Surgery (Austin & Northern Health) - Research Publications
Now showing items 1-12 of 193
Postoperative complications and hospital costs following small bowel resection surgery.
(Public Library of Science (PLoS), 2020)
BACKGROUND: Postoperative complications after major gastrointestinal surgery are a major contributor to hospital costs. Thus, reducing postoperative complications is a key target for cost-containment strategies. We aimed to evaluate the relationship between postoperative complications and hospital costs following small bowel resection. METHODS: Postoperative complications were recorded for 284 adult patients undergoing major small bowel resection surgery between January 2013 and June 2018. Complications were defined and graded according to the Clavien-Dindo classification system. In-hospital cost of index admission was calculated using an activity-based costing methodology; it was reported in US dollars at 2019 rates. Regression modeling was used to investigate the relationships among a priori selected perioperative variables, complications, and costs. FINDINGS: The overall complication prevalence was 81.6% (95% CI: 85.7-77.5). Most complications (69%) were minor, but 22.9% of patients developed a severe complication (Clavien-Dindo grades III or IV). The unadjusted median total hospital cost for patients with any complication was 70% higher than patients without complications (median [IQR] USD 19,659.64 [13,545.81-35,407.14] vs. 11,551.88 [8,849.46-15,329.87], P < 0.001). The development of 1, 2, 3, and ≥ 4 complications increased hospital costs by 11%, 41%, 50%, and 195%, respectively. Similarly, more severe complications incurred higher hospital costs (P < 0.001). After adjustments were made (for the Charlson Comorbidity Index, anemia, surgical urgency and technique, intraoperative fluid administration, blood transfusion, and hospital readmissions), a greater number and increased severity of complications were associated with a higher adjusted median hospital cost. Patients who experienced complications had an adjusted additional median cost of USD 4,187.10 (95% CI: 1,264.89-7,109.31, P = 0.005) compared to those without complications. CONCLUSIONS: Postoperative complications are a key target for cost-containment strategies. Our findings demonstrate a high prevalence of postoperative complications following small bowel resection surgery and quantify their associated increase in hospital costs. TRIAL REGISTRATION: Australian Clinical Trials Registration number: 12620000322932.
Impact of COVID-19 on Urology Practice: A Global Perspective and Snapshot Analysis
The global impact of the 2019 novel coronavirus disease (COVID-19) pandemic on urology practice remains unknown. Self-selected urologists worldwide completed an online survey by the Société Internationale d'Urologie (SIU). A total of 2494 urologists from 76 countries responded, including 1161 (46.6%) urologists in an academic setting, 719 (28.8%) in a private practice, and 614 (24.6%) in the public sector. The largest proportion (1074 (43.1%)) were from Europe, with the remainder from East/Southeast Asia (441 (17.7%)), West/Southwest Asia (386 (15.5%)), Africa (209 (8.4%)), South America (198 (7.9%)), and North America (186 (7.5%)). An analysis of differences in responses was carried out by region and practice setting. The results reveal significant restrictions in outpatient consultation and non-emergency surgery, with nonspecific efforts towards additional precautions for preventing the spread of COVID-19 during emergency surgery. These restrictions were less notable in East/Southeast Asia. Urologists often bear the decision-making responsibility regarding access to elective surgery (40.3%). Restriction of both outpatient clinics and non-emergency surgery is considerable worldwide but is lower in East/Southeast Asia. Measures to control the spread of COVID-19 during emergency surgery are common but not specific. The pandemic has had a profound impact on urology practice. There is an urgent need to provide improved guidance for this and future pandemics.
