Search

Objectives: Observational studies have suggested that a higher 25-hydroxyvitamin D concentration may be associated with longer telomere length; however, this has not been investigated in randomised controlled trials. We conducted an ancillary study within a randomised, double-blind, placebo-controlled trial of monthly vitamin D (the D-Health Trial) for the prevention of all-cause mortality, conducted from 2014 to 2020, to assess the effect of vitamin D supplementation on telomere length (measured as the telomere to single copy gene (T/S) ratio). Design, Setting, Participants, and Intervention: Participants were Australians aged 60–84 years and we randomly selected 1,519 D-Health participants (vitamin D: n=744; placebo: n=775) for this analysis. We used quantitative polymerase chain reaction to measure the relative telomere length (T/S ratio) at 4 or 5 years after randomisation. We compared the mean T/S ratio between the vitamin D and placebo groups to assess the effect of vitamin D supplementation on relative telomere length, using a linear regression model with adjustment for age, sex, and state which were used to stratify the randomisation. Results: The mean T/S ratio was 0.70 for both groups (standard deviation 0.18 and 0.16 for the vitamin D and placebo groups respectively). The adjusted mean difference (vitamin D minus placebo) was −0.001 (95% CI −0.02 to 0.02). There was no effect modification by age, sex, body mass index, or predicted baseline 25-hydroxyvitamin D concentration. Conclusion: In conclusion, routinely supplementing older adults, who are largely vitamin D replete, with monthly doses of vitamin D is unlikely to influence telomere length. [ABSTRACT FROM AUTHOR]

Single tablet regimens (STRs) for HIV infection improve patient satisfaction, quality of life, medication adherence, and virological suppression compared to multitablet regimens (MTRs). This is the first study assessing STR uptake and durability in Australia. This retrospective audit of all patients receiving an STR (n=299) at a large Sydney HIV clinic (January 2012–December 2013) assessed patient demographics, treatment prior to STR, HIV RNA load and CD4 during MTR and STR dosing, and reasons for STR switch. 206 patients switched from previous antiretroviral treatment to an STR, of which 88% switched from an MTR. Reasons for switching included desire to simplify treatment (57%), reduced side effects or toxicity (18%), and cost-saving for the patient. There was no switching for virological failure. Compared to when on an MTR, patients switching to an STR had significantly lower HIV RNA counts (p<0.001) and significantly higher CD4 counts (p<0.001). The discontinuation rate from STR was very low and all patients who switched to an STR maintained virological suppression throughout the study duration, although the study is limited by the absence of a control group. [ABSTRACT FROM AUTHOR]

Observational studies suggest that people with a high serum 25-hydroxyvitamin D (25(OH)D) concentration may have reduced risk of chronic diseases such as osteoporosis, multiple sclerosis, type 1 diabetes, cardiovascular disease, and some cancers. The AusD Study (A Quantitative Assessment of Solar UV Exposure for Vitamin D Synthesis in Australian Adults) was conducted to clarify the relationships between ultraviolet (UV) radiation exposure, dietary intake of vitamin D, and serum 25(OH)D concentration among Australian adults residing in Townsville (19.3°S), Brisbane (27.5°S), Canberra (35.3°S), and Hobart (42.8°S). Participants aged 18–75 years were recruited from the Australian Electoral Roll between 2009 and 2010. Measurements were made of height, weight, waist:hip ratio, skin, hair, and eye color, blood pressure, and grip strength. Participants completed a questionnaire on sun exposure and vitamin D intake, together with 10 days of personal UV dosimetry and an associated sun-exposure and physical-activity diary that was temporally linked to a blood test for measurement of 25(OH)D concentration. Ambient solar UV radiation was also monitored at all study sites. We collected comprehensive, high-quality data from 1,002 participants (459 males, 543 females) assessed simultaneously across a range of latitudes and through all seasons. Here we describe the scientific and methodological issues considered in designing the AusD Study. [ABSTRACT FROM PUBLISHER]

Pesticide exposure may be a risk factor for non-Hodgkin's lymphoma, but it is not certain which types of pesticides are involved. A population-based case-control study was undertaken in 2000–2001 using detailed methods of assessing occupational pesticide exposure. Cases with incident non-Hodgkin's lymphoma in two Australian states (n = 694) and controls (n = 694) were chosen from Australian electoral rolls. Logistic regression was used to estimate the risks of non-Hodgkin's lymphoma associated with exposure to subgroups of pesticides after adjustment for age, sex, ethnic origin, and residence. Approximately 10% of cases and controls had incurred pesticide exposure. Substantial exposure to any pesticide was associated with a trebling of the risk of non-Hodgkin's lymphoma (odds ratio = 3.09, 95% confidence interval: 1.42, 6.70). Subjects with substantial exposure to organochlorines, organophosphates, and “other pesticides” (all other pesticides excluding herbicides) and herbicides other than phenoxy herbicides had similarly increased risks, although the increase was statistically significant only for “other pesticides.” None of the exposure metrics (probability, level, frequency, duration, or years of exposure) were associated with non-Hodgkin's lymphoma. Analyses of the major World Health Organization subtypes of non-Hodgkin's lymphoma suggested a stronger effect for follicular lymphoma. These increases in risk of non-Hodgkin's lymphoma with substantial occupational pesticide exposure are consistent with previous work. [ABSTRACT FROM AUTHOR]

In a population-based series of 2109 women with ductal carcinoma in situ (DCIS) diagnosed in 1995-2000 in New South Wales, Australia, incidence increased by an average of 5.5% a year, mostly between 1995 and 1996 and in women 50-69 years of age. This increase paralleled the increases in mammographic screening. BreastScreen NSW, an organised mammographic screening programme, detected 65% of all DCIS. High-grade lesions were 54% of all lesions and were more likely to be 2+?cm in diameter (OR=2.12, 95%CI 1.46-3.14) than low-grade lesions. In all, 40% of DCIS in women younger than 40 years was 2+?cm in diameter compared with 21% in women 40 years and older. Young age, high grade, mixed architecture and multifocality were significant and independent predictors of 2+?cm DCIS.British Journal of Cancer (2004) 90, 1382-1385. doi:10.1038/sj.bjc.6601677 www.bjcancer.com Published online 24 February 2004 [ABSTRACT FROM AUTHOR]

To measure the quality of pathology reporting of breast cancer and establish a baseline against which future changes can be measured, we audited item completeness in breast cancer reports in Australia in 1995 before the release of specific recommendations from the Australian Cancer Network. Tumour type and size were given in reports of invasive breast cancer for 93% of women, 70% had, in addition, grade and clearance of the margins while only 28% had all recommended information. The most complete items in reports were histological type of breast cancer (99.6% of cases), tumour size (94%, 95% confidence interval (CI) 92-95) and margins of excision (87%, 95% CI 85-89). Histological grade (84%, 95% CI 82-86 of cases) and presence or absence of ductal carcinoma in situ (DCIS) (79%, 95% CI 77-81) were less complete and vessel invasion (61%, 95% CI 58-63) and changes in non-neoplastic breast tissue adjacent to the breast cancer (68%, 95% CI 66-71) the least complete. Less than half the reports of DCIS reported on tumour size (49%, 95% CI 42-57), presence or absence of necrosis (41%, 95% CI 34-49) or nuclear grade (39%, 95% CI 31-46). Around 1500 reports were identified as issued by 147 laboratories and 392 pathologists; 69% of pathologists issued fewer than two reports a month in the audit. We concluded that infrequency of reporting may have contributed to incompleteness of reporting. In addition, we found significant variation across Australian states with some indication that reporting was consistently poor in one state. The audit highlighted areas for improvement for breast cancer reporting in Australia. Research evidence suggests that multifaceted strategies are needed to assist practitioners with implementing more uniform reporting standards. [ABSTRACT FROM AUTHOR]

