Search

Precision public health holds promise to improve disease prevention and health promotion strategies, allowing the right intervention to be delivered to the right population at the right time. Growing concerns underscore the potential for precision-based approaches to exacerbate health disparities by relying on biased data inputs and recapitulating existing access inequities. To achieve its full potential, precision public health must focus on addressing social and structural drivers of health and prominently incorporate equity-related concerns, particularly with respect to race and ethnicity. In this article, we discuss how an antiracism lens could be applied to reduce health disparities and health inequities through equity-informed research, implementation, and evaluation of precision public health interventions. (Am J Public Health. 2023;113(11):1210–1218. https://doi.org/10.2105/AJPH.2023.307386) [ABSTRACT FROM AUTHOR]

CONTEXT Abortion stigma may cause psychological distress in women who are considering having an abortion or have had one. This phenomenon has been relatively underexplored in low-income women, who may already be at an increased risk for poor abortion-related outcomes because of difficulties accessing timely and safe abortion services. METHODS A qualitative study conducted between 2010 and 2013 used semistructured interviews to explore pregnancy intentions among low-income women recruited from six reproductive health clinics in Western Pennsylvania. Transcripts from interviews with 19 participants who were planning to terminate a pregnancy or had had an abortion in the last two weeks were examined through content analysis to identify the range of attitudes they encountered that could contribute to or reflect abortion stigma, the sources of these attitudes and women's responses to them. RESULTS Women commonly reported that partners, family members and they themselves held antiabortion attitudes. Such attitudes communicated that abortion is morally reprehensible, a rejection of motherhood, rare and thus potentially deviant, detrimental to future fertility and an irresponsible choice. Women reacted to external and internal negative attitudes by distinguishing themselves from other women who obtain abortions, experiencing negative emotions, and concealing or delaying their abortions. CONCLUSIONS Women's reactions to antiabortion attitudes may perpetuate abortion stigma. Further research is needed to inform interventions to address abortion stigma and improve women's abortion experiences. [ABSTRACT FROM AUTHOR]

Introduction: There have been significant advancements in risk identification and treatment for ovarian cancer over the last decade. However, their impact on health services costs is unclear. This study estimated the direct health system costs (government perspective) for women diagnosed with ovarian cancer in Australia during 2006–2013, as a benchmark prior to opportunities for precision-medicine approaches to treatment, and for health care planning. Methods: Using cancer registry data, we identified 176 incident ovarian cancers (including fallopian tube and primary peritoneal cancer) in the Australian 45 and Up Study cohort. Each case was matched with four cancer-free controls on sex, age, geography, and smoking history. Costs were derived from linked health records on hospitalisations, subsidised prescription medicines and medical services to 2016. Excess costs for cancer cases were estimated for different phases of care relative to cancer diagnosis. Overall costs for prevalent ovarian cancers in Australia in 2013 were estimated based on 5-year prevalence statistics. Results: At diagnosis, 10% of women had localised disease, 15% regional spread and 70% distant metastasis (5% unknown). The mean excess cost per ovarian cancer case was $40,556 in the initial treatment phase (≤12 months post-diagnosis), $9,514 per annum in the continuing care phase and $49,208 in the terminal phase (up to 12 months before death). Hospital admissions accounted for the greatest proportion of costs during all phases (66%, 52% and 68% respectively). Excess costs were higher for patients diagnosed with distant metastatic disease, particularly during the continuing care phase ($13,814 versus $4,884 for localised/regional disease). The estimated overall direct health services cost of ovarian cancer in 2013 was AUD$99million (4,700 women nationally). Conclusion: The excess health system costs of ovarian cancer are substantial. Continued investment in ovarian cancer research, particularly prevention, early detection and more effective personalised treatments is necessary to reduce the burden of disease. [ABSTRACT FROM AUTHOR]

Considerable progress continues to be made with regards to the value and use of disease associated polygenic scores (PGS). PGS aim to capture a person's genetic liability to a condition, disease, or a trait, combining information across many risk variants and incorporating their effect sizes. They are already available for clinicians and consumers to order in Australasia. However, debate is ongoing over the readiness of this information for integration into clinical practice and population health. This position statement provides the viewpoint of the Human Genetics Society of Australasia (HGSA) regarding the clinical application of disease-associated PGS in both individual patients and population health. The statement details how PGS are calculated, highlights their breadth of possible application, and examines their current challenges and limitations. We consider fundamental lessons from Mendelian genetics and their continuing relevance to PGS, while also acknowledging the distinct elements of PGS. Use of PGS in practice should be evidence based, and the evidence for the associated benefit, while rapidly emerging, remains limited. Given that clinicians and consumers can already order PGS, their current limitations and key issues warrant consideration. PGS can be developed for most complex conditions and traits and can be used across multiple clinical settings and for population health. The HGSA's view is that further evaluation, including regulatory, implementation and health system evaluation are required before PGS can be routinely implemented in the Australasian healthcare system. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is the third most diagnosed cancer globally and the second leading cause of cancer death. We examined colon and rectal cancer treatment patterns in Australia. Methods: From cancer registry records, we identified 1,236 and 542 people with incident colon and rectal cancer, respectively, diagnosed during 2006-2013 in the 45 and Up Study cohort (267,357 participants). Cancer treatment and deaths were determined via linkage to routinely collected data, including hospital and medical services records. For colon cancer, we examined treatment categories of "surgery only", "surgery plus chemotherapy", "other treatment" (i.e. other combinations of surgery/chemotherapy/radiotherapy), "no record of cancer-related treatment, died"; and, for rectal cancer, "surgery only", "surgery plus chemotherapy and/or radiotherapy", "other treatment", and "no record of cancer-related treatment, died". We analysed survival, time to first treatment, and characteristics associated with treatment receipt using competing risks regression. Results: 86.4% and 86.5% of people with colon and rectal cancer, respectively, had a record of receiving any treatment ≤2 years post-diagnosis. Of those treated, 93.2% and 90.8% started treatment ≤2 months post-diagnosis, respectively. Characteristics significantly associated with treatment receipt were similar for colon and rectal cancer, with strongest associations for spread of disease and age at diagnosis (p<0.003). For colon cancer, the rate of "no record of cancer-related treatment, died" was higher for people with distant spread of disease (versus localised, subdistribution hazard ratio (SHR)=13.6, 95% confidence interval (CI):5.5-33.9), age ≥75 years (versus age 45-74, SHR=3.6, 95%CI:1.8-7.1), and visiting an emergency department ≤1 month pre-diagnosis (SHR=2.9, 95%CI:1.6-5.2). For rectal cancer, the rate of "surgery plus chemotherapy and/or radiotherapy" was higher for people with regional spread of disease (versus localised, SHR=5.2, 95%CI:3.6-7.7) and lower for people with poorer physical functioning (SHR=0.5, 95%CI:0.3-0.8) or no private health insurance (SHR=0.7, 95%CI:0.5-0.9). Conclusion: Before the COVID-19 pandemic, most people with colon or rectal cancer received treatment ≤2 months post-diagnosis, however, treatment patterns varied by spread of disease and age. This work can be used to inform future healthcare requirements, to estimate the impact of cancer control interventions to improve prevention and early diagnosis, and serve as a benchmark to assess treatment delays/disruptions during the pandemic. Future work should examine associations with clinical factors (e.g. performance status at diagnosis) and interdependencies between characteristics such as age, comorbidities, and emergency department visits. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors have been approved in the USA for tumours exhibiting mismatch repair deficiency (dMMR), microsatellite instability (MSI), or high tumour mutational burden (TMB), with regulatory and reimbursement applications in multiple other countries underway. As the estimated budget impacts of future reimbursements depend on the size of the potential target population, we performed a scoping review and meta-analysis of the prevalence of these pan-tumour biomarkers in different cancers. We systematically searched Medline/Embase and included studies reporting the prevalence of dMMR/MSI/high TMB in solid tumours published 01/01/2018–31/01/2021. Meta-analyses were performed separately for the pan-cancer prevalence of each biomarker, and by cancer type and stage where possible. The searches identified 3890 papers, with 433 prevalence estimates for 32 different cancer types from 201 studies included in meta-analyses. The pooled overall prevalence of dMMR, MSI and high TMB (≥ 10 mutations/Mb) in pan-cancer studies was 2.9%, 2.7% and 14.0%, respectively. The prevalence profiles of dMMR/MSI and high TMB differed across cancer types. For example, endometrial, colorectal, small bowel and gastric cancers showed high prevalence of both dMMR and MSI (range: 8.7–26.8% and 8.5–21.9%, respectively) and high TMB (range: 8.5–43.0%), while cervical, esophageal, bladder/urothelial, lung and skin cancers showed low prevalence of dMMR and MSI (< 5%), but high prevalence of high TMB (range: 23.7–52.6%). For other cancer types, prevalence of all three biomarkers was generally low (< 5%). This structured review of dMMR/MSI/high TMB prevalence across cancers and for specific cancer types and stages provide timely evidence to inform budget impact forecasts in health technology assessments for drug approvals based on these pan-tumour biomarkers. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PC) aetiology is unclear. PC risk was examined in relation to several factors in a large population-based prospective study.Methods: Male participants were from Sax Institute's 45 and Up Study (Australia) recruited between 2006 and 2009. Questionnaire and linked administrative health data from the Centre for Health Record Linkage and Services Australia were used to identify incident PC, healthcare utilisations, Prostate Specific Antigen (PSA) testing reimbursements and dispensing of metformin and benign prostatic hyperplasia (BPH) prescriptions. Multivariable Cox and Joint Cox regression analyses were used to examine associations by cancer spread, adjusting for various confounders.Results: Of 107,706 eligible men, 4257 developed incident PC up to end 2013. Risk of PC diagnosis increased with: PC family history (versus no family history of cancer; HRadjusted = 1.36; 95% CI:1.21-1.52); father and brother(s) diagnosed with PC (versus cancer-free family history; HRadjusted = 2.20; 95% CI:1.61-2.99); severe lower-urinary-tract symptoms (versus mild; HRadjusted = 1.77; 95% CI:1.53-2.04) and vasectomy (versus none; HRadjusted = 1.08; 95% CI:1.00-1.16). PC risk decreased with dispensed prescriptions (versus none) for BPH (HRadjusted = 0.76; 95% CI:0.69-0.85) and metformin (HRadjusted = 0.57; 95% CI:0.48-0.68). Advanced PC risk increased with vasectomy (HRadjusted = 1.28; 95% CI:1.06-1.55) and being obese (versus normal weight; HRadjusted = 1.31; 95% CI:1.01-1.69).Conclusion: Vasectomy and obesity are associated with an increased risk of advanced PC. The reduced risk of localised and advanced PC associated with BPH, and diabetes prescriptions warrants investigation. [ABSTRACT FROM AUTHOR]

