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Sensitivity Analysis - Lung

Exposure to diesel engine exhaust (DEE) contributes appreciably to the burden of occupational cancer. This study aims to estimate the potential impact of a range of interventions on the future burden of cancer from occupational exposure to DEE in Australia. The future excess fraction method, a novel method based on the lifetime risk approach, was used to model changes in the future burden of cancer among the Australian working age population exposed to DEE at work in 2012 under various intervention strategies. The interventions modeled were based on the widely accepted hierarchy of control model. At baseline, 600 (0.4%) future bladder and 4,450 (0.6%) future lung cancer cases over the lifetime of the cohort were estimated to be attributable to occupational exposure to DEE in those exposed in 2012. Up to 2,000 of these cases were estimated to be avoidable through the use of various interventions. Exhaust hoses (engineering controls) were estimated to be particularly effective. This study provides an indication of which intervention strategies may be most useful in reducing the future burden of cancer associated with occupational DEE exposure. These results show the potential effect of changing current exposure, rather than focusing on past exposures, and thus provide relevant information for policy planning.

To understand the geographic distribution of and area-level factors associated with malignant mesothelioma incidence and survival in Australia.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.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.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.

Home care is a rapidly growing industry. Violence towards home care workers is common, while also likely underreported. This violence adversely affects the physical and mental health of both workers and care recipients. The current study aims to identify and appraise recent evidence on the determinants of violence towards care workers working in the home setting.Six electronic databases: the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Informit, Medline, PsycINFO, and Web of Science, were systematically searched. A systematic review was conducted in accordance with the Joanna Briggs Institute manual for evidence synthesis.A total of 18 papers met the inclusion criteria. All were cross-sectional surveys. The majority of studies were from the United States. The most commonly investigated associations were those between the medical history of clients, workers' apprehension of violence, worker-client relationship, or care plans, and any form of violence or verbal abuse.Violence was common in clients with cognitive disorders, substance abuse disorder, and limited mobility; toward workers who feared that violence might happen; toward those who had very close or very distant worker-client relationships; and when care plans were not inclusive of clients' needs. The current review highlights a gap in evidence on determinants of violence towards care workers working in the home setting, and suggests potential areas to be addressed to reduce such violence.

A dose-escalation, phase I study evaluated the safety, pharmacokinetics, pharmacogenomics, and efficacy of ES-285, a novel agent isolated from a marine mollusc, in adult cancer patients. Patients received a 24-hour i.v. infusion of ES-285 once every 3 weeks until disease progression or unacceptable toxicity. The starting dose was 4 mg/m2. Dose escalation in cohorts of at least three patients proceeded according to the worst toxicity observed in the previous cohort. Twenty-eight patients were treated with 72 courses of ES-285 across eight dose levels. No dose-limiting toxicities were seen between 4 and 128 mg/m2. Two of four patients treated at 256 mg/m2 had dose-limiting reversible grade 3 transaminitis; one patient at 256 mg/m2 also had transient grade 3 central neurotoxicity. One of three patients subsequently treated at 200 mg/m2 died following drug-related central neurotoxicity. Other toxicities included phlebitis, nausea, fatigue, and fever. Pharmacokinetic studies indicated dose proportionality with high volume of distribution (median Vss at 256 mg/m2 was 2,389 liters; range, 1,615–4,051 liters) and long elimination half life (median t1/2 at 256 mg/m2 was 28 h; range, 21–32 h). The three patients with dose-limiting toxicity had the highest drug exposure. Pharmacogenomic studies of paired surrogate tissue samples identified changes in gene expression following treatment that correlated with increasing dose. Disease stabilization for 6 to 18 weeks was recorded in nine patients. Using this schedule, 128 mg/m2 was considered safe and feasible. At this dose, pharmacologically relevant concentrations of the drug were safely achieved with pharmacogenomic studies indicating changes in the expression of genes of potential mechanistic relevance. [Mol Cancer Ther 2009;8(6):1430–7]

