Surgery (St Vincent's) - Research Publications

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    Effect of Disease-Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years
    Kalincik, T ; Diouf, I ; Sharmin, S ; Malpas, C ; Spelman, T ; Horakova, D ; Havrdova, EK ; Trojano, M ; Izquierdo, G ; Lugaresi, A ; Prat, A ; Girard, M ; Duquette, P ; Grammond, P ; Jokubaitis, V ; Van der Walt, A ; Grand'Maison, F ; Sola, P ; Ferraro, D ; Shaygannejad, V ; Alroughani, R ; Hupperts, R ; Terzi, M ; Boz, C ; Lechner-Scott, J ; Pucci, E ; Van Pesch, V ; Granella, F ; Bergamaschi, R ; Spitaleri, D ; Slee, M ; Vucic, S ; Ampapa, R ; McCombe, P ; Ramo-Tello, C ; Prevost, J ; Olascoaga, J ; Cristiano, E ; Barnett, M ; Saladino, ML ; Sanchez-Menoyo, JL ; Hodgkinson, S ; Rozsa, C ; Hughes, S ; Moore, F ; Shaw, C ; Butler, E ; Skibina, O ; Gray, O ; Kermode, A ; Csepany, T ; Singhal, B ; Shuey, N ; Piroska, I ; Taylor, B ; Simo, M ; Sirbu, C-A ; Sas, A ; Butzkueven, H (LIPPINCOTT WILLIAMS & WILKINS, 2021-02-02)
    OBJECTIVE: To test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis (MS), we modeled disability outcomes in 14,717 patients. METHODS: We studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year, and exposed to MS therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the cumulative hazards of 12-month confirmed increase and decrease in disability, Expanded Disability Status Scale (EDSS) step 6, and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously readjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability, and MRI activity. RESULTS: A total of 14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval [CI] 0.43-0.82, p = 0.0016), worsening of disability (0.56, 0.38-0.82, p = 0.0026), and progress to EDSS step 6 (0.33, 0.19-0.59, p = 0.00019). Among 1,085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50-0.70, p = 10-9) and worsening of disability (0.81, 0.67-0.99, p = 0.043). CONCLUSION: Continued treatment with MS immunotherapies reduces disability accrual by 19%-44% (95% CI 1%-62%), the risk of need of a walking aid by 67% (95% CI 41%-81%), and the frequency of relapses by 40-41% (95% CI 18%-57%) over 15 years. This study provides evidence that disease-modifying therapies are effective in improving disability outcomes in relapsing-remitting MS over the long term. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that, for patients with relapsing-remitting MS, long-term exposure to immunotherapy prevents neurologic disability.
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    Predictors of treatment switching in the Big Multiple Sclerosis Data Network.
    Spelman, T ; Magyari, M ; Butzkueven, H ; Van Der Walt, A ; Vukusic, S ; Trojano, M ; Iaffaldano, P ; Horáková, D ; Drahota, J ; Pellegrini, F ; Hyde, R ; Duquette, P ; Lechner-Scott, J ; Sajedi, SA ; Lalive, P ; Shaygannejad, V ; Ozakbas, S ; Eichau, S ; Alroughani, R ; Terzi, M ; Girard, M ; Kalincik, T ; Grand'Maison, F ; Skibina, O ; Khoury, SJ ; Yamout, B ; Sa, MJ ; Gerlach, O ; Blanco, Y ; Karabudak, R ; Oreja-Guevara, C ; Altintas, A ; Hughes, S ; McCombe, P ; Ampapa, R ; de Gans, K ; McGuigan, C ; Soysal, A ; Prevost, J ; John, N ; Inshasi, J ; Stawiarz, L ; Manouchehrinia, A ; Forsberg, L ; Sellebjerg, F ; Glaser, A ; Pontieri, L ; Joensen, H ; Rasmussen, PV ; Sejbaek, T ; Poulsen, MB ; Christensen, JR ; Kant, M ; Stilund, M ; Mathiesen, H ; Hillert, J ; Big MS Data Network: a collaboration of the Czech MS Registry, the Danish MS Registry, Italian MS Registry, Swedish MS Registry, MSBase Study Group, and OFSEP, (Frontiers Media SA, 2023)
    BACKGROUND: Treatment switching is a common challenge and opportunity in real-world clinical practice. Increasing diversity in disease-modifying treatments (DMTs) has generated interest in the identification of reliable and robust predictors of treatment switching across different countries, DMTs, and time periods. OBJECTIVE: The objective of this retrospective, observational study was to identify independent predictors of treatment switching in a population of relapsing-remitting MS (RRMS) patients in the Big Multiple Sclerosis Data Network of national clinical registries, including the Italian MS registry, the OFSEP of France, the Danish MS registry, the Swedish national MS registry, and the international MSBase Registry. METHODS: In this cohort study, we merged information on 