Medicine (St Vincent's) - Research Publications

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    Background and Breakthrough Opioid Choice May Determine Different Pain Outcomes
    Wong, AK ; Vogrin, S ; Le, B ; Klepstad, P ; Rubio, JP ; Somogyi, AA ; Philip, J (ELSEVIER SCIENCE INC, 2024-03)
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    Effect of gene variants on opioid dose, pain and adverse effect outcomes in advanced cancer: an explorative study
    Wong, AK ; Klepstad, P ; Somogyi, AA ; Vogrin, S ; Le, B ; Philip, J ; Rubio, JP (FUTURE MEDICINE LTD, 2023-12)
    Aim: Associations between gene variants and opioid net effect are unclear. We conducted an exploratory pharmacogenetic analysis of 35 gene variants and opioid response in advanced cancer. Patients & methods: This multi-center prospective cohort study included clinical data, questionnaires (pain and adverse effects) and DNA (blood). Negative binomial regression and logistic regression were used. Results: Within 54 participants, eight statistically significant associations (p = 0.002-0.038) were observed between gene variants and opioid dose, pain scores or adverse effects, the majority being within the neuroimmune TLR4 pathway (IL1B [rs1143634], IL2 [rs2069762], IL6 [rs1800795], BDNF [rs6265]) and ARRB2 pathway (ARRB2 [rs3786047], DRD2 [rs6275]). Conclusion: Neuroimmune pathway genes may contribute to differences in opioid response in cancer and may be included in future similar studies.
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    Opioid Switch Dosing in Chronic Cancer Pain: A Prospective Longitudinal Study
    Wong, AK ; Klepstad, P ; Rubio, JP ; Somogyi, AA ; Vogrin, S ; Le, B ; Philip, J (Mary Ann Liebert, 2024-03)
    Background: Opioid switching is common, however, conversion tables have limitations. Guidelines suggest postswitch dose reduction, yet, observations show opioid doses may increase postswitch. Objectives: To document the opioid conversion factor postswitch in cancer, and whether pain and adverse effect outcomes differ between switched opioid groups. Design/Setting: This multicenter prospective longitudinal study included people with advanced cancer in Australia. Clinical data (demographics, opioids) and validated instruments (pain, adverse effects) were collected twice, seven days apart. Results: Opioid switch resulted in dose increase (median oral morphine equivalent daily dose 90 mg [interquartile range {IQR} 45-184] to 150 mg [IQR 79-270]), reduced average pain (5.1 [standard deviation {SD} 1.7] to 3.8 [SD 1.6]), and reduced adverse effects. Hydromorphone dose increased 2.5 times (IQR 1.0-3.6) above the original conversion factor used. Conclusions: Opioid switching resulted in overall dose increase, particularly when switching to hydromorphone. Higher preswitch dosing may require higher dose conversion ratios. Dose reduction postswitch risks undertreatment and may not be always appropriate.
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    Phenotypic distribution and tolerability of re-vaccination in individuals with delayed hypersensitivity to COVID-19 vaccines
    De Luca, J ; Awad, A ; Vogrin, S ; Waldron, J ; Douglas, A ; Chua, K ; Holmes, N ; Trubiano, J (MOSBY-ELSEVIER, 2023-02)
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    Exploring new balance and gait factors that are associated with osteosarcopenia in patients with a previous fall and/or fracture history
    Debruin, D ; Miksa, K ; Vogrin, S ; Duque, G ; Sales, M ; Hayes, A (ELSEVIER IRELAND LTD, 2024-02)
    Osteosarcopenic individuals have poor muscle function and increased bone fragility, which results in a severe detriment to health outcomes. Hence, there is a necessity to discover easily accessible factors associated with osteosarcopenia to develop timely interventions. This study aimed to determine new sensitive balance and/or gait variables that are associated with osteosarcopenia in a population of older people with a history of falls and/or fractures. In a cross-sectional cohort study, 306 men and women aged ≥65 years completed a series of questionnaires, clinical assessments and muscle strength and function tests. Subsequently, participants were separated into osteopenia, osteoporosis and osteosarcopenia, groups for comparison and further analysis. Osteosarcopenia performed worse than osteopenia and osteoporosis in grip strength, gait speed, physical function scores and in multiple gait and balance indices (p<0.001). During posturography testing, there were larger elliptical areas with eyes open (p = 0.003), and eyes closed (p = 0.043) and increased sway velocity on a firm platform (p = 0.007) in the osteosarcopenia group, compared to osteoporosis. Limits of stability and eyes open ellipse area significantly contributed to the multivariable model (p = 0.029 and p = 0.038, respectively), suggesting that these balance parameters, along with grip strength, may be useful in identifying older adults with osteosarcopenia from those with only osteopenia/osteoporosis. Older adults with osteosarcopenia and a history of falls and/or fractures demonstrated inferior strength, function, and gait characteristics. This study identified indices of balance that were sensitive discriminators for osteosarcopenia and could be easily implemented into routine assessment.
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    Have changing practices in salvage medical options affected colectomy rates in acute severe ulcerative colitis?
