Medicine (RMH) - Research Publications
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ItemPatterns of Medication Dispensation for Multiple Comorbidities among Older Adults in Australia.(MDPI AG, 2018-12-17)Background: The increasing burden of chronic (medical) conditions (CCs) is a major issue for healthcare systems across the world. We aimed to examine the changes in the rate of medication dispensation for multiple CCs among Australians aged ≥65 years. Methods: A repeated cross-sectional study was performed using the 2013⁻2016 Pharmaceutical Benefits Scheme (PBS) data on reimbursed prescriptions for a 10% random sample of the Australian population. Twenty-two CCs were identified via the RxRisk-V tool. The yearly changes in the proportion of older adults dispensed medications for ≥2 CCs were determined through Poisson regression modelling using 2013 as the reference year. The occurrence of CC dyads and triads for which medications were dispensed within a 180-day window were characterised, and the observed and expected rate of medication dispensation for each CC dyad or triad were calculated to identify the top 15 combinations. Results: The proportion of older adults dispensed medications for ≥2 CCs remained stable from 2013 to 2016, at >79% in each year. The proportion who were dispensed medications for multiple CCs increased with age. No gender differences in the dispensation of medications for multiple CCs were observed. Over 60% had medications dispensed for ≥3 CCs. The most frequent CC dyad and triad for which medications were dispensed were dyslipidaemia + hypertension (38.6%) and dyslipidaemia + gastroesophageal reflux disease + hypertension (18.7%), respectively. For the majority of CC dyads and all triads examined, the observed rate of medication dispensation exceeded that expected by chance. Conclusions: A high proportion of older Australians are dispensed medications for multiple CCs, suggestive of multimorbidity. The results reiterate the need for increased research into understanding the causal mechanisms of multimorbidity to inform the design of cost-effective interventions.
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ItemDr Foster global frailty score: an international retrospective observational study developing and validating a risk prediction model for hospitalised older persons from administrative data sets.(BMJ, 2019-06-22)OBJECTIVES: This study aimed to examine the prevalence of frailty coding within the Dr Foster Global Comparators (GC) international database. We then aimed to develop and validate a risk prediction model, based on frailty syndromes, for key outcomes using the GC data set. DESIGN: A retrospective cohort analysis of data from patients over 75 years of age from the GC international administrative data. A risk prediction model was developed from the initial analysis based on seven frailty syndrome groups and their relationship to outcome metrics. A weighting was then created for each syndrome group and summated to create the Dr Foster Global Frailty Score. Performance of the score for predictive capacity was compared with an established prognostic comorbidity model (Elixhauser) and tested on another administrative database Hospital Episode Statistics (2011-2015), for external validation. SETTING: 34 hospitals from nine countries across Europe, Australia, the UK and USA. RESULTS: Of 6.7 million patient records in the GC database, 1.4 million (20%) were from patients aged 75 years or more. There was marked variation in coding of frailty syndromes between countries and hospitals. Frailty syndromes were coded in 2% to 24% of patient spells. Falls and fractures was the most common syndrome coded (24%). The Dr Foster Global Frailty Score was significantly associated with in-hospital mortality, 30-day non-elective readmission and long length of hospital stay. The score had significant predictive capacity beyond that of other known predictors of poor outcome in older persons, such as comorbidity and chronological age. The score's predictive capacity was higher in the elective group compared with non-elective, and may reflect improved performance in lower acuity states. CONCLUSIONS: Frailty syndromes can be coded in international secondary care administrative data sets. The Dr Foster Global Frailty Score significantly predicts key outcomes. This methodology may be feasibly utilised for case-mix adjustment for older persons internationally.
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ItemCardiac fibrosis in the ageing heart: Contributors and mechanisms(WILEY, 2017-12)Cardiac fibrosis refers to an excessive deposition of extracellular matrix (ECM) in cardiac tissue. Fibrotic tissue is stiffer and less compliant, resulting in subsequent cardiac dysfunction and heart failure. Cardiac fibrosis in the ageing heart may involve activation of fibrogenic signalling and inhibition of anti-fibrotic signalling, leading to an imbalance of ECM turnover. Excessive accumulation of ECM such as collagen in older patients contributes to progressive ventricular dysfunction. Overexpression of collagen is derived from various sources, including higher levels of fibrogenic growth factors, proliferation of fibroblasts and cellular transdifferentiation. These may be triggered by factors, such as oxidative stress, inflammation, hypertension, cellular senescence and cell death, contributing to age-related fibrotic cardiac remodelling. In this review, we will discuss the fibrogenic contributors in age-related cardiac fibrosis, and the potential mechanisms by which fibrogenic processes can be interrupted for therapeutic intent.