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

Objective: Menopausal status impacts risk for many health outcomes. However, factors including hysterectomy without oophorectomy and Menopausal Hormone Therapy (MHT) can mask menopause, affecting reliability of self-reported menopausal status in surveys. We describe a step-by-step algorithm for classifying menopausal status using: directly self-reported menopausal status; MHT use; hysterectomy; oophorectomy; intervention timing; and attained age. We illustrate this approach using the Australian 45 and Up Study cohort (142,973 women aged ≥ 45 years). Results: We derived a detailed seven-category menopausal status, able to be further consolidated into four categories ("pre-menopause"/"peri-menopause"/"post-menopause"/"unknown") accounting for participants' ages. 48.3% of women had potentially menopause-masking interventions. Overall, 93,107 (65.1%), 9076 (6.4%), 17,930 (12.5%) and 22,860 (16.0%) women had a directly self-reported "post-menopause", "peri-menopause", "pre-menopause" and "not sure"/missing status, respectively. 61,464 women with directly self-reported "post-menopause" status were assigned a "natural menopause" detailed derived status (menopause without MHT use/hysterectomy/oophorectomy). By accounting for participants' ages, 105,817 (74.0%) women were assigned a "post-menopause" consolidated derived status, including 15,009 of 22,860 women with "not sure"/missing directly self-reported status. Conversely, 3178 of women with directly self-reported "post-menopause" status were assigned "unknown" consolidated derived status. This algorithm is likely to improve the accuracy and reliability of studies examining outcomes impacted by menopausal status. [ABSTRACT FROM AUTHOR]

Background: We examined whether experiencing more types of lifetime intimate partner violence (IPV) was independently associated with the effectiveness level of the contraceptive method women chose following an abortion. Materials and Methods: Using data on 245 women who were attending an urban hospital abortion clinic, we assessed whether women had ever experienced emotional, physical, or sexual IPV. Effectiveness of women's post-abortion contraceptive method selection was categorized into high (intrauterine device [IUD] and implant), moderate (pill, patch, ring, and shot), and low (condoms, emergency contraception, and none) effectiveness. Using multinomial logistic regression, we examined the relationship between number of types of IPV experienced and post-abortion contraceptive method effectiveness, adjusting for sociodemographics, prior abortion, having children, abortion trimester, importance of avoiding pregnancy in the next year, pre-abortion psychological distress, and effectiveness level of the contraceptive method women were planning to use before contraceptive counseling. Results: Twenty-seven percent (27%) of women experienced two or three types of IPV, 35% experienced one IPV type, and 38% experienced no IPV. Compared to women with no histories of IPV, women who experienced two or more types of IPV during their lifetimes were more likely to choose contraceptive methods with moderate effectiveness (adjusted odds ratio [AOR] = 5.23, 95% confidence interval [CI]: 1.13–24.23, p = 0.035) and high effectiveness (AOR = 5.01, 95% CI: 1.12–22.39, p = 0.035) than those with low effectiveness. Conclusion: Women who experienced two or more types of lifetime IPV selected more effective contraceptive methods post-abortion. Access to contraceptives that are not partner dependent, including long-acting reversible contraceptives (LARC), may be particularly important for women who have experienced multiple types of IPV. [ABSTRACT FROM AUTHOR]

The Schwinger boson theory of the frustrated square lattice antiferromagnet yields a stable, gapped Z2 spin liquid ground state with time-reversal symmetry, incommensurate spin correlations, and long-range Ising-nematic order. We obtain an equivalent description of this state using fermionic spinons (the fermionic spinons can be considered to be bound states of the bosonic spinons and the visons). Upon doping, the Z2 spin liquid can lead to a fractionalized Fermi liquid (FL*) with small Fermi pockets of electronlike quasiparticles, while preserving the Z2 topological and Ising-nematic orders. We describe a Higgs transition out of this deconfined metallic state into a confining superconducting state which is almost always of the Fulde-Ferrell-Larkin-Ovchinnikov type, with spatial modulation of the superconducting order. [ABSTRACT FROM AUTHOR]

Background: The proportion of abortions provided by medication in the United States and worldwide has increased greatly since the U.S. Food and Drug Administration approved mifepristone in 2000. While existing research has shown that abortion does not increase risk of mental health problems, no population-based study has examined specifically whether a procedural or medication abortion increases risk of mental health disorders., Objective: This study examined whether mental health disorders increased in the shorter and longer-term after a medication or procedural abortion., Study Design: Using Danish population registers' data, we conducted a prospective cohort study in which we included 72,424 females born in Denmark between 1980 and 2006, who were ages 12 to 38 during the study period and had a first first-trimester abortion before 13 weeks gestation in 2000 to 2018. Females with no previous psychiatric diagnoses were followed from 1 year before their abortion until their first psychiatric diagnosis, December 31, 2018, emigration from Demark, or death, whichever came first. Risk of any first psychiatric disorder was defined as a recorded psychiatric diagnosis at an in- or out-patient facility from the 1 year after to more than 5 years after a medication or procedural abortion relative to the year beforehand. Results were adjusted for calendar year, age, gestational age, partner status, prior mental and physical health, childbirth history, childhood environment, and parental mental health history., Results: Females having medication (n=37,155) and procedural abortions (n=35,269) had the same risk of any first psychiatric diagnosis in the year after their abortion relative to the year before their abortion (medication abortion adjusted incidence rate ratio [MaIRR]=1.02, 95% confidence interval [CI]: 0.93-1.12; procedural abortion adjusted incidence rate ratio [PaIRR]=0.94, 95% CI: 0.86-1.02). Moreover, as more time from the abortion passed, the risk of a psychiatric diagnoses decreased relative to the year before their abortion for each abortion method (MaIRR 1-2 years after=0.89, 95% CI: 0.80-0.98; PaIRR 1-2 years after=0.81, 95% CI: 0.88-1.05; MaIRR 2-5 years after=0.77, 95% CI: 0.71-0.84; PaIRR 2-5 years after=0.72, 95% CI: 0.67-0.78; MaIRR 5+ years after=0.58, 95% CI: 0.53-0.63; PaIRR 5+ years after=0.54, 95% CI: 0.50-0.58)., Conclusion: Because the risk of psychiatric diagnoses was the same in the year after relative to the year before a medication and procedural abortion and the risk did not increase as more time after the abortion increased, neither abortion method increased risk of mental health disorders in the shorter or longer-term., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Genomic testing can inform the diagnosis and personalise management of cancers in children, adolescents, and young adults (CAYA). This scoping review explored the clinical utility and impact of genomic testing in general CAYA cancer cohorts. Relevant records published in English between 2017-2024 were identified by searching PubMed. 36 studies (32 original articles; 4 reviews) were identified on genomic testing in CAYA cancers, most of which were advanced cancers. Studies internationally reported that approximately 16-18% of CAYAs with cancer carry an associated pathogenic germline variant where 40% are de-novo, and can guide treatment (eg, DNA repair gene variants). Somatic variants, predominantly copy number or structural rearrangements, inform diagnosis in up to 95% of primary cancers. Between 18-69% of patients have a somatic variant with a matched therapy, but only one third receive the genomic-guided recommendation, predominantly due to declining patient condition. Few studies evaluated the impact of matched therapies on response and survival. Combining comprehensive DNA and RNA sequencing maximises sensitivity. Circulating tumour DNA was detected in most primary cancers and shows high concordance with tumour tissue. In conclusion, genomic testing of CAYA cancers is feasible, informs diagnoses and guides personalised care. Further research is needed on response to genomic-guided treatments., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

