study assessed uptake of BMD testing and osteoporosis medicines following two national Australian quality improvement initiatives targeting women (70-79 years) and men (75-85 years) at risk of osteoporosis. Administrative health claims data were used to determine monthly rates of BMD testing and initiation of osteoporosis medicines in the 9-months post-intervention among targeted men and women compared to older cohorts of men and women. Log binomial regression models were used to assess differences between groups. In 2008 91,794 patients were targeted and 52,427 were targeted in 2011. There was a twofold increase in BMD testing after each intervention among targeted patients compared to controls (p < 0.001). Initiation of osteoporosis medicines increased by 21% among men targeted in 2008 and 34% among men targeted in 2011 compared to older controls (p < 0.01). Initiation of osteoporosis medicines among targeted women was similar to the older controls. Programs underpinned by behavioural theory and stakeholder engagement that target both primary care clinicians and patients can improve osteoporosis screening and management at the national level.
Publisher: Elsevier BV
Date: 10-2022
DOI: 10.1016/J.JVAL.2022.09.001
Abstract: Ambiguity in communication of key study parameters limits the utility of real-world evidence (RWE) studies in healthcare decision-making. Clear communication about data provenance, design, analysis, and implementation is needed. This would facilitate reproducibility, replication in independent data, and assessment of potential sources of bias. The International Society for Pharmacoepidemiology (ISPE) and ISPOR-The Professional Society for Health Economics and Outcomes Research (ISPOR) convened a joint task force, including representation from key international stakeholders, to create a harmonized protocol template for RWE studies that evaluate a treatment effect and are intended to inform decision-making. The template builds on existing efforts to improve transparency and incorporates recent insights regarding the level of detail needed to enable RWE study reproducibility. The over-arching principle was to reach for sufficient clarity regarding data, design, analysis, and implementation to achieve 3 main goals. One, to help investigators thoroughly consider, then document their choices and rationale for key study parameters that define the causal question (e.g., target estimand), two, to facilitate decision-making by enabling reviewers to readily assess potential for biases related to these choices, and three, to facilitate reproducibility. Recognizing that the impact of this harmonized template relies on uptake, we have outlined a plan to introduce and pilot the template with key international stakeholders over the next 2 years. The HARmonized Protocol Template to Enhance Reproducibility (HARPER) helps to create a shared understanding of intended scientific decisions through a common text, tabular and visual structure. The template provides a set of core recommendations for clear and reproducible RWE study protocols and is intended to be used as a backbone throughout the research process from developing a valid study protocol, to registration, through implementation and reporting on those implementation decisions.
Publisher: BMJ
Date: 05-02-2022
DOI: 10.1136/BMJMILITARY-2020-001456
Abstract: The use of health services is likely to vary among veterans with an accepted disability of post-traumatic stress disorder (PTSD), however, the extent of variation is not known. We aimed to determine the extent and type of health services used by veterans with an accepted disability of PTSD. The cohort included veterans who served post 1975, were eligible for all Australian Government Department of Veterans’ Affairs funded health services, had PTSD as an accepted disability prior to July 2015 and were alive at the 30 June 2016. Veterans were assigned to groups based on their use of health services using K-means cluster analysis. The cohort comprised five clusters involving 2286 veterans. The largest cluster (43%) were a younger, general practitioner (GP) managed cluster who saw their GP quarterly and the psychiatrist twice a year. The second GP cluster (30%) had higher levels of physical comorbidity. The psychiatrist managed cluster (14%) had a mean of 12 psychiatrist visits and one PTSD hospitalisation in the year. The remaining two clusters involved GP and allied healthcare, but no psychologist care. High levels of antidepressant use occurred in all clusters, ranging from 44% up to 69%. The psychiatrist managed cluster had 47% on antipsychotics and 58% on anxiolytics. Our study highlights the heterogeneity in health service use. These results identify the significant health utilisation required for up to one-sixth of veterans with PTSD and the significant role of primary care physicians in supporting veterans with PTSD.