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ItemProjected Burden of Osteoarthritis and Rheumatoid Arthritis in Australia: A Population-Level Analysis(WILEY, 2017-09-12)Objective To forecast the prevalence and direct health care costs of osteoarthritis (OA) and rheumatoid arthritis (RA) in Australia to the year 2030. Methods An epidemiologic model of the Australian population was developed. Data on the national prevalence of OA and RA were obtained from the Australian Bureau of Statistics (ABS) 2014–2015 National Health Survey. Future prevalence was estimated using ABS population projections for 2020, 2025, and 2030. Available government data on direct health care expenditure for OA and RA were modeled to forecast costs (in Australian $) for the years 2020, 2025, and 2030, from the perspective of the Australian public health care system. Results The number of people with OA is expected to increase nationally from almost 2.2 million in 2015 to almost 3.1 million Australians in 2030. The number of people with RA is projected to increase from 422,309 in 2015 to 579,915 in 2030. Health care costs for OA were estimated to be over $2.1 billion in 2015; by the year 2030, these are forecast to exceed $2.9 billion ($970 for every person with the condition). Health care costs for RA were estimated to be over $550 million in 2015, including $273 million spent on biologic disease‐modifying antirheumatic drugs. Health care costs for RA are projected to rise to over $755 million by the year 2030. Conclusion OA and RA are costly conditions that will impose an increasing health care burden at the population level. These projections provide tangible data that can be used to map future health service provision to expected need.
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ItemDementia, cognitive impairment and proton pump inhibitor therapy: A systematic review(WILEY, 2017-08)BACKGROUND AND AIM: Proton pump inhibitors (PPIs) are among the most widely used medications worldwide. Dementia is an increasingly common cause of disability in older populations. Recent studies have suggested an increased risk of cognitive impairment and dementia diagnosis among people who consume PPIs. This systematic review explores dementia, cognitive impairment, and the use of PPIs. METHODS: Systematic searches were conducted in the databases of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), PSYCinfo, Scopus, Web of Science, and ClinicalTrials.gov for articles published from inception to June 30, 2016. Primary outcomes of interest were the use of PPIs and diagnosis of dementia or acute cognitive impairment. Studies conducted on people aged less than 18 years old were excluded. All study designs were eligible for inclusion. Two reviewers independently assessed study quality and extracted data from included studies. RESULTS: The systematic search strategy and screening process yielded 11 studies for inclusion in the systematic review. Four studies explored PPI use and dementia, and seven studies explored PPI use and acute cognitive impairment. Three of the four studies exploring dementia identified a positive association with PPI use. A positive association was also observed in the majority of studies exploring acute cognitive impairment. CONCLUSIONS: Based on the current published literature, this systematic review has identified that the reported association between PPI use and dementia is limited by methodological issues and conflicting results. Further longitudinal studies with robust bias limitation are required to explore the use of PPIs and dementia or acute cognitive impairment, and to ascertain the existence of any causal relationships.
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ItemNEONATAL VITAMIN D SUPPLEMENTATION(WILEY, 2017-07)
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ItemSerologic antibodies in relation to outcome in postoperative Crohn's disease(WILEY, 2017-06)BACKGROUND AND AIM: Disease recurs frequently after Crohn's disease resection. The role of serological antimicrobial antibodies in predicting recurrence or as a marker of recurrence has not been well defined. METHODS: A total of 169 patients (523 samples) were prospectively studied, with testing peri-operatively, and 6, 12 and 18 months postoperatively. Colonoscopy was performed at 18 months postoperatively. Serologic antibody presence (perinuclear anti-neutrophil cytoplasmic antibody [pANCA], anti-Saccharomyces cerevisiae antibodies [ASCA] IgA/IgG, anti-OmpC, anti-CBir1, anti-A4-Fla2, anti-Fla-X) and titer were tested. Quartile sum score (range 6-24), logistic regression analysis, and correlation with phenotype, smoking status, and endoscopic outcome were assessed. RESULTS: Patients with ≥ 2 previous resections were more likely to be anti-OmpC positive (94% vs 55%, ≥ 2 vs < 2, P = 0.001). Recurrence at 18 months was associated with anti-Fla-X positivity at baseline (49% vs 29%; positive vs negative, P = 0.033) and 12 months (52% vs 31%, P = 0.04). Patients positive (n = 28) for all four antibacterial antibodies (anti-CBir1, anti-OmpC, anti-A4-Fla2, and anti-Fla-X) at baseline were more likely to experience recurrence at 18 months than patients negative (n = 32) for all four antibodies (82% vs 18%, P = 0.034; odds ratio 6.4, 95% confidence interval 1.16-34.9). The baseline quartile sum score for all six antimicrobial antibodies was higher in patients with severe recurrence (Rutgeert's i3-i4) at 18 months, adjusted for clinical risk factors (odds ratio 1.16, 95% confidence interval 1.01-1.34, P = 0.039). Smoking affected antibody status. CONCLUSIONS: Anti-Fla-X and presence of all anti-bacterial antibodies identifies patients at higher risk of early postoperative Crohn's disease recurrence. Serologic screening pre-operatively may help identify patients at increased risk of recurrence.