Background: A strong association has been found between skin cancer and exposure to UV radiation. The p53 tumor suppressor gene (also known as TP53), which is frequently mutated in human cancers, is believed to be an early target in UV radiation-associated skin carcinogenesis. We have previously developed a sensitive, polymerase chain reaction-based method capable of detecting and quantifying a UV radiation-specific mutation in the p53 gene (codons 247 and 248: AAC CGG --> AAT TGG) in normal skin. We have used this method to examine whether UV radiation-specific mutation frequency is associated with risk of basal cell carcinoma (BCC) and with sun exposure.Methods: This case-control study in Australia involved 53 case subjects with BCC and 75 control subjects. DNA was isolated from normal skin (mirror-image anatomic site to the cancer site for case subjects and a randomly selected site for control subjects) and assayed for p53 mutation. Relationships between p53 mutation frequency and risk of BCC, sun sensitivity, or sun exposure were estimated by use of odds ratios (ORs) and 95% confidence intervals (95% CIs).Results: Case subjects were more likely to have a p53 mutation than control subjects (OR = 3.1; 95% CI = 1.3-7.1). In addition, the odds of BCC increased monotonically with increasing frequency of p53 mutation. No statistically significant associations could be demonstrated between p53 mutation frequency and age, sex, sensitivity to the sun, pigmentary characteristics, total lifetime sun exposure, or sun exposure to the biopsy site.Conclusions: Our results indicate that tandem CC --> TT mutations involving codons 247 and 248 of the p53 gene are associated with an increased risk of BCC but cannot be used as an accurate measure of total UV-radiation exposure. [ABSTRACT FROM AUTHOR]

Assessing the association between temperature frequency and mortality can provide insights into human adaptation to local ambient temperatures. We collected daily time-series data on mortality and temperature from 757 locations in 47 countries/regions during 1979-2020. We used a two-stage time series design to assess the association between temperature frequency and all-cause mortality. The results were pooled at the national, regional, and global levels. We observed a consistent decrease in the risk of mortality as the normalized frequency of temperature increases across the globe. The average increase in mortality risk comparing the 10th to 100th percentile of normalized frequency was 13.03% (95% CI: 12.17-13.91), with substantial regional differences (from 4.56% in Australia and New Zealand to 33.06% in South Europe). The highest increase in mortality was observed for high-income countries (13.58%, 95% CI: 12.56-14.61), followed by lower-middle-income countries (12.34%, 95% CI: 9.27-15.51). This study observed a declining risk of mortality associated with higher temperature frequency. Our findings suggest that populations can adapt to their local climate with frequent exposure, with the adapting ability varying geographically due to differences in climatic and socioeconomic characteristics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Abstract: In 2023, an increased number of urogenital and anorectal infections with Neisseria meningitis serogroup Y (MenY) were reported in New South Wales (NSW). Whole genome sequencing (WGS) found a common sequence type (ST-1466), with limited sequence diversity. Confirmed outbreak cases were NSW residents with a N. meningitidis isolate matching the cluster sequence type; probable cases were NSW residents with MenY isolated from a urogenital or anorectal site from 1 July 2023 without WGS testing. Of the 41 cases, most were men (n = 27), of whom six reported recent contact with a female sex worker. Five cases were men who have sex with men and two were female sex workers. Laboratory alerts regarding the outbreak were sent to all Australian jurisdictions through the laboratories in the National Neisseria Network. Two additional states identified urogenital MenY ST-1466 infections detected in late 2023. Genomic analysis showed all MenY ST-1466 sequences were interspersed, suggestive of an Australia-wide outbreak. The incidence of these infections remains unknown, due to varied testing and reporting practices both within and across jurisdictions. Isolates causing invasive meningococcal disease (IMD) in Australia are typed, and there has been no MenY ST-1466 IMD recorded in Australia to end of March 2024. Concerns remain regarding the risk of IMD, given the similarity of these sequences with a MenY ST-1466 IMD strain causing a concurrent outbreak in the United States of America., (© Commonwealth of Australia CC BY-NC-ND.)

Background: Exposure to cold spells is associated with mortality. However, little is known about the global mortality burden of cold spells., Methods: A three-stage meta-analytical method was used to estimate the global mortality burden associated with cold spells by means of a time series dataset of 1960 locations across 59 countries (or regions). First, we fitted the location-specific, cold spell-related mortality associations using a quasi-Poisson regression with a distributed lag non-linear model with a lag period of up to 21 days. Second, we built a multivariate meta-regression model between location-specific associations and seven predictors. Finally, we predicted the global grid-specific cold spell-related mortality associations during 2000-19 using the fitted meta-regression model and the yearly grid-specific meta-predictors. We calculated the annual excess deaths, excess death ratio (excess deaths per 1000 deaths), and excess death rate (excess deaths per 100 000 population) due to cold spells for each grid across the world., Findings: Globally, 205 932 (95% empirical CI [eCI] 162 692-250 337) excess deaths, representing 3·81 (95% eCI 2·93-4·71) excess deaths per 1000 deaths (excess death ratio), and 3·03 (2·33-3·75) excess deaths per 100 000 population (excess death rate) were associated with cold spells per year between 2000 and 2019. The annual average global excess death ratio in 2016-19 increased by 0·12 percentage points and the excess death rate in 2016-19 increased by 0·18 percentage points, compared with those in 2000-03. The mortality burden varied geographically. The excess death ratio and rate were highest in Europe, whereas these indicators were lowest in Africa. Temperate climates had higher excess death ratio and rate associated with cold spells than other climate zones., Interpretation: Cold spells are associated with substantial mortality burden around the world with geographically varying patterns. Although the number of cold spells has on average been decreasing since year 2000, the public health threat of cold spells remains substantial. The findings indicate an urgency of taking local and regional measures to protect the public from the mortality burdens of cold spells., Funding: Australian Research Council, Australian National Health and Medical Research Council, EU's Horizon 2020 Project Exhaustion., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate lag-response associations and effect modifications of exposure to floods with risks of all cause, cardiovascular, and respiratory mortality on a global scale., Design: Time series study., Setting: 761 communities in 35 countries or territories with at least one flood event during the study period., Participants: Multi-Country Multi-City Collaborative Research Network database, Australian Cause of Death Unit Record File, New Zealand Integrated Data Infrastructure, and the International Network for the Demographic Evaluation of Populations and their Health Network database., Main Outcome Measures: The main outcome was daily counts of deaths. An estimation for the lag-response association between flood and daily mortality risk was modelled, and the relative risks over the lag period were cumulated to calculate overall effects. Attributable fractions of mortality due to floods were further calculated. A quasi-Poisson model with a distributed lag non-linear function was used to examine how daily death risk was associated with flooded days in each community, and then the community specific associations were pooled using random effects multivariate meta-analyses. Flooded days were defined as days from the start date to the end date of flood events., Results: A total of 47.6 million all cause deaths, 11.1 million cardiovascular deaths, and 4.9 million respiratory deaths were analysed. Over the 761 communities, mortality risks increased and persisted for up to 60 days (50 days for cardiovascular mortality) after a flooded day. The cumulative relative risks for all cause, cardiovascular, and respiratory mortality were 1.021 (95% confidence interval 1.006 to 1.036), 1.026 (1.005 to 1.047), and 1.049 (1.008 to 1.092), respectively. The associations varied across countries or territories and regions. The flood-mortality associations appeared to be modified by climate type and were stronger in low income countries and in populations with a low human development index or high proportion of older people. In communities impacted by flood, up to 0.10% of all cause deaths, 0.18% of cardiovascular deaths, and 0.41% of respiratory deaths were attributed to floods., Conclusions: This study found that the risks of all cause, cardiovascular, and respiratory mortality increased for up to 60 days after exposure to flood and the associations could vary by local climate type, socioeconomic status, and older age., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the Australian Research Council, Australian National Health and Medical Research Council, and European Union’s Horizon 2020 Project Exhaustion; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The global spatiotemporal pattern of mortality risk and burden attributable to tropical cyclones is unclear. We aimed to evaluate the global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019., Methods: The wind speed associated with cyclones from 1980 to 2019 was estimated globally through a parametric wind field model at a grid resolution of 0·5° × 0·5°. A total of 341 locations with daily mortality and temperature data from 14 countries that experienced at least one tropical cyclone day (a day with maximum sustained wind speed associated with cyclones ≥17·5 m/s) during the study period were included. A conditional quasi-Poisson regression with distributed lag non-linear model was applied to assess the tropical cyclone-mortality association. A meta-regression model was fitted to evaluate potential contributing factors and estimate grid cell-specific tropical cyclone effects., Findings: Tropical cyclone exposure was associated with an overall 6% (95% CI 4-8) increase in mortality in the first 2 weeks following exposure. Globally, an estimate of 97 430 excess deaths (95% empirical CI [eCI] 71 651-126 438) per decade were observed over the 2 weeks following exposure to tropical cyclones, accounting for 20·7 (95% eCI 15·2-26·9) excess deaths per 100 000 residents (excess death rate) and 3·3 (95% eCI 2·4-4·3) excess deaths per 1000 deaths (excess death ratio) over 1980-2019. The mortality burden exhibited substantial temporal and spatial variation. East Asia and south Asia had the highest number of excess deaths during 1980-2019: 28 744 (95% eCI 16 863-42 188) and 27 267 (21 157-34 058) excess deaths per decade, respectively. In contrast, the regions with the highest excess death ratios and rates were southeast Asia and Latin America and the Caribbean. From 1980-99 to 2000-19, marked increases in tropical cyclone-related excess death numbers were observed globally, especially for Latin America and the Caribbean and south Asia. Grid cell-level and country-level results revealed further heterogeneous spatiotemporal patterns such as the high and increasing tropical cyclone-related mortality burden in Caribbean countries or regions., Interpretation: Globally, short-term exposure to tropical cyclones was associated with a significant mortality burden, with highly heterogeneous spatiotemporal patterns. In-depth exploration of tropical cyclone epidemiology for those countries and regions estimated to have the highest and increasing tropical cyclone-related mortality burdens is urgently needed to help inform the development of targeted actions against the increasing adverse health impacts of tropical cyclones under a changing climate., Funding: Australian Research Council and Australian National Health and Medical Research Council., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Per- and polyfluoroalkyl substances (PFAS) have been associated with higher cholesterol and liver function markers in some studies, but the evidence for specific cardiometabolic conditions has been inconclusive., Objectives: We quantified the associations of single and combined PFAS with cardiometabolic markers and conditions in a cross-sectional study of three Australian communities with PFAS-contaminated water from the historical use of aqueous film-forming foam in firefighting activities, and three comparison communities., Methods: Participants gave blood samples for measurement of nine PFAS, four lipids, six liver function markers, and completed a survey on sociodemographic characteristics and eight cardiometabolic conditions. We estimated differences in mean biomarker concentrations per doubling in single PFAS concentrations (linear regression) and per interquartile range increase in the PFAS mixture (Bayesian kernel machine regression). We estimated prevalence ratios of biomarker concentrations outside reference limits and self-reported cardiometabolic conditions (Poisson regression)., Results: We recruited 881 adults in exposed communities and 801 in comparison communities. We observed higher mean total cholesterol with higher single and mixture PFAS concentrations in blood serum (e.g., 0.18 mmol/L, 95% credible interval -0.06 to 0.42, higher total cholesterol concentrations with an interquartile range increase in all PFAS concentrations in Williamtown, New South Wales), with varying certainty across communities and PFAS. There was less consistency in direction of associations for liver function markers. Serum perfluorooctanoic acid (PFOA) concentrations were positively associated with the prevalence of self-reported hypercholesterolemia in one of three communities, but PFAS concentrations were not associated with self-reported type II diabetes, liver disease, or cardiovascular disease., Discussion: Our study is one of few that has simultaneously quantified the associations of blood PFAS concentrations with multiple biomarkers and cardiometabolic conditions in multiple communities. Our findings for total cholesterol were consistent with previous studies; however, substantial uncertainty in our estimates and the cross-sectional design limit causal inference., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Professor Martyn Kirk worked part-time for the Australian Government Department of Health between 2020 and 2022 on the Australian national COVID-19 response., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Voltage-gated sodium (Na V ) channels are critical regulators of neuronal excitability and are targeted by many toxins that directly interact with the pore-forming α subunit, typically via extracellular loops of the voltage-sensing domains, or residues forming part of the pore domain. Excelsatoxin A (ExTxA), a pain-causing knottin peptide from the Australian stinging tree Dendrocnide excelsa, is the first reported plant-derived Na V channel modulating peptide toxin. Here we show that TMEM233, a member of the dispanin family of transmembrane proteins expressed in sensory neurons, is essential for pharmacological activity of ExTxA at Na V channels, and that co-expression of TMEM233 modulates the gating properties of Na V 1.7. These findings identify TMEM233 as a previously unknown Na V 1.7-interacting protein, position TMEM233 and the dispanins as accessory proteins that are indispensable for toxin-mediated effects on Na V channel gating, and provide important insights into the function of Na V channels in sensory neurons., (© 2023. The Author(s).)