Publisher: Wiley
Date: 16-04-2015
DOI: 10.1002/PDS.3785
Abstract: Many factors can increase the risk of hip fracture, including medicines. Traditional observational studies have assessed the risk, but results may be confounded by unmeasured factors. The case-crossover design is an alternative approach that controls for patient-specific, time-invariant confounding factors. This study aimed to assess associations between psychoactive medicines and hip fracture in the elderly using the case-crossover method. Data were sourced from the Australian Government Department of Veterans' Affairs healthcare claims database. The study population comprised beneficiaries aged over 65 years who were hospitalised for hip fracture between 2009 and 2012. The case-crossover method was used to compare in iduals' medicine exposure immediately before hip fracture (case window) with their exposure at an earlier time (control window). Conditional logistic regression was employed to quantify associations between medicine use and hip fracture. Alternative exposure windows were assessed in sensitivity analyses. Eight thousand eight hundred twenty-eight patients were hospitalised for hip fracture. Their median age was 88 years, and 63% were female. Odds of hip fracture were increased for opioids (odds ratio [OR] = 1.62, 95% confidence interval [CI] = 1.42-1.84), selective serotonin reuptake inhibitors (OR = 1.54, 95% CI = 1.28-1.86) and antipsychotics (OR = 1.47, 95% CI = 1.21-1.80). There was no significant association for tricyclic antidepressants in the primary analysis (OR = 1.18, 95% CI = 0.91-1.52), but there was a significant association in the sensitivity analysis using an alternative, earlier control window (OR = 1.43, 95% CI = 1.11-1.83). Increased risk of hip fracture in older people was found for opioids, selective serotonin reuptake inhibitors and antipsychotics. The choice of control window influenced the result for tricyclic antidepressants.
Publisher: Springer Science and Business Media LLC
Date: 28-09-2018
Publisher: Wiley
Date: 22-04-2015
DOI: 10.1002/PDS.3780
Publisher: BMJ
Date: 27-04-2023
DOI: 10.1136/BMJQS-2022-015716
Abstract: Many countries have high opioid use among people with chronic non-cancer pain. Knowledge about effective interventions that could be implemented at scale is limited. We designed a national intervention that included audit and feedback, deprescribing guidance, information on catastrophising assessment, pain neuroscience education and a cognitive tool for use by patients with their healthcare providers. We used a single-arm time series with segmented regression to assess rates of people using opioids before (January 2015 to September 2017), at the time of (October 2017) and after the intervention (November 2017 to August 2019). We used a cohort with historical comparison group and log binomial regression to examine the rate of psychologist claims in opioid users not using psychologist services prior to the intervention. 13 968 patients using opioids, 8568 general practitioners, 8370 pharmacies and accredited pharmacists and 689 psychologists were targeted. The estimated difference in opioid use was −0.51 persons per 1000 persons per month (95% CI −0.69, –0.34 p .001) as a result of the intervention, equating to 25 387 (95% CI 24 676, 26 131) patient-months of opioid use avoided during the 22-month follow-up. The targeted group had a significantly higher rate of incident patient psychologist claims compared with the historical comparison group (rate ratio: 1.37, 95% CI 1.16, 1.63 p .001), equating to an additional 690 (95% CI 289, 1167) patient-months of psychologist treatment during the 22-month follow-up. Our intervention addressed the cognitive, affective and sensory factors that contribute to pain and consequent opioid use, demonstrating it could be implemented at scale and was associated with a reduction in opioid use and increasing utilisation of psychologist services.
