Association between unstable diabetes mellitus and risk of pancreatic cancer.

BACKGROUND: Deterioration of glycaemic control in people with long-standing diabetes mellitus (diabetes) may be a possible indicator of pancreatic cancer. However, the magnitude of the association between diabetes deterioration and pancreatic cancer has received little attention. METHODS: We conducted a matched cohort study, nested within a population-based cohort of Australian women with diabetes. Women with unstable diabetes, defined as a change in medication after a 2-year period of stable medication use, were matched by birth year to those with stable diabetes, in a 1:4 ratio. We used flexible parametric survival models to estimate hazard ratios (HRs) and 95% confidence intervals (CI). RESULTS: We included 134,954 and 539,789 women in the unstable and stable diabetes cohorts, respectively (mean age 68 years). In total, 1,315 pancreatic cancers were diagnosed. Deterioration of stable diabetes was associated with a 2.5-fold increased risk of pancreatic cancer (HR 2.55; 95% CI 2.29-2.85). The risk was particularly high within the first year after diabetes deteriorated. HRs at 3 months, 6 months and 1 year were: 5.76 (95% CI 4.72-7.04); 4.56 (95% CI 3.81-5.46); and 3.33 (95% CI 2.86-3.89), respectively. The risk was no longer significantly different after 7 years. CONCLUSIONS: Deterioration in glycaemic control in people with previously stable diabetes may be an indicator of pancreatic cancer, suggesting investigations of the pancreas may be appropriate. The weaker longer-term (3-7 years) association between diabetes deterioration and pancreatic cancer may indicate that poor glycaemic control can be a risk factor for pancreatic cancer.

Predicting the risk of pancreatic cancer in women with new-onset diabetes mellitus.

BACKGROUND AND AIM: People with new-onset diabetes mellitus (diabetes) could be a possible target population for pancreatic cancer surveillance. However, distinguishing diabetes caused by pancreatic cancer from type 2 diabetes remains challenging. We aimed to develop and validate a model to predict pancreatic cancer among women with new-onset diabetes. METHODS: We conducted a retrospective cohort study among Australian women newly diagnosed with diabetes, using first prescription of anti-diabetic medications, sourced from administrative data, as a surrogate for the diagnosis of diabetes. The outcome was a diagnosis of pancreatic cancer within 3 years of diabetes diagnosis. We used prescription medications, severity of diabetes (i.e., change/addition of medication within 2 months after first medication), and age at diabetes diagnosis as potential predictors of pancreatic cancer. RESULTS: Among 99 687 women aged ≥ 50 years with new-onset diabetes, 602 (0.6%) were diagnosed with pancreatic cancer within 3 years. The area under the receiver operating curve for the risk prediction model was 0.73. Age and diabetes severity were the two most influential predictors followed by beta-blockers, acid disorder drugs, and lipid-modifying agents. Using a risk threshold of 50%, sensitivity and specificity were 69% and the positive predictive value (PPV) was 1.3%. CONCLUSIONS: Our model doubled the PPV of pancreatic cancer in women with new-onset diabetes from 0.6% to 1.3%. Age and rapid progression of diabetes were important risk factors, and pancreatic cancer occurred more commonly in women without typical risk factors for type 2 diabetes. This model could prove valuable as an initial screening tool, especially as new biomarkers emerge.

Validation of a tool for determining the clinical utility of stillbirth investigations.

BACKGROUND: Up to 20% of all stillbirths and 45% of term stillbirths are currently classified as unexplained. Many of these stillbirths do not undergo currently recommended investigations. This may leave questions unanswered and not identify stillbirths with a recurrence risk in subsequent pregnancies. AIMS: To validate a new tool (Stillbirth Investigation Utility Tool) to identify the clinical utility of investigations in stillbirth and the inter-rater agreement on cause of stillbirth using the Perinatal Society of Australia and New Zealand-Perinatal Death Classification (PSANZ-PDC). MATERIALS AND METHODS: Thirty-four stillbirths were randomly selected for inclusion, each assessed independently by five blinded assessors. The investigations were grouped into three categories: clinical and laboratory; placental pathology; and autopsy examination. The cause of death was assigned at the end of each group. Outcome measures were clinical utility of investigations measured by assessor rated usefulness and inter-rater agreement on the assigned cause of death. RESULTS: Comprehensive maternal history, maternal full blood count, maternal blood group and screen and placenta histopathology were useful in all cases. Clinical photographs were not performed and should have been performed in 50% of cases. The inter-rater agreement on cause of death assigned after all investigation results was 0.93 (95% CI 0.87-1.0). CONCLUSIONS: The new Stillbirth Investigation Utility Tool showed very good agreement in assigning the cause of death using PSANZ-PDC. Four investigations were useful in all cases. Minor refinements will be made based on feedback to enhance usability for wider implementation in research studies to assess the yield of investigations in stillbirths.