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ItemVitamin D in newborns. A randomised controlled trial comparing daily and single oral bolus vitamin D in infants(WILEY, 2017-02)AIM: There are no published data to demonstrate the efficacy of bolus dose vitamin D in newborn infants. The study sought to evaluate this alternative approach of supplementation. METHODS: This single centre, open randomised controlled trial was conducted from August 2013 to May 2014. It compared the efficacy and safety of daily (400 IU) versus a bolus dose (50 000 IU) of cholecalciferol in newborn infants of vitamin D deficient mothers. The primary outcome measure was the rate of 25 hydroxyvitamin D (25OHD) repletion-defined as 25OHD greater than 50 nmol/L. The secondary objective was determining safety using adjusted total serum calcium. RESULTS: Of 70 eligible infants, 36 received a daily dose and 34 received a single high-dose cholecalciferol. Mean 25OHD in the bolus group (154 nmol/L, 95% confidence interval (CI) 131-177) was higher than the daily group (48 nmol/L, 95% CI 42-54) at 1-2 weeks of age. This was reversed at 3-4 months, (65 nmol/L, 95% CI 59-71) compared with the daily group (81 nmol/L, 95% CI 77-85). More infants in the single bolus group achieved vitamin D repletion (100 vs. 31%) at 1-2 weeks. By 3-4 months, both groups achieved similar vitamin D repletion rates (91 vs. 89%). Mean adjusted total serum calcium in the bolus group were normal at 1-2 weeks (2.73 mmol/L) and 3-4 months (2.55 mmol/L). CONCLUSION: Single bolus dosing of 50 000 IU cholecalciferol achieves higher 25OHD repletion rates at 1-2 weeks of age compared with daily dosing, but repletion rates were similar by 3-4 months. There was no hypercalcaemia documented with single bolus dosing in this study.
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ItemCirculating CD147 predicts mortality in advanced hepatocellular carcinoma(WILEY-BLACKWELL, 2016-02)BACKGROUND AND AIM: The glycoprotein CD147 has a role in tumor progression, is readily detectable in the circulation, and is abundantly expressed in hepatocellular carcinoma (HCC). Advanced HCC patients are a heterogeneous group with some individuals having dismal survival. The aim of this study was to examine circulating soluble CD147 levels as a prognostic marker in HCC patients. METHODS: CD147 was measured in 277 patients (110 HCC, 115 chronic liver disease, and 52 non-liver disease). Clinical data included etiology, tumor progression, Barcelona Clinic Liver Cancer (BCLC) stage, and treatment response. Patients with HCC were stratified into two groups based upon the 75th percentile of CD147 levels (24 ng/mL). RESULTS: CD147 in HCC correlated inversely with poor survival (P = 0.031). Increased CD147 predicted poor survival in BCLC stages C and D (P = 0.045), and CD147 levels >24 ng/mL predicted a significantly diminished 90-day and 180-day survival time (hazard ratio [HR] = 6.1; 95% confidence interval [CI]: 2.1-63.2; P = 0.0045 and HR = 2.8; 95% CI: 1.2-12.6; P = 0.028, respectively). In BCLC stage C, CD147 predicted prognosis; levels >24 ng/mL were associated with a median survival of 1.5 months compared with 6.5 months with CD147 levels ≤24 ng/mL (P = 0.03). CD147 also identified patients with a poor prognosis independent from treatment frequency, modality, and tumor size. CONCLUSIONS: Circulating CD147 is an independent marker of survival in advanced HCC. CD147 requires further evaluation as a potential new prognostic measure in HCC to identify patients with advanced disease who have a poor prognosis.
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ItemComparisons of direct and indirect utilities in adult epilepsy populations: A systematic review(WILEY, 2019-12)OBJECTIVE: Epilepsy is common and carries substantial morbidity, and therefore identifying cost-effective health interventions is essential. Cost-utility analysis is a widely used method for such analyses. For this, health conditions are rated in terms of utilities, which provide a standardized score to reflect quality of life. Utilities are obtained either indirectly using quality of life questionnaires, or directly from patients or the general population. We sought to describe instruments used to estimate utilities in epilepsy populations, and how results differ according to methods used. METHODS: We undertook a systematic review of studies comparing at least two instruments for obtaining utilities in epilepsy populations. MEDLINE, Embase, ScienceDirect, Cochrane Library, Google Scholar, and gray literature were searched from inception to June 2019. Mean utilities were recorded and compared for each method. RESULTS: Of the 38 unique records initially identified, eight studies met inclusion criteria. Utilities were highest for direct "tradeoff" methods, obtained via instruments including standard gamble (0.93) and time tradeoff (0.92), compared to indirect methods, obtained via instruments including EuroQoL five-dimensional form (range = 0.72-0.86) and Health Utilities Index Mark 3 (range = 0.52-0.71). Visual analog scale (VAS), a direct "nontradeoff" instrument, provided equal or lower utilities (range = 68.0-79.8) compared to indirect instruments. SIGNIFICANCE: Direct methods, with the important exception of VAS, may provide higher utilities than indirect methods. More studies are needed to identify the most appropriate utility instruments for epilepsy populations, and to investigate whether there is variation between utilities for different types of epilepsy and other patient- and disease-specific factors.