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.ARTMED.2016.06.002
Abstract: Prescribing cascade (PC) occurs when an adverse drug reaction (ADR) is misinterpreted as a new medical condition, leading to further prescriptions for treatment. Additional prescriptions, however, may worsen the existing condition or introduce additional adverse effects (AEs). Timely detection and prevention of detrimental PCs is essential as drug AEs are among the leading causes of hospitalization and deaths. Identifying detrimental PCs would enable warnings and contraindications to be disseminated and assist the detection of unknown drug AEs. Nonetheless, the detection is difficult and has been limited to case reports or case assessment using administrative health claims data. Social media is a promising source for detecting signals of detrimental PCs due to the public availability of many discussions regarding treatments and drug AEs. In this paper, we investigate the feasibility of detecting detrimental PCs from social media. The detection, however, is challenging due to the data uncertainty and data rarity in social media. We propose a framework to mine sequences of drugs and AEs that signal detrimental PCs, taking into account the data uncertainty and data rarity. We conduct experiments on two real-world datasets collected from Twitter and Patient health forum. Our framework achieves encouraging results in the validation against known detrimental PCs (F1=78% for Twitter and 68% for Patient) and the detection of unknown potential detrimental PCs (Precision@50=72% and NDCG@50=95% for Twitter, Precision@50=86% and NDCG@50=98% for Patient). In addition, the framework is efficient and scalable to large datasets. Our study demonstrates the feasibility of generating hypotheses of detrimental PCs from social media to reduce pharmacists' guesswork.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.JOCA.2016.05.006
Abstract: To evaluate the 90 days and 1 year mortality predictive ability of the RxRisk-V, Charlson, and Elixhauser co-morbidity measures in total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients. A retrospective study of 11,848 THAs and 18,972 TKAs (2001-2002) was conducted. Death within 90 days and 1 year of the surgery were the main endpoints. Co-morbidity measures were calculated using either medication or hospitalisation history. Logistic regression models were employed and discrimination and calibration were assessed. Specifically, models with unweighted and weighted measure scores, models with the specific conditions, and a model combining conditions identified by all measures were assessed. In THAs, the best performing prediction models included co-morbidities from all three measures (90 days: c = 0.84, P = 0.284, 1 year: c = 0.79, P = 0.158). In idually, the model with Charlson conditions performed best at 90 days mortality (c = 0.80, P = 0.777) and the Charlson and Elixhauser performed similarly at 1 year (both c = 0.77, P > 0.05). In TKAs, the best performing prediction model included co-morbidities from all measures (90 days: c = 0.82, P = 0.349, 1 year: c = 0.78, P = 0.873). In idually, the model with Elixhauser conditions performed best with 90 days mortality (c = 0.79, P = 0.435) and all performed similarly at 1 year (c = 0.74-0.75, all P > 0.05). A combined model with co-morbidities identified by the Elixhauser, Charlson, and RxRisk-V was the best mortality prediction model. The RxRisk-V did not perform as well as the others. Because of the Elixhauser and Charlson's similar performance we suggest basing the choice of measurement use on factors such as the need of specific conditions and modelling limitations.
Publisher: Informa UK Limited
Date: 2006
Publisher: Springer Science and Business Media LLC
Date: 24-06-2013
Publisher: Oxford University Press (OUP)
Date: 16-04-2021
DOI: 10.1093/AJE/KWAB110
Abstract: For self-controlled studies of medication-related effects, time-varying confounding by indication can occur if the indication varies over time. We describe how active comparators might mitigate such bias, using an empirical ex le. Approaches to using active comparators are described for case-crossover design, case-time-control design, self-controlled case-series, and sequence symmetry analyses. In the empirical ex le, we used Danish data from 1996–2018 to study the association between penicillin and venous thromboembolism (VTE), using roxithromycin, a macrolide antibiotic, as comparator. Upper respiratory infection is a transient risk factor for VTE, thus representing time-dependent confounding by indication. Odds ratios for case-crossover analysis were 3.35 (95% confidence interval: 3.23, 3.49) for penicillin and 3.56 (95% confidence interval: 3.30, 3.83) for roxithromycin. We used a Wald-based method or an interaction term to estimate the odds ratio for penicillin with roxithromycin as comparator. These 2 estimates were 0.94 (95% confidence interval: 0.87, 1.03) and 1.03 (95% confidence interval: 0.95, 1.13). Results were similar for the case-time-control analysis, but both the self-controlled case-series and sequence symmetry analysis suggested a weak protective effect of penicillin, seemingly explained by VTE affecting future exposure exclusively for penicillin. The strong association of antibiotics with VTE suggests presence of confounding by indication. Such confounding can be mitigated by using an active comparator.