During the COVID-19 pandemic, countries adopted mitigation strategies to reduce disruptions to cancer services. We reviewed their implementation across health system functions and their impact on cancer diagnosis and care during the pandemic. A systematic search was performed using terms related to cancer and COVID-19. Included studies reported on individuals with cancer or cancer care services, focusing on strategies/programs aimed to reduce delays and disruptions. Extracted data were grouped into four functions (governance, financing, service delivery, and resource generation) and sub-functions of the health system performance assessment framework. We included 30 studies from 16 countries involving 192,233 patients with cancer. Multiple mitigation approaches were implemented, predominantly affecting sub-functions of service delivery to control COVID-19 infection via the suspension of non-urgent cancer care, modified treatment guidelines, and increased telemedicine use in routine cancer care delivery. Resource generation was mainly ensured through adequate workforce supply. However, less emphasis on monitoring or assessing the effectiveness and financing of these strategies was observed. Seventeen studies suggested improved service uptake after mitigation implementation, yet the resulting impact on cancer diagnosis and care has not been established. This review emphasizes the importance of developing effective mitigation strategies across all health system (sub)functions to minimize cancer care service disruptions during crises. Deficiencies were observed in health service delivery (to ensure equity), governance (to monitor and evaluate the implementation of mitigation strategies), and financing. In the wake of future emergencies, implementation research studies that include pre-prepared protocols will be essential to assess mitigation impact across cancer care services., Competing Interests: Declaration of Competing Interest Prof Karen Canfell is co-PI of an investigator-initiated trial of cervical screening, "Compass", run by the VCS Foundation Australia, which is a government-funded not-for-profit charity. She is also co-PI on a major implementation program "Elimination of Cervical Cancer in the Western Pacific" which will receive support from the Minderoo Foundation and the Frazer Family Foundation and equipment donations from Cepheid Inc. Dr Michael Caruana is an investigator on an investigator-initiated trial of cytology and primary HPV screening in Australia (‘Compass’) (ACTRN12613001207707 and NCT02328872), which is also conducted and funded by the VCS Foundation. The VCS Foundation has received equipment and a funding contribution for the Compass trial from Roche Molecular Systems and Ventana Inc USA. However, KC, MC, and their institution on their behalf (the Daffodil Centre, a joint venture between Cancer Council NSW and The University of Sydney) do not receive direct funding from the industry for these or any other research project. Dr. Ethna McFerran receives funding from Health Data Research UK and Cancer Focus Northern Ireland unrelated to this work., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: To examine changes in multiple myeloma incidence and mortality rates during 1982-2018, and to estimate its incidence, mortality, and prevalence for 2019-2043., Study Design: Population-based statistical modelling study; analysis of and projections based on Australian Institute of Health and Welfare multiple myeloma incidence, mortality, and survival data., Setting: Australia, 1982-2018 (historical data) and projections to 2043., Main Outcome Measures: Changes in multiple myeloma incidence and mortality rates, 1982-2018, determined by joinpoint regression analysis (age-standardised to 2021 Australian population); projection of rates to 2043 based on age-period-cohort models; estimated 5- and 30-year prevalence of multiple myeloma (modified counting method)., Results: The incidence of multiple myeloma increased during 1982-2018 (eg, annual percentage change [APC], 2006-2018, 1.9%; 95% confidence interval [CI], 1.7-2.2%), but the mortality rate declined during 1990-2018 (APC, -0.4%; 95% CI, -0.5% to -0.2%). The age-standardised incidence rate was projected to increase by 14.9% during 2018-2043, from 8.7 in 2018 to 10.0 (95% CI, 9.4-10.7) new cases per 100 000 population in 2043; the mortality rate was projected to decline by 27.5%, from 4.0 to 2.9 (95% CI, 2.6-3.3) deaths per 100 000 population. The annual number of people newly diagnosed with multiple myeloma was estimated to increase by 89.2%, from 2120 in 2018 to 4012 in 2043; the number of deaths from multiple myeloma was projected to increase by 31.7%, from 979 to 1289. The number of people living with multiple myeloma up to 30 years after initial diagnosis was projected to increase by 163%, from 10 288 in 2018 to 27 093 in 2043, including 13 019 people (48.1%) diagnosed during the preceding five years., Conclusion: Although the decline in the mortality rate was projected to continue, the projected increases in the incidence and prevalence of multiple myeloma in Australia over the next 25 years indicate that investment in prevention and early detection research, and planning for prolonged treatment and care, are needed., (© 2024 The Author(s). Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Objectives: To investigate self-reported out-of-pocket health care expenses, both overall and by cost type, for a large population-based sample of Australians, by cancer status and socio-demographic and medical characteristics., Study Design: Cross-sectional study., Setting, Participants: New South Wales residents participating in the 45 and Up Study (recruited aged 45 years or older during 2005-2009) who completed the 2020 follow-up questionnaire; survey responses linked with New South Wales Cancer Registry data., Main Outcome Measures: Proportions of respondents who reported that out-of-pocket health care expenses during the preceding twelve months exceeded $1000 or $10 000; adjusted odds ratios (aORs) for associations with socio-demographic and medical characteristics., Results: Of the 267 357 recruited 45 and Up Study participants, 45 061 completed the 2020 survey (response rate, 53%); 42.7% (95% confidence interval [CI], 42.2-43.1%) reported that overall out-of-pocket health care expenses during the previous year exceeded $1000, including 55.4% (52.1-58.7%) of participants diagnosed in the preceding two years and 44.9% (43.7-46.1%) of participants diagnosed with cancer more than two years ago. After adjustment for socio-demographic factors, out-of-pocket expenses greater than $1000 were more likely to be reported by participants with cancer than by those without cancer (diagnosis in past two years: aOR, 2.06 [95% CI, 1.77-2.40]; diagnosis more than two years ago: aOR, 1.22 [95% CI, 1.15-1.29]). The odds of out-of-pocket expenses exceeding $1000 increased with area-based socio-economic advantage and household income, and were higher for people with private health insurance (v people with Medicare coverage only: aOR, 1.64; 95% CI, 1.53-1.75). Out-of-pocket expenses exceeding $10 000 were also more likely for participants diagnosed with cancer during the past two years (v no cancer: aOR, 3.30; 95% CI, 2.56-4.26)., Conclusions: People diagnosed with cancer during the past two years were much more likely than people without cancer to report twelve-month out-of-pocket health care expenses that exceeded $1000. Out-of-pocket expenses for people with cancer can exacerbate financial strain at a time of vulnerability, and affect health care equity because some people cannot pay for all available treatments., (© 2024 The Author(s). Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Purpose: Genetic and genomic testing can provide valuable information on individuals' risk of chronic diseases, presenting an opportunity for risk-tailored disease screening to improve early detection and health outcomes. The acceptability, uptake and effectiveness of such programmes is dependent on public preferences for the programme features. This study aims to conduct a systematic review of discrete choice experiments assessing preferences for genetic/genomic risk-tailored chronic disease screening., Methods: PubMed, Embase, EconLit and Cochrane Library were searched in October 2023 for discrete choice experiment studies assessing preferences for genetic or genomic risk-tailored chronic disease screening. Eligible studies were double screened, extracted and synthesised through descriptive statistics and content analysis of themes. Bias was assessed using an existing quality checklist., Results: Twelve studies were included. Most studies focused on cancer screening (n = 10) and explored preferences for testing of rare, high-risk variants (n = 10), largely within a targeted population (e.g. subgroups with family history of disease). Two studies explored preferences for the use of polygenic risk scores (PRS) at a population level. Twenty-six programme attributes were identified, with most significantly impacting preferences. Survival, test accuracy and screening impact were most frequently reported as most important. Depending on the clinical context and programme attributes and levels, estimated uptake of hypothetical programmes varied from no participation to almost full participation (97%)., Conclusion: The uptake of potential programmes would strongly depend on specific programme features and the disease context. In particular, careful communication of potential survival benefits and likely genetic/genomic test accuracy might encourage uptake of genetic and genomic risk-tailored disease screening programmes. As the majority of the literature focused on high-risk variants and cancer screening, further research is required to understand preferences specific to PRS testing at a population level and targeted genomic testing for different disease contexts., (© 2024. The Author(s).)

