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.

Trends and projections of cause-specific premature mortality in Australia to 2044: a statistical modelling study.

Background: Long-term projections of premature mortality (defined as deaths age <75 years) help to inform decisions about public health priorities. This study aimed to project premature mortality rates in Australia to 2044, and to estimate numbers of deaths and potential years of life lost (PYLL) due to premature mortality overall and for 59 causes. Methods: We examined the past trends in premature mortality rates using Australian mortality data by sex, 5-year age group and 5-year calendar period up to 2019. Cigarette smoking exposure data (1945-2019) were included to project lung cancer mortality. Age-period-cohort or generalised linear models were developed and validated for each cause to project premature mortality rates to 2044. Findings: Over the 25-year period from 1990-1994 to 2015-2019, there was a 44.4% decrease in the overall age-standardised premature mortality rate. This decline is expected to continue, from 162.4 deaths/100,000 population in 2015-2019 to 141.7/100,000 in 2040-2044 (12.7% decrease). Despite declining rates, total numbers of premature deaths are projected to increase by 22.8%, rising from 272,815 deaths in 2015-2019 to 334,894 deaths in 2040-2044. This is expected to result in 1.58 million premature deaths over the 25-year period 2020-2044, accounting for 24.5 million PYLL. Of the high-level cause categories, cancer is projected to remain the most common cause of premature death in Australia by 2044, followed by cardiovascular disease, external causes (including injury, poisoning, and suicide), and respiratory diseases. Interpretation: Despite continuously declining overall premature mortality rates, the total number of premature deaths in Australia is projected to remain substantial, and cancer will continue to be the leading cause. These projections can inform the targeting of public health efforts and can serve as benchmarks against which to measure the impact of future interventions. They emphasise the ongoing importance of accelerating the prevention, early detection, and treatment of key health conditions. Funding: No funding was provided for this study.

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.

Breast Cancer Risk Assessment Tools for Stratifying Women into Risk Groups: A Systematic Review.

BACKGROUND: The benefits and harms of breast screening may be better balanced through a risk-stratified approach. We conducted a systematic review assessing the accuracy of questionnaire-based risk assessment tools for this purpose. METHODS: Population: asymptomatic women aged ≥40 years; Intervention: questionnaire-based risk assessment tool (incorporating breast density and polygenic risk where available); Comparison: different tool applied to the same population; Primary outcome: breast cancer incidence; Scope: external validation studies identified from databases including Medline and Embase (period 1 January 2008-20 July 2021). We assessed calibration (goodness-of-fit) between expected and observed cancers and compared observed cancer rates by risk group. Risk of bias was assessed with PROBAST. RESULTS: Of 5124 records, 13 were included examining 11 tools across 15 cohorts. The Gail tool was most represented (n = 11), followed by Tyrer-Cuzick (n = 5), BRCAPRO and iCARE-Lit (n = 3). No tool was consistently well-calibrated across multiple studies and breast density or polygenic risk scores did not improve calibration. Most tools identified a risk group with higher rates of observed cancers, but few tools identified lower-risk groups across different settings. All tools demonstrated a high risk of bias. CONCLUSION: Some risk tools can identify groups of women at higher or lower breast cancer risk, but this is highly dependent on the setting and population.

Cancer incidence and mortality in Australia from 2020 to 2044 and an exploratory analysis of the potential effect of treatment delays during the COVID-19 pandemic: a statistical modelling study.