Publisher: Elsevier BV
Date: 08-2006
DOI: 10.1111/J.1467-842X.2006.TB00842.X
Abstract: To measure the association between major causes of mortality and tobacco use and the association between major causes of mortality and alcohol use, after adjusting for tobacco use. Employees of Australian Institute of Petroleum member companies were enrolled in the cohort in four industry-wide surveys between 1981 and 1999. Mortality of 16,547 men was determined up to 31 December 2001 and cancer incidence to 31 December 2000. Relative mortality and cancer incidence rates were computed for smoking categories compared with never smokers, and for alcohol consumption compared with total abstainers. The highest category of smoking, more than 30 cigarettes per day, was associated with more than a threefold increase in all-cause mortality, a 60% increase in cancer incidence, a 43-fold increase in lung cancer incidence, and a more than fourfold increase in mortality from ischaemic heart disease. There were only four cancers in lifelong non-smokers. Moderate alcohol consumption provided a protective effect from death from all causes combined, relative to nil or low consumption, and relative to heavy alcohol consumption. The main contributor to the protective effect was protection against death from ischaemic heart disease. Lifelong avoidance of tobacco and moderate alcohol consumption confer significant improvements on life expectancy.
Publisher: Springer Science and Business Media LLC
Date: 06-06-2022
DOI: 10.1186/S12874-022-01644-3
Abstract: There is increasing interest in the development and use of clinical prediction models, but a lack of evidence-supported guidance on the merits of different modelling approaches. This is especially true for time-to-event outcomes, where limited studies have compared the vast number of modelling approaches available. This study compares prediction accuracy and variable importance measures for four modelling approaches in prediction of time-to-revision surgery following total knee arthroplasty (TKA) and total hip arthroplasty (THA). The study included 321,945 TKA and 151,113 THA procedures performed between 1 January 2003 and 31 December 2017. Accuracy of the Cox model, Weibull parametric model, flexible parametric model, and random survival forest were compared, with patient age, sex, comorbidities, and prosthesis characteristics considered as predictors. Prediction accuracy was assessed using the Index of Prediction Accuracy (IPA), c-index, and smoothed calibration curves. Variable importance rankings from the Cox model and random survival forest were also compared. Overall, the Cox and flexible parametric survival models performed best for prediction of both TKA (integrated IPA 0.056 (95% CI [0.054, 0.057]) compared to 0.054 (95% CI [0.053, 0.056]) for the Weibull parametric model), and THA revision. (0.029 95% CI [0.027, 0.030] compared to 0.027 (95% CI [0.025, 0.028]) for the random survival forest). The c-index showed broadly similar discrimination between all modelling approaches. Models were generally well calibrated, but random survival forest underfitted the predicted risk of TKA revision compared to regression approaches. The most important predictors of revision were similar in the Cox model and random survival forest for TKA (age, opioid use, and patella resurfacing) and THA (femoral cement, depression, and opioid use). The Cox and flexible parametric models had superior overall performance, although all approaches performed similarly. Notably, this study showed no benefit of a tuned random survival forest over regression models in this setting.
Publisher: BMJ
Date: 04-2018
Publisher: Wiley
Date: 02-06-2015
DOI: 10.1111/AJAG.12184
Abstract: To determine the prevalence of frailty in a cohort of older Australians. Frailty status of the 2087 participants of the Australian Longitudinal Study of Ageing was assessed based on the questionnaire responses at the baseline interview. Frailty status and prevalence were assessed using four measures: two unidimensional measures (the Frailty Phenotype and Simplified Frailty Phenotype) and two multidimensional measures (Frailty Index and Prognostic Frailty Score). Agreement between the four measures was determined. The multidimensional measures identified more people as frail (17.5 and 49.4%) than did the unidimensional (2 and 8.8%). There was little agreement between the measures only 0.5% of the participants were identified as frail by all four measures. The apparent prevalence of frailty varied when different measures were used. It is important for clinicians and researchers to be aware that different frailty measures may identify different groups of older people as frail.
Publisher: Wiley
Date: 25-09-2023
DOI: 10.1002/PDS.5701
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1016/J.JAMDA.2019.08.017
Abstract: To examine the association between benzodiazepine use and the risk of dementia. We conducted a retrospective cohort study, using a nationwide healthcare database of South Korea (2002-2016). The participants included new users of benzodiazepines aged ≥50 years, with no prior prescription record of benzodiazepines or a history of dementia within the previous 5 years (2002-2006). Outcome was defined as an incident dementia with specified algorithms using diagnosis and prescription records, with the application of a 5-year lag-time following the index date during which outcomes were censored. We used a multivariable Cox proportional hazard model to estimate hazard ratio (HR) and the 95% confidence interval (CI). Comorbidities and comedications were treated as time-varying covariates in 90-day windows, and an active comparator was used to reduce potential bias from confounding by indication. Active comparators were defined as new-users of antidepressants. Our final participants included 616,256 patients, after propensity score estimation and matching on a 1:1 ratio. We observed a 23% increase in the risk of dementia in benzodiazepine users, compared with that in nonusers, over a mean follow-up period of 5.5 years (HR 1.23, 95% CI 1.14-1.32). A consistent finding was observed when the lag-time duration was extended to 7 years, revealing a close to null association (HR 1.17, 95% CI 1.04-1.30). When new-users of antidepressants were used as the active comparator, no increase in the risk of dementia with benzodiazepines was observed over 7 years (HR 1.01, 95% CI 0.81-1.27). A significant association was observed between benzodiazepine use and the risk of dementia, compared with nonusers. However, a null or negative association was observed with the use of the active comparator, suggesting the absence of a causal association between dementia and benzodiazepine use.