    Clark, N ; MacIsaac, M ; Little, R ; Vogrin, S ; Harrison, M ; Tiang, T ; Keck, J ; Johnston, M ; Cunningham, G ; Wright, E ; Connell, W (WILEY, 2023-12)
    BACKGROUND: In 2014, infliximab (IFX) was listed on the Australian Pharmaceutical Benefits Scheme for acute severe ulcerative colitis (ASUC) and is now the preferred option for medical salvage, superseding cyclosporin A (CsA). Optimal dosing schedules for IFX remain unknown. AIM: The authors aim to evaluate the effect of changing from predominantly CsA to almost exclusively IFX for the treatment of steroid-refractory ASUC on colectomy rates. METHODS: A retrospective review was performed of patients admitted with ASUC between 2012 and 2020. Patients were categorised into two groups according to year of presentation - either 'historical treatment' cohort (2012-2014), when CsA was primarily used, or 'contemporary treatment' cohort (2014-2020), when IFX was mostly prescribed, in either standard or intensive doses. RESULTS: One hundred thirty-nine patients were included; 37 in the historical treatment cohort and 102 in the contemporary treatment cohort. In the historical treatment cohort, 12 of 37 received salvage therapy and eight (67%) received CsA. In the contemporary treatment cohort, 49 of 102 patients received salvage therapy, 40 (82%) with IFX, of whom 22 (53%) received intensified doses. Colectomy rates were similar at 30 days, 6 months and 12 months between historical and contemporary treatment cohorts (14% vs 12% [P = 0.77], 19% vs 18% [P > 0.99],and 22% vs 18% [P = 0.63], respectively). Difference in 12-month colectomy rates between standard versus intensive IFX did not meet statistical significance (three of 21 [14%] vs nine of 22 [41%]. respectively; P = 0.09). CONCLUSION: There was no difference in 30-day, 6-month or 12-month colectomy rates between the historical treatment and contemporary treatment cohorts. The use of IFX, rather than CsA, even at intensified dosing, does not appear to reduce the colectomy rate observed in our patients.
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    Penicillin Allergy Delabeling Program: an exploratory economic evaluation in the Australian context
    Brusco, NK ; Bury, S ; Chua, KYL ; Vogrin, S ; Holmes, NE ; Trubiano, JA (WILEY, 2023-01)
    BACKGROUND: Internationally, clinical and economic advantages of low-risk penicillin delabelling have been explored, supporting changes to healthcare delivery systems where penicillin delabelling is embedded into inpatient usual care. AIMS: To determine if economic advantages of low-risk inpatient penicillin delabelling, described in the international literature, are realised in the Australian context. METHODS: This explorative economic evaluation had prospective patient data collection between January and August 2019, across two Australian health services. Part 1: determine the cost per effectively delabelled patient for Penicillin Allergy Delabeling Program inpatients (PADP cohort) compared with Outpatient Antibiotic Allergy Testing Service outpatients (OAATS cohort). Part 2: a cost analysis to compare hospital costs for inpatients with low-risk penicillin allergy who did (PADP cohort) and did not (usual care cohort) undergo PADP delabelling. RESULTS: Part 1: the PADP (n = 350) and OAATS (n = 27 patients, n = 36 individual visits) cohorts were comparable. In PADP, costs/proportion delabelled was $20.10/0.98, equating to $20.51 per effectively delabelled patient; in OAATS, it was $181.24/0.50, equating to $362. Compared with OAATS, PADP was associated with savings of $341.97 per effectively delabelled patient, indicating the outpatient testing was the dominated strategy, being more costly and less effective. Part 2: the PADP (n = 218) and usual care (n = 32) cohorts were comparable. Significantly favouring the delabelled PADP cohort, the mean difference per patient was -4.41 days (95% confidence interval: -7.64, -1.18) and -$9467.72 (95% confidence interval: -$15 419.98, -$3515.46). CONCLUSIONS: Consistent with international literature, delabelling low-risk penicillin allergies in the inpatient setting had economic advantages in the Australian context. Fully powered economic evaluations are urgently required to consolidate these findings.