Background: Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants that are potentially harmful to health. We examined if rates of selected cancers and causes of deaths were elevated in three Australian communities with local environmental contamination caused by firefighting foams containing PFAS. The affected Australian communities were Katherine in Northern Territory, Oakey in Queensland and Williamtown in New South Wales., Methods: All residents identified in the Medicare Enrolment File (1983-2019)-a consumer directory for Australia's universal healthcare-who ever lived in an exposure area (Katherine, Oakey and Williamtown), and a sample of those who ever lived in selected comparison areas, were linked to the Australian Cancer Database (1982-2017) and National Death Index (1980-2019). We estimated standardised incidence ratios (SIRs) for 23 cancer outcomes, four causes of death and three control outcomes, adjusting for sex, age and calendar time of diagnosis., Findings: We observed higher rates of prostate cancer (SIR=1·76, 95 % confidence interval (CI) 1·36-2·24) in Katherine; laryngeal cancer (SIR=2·71, 95 % CI 1·30-4·98), kidney cancer (SIR=1·82, 95 % CI 1·04-2·96) and coronary heart disease (CHD) mortality (SIR=1·81, 95 % CI 1·46-2·33) in Oakey; and lung cancer (SIR=1·83, 95 % CI 1·39-2·38) and CHD mortality (SIR=1·22, 95 % CI 1·01-1·47) in Williamtown. We also saw elevated SIRs for control outcomes. SIRs for all other outcomes and overall cancer were similar across exposure and comparison areas., Interpretation: There was limited evidence to support an association between living in a PFAS exposure area and risks of cancers or cause-specific deaths., Competing Interests: Declaration of interests MDK worked part-time for the Australian Government Department of Health between 2020 and 2022 on national COVID-19 response. The other authors declare that they have no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To understand the geographic distribution of and area-level factors associated with malignant mesothelioma incidence and survival in Australia., Materials and Methods: Generalised linear models and Bayesian spatial models were fitted using population registry data. Area-level covariates were socioeconomic quintile, remoteness category and state or territory. The maximised excess events test was used to test for spatial heterogeneity., Results: There was strong evidence of spatial differences in standardised incidence rates for malignant mesothelioma but survival was uniformly poor. Incidence rates varied by state or territory and were lower in remote areas. Patterns in the geographic distribution of modelled incidence counts for malignant mesothelioma differed substantially from patterns of standardised incidence rates., Conclusions: Geographic variation in the modelled incidence counts of malignant mesothelioma demonstrates varying demand for diagnostic and management services. The long latency period for this cancer coupled with migration complicates any associations with patterns of exposure, however some of the geographic distribution of diagnoses can be explained by the location of historical mines and asbestos-related industries., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Increased mortality risk is associated with short-term temperature variability. However, to our knowledge, there has been no comprehensive assessment of the temperature variability-related mortality burden worldwide. In this study, using data from the MCC Collaborative Research Network, we first explored the association between temperature variability and mortality across 43 countries or regions. Then, to provide a more comprehensive picture of the global burden of mortality associated with temperature variability, global gridded temperature data with a resolution of 0·5° × 0·5° were used to assess the temperature variability-related mortality burden at the global, regional, and national levels. Furthermore, temporal trends in temperature variability-related mortality burden were also explored from 2000-19., Methods: In this modelling study, we applied a three-stage meta-analytical approach to assess the global temperature variability-related mortality burden at a spatial resolution of 0·5° × 0·5° from 2000-19. Temperature variability was calculated as the SD of the average of the same and previous days' minimum and maximum temperatures. We first obtained location-specific temperature variability related-mortality associations based on a daily time series of 750 locations from the Multi-country Multi-city Collaborative Research Network. We subsequently constructed a multivariable meta-regression model with five predictors to estimate grid-specific temperature variability related-mortality associations across the globe. Finally, percentage excess in mortality and excess mortality rate were calculated to quantify the temperature variability-related mortality burden and to further explore its temporal trend over two decades., Findings: An increasing trend in temperature variability was identified at the global level from 2000 to 2019. Globally, 1 753 392 deaths (95% CI 1 159 901-2 357 718) were associated with temperature variability per year, accounting for 3·4% (2·2-4·6) of all deaths. Most of Asia, Australia, and New Zealand were observed to have a higher percentage excess in mortality than the global mean. Globally, the percentage excess in mortality increased by about 4·6% (3·7-5·3) per decade. The largest increase occurred in Australia and New Zealand (7·3%, 95% CI 4·3-10·4), followed by Europe (4·4%, 2·2-5·6) and Africa (3·3, 1·9-4·6)., Interpretation: Globally, a substantial mortality burden was associated with temperature variability, showing geographical heterogeneity and a slightly increasing temporal trend. Our findings could assist in raising public awareness and improving the understanding of the health impacts of temperature variability., Funding: Australian Research Council, Australian National Health & Medical Research Council., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Many regions of the world are now facing more frequent and unprecedentedly large wildfires. However, the association between wildfire-related PM 2·5 and mortality has not been well characterised. We aimed to comprehensively assess the association between short-term exposure to wildfire-related PM 2·5 and mortality across various regions of the world., Methods: For this time series study, data on daily counts of deaths for all causes, cardiovascular causes, and respiratory causes were collected from 749 cities in 43 countries and regions during 2000-16. Daily concentrations of wildfire-related PM 2·5 were estimated using the three-dimensional chemical transport model GEOS-Chem at a 0·25° × 0·25° resolution. The association between wildfire-related PM 2·5 exposure and mortality was examined using a quasi-Poisson time series model in each city considering both the current-day and lag effects, and the effect estimates were then pooled using a random-effects meta-analysis. Based on these pooled effect estimates, the population attributable fraction and relative risk (RR) of annual mortality due to acute wildfire-related PM 2·5 exposure was calculated., Findings: 65·6 million all-cause deaths, 15·1 million cardiovascular deaths, and 6·8 million respiratory deaths were included in our analyses. The pooled RRs of mortality associated with each 10 μg/m 3 increase in the 3-day moving average (lag 0-2 days) of wildfire-related PM 2·5 exposure were 1·019 (95% CI 1·016-1·022) for all-cause mortality, 1·017 (1·012-1·021) for cardiovascular mortality, and 1·019 (1·013-1·025) for respiratory mortality. Overall, 0·62% (95% CI 0·48-0·75) of all-cause deaths, 0·55% (0·43-0·67) of cardiovascular deaths, and 0·64% (0·50-0·78) of respiratory deaths were annually attributable to the acute impacts of wildfire-related PM 2·5 exposure during the study period., Interpretation: Short-term exposure to wildfire-related PM 2·5 was associated with increased risk of mortality. Urgent action is needed to reduce health risks from the increasing wildfires., Funding: Australian Research Council, Australian National Health & Medical Research Council., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Exposure to cold or hot temperatures is associated with premature deaths. We aimed to evaluate the global, regional, and national mortality burden associated with non-optimal ambient temperatures., Methods: In this modelling study, we collected time-series data on mortality and ambient temperatures from 750 locations in 43 countries and five meta-predictors at a grid size of 0·5° × 0·5° across the globe. A three-stage analysis strategy was used. First, the temperature-mortality association was fitted for each location by use of a time-series regression. Second, a multivariate meta-regression model was built between location-specific estimates and meta-predictors. Finally, the grid-specific temperature-mortality association between 2000 and 2019 was predicted by use of the fitted meta-regression and the grid-specific meta-predictors. Excess deaths due to non-optimal temperatures, the ratio between annual excess deaths and all deaths of a year (the excess death ratio), and the death rate per 100 000 residents were then calculated for each grid across the world. Grids were divided according to regional groupings of the UN Statistics Division., Findings: Globally, 5 083 173 deaths (95% empirical CI [eCI] 4 087 967-5 965 520) were associated with non-optimal temperatures per year, accounting for 9·43% (95% eCI 7·58-11·07) of all deaths (8·52% [6·19-10·47] were cold-related and 0·91% [0·56-1·36] were heat-related). There were 74 temperature-related excess deaths per 100 000 residents (95% eCI 60-87). The mortality burden varied geographically. Of all excess deaths, 2 617 322 (51·49%) occurred in Asia. Eastern Europe had the highest heat-related excess death rate and Sub-Saharan Africa had the highest cold-related excess death rate. From 2000-03 to 2016-19, the global cold-related excess death ratio changed by -0·51 percentage points (95% eCI -0·61 to -0·42) and the global heat-related excess death ratio increased by 0·21 percentage points (0·13-0·31), leading to a net reduction in the overall ratio. The largest decline in overall excess death ratio occurred in South-eastern Asia, whereas excess death ratio fluctuated in Southern Asia and Europe., Interpretation: Non-optimal temperatures are associated with a substantial mortality burden, which varies spatiotemporally. Our findings will benefit international, national, and local communities in developing preparedness and prevention strategies to reduce weather-related impacts immediately and under climate change scenarios., Funding: Australian Research Council and the Australian National Health and Medical Research Council., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Melanoma aetiology has been proposed to have two pathways, which are determined by naevi and type of sun exposure and related to the anatomical site where melanoma develops., Objectives: We examined associations with melanoma by anatomical site for a comprehensive set of risk factors including pigmentary and naevus phenotypes, ultraviolet radiation exposure and polygenic risk., Methods: We analysed harmonized data from 2617 people with incident first invasive melanoma and 975 healthy controls recruited through two population-based case-control studies in Australia and the UK. Questionnaire data were collected by interview using a single protocol, and pathway-specific polygenic risk scores were derived from DNA samples. We estimated adjusted odds ratios using unconditional logistic regression that compared melanoma cases at each anatomical site with all controls., Results: When cases were compared with control participants, there were stronger associations for many naevi vs. no naevi for melanomas on the trunk, and upper and lower limbs than on the head and neck (P-heterogeneity < 0·001). Very fair skin (vs. olive/brown skin) was more weakly related to melanoma on the trunk than to melanomas at other sites (P-heterogeneity = 0·04). There was no significant difference by anatomical site for polygenic risk. Increased weekday sun exposure was positively associated with melanoma on the head and neck but not on other sites., Conclusions: We found evidence of aetiological heterogeneity for melanoma, supporting the dual pathway hypothesis. These findings enhance understanding of risk factors for melanoma and can guide prevention and skin examination education and practices., (© 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: The Australian National Bowel Cancer Screening Program is a free population-based screening program aiming to identify precancerous lesions and early colorectal cancer using faecal occult blood tests in average-risk Australians. The participation rate in people invited to screening was 42 % in 2017-2018, well below the 56.6 % target level. Increasing screening in high-risk groups; such as those with a subsequent diagnosis of colorectal cancer, will improve the efficiency of the program., Methods: Patients were participants in the Australian 45 and Up (cohort) study; aged 55 or 65 years between May 2006 and June 2008. Patients reported a history of colorectal cancer in their enrolment questionnaire and whether or not they had screened before diagnosis. Demographic, lifestyle, dietary and health related characteristics were compared between those who did and did not participate in screening., Results: 339 participants who self-reported having colorectal cancer were included. Participants who were female, overweight (≥ 25 kg/m 2 ), consumed less than the recommended five servings of vegetables per day, consumed ≤ 14 standard drinks per week (compared to non-drinkers) or did not meet physical activity guidelines were significantly less likely to have participated in screening., Conclusion: Considerable investment has been placed in the National Bowel Cancer Screening Program and the focus now is on improving participation. Our study has taken a unique approach to identifying high-risk groups by exploring factors related to screening participation in colorectal cancer patients. These findings can further leverage the program by targeting high-risk populations to reduce the colorectal cancer burden in Australia., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Melanoma risk prediction models could be useful for matching preventive interventions to patients' risk., Objectives: To develop and validate a model for incident first-primary cutaneous melanoma using clinically assessed risk factors., Methods: We used unconditional logistic regression with backward selection from the Australian Melanoma Family Study (461 cases and 329 controls) in which age, sex and city of recruitment were kept in each step, and we externally validated it using the Leeds Melanoma Case-Control Study (960 cases and 513 controls). Candidate predictors included clinically assessed whole-body naevi and solar lentigines, and self-assessed pigmentation phenotype, sun exposure, family history and history of keratinocyte cancer. We evaluated the predictive strength and discrimination of the model risk factors using odds per age- and sex-adjusted SD (OPERA) and the area under curve (AUC), and calibration using the Hosmer-Lemeshow test., Results: The final model included the number of naevi ≥ 2 mm in diameter on the whole body, solar lentigines on the upper back (a six-level scale), hair colour at age 18 years and personal history of keratinocyte cancer. Naevi was the strongest risk factor; the OPERA was 3·51 [95% confidence interval (CI) 2·71-4·54] in the Australian study and 2·56 (95% CI 2·23-2·95) in the Leeds study. The AUC was 0·79 (95% CI 0·76-0·83) in the Australian study and 0·73 (95% CI 0·70-0·75) in the Leeds study. The Hosmer-Lemeshow test P-value was 0·30 in the Australian study and < 0·001 in the Leeds study., Conclusions: This model had good discrimination and could be used by clinicians to stratify patients by melanoma risk for the targeting of preventive interventions. What's already known about this topic? Melanoma risk prediction models may be useful in prevention by tailoring interventions to personalized risk levels. For reasons of feasibility, time and cost many melanoma prediction models use self-assessed risk factors. However, individuals tend to underestimate their naevus numbers. What does this study add? We present a melanoma risk prediction model, which includes clinically-assessed whole-body naevi and solar lentigines, and self-assessed risk factors including pigmentation phenotype and history of keratinocyte cancer. This model performs well on discrimination, the model's ability to distinguish between individuals with and without melanoma, and may assist clinicians to stratify patients by melanoma risk for targeted preventive interventions., (© 2019 British Association of Dermatologists.)

