Benefits and harms of prostate specific antigen testing according to Australian guidelines.

Guidelines for prostate specific antigen (PSA) testing in Australia recommend that men at average risk of prostate cancer who have been informed of the benefits and harms, and who decide to undergo regular testing, should be offered testing every 2 years from 50 to 69 years. This study aimed to estimate the benefits and harms of regular testing in this context. We constructed Policy1-Prostate, a discrete event microsimulation platform of the natural history of prostate cancer and prostate cancer survival, and PSA testing patterns and subsequent management in Australia. The model was calibrated to pre-PSA (before 1985) prostate cancer incidence and mortality and validated against incidence and mortality trends from 1985 to 2011 and international trials. The model predictions were concordant with trials and Australian observed incidence and mortality data from 1985 to 2011. Out of 1000 men who choose to test according to the guidelines, 36 [21-41] men will die from prostate cancer and 126 [119-133] men will be diagnosed with prostate cancer, compared with 50 [47-54] and 94 [90-98] men who do not test, respectively. During the 20 years of active PSA testing, 32.3% [25.6%-38.8%] of all PSA-test detected cancers are overdiagnosed cases that is, 30 [21-42] out of 94 [83-107] PSA-test detected cancers. Australian men choosing to test with PSA every two years from 50 to 69 will reduce their risk of ever dying from prostate cancer and incur a risk of overdiagnosis: for every man who avoids dying from prostate cancer, two will be overdiagnosed with prostate cancer between 50 and 69 years of age. Australian men, with health professionals, can use these results to inform decision-making about PSA testing.

Sociodemographic, behavioral, and clinical characteristics associated with perceived discrimination in healthcare settings among Black persons with diagnosed HIV in the United States.

Research that explores the intra-racial socio-demographic and clinical characteristics associated with perceived discrimination in healthcare settings in the US is lacking. We examined the prevalence of self-reported discrimination in HIV care settings during the past 12 months among Black persons from a nationally representative sample of US adults with diagnosed HIV collected 6/2018-5/2019. We assessed the prevalence of self-reported discrimination in HIV care settings during the past 12 months, perceived reasons for discrimination, and factors associated with discrimination among Black persons with diagnosed HIV (n = 1,631). Overall, 22% reported experiencing discrimination in a healthcare setting; discrimination was most often attributed to HIV status. Those reporting discrimination were younger, MSM, and living at or below the federal poverty level. They also experienced homelessness, incarceration and illicit substance use in the past 12 months, and anxiety and depression symptoms in the past 2 weeks. They were less likely to use ART or report 100% ART dose adherence in the past 30 days. No associations were found with viral suppression. Systems are needed to monitor, evaluate reports of, and address discrimination in healthcare settings. Incorporating anti-discrimination policies and continuing education opportunities for providers and staff may reduce experiences of discrimination among persons with HIV.

Exploring HONO formation and its role in driving secondary pollutants formation during winter in the North China Plain.

Daytime HONO photolysis is an important source of atmospheric hydroxyl radicals (OH). Knowledge of HONO formation chemistry under typical haze conditions, however, is still limited. In the Multiphase chemistry experiment in Fogs and Aerosols in the North China Plain in 2018, we investigated the wintertime HONO formation and its atmospheric implications at a rural site Gucheng. Three different episodes based on atmospheric aerosol loading levels were classified: clean periods (CPs), moderately polluted periods (MPPs) and severely polluted periods (SPPs). Correlation analysis revealed that HONO formation via heterogeneous conversion of NO2 was more efficient on aerosol surfaces than on ground, highlighting the important role of aerosols in promoting HONO formation. Daytime HONO budget analysis indicated a large missing source (with an average production rate of 0.66 ± 0.26, 0.97 ± 0.47 and 1.45 ± 0.55 ppbV/hr for CPs, MPPs and SPPs, respectively), which strongly correlated with photo-enhanced reactions (NO2 heterogeneous reaction and particulate nitrate photolysis). Average OH formation derived from HONO photolysis reached up to (0.92 ± 0.71), (1.75 ± 1.26) and (1.82 ± 1.47) ppbV/hr in CPs, MPPs and SPPs respectively, much higher than that from O3 photolysis (i.e., (0.004 ± 0.004), (0.006 ± 0.007) and (0.0035 ± 0.0034) ppbV/hr). Such high OH production rates could markedly regulate the atmospheric oxidation capacity and hence promote the formation of secondary aerosols and pollutants.