Background: Weighting can improve study estimate representativeness. We examined the impact of weighting on associations between participants' characteristics and cancer, cardiovascular and all-cause mortality in the Australian 45 and Up Study cohort., Methods: Raking weighted cohort data to the 2006 Australian population for seven sociodemographic characteristics. Deaths were ascertained via linkage to routinely collected data. Cox's proportional hazards regression quantified associations between 11 sociodemographic and health characteristics and cancer, cardiovascular and all-cause mortality. The ratios of hazard ratios (RHRs) compared unweighted and weighted estimates., Results: Among 195,052 included participants (median follow-up 11.4 years), there were 7200 cancer, 5912 cardiovascular and 21,840 all-cause deaths. Overall, 102/111 (91.9%) weighted HRs did not differ significantly from unweighted HRs (100%, 86.5% and 89.2% of 37 HRs for cancer, cardiovascular and all-cause mortality, respectively). Significant differences included a somewhat stronger association between single/widowed/divorced (versus married/de-facto) and cardiovascular mortality (unweighted HR=1.25 (95%CI:1.18-1.32), weighted HR=1.33 (95%CI:1.24-1.42), RHR=1.06 (95%CI:1.02-1.11)); and between no school certificate/qualification (versus university degree) and all-cause mortality (unweighted HR=1.21 (95%CI:1.15-1.27), weighted HR=1.28 (95%CI:1.19-1.38), RHR=1.06 (95%CI:1.03-1.10))., Conclusion: Our results support the generalisability of most estimates of associations in the 45 and Up Study, particularly in relation to cancer mortality. Slight distortion of a few associations with cardiovascular or all-cause mortality were observed., Competing Interests: Declaration of Competing Interest Sarsha Yap, Qingwei Luo, Stephen Wade, Preston Ngo, David Goldsbury, Peter Sarich, Emily Banks, Marianne Weber, Michael David, Julia Steinberg have no competing interests to declare. Karen Canfell is co-principal investigator (PI) of an investigator-initiated trial of cervical screening, “Compass”, run by the Australian Centre for Prevention of Cervical Cancer (ACPCC), which is a government-funded not-for-profit charity. Compass receives infrastructure support from the Australian government and the ACPCC has received equipment and a funding contribution from Roche Molecular Diagnostics, USA. KC is also co-PI on a major implementation program Elimination of Cervical Cancer in the Western Pacific (ECCWP) which has received support from the Minderoo Foundation and equipment donations from Cepheid Inc. If there are other authors, they 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: Large-scale studies investigating health-related quality of life (HRQL) in cancer survivors are limited. This study aims to investigate HRQL and its relation to optimism and social support among Australian women following a cancer diagnosis., Methods: Data were from the Australian Longitudinal Study on Women's Health, a large cohort study (n = 14,715; born 1946-51), with 1428 incident cancer cases ascertained 1996-2017 via linkage to the Australian Cancer Database. HRQL was measured using the Short Form-36 (median 1.7 years post-cancer-diagnosis). Multivariable linear regression was performed on each HRQL domain, separately for all cancers combined, major cancer sites, and cancer-free peers., Results: Higher optimism and social support were significantly associated with better HRQL across various domains in women with and without a cancer diagnosis (p < 0.05). Mean HRQL scores across all domains for all cancer sites were significantly higher among optimistic versus not optimistic women with cancer (p < 0.05). Adjusting for sociodemographic and other health conditions, lower optimism was associated with reduced scores across all domains, with greater reductions in mental health (adjusted mean difference (AMD) = -11.54, p < 0.01) followed by general health (AMD = -11.08, p < 0.01). Social support was less consistently related to HRQL scores, and following adjustment was only significantly associated with social functioning (AMD = -7.22, p < 0.01) and mental health (AMD = -6.34, p < 0.01)., Conclusions: Our findings highlight a strong connection between optimism, social support, and HRQL among cancer survivors. Providing psychosocial support and addressing behavioral and socioeconomic factors and other health conditions associated with optimism and social support may improve HRQL., (© 2024 The Authors. Asia‐Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.)

This is a protocol for a systematic review and meta-analysis of research on mental health outcomes of abortion. Does abortion increase the risk of adverse mental health outcomes? That is the central question for this review. Our review aims to inform policy and practice by locating, critically appraising, and synthesizing empirical evidence on associations between abortion and subsequent mental health outcomes. Given the controversies surrounding this topic and the complex social, political, legal, and ideological contexts in which research and reviews on abortion are conducted, it is especially important to conduct this systematic review and meta-analysis with comprehensive, rigorous, unbiased, and transparent methods. We will include a variety of study designs to enhance understanding of studies' methodological strengths and weaknesses and to identify potential explanations for conflicting results. We will follow open science principles, providing access to our methods, measures, and results, and making data available for re-analysis., (© 2024 The Authors. Campbell Systematic Reviews published by John Wiley & Sons Ltd on behalf of The Campbell Collaboration.)

While previous reviews found a positive association between pre-existing cancer diagnosis and COVID-19-related death, most early studies did not distinguish long-term cancer survivors from those recently diagnosed/treated, nor adjust for important confounders including age. We aimed to consolidate higher-quality evidence on risk of COVID-19-related death for people with recent/active cancer (compared to people without) in the pre-COVID-19-vaccination period. We searched the WHO COVID-19 Global Research Database (20 December 2021), and Medline and Embase (10 May 2023). We included studies adjusting for age and sex, and providing details of cancer status. Risk-of-bias assessment was based on the Newcastle-Ottawa Scale. Pooled adjusted odds or risk ratios (aORs, aRRs) or hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated using generic inverse-variance random-effects models. Random-effects meta-regressions were used to assess associations between effect estimates and time since cancer diagnosis/treatment. Of 23 773 unique title/abstract records, 39 studies were eligible for inclusion (2 low, 17 moderate, 20 high risk of bias). Risk of COVID-19-related death was higher for people with active or recently diagnosed/treated cancer (general population: aOR = 1.48, 95% CI: 1.36-1.61, I 2  = 0; people with COVID-19: aOR = 1.58, 95% CI: 1.41-1.77, I 2  = 0.58; inpatients with COVID-19: aOR = 1.66, 95% CI: 1.34-2.06, I 2  = 0.98). Risks were more elevated for lung (general population: aOR = 3.4, 95% CI: 2.4-4.7) and hematological cancers (general population: aOR = 2.13, 95% CI: 1.68-2.68, I 2  = 0.43), and for metastatic cancers. Meta-regression suggested risk of COVID-19-related death decreased with time since diagnosis/treatment, for example, for any/solid cancers, fitted aOR = 1.55 (95% CI: 1.37-1.75) at 1 year and aOR = 0.98 (95% CI: 0.80-1.20) at 5 years post-cancer diagnosis/treatment. In conclusion, before COVID-19-vaccination, risk of COVID-19-related death was higher for people with recent cancer, with risk depending on cancer type and time since diagnosis/treatment., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have the following interests to declare: MAB, BM, and JRS have been paid as expert scientists in the area of abortion and mental health in legal cases challenging abortion policies. NLS received reimbursement for travel expenses related to pro bono expert testimony. MAB, RWB, DGF, CBP, CHR, JRS, JVD, and UDU were awarded grants to conduct research or reviews on the relationship between abortion and mental health. LBH is a named plaintiff in a case regarding abortion rights (SisterSong v State of Georgia). NLS served on the board of directors of Physicians for Reproductive Health. TMO received a speaker fee from Lundbeck Pharma A/S for a talk on prediction of postpartum depression. The views expressed here are those of the authors and do not necessarily reflect those of their employers or other organisations. Provenance and peer review: Not commissioned; externally peer reviewed.