Supplementary Table S3 from Phase I safety, pharmacokinetic, and pharmacogenomic trial of ES-285, a novel marine cytotoxic agent, administered to adult patients with advanced solid tumors

Supplementary Fig. S1 from Phase I safety, pharmacokinetic, and pharmacogenomic trial of ES-285, a novel marine cytotoxic agent, administered to adult patients with advanced solid tumors

Australian HIV notification rates are higher for people born in Northeast Asia, Southeast Asia and sub-Saharan Africa compared to Australian-born people. The Migrant Blood-Borne Virus and Sexual Health Survey represents the first attempt to build the national evidence base regarding HIV knowledge, risk behaviors and testing among migrants in Australia. To inform survey development, preliminary qualitative research was conducted with a convenience sample of n = 23 migrants. A survey was developed with reference to the qualitative data and existing survey instruments. Non-probability sampling of adults born in Northeast Asia, Southeast Asia and sub-Saharan Africa was undertaken (n = 1489), and descriptive and bivariate analyses of data were conducted. Knowledge of pre-exposure prophylaxis was low (15.59%), and condom use at last sexual encounter was reported by 56.63% of respondents engaging in casual sex, and 51.80% of respondents reported multiple sexual partners. Less than one-third (31.33%) of respondents reported testing for any sexually transmitted infection or blood-borne virus in the previous two years and, of these, less than half (45.95%) tested for HIV. Confusion surrounding HIV testing practices was reported. These findings identify policy interventions and service improvements critically needed to reduce widening disparities regarding HIV in Australia.

Quantitatively eliciting perspectives about a large number of similar entities (such as a list of competences) is a challenge for researchers in health profession education (HPE). Traditional survey methods may include using Likert items. However, a Likert item approach that generates absolute ratings of the entities may suffer from the “ceiling effect”, as ratings cluster at one end of the scale. This impacts on researchers’ ability to detect differences in ratings between the entities themselves and between respondent groups. This paper describes the use of pairwise comparison questions and a novel application of the Elo algorithm to generate relative ratings and rankings of a large number of entities on a unidimensional scale. A study assessing 91 student “preparedness characteristics” for veterinary workplace clinical training (WCT) in terms of their relative importance is presented as an example of this method in action. The Elo algorithm generates continuous data with measurement variability which, by definition, spans an entire spectrum: a normalised rating for each entity on a scale from zero to one. Since the ratings are relative to each other they are not susceptible to the ceiling effect. Additional advantages of the pairwise comparison question style are their low susceptibility to systematic bias and measurement error, they can be quicker and arguably more engaging to complete than Likert items, and they should carry a low cognitive load for respondents. Methods for evaluating the validity and reliability of this survey design are also described.Using pairwise comparison style questions and the Elo algorithm is an effective methodology to derive relative ratings (and rankings) of a large number of survey entities within HPE research.

Cancers evolve obeying Darwinian laws and therefore the evolutionary paradigm lays the ground for predictive oncology. However, the predictive power of evolutionary metrics in cancer has been seldom tested. There is a need for quantitative measurements in controlled clinical trials with long term follow-up information. This is particularly true in locally-advanced prostate cancer, which can recur more than a decade after diagnosis. Here we mapped genomic intra-tumour heterogeneity in 642 samples from 114 patients who took part in the prostate radiotherapy trials at The Royal Marsden Hospital, for which full clinical information and 12y median follow-up was available. We concomitantly assessed phenotypic (morphological) heterogeneity using deep learning in 1,923 histological sections from 250 IMRT patients (fully overlapping with the genetic set). We found that evolvability, measured as genetic divergence as well as morphological diversity, was a strong independent predictor of recurrence (respectively HR=72.06, 95% CI 2.97-1748.5, p=0.009 and HR=6.2, 95% CI 1.86-20.72, p=0.003). Combined, these two measurements together also identified a group of patients with half the median time to recurrence compared to the rest of the cohort (5.6 vs 11.5 years). We also found a small subset of MYC/FGFR1 amplified cases (4.4%) with particularly poor prognosis. The overall burden of chromosomal alterations correlated with higher Gleason score. We identified associations between 24 chromosomal arm copy number changes and Gleason score (e.g. -22q, +5p, +8q, +16p, +7p), and show that loss of chromosome 6p (encompassing the HLA locus) was correlated with markedly reduced immune cell infiltration. This study shows that combining genomics with AI-aided histopathology in clinical trials leads to the identification of novel clinical biomarkers.