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    Cognition in healthy older women is a predictor of 14‐year falls risk
    Faux, NG ; Bird, S ; Michalewicz, A ; Pasco, JA ; Sales, MPR ; Russo‐Batterham, D ; Vogrin, S ; Williams, LJ ; Duque, G ; Szoeke, C (Wiley, 2021-12)
    Background: Falls are a significant cause of injuries, loss of confidence, increased morbidity, and institutionalisation in all older people, with women at 50% greater risk than men. The relationship between dementia and falls is well established and 2/3 of all dementia occurs in women. In this study we explored risk factors associated with a 14 year falls risk in a community-based cohort of women, which included validated measures across a wide range of clinical domains including neuropsychological, mood, quality of life and biomarkers (including hormonal). Method: The Australian Women’s Healthy Aging Project is an longitudinal observation study, assessments every year (1991 –1999), followed by assessments in 2002, 2004, 2012 and 2014. The assessments included cognitive (as of 2002), blood, and cardiovascular disease risk assessment, and questions related to falls. After data cleaning, the remaining cohort consisted of 180 participants (Table 1). Missing data were imputed using mice random forest. To identify key risk factors associated with a 14 year falls risk, random survival (time to event) forest (RSF) machine learning was used. Result: The RSF model, using all 290+ possible predictive variables, performed well with an Out Of Bag (OOB, withheld data) prediction error (C-index) of 32.8%. The most predictive variables in the model were identified using the variable importance measure (VIM). The initial model was refined by taking the top 30 predictive variables and retraining the RSF. This refined model resulted in an improved OOB C-index of 5.8% (27%). The top 20 predictive variables, Figure 1, include those associated with cardiovascular disease risk, cognitive performance, and hormone levels (e.g., family history of heart attack, digit symbol coding, and estradiol levels). Conclusion: Ninety percent of the top 20 predictive risk variables for the 14 year fall risk in women, were from three key domains, cognition (40%), cardiovascular (25%) and hormone-related measurements (25%). Our data suggest that for long term prevention of falls these domains may be important reducing risk of falls in the senior female population.
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    Relationship Between Plasma Homocysteine and Bone Density, Lean Mass, Muscle Strength and Physical Function in 1480 Middle-Aged and Older Adults: Data from NHANES
    Kositsawat, J ; Vogrin, S ; French, C ; Gebauer, M ; Candow, DG ; Duque, G ; Kirk, B (SPRINGER, 2023-01)
    Hyperhomocysteinemia induces oxidative stress and chronic inflammation (both of which are catabolic to bone and muscle); thus, we examined the association between homocysteine and body composition and physical function in middle-aged and older adults. Data from the National Health and Nutrition Examination Survey was used to build regression models. Plasma homocysteine (fluorescence immunoassay) was used as the exposure and bone mineral density (BMD; dual-energy X-ray absorptiometry; DXA), lean mass (DXA), knee extensor strength (isokinetic dynamometer; newtons) and gait speed (m/s) were used as outcomes. Regression models were adjusted for confounders (age, sex, race/Hispanic origin, height, fat mass %, physical activity, smoking status, alcohol intakes, cardiovascular disease, diabetes, cancer and vitamin B12). All models accounted for complex survey design by using sampling weights provided by NHANES. 1480 adults (median age: 64 years [IQR: 56, 73]; 50.3% men) were included. In multivariable models, homocysteine was inversely associated with knee extensor strength (β = 0.98, 95% CI 0.96, 0.99, p = 0.012) and gait speed (β = 0.85, 95% CI 0.78, 0.94, p = 0.003) and borderline inversely associated with femur BMD (β = 0.84, 95% CI 0.69, 1.03, p = 0.086). In the sub-group analysis of older adults (≥ 65 years), homocysteine was inversely associated with gait speed and femur BMD (p < 0.05) and the slope for knee extensor strength and whole-body BMD were in the same direction. No significant associations were observed between homocysteine and total or appendicular lean mass in the full or sub-group analysis. We found inverse associations between plasma homocysteine and muscle strength/physical function, and borderline significant inverse associations for femur BMD.
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    Discontinuation of nucleot(s)ide analogue therapy in HBeAg-negative chronic hepatitis B: a meta-analysis
    Hall, SAL ; Vogrin, S ; Wawryk, O ; Burns, GS ; Visvanathan, K ; Sundararajan, V ; Thompson, A (BMJ PUBLISHING GROUP, 2022-08)
    BACKGROUND AND AIMS: Sustained virological suppression and hepatitis B surface antigen (HBsAg) loss have been described after nucleot(s)ide analogue (NA) discontinuation for patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). We performed a meta-analysis of the clinical outcomes after NA discontinuation for HBeAg-negative CHB. METHODS: Studies involving NA cessation in HBeAg-negative CHB individuals with a median follow-up of ≥12 months were included. Participants were HBeAg-negative at the time of NA initiation. Random effects meta-analyses were performed for the following clinical outcomes: (1) virological relapse (VR) at 6 and 12 months; (2) clinical relapse (CR) at 6 and 12 months and (3) HBsAg loss. Effect of other variables was estimated using subgroup analysis and meta-regression. Studies including patients stopping entecavir (ETV) and/or tenofovir disoproxil fumarate (TDF) were considered separately to studies including patients stopping older generation NA. RESULTS: N=37 studies met inclusion criteria. Cumulative incidence of VR and CR after stopping ETV/TDF was 44% and 17% at 6 months and 63% and 35% at 12 months. Similar relapse rates were observed after stopping older NAs. Among patients stopping ETV/TDF, TDF cessation was associated with increased CR rates at 6 months versus ETV. There was an association between follow-up ≥4 years and HBsAg loss rates when stopping older NAs. Hepatic decompensation and hepatocellular carcinoma were rare but occurred more frequently in studies including cirrhotic individuals. CONCLUSION: VR is common after NA discontinuation, however, CR was only seen in one-third of patients at 12 months. Stopping NA therapy can be followed by HBsAg clearance, and rates are higher with longer follow-up.