Publisher: BMJ
Date: 04-2020
DOI: 10.1136/BMJOPEN-2019-032851
Abstract: Many medicines have adverse effects which are difficult to detect and frequently go unrecognised. Pharmacist monitoring of changes in signs and symptoms of these adverse effects, which we describe as medicine-induced deterioration, may reduce the risk of developing frailty. The aim of this trial is to determine the effectiveness of a 12-month pharmacist service compared with usual care in reducing medicine-induced deterioration, frailty and adverse reactions in older people living in aged-care facilities in Australia. The reducing medicine-induced deterioration and adverse reactions trial is a multicentre, open-label randomised controlled trial. Participants will be recruited from 39 facilities in South Australia and Tasmania. Residents will be included if they are using four or more medicines at the time of recruitment, or taking more than one medicine with anticholinergic or sedative properties. The intervention group will receive a pharmacist assessment which occurs every 8 weeks. The pharmacists will liaise with the participants’ general practitioners when medicine-induced deterioration is evident or adverse events are considered serious. The primary outcome is a reduction in medicine-induced deterioration from baseline to 6 and 12 months, as measured by change in frailty index. The secondary outcomes are changes in cognition scores, 24-hour movement behaviour, grip strength, weight, percentage robust, pre-frail and frail classification, rate of adverse medicine events, health-related quality of life and health resource use. The statistical analysis will use mixed-models adjusted for baseline to account for repeated outcome measures. A health economic evaluation will be conducted following trial completion using data collected during the trial. Ethics approvals have been obtained from the Human Research Ethics Committee of University of South Australia (ID:0000036440) and University of Tasmania (ID:H0017022). A copy of the final report will be provided to the Australian Government Department of Health. Australian and New Zealand Trials Registry ACTRN12618000766213.
Publisher: American Academy of Pediatrics (AAP)
Date: 06-2002
Abstract: Objectives. To determine the natural history of infant spilling (regurgitation/vomiting) during the first 2 years of life and to determine the relationship between infant spilling and gastroesophageal reflux (GER) symptoms at 9 years of age. Methods. A prospective birth cohort was followed with daily symptom diaries during the first 2 years of life and reviewed at 9 years of age (range: 8–11 years). The prevalence of infant spilling during the first 2 years of life, the prevalence of GER symptoms between 8 and 11 years of age (mean age: 9.7 years), relative risk of infant spilling predisposing to GER symptoms at 9 years of age, and prevalence of maternal GER symptoms and relationship with infant spilling and GER at 9 years of age were measured. Results. A total of 693 children who represented 83% of an original s le of 836 children and were followed for 2 years from birth with daily symptom diaries were contacted at 9 (8–11) years of age. Spilling of most feeds each day was common in infancy and reached a peak prevalence of 41% between 3 and 4 months of age and thereafter declined to & 5% between 13 and 14 months of age. Infants with spilling on 90 days or more during the first 2 years of life (classified as frequent spilling) were more likely to have GER symptoms at 9 years of age. Children with frequent infant spilling, compared with those with no spilling, had a relative risk of 2.3 (95% confidence interval [CI]: 1.3–4.0) of 1 or more GER symptoms at 9 years of age, 4.6 (95% CI: 1.5–13.8) for heartburn, 2.7 (95% CI: 1.4–5.5) for vomiting, and 4.7 (95% CI: 1.6–14.0) for acid regurgitation. Gender, breastfeeding, and environmental tobacco smoke exposure were not significant factors related to infant spilling. Prepregnancy smoking and smoking in the same room as the child at the 9-month and 18-month follow-ups had a significant effect on GER symptoms at 9 years of age. Infant spilling and GER at 9 years of age were significantly related to maternal GER symptoms but not to paternal GER symptoms. Conclusions. Spilling in infancy is very common, but the majority of children settle by 13 to 14 months of age. However, those with frequent spilling (& days) are more likely to have GER symptoms at 9 years of age. In addition, a maternal history of GER was significantly related both to infant spilling and to GER at 9 years, suggesting that a genetic component may be involved. Physicians should consider studying children with a history of frequent infant spilling to determine whether this group is at increased risk for GER disease.