Raking of data from a large Australian cohort study improves generalisability of estimates of prevalence of health and behaviour characteristics and cancer incidence.

BACKGROUND: Health surveys are commonly somewhat non-representative of their target population, potentially limiting the generalisability of prevalence estimates for health/behaviour characteristics and disease to the population. To reduce bias, weighting methods have been developed, though few studies have validated weighted survey estimates against generally accepted high-quality independent population benchmark estimates. METHODS: We applied post-stratification and raking methods to the Australian 45 and Up Study using Census data and compared the resulting prevalence of characteristics to accepted population benchmark estimates and separately, the incidence rates of lung, colorectal, breast and prostate cancer to whole-of-population estimates using Standardised Incidence Ratios (SIRs). RESULTS: The differences between 45 and Up Study and population benchmark estimates narrowed following sufficiently-informed raking, e.g. 13.6% unweighted prevalence of self-reported fair/poor overall health, compared to 17.0% after raking and 17.9% from a population benchmark estimate. Raking also improved generalisability of cancer incidence estimates. For example, unweighted 45 and Up Study versus whole-of-population SIRs were 0.700 (95%CI:0.574-0.848) for male lung cancer and 1.098 (95%CI:1.002-1.204) for prostate cancer, while estimated SIRs after sufficiently-informed raking were 0.828 (95%CI:0.684-0.998) and 1.019 (95%CI:0.926-1.121), respectively. CONCLUSION: Raking may be a useful tool for improving the generalisability of exposure prevalence and disease incidence from surveys to the population.

Antiretroviral prescription, retention in care and viral suppression by place of birth among adults with diagnosed HIV in the United States-2015-2017, medical monitoring project.

HIV clinical outcomes have not been fully assessed by place of birth at the national level. We analyzed the Medical Monitoring Project data, an annual cross-sectional survey designed to produce nationally representative estimates on adults with diagnosed HIV in the United States, collected during 2015-2017 (n = 7617). We compared sociodemographic, behavioral, and clinical outcomes by place of birth using Rao-Scott chi-square tests (P < .05). Overall, 13.6% of adults with diagnosed HIV were non-US-born. During the past 12 months, a higher percentage of non-US-born than US-born adults, respectively, were prescribed ART (89.4% vs. 84.1%), retained in care (87.1% vs. 80.0%), virally suppressed at the last test (77.2% vs. 70.9%), and had sustained viral suppression (70.9% vs. 63.3%). A lower percentage of non-US-born adults reported binge drinking (13.0% vs. 16.1%), using non-injection drugs (15.3% vs. 31.7%), and suffering from depression (15.9% vs. 23.3%) or anxiety (10.0% vs. 20.2%). A significantly higher percentage of non-US-born adults had Ryan White HIV/AIDS Program (RWHAP) coverage (54.4% vs. 43.1%) and attended a RWHAP-funded health care facility (73.9% vs. 66.6%). Factors contributing to better HIV clinical outcomes among non-US-born persons may include access to RWHAP coverage, lower levels of substance use, and better mental health.

Missed opportunities for prevention and treatment of hepatitis C among persons with HIV/HCV coinfection.