Value of laboratory results in addition to vital signs in a machine learning algorithm to predict in-hospital cardiac arrest: A single-center retrospective cohort study
(PUBLIC LIBRARY SCIENCE, 2020-07-13)
BACKGROUND: Although machine learning-based prediction models for in-hospital cardiac arrest (IHCA) have been widely investigated, it is unknown whether a model based on vital signs alone (Vitals-Only model) can perform similarly to a model that considers both vital signs and laboratory results (Vitals+Labs model). METHODS: All adult patients hospitalized in a tertiary care hospital in Japan between October 2011 and October 2018 were included in this study. Random forest models with/without laboratory results (Vitals+Labs model and Vitals-Only model, respectively) were trained and tested using chronologically divided datasets. Both models use patient demographics and eight-hourly vital signs collected within the previous 48 hours. The primary and secondary outcomes were the occurrence of IHCA in the next 8 and 24 hours, respectively. The area under the receiver operating characteristic curve (AUC) was used as a comparative measure. Sensitivity analyses were performed under multiple statistical assumptions. RESULTS: Of 141,111 admitted patients (training data: 83,064, test data: 58,047), 338 had an IHCA (training data: 217, test data: 121) during the study period. The Vitals-Only model and Vitals+Labs model performed comparably when predicting IHCA within the next 8 hours (Vitals-Only model vs Vitals+Labs model, AUC = 0.862 [95% confidence interval (CI): 0.855-0.868] vs 0.872 [95% CI: 0.867-0.878]) and 24 hours (Vitals-Only model vs Vitals+Labs model, AUC = 0.830 [95% CI: 0.825-0.835] vs 0.837 [95% CI: 0.830-0.844]). Both models performed similarly well on medical, surgical, and ward patient data, but did not perform well for intensive care unit patients. CONCLUSIONS: In this single-center study, the machine learning model predicted IHCAs with good discrimination. The addition of laboratory values to vital signs did not significantly improve its overall performance.
A reference collection of patient-derived cell line and xenograft models of proneural, classical and mesenchymal glioblastoma
(NATURE PUBLISHING GROUP, 2019-03-20)
Low-passage, serum-free cell lines cultured from patient tumour tissue are the gold-standard for preclinical studies and cellular investigations of glioblastoma (GBM) biology, yet entrenched, poorly-representative cell line models are still widely used, compromising the significance of much GBM research. We submit that greater adoption of these critical resources will be promoted by the provision of a suitably-sized, meaningfully-described reference collection along with appropriate tools for working with them. Consequently, we present a curated panel of 12 readily-usable, genetically-diverse, tumourigenic, patient-derived, low-passage, serum-free cell lines representing the spectrum of molecular subtypes of IDH-wildtype GBM along with their detailed phenotypic characterisation plus a bespoke set of lentiviral plasmids for bioluminescent/fluorescent labelling, gene expression and CRISPR/Cas9-mediated gene inactivation. The cell lines and all accompanying data are readily-accessible via a single website, Q-Cell (qimrberghofer.edu.au/q-cell/) and all plasmids are available from Addgene. These resources should prove valuable to investigators seeking readily-usable, well-characterised, clinically-relevant, gold-standard models of GBM.
Tumor size and postoperative kidney function following radical nephrectomy
(DOVE MEDICAL PRESS LTD, 2019-01-01)
Background: Chronic kidney disease (CKD) following nephrectomy for kidney tumors is common, and both patient and tumor characteristics may affect postoperative kidney function. Several studies have reported that surgery for large tumors is associated with a lower likelihood of postoperative CKD, but others have reported CKD to be more common before surgery in patients with large tumors. Objective: The aim of this study was to clarify inconsistencies in the literature regarding the prognostic significance of tumor size for postoperative kidney function. Study design and setting: We analyzed data from 944 kidney cancer patients managed with radical nephrectomy between January 2012 and December 2013, and 242 living kidney donors who underwent surgery between January 2011 and December 2014 in the Australian states of Queensland and Victoria. Multivariable logistic regression was used to assess the primary outcome of CKD upstaging. Structural equation modeling was used to evaluate causal models, to delineate the influence of patient and tumor characteristics on postoperative kidney function. Results: We determined that a significant interaction between age and tumor size (P=0.03) led to the observed inverse association between large tumor size and CKD upstaging, and was accentuated by other forms of selection bias. Subgrouping patients by age and tumor size demonstrated that all patients aged ≥65 years were at increased risk of CKD upstaging, regardless of tumor size. Risk of CKD upstaging was comparable between age-matched living donors and kidney cancer patients. Conclusion: Larger tumors are unlikely to confer a protective effect with respect to postoperative kidney function. The reason for the previously reported inconsistency is likely a combination of the analytical approach and selection bias.