Publisher: Hindawi Limited
Date: 25-08-2021
DOI: 10.1111/JCPT.13520
Abstract: Proton pump inhibitors (PPIs), used to treat and prevent gastro-oesophageal conditions, are well-tolerated but have been associated with risk including pneumonia. The extent to which initiation of PPIs can contribute to other respiratory conditions such as chronic obstructive pulmonary disease (COPD) is largely unknown. A sequence symmetry analysis (SSA) approach was applied to the Australian Department of Human Services, Pharmaceutical Benefits Scheme 10% extract. Participants were aged 45 years and older and were dispensed PPIs (ATC Codes A02BC01, A02BC02, A02BC03, A02BC04 and A02BC05) and long-acting bronchodilators (LABDs) for COPD (ATC Codes R03BB04 (PBS Item Code 10509D and 08626B), R03BB05, R03BB06, R03BB07 and R03AC18 (PBS Item Code 05137J and 05134F)) between 2013 and 2019. The analysis included patients initiated on an LABD within 12 months before or after their first prescription of a PPI. The crude sequence ratio (cSR) was calculated as the number of patients prescribed their first LABD after starting a PPI ided by the number of patients prescribed their first LABD before starting a PPI. Calculation of the adjusted sequence ratio (aSR) accounted for prescribing trends over time in initiation of each of the medicines. A signal was identified where the aSR lower 95% confidence interval (CI) was greater than one. Initiation of omeprazole was associated with a 29% increased risk of initiating a LABD (ASR = 1.29 95% CI 1.22-1.36). Initiation of esomeprazole, rabeprazole, pantoprazole or lansoprazole was associated with 25%, 15%, 8% and 8% increased risk, respectively. There is an established association between gastro-oesophageal reflux disease and COPD which has been confirmed by implementation of a sequence symmetry-based approach which demonstrated that PPI initiation is potentially associated with progression or exacerbation of COPD. The impact PPI use has directly on this association requires further investigation.
Publisher: BMJ
Date: 04-2016
Publisher: Medical Journals Sweden AB
Date: 19-10-2016
Publisher: Swansea University
Date: 13-06-2021
Abstract: Regulators and payers play a pivotal role in facilitating timely and affordable access to safe and efficacious medicines. They use evidence generated from randomised clinical trials (RCTs) to support decisions to register and subsidise medicines. However, at the time of registration and subsidy approval, regulators and payers face uncertainty about how RCT outcomes will translate to real-world clinical practice. In response to this situation, medicines policy agencies worldwide have endorsed the use of real-world data (RWD) to derive novel insights on the use and outcomes of prescribed medicines. Recent reforms around data availability and use in Australia are creating unparalleled data access and opportunities for Australian researchers to undertake large-scale research to generate evidence on the safety and effectiveness of medicines in the real world. Highlighting the critical importance of research in this area, Quality Use of Medicines and Medicine Safety was announced as Australia's 10th National Health Priority in 2019. The National Health and Medical Research Council, Medicines Intelligence Centre of Research Excellence (MI-CRE) has been formed to take advantage of the renewed focus on quality use of medicines and the changing data landscape in Australia. It will generate timely research supporting the evidentiary needs of Australian medicines regulators and payers by accelerating the development and translation of real-world evidence on medicines use and outcomes. MI-CRE is developing a coordinated approach to identify, triage and respond to priority questions where there are significant uncertainties about medicines use, (cost)-effectiveness, and/or safety and creating a data ecosystem that will streamline access to Australian data to enable researchers to generate robust evidence in a timely manner. This paper outlines how MI-CRE will partner with policy makers, clinicians, and consumer advocates to leverage real-world data to co-create real-world evidence, to improve quality use of medicines and reduce medicine-related harm.