Background: Guidelines for follow-up of patients with melanoma are based on limited evidence., Objectives: To guide skin surveillance, we developed a risk prediction model for subsequent primary melanomas, using demographic, phenotypical, histopathological, sun exposure and genomic risk factors., Methods: Using Cox regression frailty models, we analysed data for 2613 primary melanomas from 1266 patients recruited to the population-based Genes, Environment and Melanoma study in New South Wales, Australia, with a median of 14 years' follow-up via the cancer registry. Discrimination and calibration were assessed., Results: The median time to diagnosis of a subsequent primary melanoma decreased with each new primary melanoma. The final model included 12 risk factors. Harrell's C-statistic was 0·73 [95% confidence interval (CI) 0·68-0·77], 0·65 (95% CI 0·62-0·68) and 0·65 (95% CI 0·61-0·69) for predicting second, third and fourth primary melanomas, respectively. The risk of a subsequent primary melanoma was 4·75 times higher (95% CI 3·87-5·82) for the highest vs. the lowest quintile of the risk score. The mean absolute risk of a subsequent primary melanoma within 5 years was 8·0 ± SD 4.1% after the first primary melanoma, and 46·8 ± 15·0% after the second, but varied substantially by risk score., Conclusions: The risk of developing a subsequent primary melanoma varies considerably between individuals and is particularly high for those with two or more primary melanomas. The risk prediction model and its associated nomograms enable estimation of the absolute risk of subsequent primary melanoma, on the basis of on an individual's risk factors, and can be used to tailor surveillance intensity, communicate risk and provide patient education. What's already known about this topic? Current guidelines for the frequency and length of follow-up to detect new primary melanomas in patients with one or more previous primary melanomas are based on limited evidence. People with one or more primary melanomas have, on average, a higher risk of developing another primary invasive melanoma, compared with the general population, but an accurate way of estimating individual risk is needed. What does this study add? We provide a comprehensive risk prediction model for subsequent primary melanomas, using data from 1266 participants with melanoma (2613 primary melanomas), over a median 14 years' follow-up. The model includes 12 risk factors comprising demographic, phenotypical, histopathological and genomic factors, and sun exposure. It enables estimation of the absolute risk of subsequent primary melanomas, and can be used to tailor surveillance intensity, communicate individual risk and provide patient education., (© 2019 British Association of Dermatologists.)