Background: Long-term projections of premature mortality (defined as deaths age <75 years) help to inform decisions about public health priorities. This study aimed to project premature mortality rates in Australia to 2044, and to estimate numbers of deaths and potential years of life lost (PYLL) due to premature mortality overall and for 59 causes., Methods: We examined the past trends in premature mortality rates using Australian mortality data by sex, 5-year age group and 5-year calendar period up to 2019. Cigarette smoking exposure data (1945-2019) were included to project lung cancer mortality. Age-period-cohort or generalised linear models were developed and validated for each cause to project premature mortality rates to 2044., Findings: Over the 25-year period from 1990-1994 to 2015-2019, there was a 44.4% decrease in the overall age-standardised premature mortality rate. This decline is expected to continue, from 162.4 deaths/100,000 population in 2015-2019 to 141.7/100,000 in 2040-2044 (12.7% decrease). Despite declining rates, total numbers of premature deaths are projected to increase by 22.8%, rising from 272,815 deaths in 2015-2019 to 334,894 deaths in 2040-2044. This is expected to result in 1.58 million premature deaths over the 25-year period 2020-2044, accounting for 24.5 million PYLL. Of the high-level cause categories, cancer is projected to remain the most common cause of premature death in Australia by 2044, followed by cardiovascular disease, external causes (including injury, poisoning, and suicide), and respiratory diseases., Interpretation: Despite continuously declining overall premature mortality rates, the total number of premature deaths in Australia is projected to remain substantial, and cancer will continue to be the leading cause. These projections can inform the targeting of public health efforts and can serve as benchmarks against which to measure the impact of future interventions. They emphasise the ongoing importance of accelerating the prevention, early detection, and treatment of key health conditions., Funding: No funding was provided for this study., Competing Interests: KC's research is funded by the National Health and Medical Research Council (NHMRC) of Australia (Fellowship APP1194679, Centre of Research Excellence in Cervical Cancer Control 1135172). KC is co-PI and MC is an investigator of an investigator-initiated trial of cervical screening, Compass, run by the Australian Centre for Prevention of Cervical Cancer (ACPCC), which is a government-funded not-for-profit charity; the ACPCC has received equipment and a funding contribution from Roche Molecular Diagnostics, and operational support from the Australian Government. KC is also co-PI on a major investigator-initiated implementation program Elimination of Cervical Cancer in the Western Pacific (ECCWP) which will receive support from the Minderoo Foundation, the Frazer Family Foundation and equipment donations from Cepheid Inc. Neither KC and MC nor their institution on their behalf receives direct or indirect funding from industry for any project. No other conflicts of interest are declared. The remaining authors declare that they have no conflicts of interest., (© 2023 The Author(s).)

Introduction: Despite growing calls for the explicit application of theory when designing behaviour change interventions, limited empirical evidence exists regarding the effectiveness of these methods compared to non-theoretical approaches. A cluster randomized controlled trial (Hide and Seek Project - HaSP) tested two implementation approaches for improving hereditary cancer referral practices with one key distinction: implementation strategies were designed based explicitly on psychological theory or based on stakeholder intuition. This study presents the detailed methods and resources used to facilitate this comparison, whilst examining the strategies generated through both approaches., Methods: Across seven Australian hospitals, clinical stakeholders attended focus groups to co-design site-specific strategies for improving Lynch syndrome referral. Co-design methods differed according to trial arm. Implementation strategy content was examined, with intuitively derived strategies retrospectively coded to determine theoretical alignment., Results: Fifty-one strategies were proposed across all sites (theory-based arm = 32, intuition-based arm = 19). Overall, nine behaviour change technique (BCT) categories were used on 77 occasions. In the theory-based trial arm, eight BCT categories were identified on 53 occasions; and five BCT categories on 24 occasions in the intuition-based arm. BCT categories were largely similar across both arms. After retrospectively coding intuitively derived strategies, 42% contained mechanistic links, thereby demonstrating theoretical alignment., Conclusion: Methods facilitated robust comparison of theoretical and intuitive approaches to implementation strategy design. Recognizing the known benefits of theory for enhancing scientific learning, applying these methods on a larger scale may provide definitive evidence about the comparative effectiveness of theoretical approaches., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Genetic referral for Lynch syndrome (LS) exemplifies complex clinical pathways. Identifying target behaviours (TBs) for change and associated barriers requires structured group consultation activities with busy clinicians - consolidating implementation activities whilst retaining rigour is crucial. This study aimed to: i) use process mapping to gain in-depth understandings of site-specific LS testing and referral practices in Australian hospitals and support identification of TBs for change, ii) explore if barriers to identified TBs could be identified through process mapping focus-group data, and iii) demonstrate pandemic-induced transition from in-person to virtual group interactive process mapping methods. LS clinical stakeholders attended interactive in-person or virtual focus groups to develop site-specific "process maps" visually representing referral pathways. Content analysis of transcriptions informed site-specific process maps, then clinical audit data was compared to highlight TBs for change. TBs were reviewed in follow-up focus groups. Secondary thematic analysis explored barriers to identified TBs, coded against the Theoretical Domains Framework (TDF). The transition from in-person to pandemic-induced virtual group interactive process mapping methods was documented. Process mapping highlighted six key areas of clinical practice variation across sites and site-specific TBs for change were identified. Key barriers to identified TBs emerged, categorised to seven TDF domains. Process mapping revealed variations in clinical practices surrounding LS referral between sites. Incorporating qualitative perspectives enhances process mapping by facilitating identification of TBs for change and barriers, providing a pathway to developing targeted interventions. Virtual process mapping activities produced detailed data and enabled comprehensive map development., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Behavioral Medicine.)

There is growing, but inconsistent evidence suggesting oestrogen may play a key role in lung cancer development, especially among never-smoking women for whom lung cancer risk factors remain largely elusive. Using the China Kadoorie Biobank, a large-scale prospective cohort with 302 510 women aged 30 to 79 years recruited from 10 regions in China during 2004 to 2008, we assessed the risk of lung cancer death among self-reported never-smoking women who were cancer-free at baseline, in relation to age at menarche, age at menopause, time since menopause, prior use of oral contraceptives (OCP), number of livebirths, breastfeeding and age at first livebirth. Women were followed up to December 31, 2016 with linkage to mortality data. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression, adjusting for key confounders including several socio-demographic, environmental and lifestyle factors. Among 287 408 never-smoking women, 814 died from lung cancer with a median follow-up of 10.3 years. Women who had used OCP within 15 years prior to baseline had a significantly higher hazard of lung cancer death compared with never-users: HR = 1.85 (95% CI: 1.14-3.00) and risk increased by 6% with each additional year of use: HR = 1.06 (1.01-1.10). Among parous women, the hazard of lung cancer death increased by 13% with each single livebirth: HR = 1.13 (1.05-1.23); and among post-menopausal women, the risk increased by 2% with each year since menopause: HR = 1.02 (1.01-1.04). These results suggest that reproductive factors which were proxies for lower endogenous oestrogen level, for example, longer duration of OCP use, could play a role in lung cancer development., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Purpose: To determine pathways to endometrial or ovarian cancer diagnosis by comparing health service utilization between cancer cases and matched cancer-free controls, using linked health records., Methods: From cancer registry records, we identified 238 incident endometrial and 167 ovarian cancer cases diagnosed during 2006-2013 in the Australian 45 and Up Study cohort (142,973 female participants). Each case was matched to four cancer-free controls on birthdate, sex, place of residence, smoking status, and body mass index. The use of relevant health services during the 13-18-, 7-12-, 0-6-, and 0-1-months pre-diagnosis for cases and the corresponding dates for their matched controls was determined through linkage with subsidized medical services and hospital records., Results: Healthcare utilization diverged between women with cancer and controls in the 0-6-months, particularly 0-1 months, pre-diagnosis. In the 0-1 months, 74.8% of endometrial and 50.3% of ovarian cases visited a gynecologist/gynecological oncologist, 11.3% and 59.3% had a CA125 test, 5.5% and 48.5% an abdominal pelvic CT scan, and 34.5% and 30.5% a transvaginal pelvic ultrasound, respectively (versus ≤ 1% of matched controls). Moreover, 25.1% of ovarian cancer cases visited an emergency department in the 0-1-months pre-diagnosis (versus 1.3% of matched controls), and GP visits were significantly more common for cases than controls in this period., Conclusion: Most women with endometrial or ovarian cancer accessed recommended specialists and tests in the 0-1-months pre-diagnosis, but a high proportion of women with ovarian cancer visited an emergency department. This reinforces the importance of timely specialist referral., (© 2022. The Author(s).)

A long standing challenge in biological and artificial intelligence is to understand how new knowledge can be constructed from known building blocks in a way that is amenable for computation by neuronal circuits. Here we focus on the task of storage and recall of structured knowledge in long-term memory. Specifically, we ask how recurrent neuronal networks can store and retrieve multiple knowledge structures. We model each structure as a set of binary relations between events and attributes (attributes may represent e.g., temporal order, spatial location, role in semantic structure), and map each structure to a distributed neuronal activity pattern using a vector symbolic architecture scheme.We then use associative memory plasticity rules to store the binarized patterns as fixed points in a recurrent network. By a combination of signal-to-noise analysis and numerical simulations, we demonstrate that our model allows for efficient storage of these knowledge structures, such that the memorized structures as well as their individual building blocks (e.g., events and attributes) can be subsequently retrieved from partial retrieving cues. We show that long-term memory of structured knowledge relies on a new principle of computation beyond the memory basins. Finally, we show that our model can be extended to store sequences of memories as single attractors., (© 2022. The Author(s).)