269,822 treatment episodes in 110,326 patients from 1997 to 2018 from five clinical registries. Patients were included in the final pooled analysis set if they had initiated at least one DMT during the relapsing-remitting MS (RRMS) stage. Patients not diagnosed with RRMS or RRMS patients not initiating DMT therapy during the RRMS phase were excluded from the analysis. The primary study outcome was treatment switching. A multilevel mixed-effects shared frailty time-to-event model was used to identify independent predictors of treatment switching. The contributing MS registry was included in the pooled analysis as a random effect. RESULTS: Every one-point increase in the Expanded Disability Status Scale (EDSS) score at treatment start was associated with 1.08 times the rate of subsequent switching, adjusting for age, sex, and calendar year (adjusted hazard ratio [aHR] 1.08; 95% CI 1.07-1.08). Women were associated with 1.11 times the rate of switching relative to men (95% CI 1.08-1.14), whilst older age was also associated with an increased rate of treatment switching. DMTs started between 2007 and 2012 were associated with 2.48 times the rate of switching relative to DMTs that began between 1996 and 2006 (aHR 2.48; 95% CI 2.48-2.56). DMTs started from 2013 onwards were more likely to switch relative to the earlier treatment epoch (aHR 8.09; 95% CI 7.79-8.41; reference = 1996-2006). CONCLUSION: Switching between DMTs is associated with female sex, age, and disability at baseline and has increased in frequency considerably in recent years as more treatment options have become available. Consideration of a patient's individual risk and tolerance profile needs to be taken into account when selecting the most appropriate switch therapy from an expanding array of treatment choices.
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    Evaluation of Managing Cancer and Living Meaningfully (CALM) in people with advanced non-small cell lung cancer treated with immunotherapies or targeted therapies: protocol for a single-arm, mixed-methods pilot study
    Lynch, FA ; Rodin, G ; Jefford, M ; Duffy, M ; Lai-Kwon, J ; Heynemann, S ; Mileshkin, L ; Briggs, L ; Burke, J ; Leigh, L ; Spelman, T ; Ftanou, M (BMJ PUBLISHING GROUP, 2023-07)
    INTRODUCTION: People with advanced non-small cell lung cancer (NSCLC) treated with immunotherapies (IT) or targeted therapies (TT) may have improved outcomes in a subset of people who respond, raising unique psychological concerns requiring specific attention. These include the need for people with prolonged survival to reframe their life plans and tolerate uncertainty related to treatment duration and prognosis. A brief intervention for people with advanced cancer, Managing Cancer and Living Meaningfully (CALM), could help people treated with IT or TT address these concerns. However, CALM has not been specifically evaluated in this population. This study aims to evaluate the acceptability and feasibility of CALM in people with advanced NSCLC treated with IT or TT and obtain preliminary evidence regarding its effectiveness in this population. METHODS AND ANALYSIS: Twenty people with advanced NSCLC treated with IT or TT will be recruited from Peter MacCallum Cancer Centre, Melbourne, Australia. Participants will complete three to six sessions of CALM delivered over 3-6 months. A prospective, single-arm, mixed-methods pilot study will be conducted. Participants will complete outcome measures at baseline, post-intervention, 3 months and 6 months, including Patient Health Questionnaire, Death and Dying Distress Scale, Functional Assessment of Cancer Therapy General and Clinician Evaluation Questionnaire. The acceptability of CALM will be assessed using patient experiences surveys and qualitative interviews. Feasibility will be assessed by analysis of recruitment rates, treatment adherence and intervention delivery time. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Peter MacCallum Cancer Centre Human Research Ethics Committee (HREC/82047/PMCC). Participants with cancer will complete a signed consent form prior to participation, and carers and therapists will complete verbal consent. Results will be made available to funders, broader clinicians and researchers through conference presentations and publications. If CALM is found to be acceptable in this cohort, this will inform a potential phase 3 trial.