Objectives and importance of the study: To determine whether use of selected therapies for prostate, breast and colorectal cancer in farm residents differs from that in rural nonfarm and urban counterparts. Little is known about cancer therapies used by farm residents., Study Type: Data linkage cohort study., Methods: Baseline survey information from the Sax Institute's 45 and Up Study cohort was linked with data from the New South Wales Admitted Patient Data Collection for 2006-2012. Adjusted odds of receiving surgery, chemotherapy, radiotherapy and/or brachytherapy for each cancer were compared between groups, controlling for selected variables., Results: Differences in the likelihood of surgery for breast and colorectal cancer between groups were not significant. However, for prostate cancer, farm men had 35% greater odds of prostatectomy than rural nonfarm men (odds ratio [OR] 1.35; 95% CI 1.05, 1.72). Urban men were most likely to have had brachytherapy, with three times greater odds of treatment than farm men (OR 2.90; 95% CI 1.51, 5.56). Urban women were most likely to have had chemotherapy for breast cancer, having twice the odds of receiving this treatment as farm women (OR 2.24; 95% CI 1.25, 4.04). The odds of chemotherapy for colorectal cancer among rural nonfarm residents were two-thirds the odds among urban men (OR 0.62; 95% CI 0.44, 0.90) and urban women (OR 0.57; 95% CI 0.37, 0.88). Age, distance, income and health insurance factors contributed to differences in nonsurgical care between groups., Conclusions: Cancer-related surgical services for breast and colorectal cancer were comparable between groups. Farm and rural nonfarm residents may have been disadvantaged in relation to nonsurgical therapies for prostate, breast and colorectal cancer compared with urban counterparts., Competing Interests: None declared.

Background: People at high risk of developing melanoma are usually identified by pigmentary and naevus phenotypes., Objective: We examined whether associations of these phenotypes with melanoma risk differed by ambient sun exposure or participant characteristics in two population-based, case-control studies with comparable ancestry but different ambient sun exposure., Methods: Data were analysed from 616 cases and 496 controls from the Australian Melanoma Family Study and 2012 cases and 504 controls from the Leeds (UK) case-control study. Questionnaire, interview and dermatological skin examination data were collected using the same measurement protocols. Relative risks were estimated as odds ratios using unconditional logistic regression, adjusted for potential confounders., Results: Hair and skin colour were the strongest pigmentary phenotype risk factors. All associations of pigmentary phenotype with melanoma risk were similar across countries. The median number of clinically assessed naevi was approximately three times higher in Australia than Leeds, but the relative risks for melanoma associated with each additional common or dysplastic naevus were higher for Leeds than Australia, especially for naevi on the upper and lower limbs. Higher naevus counts on the head and neck were associated with a stronger relative risk for melanoma for women than men. The two countries had similar relative risks for melanoma based on self-reported naevus density categories, but personal perceptions of naevus number differed by country. There was no consistent evidence of interactions between phenotypes on risk., Conclusions: Classifying people at high risk of melanoma based on their number of naevi should ideally take into account their country of residence, type of counts (clinical or self-reported), body site on which the naevus counts are measured and sex. The presence of naevi may be a stronger indicator of a genetic predisposition in the UK than in Australia based on less opportunity for sun exposure to influence naevus development., (© 2019 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Attention-deficit/hyperactivity disorder (ADHD) is common and may require treatment in adulthood. We aimed to investigate the treatment patterns and perinatal outcomes of women with any history of stimulant treatment for ADHD., Methods: We used health records of the New South Wales (NSW, Australia) population to compare perinatal outcomes of women treated with stimulants (dexamphetamine or methylphenidate) for ADHD from 1982 to 2012 who gave birth between 1994 and 2012, with perinatal outcomes of women with no known ADHD or stimulant treatment (comparison cohort). Five comparison women, matched by maternal age and infant year of birth, were selected for each treated woman. Pregnancy outcome odds ratios in the two groups were adjusted for confounders including maternal age and smoking., Results: Of 5056 women treated for ADHD with stimulant medication, 3351 (66.3%) had stimulant treatment documented before the index pregnancy but not within 1 year before the expected date of delivery, 175 (3.5%) had stimulant treatment before and possibly during pregnancy (stimulant prescription within the 12 months directly before the expected date of the index birth and earlier), and 1530 (30.2%) had no stimulant treatment until after the index pregnancy. Treatment for ADHD at any time (before, before and during and only after the index pregnancy) was associated with reduced likelihood of spontaneous labour-odds ratios (ORs) 0.7 [0.7, 0.8], 0.7 [0.5, 0.9], and 0.7 [0.7, 0.8], respectively-and increased risk of caesarean delivery (1.2 [1.1, 1.3], 1.3 [0.9, 1.8], 1.3 [1.1, 1.4]); active neonatal resuscitation (1.2 [1.0, 1.3], 1.7 [1.1, 2.7], 1.3 [1.0, 1.7]); and neonatal admission > 4 h (1.2 [1.1, 1.3], 1.7 [1.2, 2.4], 1.2 [1.0, 1.4]). Treatment before or before and during pregnancy was, in addition, associated with increased risk of pre-eclampsia (1.2 [1.0, 1.4], 1.5 [0.8, 2.6]); preterm birth < 37 weeks (1.2 [1.0, 1.3], 1.4 [0.9, 2.3]); and 1-min Apgar < 7 (1.2 [1.1, 1.3], 2.0 [1.4, 2.9]). Stimulant prescribing was low during pregnancy (3.5% of women received such a prescription) and dropped during the 12 months before the due date from an average of 24.7 prescriptions per month in the first 6 months to 4.5 per month in the final 6 months., Conclusions: Compared with no treatment, ADHD stimulant treatment at any time was associated with small increases in the risk of some adverse pregnancy outcomes; treatment before, or before and during pregnancy, was associated with additional adverse outcomes, even after a treatment-free period of several years. None of these associations can be confidently attributed to stimulant treatment; in all cases ADHD per se or correlates of it could be responsible for the association.

