Under-screened Aboriginal and Torres Strait Islander women's perspectives on cervical screening.

Aboriginal and Torres Strait Islander women have lower participation in Australia's National Cervical Screening Program than other Australian women. Under-screened (including never screened) women's voices are rarely heard in research evidence, despite being a priority group for interventions to increase cervical screening participation. This study aimed to describe under-screened Aboriginal and Torres Strait Islander women's perspectives on cervical screening. Participants were 29 under-screened (women who had either never screened, had not screened in the previous five years or had recently screened in the past three months after more than five years) Aboriginal and Torres Strait Islander women from five communities across three states/territories. Female Aboriginal and Torres Strait Islander researchers Yarned with women about why they did not participate in screening and how to improve screening. Yarning is an Indigenous qualitative research method in which relationships and trust facilitate culturally safe conversation. Transcripts were analysed thematically. The proportion of eligible women who screened within 30 days after the Yarn was calculated. We identified four themes describing how the harms outweighed the benefits of cervical screening for under-screened women. These were: 1) distress, discomfort, and trauma; 2) lack of privacy and control; 3) complicated relationships with health care providers (HCPs); and 4) pressured, insensitive, and/or culturally unsafe communication from HCPs. Under-screened women who had recently screened had maintained privacy and control through self-collection and had experienced trauma-informed and empathetic care from their HCPs. While we cannot unequivocally attribute women's subsequent participation in screening to their involvement in this study, it is notable that one third of eligible under-screened women were screened within 30 days after the Yarn. Enhancing privacy, implementing trauma-informed approaches to care and sensitivity to the clinician-client relationship dynamics could enhance women's sense of comfort in, and control over, the screening procedure. The opportunity to Yarn about cervical screening and self-collection may address these issues and support progress toward cervical cancer elimination in Australia.

Aboriginal and Torres Strait Islander women's views of cervical screening by self-collection: a qualitative study.

OBJECTIVE: This study aimed to describe Aboriginal and Torres Strait Islander women's views of self-collection introduced in the renewed National Cervical Screening Program. METHODS: A total of 79 Aboriginal and/or Torres Strait Islander women (50 screened in previous five years, 29 under-screened) from five clinics across three Australian states/territories participated. Topics discussed were perceptions of self-collection, the instruction card and suggestions for implementing self-collection. We employed yarning (a qualitative method), which established relationships and trust between participants and researchers to facilitate culturally safe conversations. Transcripts were analysed thematically. RESULTS: Most women were unaware of self-collection before the yarn but found it to be an acceptable way to participate in cervical screening. Women perceived self-collection would be convenient, provide a sense of control over the screening experience, and maintain privacy and comfort. The instructions were perceived to be simple and easy to follow. Women had concerns about collecting the sample correctly and the accuracy of the sample (compared to clinician-collected samples). CONCLUSIONS: Self-collection is acceptable to Aboriginal and Torres Strait Islander women. IMPLICATIONS FOR PUBLIC HEALTH: Given the inequitable burden of cervical cancer experienced by Aboriginal and Torres Strait Islander women, self-collection is likely to significantly improve participation and ultimately improve cervical cancer outcomes.

Access to Aboriginal Community-Controlled Primary Health Organizations Can Explain Some of the Higher Pap Test Participation Among Aboriginal and Torres Strait Islander Women in North Queensland, Australia.

