The myometrial-cervical ratio: Can a simple sonographic measurement improve diagnosis of adenomyosis in a regional setting?

Introduction: Adenomyosis is histologically defined by the presence of endometrial glands and stroma in the myometrium. Ultrasound findings of adenomyosis are being redefined to better diagnose adenomyosis pre-operatively. Methods: A single-centre retrospective study was performed at a regional hospital. The myometrial-cervical ratio was calculated on pre-operative ultrasounds, and histopathology reviewed for each case. Logistic regression was used to estimate the association between the myometrial-cervical ratio and adenomyosis confirmed on histopathology, and the area under the receiver operating characteristic curve was calculated. Comparisons were performed based on the presence of fibroids on ultrasound. Results: Complete data were available for 136 benign hysterectomies between 1 January 2015 and 31 December 2020. When the myometrial-cervical ratio was treated as a continuous variable in a logistic regression of adenomyosis on histopathology, there was no statistical evidence (χ2(1) < 0.01, p = 0.98) of an association. When cases including fibroids in the myometrial-cervical ratio were excluded, there was a non-significant association between myometrial-cervical ratio and adenomyosis on histopathology (odds ratio = 3.435, 95% confidence interval = 0.964, 12.235; χ2(1) = 3.62, p = 0.057); area under the receiver operating characteristic = 0.637 (95% confidence interval = 0.504, 0.770). The optimal myometrial-cervical ratio cutpoint was 1.875 (95% confidence interval = 1.698, 2.051), which achieved 71.43% sensitivity and 60.00% specificity. There was strong statistical evidence (χ2(1) = 9.02, p = 0.003) that the myometrial-cervical ratio outperformed standard pre-operative ultrasound identification of adenomyosis. Conclusion: While accuracy remains suboptimal, the myometrial-cervical ratio outperformed standard ultrasound diagnostic features of adenomyosis in a regional setting. The myometrial-cervical ratio may offer a simple imaging measurement for adenomyosis in inexperienced hands when fibroids are absent.

Randomized Trial of Information for Older Women About Cessation of Breast Cancer Screening Invitations.

BACKGROUND: Older women receive no information about why Australia's breast screening program (BreastScreen) invitations cease after 74 years. We tested how providing older women with the rationale for breast screening cessation impacted informed choice (adequate knowledge; screening attitudes aligned with intention). METHODS: In a three-arm online randomized trial, eligible participants were females aged 70-74 years who had recently participated in breast screening (within 5 years), without personal breast cancer history, recruited through Qualtrics. Participants read a hypothetical scenario in which they received a BreastScreen letter reporting no abnormalities on their mammogram. They were randomized to receive the letter: (1) without any rationale for screening cessation (control); (2) with screening cessation rationale in printed-text form (e.g., downsides of screening outweigh the benefits after age 74); or (3) with screening cessation rationale presented in an animation video form. The primary outcome was informed choice about continuing/stopping breast screening beyond 74 years. RESULTS: A total of 376 participant responses were analyzed. Compared to controls (n = 122), intervention arm participants (text [n = 132] or animation [n = 122]) were more likely to make an informed choice (control 18.0%; text 32.6%, p = .010; animation 40.5%, p < .001). Intervention arm participants had more adequate knowledge (control 23.8%; text 59.8%, p < .001; animation 68.9%, p < .001), lower screening intentions (control 17.2%; text 36.4%, p < .001; animation 49.2%, p < .001), and fewer positive screening attitudes regarding screening for themselves in the animation arm, but not in the text arm (control 65.6%; text 51.5%, p = .023; animation 40.2%, p < .001). CONCLUSIONS: Providing information to older women about the rationale for breast cancer screening cessation increased informed decision-making in a hypothetical scenario. This study is an important first step in improving messaging provided by national cancer screening providers direct to older adults. Further research is needed to assess the impact of different elements of the intervention and the impact of providing this information in clinical practice, with more diverse samples. TRIAL REGISTRATION: ANZCTRN12623000033640.

Screening for cancer beyond recommended upper age limits: views and experiences of older people.