My Baby's Movements: An assessment of the effectiveness of the My Baby's Movements phone program in reducing late-gestation stillbirth rates.

BACKGROUND: Delayed reporting of decreased fetal movements (DFM) could represent a missed opportunity to prevent stillbirth. Mobile phone applications (apps) have the potential to improve maternal awareness and reporting of DFM and contribute to stillbirth prevention. AIMS: To evaluate the effectiveness of the My Baby's Movements (MBM) app on late-gestation stillbirth rates. MATERIALS AND METHODS: The MBM trial evaluated a multifaceted fetal movements awareness package across 26 maternity services in Australia and New Zealand between 2016 and 2019. In this secondary analysis, generalised linear mixed models were used to compare rates of late-gestation stillbirth, obstetric interventions, and neonatal outcomes between app users and non-app users including calendar time, cluster, primiparity and other potential confounders as fixed effects, and hospital as a random effect. RESULTS: Of 140 052 women included, app users comprised 9.8% (n = 13 780). The stillbirth rate was not significantly lower among app users (1.67/1000 vs 2.29/1000) (adjusted odds ratio (aOR) 0.79; 95% CI 0.51-1.23). App users were less likely to have a preterm birth (aOR 0.81; 0.75-0.88) or a composite adverse neonatal outcome (aOR 0.87; 0.81-0.93); however, they had higher rates of induction of labour (IOL) (aOR 1.27; 1.22-1.32) and early term birth (aOR 1.08; 1.04-1.12). CONCLUSIONS: The MBM app had low uptake and its use was not associated with stillbirth rates but was associated with some neonatal benefit, and higher rates of IOL and early term birth. Use and acceptability of tools designed to promote fetal movement awareness is an important knowledge gap. The implications of increased IOL and early term births warrant consideration in future studies.

A Simple Clinical Tool for Stratifying Risk of Clinically Significant CKD after Nephrectomy: Development and Multinational Validation.

BACKGROUND: Clinically significant CKD following surgery for kidney cancer is associated with increased morbidity and mortality, but identifying patients at increased CKD risk remains difficult. Simple methods to stratify risk of clinically significant CKD after nephrectomy are needed. METHODS: To develop a tool for stratifying patients' risk of CKD arising after surgery for kidney cancer, we tested models in a population-based cohort of 699 patients with kidney cancer in Queensland, Australia (2012-2013). We validated these models in a population-based cohort of 423 patients from Victoria, Australia, and in patient cohorts from single centers in Queensland, Scotland, and England. Eligible patients had two functioning kidneys and a preoperative eGFR ≥60 ml/min per 1.73 m2. The main outcome was incident eGFR <45 ml/min per 1.73 m2 at 12 months postnephrectomy. We used prespecified predictors-age ≥65 years old, diabetes mellitus, preoperative eGFR, and nephrectomy type (partial/radical)-to fit logistic regression models and grouped patients according to degree of risk of clinically significant CKD (negligible, low, moderate, or high risk). RESULTS: Absolute risks of stage 3b or higher CKD were <2%, 3% to 14%, 21% to 26%, and 46% to 69% across the four strata of negligible, low, moderate, and high risk, respectively. The negative predictive value of the negligible risk category was 98.9% for clinically significant CKD. The c statistic for this score ranged from 0.84 to 0.88 across derivation and validation cohorts. CONCLUSIONS: Our simple scoring system can reproducibly stratify postnephrectomy CKD risk on the basis of readily available parameters. This clinical tool's quantitative assessment of CKD risk may be weighed against other considerations when planning management of kidney tumors and help inform shared decision making between clinicians and patients.

Prospective cohort study: Causes of stillbirth in Australia 2013-2018.