BACKGROUND: Long-term projections of cancer incidence and mortality estimate the future burden of cancer in a population, and can be of great use in informing the planning of health services and the management of resources. We aimed to estimate incidence and mortality rates and numbers of new cases and deaths up until 2044 for all cancers combined and for 21 individual cancer types in Australia. We also illustrate the potential effect of treatment delays due to the COVID-19 pandemic on future colorectal cancer mortality rates. METHODS: In this statistical modelling study, cancer incidence and mortality rates in Australia from 2020 to 2044 were projected based on data up to 2017 and 2019, respectively. Cigarette smoking exposure (1945-2019), participation rates in the breast cancer screening programme (1996-2019), and prostate-specific antigen testing rates (1994-2020) were included where relevant. The baseline projection model using an age-period-cohort model or generalised linear model for each cancer type was selected based on model fit statistics and validation with pre-COVID-19 observed data. To assess the impact of treatment delays during the COVID-19 pandemic on colorectal cancer mortality, we obtained data on incidence, survival, prevalence, and cancer treatment for colorectal cancer from different authorities. The relative risks of death due to system-caused treatment delays were derived from a published systematic review. Numbers of excess colorectal cancer deaths were estimated using the relative risk of death per week of treatment delay and different durations of delay under a number of hypothetical scenarios. FINDINGS: Projections indicate that in the absence of the COVID-19 pandemic effects, the age-standardised incidence rate for all cancers combined for males would decline over 2020-44, and for females the incidence rate would be relatively stable in Australia. The mortality rates for all cancers combined for both males and females are expected to continuously decline during 2020-44. The total number of new cases are projected to increase by 47·4% (95% uncertainty interval [UI] 35·2-61·3) for males, from 380 306 in 2015-19 to 560 744 (95% UI 514 244-613 356) in 2040-44, and by 54·4% (95% UI 40·2-70·5) for females, from 313 263 in 2015-19 to 483 527 (95% UI 439 069-534 090) in 2040-44. The number of cancer deaths are projected to increase by 36·4% (95% UI 15·3-63·9) for males, from 132 440 in 2015-19 to 180 663 (95% UI 152 719-217 126) in 2040-44, and by 36·6% (95% UI 15·8-64·1) for females, from 102 103 in 2015-19 to 139 482 (95% UI 118 186-167 527) in 2040-44, due to population ageing and growth. The example COVID-19 pandemic scenario of a 6-month health-care system disruption with 16-week treatment delays for colorectal cancer patients could result in 460 (95% UI 338-595) additional deaths and 437 (95% UI 314-570) deaths occurring earlier than expected in 2020-44. INTERPRETATION: These projections can inform health service planning for cancer care and treatment in Australia. Despite the continuous decline in cancer mortality rates, and the decline or plateau in incidence rates, our projections suggest an overall 51% increase in the number of new cancer cases and a 36% increase in the number of cancer deaths over the 25-year projection period. This means that continued efforts to increase screening uptake and to control risk factors, including smoking exposure, obesity, physical inactivity, alcohol use, and infections, must remain public health priorities. FUNDING: Partly funded by Cancer Council Australia.

Projections of smoking-related cancer mortality in Australia to 2044.

BACKGROUND: While many high-income countries including Australia have successfully implemented a range of tobacco control policies, smoking remains the leading preventable cause of cancer death in Australia. We have projected Australian mortality rates for cancer types, which have been shown to have an established relationship with cigarette smoking and estimated numbers of cancer deaths attributable to smoking to 2044. METHODS: Cancer types were grouped according to the proportion of cases currently caused by smoking: 8%-30% and >30%. For each group, an age-period- cohort model or generalised linear model with cigarette smoking exposure as a covariate was selected based on the model fit statistics and validation using observed data. The smoking-attributable fraction (SAF) was calculated for each smoking-related cancer using Australian smoking prevalence data and published relative risks. RESULTS: Despite the decreasing mortality rates projected for the period 2015-2019 to 2040-2044 for both men and women, the overall number of smoking-related cancer deaths is estimated to increase by 28.7% for men and 35.8% for women: from 138 707 (77 839 men and 60 868 women) in 2015-2019 to 182 819 (100 153 men and 82 666 women) in 2040-2044. Over the period 2020-2044, there will be 254 583 cancer deaths (173 943 men and 80 640 women) directly attributable to smoking, with lung, larynx, oesophagus and oral (comprising lip, oral cavity and pharynx) cancers having the largest SAFs. INTERPRETATION: Cigarette smoking will cause over 250 000 cancer deaths in Australia from 2020 to 2044. Continued efforts in tobacco control remain a public health priority, even in countries where smoking prevalence has substantially declined.

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.