BACKGROUND: Aboriginal and Torres Strait Islander Community-Controlled Health Organisations (ACCHOs) provides culturally appropriate primary care for Aboriginal and Torres Strait Islander people in Australia. The population of North Queensland has a higher proportion of Aboriginal and Torres Strait Islander people, a greater population coverage of ACCHOs, and higher cervical screening participation than the Rest of Queensland. The association between regional differences in the use of ACCHOs for cervical screening and variations in screening participation among Aboriginal and Torres Strait Islander women is currently unknown. METHODS: This is a population-based study of 1,107,233 women, aged 20-69 years who underwent cervical screening between 2013 and 2017. Of these women, 132,972 (12%) were from North Queensland, of which 9% were identified as Aboriginal and Torres Strait Islander women (2% Rest of Queensland) through linkage to hospital records. Regional differentials in screening by Aboriginal and Torres Strait Islander status were quantified using participation rate ratios (PRRs) with 95% confidence intervals (CIs) from negative binomial regression models. Logistic regression was used to identify factors associated with Aboriginal and Torres Strait Islander women being screened at ACCHOs. RESULTS: Aboriginal and Torres Strait Islander women from North Queensland (versus) Rest of Queensland had higher odds of screening at ACCHOs after adjusting for age and area-level variables. After adjustment for non-ACCHO variables, the regional differential in screening among Aboriginal and Torres Strait Islander women was significantly higher (PRR 1.28, 95% CI 1.20-1.37) than that among other Australian women [PRR = 1.11 (1.02-1.18)], but was attenuated on further adjustment for ACCHO variables, [PRR = 1.15, (1.03-1.28)] to become similar to the corresponding point estimate for other Australian women [PRR = 1.09, (1.01-1.20)]. However, the significant interaction between Aboriginal and Torres Strait Islander status and region (p < 0.001) remained, possibly reflecting the large cohort size. Screening participation increased with better access to health services for all women. CONCLUSIONS: Improving access to primary health care for Aboriginal and Torres Strait Islander women, especially through ACCHOs, may reduce existing disparities in cervical screening participation. Further gains will require greater levels of local community engagement and understanding of the experiences of screened Aboriginal and Torres Strait Islander women to inform effective interventions.

Health care provider perspectives on cervical screening for Aboriginal and Torres Strait Islander women: a qualitative study.

OBJECTIVE: To investigate perspectives of primary health care providers (HCPs) on providing cervical screening for Aboriginal and Torres Strait Islander women, who experience a higher burden of cervical cancer than other Australian women. METHODS: Semi-structured interviews with 13 HCPs from four Australian Indigenous primary health care centres (PHCCs). Transcripts were thematically analysed. RESULTS: HCPs discussed the need to approach cervical screening with sensitivity to women's emotional and cultural needs and sustaining relationships built on trust and respect. HCPs reported challenges in promoting screening to Aboriginal and Torres Strait Islander women due to cumbersome systems, competing clinical priorities, workforce capacity limitations and specific challenges associated with implementing the renewed National Cervical Screening Program. CONCLUSIONS: In practice, HCPs experience several challenges to delivering cervical screening. Understanding HCPs' perspectives on their approach to cervical screening delivery, and the systems in which this occurs, can help to ensure that they receive adequate support and resources to deliver cervical screening to Aboriginal and Torres Strait Islander women. Implications for public health: It is important that HCPs adopt a multi-faceted, person-centred approach to cervical screening that is responsive to women's needs and that works synchronously with supportive PHCC services and systems and the National Cancer Screening Register.

Temporal and area-level variation in prevalence of high-grade histologically confirmed cervical abnormalities among Indigenous and non-Indigenous women, Queensland, Australia, 2008-2017.

OBJECTIVE: Despite Australia's National Cervical Screening Program, Indigenous women have a disproportionately high burden of cervical cancer. We describe temporal and area-level patterns in prevalence of histologically conformed high-grade cervical abnormalities (hHGA) among cytologically screened women by Indigenous status. METHODS: This was a population-based study of 2,132,925 women, aged 20-69, who underwent cervical screening between 2008 and 2017, in Queensland, Australia. Of these, 47,136 were identified as Indigenous from linked hospital records. Overall patterns in hHGA prevalence by Indigenous status were quantified using prevalence rate ratios (PrRR) from negative binomial models. Bayesian spatial models were used to obtain smoothed prevalence estimates of hHGA across 528 small areas compared to the state average. Results are presented as maps and graphs showing the associated uncertainty of the estimates. RESULTS: Overall, screened Indigenous women had significantly higher hHGA prevalence than non-Indigenous women. However, the magnitude of the difference reduced over time (p < 0.001). Adjusted for age and area-level variables, Indigenous women had 36% higher hHGA prevalence (PrRR 1.36, 95% confidence interval [1.21-1.52]) than non-Indigenous women between 2013 and 2017. The overall effect of age decreased over time (p = 0.021). Although there was evidence of moderate spatial variation in 10-year prevalence estimates for both groups of women, the high levels of uncertainty for many estimates, particularly for Indigenous women, limited our ability to draw definitive conclusions about the spatial patterns. CONCLUSIONS: While the temporal reduction in Indigenous: non-Indigenous differential in hHGA prevalence is encouraging, further research into the key drivers of the continuing higher risk among Indigenous women is warranted.

Spatial and temporal variations in cervical cancer screening participation among indigenous and non-indigenous women, Queensland, Australia, 2008-2017.