Background: Australia is known to have had one of the highest per-capita asbestos consumption rates, yet there are few contemporary reports on malignant mesothelioma trends., Methods: Data on 10 930 people with malignant pleural mesothelioma (MPM) and 640 people with malignant peritoneal mesothelioma diagnosed in Australia during 1982-2009 were analysed. Observed incidence rate trends were quantified. Incidence rates were projected up to 2030 using observed incident cases during 1982-2012. The relative per-decade change in excess mortality during 1999-2009 was estimated., Results: During 1982-2009, acceleration in MPM age-standardised incidence rates were highest for women and those aged 75 years and above, with average annual percentage changes of +4.9 (95% CI 3.6 to 6.2) and +7.2 (95% CI 5.4 to 9.0), respectively. Age-standardised incidence rates for men with MPM aged 0-64 years decelerated rapidly during 2003-2009, an average annual percentage change of -5.1% (95% CI -7.6% to -2.5%). Overall, male age-specific MPM incidence rates in the age group of 65-74 year during 2010-2030 are projected to decline with rates projected to increase for older men and women with MPM. There was a statistically significant 16% relative reduction in the excess mortality rate (EMR) up to 5 years postdiagnosis for people diagnosed with malignant pleural and peritoneal mesothelioma combined in 2009 compared with those diagnosed in 1999, an EMR ratio of 0.84 (95% CI 0.77 to 0.92)., Conclusions: Australia's malignant mesothelioma incidence rates appear to have reached maximum levels but with differences over time by age, gender and tumour location. Improvements over time in survival provide a glimpse of hope for this almost invariably fatal disease., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Access to specialist services may influence stage at cancer diagnosis and whether cancer is ever adequately staged. We investigated associations of distance to the nearest accessible specialist hospital (NASH) with likelihood of advanced or unknown stage cancer at diagnosis in Australian non-small cell lung cancer (NSCLC) patients., Methods: Cancer registry records for 22,260 consecutively diagnosed NSCLC patients, 11,147 with linked records of hospital admissions, were analysed. Distances from patients' homes to the NASH were measured using geographical coordinates. Multinomial logistic regression analysis examined associations of distance from the NASH, type of hospital of treatment and other characteristics of NSCLC patients with advanced and unknown cancer stage., Results: Odds of advanced stage and unknown stage NSCLC were higher in people who lived 40-99 km, OR 1.18 (95%CI 1.07-1.31) advanced stage and 1.18 (1.04-1.33) unknown stage, and 100 km+ from the NASH, OR 1.17 (1.08-1.27) advanced stage and OR 1.38 (1.25-1.52) unknown stage (reference group patients living 0-39 km from the NASH). For hospitalised patients likelihoods of advanced stage and unknown stage NSCLC were also significantly higher in patients treated in general hospitals than in those treated in specialist hospitals. When both distance and hospital type were considered, patients who lived 100 km+ from the NASH had low odds of unknown stage cancer if admitted to a specialist hospital, OR 0.63 (95%CI 0.47-0.85), but a high odds of unknown stage if admitted to a general hospital, OR 2.13 (1.78-2.54). These associations were independent of age, sex, socioeconomic status, comorbidity, period and method of diagnosis, and histopathological subtype., Conclusions: People living remotely from accessible specialist services are at greatest risk of advanced stage or unknown stage disease if diagnosed with NSCLC. This risk is greater again if the patient is treated in a general hospital. Barriers to referral for specialist care require investigation., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Voltage-gated sodium (NaV) channels are responsible for propagating action potentials in excitable cells. NaV1.7 plays a crucial role in the human pain signalling pathway and it is an important therapeutic target for treatment of chronic pain. Numerous spider venom peptides have been shown to modulate the activity of NaV channels and these peptides represent a rich source of research tools and therapeutic lead molecules. The aim of this study was to determine the diversity of NaV1.7-active peptides in the venom of an Australian Phlogius sp. tarantula and to characterise their potency and subtype selectivity. We isolated three novel peptides, μ-TRTX-Phlo1a, -Phlo1b and -Phlo2a, that inhibit human NaV1.7 (hNaV1.7). Phlo1a and Phlo1b are 35-residue peptides that differ by one amino acid and belong in NaSpTx family 2. The partial sequence of Phlo2a revealed extensive similarity with ProTx-II from NaSpTx family 3. Phlo1a and Phlo1b inhibit hNaV1.7 with IC50 values of 459 and 360 nM, respectively, with only minor inhibitory activity on rat NaV1.2 and hNaV1.5. Although similarly potent at hNaV1.7 (IC50 333 nM), Phlo2a was less selective, as it also potently inhibited rNaV1.2 and hNaV1.5. All three peptides cause a depolarising shift in the voltage-dependence of hNaV1.7 activation.

Background: Lung cancer patients have better survival when treated in thoracic surgical (specialist) centres., Aims: To determine whether outcome of non-small cell lung cancer (NSCLC) patients is poorer with increasing distance to the nearest accessible specialist hospital (NASH)., Methods: We linked cancer registry, hospital and death records of 23,871 NSCLC patients; 3240 localised, 2435 regional and 3540 distant stage patients hospitalised within 12 months of diagnosis were analysed. Distance from patients' residences to the NASH was measured using geographical coordinates. Cox proportional hazards models examined predictors of NSCLC death., Results: Having a resection of the cancer, which admission to a specialist hospital made more likely, substantially reduced hazard of NSCLC death. Distance influenced hazard of death through both these variables; a patient was less likely to be admitted to a specialist hospital than a general hospital and less likely to have a resection the further they lived from the NASH. However, patients who lived distant from the NASH and were admitted to a specialist hospital were more likely to have a resection and less likely to die from NSCLC than patients admitted to a specialist hospital and living closer to the NASH. These patterns varied little with lung cancer stage., Conclusions: NSCLC outcome is best when patients are treated in a specialist hospital. Greater distance to the NASH can affect its outcome by reducing the likelihood of being treated in a specialist hospital. Research is needed into patient and health service barriers to referral of NSCLC patients for specialist care., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Despite the widespread use of ambient ultraviolet radiation (UVR) as a proxy measure of personal exposure to UVR, the relationship between the two is not well-defined. This paper examines the effects of season and latitude on the relationship between ambient UVR and personal UVR exposure. We used data from the AusD Study, a multi-centre cross-sectional study among Australian adults (18-75 years), where personal UVR exposure was objectively measured using polysulphone dosimeters. Data were analysed for 991 participants from 4 Australian cities of different latitude: Townsville (19.3°S), Brisbane (27.5°S), Canberra (35.3°S) and Hobart (42.8°S). Daily personal UVR exposure varied from 0.01 to 21 Standard Erythemal Doses (median = 1.1, IQR: 0.5-2.1), on average accounting for 5% of the total available ambient dose. There was an overall positive correlation between ambient UVR and personal UVR exposure (r = 0.23, p < 0.001). However, the correlations varied according to season and study location: from strong correlations in winter (r = 0.50) and at high latitudes (Hobart, r = 0.50; Canberra, r = 0.39), to null or even slightly negative correlations, in summer (r = 0.01) and at low latitudes (Townsville, r = -0.06; Brisbane, r = -0.16). Multiple regression models showed significant effect modification by season and location. Personal exposure fraction of total available ambient dose was highest in winter (7%) and amongst Hobart participants (7%) and lowest in summer (1%) and in Townsville (4%). These results suggest season and latitude modify the relationship between ambient UVR and personal UVR exposure. Ambient UVR may not be a good indicator for personal exposure dose under some circumstances.