Changes in prostate cancer incidence, mortality and survival in relation to prostate specific antigen testing in New South Wales, Australia.

BACKGROUND: To examine changes in prostate cancer incidence and mortality rates, and 5-year relative survival, in relation to changes in the rate of prostate specific antigen (PSA) screening tests and the use of radical prostatectomy (RP) in the Australian population. METHODS: Prostate cancer stage-specific incidence rates, 5-year relative survival and mortality rates were estimated using New South Wales Cancer Registry data. PSA screening test rates and RP/Incidence ratios were estimated from Medicare Benefits Schedule claims data. We used multiple imputation to impute stage for cases with "unknown" stage at diagnosis. Annual percentage changes (APC) in rates were estimated using Joinpoint regression. RESULTS: Trends in the age-standardized incidence rates for localized disease largely mirrored the trends in PSA screening test rates, with a substantial 'spike' in the rates occurring in 1994, followed by a second 'spike' in 2008, and then a significant decrease from 2008 to 2015 (APC -6.7, 95% CI -8.2, -5.1). Increasing trends in incidence rates were observed for regional stage from the early 2000s, while decreasing or stable trends were observed for distant stage since 1993. The overall RP/Incidence ratio increased from 1998 to 2003 (APC 9.6, 95% CI 3.8, 15.6), then remained relatively stable to 2015. The overall 5-year relative survival for prostate cancer increased from 58.4% (95% CI: 55.0-61.7%) in 1981-1985 to 91.3% (95% CI: 90.5-92.1%) in 2011-2015. Prostate cancer mortality rates decreased from 1990 onwards (1990-2006: APC -1.7, 95% CI -2.1, -1.2; 2006-2017: APC -3.8, 95% CI -4.4, -3.1). CONCLUSIONS: Overall, there was a decrease in the incidence rate of localized prostate cancer after 2008, an increase in survival over time and a decrease in the mortality rate since the 1990s. This seems to indicate that the more conservative use of PSA screening tests in clinical practice since 2008 has not had a negative impact on population-wide prostate cancer outcomes.

Trends in colon and rectal cancer mortality in Australia from 1972 to 2015 and associated projections to 2040.

Previously published sub-site Australian projections for colon and rectal cancers to 2035 using the World Health Organization's mortality database sourced from the Australian Bureau of Statistics (ABS) predicted mortality rate decreases for colon cancer and increases for rectal cancer. There are complexities related to the interpretation of ABS's Australian colon and rectal cancer mortality rates, which could lead to possible inaccuracies in mortality rates for these sub-sites. The largest Australian population-wide registry, New South Wales Cancer Registry (NSWCR), compares routinely-reported causes of death with the recorded medical history from multiple data sources. Therefore, this study used the NSWCR data to project mortality rates for colon and rectal cancers separately to 2040 in Australia. The mortality rates for colon cancer are projected to continuously decline over the period 2015-2040, from 7.0 to 4.7 per 100,000 males, and from 5.3 to 3.2 per 100,000 females. Similar decreasing trends in mortality rates for rectal cancer were projected over the period 2015-2040, from 4.9 to 3.7 per 100,000 males, and from 2.6 to 2.3 per 100,000 females. These projections provide benchmark estimates for the colorectal cancer burden in Australia against which the effectiveness of cancer control interventions can be measured.

How Well Have Projected Lung Cancer Rates Predicted the Actual Observed Rates?