BACKGROUND: Cervical cancer incidence and mortality have declined in Australia since the implementation of a national cervical screening program in 1991, however, disparities in both measures between Indigenous and non-Indigenous women remain. We describe spatial and temporal changes in Pap test participation rates by Indigenous status for Queensland (Australia). Analyses were done in the context of renewed screening program in December 2017. METHODS: Population-based study 2,132,925 Queensland female residents, aged 20-69 years who underwent cervical screening from 2008 to December 2017; 47,136 were identified as Indigenous through linkage to hospital records. Bayesian spatial models were used to generate smoothed estimates of participation across 528 small areas during 2008-2012 and 2013-2017 compared to the overall state average (2008-2017). Results are presented as thematic maps and graphs showing the associated uncertainty of the estimates. RESULTS: Overall screening participation decreased over time for both Indigenous and non-Indigenous women. Strong spatial patterns were evident in five-year participation for both groups. Indigenous women had significantly lower participation than the Queensland average for ≥ 88 % of areas during both reporting periods whereas corresponding estimates were lower than average for <30 % of areas among non-Indigenous women. Disparities by Indigenous status persisted over time and remained across broader geographical groups of accessibility and area disadvantage. CONCLUSIONS: Cervical cancer burden in Australia can only be reduced through concentrated efforts on identifying and addressing key drivers of the continuing disparities in screening participation. Achieving equitable screening participation for all women especially Indigenous women requires community engagement and localised interventions.

Indigenous Australian women's experiences of participation in cervical screening.

Aboriginal and Torres Strait Islander (collectively, Indigenous Australian) women experience a higher burden of cervical cancer than other women. The National Cervical Screening Program (NCSP) is failing to meet the needs of Indigenous Australian women, resulting in many women not regularly participating in cervical screening. However, one third of Indigenous Australian women do participate in cervical screening. The reasons that some women in this population commence and continue to screen remain unheard but could provide insights to support women who currently do not participate. We aimed to describe Indigenous Australian women's experiences and views of participation in cervical screening by yarning (a culturally-appropriate interview technique) with 50 Indigenous Australian women aged 25-70 years who had completed cervical screening in the past five years, recruited via Primary Health Care Centres (PHCCs) from three jurisdictions. Aboriginal or Torres Strait Islander women researchers conducted the interviews. Thematic analysis identified six themes: screening as a means of staying strong and in control; overcoming fears, shame, and negative experiences of screening; needing to talk openly about screening; the value of trusting relationships with screening providers; logistical barriers; and overcoming privacy concerns for women employed at PHCCs. Despite describing screening as shameful, invasive, and uncomfortable, women perceived it as a way of staying healthy and exerting control over their health. This ultimately supported their participation and a sense of empowerment. Women valued open discussion about screening and strong relationships with health providers. We identified logistical barriers and specific barriers faced by women employed at PHCCs. This study is strengthened by a research approach that centred Indigenous Australian women's voices. Understanding the experiences of Indigenous Australian women who participate in screening will help screening providers support women to start and continue to screen regularly. Recommendations for practice are provided.

Recurrence patterns identify aggressive form of human papillomavirus-dependent vulvar cancer.

BACKGROUND: Vulvar cancer is rare and, as a result, is understudied. Treatment is predominantly surgery, irrespective of the type of vulvar cancer, and is associated with physical, emotional and sexual complications. A cluster of human papillomavirus (HPV)-dependent vulvar cancer patients was identified in Arnhem Land Northern Territory (NT), Australia, in which young Indigenous women were diagnosed at 70 times the national incidence rate. AIMS: To assess whether women from the Arnhem Land cluster differ from women with vulvar squamous cell carcinoma (VSCC) and vulvar intraepithelial neoplasia (VIN) resident elsewhere in the NT in recurrence after treatment, disease progression and mortality. MATERIALS AND METHODS: A retrospective cohort study of NT-resident women diagnosed with VIN or invasive vulvar cancer (VSCC) between 1 January 1993 and 30 June 2015 was undertaken. Time to recurrence was assessed using cumulative incidence plots and Fine and Gray competing risk regression models. Mean cumulative count was used to estimate the burden of recurrent events. RESULTS: Indigenous women from Arnhem Land experienced more recurrences after treatment than non-Indigenous women, the cancers recurred faster, and Indigenous women have worse survival at five years. CONCLUSIONS: In characterising the epidemiological features of this cluster, we have identified a particularly aggressive form of vulvar cancer. This provides a unique opportunity for elucidating the aetiopathological pathways driving vulvar cancer development that may ultimately lead to preventive and therapeutic targets for this neglected malignancy. Further, these findings have important implications for clinical practice and HPV vaccination policy in the affected population.