Hepatitis C (HCV) and HIV have common modes of transmission but information about HCV transmission risk, prevention, and treatment among persons with coinfection is lacking. The Medical Monitoring Project produces nationally representative estimates describing adults with diagnosed HIV in the United States. Using medical record data recorded during 6/2013-5/2017, we identified persons with detectable HCV RNA documented during the past 24 months. Among persons with coinfection, we described HCV transmission risk factors and receipt of HCV prevention services during the past 12 months and prescription of HCV treatment during the past 24 months. Overall, 4.9% had documented active HCV coinfection, among whom 30.2% were men who have sex with men (MSM), 6.7% reported injection drug use, and 62.1% were prescribed HCV treatment. Among MSM, 45.5% reported condomless anal sex and 42.3% received free condoms. Among persons who used drugs, 30.8% received drug or alcohol counseling, and among persons who injected drugs, 79.2% received sterile syringes. Among persons with HIV/HCV coinfection, recent drug injection was uncommon and most received sterile syringes. However, 1 in 3 were MSM, of whom half reported recent HCV sexual transmission risk behaviors. More than one-third of those with coinfection were not prescribed curative HCV treatment.

Platinum-containing regimens for triple-negative metastatic breast cancer.

BACKGROUND: In a previous Cochrane Review, we found that for women with metastatic breast cancer unselected for triple-negative disease, there is little or no survival benefit and excess toxicity from platinum-based regimens. In subgroup analyses, however, we found preliminary low-quality evidence of a survival benefit from platinum-based regimens for women with metastatic triple-negative breast cancer (mTNBC). This review updates the evidence from the mTNBC subgroup analyses in the previous Cochrane Review. OBJECTIVES: To assess the effects of platinum-containing chemotherapy regimens with regimens not containing platinum in the management of women with mTNBC. SEARCH METHODS: We obtained relevant studies published prior to 2015 and their extracted results from the mTNBC subgroup analysis in the previous Cochrane Review. We searched the Cochrane Breast Cancer Group's Specialised Register, CENTRAL, MEDLINE, Embase, the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov between 2015 and 27 September 2019. We identified further potentially relevant studies from previous trial reports, systematic reviews, and meta-analyses. SELECTION CRITERIA: Randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in women with mTNBC. Individual trials could compare one or more platinum-based regimens to one or more non-platinum regimens; hence there could be more 'treatment-comparisons' (i.e. platinum regimen versus non-platinum regimen comparison) than trials. Trial participants may have been purposely selected for mTNBC or inadvertently selected as a subgroup. DATA COLLECTION AND ANALYSIS: At least two independent reviewers assessed studies for eligibility and quality, and extracted all relevant data from each study. We derived hazard ratios (HRs) for time-to-event outcomes, where possible, and used fixed-effect models for meta-analyses. We analysed objective tumour response rates (OTRRs) and toxicities as binary (dichotomous) outcomes with risk ratios (RRs) used as measures of effects. We extracted quality of life data, if available. We used GRADE to rate the quality of evidence for time-to-event and tumour response outcomes. MAIN RESULTS: This review includes 13 treatment-comparisons involving 1349 women from 10 studies. Twelve of the 13 treatment-comparisons were included in one or more meta-analyses. Of the 13 treatment-comparisons, six and eight had published or provided time-to-event data on overall survival (OS) or progression-free survival/time to progression (PFS/TTP), respectively, that could be included in meta-analyses. Ten treatment-comparisons published or provided OTRR data that could be included in meta-analyses. Eight of the 13 treatment-comparisons were from studies that selected participants on the basis of mTNBC status, while the other five treatment-comparisons were from studies that reported mTNBC results as part of subgroup analyses. Analysis of six treatment-comparisons indicated that platinum-containing regimens may have provided a small survival benefit to mTNBC patients (HR 0.85, 95% CI 0.73 to 1.00; 958 women; moderate-quality evidence) with no evidence of heterogeneity (P = 0.41; I2 = 1%). Data from eight treatment-comparisons showed that platinum regimens may improve PFS/TTP (HR 0.77, 95% CI 0.68 to 0.88; 1077 women; very low-quality evidence). There was marked evidence of heterogeneity (P < 0.0001; I2 = 80%). There was also low-quality evidence of better tumour response for platinum recipients (RR 1.40, 95% CI 1.22 to 1.59; 1205 women) with some evidence of heterogeneity (P = 0.01; I2 = 58%). The observed heterogeneity for the PFS/TTP and OTRR outcomes may reflect between-study differences and general difficulties in assessing tumour response, as well as the varying potencies of the comparators. Compared with women receiving non-platinum regimens: rates of grade 3 and 4 nausea/vomiting were higher for platinum recipients (RR 4.77, 95% CI 1.93 to 11.81; 655 women; low-quality evidence) and rates of grade 3 and 4 anaemia were higher for platinum recipients (RR 3.80, 95% CI 2.25 to 6.42; 843 women; low-quality evidence). In general, however, relatively few intervention-comparisons could be included in meta-analyses for adverse events. None of the studies reported quality of life. AUTHORS' CONCLUSIONS: For women with mTNBC, there was moderate-quality evidence of a small survival benefit from platinum-based regimens compared to non-platinum regimens. This finding is consistent with findings of a PFS/TTP benefit and improved tumour response from platinum-based regimens. These potential benefits, however, should be weighed against previously identified excess toxicities from platinum-based regimens, particularly regimens containing cisplatin. Further randomised trials of platinum-based regimens among women with mTNBC are required.