BACKGROUND: While many past studies have constructed projections of future lung cancer rates, little is known about their consistency with the corresponding observed data for the time period covered by the projections. The aim of this study was to assess the agreement between previously published lung cancer incidence and/or mortality rate projections and observed rates. METHODS: Published studies were included in the current study if they projected future lung cancer rates for at least 10 years beyond the period for which rates were used to obtain the projections, and if more recent observed rates for comparison covered a minimum of 10 years from the beginning of the projection period. Projected lung cancer incidence and/or mortality rates from these included studies were extracted from the publications. Observed rates were obtained from cancer registries or the World Health Organization's Mortality Database. Agreement between projected and observed rates was assessed and the relative difference (RD) for each projected rate was calculated as the percentage difference between the projected and observed rates. RESULTS: A total of 59 projections reported in 14 studies were included. Nine studies provided projections for 20 years or more. RDs were higher for those projections in which the lung cancer rates peaked during the projection period, and RDs increased substantially with the length of the projection period. When lung cancer rates peaked during the projection period, methods incorporating smoking data were generally more successful at predicting the trend reversal than those which did not incorporate smoking data. Mean RDs for 15-year projections comparing methods with or without smoking data were 12.7% versus 48.0% for males and 8.2% versus 42.3% for females. CONCLUSIONS: The agreement between projected and observed lung cancer rates is dependent on the trends in the observed rates and characteristics of the population, particularly trends in smoking.

Changes in cancer incidence and mortality in Australia over the period 1996-2015.

OBJECTIVE: A previous Australian study compared the observed numbers of cancer cases and deaths in 2007 with the expected numbers based on 1987 rates. This study examines the impact of cancer rate changes over the 20-year period 1996-2015, for people aged under 75 years. RESULTS: The overall age-standardised cancer incidence rate increased from 350.7 in 1995 to 364.4 per 100,000 in 2015. Over the period 1996-2015, there were 29,226 (2.0%) more cases (males: 5940, 0.7%; females: 23,286, 3.7%) than expected numbers based on 1995 rates. Smaller numbers of cases were observed compared to those expected for cancers of the lung for males and colorectum, and cancers with unknown primary. Larger numbers of cases were observed compared to those expected for cancers of the prostate, thyroid and female breast. The overall age-standardised cancer mortality rate decreased from 125.6 in 1995 to 84.3 per 100,000 in 2015. During 1996 to 2015 there were 106,903 (- 20.6%) fewer cancer deaths (males: - 69,007, - 22.6%; females: - 37,896, - 17.9%) than expected based on the 1995 mortality rates. Smaller numbers of deaths were observed compared to those expected for cancers of the lung, colorectum and female breast, and more cancer deaths were observed for liver cancer.

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.

Statistical projection methods for lung cancer incidence and mortality: a systematic review.

OBJECTIVES: To identify and summarise all studies using statistical methods to project lung cancer incidence or mortality rates more than 5 years into the future. STUDY TYPE: Systematic review. METHODS: We performed a systematic literature search in multiple electronic databases to identify studies published from 1 January 1988 to 14 August 2018, which used statistical methods to project lung cancer incidence and/or mortality rates. Reference lists of relevant articles were checked for additional potentially relevant articles. We developed an organisational framework to classify methods into groups according to the type of data and the statistical models used. Included studies were critically appraised using prespecified criteria. RESULTS: One hundred and one studies met the inclusion criteria; six studies used more than one statistical method. The number of studies reporting statistical projections for lung cancer increased substantially over time. Eighty-eight studies used projection methods, which did not incorporate data on smoking in the population, and 16 studies used a method which did incorporate data on smoking. Age-period-cohort models (44 studies) were the most commonly used methods, followed by other generalised linear models (35 studies). The majority of models were developed using observed rates for more than 10 years and used data that were considered to be good quality. A quarter of studies provided comparisons of fitted and observed rates. While validation by withholding the most recent observed data from the model and then comparing the projected and observed rates for the most recent period provides important information on the model's performance, only 12 studies reported doing this. CONCLUSION: This systematic review provides an up-to-date summary of the statistical methods used in published lung cancer incidence or mortality projections. The assessment of the strengths of existing methods will help researchers to better apply and develop statistical methods for projecting lung cancer rates. Some of the common methods described in this review can be applied to the projection of rates for other cancer types or other non-infectious diseases.

Use of Recommended Preventive Health Care Services and Variations in HIV Care Among Women With HIV in the United States, 2013-2014: Opportunities for Expanded Partnerships in Support of Ending the HIV Epidemic.