Possible role for glucagon in the control of Paget's disease of bone.

Paget's disease of bone is characterised by overactive osteoclasts that resorb bone at a higher rate than normal. Osteoblasts attempt to repair the damage by laying down new bone which in turn is resorbed leaving a chaotic pattern of lytic and dense sclerotic bone behind. Deformed bone enlarges, becomes vascularised, bends and fractures. No bone is exempt but the skull, pelvis, vertebrae and long bones are commonly affected. Pressure from pagetic bone impinges on the auditory, facial, optic, trigeminal nerves and the spinal cord, risking paraplegia or quadriplegia. Vascular complications include cardiac failure and vertebrobasilar insufficiency. Serum alkaline phosphatase and urine N-telopeptide were used to assess response to treatment with porcine, salmon and human calcitonins, glucagon and bisphonates given alone or in combination. Glucagon has few side effects and controls the disease very rapidly. It can be given alone but because remissions last a few months, repeat courses may be necessary to achieve a long-term permanent quiescent bone state. If complete disease remission is not achieved with the hormone alone, an oral or intravenous bisphosphonate is given at the end of glucagon treatment. Other options are a second-generation bisphosphonate given orally to patients who decline parenteral medication. It remains to be seen whether glucagon affects other bone disorders.

Aboriginal women have a higher risk of cervical abnormalities at screening; South Australia, 1993-2016.

OBJECTIVE: Cervical cancer mortality has halved in Australia since the national cervical screening program began in 1991, but elevated mortality rates persist for Aboriginal and Torres Strait Islander women (referred to as Aboriginal women in this report). We investigated differences by Aboriginal status in abnormality rates predicted by cervical cytology and confirmed by histological diagnoses among screened women. METHODS: Using record linkage between cervical screening registry and public hospital records in South Australia, we obtained Aboriginal status of women aged 20-69 for 1993-2016 (this was not recorded by the registry). Differences in cytological abnormalities were investigated by Aboriginal status, using relative risk ratios from mixed effect multinomial logistic regression modelling. Odds ratios were calculated for histological high grade results for Aboriginal compared with non-Aboriginal women. RESULTS: Of 1,676,141 linkable cytology tests, 5.8% were abnormal. Abnormal results were more common for women who were younger, never married, and living in a major city or socioeconomically disadvantaged area. After adjusting for these factors and numbers of screening episodes, the relative risk of a low grade cytological abnormality compared with a normal test was 14% (95% confidence interval 5-24%) higher, and the relative risk of a high grade cytological abnormality was 61% (95% confidence interval 44-79%) higher, for Aboriginal women. The adjusted odds ratio of a histological high grade was 76% (95% confidence interval 46-113%) higher. CONCLUSIONS: Ensuring that screen-detected abnormalities are followed up in a timely way by culturally acceptable services is important for reducing differences in cervical cancer rates between Aboriginal and non-Aboriginal women.

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

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).

Development of a National Aboriginal and Torres Strait Islander Cancer Framework: A Shared Process to Guide Effective Policy and Practice.

Indigenous Australians experience a substantially higher cancer mortality rate than non-Indigenous Australians. While cancer outcomes are improving for non-Indigenous Australians, they are worsening for Indigenous Australians. Reducing this disparity requires evidence-based and culturally-appropriate guidance. The purpose of this paper is to describe an initiative by Cancer Australia and Menzies School of Health Research (Menzies) to develop Australia’s first National Aboriginal and Torres Strait Islander Cancer Framework using a process of co-design with relevant stakeholders. The initiative was guided by three core principles: achieving policy-relevant evidence-based outcomes; engaging and maintaining trust with Indigenous Australians at every phase; and employing best-practice and appropriate research methods. Four components of research comprised the Framework development: evidence review; multifaceted stakeholder consultation and input; triangulation of findings; and direct stakeholder input in drafting and refining the Framework. The evidence review confirmed the increasing burden of cancer on Indigenous Australians, while stakeholder consultations facilitated comprehensive input from those with lived experience. The consultations revealed issues not identified in existing literature, and gave different emphases of priority, thus reinforcing the value of including stakeholder perspectives. This paper focuses primarily on documenting the methods used; findings are presented only in order to illustrate the results of the process. The published Framework is available at www.canceraustralia.gov.au; further description and analyses of findings from the consultations will be published elsewhere. The logistics inherent in large-scale consultation are considerable. However, the quality of data and the foundation for sustained partnership with stakeholders and knowledge translation vastly outweighed the challenges. The process of wide-ranging stakeholder consultation described in this paper offers a model for other areas of national and international Indigenous priority setting and policy and practice development that meets the needs of those most affected. The Framework, through the establishment of an agreed, shared and evidence-based agenda, provides guidance for jurisdictional cancer plans, optimal care pathways, and program and service planning for the multiple players across all levels of the health system.