Rationale: Household air pollution and secondhand tobacco smoke are known carcinogens for lung cancer, but large-scale estimates of the relationship with lung cancer mortality are lacking. Objectives: Using the large-scale cohort China Kadoorie Biobank, we prospectively investigated associations between these two risk factors and lung cancer death among never-smokers. Methods: The Biobank recruited 512,715 adults aged 30-79 years from 10 regions in China during 2004-2008. Self-reported never-smoking participants were followed up to December 31, 2016, with linkage to mortality data. Total duration of exposure to household air pollution was calculated from self-reported domestic solid fuel use. Exposure to secondhand tobacco smoke was ascertained using exposure at home and/or other places. Hazard ratios and 95% confidence intervals for associations between these two exposures and lung cancer death were estimated using Cox regression, adjusting for key confounders. Measurements and Main Results: There were 979 lung cancer deaths among 323,794 never-smoking participants without a previous cancer diagnosis during 10.2 years of follow-up. There was a log-linear positive association between exposure to household air pollution and lung cancer death, with a 4% increased risk per 5-year increment of exposure (hazard ratio = 1.04; 95% confidence interval = 1.01-1.06; P trend = 0.0034), and participants with 40.1-50.0 years of exposure had the highest risk compared with the never-exposed (hazard ratio = 1.53; 95% confidence interval = 1.13-2.07). The association was largely consistent across various subgroups. No significant association was found between secondhand smoke and lung cancer death. Conclusions: This cohort study provides new prospective evidence suggesting that domestic solid fuel use is associated with lung cancer death among never-smokers.

Recognition of RNA by receptors of the innate immune system is regulated by various posttranslational modifications. Different single 2'-O-ribose (2'-O-) methylations have been shown to convert TLR7/TLR8 ligands into specific TLR8 ligands, so we investigated whether the position of 2'-O-methylation is crucial for its function. To this end, we designed different 2'-O-methylated RNA oligoribonucleotides (ORN), investigating their immune activity in various cell systems and analyzing degradation under RNase T2 treatment. We found that the 18S rRNA-derived TLR7/8 ligand, RNA63, was differentially digested as a result of 2'-O-methylation, leading to variations in TLR8 and TLR7 inhibition. The suitability of certain 2'-O-methylated RNA63 derivatives as TLR8 agonists was further demonstrated by the fact that other RNA sequences were only weak TLR8 agonists. We were thus able to identify specific 2'-O-methylated RNA derivatives as optimal TLR8 ligands.

Background: Overweight and obesity is a growing public health issue as it contributes to the future burden of obesity-related diseases, including cancer, especially in high-income countries. In Australia, 4.3% of all cancers diagnosed in 2013 were attributable to overweight and obesity. Our aim was to examine Australian age-specific incidence trends over the last 35 years for obesity-related cancers based on expert review (colorectal, liver, gallbladder, pancreas, breast in postmenopausal women, uterine, ovary, kidney, thyroid, and multiple myeloma) individually and pooled., Methods: Australian incidence data for 10 obesity-related cancers among people aged 25-84 years, diagnosed from 1983 to 2017, were obtained from the Australian Cancer Database. We used age-period-cohort modelling and joinpoint analysis to assess trends, estimating incidence rate ratios (IRR) by birth-cohort for each individual cancer and pooled, and the annual percentage change. The analyses were also conducted for non-obesity-related cancers over the same period., Findings: The total number of cancers where some proportion is obesity-related, diagnosed from 1983-2017, was 1,005,933. This grouping was 34.7% of cancers diagnosed. The IRR of obesity-related cancers increased from 0.77 (95% CI 0.73, 0.81) for the 1903 birth-cohort to 2.95 (95% CI 2.58, 3.38) for the recent 1988 cohort relative to the 1943 cohort. The IRRs of non-obesity related cancers were stable with non-significant decreases in younger cohorts. These trends were broadly similar across sex and age groups., Interpretation: The incidence of obesity-related cancers in Australia has increased by birth-cohort across all age-groups, which should be monitored. Obesity, a public health epidemic, needs to be addressed through increased awareness, policy support and evidence-based interventions., Funding: This research received no specific funding., Competing Interests: The Daffodil Centre has received competitive grant and contract funding for non-related projects from the Australian National Health and Medical Research Council (NHMRC), the Australian Department of Health and Cancer Council Australia that include Dr Eleonora Feletto, Mr Paul Grogan and Professor Karen Canfell. Dr Eleonora Feletto received honoraria for presentations at the Japanese Cancer Association Conference and the APEC Regional Workshop on Capacity Building of Cancer Prevention and Control. Dr David Mizrahi has received a Fullbright Association Fellowship. Ms Clare Hughes has received funding through nib Healthsmart and NHMRC, the latter in collaboration with the University of Wollongong. Professor Karen Canfell is co-PI of an investigator-initiated trial of cervical screening, “Compass”, run by the Australian Centre for Prevention of Cervical Cancer (ACPCC), which is a government-funded not-for-profit charity. Compass receives infrastructure support from the Australian government and the ACPCC has received equipment and a funding contribution from Roche Molecular Diagnostics, USA. She is also co-PI on a major implementation program Elimination of Cervical Cancer in the Western Pacific which has received support from the Minderoo Foundation and the Frazer Family Foundation and equipment donations from Cepheid Inc., (© 2022 The Author(s).)

Background: The early COVID-19 literature suggested that people with cancer may be more likely to be infected with SARS-CoV-2 or develop COVID-19 than people without cancer, due to increased health services contact and/or immunocompromise. While some studies were criticised due to small patient numbers and methodological limitations, they created or reinforced concerns of clinicians and people with cancer. These risks are also important in COVID-19 vaccine prioritisation decisions. We performed a systematic review to critically assess and summarise the early literature., Methods and Findings: We conducted a systematic search of Medline/Embase/BioRxiv/MedRxiv/SSRN databases including peer-reviewed journal articles, letters/commentaries, and non-peer-reviewed pre-print articles for 1 January-1 July 2020. The primary endpoints were diagnosis of COVID-19 and positive SARS-CoV-2 test. We assessed risk of bias using a tool adapted from the Newcastle-Ottawa Scale. Twelve studies were included in the quantitative synthesis. All four studies of COVID-19 incidence (including 24,181,727 individuals, 125,649 with pre-existing cancer) reported that people with cancer had higher COVID-19 incidence rates. Eight studies reported SARS-CoV-2 test positivity for > 472,000 individuals, 48,370 with pre-existing cancer. Seven of these studies comparing people with any and without cancer, were pooled using random effects [pooled odds ratio 0.91, 95 %CI: 0.57-1.47; unadjusted for age, sex, or comorbidities]. Two studies suggested people with active or haematological cancer had lower risk of a positive test. All 12 studies had high risk of bias; none included universal or random COVID-19/SARS-CoV-2 testing., Conclusions: The early literature on susceptibility to SARS-CoV-2/COVID-19 for people with cancer is characterised by pervasive biases and limited data. To provide high-quality evidence to inform decision-making, studies of risk of SARS-CoV-2/COVID-19 for people with cancer should control for other potential modifiers of infection risk, including age, sex, comorbidities, exposure to the virus, protective measures taken, and vaccination, in addition to stratifying analyses by cancer type, stage at diagnosis, and treatment received., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Early reports suggested that COVID-19 patients with cancer were at higher risk of COVID-19-related death. We conducted a systematic review with risk of bias assessment and synthesis of the early evidence on the risk of COVID-19-related death for COVID-19 patients with and without cancer., Methods and Findings: We searched Medline/Embase/BioRxiv/MedRxiv/SSRN databases to 1 July 2020. We included cohort or case-control studies published in English that reported on the risk of dying after developing COVID-19 for people with a pre-existing diagnosis of any cancer, lung cancer, or haematological cancers. We assessed risk of bias using tools adapted from the Newcastle-Ottawa Scale. We used the generic inverse-variance random-effects method for meta-analysis. Pooled odds ratios (ORs) and hazard ratios (HRs) were calculated separately. Of 96 included studies, 54 had sufficient non-overlapping data to be included in meta-analyses (>500,000 people with COVID-19, >8000 with cancer; 52 studies of any cancer, three of lung and six of haematological cancers). All studies had high risk of bias. Accounting for at least age consistently led to lower estimated ORs and HRs for COVID-19-related death in cancer patients (e.g. any cancer versus no cancer; six studies, unadjusted OR=3.30,95%CI:2.59-4.20, adjusted OR=1.37,95%CI:1.16-1.61). Adjusted effect estimates were not reported for people with lung or haematological cancers. Of 18 studies that adjusted for at least age, 17 reported positive associations between pre-existing cancer diagnosis and COVID-19-related death (e.g. any cancer versus no cancer; nine studies, adjusted OR=1.66,95%CI:1.33-2.08; five studies, adjusted HR=1.19,95%CI:1.02-1.38)., Conclusions: The initial evidence (published to 1 July 2020) on COVID-19-related death in people with cancer is characterised by multiple sources of bias and substantial overlap between data included in different studies. Pooled analyses of non-overlapping early data with adjustment for at least age indicated a significantly increased risk of COVID-19-related death for those with a pre-existing cancer diagnosis., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: Afghanistan is one of the countries with the highest prevalence of spousal violence (56%) and a low prevalence of contraceptive use (23%), yet there is no study assessing how spousal violence is related to contraceptive use, and what methods are most used by women. Therefore, this study examined the association between the number of types of spousal violence and contraceptive use., Method: Using data from 18,985 Afghan married women, aged 15 to 49, who responded to the 2015 Afghanistan Demographic and Health Survey, the current contraceptive method was grouped into five categories: male-involved methods, pills, injectables, long-acting reversible contraception, female sterilization, and Lactation Amenorrhea Method. The number of types of spousal violence in the past 12 months was categorized as none, one type, or two or more types, based on women's experiences with verbal, physical, and sexual violence. For analysis, binary and multinomial logistic regression were used., Results: After adjusting for the covariates, the experience of any spousal violence was associated with contraception use (adjusted odds ratio (aOR) = 1.93, 95% CI: 1.64-2.27, p = 0.0001). Among those using contraception, experiencing two or three types of spousal violence was associated with using pills (adjusted risk ratio (aRRR) = 2.12, 95% CI: 1.63-2.77, p = 0.0001), injections (aRRR = 1.75, 95% CI: 1.26-2.41, p = 0.001), and LAM (aRRR = 3.27, 95% CI: 2.05-5.20, p = 0.0001), compared to male-involved methods., Conclusions: The findings of this study may inform policymakers and program implementers in designing interventions to address the pervasive problem of violence against women, and make pills and injectables more accessible to Afghan women, since these methods are under women's control and more often used in Afghanistan.