BACKGROUND: Despite recommendations for preventive health services and routine HIV care for HIV-positive women, limited data are available regarding uptake of recommendations. METHODS: We used data from the 2013-2014 data cycles of the Medical Monitoring Project. We calculated weighted estimates and used multivariable logistic regression with adjusted prevalence ratios and 95% confidence intervals to examine associations between preventive health screenings, routine HIV care [based on viral load (VL) and CD4 measures as proxies], and sociodemographic factors. RESULTS: Of 2766 women, 47.7% were 50 years and older, 61.7% non-Hispanic black, 37.2% had >high school education, 63.3% had been living with HIV for ≥10 years, 68.4% were living ≤the federal poverty level, 67.3% had public health insurance, 93.8% were prescribed antiretroviral therapy, and 66.1% had sustained/durable suppression (12 months). For women aged 18 years and older, cervical cancer, breast cancer, and sexually transmitted infection screenings were documented for 44.3%, 27.6%, and 34.7%, respectively; 26% did not meet 6-month, and 37% did not meet 12-month, VL and CD4 test measure goals. In multivariable analyses, women with no VLs in the past 6 months were less likely to be durably suppressed, and women who did not have ≥3 CD4 or VL tests (past 12 months) were less likely to be living above the poverty level and more likely to have public insurance compared with private health insurance (P < 0.05). CONCLUSION: Receipt of recommended preventive care was suboptimal. Targeted interventions are warranted to help ensure access to comprehensive HIV care and prevention services for women.

Lung cancer mortality in Australia in the twenty-first century: How many lives can be saved with effective tobacco control?

OBJECTIVES: To estimate the number of past and future lung cancer deaths that have already been averted by tobacco control initiatives in Australia, and to estimate the number of additional deaths averted under various smoking scenarios. METHODS: We predicted lung cancer mortality rates and case numbers to 2100 using a previously validated generalized linear model based on age, birth cohort and population cigarette smoking exposure. We estimated the impact of various tobacco control scenarios: 'actual tobacco control' (incorporating the aggregate effect of past and current taxation, plain packaging, mass media campaigns and other initiatives) and scenarios where 10%, 5% and 0% smoking prevalence was achieved by 2025, all of which were compared to a counterfactual scenario with the highest historical smoking consumption level continuing into the future as if no tobacco control initiatives had been implemented. RESULTS: Without tobacco control, there would have been an estimated 392,116 lung cancer deaths over the period 1956-2015; of these 20% (78,925 deaths; 75,839 males, 3086 females) have been averted due to tobacco control. However, if past and current measures continue to have the expected effect, an estimated 1.9 million deaths (1,579,515 males, 320,856 females; 67% of future lung cancer deaths) will be averted in 2016-2100. If smoking prevalence is reduced to 10%, 5% or 0% by 2025, an additional 97,432, 208,714 or 360,557 deaths could be averted from 2016 to 2100, respectively. CONCLUSION: Tobacco control in Australia has had a dramatic impact on the number of people dying from lung cancer. Several hundred thousand more lung cancer deaths could be averted over the course of the century if close-to-zero smoking prevalence could be achieved in the next decade.

Lung cancer mortality in Australia: Projected outcomes to 2040.

OBJECTIVES: The aim was to develop and validate a statistical model which uses past trends for lung cancer mortality and historical and current data on tobacco consumption to project lung cancer mortality rates into the future for Australia. METHODS: We used generalized linear models (GLMs) with Poisson distribution including either age, birth cohort or period, and/or various measures of population tobacco exposure (considering cross-sectional smoking prevalence, cigarettes smoked and tar exposure per capita). Sex-specific models were fitted to data for 1956-2015 and age-standardized lung cancer mortality rates were projected forward to 2040. Possible lags of 20-30 years between tobacco exposure and lung cancer mortality were examined. The best model was selected using analysis of deviance. To validate the selected model, we temporarily re-fitted it to data for 1956-1990 and compared the projected rates to 2015 with the observed rates for 1991-2015. RESULTS: The best fitting model used information on age, birth cohort and tar exposure per capita; close concordance with the observed data was achieved in the validation. The forward projections for lung cancer mortality using this model indicate that male and female age-standardized rates will decline over the period 2011-2015 to 2036-2040 from 27.2 to 15.1 per 100,000, and 15.8 to 11.8 per 100,000, respectively. However, due to population growth and ageing the number of deaths will increase by 7.9% for males and 57.9% for females; from 41,040 (24,831 males, 16,209 females) in 2011-2015 to 52,403 (26,805 males, 25,598 females) in 2036-2040. CONCLUSION: In the context of the mature tobacco epidemic with past peaks in tobacco consumption for both males and females, lung cancer mortality rates are expected to continually decline over the next 25 years. However, the number of lung cancer deaths will continue to be substantial, and to increase, in Australia's ageing population.