Time to clinical investigation for Indigenous and non-Indigenous Queensland women after a high grade abnormal Pap smear, 2000-2009.

OBJECTIVES: To investigate time to follow-up (clinical investigation) for Indigenous and non-Indigenous women in Queensland after a high grade abnormality (HGA) being detected by Pap smear. DESIGN, SETTING, PARTICIPANTS: Population-based retrospective cohort analysis of linked data from the Queensland Pap Smear Register (PSR), the Queensland Hospital Admitted Patient Data Collection, and the Queensland Cancer Registry. 34 980 women aged 20-68 years (including 1592 Indigenous women) with their first HGA Pap smear result recorded on the PSR (index smear) during 2000-2009 were included and followed to the end of 2010. MAIN OUTCOME MEASURES: Time from the index smear to clinical investigation (histology test or cancer diagnosis date), censored at 12 months. RESULTS: The proportion of women who had a clinical investigation within 2 months of a HGA finding was lower for Indigenous (34.1%; 95% CI, 31.8-36.4%) than for non-Indigenous women (46.5%; 95% CI, 46.0-47.0%; unadjusted incidence rate ratio [IRR], 0.65; 95% CI, 0.60-0.71). This difference remained after adjusting for place of residence, area-level disadvantage, and age group (adjusted IRR, 0.74; 95% CI, 0.68-0.81). However, Indigenous women who had not been followed up within 2 months were subsequently more likely to have a clinical investigation than non-Indigenous women (adjusted IRR for 2-4 month interval, 1.21; 95% CI, 1.08-1.36); by 6 months, a similar proportion of Indigenous (62.2%; 95% CI, 59.8-64.6%) and non-Indigenous women (62.8%; 95% CI, 62.2-63.3%) had been followed up. CONCLUSIONS: Prompt follow-up after a HGA Pap smear finding needs to improve for Indigenous women. Nevertheless, slow follow-up is a smaller contributor to their higher cervical cancer incidence and mortality than their lower participation in cervical screening.

Different survival analysis methods for measuring long-term outcomes of Indigenous and non-Indigenous Australian cancer patients in the presence and absence of competing risks.

BACKGROUND: Net survival is the most common measure of cancer prognosis and has been used to study differentials in cancer survival between ethnic or racial population subgroups. However, net survival ignores competing risks of deaths and so provides incomplete prognostic information for cancer patients, and when comparing survival between populations with different all-cause mortality. Another prognosis measure, "crude probability of death", which takes competing risk of death into account, overcomes this limitation. Similar to net survival, it can be calculated using either life tables (using Cronin-Feuer method) or cause of death data (using Fine-Gray method). The aim of this study is two-fold: (1) to compare the multivariable results produced by different survival analysis methods; and (2) to compare the Cronin-Feuer with the Fine-Gray methods, in estimating the cancer and non-cancer death probability of both Indigenous and non-Indigenous cancer patients and the Indigenous cancer disparities. METHODS: Cancer survival was investigated for 9,595 people (18.5% Indigenous) diagnosed with cancer in the Northern Territory of Australia between 1991 and 2009. The Cox proportional hazard model along with Poisson and Fine-Gray regression were used in the multivariable analysis. The crude probabilities of cancer and non-cancer methods were estimated in two ways: first, using cause of death data with the Fine-Gray method, and second, using life tables with the Cronin-Feuer method. RESULTS: Multivariable regression using the relative survival, cause-specific survival, and competing risk analysis produced similar results. In the presence of competing risks, the Cronin-Feuer method produced similar results to Fine-Gray in the estimation of cancer death probability (higher Indigenous cancer death probabilities for all cancers) and non-cancer death probabilities (higher Indigenous non-cancer death probabilities for all cancers except lung cancer and head and neck cancers). Cronin-Feuer estimated much lower non-cancer death probabilities than Fine-Gray for non-Indigenous patients with head and neck cancers and lung cancers (both smoking-related cancers). CONCLUSION: Despite the limitations of the Cronin-Feuer method, it is a reasonable alternative to the Fine-Gray method for assessing the Indigenous survival differential in the presence of competing risks when valid and reliable subgroup-specific life tables are available and cause of death data are unavailable or unreliable.