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    Patients' Views on AI for Risk Prediction in Shared Decision-Making for Knee Replacement Surgery: Qualitative Interview Study
    Gould, DJ ; Dowsey, MM ; Glanville-Hearst, M ; Spelman, T ; Bailey, JA ; Choong, PFM ; Bunzli, S (JMIR PUBLICATIONS, INC, 2023-09-18)
    BACKGROUND: The use of artificial intelligence (AI) in decision-making around knee replacement surgery is increasing, and this technology holds promise to improve the prediction of patient outcomes. Ambiguity surrounds the definition of AI, and there are mixed views on its application in clinical settings. OBJECTIVE: In this study, we aimed to explore the understanding and attitudes of patients who underwent knee replacement surgery regarding AI in the context of risk prediction for shared clinical decision-making. METHODS: This qualitative study involved patients who underwent knee replacement surgery at a tertiary referral center for joint replacement surgery. The participants were selected based on their age and sex. Semistructured interviews explored the participants' understanding of AI and their opinions on its use in shared clinical decision-making. Data collection and reflexive thematic analyses were conducted concurrently. Recruitment continued until thematic saturation was achieved. RESULTS: Thematic saturation was achieved with 19 interviews and confirmed with 1 additional interview, resulting in 20 participants being interviewed (female participants: n=11, 55%; male participants: n=9, 45%; median age: 66 years). A total of 11 (55%) participants had a substantial postoperative complication. Three themes captured the participants' understanding of AI and their perceptions of its use in shared clinical decision-making. The theme Expectations captured the participants' views of themselves as individuals with the right to self-determination as they sought therapeutic solutions tailored to their circumstances, needs, and desires, including whether to use AI at all. The theme Empowerment highlighted the potential of AI to enable patients to develop realistic expectations and equip them with personalized risk information to discuss in shared decision-making conversations with the surgeon. The theme Partnership captured the importance of symbiosis between AI and clinicians because AI has varied levels of interpretability and understanding of human emotions and empathy. CONCLUSIONS: Patients who underwent knee replacement surgery in this study had varied levels of familiarity with AI and diverse conceptualizations of its definitions and capabilities. Educating patients about AI through nontechnical explanations and illustrative scenarios could help inform their decision to use it for risk prediction in the shared decision-making process with their surgeon. These findings could be used in the process of developing a questionnaire to ascertain the views of patients undergoing knee replacement surgery on the acceptability of AI in shared clinical decision-making. Future work could investigate the accuracy of this patient group's understanding of AI, beyond their familiarity with it, and how this influences their acceptance of its use. Surgeons may play a key role in finding a place for AI in the clinical setting as the uptake of this technology in health care continues to grow.