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.

Patterns of care of nonsmall cell lung cancer patients in China and implications for survival.

PURPOSE: We reported the patterns of care for a cohort of Chinese patients with nonsmall cell lung cancer (NSCLC) and examined the characteristics of those patients who did not receive cancer-specific treatment. MATERIALS AND METHODS: This was a prospective cohort study. The study population was patients with first primary NSCLC diagnosed and admitted to Hebei Cancer Hospital in Hebei Province in China from January 2004 to December 2005. Logistic regression was used to examine factors associated with no cancer-specific treatment. Cox proportional hazard regression was used to examine the effects of cancer treatment on survival. RESULTS: Of 579 NSCLC patients included in the study, 73.4% were male, 84.3% died by the end of the study after 7 years follow-up, 40.1% were diagnosed at a late stage of disease, and 33.7% had unknown disease stage. Over half (50.8%) of the patients received palliative care, 23.8% for curative care, and 25.4% did not receive any cancer-specific treatment. The probability of not receiving cancer-specific treatment was significantly higher for those who diagnosed at older age (odds ratio [OR] =3.01, 95% confidence interval [95% CI]: 1.79-5.06), had unknown stage at diagnosis (OR = 2.77, 95% CI: 1.41-5.47), or had unclassified histological type (OR = 3.48, 95% CI: 1.94-6.21). After adjusted for other factors, patients received anti-cancer treatment had significantly lower risk of dying from NSCLC P < 0.0001) compared with patients who did not receive any cancer-specific treatment. CONCLUSIONS: Despite the benefits of anti-cancer treatments confirmed in this study, over a quarter patients did not receive any such treatment. Finding the reasons for the patients who did not receive cancer-specific treatment may improve the quality of patient care in this population.

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.

Contrasting temporal trends in lung cancer incidence by socioeconomic status among women in New South Wales, Australia, 1985-2009.

OBJECTIVE: We examined long-term trends in lung cancer incidence for women by socioeconomic groups in New South Wales (NSW), Australia. METHODS: Data on lung cancer incidence for women were extracted from the NSW Cancer Registry database. We divided the study cohort into five quintiles according to an area-based index of education and occupation (IEO) and calculated annual age-standardised incidence rates by IEO quintile for the period 1985-2009. The age-standardised incidence ratio (SIR) was estimated for IEO quintiles and 5-year period of diagnosis using the highest IEO quintile as the reference. RESULTS: Overall, lung cancer incidence for women aged 25-69 years increased gradually from 19.8 per 100,000 in 1985 to 25.7 per 100,000 in 2009. The trends by IEO quintile were somewhat comparable from 1985 through to 1995, but from then on rates remained relatively stable for women residing in the highest quintile while increasing for women residing in the remaining four quintiles. Consequently, the SIR for all four of the lower IEO quintiles increased significantly over the 25-year period. For example, the SIR in the lowest IEO quintile increased from 1.16 (95% CI, 0.99-1.37) during 1985-1989 to 1.70 (95% CI, 1.50-1.93) during 2005-2009. The corresponding estimates for women aged 70 years or older showed no clear pattern of socioeconomic gradient. CONCLUSION: The increasing gap in lung cancer incidence between women in the highest socioeconomic group and all others suggests that there is a continued need for the broad implementation of tobacco control interventions, so that smoking prevalence is reduced across all segments of the population and the subsequent benefits are shared more equitably across all demographic groups.