Association between comorbidity and participation in breast and cervical cancer screening: A systematic review and meta-analysis.

BACKGROUND: Comorbidity is associated with poor outcomes for cancer patients but it is less clear how it influences cancer prevention and early detection. This review synthesizes evidence from studies that have quantified the association between comorbidity and participation in breast and cervical screening. METHODS: PubMed, CINAHL and EMBASE databases were systematically searched using key terms related to cancer screening and comorbidity for original research articles published between 1 January 1991 and 21 March 2016. Two reviewers independently screened 1283 studies that met eligibility criteria related to Population (adult, non-cancer populations), Exposure (comorbidity), Comparison (a 'no comorbidity' group), and Outcome (participation in breast cancer or cervical screening). Data was extracted and risk of bias assessed using a standardised tool from the 22 studies identified for inclusion (17 breast; 13 cervical). Meta-analyses were performed for participation in breast and cervical screening, stratified by important study characteristics. RESULTS: The majority of studies were conducted in the United States. Results of individual studies were variable. Most had medium to high risk of bias. Based on the three "low risk of bias" studies, mammography screening was less common among those with comorbidity (pooled Odds Ratio 0.66, 95%CI 0.44-0.88). The one "low risk of bias" study of cervical screening reported a negative association between comorbidity and participation. CONCLUSION: While a definitive conclusion could not be drawn, the results from high quality studies suggest that women with comorbidity are less likely to participate in breast, and possibly cervical, cancer screening.

Inhibition of cancer cell mitosis by reducing the availability of phosphate.

The addition of phosphate groups is an essential requirement for the proper functioning of cyclin and cyclin dependent kinase which control various stages in the mitotic division of cancer cells. Thus limiting the availability of phosphate is likely to interfere with the metabolism of rapidly growing malignant cells. The human hormone glucagon and the anti metabolite mithramycin reduce serum phosphate by increasing phosphaturia and are both very effective in treating Paget's disease of bone, a precancerous condition. In this disorder large doses of glucagon given intravenously relieve bone pain and cause serum phosphate and alkaline phosphatase as well as urine hydroxyproline to fall, indicating a marked reduction in bone turnover. A constant iv infusion of glucagon was given to each of three patients all of whom had secondary malignant bone deposits. Two of the patients had primary prostate cancer and one had a squamous cell lung tumour. All three patients had relief of bone pain and a fall in serum alkaline phosphatase. Serum acid phosphatase also fell in the two patients with prostate cancer. It is proposed that the marked drop in serum phosphate due to glucagon causes intracellular phosphate to fall. This in turn disrupts the addition and removal of phosphate groups essential for the proper functioning of cyclin and cyclin dependent kinase. These two proteins control the transition from G1 to S (DNA synthesis phase) and G2 to M (mitotic phase) in the dividing cycle of malignant cells. Depriving a tumour of an essential ingredient used in phosphorylation reactions will disrupt its growth. It is also proposed that, by the same mechanism, glucagon induced hypophosphataemia renders malignant cells more sensitive to established chemotherapeutic agents and radiation waves. If this hypothesis proves to be correct, lowering intracellular phosphate may become an useful tool in cancer therapy. However extensive studies are necessary to determine whether mitosis in cancer cells can be advantageously disrupted by glucagon induced hypophosphataemia.

Trends in cancer incidence and survival for Indigenous and non-Indigenous people in the Northern Territory.