Behavioral and Clinical Characteristics of American Indian/Alaska Native Adults in HIV Care - Medical Monitoring Project, United States, 2011-2015.

The rate of diagnosis of human immunodeficiency virus (HIV) infection among American Indians and Alaska Natives (AI/ANs) in 2016 (10.2 per 100,000 population) was the fourth highest among seven racial/ethnic groups in the United States (1); the number of diagnoses of HIV infection among AI/AN persons increased by 70%, from 143 in 2011 to 243 in 2016 (1). However, little has been published about the sociodemographic, behavioral, and clinical characteristics of AI/AN patients with HIV infection in care because small sample sizes have led to infrequent analysis of AI/AN-specific estimates (2) and because of underestimation of AI/AN race/ethnicity in surveillance and other data sources (3). CDC analyzed data from the Medical Monitoring Project (MMP), a surveillance system that collects information about the experiences and needs of persons with diagnosed HIV infection, collected during 2011-2015 among AI/AN adults receiving HIV medical care. The results indicated that 64% of AI/AN patients with HIV infection in care achieved sustained viral suppression, and 76% achieved viral suppression at their most recent viral load test within the past 12 months, which is below the national HIV prevention goal of 80%, but comparable to or better than some other racial/ethnic groups (4). Based on self-report, 51% of AI/AN patients with HIV infection had incomes at or below the U.S. Department of Health and Human Services' (HHS) annual poverty limit, 27% had symptoms of depression, 78% reported internalized HIV-related stigma, and 20% reported binge drinking in the past 30 days. To improve the health of AI/AN patients with HIV infection, it is important that health care providers, tribal organizations, and state and local health departments consider the sociodemographic and behavioral barriers to AI/AN patients with HIV infection achieving viral suppression and design care plans that seek to eliminate those barriers.

Depression Prevalence, Antidepressant Treatment Status, and Association with Sustained HIV Viral Suppression Among Adults Living with HIV in Care in the United States, 2009-2014.

Previous research indicates a high burden of depression among adults living with HIV and an association between depression and poor HIV clinical outcomes. National estimates of diagnosed depression, depression treatment status, and association with HIV clinical outcomes are lacking. We used 2009-2014 data from the Medical Monitoring Project to estimate diagnosed depression, antidepressant treatment status, and associations with sustained viral suppression (all viral loads in past year < 200 copies/mL). Data were obtained through interview and medical record abstraction and were weighted to account for unequal selection probabilities and non-response. Of adults receiving HIV medical care in the U.S. and prescribed ART, 27% (95% confidence interval [CI] 25-29%) had diagnosed depression during the surveillance period; the majority (65%) were prescribed antidepressants. The percentage with sustained viral suppression was highest among those without depression (72%, CI 71-73%) and lowest among those with untreated depression (66%, CI 64-69%). Compared to those without depression, those with a depression diagnosis were less likely to achieve sustained viral suppression (aPR 0.95, CI 0.93-0.97); this association held for persons with treated depression compared to no depression (aPR 0.96, CI 0.94-0.99) and untreated depression compared to no depression (aPR 0.92, CI 0.89-0.96). The burden of depression among adults living with HIV in care is high. While in our study depression was only minimally associated with a lower prevalence of sustained viral suppression, diagnosing and treating depression in persons living with HIV remains crucial in order to improve mental health and avoid other poor health outcomes.