BioStructMap: a Python tool for integration of protein structure and sequence-based features
(OXFORD UNIV PRESS, 2018-11-15)
Summary: A sliding window analysis over a protein or genomic sequence is commonly performed, and we present a Python tool, BioStructMap, that extends this concept to three-dimensional (3D) space, allowing the application of a 3D sliding window analysis over a protein structure. BioStructMap is easily extensible, allowing the user to apply custom functions to spatially aggregated data. BioStructMap also allows mapping of underlying genomic sequences to protein structures, allowing the user to perform genetic-based analysis over spatially linked codons-this has applications when selection pressures arise at the level of protein structure. Availability and implementation: The Python BioStructMap package is available at https://github.com/andrewguy/biostructmap and released under the MIT License. An online server implementing standard functionality is available at https://biostructmap.burnet.edu.au. Supplementary information: Supplementary data are available at Bioinformatics online.
The Australian Trauma Registry
INTRODUCTION: Injuries are a major cause of disability and lost productivity. The case for a national trauma registry has been recognized by the Australian Commission on Safety and Quality in Health Care and at a policy level. BACKGROUND: The need was flagged in 1993 by the Royal Australasian College of Surgeons and the Australasian Trauma Society. In 2003, the Centre of National Research and Disability funded the Australian and New Zealand National Trauma Registry Consortium, which produced three consecutive annual reports. The bi-national trauma minimum dataset was also developed during this time. Operations were suspended thereafter. METHOD: In response to sustained lobbying the Australian Trauma Quality Improvement Program including the Australian Trauma Registry (ATR) commenced in 2012, with data collection from 26 major trauma centres. An inaugural report was released in late 2014. RESULT: The Federal Government provided funding in December 2016 enabling the work of the ATR to continue. Data are currently being collected for cases that meet inclusion criteria with dates of injury in the 2017-2018 financial year. Since implementation, the number of submitted records has been increased from fewer than 7000 per year to over 8000 as completeness has improved. Four reports have been released and are available to stakeholders. CONCLUSION: The commitment shown by the College, other organizations and individuals to the vision of a national trauma registry has been consistent since 1993. The ATR is now well placed to improve the care of injured people.
BCL-XL and MCL-1 are the key BCL-2 family proteins in melanoma cell survival
(NATURE PUBLISHING GROUP, 2019-04-24)
Malignant melanoma is one of the most difficult cancers to treat due to its resistance to chemotherapy. Despite recent successes with BRAF inhibitors and immune checkpoint inhibitors, many patients do not respond or become resistant to these drugs. Hence, alternative treatments are still required. Due to the importance of the BCL-2-regulated apoptosis pathway in cancer development and drug resistance, it is of interest to establish which proteins are most important for melanoma cell survival, though the outcomes of previous studies have been conflicting. To conclusively address this question, we tested a panel of established and early passage patient-derived cell lines against several BH3-mimetic drugs designed to target individual or subsets of pro-survival BCL-2 proteins, alone and in combination, in both 2D and 3D cell cultures. None of the drugs demonstrated significant activity as single agents, though combinations targeting MCL-1 plus BCL-XL, and to a lesser extent BCL-2, showed considerable synergistic killing activity that was elicited via both BAX and BAK. Genetic deletion of BFL-1 in cell lines that express it at relatively high levels only had minor impact on BH3-mimetic drug sensitivity, suggesting it is not a critical pro-survival protein in melanoma. Combinations of MCL-1 inhibitors with BRAF inhibitors also caused only minimal additional melanoma cell killing over each drug alone, whilst combinations with the proteasome inhibitor bortezomib was more effective in multiple cell lines. Our data show for the first time that therapies targeting specific combinations of BCL-2 pro-survival proteins, namely MCL-1 plus BCL-XL and MCL-1 plus BCL-2, could have significant benefit for the treatment of melanoma.