Publisher: Springer Science and Business Media LLC
Date: 23-06-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2015
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/567387
Abstract: Introduction . Ophthalmic timolol, a topical nonselective beta-blocker, has the potential to be absorbed systemically which may cause adverse cardiovascular effects. This study was conducted to determine whether initiation of ophthalmic timolol was associated with an increased risk of hospitalisation for bradycardia. Materials and Methods . A self-controlled case-series study was undertaken in patients who were hospitalised for bradycardia and were exposed to timolol. Person-time after timolol initiation was partitioned into risk periods: 1–30 days, 31–180 days, and days. A 30-day risk period prior to initiating timolol was also included. All remaining time was considered unexposed. Results . There were 6,373 patients with at least one hospitalisation for bradycardia during the study period 267 were exposed to timolol. Risk of bradycardia was significantly increased in the 31–180 days after timolol initiation (incidence rate ratio (IRR) = 1.93 95% confidence interval (CI) 1.00–1.87). No increased risk was observed in the first 30 days or beyond 180 days of continuous exposure (IRR = 1.40 95% CI 0.87–2.26 and IRR = 1.21 95% CI 0.64–2.31, resp.). Conclusion . Bradycardia is a potential adverse event following timolol initiation. Practitioners should consider patient history before choosing a glaucoma regime and closely monitor patients after treatment initiation with topical nonselective beta-blocker eye drops.
Publisher: Springer Science and Business Media LLC
Date: 07-2017
DOI: 10.1007/S10654-017-0281-8
Abstract: Sequence symmetry analysis (SSA) is a method for detecting adverse drug events by utilizing computerized claims data. The method has been increasingly used to investigate safety concerns of medications and as a pharmacovigilance tool to identify unsuspected side effects. Validation studies have indicated that SSA has moderate sensitivity and high specificity and has robust performance. In this review we present the conceptual framework of SSA and discuss advantages and potential pitfalls of the method in practice. SSA is based on analyzing the sequences of medications if one medication (drug B) is more often initiated after another medication (drug A) than before, it may be an indication of an adverse effect of drug A. The main advantage of the method is that it requires a minimal dataset and is computationally efficient. By design, SSA controls time-constant confounders. However, the validity of SSA may be affected by time-varying confounders, as well as by time trends in the occurrence of exposure or outcome events. Trend effects may be adjusted by modeling the expected sequence ratio in the absence of a true association. There is a potential for false positive or negative results and careful consideration should be given to potential sources of bias when interpreting the results of SSA studies.
Publisher: Wiley
Date: 27-06-2021
DOI: 10.1111/AJAG.12975
Abstract: To determine the prevalence of medication‐related hospitalisations preceded by potentially suboptimal processes of care in aged care residents. We conducted a retrospective analysis of administrative claims data from the Australian Government Department of Veterans’ Affairs (DVA). We identified all hospital admissions for aged care residents between 1 July 2014 and 30 June 2019. The proportion of hospital admissions preceded by potentially suboptimal medication‐related processes of care was determined. A total of 18 874 hospitalisations were included, and 46% were preceded by potentially suboptimal medication‐related care. One‐quarter of fracture admissions occurred in residents at risk of fracture who were not using a medicine to prevent fracture, and 87% occurred in residents using falls‐risk medicines. Thirty per cent of heart failure admissions occurred in patients who were not using an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker. Nearly half of hospital admissions were preceded by potentially suboptimal medication‐related processes of care. Interventions to improve use of medicines for aged care residents in these areas are warranted.