Molecular Determinants of Enterotoxigenic Escherichia coli Heat-Stable Toxin Secretion and Delivery.

Enterotoxigenic Escherichia coli (ETEC), a heterogeneous diarrheal pathovar defined by production of heat-labile (LT) and/or heat-stable (ST) toxins, causes substantial morbidity among young children in the developing world. Studies demonstrating a major burden of ST-producing ETEC have focused interest on ST toxoids for ETEC vaccines. We examined fundamental aspects of ST biology using ETEC strain H10407, which carries estH and estP genes encoding STh and STp, respectively, in addition to eltAB genes responsible for LT. Here, we found that deletion of estH significantly diminished cyclic GMP (cGMP) activation in target epithelia, while deletion of estP had a surprisingly modest impact, and a dual estH estP mutant was not appreciably different from the estH mutant. However, we noted that either STh or STp recombinant peptides stimulated cGMP production and that the loss of estP was compensated by enhanced estH transcription. We also found that the TolC efflux protein was essential for toxin secretion and delivery, providing a potential avenue for efflux inhibitors in treatment of acute diarrheal illness. In addition, we demonstrated that the EtpA adhesin is required for optimal delivery of ST and that antibodies against either the adhesin or STh significantly impaired toxin delivery and cGMP activation in target T84 cells. Finally, we used FLAG epitope fusions to demonstrate that the STh propeptide sequence is secreted by ETEC, potentially providing additional epitopes for antibody neutralization. These studies collectively extend our understanding of ETEC pathogenesis and potentially inform additional avenues to mitigate disease by these common diarrheal pathogens.

Differences in Characteristics and Clinical Outcomes Among Hispanic/Latino Men and Women Receiving HIV Medical Care - United States, 2013-2014.

The prevalence of diagnosed human immunodeficiency virus (HIV) infection among Hispanics/Latinos in the United States is approximately twice that of non-Hispanic whites (1). Barriers to, and experiences with, medical care have been found to vary by sex (2). Describing characteristics of Hispanics/Latinos in care by sex can help identify disparities and inform delivery of tailored services to this underserved population. Data from the 2013 and 2014 cycles of the Medical Monitoring Project (MMP) were analyzed to describe demographic, behavioral, and clinical characteristics among Hispanics/Latinos by sex. MMP is an annual cross-sectional, nationally representative surveillance system that, during 2013-2014, collected information about behaviors, medical care, and clinical outcomes among adults receiving outpatient HIV care. Hispanic/Latina women were significantly more likely than were men to live in poverty (78% versus 54%), report not speaking English well (38% versus 21%), and receive interpreter (27% versus 16%), transportation (35% versus 21%), and meal (44% versus 26%) services. There were no significant differences between Hispanic/Latino women and men in prescription of antiretroviral therapy (ART) (95% versus 96%) or sustained viral suppression (68% versus 73%). Although women faced greater socioeconomic and language-related challenges, the clinical outcomes among Hispanic/Latina women were similar to those among men, perhaps reflecting their higher use of ancillary services. Levels of viral suppression for Hispanics/Latinos are lower than those found among non-Hispanic whites (3) and lower than the national prevention goal of at least 80% of persons with diagnosed HIV infection. Providers should be cognizant of the challenges faced by Hispanics/Latinos with HIV infection in care and provide referrals to needed ancillary services.