Background: Long-term projections of cancer incidence and mortality estimate the future burden of cancer in a population, and can be of great use in informing the planning of health services and the management of resources. We aimed to estimate incidence and mortality rates and numbers of new cases and deaths up until 2044 for all cancers combined and for 21 individual cancer types in Australia. We also illustrate the potential effect of treatment delays due to the COVID-19 pandemic on future colorectal cancer mortality rates., Methods: In this statistical modelling study, cancer incidence and mortality rates in Australia from 2020 to 2044 were projected based on data up to 2017 and 2019, respectively. Cigarette smoking exposure (1945-2019), participation rates in the breast cancer screening programme (1996-2019), and prostate-specific antigen testing rates (1994-2020) were included where relevant. The baseline projection model using an age-period-cohort model or generalised linear model for each cancer type was selected based on model fit statistics and validation with pre-COVID-19 observed data. To assess the impact of treatment delays during the COVID-19 pandemic on colorectal cancer mortality, we obtained data on incidence, survival, prevalence, and cancer treatment for colorectal cancer from different authorities. The relative risks of death due to system-caused treatment delays were derived from a published systematic review. Numbers of excess colorectal cancer deaths were estimated using the relative risk of death per week of treatment delay and different durations of delay under a number of hypothetical scenarios., Findings: Projections indicate that in the absence of the COVID-19 pandemic effects, the age-standardised incidence rate for all cancers combined for males would decline over 2020-44, and for females the incidence rate would be relatively stable in Australia. The mortality rates for all cancers combined for both males and females are expected to continuously decline during 2020-44. The total number of new cases are projected to increase by 47·4% (95% uncertainty interval [UI] 35·2-61·3) for males, from 380 306 in 2015-19 to 560 744 (95% UI 514 244-613 356) in 2040-44, and by 54·4% (95% UI 40·2-70·5) for females, from 313 263 in 2015-19 to 483 527 (95% UI 439 069-534 090) in 2040-44. The number of cancer deaths are projected to increase by 36·4% (95% UI 15·3-63·9) for males, from 132 440 in 2015-19 to 180 663 (95% UI 152 719-217 126) in 2040-44, and by 36·6% (95% UI 15·8-64·1) for females, from 102 103 in 2015-19 to 139 482 (95% UI 118 186-167 527) in 2040-44, due to population ageing and growth. The example COVID-19 pandemic scenario of a 6-month health-care system disruption with 16-week treatment delays for colorectal cancer patients could result in 460 (95% UI 338-595) additional deaths and 437 (95% UI 314-570) deaths occurring earlier than expected in 2020-44., Interpretation: These projections can inform health service planning for cancer care and treatment in Australia. Despite the continuous decline in cancer mortality rates, and the decline or plateau in incidence rates, our projections suggest an overall 51% increase in the number of new cancer cases and a 36% increase in the number of cancer deaths over the 25-year projection period. This means that continued efforts to increase screening uptake and to control risk factors, including smoking exposure, obesity, physical inactivity, alcohol use, and infections, must remain public health priorities., Funding: Partly funded by Cancer Council Australia., Competing Interests: Declaration of interests KC is co-principal investigator of an investigator-initiated trial of cervical screening, Compass, run by the Australian Centre for Prevention of Cervical Cancer (ACPCC), which is a government-funded not-for-profit charity; the ACPCC has received equipment and a funding contribution from Roche Molecular Diagnostics, and operational support from the Australian Government. KC is also co-principal investigator on a major investigator-initiated implementation programme Elimination of Cervical Cancer in the Western Pacific (ECCWP) which will receive support from the Minderoo Foundation, the Frazer Family Foundation, and equipment donations from Cepheid. Neither KC nor her institution on her behalf receives direct funding from industry for any project. MC is an investigator on an investigator-initiated trial of cytology and primary human papillomavirus screening in Australia (Compass; ACTRN12613001207707 and NCT02328872), which is conducted and funded by the Australian Centre for the Prevention of Cervical Cancer, a government-funded health promotion charity. The Australian Centre for the Prevention of Cervical Cancer has received equipment and a funding contribution for the Compass trial from Roche Molecular Systems and operational support from the Australian Government. However neither MC nor his institution on his behalf (the Daffodil Centre, a joint venture between Cancer Council NSW and The University of Sydney) receive direct funding from industry for Compass Australia or any other project. All other authors declare no competing interests., (Copyright © 2022 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: To inform effective genomic medicine strategies, it is important to examine current approaches and gaps in well-established applications. Lynch syndrome (LS) causes 3-5% of colorectal cancers (CRCs). While guidelines commonly recommend LS tumour testing of all CRC patients, implementation in health systems is known to be highly variable. To provide insights on the heterogeneity in practice and current bottlenecks in a high-income country with universal healthcare, we characterise the approaches and gaps in LS testing and referral in seven Australian hospitals across three states., Methods: We obtained surgery, pathology, and genetics services data for 1,624 patients who underwent CRC resections from 01/01/2017 to 31/12/2018 in the included hospitals., Results: Tumour testing approaches differed between hospitals, with 0-19% of patients missing mismatch repair deficiency test results (total 211/1,624 patients). Tumour tests to exclude somatic MLH1 loss were incomplete at five hospitals (42/187 patients). Of 74 patients with tumour tests completed appropriately and indicating high risk of LS, 36 (49%) were missing a record of referral to genetics services for diagnostic testing, with higher missingness for older patients (0% of patients aged ≤ 40 years, 76% of patients aged > 70 years). Of 38 patients with high-risk tumour test results and genetics services referral, diagnostic testing was carried out for 25 (89%) and identified a LS pathogenic/likely pathogenic variant for 11 patients (44% of 25; 0.7% of 1,624 patients)., Conclusions: Given the LS testing and referral gaps, further work is needed to identify strategies for successful integration of LS testing into clinical care, and provide a model for hereditary cancers and broader genomic medicine. Standardised reporting may help clinicians interpret tumour test results and initiate further actions., (© 2022. The Author(s).)