BACKGROUND: Stillbirth is a major public health problem that is slow to improve in Australia. Understanding the causes of stillbirth through appropriate investigation is the cornerstone of prevention and important for parents to understand why their baby died. AIM: The aim of this study is to assess compliance with the Perinatal Society of Australia and New Zealand (PSANZ) Perinatal Mortality Clinical Practice Guidelines (2009) for stillbirths. METHODS: This is a prospective multi-centred cohort study of stillbirths at participating hospitals (2013-2018). Data were recorded into a purpose-built database. The frequency of the recommended core investigations was calculated, and χ2 test was performed for subgroup analyses by gestational age groups and timing of fetal death. A 70% compliance threshold was defined for investigations. The cause of death categories was provided according to PSANZ Perinatal Death Classification. RESULTS: Among 697 reported total stillbirths, 562 (81%) were antepartum, and 101 (15%) were intrapartum. The most common cause of death categories were 'congenital abnormality' (12.5%), 'specific perinatal conditions' (12.2%) and 'unexplained antepartum death' (29%). According to 2009 guidelines, there were no stillbirths where all recommended investigations were performed (including or excluding autopsy). A compliance of 70% was observed for comprehensive history (82%), full blood count (94%), cytomegalovirus (71%), toxoplasmosis (70%), renal function (75%), liver function (79%), external examination (86%), post-mortem examination (84%) and placental histopathology (92%). The overall autopsy rate was 52%. CONCLUSIONS: Compliance with recommended investigations for stillbirth was suboptimal, and many stillbirths remain unexplained. Education on the value of investigations for stillbirth is needed. Future studies should focus on understanding the yield and value of investigations and service delivery gaps that impact compliance.

Randomised clinical endpoint studies for trastuzumab biosimilars: a systematic review.

PURPOSE: Uptake of biosimilars depends on clinicians and patients having confidence in the evidential basis of marketing approval. The aim of this systematic review was to assess the evidential role of randomised clinical endpoint studies in the marketing approval of trastuzumab biosimilars. METHODS: We searched PubMed for any published reports of randomised studies associated with the five trastuzumab biosimilars approved by the EMA, as on 31 January 2019. We also searched ClinicalTrials.gov for any ongoing studies for other trastuzumab biosimilars. RESULTS: We identified eight published papers or abstracts for seven randomised clinical endpoint studies for five trastuzumab biosimilars approved by the EMA: four studies in the neoadjuvant setting and three in the first-line metastatic setting. Another six unpublished or ongoing studies for other trastuzumab biosimilars were identified via ClinicalTrials.gov. According to GRADE, and considered in isolation, the randomised studies would be categorised as low-quality evidence because of the use of surrogate endpoints and the small sample size. However, according to GRADE, the totality-of-evidence for each of the five approved trastuzumab biosimilars would be categorised as high quality in that further data would be unlikely to change the conclusion that each biosimilar was not different from Herceptin in any clinically important way. CONCLUSION: The pivotal data for each marketing approval was not the randomised clinical endpoint study, but the in vitro analytic characterisation. Regulatory confidence in in vitro analytic characterisation stems from years of experience with manufacturing changes for originator biological medicines. This emphasis on in vitro data, as the most sensitive way to detect clinically important differences, will be a new way of thinking for many oncologists.

Age at diagnosis and the surgical management of small renal carcinomas: findings from a cross-sectional population-based study.

OBJECTIVES: To describe the use of partial nephrectomy (PN) for patients with stage T1a renal cell carcinoma (RCC) by age group (<65 and ≥65 years) in two Australian states. MATERIALS AND METHODS: All adults diagnosed with RCC in 2012 and 2013 were identified through population-based cancer registries in the Australian states of Queensland and Victoria. For each patient, research assistants extracted patient, tumour and treatment data from medical records. Percentages of patients treated by PN were determined for the two age groups. Multivariable logistic regression analyses examined factors associated with PN. Clinicians treating RCC were sent surveys to assess attitudes towards PN. RESULTS: Data were collected on 956 patients (Victoria: n = 548; Queensland: n = 404) with stage T1a RCC. Of those undergoing surgery (n = 865), PN was more common for those aged <65 years (61%) than for those aged ≥65 years (44%), with this difference significant after adjusting for patient, tumour (odds ratio 0.50, 95% confidence interval 0.36-0.70). There were significant interactions between age and treatment centre volume (P < 0.05) and residential state (P < 0.05). PN was less likely for younger patients treated at lower-volume hospitals (<24 patients a year) but hospital volume was not associated with PN for older patients. PN was less likely for older patients in Queensland than Victoria. In multivariable analyses, age was not related to laparoscopic surgery. Queensland clinicians were less likely than those from Victoria to agree that PN was the treatment of choice for most T1aN0M0 tumours (P < 0.001). CONCLUSIONS: In Australia, patients aged > 65 years with small renal cancers were less likely to be treated by PN than younger patients. The variation in the surgical procedure used to treat older T1a RCC patients by state and hospital volume indicates that better evidence is needed to direct practice in this area.