Widening socioeconomic disparity in lung cancer incidence among men in New South Wales, Australia, 1987-2011.

OBJECTIVE: We assessed the trends in lung cancer incidence over a 25-year period by socioeconomic groups for men in New South Wales (NSW), Australia. METHODS: Men diagnosed with lung cancer between 1987 and 2011 were divided into five quintiles according to an Index of Education and Occupation (IEO). We assessed relative socioeconomic differences over time by calculating age-standardized incidence ratios (SIRs) by 5-year period of diagnosis, and estimated absolute differences by comparing the observed and expected numbers of cases using the highest IEO quintile as the reference. RESULTS: Lung cancer incidence for men decreased from 1987 to 2011 for all IEO quintiles, with a greater rate of decline for men living in the highest IEO areas. Thus, the relative disparity increased significantly over the 25-year period (P=0.0006). For example, the SIR for the lowest IEO quintile increased from 1.28 during 1987-1991 to 1.74 during 2007-2011. Absolute differences also increased with the proportion of " potentially preventable" cases doubling from 14.5% in 1987-1991 to 30.2% in 2007-2011. CONCLUSIONS: Despite the overall decline in lung cancer incidence among men in NSW over the past 25 years, there was a significant increase in disparity across socioeconomic areas in both relative and absolute terms.

Dynamic Interactions of a Conserved Enterotoxigenic Escherichia coli Adhesin with Intestinal Mucins Govern Epithelium Engagement and Toxin Delivery.

At present, there is no vaccine for enterotoxigenic Escherichia coli (ETEC), an important cause of diarrheal illness. Nevertheless, recent microbial pathogenesis studies have identified a number of molecules produced by ETEC that contribute to its virulence and are novel antigenic targets to complement canonical vaccine approaches. EtpA is a secreted two-partner adhesin that is conserved within the ETEC pathovar. EtpA interacts with the tips of ETEC flagella to promote bacterial adhesion, toxin delivery, and intestinal colonization by forming molecular bridges between the bacteria and the epithelial surface. However, the nature of EtpA interactions with the intestinal epithelium remains poorly defined. Here, we demonstrate that EtpA interacts with glycans presented by transmembrane and secreted intestinal mucins at epithelial surfaces to facilitate pathogen-host interactions that culminate in toxin delivery. Moreover, we found that a major effector molecule of ETEC, the heat-labile enterotoxin (LT), may enhance these interactions by stimulating the production of the gel-forming mucin MUC2. Our studies suggest, however, that EtpA participates in complex and dynamic interactions between ETEC and the gastrointestinal mucosae in which host glycoproteins promote bacterial attachment while simultaneously limiting the epithelial engagement required for effective toxin delivery. Collectively, these data provide additional insight into the intricate nature of ETEC interactions with the intestinal epithelium that have potential implications for rational approaches to vaccine design.

Contribution of the highly conserved EaeH surface protein to enterotoxigenic Escherichia coli pathogenesis.

Enterotoxigenic Escherichia coli (ETEC) strains are among the most common causes of diarrheal illness worldwide. These pathogens disproportionately afflict children in developing countries, where they cause substantial morbidity and are responsible for hundreds of thousands of deaths each year. Although these organisms are important targets for enteric vaccines, most development efforts to date have centered on a subset of plasmid-encoded fimbrial adhesins known as colonization factors and heat-labile toxin (LT). Emerging data suggest that ETEC undergoes considerable changes in its surface architecture, sequentially deploying a number of putative adhesins during its interactions with the host. We demonstrate here that one putative highly conserved, chromosomally encoded adhesin, EaeH, engages the surfaces of intestinal epithelial cells and contributes to bacterial adhesion, LT delivery, and colonization of the small intestine.

EatA, an immunogenic protective antigen of enterotoxigenic Escherichia coli, degrades intestinal mucin.