Background: Globally, tobacco smoking remains the largest preventable cause of premature death. The COVID-19 pandemic has forced nations to take unprecedented measures, including 'lockdowns' that might impact tobacco smoking behaviour. We performed a systematic review and meta-analyses to assess smoking behaviour changes during the early pre-vaccination phases of the COVID-19 pandemic in 2020., Methods: We searched Medline/Embase/PsycINFO/BioRxiv/MedRxiv/SSRN databases (January-November 2020) for published and pre-print articles that reported specific smoking behaviour changes or intentions after the onset of the COVID-19 pandemic. We used random-effects models to pool prevalence ratios comparing the prevalence of smoking during and before the pandemic, and the prevalence of smoking behaviour changes during the pandemic. The PROSPERO registration number for this systematic review was CRD42020206383., Findings: 31 studies were included in meta-analyses, with smoking data for 269,164 participants across 24 countries. The proportion of people smoking during the pandemic was lower than that before, with a pooled prevalence ratio of 0·87 (95%CI:0·79-0·97). Among people who smoke, 21% (95%CI:14-30%) smoked less, 27% (95%CI:22-32%) smoked more, 50% (95%CI:41%-58%) had unchanged smoking and 4% (95%CI:1-9%) reported quitting smoking. Among people who did not smoke, 2% (95%CI:1-3%) started smoking during the pandemic. Heterogeneity was high in all meta-analyses and so the pooled estimates should be interpreted with caution ( I 2 >91% and p -heterogeneity<0·001). Almost all studies were at high risk of bias due to use of non-representative samples, non-response bias, and utilisation of non-validated questions., Interpretation: Smoking behaviour changes during the first phases of the COVID-19 pandemic in 2020 were highly mixed. Meta-analyses indicated that there was a relative reduction in overall smoking prevalence during the pandemic, while similar proportions of people who smoke smoked more or smoked less, although heterogeneity was high. Implementation of evidence-based tobacco control policies and programs, including tobacco cessation services, have an important role in ensuring that the COVID-19 pandemic does not exacerbate the smoking pandemic and associated adverse health outcomes., Funding: No specific funding was received for this study., Competing Interests: KC is co-PI of an investigator-initiated trial of cervical screening, Compass, run by the VCS Foundation, which is a government-funded not-for-profit charity; the VCS Foundation has received equipment and a funding contribution from Roche Molecular Diagnostics. She is also co-PI on a major investigator-initiated implementation program Elimination of Cervical Cancer in the Western Pacific (ECCWP) which will receive support from the Minderoo Foundation, the Frazer Family Foundation and equipment donations from Cepheid Inc. Neither KC nor her institution on her behalf receives direct funding from industry for any project. KC's research is supported via a National Health and Research Council Australia Leadership Fellowship (NHMRC; APP1194679). KC chairs and participates in a number of advisory committees to government and not-for-profit agencies; no committee participation for commercial companies. MC is an investigator on an investigator-initiated trial of cytology and primary HPV screening in Australia (‘Compass’) (ACTRN12613001207707 and NCT02328872), which is conducted and funded by the VCS Foundation a government-funded not-for-profit charity. The VCS Foundation has received equipment and a funding contribution for the Compass trial from Roche Molecular Systems. However neither MC nor his institution on his behalf (The Daffodil Centre, a joint venture between Cancer Council NSW and The University of Sydney) receive direct or indirect funding from industry for Compass Australia or any other project. MW's institution (The Daffodil Centre) received competitive grant and contract funding from the Australian Government for various projects outside the submitted work on which she is a named investigator, and received an honorarium from scientific meeting organisers for a presentation outside the submitted work. Where authors are identified as personnel of the International Agency for Research on Cancer or World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer or World Health Organization. The opinions expressed in this article are the authors own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States Government., (© 2022 Published by Elsevier Ltd.)

Lung cancer is the leading cause of cancer-related mortality globally, accounting for 1.8 million deaths in 2020. While the vast majority are caused by tobacco smoking, 15%-25% of all lung cancer cases occur in lifelong never-smokers. The International Agency for Research on Cancer (IARC) has classified multiple agents with sufficient evidence for lung carcinogenesis in humans, which include tobacco smoking, as well as several environmental exposures such as radon, second-hand tobacco smoke, outdoor air pollution, household combustion of coal and several occupational hazards. However, the IARC evaluation had not been stratified based on smoking status, and notably lung cancer in never-smokers (LCINS) has different epidemiological, clinicopathologic and molecular characteristics from lung cancer in ever-smokers. Among several risk factors proposed for the development of LCINS, environmental factors have the most available evidence for their association with LCINS and their roles cannot be overemphasized. Additionally, while initial genetic studies largely focused on lung cancer as a whole, recent studies have also identified genetic risk factors for LCINS. This article presents an overview of several environmental factors associated with LCINS, and some of the emerging evidence for genetic factors associated with LCINS. An increased understanding of the risk factors associated with LCINS not only helps to evaluate a never-smoker's personal risk for lung cancer, but also has important public health implications for the prevention and early detection of the disease. Conclusive evidence on causal associations could inform longer-term policy reform in a range of areas including occupational health and safety, urban design, energy use and particle emissions, and the importance of considering the impacts of second-hand smoke in tobacco control policy., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (Copyright ©2021Chinese Journal of Cancer Research. All rights reserved.)

Objective: We examined whether contraceptive method type, satisfaction with use, and confidence in correct use were independently associated with switching intentions, a precursor of switching behaviors., Study Design: Data were from a probability-based sample survey carried out in Delaware and Maryland in 2016 and 2017 among women ages 18 to 44. Women's current contraceptive methods were classified into 5 categories: coitally-dependent methods (barrier methods, withdrawal, and natural family planning); oral contraceptive pills, patches, and rings; injections; implants; and intrauterine contraception (IUC). Satisfaction, confidence, and switching intentions were dichotomized into being very versus less satisfied, being completely versus less confident, and having very low versus not very low switching intentions. We conducted binomial logistic regression to examine whether method type, satisfaction, and confidence were independently associated with having very low switching intentions, adjusting for a range of covariates including sociodemographics, perceived health, religious attendance frequency, sexual, contraceptive, and reproductive experiences, and state of residence (Maryland or Delaware)., Results: Among 1,077 women using reversible contraception, those using IUC relative to implants, pills, patches, or rings, and coitally-dependent methods were more likely to have very low switching intentions. Among all survey respondents, those who were very satisfied and those who were completely confident in correct use were also more likely to report very low switching intentions., Conclusions: Using IUC, being very satisfied, and being very confident in correct use were independently associated with having very low switching intentions., Implications: These results suggest that those using IUC have very low intentions to switch for reasons in addition to satisfaction-level with their method. Other aspects of using IUC such as ease of use, perceived barriers to switching, or having very low switching intentions before beginning IUC may be such reasons., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Osteoarthritis causes pain and functional disability for over 500 million people worldwide. To develop disease-stratifying tools and modifying therapies, we need a better understanding of the molecular basis of the disease in relevant tissue and cell types. Here, we study primary cartilage and synovium from 115 patients with osteoarthritis to construct a deep molecular signature map of the disease. By integrating genetics with transcriptomics and proteomics, we discover molecular trait loci in each tissue type and omics level, identify likely effector genes for osteoarthritis-associated genetic signals and highlight high-value targets for drug development and repurposing. These findings provide insights into disease aetiopathology, and offer translational opportunities in response to the global clinical challenge of osteoarthritis.

Exposures to cancer risk factors such as smoking and alcohol are not mutually independent. We aimed to identify risk factor exposure patterns and their associations with sociodemographic characteristics and cancer incidence. We considered 120,771 female and, separately, 100,891 male participants of the Australian prospective cohort 45 and Up Study. Factor analysis grouped 36 self-reported variables into 8 combined factors each for females (largely representing 'smoking', 'alcohol', 'vigorous exercise', 'age at childbirth', 'Menopausal Hormone Therapy', 'parity and breastfeeding', 'standing/sitting', 'fruit and vegetables') and males (largely representing 'smoking', 'alcohol', 'vigorous exercise', 'urology and health', 'moderate exercise', 'standing/sitting', 'fruit and vegetables', 'meat and BMI'). Associations with cancer incidence were investigated using multivariable logistic regression (4-8 years follow-up: 6193 females, 8749 males diagnosed with cancer). After multiple-testing correction, we identified 10 associations between combined factors and cancer incidence for females and 6 for males, of which 14 represent well-known relationships (e.g. bowel cancer: females 'smoking' factor Odds Ratio (OR) 1.16 (95% Confidence Interval (CI) 1.08-1.25), males 'smoking' factor OR 1.15 (95% CI 1.07-1.23)), providing evidence for the validity of this approach. The catalogue of associations between exposure patterns, sociodemographic characteristics, and cancer incidence can help inform design of future studies and targeted prevention programmes.

Osteoarthritis causes debilitating pain and disability, resulting in a considerable socioeconomic burden, yet no drugs are available that prevent disease onset or progression. Here, we develop, validate and use rapid-throughput imaging techniques to identify abnormal joint phenotypes in randomly selected mutant mice generated by the International Knockout Mouse Consortium. We identify 14 genes with functional involvement in osteoarthritis pathogenesis, including the homeobox gene Pitx1, and functionally characterize 6 candidate human osteoarthritis genes in mouse models. We demonstrate sensitivity of the methods by identifying age-related degenerative joint damage in wild-type mice. Finally, we phenotype previously generated mutant mice with an osteoarthritis-associated polymorphism in the Dio2 gene by CRISPR/Cas9 genome editing and demonstrate a protective role in disease onset with public health implications. We hope this expanding resource of mutant mice will accelerate functional gene discovery in osteoarthritis and offer drug discovery opportunities for this common, incapacitating chronic disease.