BACKGROUND: Internationally, screening programmes and clinical practice guidelines recommend when older adults should stop cancer screening using upper age limits, but it is unknown how older adults view these recommendations. OBJECTIVE: To examine older adults' views and experiences about continuing or stopping cancer screening beyond the recommended upper age limit for breast, cervical, prostate and bowel cancer. DESIGN: Qualitative, semi-structured interviews. SETTING: Australia, telephone. SUBJECTS: A total of 29 community-dwelling older adults (≥70-years); recruited from organisation newsletters, mailing lists and Facebook advertisements. METHODS: Interviews were audio-recorded, transcribed and analysed thematically using Framework Analysis. RESULTS: Firstly, older adults were on a spectrum between trusting recommendations and actively deciding about cancer screening, with some who were uncertain. Secondly, participants reported limited in-depth discussions with health professionals about cancer screening. In primary care, discussions were focused on checking they were up to date with screening or going over results. Discussions mostly only occurred if older adults initiated themselves. Finally, participants had a socially- and self-constructed understanding of screening recommendations and potential outcomes. Perceived reasons for upper age limits were cost, reduced cancer risk or ageism. Risks of screening were understood in relation to their own social experiences (e.g. shared stories about friends with adverse outcomes of cancer treatment or conversations with friends/family about controversy around prostate screening). CONCLUSIONS: Direct-to-patient information and clinician support may help improve communication about the changing benefit to harm ratio of cancer screening with increasing age and increase understanding about the rationale for an upper age limit for cancer screening programmes.

Psychosocial outcomes and health service use after notifying women participating in population breast screening when they have dense breasts: a BreastScreen Queensland randomised controlled trial.

BACKGROUND: Robust evidence regarding the benefits and harms of notifying Australian women when routine breast screening identifies that they have dense breasts is needed for informing future mammography population screening practice and policy. OBJECTIVES: To assess the psychosocial and health services use effects of notifying women participating in population-based breast cancer screening that they have dense breasts; to examine whether the mode of communicating this information about its implications (print, online formats) influences these effects. METHODS AND ANALYSIS: The study population comprises women aged 40 years or older who attend BreastScreen Queensland Sunshine Coast services for mammographic screening and are found to have dense breasts (BI-RADS density C or D). The randomised controlled trial includes three arms (952 women each): standard BreastScreen care (no notification of breast density; control arm); notification of dense breasts in screening results letter and print health literacy-sensitive information (intervention arm 1) or a link or QR code to online video-based health literacy-sensitive information (intervention arm 2). Baseline demographic data will be obtained from BreastScreen Queensland. Outcomes data will be collected in questionnaires at baseline and eight weeks, twelve months, and 27 months after breast screening. Primary outcomes will be psychological outcomes and health service use; secondary outcomes will be supplemental screening outcomes, cancer worry, perceived breast cancer risk, knowledge about breast density, future mammographic screening intentions, and acceptability of notification about dense breasts. ETHICS APPROVAL: Gold Coast Hospital and Health Service Ethics Committee (HREC/2023/QGC/89770); Sunshine Coast Hospital and Health Service Research Governance and Development (SSA/2023/QSC/89770). DISSEMINATION OF FINDINGS: Findings will be reported in peer-reviewed journals and at national and international conferences. They will also be reported to BreastScreen Queensland, BreastScreen Australia, Cancer Australia, and other bodies involved in cancer care and screening, including patient and support organisations. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12623000001695p (prospective: 9 January 2023).

Understanding the Relationship between Illness Perceptions and Health Behaviour among Women with Polycystic Ovary Syndrome.