Enterotoxigenic Escherichia coli (ETEC) is a major cause of morbidity and mortality due to infectious diarrhea in developing countries for which there is presently no effective vaccine. A central challenge in ETEC vaccinology has been the identification of conserved surface antigens to formulate a broadly protective vaccine. Here, we demonstrate that EatA, an immunogenic secreted serine protease of ETEC, contributes to virulence by degrading MUC2, the major protein present in the small intestinal mucous layer, and that removal of this barrier in vitro accelerates toxin access to the enterocyte surface. In addition, we demonstrate that vaccination with the recombinant secreted passenger domain of EatA (rEatAp) elicits high titers of antibody and is protective against intestinal infection with ETEC. These findings may have significant implications for development of both subunit and live-attenuated vaccines against ETEC and other enteric pathogens, including Shigella flexneri, that express similar proteins.

Enterotoxigenic Escherichia coli secretes a highly conserved mucin-degrading metalloprotease to effectively engage intestinal epithelial cells.

Enterotoxigenic Escherichia coli (ETEC) is a leading cause of death due to diarrheal illness among young children in developing countries, and there is currently no effective vaccine. Many elements of ETEC pathogenesis are still poorly defined. Here we demonstrate that YghJ, a secreted ETEC antigen identified in immunoproteomic studies using convalescent patient sera, is required for efficient access to small intestinal enterocytes and for the optimal delivery of heat-labile toxin (LT). Furthermore, YghJ is a highly conserved metalloprotease that influences intestinal colonization of ETEC by degrading the major mucins in the small intestine, MUC2 and MUC3. Genes encoding YghJ and its cognate type II secretion system (T2SS), which also secretes LT, are highly conserved in ETEC and exist in other enteric pathogens, including other diarrheagenic E. coli and Vibrio cholerae bacteria, suggesting that this mucin-degrading enzyme may represent a shared virulence feature of these important pathogens.

A population-based study of breast cancer prevalence in Australia: predicting the future health care needs of women living with breast cancer.

BACKGROUND: Breast cancer places a heavy burden on the Australian healthcare system, but information about the actual number of women living with breast cancer and their current or future health service needs is limited. We used existing population-based data and innovative statistical methods to address this critical research question in a well-defined geographic region. METHODS: Breast cancer data from the New South Wales (NSW) Central Cancer Registry and PIAMOD (Prevalence and Incidence Analysis MODel) software were used to project future breast cancer prevalence in NSW. Parametric models were fitted to incidence and survival data, and the modelled incidence and survival estimates were then used to estimate current and future prevalence. To estimate future healthcare requirements the projected prevalence was then divided into phases of care according to the different stages of the survivorship trajectory. RESULTS: The number of women in NSW living with a breast cancer diagnosis had increased from 19,305 in 1990 to 48,754 in 2007. This number is projected to increase further to 68,620 by 2017. The majority of these breast cancer survivors will require continued monitoring (31,974) or will be long-term survivors (29,785). About 9% will require active treatment (either initial therapy, or treatment for subsequent metastases or second cancer) and 1% will need end of life care due to breast cancer. CONCLUSIONS: Extrapolating these projections to the national Australian population would equate to 209,200 women living with breast cancer in Australia in 2017, many of whom will require active treatment or post-treatment monitoring. Thus, careful planning and development of a healthcare system able to respond to this increased demand is required.

Absence of developmental and unconventional myosin heavy chain in human suprahyoid muscles.

INTRODUCTION: Contradictory reports of the myosin heavy chain (MHC) composition of adult human suprahyoid muscles leave unresolved the extent to which these muscles express developmental and unconventional MHC. METHODS: By immunohistochemistry, separation sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)-Coomassie, separation SDS-PAGE-Western blot, and mRNA PCR, we tested for conventional MHCI, MHCIIA, MHCIIX, developmental MHC embryonic and MHC neonatal, and unconventional MHC alpha-cardiac, MHC extraocular, and MHC slow tonic in adult human anterior digastric (AD), geniohyoid (GH), and mylohyoid (MH) muscles. RESULTS: By separation SDS-PAGE-Coomassie and Western blot, only conventional MHC are present. By immunohistochemistry all muscle fibers are positive for MHCI, MHCIIA, or MHCIIX, and fewer than 4 fibers/mm(2) are positive for developmental or unconventional MHC. By PCR, mRNA of MHCI and MHCIIA dominate, with sporadically detectable MHC alpha-cardiac and without detectable mRNA of other developmental and unconventional MHC. CONCLUSIONS: We conclude that human suprahyoid muscles AD, GH, and MH are composed almost exclusively of conventional MHC isoforms.