Do Australian adolescents' and young adults' experiences of cancer care influence their quality of life?

OBJECTIVE: To examine the relationship between the cancer care experiences of adolescents and young adults (AYAs) and their quality of life. METHODS: Two hundred and nine AYAs completed a cross-sectional, self-report survey distributed through the population-based cancer registries in 2 Australian states (New South Wales and Victoria). Eligible AYAs were 15 to 24 years old when diagnosed with any cancer (excluding early-stage melanoma) and were 3 to 24 months post-diagnosis. Questions examined whether particular care experiences occurred for the patient at different points in the cancer care pathway, including diagnosis, treatment, inpatient care, and at the end of treatment. Quality of life was assessed using the Functional Assessment of Cancer Therapy-General scale. RESULTS: Positive experiences of care at diagnosis, during treatment, during inpatient stays, and when finishing treatment were associated with higher functional, emotional, and social well-being. However, these associations generally became nonsignificant when communication and support experiences were included in the model. Inpatient experiences positively influenced emotional well-being over and above the effect of communication and support experiences. CONCLUSIONS: The results suggest that, for most AYAs' quality of life outcomes, positive experiences of age-appropriate communication and emotional support may underpin the effect of positive experiences of care throughout the cancer care pathway. The results support the need for communication and support tailored to an AYA audience, as recognised by recent Australian and international guidelines on the care of AYAs with cancer.

Predictors of new-onset chronic kidney disease in patients managed surgically for T1a renal cell carcinoma: An Australian population-based analysis.

BACKGROUND: New-onset chronic kidney disease (CKD) following surgical management of kidney tumors is common. This study evaluated risk factors for new-onset CKD after nephrectomy for T1a renal cell carcinoma (RCC) in an Australian population-based cohort. METHODS: There were 551 RCC patients from the Australian states of Queensland and Victoria included in this study. The primary outcome was new-onset CKD (eGFR <60 mL/min per 1.73 m2 ) and the secondary outcome was new-onset moderate-severe CKD (<45 mL/min per 1.73 m2 ). Multivariable logistic regression was used to evaluate associations between patient, tumor and health-service characteristics and these outcomes. RESULTS: Forty percent (219/551) of patients developed new-onset CKD, and 12% (68/551) experienced new-onset moderate-severe CKD. Risk factors for new-onset CKD were age, lower preoperative eGFR, tumor size >20 mm, radical nephrectomy, lower hospital caseloads (<20 cases/year), and rural place of residence. The associations between rural place of residence and low center volume were a consequence of higher radical nephrectomy rates. CONCLUSION: Risk factors for CKD after nephrectomy generally relate to worse baseline health, or likelihood of undergoing radical nephrectomy. Surgeons in rural centres and hospitals with low caseloads may benefit from formalized integration with specialist centers for continued professional development and case-conferencing, to assist in management decisions.

Factors influencing the provision of fertility counseling and impact on quality of life in adolescents and young adults with cancer.

PURPOSE: This study investigated the impact of fertility-related discussions on Adolescent and Young Adult (AYA) cancer patients' quality of life (QoL) and the factors influencing provision of these discussions. METHODS: Recruitment was conducted through population-based state cancer registries. Eligible AYAs were 15-24 years at diagnosis, 3-24 months postdiagnosis, with any cancer (except early stage melanoma). As part of a larger survey, AYAs were asked about their experiences of fertility-related discussions and QoL (FACT-G). RESULTS: Of the 207 AYAs returning surveys (29% response rate) 88% reported a discussion about infertility risks, 75% reported a discussion about preservation options and 59% were offered a referral to a fertility specialist. Patients attending health services with an AYA focus were more likely than those attending other types of centers to report discussions of fertility preservation (FP) options (85% versus 67%) and referrals (75% versus 49%). Social well-being was positively related to discussions about preservation options and being provided fertility risk information in a sensitive, supportive manner. CONCLUSIONS: Providing a sensitive and proactive discussion about fertility-related risks may benefit AYAs' well-being. Services with an AYA focus are fulfilling their mandate of ensuring optimal fertility-related care for AYA cancer patients.

