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      Comorbidity and cervical cancer survival of Indigenous and non-Indigenous Australian women: A semi-national registry-based cohort study (2003-2012)

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          Abstract

          Background

          Little is known about the impact of comorbidity on cervical cancer survival in Australian women, including whether Indigenous women’s higher prevalence of comorbidity contributes to their lower survival compared to non-Indigenous women.

          Methods

          Data for cervical cancers diagnosed in 2003–2012 were extracted from six Australian state-based cancer registries and linked to hospital inpatient records to identify comorbidity diagnoses. Five-year cause-specific and all-cause survival probabilities were estimated using the Kaplan-Meier method. Flexible parametric models were used to estimate excess cause-specific mortality by Charlson comorbidity index score (0,1,2+), for Indigenous women compared to non-Indigenous women.

          Results

          Of 4,467 women, Indigenous women (4.4%) compared to non-Indigenous women had more comorbidity at diagnosis (score ≥1: 24.2% vs. 10.0%) and lower five-year cause-specific survival (60.2% vs. 76.6%). Comorbidity was associated with increased cervical cancer mortality for non-Indigenous women, but there was no evidence of such a relationship for Indigenous women. There was an 18% reduction in the Indigenous: non-Indigenous hazard ratio (excess mortality) when comorbidity was included in the model, yet this reduction was not statistically significant. The excess mortality for Indigenous women was only evident among those without comorbidity (Indigenous: non-Indigenous HR 2.5, 95%CI 1.9–3.4), indicating that factors other than those measured in this study are contributing to the differential. In a subgroup of New South Wales women, comorbidity was associated with advanced-stage cancer, which in turn was associated with elevated cervical cancer mortality.

          Conclusions

          Survival was lowest for women with comorbidity. However, there wasn’t a clear comorbidity-survival gradient for Indigenous women. Further investigation of potential drivers of the cervical cancer survival differentials is warranted.

          Impact

          The results highlight the need for cancer care guidelines and multidisciplinary care that can meet the needs of complex patients. Also, primary and acute care services may need to pay more attention to Indigenous Australian women who may not obviously need it (i.e. those without comorbidity).

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          Most cited references37

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          Comorbidity measures for use with administrative data.

          This study attempts to develop a comprehensive set of comorbidity measures for use with large administrative inpatient datasets. The study involved clinical and empirical review of comorbidity measures, development of a framework that attempts to segregate comorbidities from other aspects of the patient's condition, development of a comorbidity algorithm, and testing on heterogeneous and homogeneous patient groups. Data were drawn from all adult, nonmaternal inpatients from 438 acute care hospitals in California in 1992 (n = 1,779,167). Outcome measures were those commonly available in administrative data: length of stay, hospital charges, and in-hospital death. A comprehensive set of 30 comorbidity measures was developed. The comorbidities were associated with substantial increases in length of stay, hospital charges, and mortality both for heterogeneous and homogeneous disease groups. Several comorbidities are described that are important predictors of outcomes, yet commonly are not measured. These include mental disorders, drug and alcohol abuse, obesity, coagulopathy, weight loss, and fluid and electrolyte disorders. The comorbidities had independent effects on outcomes and probably should not be simplified as an index because they affect outcomes differently among different patient groups. The present method addresses some of the limitations of previous measures. It is based on a comprehensive approach to identifying comorbidities and separates them from the primary reason for hospitalization, resulting in an expanded set of comorbidities that easily is applied without further refinement to administrative data for a wide range of diseases.
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            The impact of comorbidity on cancer and its treatment.