BACKGROUND Reliable data about sexual behaviors is fundamental in the prevention and control of HIV, hepatitis, and other sexually transmitted infections. Generally, sexual behaviors are regarded as a sociocultural taboo in Africa and Asia, and this results in biased sexual behavior survey data due to social desirability. Various modes of survey delivery, including audio computer-assisted self-interviews (ACASIs), have been investigated to improve data quality. OBJECTIVE This study aimed to review studies that compared the ACASI mode to other survey modes in sexual behavior surveys in Asia and sub-Saharan Africa to ascertain the impact of survey mode on responses to sexual behavior questions. METHODS A systematic literature review was conducted according to the Joanna Briggs Institute Manual for Evidence Synthesis. The review protocol was registered at PROSPERO (International Prospective Register of Systematic Reviews). Six databases were searched. RESULTS A total of 21 papers were included. The face-to-face interview (FTFI) mode was the survey mode most frequently compared to the ACASI mode. Among the most commonly reported outcome variable groups, ACASI participants were more likely to report sexual behaviors, such as “forced sex,” “multiple partners,” “transactional sex,” and “ever had sex,” as compared to FTFI participants. In addition to the survey mode effect, other factors were found to have had an impact on data quality, for example, participant characteristics, social norms, study design, and data collection setting. CONCLUSIONS Use of ACASIs for administering sexual behavior surveys among populations in Asia and sub-Saharan Africa demonstrated higher reports for some sexual behaviors than the use of FTFIs. More studies that compare the ACASI mode to other survey modes would improve our understanding of the usefulness of ACASIs in sexual behavior surveys in these regions.

BACKGROUND Self-administered paper or electronic surveys can create accessibility issues for people with language barriers and limited literacy, whereas face-to-face interviews can create privacy issues and give rise to reporting biases, particularly in the context of sensitive subject matters. An audio computer-assisted self-interview (ACASI) offers an alternative mode of survey administration, and its use has been tested against other survey modes to determine whether the presence of a background narration helps overcome literacy and privacy issues. There are still gaps with the ACASI survey administration because audio narration alone does not assist respondents with limited literacy in choosing response options. To overcome literacy issues, a few studies have used illustrated pictures for a limited number of response options. OBJECTIVE This study aimed to illustrate all the questions and response options in an ACASI application. This research is part of a larger study comparing different modes of survey administration (ACASI, face-to-face interviews, and self-administered paper surveys) to collect data on hepatitis B knowledge, attitudes, and practices among the Myanmar-born community in Perth, Australia. This study describes the 2-phase process of developing a web-based ACASI application using illustrated pictures. METHODS The first phase was the preparation of the ACASI elements, such as questionnaire, pictures, brief descriptions of response options, and audio files. Each element was pretested on 20 participants from the target population. The second phase involved synchronizing all the elements into the web-based ACASI application and adapting the application features, in particular, autoplay audio and illustrated pictures. The preprototype survey application was tested for user acceptance on 5 participants from the target population, resulting in minor adjustments to the display and arrangement of response options. RESULTS After a 12-month development process, the prototype ACASI application with illustrated pictures was fully functional for electronic survey administration and secure data storage and export. CONCLUSIONS Pretesting each element separately was a useful approach because it saved time to reprogram the application at a later stage. Future studies should also consider the participatory development of pictures and visual design of user interfaces. This picture-assisted ACASI survey administration mode can be further developed and used to collect sensitive information from populations that are usually marginalized because of literacy and language barriers.