Assessment of agreement and interchangeability between the TEG5000 and TEG6S thromboelastography haemostasis analysers: a prospective validation study
BACKGROUND: TEG6S® and TEG5000® (Haemonetics Corp, USA) are haemostasis analysers that measure viscoelasticity properties of whole blood. Both use different mechanisms to assess similar components of the coagulation process. The aim of this study was to assess agreement and interchangeability between the TEG6S and TEG5000 analysers. METHODS: 3.5 mL whole blood was collected from 25 adult patients in a tertiary intensive care unit (ICU). Analysis was performed using TEG6S and TEG5000 haemostatic platforms. Agreement between platforms was measured using Lin's concordance coefficient (Lin's CC), further validated using intraclass correlation coefficients and reduced major axis regression (RMAR). RESULTS: Sixteen (64%) patients were male; mean (range) age: 59yo (23-86). TEG6S and TEG5000 systems were broadly interchangeable. The majority of TEG variables demonstrated almost perfect or substantial agreement and minimal proportional bias (maximum amplitude demonstrated a fixed bias). LY30%, however, demonstrated poor agreement and a proportional bias. Lin's CC coefficients (95% CI, RMAR slope, intercept) between TEG6S and TEG5000 variables were: R time: 0.78 (0.64-0.92, 0.76, 0.92); K time: 0.82 (0.69-0.94, 1.30, - 0.93); alpha angle: 0.79 (0.64-0.95, 1.04, - 1.43); maximum amplitude (MA): 0.90 (0.83-0.96, 0.99, - 5.0); LY30%: 0.34 (0.1-0.58, 0.43, 0.04). CONCLUSIONS: Adult patients with critical illness demonstrate almost perfect agreement in the R time and MA, substantial agreement in K time and alpha angle, but poor agreement in LY30%, as measured by the TEG6S and TEG5000 analysers. With the exception of LY30%, the TEG6S and TEG5000 platforms appear interchangeable. This has important implications for use in clinical practice and multi-site research programs. TRIAL REGISTRATION: ANZCRT number: 12617000062325 , registered 12/Jan17. Retrospectively registered.
Improving rectal dosimetry for patients with intermediate and high-risk prostate cancer undergoing combined high-dose-rate brachytherapy and external beam radiotherapy with hydrogel space
(TERMEDIA PUBLISHING HOUSE LTD, 2019-01-01)
Purpose: To report on rectal dosimetric and toxicity outcomes of intermediate and high-risk prostate cancer patients undergoing combined high-dose-rate (HDR) brachytherapy and external beam radiotherapy (EBRT) with or without hydrogel spacer (HS) insertion. Material and methods: A total of 97 patients were analyzed in this study, with 32 patients (33%) who had HS insertion compared with a preceding group of 65 patients (67%) without HS. HS safety, the dosimetric effects on organs at risk (rectal, urethral, penile bulb, and bladder) as well as gastrointestinal (GI) and genitourinary toxicity were evaluated and compared between the two groups. Results: The median prostate-rectal separation achieved with HS was 10 mm (range, 5-14 mm). There were no post-operative complications following HS insertion. Patients with HS had significantly lower radiation dose to the rectum across all rectal dose volumes from rV30 to rV80, whether in absolute volume (cc) or as percentage of contoured OAR (p < 0.001). There was also significantly less acute > grade 1 GI toxicity (12.5% vs. 30.8%, p = 0.05) and a trend towards less late grade 1 GI toxicity (0% vs. 7.7%; p = 0.11) in the HS group compared to the non-HS group. Conclusions: Insertion of HS in prostate cancer patients receiving combined HDR and EBRT is safe and has resulted in a significant radiation dose reduction to the rectum, resulting in significantly less acute GI toxicity and a trend towards less late GI toxicity.