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    Trial of Vancomycin and Cefazolin as Surgical Prophylaxis in Arthroplasty
    Peel, TN ; Astbury, S ; Cheng, AC ; Paterson, DL ; Buising, KL ; Spelman, T ; An, T-D ; Adie, S ; Boyce, G ; McDougall, C ; Molnar, R ; Mulford, J ; Rehfisch, P ; Solomon, M ; Crawford, R ; Harris-Brown, T ; Roney, J ; Wisniewski, J ; de Steiger, R ; ASAP, TG (MASSACHUSETTS MEDICAL SOC, 2023-10-19)
    BACKGROUND: The addition of vancomycin to beta-lactam prophylaxis in arthroplasty may reduce surgical-site infections; however, the efficacy and safety are unclear. METHODS: In this multicenter, double-blind, superiority, placebo-controlled trial, we randomly assigned adult patients without known methicillin-resistant Staphylococcus aureus (MRSA) colonization who were undergoing arthroplasty to receive 1.5 g of vancomycin or normal saline placebo, in addition to cefazolin prophylaxis. The primary outcome was surgical-site infection within 90 days after surgery. RESULTS: A total of 4239 patients underwent randomization. Among 4113 patients in the modified intention-to-treat population (2233 undergoing knee arthroplasty, 1850 undergoing hip arthroplasty, and 30 undergoing shoulder arthroplasty), surgical-site infections occurred in 91 of 2044 patients (4.5%) in the vancomycin group and in 72 of 2069 patients (3.5%) in the placebo group (relative risk, 1.28; 95% confidence interval [CI], 0.94 to 1.73; P = 0.11). Among patients undergoing knee arthroplasty, surgical-site infections occurred in 63 of 1109 patients (5.7%) in the vancomyin group and in 42 of 1124 patients (3.7%) in the placebo group (relative risk, 1.52; 95% CI, 1.04 to 2.23). Among patients undergoing hip arthroplasty, surgical-site infections occurred in 28 of 920 patients (3.0%) in the vancomyin group and in 29 of 930 patients (3.1%) in the placebo group (relative risk, 0.98; 95% CI, 0.59 to 1.63). Adverse events occurred in 35 of 2010 patients (1.7%) in the vancomycin group and in 35 of 2030 patients (1.7%) in the placebo group, including hypersensitivity reactions in 24 of 2010 patients (1.2%) and 11 of 2030 patients (0.5%), respectively (relative risk, 2.20; 95% CI, 1.08 to 4.49), and acute kidney injury in 42 of 2010 patients (2.1%) and 74 of 2030 patients (3.6%), respectively (relative risk, 0.57; 95% CI, 0.39 to 0.83). CONCLUSIONS: The addition of vancomycin to cefazolin prophylaxis was not superior to placebo for the prevention of surgical-site infections in arthroplasty among patients without known MRSA colonization. (Funded by the Australian National Health and Medical Research Council; Australian New Zealand Clinical Trials Registry number, ACTRN12618000642280.).
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    COVID-19 infection among patients with cancer in Australia from 2020 to 2022: a national multicentre cohort study
    Hall, VG ; Sim, BZ ; Lim, C ; Hocking, C ; Teo, T ; Runnegar, N ; Boan, P ; Heath, CH ; Rainey, N ; Lyle, M ; Steer, C ; Liu, E ; Doig, C ; Drummond, K ; Charles, PGP ; See, K ; Lim, L-L ; Shum, O ; Bak, N ; Mclachlan, S-A ; Singh, KP ; Laundy, N ; Gallagher, J ; Stewart, M ; Saunders, NR ; Klimevski, E ; Demajo, J ; Reynolds, G ; Thursky, KA ; Worth, LJ ; Spelman, T ; Yong, MK ; Slavin, MA ; Teh, BW (ELSEVIER, 2023-09)
    BACKGROUND: The global COVID-19 pandemic disproportionately affected certain populations and its management differed between countries. This national study describes characteristics and outcomes of COVID-19 in patients with cancer in Australia. METHODS: We performed a multicentre cohort study of patients with cancer and COVID-19 from March 2020 to April 2022. Data were analysed to determine varying characteristics between cancer types and changes in outcomes over time. Multivariable analysis was performed to determine risk factors associated with oxygen requirement. FINDINGS: 620 patients with cancer from 15 hospitals had confirmed COVID-19. There were 314/620 (50.6%) male patients, median age 63.5 years (IQR 50-72) and majority had solid organ tumours (392/620, 63.2%). The rate of COVID-19 vaccination (≥1 dose) was 73.4% (455/620). Time from symptom onset to diagnosis was median 1 day (IQR 0-3), patients with haematological malignancy had a longer duration of test positivity. Over the study period, there was a significant decline in COVID-19 severity. Risk factors associated with oxygen requirement included male sex (OR 2.34, 95% CI 1.30-4.20, p = 0.004), age (OR 1.03, 95% CI 1.01-1.06, p = 0.005); not receiving early outpatient therapy (OR 2.78, 95% CI 1.41-5.50, p = 0.003). Diagnosis during the omicron wave was associated with lower odds of oxygen requirement (OR 0.24, 95% CI 0.13-0.43, p < 0.0001). INTERPRETATION: Outcomes from COVID-19 in patients with cancer in Australia over the pandemic have improved, potentially related to changing viral strain and outpatient therapies. FUNDING: This study was supported by research funding from MSD.