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer.

IntroductionMore research and policy action are needed to improve migrant health in areas such as sexual health and blood-borne viruses (SHBBV). While Knowledge, Attitudes and Practice Surveys (KAPS) can inform planning, there are no SHBBV KAPS suitable for use across culturally and linguistically diverse contexts. This study pretests one instrument among people born in Sub-Saharan Africa, South-East and North-East Asia living in Australia.MethodsEmployees of multicultural organisations were trained to collect data over three rounds using a hybrid qualitative pretesting method. Two researchers independently coded data. Researchers made revisions to survey items after each round. Responses to feedback questions in the final survey were analysed.ResultsSixty-two participants pretested the survey. Issues were identified in all three rounds of pretesting. Of the 77 final survey respondents who responded to a survey experience question, 21% agreed and 3% strongly agreed with the statement ‘I found it hard to understand some questions/words’.ConclusionIt is essential to pretest SHBBV surveys in migrant contexts. We offer the following pretesting guidance: (1) large samples are needed in heterogeneous populations; (2) intersectionality must be considered; (3) it may be necessary to pretest English language surveys in the participants’ first language; (4) bilingual/bicultural workers must be adequately trained to collect data; (5) results need to be interpreted in the context of other factors, including ethics and research aims; and (6) pretesting should occur over multiple rounds.

In this article, we describe the approaches taken to recruit adult migrants living in Australia for a sexual health and blood-borne virus survey (paper and online) and present data detailing the outcomes of these approaches. The purpose was to offer guidance to redress the under-representation of migrants in public health research. Methods of recruitment included directly contacting people in individual/organizational networks, social media posts/advertising, promotion on websites, and face-to-face recruitment at public events/venues. Search query strings were used to provide information about an online referral source, and project officers kept records of activities and outcomes. Descriptive statistical analyses were used to determine respondent demographic characteristics, proportions recruited to complete the paper and online surveys, and sources of referral. Logistic regression analyses were run to predict online participation according to demographic characteristics. The total sample comprised 1454 African and Asian migrants, with 59% identifying as female. Most respondents (72%) were recruited to complete the paper version of the survey. Face-to-face invitations resulted in the highest number of completions. Facebook advertising did not recruit large numbers of respondents. Same-sex attraction and age (40–49 years) were statistically significant predictors of online completion. We encourage more researchers to build the evidence base on ways to produce research that reflects the needs and perspectives of minority populations who often bear the greatest burden of disease.

Background Many cancers are caused by exposure to lifestyle, environmental, and occupational factors. Earlier studies have estimated the number of cancers occurring in a single year which are attributable to past exposures to these factors. However, there is now increasing appreciation that estimates of the future burden of cancer may be more useful for policy and prevention. We aimed to calculate the future number of cancers expected to arise as a result of exposure to 23 modifiable risk factors. Methods We used the future excess fraction (FEF) method to estimate the lifetime burden of cancer (2016–2098) among Australian adults who were exposed to modifiable lifestyle, environmental, and occupational risk factors in 2016. Calculations were conducted for 26 cancer sites and 78 cancer-risk factor pairings. Results The cohort of 18.8 million adult Australians in 2016 will develop an estimated 7.6 million cancers during their lifetime, of which 1.8 million (24%) will be attributable to exposure to modifiable risk factors. Cancer sites with the highest number of future attributable cancers were colon and rectum (n = 717,700), lung (n = 380,400), and liver (n = 103,200). The highest number of future cancers will be attributable to exposure to tobacco smoke (n = 583,500), followed by overweight/obesity (n = 333,100) and alcohol consumption (n = 249,700). Conclusion A significant proportion of future cancers will result from recent levels of exposure to modifiable risk factors. Our results provide direct, pertinent information to help determine where preventive measures could best be targeted.