Publisher: Wiley
Date: 10-2014
DOI: 10.1111/JGS.13054
Abstract: To identify the association between use of multiple anticholinergic medications and risk of hospitalization for confusion or dementia. Retrospective cohort study conducted over 2 years between July 2010 and June 2012, using administrative claims data from the Australian Department of Veterans' Affairs. Australia. Australian veterans dispensed at least one moderately or highly anticholinergic medication in the year before study start. Cumulative anticholinergic use on each day of the study period was determined. The association between hospitalization for confusion or dementia and number of anticholinergic medications used at the time of admission was compared against times during which participants were not taking anticholinergic medications. Sensitivity analyses were undertaken limiting the outcome to admissions for acute confusion and excluding in iduals taking antipsychotics. Adjusted results showed a significantly greater risk of hospitalization for confusion or dementia when in iduals were taking two or more anticholinergic medications. The adjusted incident rate ratios (IRRs) were 2.58 (95% confidence interval (CI) = 1.91-3.48) for those taking two anticholinergics and 3.87 (95% CI = 1.83-8.21) for those taking three or more. Sensitivity analyses in which participants taking antipsychotic medications were excluded and the outcome was limited to acute confusion also found similar risks for those taking two (IRR 1.82, 95% CI = 1.18-2.80) and three or more (IRR = 3.98 95% CI = 1.50-10.58) anticholinergic medications. Taking more anticholinergic medications is associated with greater risk of hospitalization for confusion or dementia. Strategies to reduce anticholinergic medication burden are likely to translate into significant health benefits.
Publisher: Wiley
Date: 19-10-2018
DOI: 10.1002/CLC.23091
Publisher: Public Library of Science (PLoS)
Date: 30-11-2022
DOI: 10.1371/JOURNAL.PONE.0278241
Abstract: Studies have identified increased cancer risk among patients undergoing total hip arthroplasty (THA) compared to the general population. However, evidence of all-cause and site-specific cancer risk associated with different bearing surfaces has varied, with previous studies having short latency periods with respect to use of modern Metal-on-Metal (MoM) bearings. Using the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) linked to Australasian Association of Cancer Registries data, our aim was to evaluate risk of all-cause and site-specific cancer according to bearing surfaces in patients undergoing THA for osteoarthritis and whether risk increased with MoM bearings. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated by comparing number of observed cancer cases to expected number based on incidence rate in the Australian population. All-cause and site-specific cancer rates were calculated for all conventional stemmed THA (csTHA) and resurfacing THA (rsTHA) procedures performed for osteoarthritis. Cox proportional hazards models were used to compare cancer rates for MoM, ceramic-on-ceramic (CoC) and resurfacing procedures with a comparison group comprising metal-on-polyethylene (MoP) or ceramic-on-polyethylene (CoP) procedures. There were 156,516 patients with csTHA procedures and 11,321 with rsTHA procedures for osteoarthritis performed between 1999 and 2012. Incidence of all-cause cancer was significantly higher for csTHA (SIR 1.24, 95% CI 1.22–1.26) and rsTHA (SIR 1.74, 95% CI 1.39–2.04) compared to the Australian population. For csTHA, there was no significant difference in all-site cancer rates for MoM (Hazard Ratio (HR) 1.01, 95%CI 0.96–1.07) or CoC (HR 0.98, 95%CI 0.94–1.02) compared to MoP and CoP bearings. Significantly increased risk of melanoma, non-Hodgkins lymphoma, myeloma, leukaemia, prostate, colon, bladder and kidney cancer was found for csTHA and, prostate cancer, melanoma for rsTHA procedures when compared to the Australian population, although risk was not significantly different across bearing surfaces. csTHA and rsTHA procedures were associated with increased cancer incidence compared to the Australian population. However, no excess risk was observed for MoM or CoC procedures compared to other bearing surfaces.
Publisher: Medical Journals Sweden AB
Date: 11-05-2016
Publisher: Springer Science and Business Media LLC
Date: 22-08-2018
DOI: 10.1007/S10803-018-3718-3
Abstract: Based on data from the Longitudinal Study of Australian Children linked with pharmacy dispensing data from the Australian Government's Pharmaceutical Benefits Scheme, we calculated the 1-year prevalence of psychotropic medicine supply in children and adolescents with Autism Spectrum Disorder (ASD) as reported by parents in 2014. The majority of children and adolescents with ASD in Australia were not treated with psychotropic medicine. One-third had claims for at least one psychotropic medication, most commonly medications for attention-deficit/hyperactivity disorder (ADHD), and antidepressants. Antipsychotics were supplied to less than one in twenty children and approximately one in ten adolescents. In line with findings from North America, psychotropic medicine was more often supplied to children and adolescents with ASD and comorbid ADHD.
No related grants have been discovered for Nicole Pratt.