Stillbirths: recall to action in high-income countries.

Variation in stillbirth rates across high-income countries and large equity gaps within high-income countries persist. If all high-income countries achieved stillbirth rates equal to the best performing countries, 19,439 late gestation (28 weeks or more) stillbirths could have been avoided in 2015. The proportion of unexplained stillbirths is high and can be addressed through improvements in data collection, investigation, and classification, and with a better understanding of causal pathways. Substandard care contributes to 20-30% of all stillbirths and the contribution is even higher for late gestation intrapartum stillbirths. National perinatal mortality audit programmes need to be implemented in all high-income countries. The need to reduce stigma and fatalism related to stillbirth and to improve bereavement care are also clear, persisting priorities for action. In high-income countries, a woman living under adverse socioeconomic circumstances has twice the risk of having a stillborn child when compared to her more advantaged counterparts. Programmes at community and country level need to improve health in disadvantaged families to address these inequities.

Trends in the surgical management of stage 1 renal cell carcinoma: findings from a population-based study.

OBJECTIVES: To determine whether the use of nephron-sparing surgery (NSS) for treatment of stage 1 renal cell carcinoma (RCC) changed between 2009 and the end of 2013 in Australia. PATIENTS AND METHODS: All adult cases of RCC diagnosed in 2009, 2012 and 2013 were identified through the population-based Victorian Cancer Registry. For each identified patient, trained data-abstractors attended treating hospitals or clinician rooms to extract tumour and treatment data through medical record review. Multivariable logistic regression analyses were carried out to examine the significance of change in use of NSS over time, after adjusting for potential confounders. RESULTS: A total of 1 836 patients with RCC were identified. Of these, the proportion of cases with stage 1 tumours was 64% in 2009, 66% in 2012 and 69% in 2013. For T1a tumours, the proportion of patients residing in metropolitan areas receiving NSS increased from 43% in 2009 to 58% in 2012 (P < 0.05), and 69% in 2013 (P < 0.05). For patients residing in non-metropolitan areas, the proportion receiving NSS increased from 27% in 2009 to 49% in 2012, and 61% in 2013 (P < 0.01). Univariable logistic regression showed patients with moderate (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.35-0.94) or severe comorbidities (OR 0.58, 95% CI 0.33-0.99), residing in non-metropolitan areas (OR 0.65, 95% CI 0.47-0.90), were less likely to be treated by NSS, while those attending high-volume hospitals (≥30 cases/year: OR 1.79, 95% CI 1.21-2.65) and those with higher socio-economic status (OR 1.45, 95% CI 1.02-2.07) were more likely to be treated by NSS. In multivariable analyses, patients with T1a tumours in 2012 (OR 2.00, 95% CI 1.34-2.97) and 2013 (OR 3.15, 95% CI 2.13-4.68) were more likely to be treated by NSS than those in 2009. For T1b tumours, use of NSS increased from 8% in 2009 to 20% in 2013 (P < 0.05). CONCLUSION: This population-based study of the management of T1 renal tumours in Australia found that the use of NSS increased over the period 2009 to 2013. Between 2009 and 2013 clinical practice for the treatment of small renal tumours in Australia has increasingly conformed to international guidelines.

Predictors of autopsy following stillbirth in Queensland, Australia: A population-based study.

BACKGROUND: Accurate determination of causes of stillbirth is critical to effective prevention. Autopsy remains the gold standard investigation for stillbirth; however, with low autopsy rates many stillbirths are likely to be 'unexplored' rather than 'unexplained'. AIM: To determine factors associated with autopsy following stillbirth. MATERIALS AND METHODS: Routinely collected population-based data on all singleton stillbirths of at least 400 g birthweight or 20 weeks gestation in Queensland between July 2000 and December 2011 were examined. Adjusted odds ratios (aOR, 99% CI) were calculated accounting for sociodemographic, pregnancy and medical factors. Of interest was initially unexplained stillbirth on the death certificate; analysis was stratified by gestational age group (<24, 24-27, 28-36 and ≥37 weeks). RESULTS: Of 3842 singleton stillbirths included in these analyses, 1356 (35.3%) had an autopsy performed. Initially unexplained stillbirth was associated with decreased odds of autopsy at late gestation (28-36 weeks, aOR 0.63 (99% CI 0.42-0.93); ≥37 weeks, aOR 0.53 (99% CI 0.35-0.81)) as was intrapartum stillbirth (<24 weeks, aOR 0.63 (99% CI 0.43-0.94); 28-36 weeks, aOR 0.37 (99% CI 0.14-0.98)). Congenital abnormality (<24 weeks, ≥37 weeks), small-for-gestational age (<24 weeks), and primigravidity (≥37 weeks) were associated with increased odds of autopsy following stillbirth. CONCLUSIONS: Pregnancy factors are associated with stillbirth autopsy. These findings have implications for development of appropriate information for parents and education of clinical staff. Further research is needed into factors influencing autopsy following stillbirth.