            Answer questions and earn CME/CNE Comorbidity is common among cancer patients and, with an aging population, is becoming more so. Comorbidity potentially affects the development, stage at diagnosis, treatment, and outcomes of people with cancer. Despite the intimate relationship between comorbidity and cancer, there is limited consensus on how to record, interpret, or manage comorbidity in the context of cancer, with the result that patients who have comorbidity are less likely to receive treatment with curative intent. Evidence in this area is lacking because of the frequent exclusion of patients with comorbidity from randomized controlled trials. There is evidence that some patients with comorbidity have potentially curative treatment unnecessarily modified, compromising optimal care. Patients with comorbidity have poorer survival, poorer quality of life, and higher health care costs. Strategies to address these issues include improving the evidence base for patients with comorbidity, further development of clinical tools to assist decision making, improved integration and coordination of care, and skill development for clinicians. CA Cancer J Clin 2016;66:337-350. © 2016 American Cancer Society.
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              Elevated cyclin B2 expression in invasive breast carcinoma is associated with unfavorable clinical outcome

              Background Breast cancer is a potentially fatal malignancy in females despite the improvement in therapeutic techniques. The identification of novel molecular signatures is needed for earlier detection, monitoring effects of treatment, and predicting prognosis. We have previously used microarray analysis to identify differentially expressed genes in aggressive breast tumors. The purpose of the present study was to investigate the prognostic value of the candidate biomarkers CCNB2, ASPM, CDCA7, KIAA0101, and SLC27A2 in breast cancer. Methods The expression levels and subcellular localization of the CCNB2, ASPM, CDCA7, KIAA0101, and SLC27A2 proteins were measured using immunohistochemistry (IHC) on a panel of 80 primary invasive breast tumors. Furthermore, the mRNA levels of CCNB2, KIAA0101, and SLC27A2 were subsequently examined by qRT-PCR to validate IHC results. Patient disease-specific survival (DSS) was evaluated in correlation to protein levels using the Kaplan-Meier method. Multivariate Cox regression analysis was used to determine the impact of aberrant protein expression of the candidate biomarkers on patient DSS and to estimate the hazard ratio at 8-year follow-up. Results Elevated cytoplasmic CCNB2 protein levels were strongly associated with short-term disease-specific survival of breast cancer patients (≤ 8 years; P<0.001) and with histological tumor type (P= 0.04). However, no association with other clinicopathological parameters was observed. Multivariate Cox regression analysis specified that CCNB2 protein expression is an independent prognostic marker of DSS in breast cancer. The predictive ability of several classical clinicopathological parameters was improved when used in conjunction with CCNB2 protein expression (C-index = 0.795) in comparison with a model without CCNB2 expression (C-index = 0.698). The protein levels of ASPM, CDCA7, KIAA0101, and SLC27A2 did not correlate with any clinicopathological parameter and had no influence on DSS. However, a significant correlation between the expression of the CCNB2 and ASPM proteins was detected (P = 0.03). Conclusion These findings suggest that cytoplasmic CCNB2 may function as an oncogene and could serve as a potential biomarker of unfavorable prognosis over short-term follow-up in breast cancer.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Project administrationRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Writing – review & editing
                Role: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Writing – review & editing
                Role: Project administrationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                8 May 2018
                2018
                : 13
                : 5
                : e0196764
                Affiliations
                [1 ] Menzies School of Health Research, Charles Darwin University, Casuarina, Northern Territory, Australia
                [2 ] Cancer Council Queensland, Spring Hill, Queensland, Australia
                [3 ] QIMR Berghofer Medical Research Institute, Queensland, Australia
                [4 ] Victorian Cytology Service, Carlton, Victoria, Australia
                [5 ] School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia
                [6 ] Cancer Council NSW, Cancer Research Division, Kings Cross, New South Wales, Australia
                [7 ] School of Public Health, University of Sydney, Sydney, New South Wales, Australia
                [8 ] Prince of Wales Clinical School, University of NSW, Sydney, New South Wales, Australia
                [9 ] University of Otago, Wellington, New Zealand
                [10 ] Cancer Epidemiology & Population Health, University of South Australia, Adelaide, South Australia, Australia
                Texas Technical University Health Sciences Center, UNITED STATES
                Author notes

                Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Karen Canfell is a co-PI of an investigator-initiated trial of cytology and primary HPV screening in Australia (‘Compass’), which is conducted and funded by the Victorian Cytology Service (VCS), a government-funded health promotion charity. The VCS have received equipment and a funding contribution for the Compass trial from Roche Molecular Systems and Ventana Inc USA. Professor Canfell is also an investigator for Compass NZ, by DML with funding to DML from Roche NZ. However neither Professor Canfell nor Professor Canfell’s institution on her behalf (Cancer Council NSW) receives direct funding from industry for this trial or any other project. All other authors declare no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0002-8637-311X
                Article
                PONE-D-17-37907
                10.1371/journal.pone.0196764
                5940188
                29738533
                8393c218-3cc2-49c5-b786-bc5aaa1cc072
                © 2018 Diaz et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 24 October 2017
                : 19 April 2018
                Page count
                Figures: 2, Tables: 4, Pages: 18
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: 1045591
                Funded by: funder-id http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: 1041111
                Funded by: funder-id http://dx.doi.org/10.13039/501100001102, Cancer Council NSW;
                Award ID: SRP 13-01
                Funded by: Cancer Council WA
                Funded by: funder-id http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: 1055587
                Award Recipient :
                Funded by: Menzies Enhanced Living Allowance (funded by the DISCOVER-TT Centre of Research Excellence)
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100008019, Sidney Myer Fund;
                Award ID: Sidney Myer Health Scholarship
                Award Recipient :
                Funded by: Menzies Enhanced Living Allowance
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100004148, Lowitja Institute;
                Award ID: Student scholarship
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: 1083090
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: 1058244
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: 1082989
                Award Recipient :
                The National Indigenous Cervical Screening Project (NICSP) was funded by a National Health and Medical Research Council (NHMRC; https://www.nhmrc.gov.au/) Project Grant (#1045591). This project was conducted under the auspice of the Centre of Research Excellence in Discovering Indigenous Strategies to improve Cancer Outcomes via Engagement, Research Translation & Training (DISCOVER-TT CRE) funded by NHMRC (#1041111) & the Strategic Research Partnership to Improve Cancer Control for Indigenous Australians (STREP Ca-CIndA), funded by Cancer Council NSW (#SRP 13-01; https://www.cancercouncil.com.au/) with supplementary funding from Cancer Council WA ( https://www.cancerwa.asn.au/). We also acknowledge the ongoing support of the Lowitja Institute ( http://www.lowitja.org.au/), Australia’s National Institute for Aboriginal and Torres Strait Islander Health Research. A Diaz was supported by a National Health and Medical Research Council (NHMRC) Training Scholarship for Indigenous Australian Health Research (#1055587) and a Menzies Enhanced Living Top-up scholarship ( www.menzies.edu.au) funded by the DISCOVER-TT CRE. PCV was supported by the NHMRC (Career Development Fellowship #1083090). LJW was supported by a Sidney Myer Health Scholarship ( http://myerfoundation.org.au/), Menzies Enhanced Living Top-up Scholarship and a student scholarship funded by the Lowitja Institute. GG was supported by an NHMRC Early Career Fellowship (#1105399). JC was supported by an NHMRC Research Fellowship (#1058244). KC receives salary support from NHMRC (Career Development Fellowship #1082989). The funding agencies had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed in this publication are those of the authors and do not necessarily reflect the views of the funding agencies.
                Categories
                Research Article
                Medicine and Health Sciences
                Diagnostic Medicine
                Cancer Detection and Diagnosis
                Medicine and Health Sciences
                Oncology
                Cancer Detection and Diagnosis
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Gynecological Tumors
                Cervical Cancer
                Biology and Life Sciences
                Population Biology
                Population Metrics
                Death Rates
                Medicine and Health Sciences
                Women's Health
                People and Places
                Geographical Locations
                Oceania
                Australia
                Medicine and Health Sciences
                Diagnostic Medicine
                Cancer Detection and Diagnosis
                Cancer Screening
                Medicine and Health Sciences
                Oncology
                Cancer Detection and Diagnosis
                Cancer Screening
                People and places
                Population groupings
                Ethnicities
                Indigenous Australian people
                Medicine and Health Sciences
                Oncology
                Cancer Treatment
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