Objective: We investigated the completeness of recording of pathology tests in Australian Medical Benefits Schedule (MBS) claims data, using the example of the prostate-specific antigen (PSA) test. With some exceptions, MBS claims data records only the three most expensive pathology items in an episode of care, and this practice ('episode coning') means that pathology tests can be under-recorded., Methods: The analysis used MBS data for male participants in the 45 and Up Study. The number and cost of items in each episode of care were used to determine whether an episode contained a PSA screening test (Item 66655), or could have lacked a record of this item because of episode coning., Results: MBS data for 1070392 episodes involving a request for a pathology test for 118074 men were analysed. Of these episodes, 11% contained a request for a PSA test; a further 7.5% may have been missing a PSA request that was not recorded because of episode coning., Conclusions: It is important to consider under-reporting of pathology tests as a result of episode coning when interpreting MBS claims data. Episode coning creates uncertainty about whether a person has received any given pathology test. The extent of this uncertainty can be estimated by determining the proportion of episodes in which the test may have been performed but was not recorded due to episode coning.

This study aimed to assess the attitudes, practices and knowledge of general practitioners (GPs) with regards to vitamin D. A cross-sectional survey of a random sample of GPs stratified by location of practice (rural/remote or metropolitan) and employment status (full-time or part-time) in New South Wales (NSW), Australia was conducted. Of 500 respondents, 58.1% (95% CI 53.8-62.4) reported that up to 39% of their tested patients showed vitamin D deficiency or insufficiency and a further 37.7% (95% CI 33.5-41.9) of respondents said that over 40% of their patients were vitamin D insufficient. Vitamin D supplementation and advice to receive more natural sunlight were the most common ways vitamin D insufficiency was managed (97.1%; 95% CI 95.6-98.6 and 82%, 95% CI 78.6-85.4, respectively). Some gaps in knowledge were identified. Most respondents (64%; 95% CI 59.8-68.2) believed that a person of average sun sensitivity required 10 min of direct sun exposure during summer in peak UV time and a further 21.6% (95% CI 18.0-25.2) believed that people required 30 min of direct sun. A third of respondents (33.1%; 95% CI 29.0-37.2) advised their patients to use sun protection at all times during winter. In general, the attitude items showed that respondents expressed greater concern about vitamin D deficiency than skin cancer. The results reveal some confusion in general practice regarding vitamin D, sun exposure, sun protection and skin cancer risk. Some of the advice that GPs are offering may needlessly increase their patients' risk for vitamin D insufficiency or skin cancer., (Copyright © 2011 UICC.)

Purpose: To develop more evidence-based guidelines for the frequency of patient follow-up after treatment of localized (American Joint Committee on Cancer [AJCC] stage I or II) melanoma., Methods: We used data from Melanoma Institute Australia on an inception cohort of 3,081 consecutive patients first diagnosed with stage I or II melanoma between January 1985 and December 2009. Kaplan-Meier curves and Cox models were used to characterize the time course and predictors for recurrence and new primaries. We modeled the delay in diagnosis of recurrence or new primary as well as the number of monitoring visits required using two monitoring schedules: first, according to 2008 Australian and New Zealand guidelines and, second, with fewer visits, especially for those at lowest risk of recurrence., Results: For every 1,000 patients beginning follow-up, 229 developed recurrence and 61 developed new primary within 10 years. There was only a small difference in modeled delay in diagnosis (extra 44.9 and 9.6 patients per 1,000 for recurrence and new primary, respectively, with delay greater than 2 months) using a schedule that requires far fewer visits (3,000 fewer visits per 1,000 patients) than recommended by current guidelines. AJCC substage was the most important predictor of recurrence, whereas age and date of primary diagnosis were important predictors of developing new primary., Conclusion: By providing less intensive monitoring, more efficient follow-up strategies are possible. Fewer visits with a more focused approach may address the needs of patients and clinicians to detect recurrent or new melanoma.

In an International Lymphoma Epidemiology Consortium pooled analysis, polymorphisms in 2 immune-system-related genes, tumor necrosis factor (TNF) and interleukin-10 (IL10), were associated with non-Hodgkin lymphoma (NHL) risk. Here, 8,847 participants were added to previous data (patients diagnosed from 1989 to 2005 in 14 case-control studies; 7,999 cases, 8,452 controls) for testing of polymorphisms in the TNF -308G>A (rs1800629), lymphotoxin-alpha (LTA) 252A>G (rs909253), IL10 -3575T>A (rs1800890, rs1800896), and nucleotide-binding oligomerization domain containing 2 (NOD2) 3020insC (rs2066847) genes. Odds ratios were estimated for non-Hispanic whites and several ethnic subgroups using 2-sided tests. Consistent with previous findings, odds ratios were increased for "new" participant TNF -308A carriers (NHL: per-allele odds ratio (OR(allelic)) = 1.10, P(trend) = 0.001; diffuse large B-cell lymphoma (DLBCL): OR(allelic) = 1.23, P(trend) = 0.004). In the combined population, odds ratios were increased for TNF -308A carriers (NHL: OR(allelic) = 1.13, P(trend) = 0.0001; DLBCL: OR(allelic) = 1.25, P(trend) = 3.7 x 10(-6); marginal zone lymphoma: OR(allelic) = 1.35, P(trend) = 0.004) and LTA 252G carriers (DLBCL: OR(allelic) = 1.12, P(trend) = 0.006; mycosis fungoides: OR(allelic) = 1.44, P(trend) = 0.015). The LTA 252A>G/TNF -308G>A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P = 2.9 x 10(-8)). Results suggested associations between IL10 -3575T>A and DLBCL (P(trend) = 0.02) and IL10 -1082A>G and mantle cell lymphoma (P(trend) = 0.04). These findings strengthen previous results for DLBCL and the LTA 252A>G/TNF -308A locus and provide robust evidence that these TNF/LTA gene variants, or others in linkage disequilibrium, are involved in NHL etiology.

Background: Our previous investigation of occupational exposure to ionizing radiation using a Finnish job-exposure matrix (JEM) showed no association with non-Hodgkin lymphoma (NHL) in a population-based case-control study in Australia., Aims: To determine whether occupational exposure to ionizing radiation assessed using an Australian JEM is associated with NHL., Methods: We analysed 694 NHL cases, first diagnosed between 1 January 2000 and 31 August 2001 and 694 controls from south-eastern Australia, matched by age, sex and region of residence. A detailed occupational history was obtained using a lifetime calendar and a telephone interview. Exposure to radiation was assessed using the ionizing radiation component of an Australian JEM. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from logistic regression models that included the matching variables as covariates., Results: The OR for workers ever exposed to ionizing radiation was 0.86 (95% CI = 0.52-1.40). Dividing the subjects into tertiles of exposure also found ORs that were close to or below the null for each exposure group., Conclusions: The application of an Australian JEM did not provide evidence for an association between NHL and occupational exposure to ionizing radiation and is consistent with previous analyses.