Geographic variation in prostate cancer survival in New South Wales.

OBJECTIVES: To determine whether the previously reported urban-rural differential in prostate cancer survival remains after adjusting for demographic and clinical factors, and to investigate temporal trends in this differential. DESIGN, SETTING AND PARTICIPANTS: Retrospective population-based survival analysis of 68 686 men diagnosed with prostate cancer from January 1982 to December 2007 in New South Wales. MAIN OUTCOME MEASURES: Survival rate and relative excess risk (RER) of death over 10 years of follow-up in relation to geographic remoteness after adjusting for other prognostic factors. RESULTS: Overall, 10-year survival increased during the study period, increasing from 57.5% in 1992-1996 and 75.7% in 1997-2001 to 83.7% in 2002-2007. The increasing trends were also observed across categories of geographic remoteness and socioeconomic status. Urban-rural differentials were significant (P < 0.001) after adjusting for five important prognostic factors, with men living outside major cities having higher risk of death from prostate cancer (RER, 1.18 and 1.32 for inner regional and rural areas, respectively). Socioeconomic status was also a significant factor (P < 0.001) for prostate cancer mortality, with the risk of dying being 34% to 40% higher for men living in socioeconomically disadvantaged areas than those living in least disadvantaged areas. There was no evidence that this inequality is reducing over time, particularly for men living in inner regional areas. CONCLUSIONS: Despite the increasing awareness of urban-rural differentials in cancer outcomes, little progress has been made. Appropriately detailed data, including details of tumour characteristics, treatment and comorbid conditions, to help understand why these inequalities exist are required urgently so interventions and policy changes can be guided by appropriate evidence.

Impact of weighting on the association between sociodemographic characteristics, health behaviours and cancer, cardiovascular and all-cause mortality in the Australian 45 and Up Study.

BACKGROUND: Weighting can improve study estimate representativeness. We examined the impact of weighting on associations between participants' characteristics and cancer, cardiovascular and all-cause mortality in the Australian 45 and Up Study cohort. METHODS: Raking weighted cohort data to the 2006 Australian population for seven sociodemographic characteristics. Deaths were ascertained via linkage to routinely collected data. Cox's proportional hazards regression quantified associations between 11 sociodemographic and health characteristics and cancer, cardiovascular and all-cause mortality. The ratios of hazard ratios (RHRs) compared unweighted and weighted estimates. RESULTS: Among 195,052 included participants (median follow-up 11.4 years), there were 7200 cancer, 5912 cardiovascular and 21,840 all-cause deaths. Overall, 102/111 (91.9%) weighted HRs did not differ significantly from unweighted HRs (100%, 86.5% and 89.2% of 37 HRs for cancer, cardiovascular and all-cause mortality, respectively). Significant differences included a somewhat stronger association between single/widowed/divorced (versus married/de-facto) and cardiovascular mortality (unweighted HR=1.25 (95%CI:1.18-1.32), weighted HR=1.33 (95%CI:1.24-1.42), RHR=1.06 (95%CI:1.02-1.11)); and between no school certificate/qualification (versus university degree) and all-cause mortality (unweighted HR=1.21 (95%CI:1.15-1.27), weighted HR=1.28 (95%CI:1.19-1.38), RHR=1.06 (95%CI:1.03-1.10)). CONCLUSION: Our results support the generalisability of most estimates of associations in the 45 and Up Study, particularly in relation to cancer mortality. Slight distortion of a few associations with cardiovascular or all-cause mortality were observed.