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    A plain language summary on the effectiveness of cladribine tablets compared with other oral treatments for multiple sclerosis: results from the MSBase registry
    Spelman, T ; Ozakbas, S ; Alroughani, R ; Terzi, M ; Hodgkinson, S ; Laureys, G ; Kalincik, T ; Van der Walt, A ; Yamout, B ; Lechner-Scott, J ; Soysal, A ; Kuhle, J ; Sanchez-Menoyo, JL ; Morgado, YB ; Spitaleri, DLA ; van Pesch, V ; Horakova, D ; Ampapa, R ; Patti, F ; Macdonell, R ; Al-Asmi, A ; Gerlach, O ; Oh, J ; Altintas, A ; Tundia, N ; Wong, SL ; Butzkueven, H ; MSBase, SG (FUTURE MEDICINE LTD, 2023-08)
    WHAT IS THIS SUMMARY ABOUT?: Patient registries contain anonymous data from people who share the same medical condition. The MSBase registry contains information from over 80,000 people living with multiple sclerosis (MS) across 41 countries. Using information from the MSBase registry, the GLIMPSE (Generating Learnings In MultiPle SclErosis) study looked at real-life outcomes in 3475 people living with MS who were treated with cladribine tablets (Mavenclad®) compared with other oral treatments. WHAT WERE THE RESULTS?: Results showed that people treated with cladribine tablets stayed on treatment for longer than other treatments given by mouth. They also had fewer relapses (also called flare ups of symptoms) than people who received a different oral treatment for their MS. WHAT DO THE RESULTS MEAN?: The results provide evidence that, compared with other oral treatments for MS, cladribine tablets are an effective medicine for people living with MS.
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    Individualized Risk Prediction for Improved Chronic Wound Management
    Velickovic, VM ; Spelman, T ; Clark, M ; Probst, S ; Armstrong, DG ; Steyerberg, E (MARY ANN LIEBERT, INC, 2023-07-01)
    Significance: Chronic wounds are associated with significant morbidity, marked loss of quality of life, and considerable economic burden. Evidence-based risk prediction to guide improved wound prevention and treatment is limited by the complexity in their etiology, clinical underreporting, and a lack of studies using large high-quality datasets. Recent Advancements: The objective of this review is to summarize key components and challenges in the development of personalized risk prediction tools for both prevention and management of chronic wounds, while highlighting several innovations in the development of better risk stratification. Critical Issues: Regression-based risk prediction approaches remain important for assessment of prognosis and risk stratification in chronic wound management. Advances in statistical computing have boosted the development of several promising machine learning (ML) and other semiautomated classification tools. These methods may be better placed to handle large number of wound healing risk factors from large datasets, potentially resulting in better risk prediction when combined with conventional methods and clinical experience and expertise. Future Directions: Where the number of predictors is large and heterogenous, the correlations between various risk factors complex, and very large data sets are available, ML may prove a powerful adjuvant for risk stratifying patients predisposed to chronic wounds. Conventional regression-based approaches remain important, particularly where the number of predictors is relatively small. Translating estimated risk derived from ML algorithms into practical prediction tools for use in clinical practice remains challenging.