The relation between intrauterine growth and risk of childhood acute lymphoblastic leukemia was investigated in an Australian population-based case-control study that included 347 cases and 762 controls aged <15 years recruited from 2003 to 2006. Information on proportion of optimal birth weight, a measure of the appropriateness of fetal growth, was collected from mothers by questionnaire. Data were analyzed by using logistic regression. Risk of acute lymphoblastic leukemia was positively associated with proportion of optimal birth weight; the odds ratio for a 1-standard-deviation increase in proportion of optimal birth weight was 1.18 (95% confidence interval: 1.04, 1.35) after adjustment for the matching variables and potential confounders. This association was also present among children who did not have a high birth weight, suggesting that accelerated growth, rather than high birth weight per se, is associated with risk of acute lymphoblastic leukemia. Similar associations between proportion of optimal birth weight and acute lymphoblastic leukemia were observed for both sexes and across age groups and leukemia subtypes. Results of this study confirm earlier findings of a positive association between rapidity of fetal growth and subsequent risk of acute lymphoblastic leukemia in childhood, and they are consistent with a role for insulin-like growth factors in the causal pathway.

Background: The evidence for a relationship between patient outcomes and clinician and hospital volume is increasing. The National Colorectal Cancer Care Survey was undertaken to determine the management patterns in Australia for individuals newly diagnosed with colorectal cancer in a 3 month period in the year 2000., Methods: All new cases of colorectal cancer registered at each Australian State Cancer Registry were entered into the survey. This generated a questionnaire that was sent to the treating surgeon. Chi-squared tests and logistic regression analyses were used to determine levels of statistical significance., Results: Of 2,383 surgical questionnaires generated, 2,015 (85%) were completed. The majority (58%) of surgeons treated one or two patients with colorectal cancer over the 3 months of the survey. There was variation across surgeon cohorts for preoperative measures including the use of deep vein thrombosis prophylaxis. Patients seen by low volume surgeons were most likely to be given a permanent stoma (P < 0.0001). Patients with rectal cancer who were operated on by high volume surgeons were significantly more likely to receive a colonic pouch (P < 0.0001)., Conclusion: This nationwide population-based survey of the treatment of colorectal cancer patients suggests that the delivery of care by surgeons (the majority) who treat patients with rectal cancer infrequently should be evaluated.

Background: Non-Hodgkin's lymphoma (NHL) is pathologically diverse. Epidemiological investigations into its increasing incidence and aetiology require accurate subtype classification., Patients and Methods: Available pathology reports of 717 cases aged from 20 to 74 years in an Australian, population-based epidemiological study of NHL were reviewed by one anatomical pathologist to assign a World Health Organization (WHO) classification category. High or low confidence was assigned to the diagnosis of NHL, cell phenotype and WHO category and reasons given for low confidence., Results: The most informative biopsy reports were from open tissue biopsy (79% of cases), tissue core biopsy (8%), cytology (4%) and bone marrow (9%); 8% of cases had inadequate biopsies for diagnostic purposes. Immunohistochemistry or flow cytometry reports were available for 96% of cases, gene rearrangement studies for 6% and cytogenetics for 3%. The reviewer assigned high confidence to the diagnosis of NHL in 93% of cases and also the phenotype in 88%. While a WHO classification could be assigned in 91% of cases, confidence was high in only 57.5%; insufficient immunophenotyping was the commonest reason for low confidence., Conclusions: Expert pathology review of a population-based sample of NHL can provide a WHO classification category for most cases. A high level of confidence in the classification, however, would require review of diagnostic material and additional phenotyping.

Objectives: To summarize for the first time evidence of the impact of cancer on Indigenous Australians., Methods: Medline search of peer-reviewed scientific journals, and extensive search of reports of government agencies, publications of cancer registries and non-government organizations, and other non-peer-reviewed sources., Results: Indigenous Australians have much higher incidence rates than other Australians of cancers of the lung, liver, and cervix; but much lower rates of cancers of the breast, colon and rectum, prostate, melanoma of skin, and lymphoma. Some of these differences can be explained, in part at least, by differences in risk factor prevalence. Indigenous Australians also have higher mortality and lower survival from cancer as a whole than other Australians. More advanced disease at diagnosis, and possibly poorer treatment, are partly responsible for these differences, but other factors may also be involved., Conclusions: Less accessible and less effective health programs are as great a problem for cancer control as for other aspects of Indigenous health in Australia. Major improvements in preventive services, screening, primary care, and specialist treatment services are required to reduce cancer incidence and improve cancer outcomes for Australia's Indigenous people.

Ethnicity, cutaneous nevi and eye color are generally accepted risk factors for melanoma of the eye, although case-control studies have produced conflicting results. We sought to determine the constitutional risk factors for melanomas of the choroid, ciliary body, iris and conjunctiva in Australia. A population-based case-control study was conducted, with case ascertainment from a prospective national incidence survey and randomly selected community controls. Two hundred and ninety cases aged 18-79 years and diagnosed between 1st January 1996 and 31st July 1998 were enrolled with 916 controls frequency matched by age, sex and State or Territory of residence. Risk of choroidal and ciliary body melanoma (n = 246) was increased in people with grey (OR 2.9, 95% CI 1.5-5.5), hazel (OR 2.2, 95% CI 1.4-3.7) and blue eyes (OR 1.7, 95% CI 1.0-2.7) compared with brown eyes. Risk was also increased in those with 4 or more nevi on their back, those unable to tan, and those who squinted when outdoors as a child. Risk was reduced in people born other than in Australia and New Zealand (OR 0.7, 95% CI 0.5-1.0). Non-brown eye color was a risk factor for iris melanoma (n = 25). No risk factors were identified for conjunctival melanoma (n = 19). Eye color is the strongest constitutional predictor of choroidal and ciliary body melanoma, and may indicate a protective effect of melanin density at these sites. An independent association with cutaneous nevi suggests a role for other genetic factors., (Copyright 2001 Wiley-Liss, Inc.)

We conducted a case-control study of sun exposure and squamous cell carcinoma (SCC) of the skin within a population-based, longitudinal study of skin cancer. Cases had histopathologically confirmed SCC. Subjects were interviewed about their lifetime sun exposure, including exposure to the site of the SCC (sites for controls were assigned randomly). Analysis was restricted to 132 cases and 1,031 controls born in Australia and with no ancestors from southern Europe. The total site-specific exposure was strongly related to risk of SCC; the odds ratio increased to a maximum of 3.3 at 65,000 hr of exposure before falling slightly. Site-specific exposure during childhood and adolescence was more strongly associated with SCC than exposure during adulthood. An intermittent pattern of weekly sun exposure was not associated with SCC and the odds ratios for hours of exposure on vacation were close to unity. The number of blistering sunburns to the site was positively associated with SCC. Use of sunscreens and hats showed inconsistent effects. Sun exposure, especially during childhood and adolescence, increases the risk of SCC. The pattern of exposure appears to be unimportant, despite the association with sunburn, which may simply be an indicator of the skin's sensitivity to sunlight.

Background: A strong association has been found between skin cancer and exposure to UV radiation. The p53 tumor suppressor gene (also known as TP53), which is frequently mutated in human cancers, is believed to be an early target in UV radiation-associated skin carcinogenesis. We have previously developed a sensitive, polymerase chain reaction-based method capable of detecting and quantifying a UV radiation-specific mutation in the p53 gene (codons 247 and 248: AAC CGG --> AAT TGG) in normal skin. We have used this method to examine whether UV radiation-specific mutation frequency is associated with risk of basal cell carcinoma (BCC) and with sun exposure., Methods: This case-control study in Australia involved 53 case subjects with BCC and 75 control subjects. DNA was isolated from normal skin (mirror-image anatomic site to the cancer site for case subjects and a randomly selected site for control subjects) and assayed for p53 mutation. Relationships between p53 mutation frequency and risk of BCC, sun sensitivity, or sun exposure were estimated by use of odds ratios (ORs) and 95% confidence intervals (95% CIs)., Results: Case subjects were more likely to have a p53 mutation than control subjects (OR = 3.1; 95% CI = 1.3-7.1). In addition, the odds of BCC increased monotonically with increasing frequency of p53 mutation. No statistically significant associations could be demonstrated between p53 mutation frequency and age, sex, sensitivity to the sun, pigmentary characteristics, total lifetime sun exposure, or sun exposure to the biopsy site., Conclusions: Our results indicate that tandem CC --> TT mutations involving codons 247 and 248 of the p53 gene are associated with an increased risk of BCC but cannot be used as an accurate measure of total UV-radiation exposure.