Gestational age specific stillbirth risk among Indigenous and non-Indigenous women in Queensland, Australia: a population based study.

BACKGROUND: In Australia, significant disparity persists in stillbirth rates between Aboriginal and Torres Strait Islander (Indigenous Australian) and non-Indigenous women. Diabetes, hypertension, antepartum haemorrhage and small-for-gestational age (SGA) have been identified as important contributors to higher rates among Indigenous women. The objective of this study was to examine gestational age specific risk of stillbirth associated with these conditions among Indigenous and non-Indigenous women. METHODS: Retrospective population-based study of all singleton births of at least 20 weeks gestation or at least 400 grams birthweight in Queensland between July 2005 and December 2011 using data from the Queensland Perinatal Data Collection, which is a routinely-maintained database that collects data on all births in Queensland. Multivariate logistic regression was used to calculate adjusted odds ratios (aOR) and 95 % confidence intervals, adjusting for maternal demographic and pregnancy factors. RESULTS: Of 360987 births analysed, 20273 (5.6 %) were to Indigenous women and 340714 (94.4 %) were to non-Indigenous women. Stillbirth rates were 7.9 (95 % CI 6.8-9.2) and 4.1 (95 % CI 3.9-4.3) per 1000 births, respectively. For both Indigenous and non-Indigenous women across most gestational age groups, antepartum haemorrhage, SGA, pre-existing diabetes and pre-existing hypertension were associated with increased risk of stillbirth. There were mixed results for pre-eclampsia and eclampsia and a consistently raised risk of stillbirth was not seen for gestational diabetes. CONCLUSION: This study highlights gestational age specific stillbirth risk for Indigenous and non-Indigenous women; and disparity in risk at term gestations. Improving access to and utilisation of appropriate and responsive healthcare may help to address disparities in stillbirth risk for Indigenous women.

Characteristics of a global classification system for perinatal deaths: a Delphi consensus study.

BACKGROUND: Despite the global burden of perinatal deaths, there is currently no single, globally-acceptable classification system for perinatal deaths. Instead, multiple, disparate systems are in use world-wide. This inconsistency hinders accurate estimates of causes of death and impedes effective prevention strategies. The World Health Organisation (WHO) is developing a globally-acceptable classification approach for perinatal deaths. To inform this work, we sought to establish a consensus on the important characteristics of such a system. METHODS: A group of international experts in the classification of perinatal deaths were identified and invited to join an expert panel to develop a list of important characteristics of a quality global classification system for perinatal death. A Delphi consensus methodology was used to reach agreement. Three rounds of consultation were undertaken using a purpose built on-line survey. Round one sought suggested characteristics for subsequent scoring and selection in rounds two and three. RESULTS: The panel of experts agreed on a total of 17 important characteristics for a globally-acceptable perinatal death classification system. Of these, 10 relate to the structural design of the system and 7 relate to the functional aspects and use of the system. CONCLUSION: This study serves as formative work towards the development of a globally-acceptable approach for the classification of the causes of perinatal deaths. The list of functional and structural characteristics identified should be taken into consideration when designing and developing such a system.

Bias and precision of measures of survival gain from right-censored data.