OBJECTIVE: To assess trends in cancer incidence and survival for Indigenous and non-Indigenous Australians in the Northern Territory. DESIGN: Retrospective analysis of population-based cancer registration data. SETTING: New cancer diagnoses in the NT, 1991-2012. MAIN OUTCOME MEASURES: Age-adjusted incidence rates; rate ratios comparing incidence in NT Indigenous and non-Indigenous populations with that for other Australians; 5-year survival; multivariable Poisson regression of excess mortality. RESULTS: The incidence of most cancers in the NT non-Indigenous population was similar to that for other Australians. For the NT Indigenous population, the incidence of cancer at several sites was much higher (v other Australians: lung, 84% higher; head and neck, 325% higher; liver, 366% higher; cervix, 120% higher). With the exception of cervical cancer (65% decrease), incidence rates in the Indigenous population did not fall between 1991-1996 and 2007-2012. The incidence of several other cancers (breast, bowel, prostate, melanoma) was much lower in 1991-1996 than for other Australians, but had increased markedly by 2007-2012 (breast, 274% increase; bowel, 120% increase; prostate, 116% increase). Five-year survival was lower for NT Indigenous than for NT non-Indigenous patients, but had increased for both populations between 1991-2000 and 2001-2010. CONCLUSION: The incidence of several cancers that were formerly less common in NT Indigenous people has increased, without a concomitant reduction in the incidence of higher incidence cancers (several of which are smoking-related). The excess burden of cancer in this population will persist until lifestyle risks are mitigated, particularly by reducing the extraordinarily high prevalence of smoking.

Lifetime direct costs of stroke for indigenous patients adjusted for comorbidities.

OBJECTIVE: To estimate the lifetime health costs of stroke by comorbidity and indigenous status in Australia's Northern Territory (NT), where a large indigenous population resides. METHODS: Incidence-based cohort study using linked hospital, primary care, and Pharmaceutical Benefits Scheme data to estimate lifetime direct costs for hemorrhagic stroke (HS), ischemic stroke (IS) and undetermined stroke (UND). Inverse probability-weighted survival analysis was adapted to adjust for loss to follow-up. Log-linear modeling was used to analyze the net stroke costs and marginal comorbidity costs by indigenous status. RESULTS: Between 1992 and 2013, there were 3,733 patients admitted with stroke in the NT (74% were incident strokes, 38% indigenous, 56% male, 56% IS). In 2012/2013 Australian dollars, the estimated lifetime cost for an incident stroke in NT was $302,538 AUD ($207,218 USD) per patient. The net lifetime cost per non-indigenous female HS patient aged <45 years without comorbidity (reference category) was $72,773 AUD ($49,844 USD); IS cost 54% and UND 9% more than HS (p < 0.01). Stroke cost was greater for indigenous patients (∆ 44%) and patients with renal disease (∆ 71%), coronary heart disease (∆ 44%), hypertension (∆ 30%), and diabetes (∆ 28%) in comparison with the reference category (all p < 0.01). Chronic obstructive pulmonary disease, atrial fibrillation, depression, and cancer were negatively associated with lifetime stroke costs. CONCLUSIONS: The costs of stroke for indigenous people and patients with different comorbidities are substantial and an integrated prevention strategy is needed.

Long-Term Outcomes From Acute Rheumatic Fever and Rheumatic Heart Disease: A Data-Linkage and Survival Analysis Approach.

BACKGROUND: We investigated adverse outcomes for people with acute rheumatic fever (ARF) and rheumatic heart disease (RHD) and the effect of comorbidities and demographic factors on these outcomes. METHODS: Using linked data (RHD register, hospital, and mortality data) for residents of the Northern Territory of Australia, we calculated ARF recurrence rates, rates of progression from ARF to RHD to severe RHD, RHD complication rates (heart failure, endocarditis, stroke, and atrial fibrillation), and mortality rates for 572 individuals diagnosed with ARF and 1248 with RHD in 1997 to 2013 (94.9% Indigenous). RESULTS: ARF recurrence was highest (incidence, 3.7 per 100 person-years) in the first year after the initial ARF episode, but low-level risk persisted for >10 years. Progression to RHD was also highest (incidence, 35.9) in the first year, almost 10 times higher than ARF recurrence. The median age at RHD diagnosis in Indigenous people was young, especially among males (17 years). The development of complications was highest in the first year after RHD diagnosis: heart failure incidence rate per 100 person-years, 9.09; atrial fibrillation, 4.70; endocarditis, 1.00; and stroke, 0.58. Mortality was higher among Indigenous than non-Indigenous RHD patients (hazard ratio, 6.55; 95% confidence interval, 2.45-17.51), of which 28% was explained by comorbid renal failure and hazardous alcohol use. RHD complications and mortality rates were higher for urban than for remote residents. CONCLUSIONS: This study provides important new prognostic information for ARF/RHD. The residual Indigenous survival disparity in RHD patients, which persisted after accounting for comorbidities, suggests that other factors contribute to mortality, warranting further research.