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    Comparative effectiveness of cladribine tablets versus other oral disease-modifying treatments for multiple sclerosis: Results from MSBase registry
    Spelman, T ; Ozakbas, S ; Alroughani, R ; Terzi, M ; Hodgkinson, S ; Laureys, G ; Kalincik, T ; Van der Walt, A ; Yamout, B ; Lechner-Scott, J ; Soysal, A ; Kuhle, J ; Sanchez-Menoyo, JL ; Morgado, YB ; La Spitaleri, D ; van Pesch, V ; Horakova, D ; Ampapa, R ; Patti, F ; Macdonell, R ; Al-Asmi, A ; Gerlach, O ; Oh, J ; Altintas, A ; Tundia, N ; Wong, SL ; Butzkueven, H (SAGE PUBLICATIONS LTD, 2023-02)
    BACKGROUND: Effectiveness of cladribine tablets, an oral disease-modifying treatment (DMT) for multiple sclerosis (MS), was established in clinical trials and confirmed with real-world experience. OBJECTIVES: Use real-world data to compare treatment patterns and clinical outcomes in people with MS (pwMS) treated with cladribine tablets versus other oral DMTs. METHODS: Retrospective treatment comparisons were based on data from the international MSBase registry. Eligible pwMS started treatment with cladribine, fingolimod, dimethyl fumarate, or teriflunomide tablets from 2018 to mid-2021 and were censored at treatment discontinuation/switch, death, loss to follow-up, pregnancy, or study period end. Treatment persistence was evaluated as time to discontinuation/switch; relapse outcomes included time to first relapse and annualized relapse rate (ARR). RESULTS: Cohorts included 633 pwMS receiving cladribine tablets, 1195 receiving fingolimod, 912 receiving dimethyl fumarate, and 735 receiving teriflunomide. Individuals treated with fingolimod, dimethyl fumarate, or teriflunomide switched treatment significantly more quickly than matched cladribine tablet cohorts (adjusted hazard ratio (95% confidence interval): 4.00 (2.54-6.32), 7.04 (4.16-11.93), and 6.52 (3.79-11.22), respectively). Cladribine tablet cohorts had significantly longer time-to-treatment discontinuation, time to first relapse, and lower ARR, compared with other oral DMT cohorts. CONCLUSION: Cladribine tablets were associated with a significantly greater real-world treatment persistence and more favorable relapse outcomes than all oral DMT comparators.
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    Medial Pivot Designs Versus Conventional Bearing Types in Primary Total Knee Arthroplasty: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
    Hoskins, W ; Smith, G ; Spelman, T ; Vince, KG (LIPPINCOTT WILLIAMS & WILKINS, 2022-12)
    BACKGROUND: Medial pivot (MP) designs are growing in popularity. They provide increased sagittal plane stability and theoretically replicate some aspects of native joint kinematics, which may improve total knee arthroplasty outcomes. METHODS: A systematic review was performed of randomized controlled trials (RCTs) that compared MP designs with cruciate-retaining, posterior-stabilized (PS), ultracongruent, or mobile-bearings in primary total knee arthroplasty, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome measures were all clinical function scores, patient-reported outcome measures, and range of motion. The secondary outcome was complications. Two authors independently selected studies, performed data extraction, and risk-of-bias assessment. Studies at high risk of bias were excluded from meta-analysis. Treatment effects were assessed using random-effects meta-analysis and quantified using pooled mean differences or incidence rate differences as appropriate. RESULTS: Eight RCTs met inclusion criteria. Five compared MP with PS, two with ultracongruent, and one with cruciate-retaining and mobile-bearing. In total, 350 knees were randomized to MP and 375 to conventional bearings. One RCT was excluded from meta-analysis because of high risk of bias. Meta-analysis comparing MP with PS only was possible and found no differences at any time points for any outcome measure, including 2-year follow-up for Oxford Knee Score (MD = 0.35 favoring PS; 95% CI -0.49 to 1.20) and range of motion (MD = 1.58 favoring MP; 95% CI -0.76 to 11.92, P = 0.30) and 12 months for Western Ontario Arthritis Index (MD = 4.42 favoring MP; 95% CI -12.04 to 3.20, P = 0.09). CONCLUSIONS: There is no difference in clinical outcomes, with contemporary measurement tools, at any time points, between MP and PS. There are insufficient RCTs comparing MP with other bearings.