In cost-effectiveness analyses of drugs or health technologies, estimates of life years saved or quality-adjusted life years saved are required. Randomised controlled trials can provide an estimate of the average treatment effect; for survival data, the treatment effect is the difference in mean survival. However, typically not all patients will have reached the endpoint of interest at the close-out of a trial, making it difficult to estimate the difference in mean survival. In this situation, it is common to report the more readily estimable difference in median survival. Alternative approaches to estimating the mean have also been proposed. We conducted a simulation study to investigate the bias and precision of the three most commonly used sample measures of absolute survival gain--difference in median, restricted mean and extended mean survival--when used as estimates of the true mean difference, under different censoring proportions, while assuming a range of survival patterns, represented by Weibull survival distributions with constant, increasing and decreasing hazards. Our study showed that the three commonly used methods tended to underestimate the true treatment effect; consequently, the incremental cost-effectiveness ratio (ICER) would be overestimated. Of the three methods, the least biased is the extended mean survival, which perhaps should be used as the point estimate of the treatment effect to be inputted into the ICER, while the other two approaches could be used in sensitivity analyses. More work on the trade-offs between simple extrapolation using the exponential distribution and more complicated extrapolation using other methods would be valuable.

Survival disparities in Australia: an analysis of patterns of care and comorbidities among indigenous and non-indigenous cancer patients.

BACKGROUND: Indigenous Australians have lower overall cancer survival which has not yet been fully explained. To address this knowledge deficit, we investigated the associations between comorbidities, cancer treatment and survival in Indigenous and non-Indigenous people in Queensland, Australia. METHODS: A cohort study of 956 Indigenous and 869 non-Indigenous patients diagnosed with cancer during 1998-2004, frequency-matched on age, sex, remoteness of residence and cancer type, and treated in Queensland public hospitals. Survival after cancer diagnosis, and effect of stage, treatment, and comorbidities on survival were examined using Cox proportional hazard models. RESULTS: Overall Indigenous people had more advanced cancer stage (p = 0.03), more comorbidities (p < 0.001), and received less cancer treatment (77% vs. 86%, p = 0.001). Among patients without comorbidities and social disadvantage, there was a lower uptake of treatment among Indigenous patients compared to non-Indigenous patients. For those who received treatment, time to commencement, duration and dose of treatment were comparable. Unadjusted cancer survival (HR = 1.30, 95% CI 1.15-1.48) and non-cancer survival (HR = 2.39, 95% CI 1.57-3.63) were lower in the Indigenous relative to non-Indigenous patients over the follow-up period. When adjusted for clinical factors, there was no difference in cancer-specific survival between the groups (HR = 1.10, 95% CI 0.96-1.27). One-year survival was lower for Indigenous people for all-causes of death (adjusted HR = 1.33, 95% CI 1.12-1.83). CONCLUSION: In this study, Indigenous Australians received less cancer treatment, had more comorbidities and had more advanced cancer stage at diagnosis, factors which contribute to poorer cancer survival. Moreover, for patients with a more favourable distribution of such prognostic factors, Indigenous patients received less treatment overall relative to non-Indigenous patients. Personalised cancer care, which addresses the clinical, social and overall health requirements of Indigenous patients, may improve their cancer outcomes.

Cancer survival for Aboriginal and Torres Strait Islander Australians: a national study of survival rates and excess mortality.

BACKGROUND: National cancer survival statistics are available for the total Australian population but not Indigenous Australians, although their cancer mortality rates are known to be higher than those of other Australians. We aimed to validate analysis methods and report cancer survival rates for Indigenous Australians as the basis for regular national reporting. METHODS: We used national cancer registrations data to calculate all-cancer and site-specific relative survival for Indigenous Australians (compared with non-Indigenous Australians) diagnosed in 2001-2005. Because of limited availability of Indigenous life tables, we validated and used cause-specific survival (rather than relative survival) for proportional hazards regression to analyze time trends and regional variation in all-cancer survival between 1991 and 2005. RESULTS: Survival was lower for Indigenous than non-Indigenous Australians for all cancers combined and for many cancer sites. The excess mortality of Indigenous people with cancer was restricted to the first three years after diagnosis, and greatest in the first year. Survival was lower for rural and remote than urban residents; this disparity was much greater for Indigenous people. Survival improved between 1991 and 2005 for non-Indigenous people (mortality decreased by 28%), but to a much lesser extent for Indigenous people (11%) and only for those in remote areas; cancer survival did not improve for urban Indigenous residents. CONCLUSIONS: Cancer survival is lower for Indigenous than other Australians, for all cancers combined and many individual cancer sites, although more accurate recording of Indigenous status by cancer registers is required before the extent of this disadvantage can be known with certainty. Cancer care for Indigenous Australians needs to be considerably improved; cancer diagnosis, treatment, and support services need to be redesigned specifically to be accessible and acceptable to Indigenous people.