This paper aims to delineate the cognitive, emotional, and behavioural responses of women with polycystic ovary syndrome (PCOS) to their illness by applying the Common-Sense Model of Self-Regulation (CSM) to their health behaviour. An online cross-sectional design was used to examine the relationship between participants' illness perceptions (illness identity, consequence, timeline, control, and cause) and emotional representations of their PCOS, and their health behaviours (diet, physical activity, and risky contraceptive behaviour). The participants were 252 women between the ages of 18 and 45 years, living in Australia, and self-reporting a diagnosis of PCOS, recruited through social media. Participants completed an online questionnaire regarding illness perceptions as well as their diet, physical activity, and risky contraceptive behaviour. Illness identity was positively associated with the number of maladaptive dietary practices (B = 0.71, 95% CI: 0.003, 0.138; p = 0.04), and perception of longer illness duration was associated with reduced physical activity (OR = 0.898, 95% CI: 0.807, 0.999; p = 0.49) and risky contraceptive behaviour (OR = 0.856, 95% CI: 0.736, 0.997; p = 0.045). The limitations of the study include all data being self-reported (including PCOS diagnosis), and the potential for analyses of physical activity and risky contraceptive use being underpowered due to reduced sample sizes. The sample was also highly educated and restricted to those who use social media. These findings suggest that illness perceptions may play a role in influencing health behaviour in women with PCOS. A better understanding of the illness perceptions of women with PCOS is needed to increase health-promoting behaviour and improve health outcomes for women with PCOS.

Factors Influencing Primary Care Practitioners' Cancer Screening Recommendations for Older Adults: a Systematic Review.

BACKGROUND: Primary care practitioners (PCPs) play a key role in cancer screening decisions for older adults (≥ 65 years), but recommendations vary by cancer type and jurisdiction. PURPOSE: To examine the factors influencing PCPs' recommendations for breast, cervical, prostate, and colorectal cancer screening for older adults. DATA SOURCES: MEDLINE, Pre-Medline, EMBASE, PsycINFO, and CINAHL, searched from 1 January 2000 to July 2021, and citation searching in July 2022. STUDY SELECTION: Assessed factors influencing PCPs' breast, prostate, colorectal, or cervical cancer screening decisions for older adults' (defined either as ≥ 65 years or < 10-year life expectancy). DATA EXTRACTION: Two authors independently conducted data extraction and quality appraisal. Decisions were crosschecked and discussed where necessary. DATA SYNTHESIS: From 1926 records, 30 studies met inclusion criteria. Twenty were quantitative, nine were qualitative, and one used a mixed method design. Twenty-nine were conducted in the USA, and one in the UK. Factors were synthesized into six categories: patient demographic characteristics, patient health characteristics, patient and clinician psycho-social factors, clinician characteristics, and health system factors. Patient preference was most reported as influential across both quantitative and qualitative studies. Age, health status, and life expectancy were also commonly influential, but PCPs held nuanced views about life expectancy. Weighing benefits/harms was also commonly reported with variation across cancer screening types. Other factors included patient screening history, clinician attitudes/personal experiences, patient/provider relationship, guidelines, reminders, and time. LIMITATIONS: We could not conduct a meta-analysis due to variability in study designs and measurement. The vast majority of included studies were conducted in the USA. CONCLUSIONS: Although PCPs play a role in individualizing cancer screening for older adults, multi-level interventions are needed to improve these decisions. Decision support should continue to be developed and implemented to support informed choice for older adults and assist PCPs to consistently provide evidence-based recommendations. REGISTRATION: PROSPERO CRD42021268219. FUNDING SOURCE: NHMRC APP1113532.

Medical management of secondary postpartum haemorrhage: A prospective cohort study.

BACKGROUND: Secondary postpartum haemorrhage (PPH) complicates ~1% of pregnancies and can cause serious maternal morbidity. However, evidence guiding optimal management is scarce and often based on case series and expert opinion. AIMS: To measure the success of primary medical therapy in managing secondary PPH and to identify factors associated with need for surgical management. MATERIALS AND METHODS: Postpartum patients presenting to a tertiary women's hospital emergency department between July 2020 and October 2021 with secondary PPH were recruited. Data from the acute presentation were prospectively collected. Antenatal and intrapartum data were collected from medical record review. The primary outcome was the success of medical management for secondary PPH, defined by the implementation of medical or expectant measures without subsequent need for surgical intervention. RESULTS: One-hundred and twenty patients underwent primary medical management for secondary PPH. Ninety-eight (82%) were managed successfully with medical management and 22 (18%) required surgery. Medical management involved misoprostol (n = 33; 27.5%), antibiotics (n = 108; 90%), and less commonly other uterotonics (n = 6; 5%). Factors associated with lower rates of successful medical management included: antecedent manual removal of placenta (MROP) (odds ratio (OR) 0.2, P = 0.047), primary PPH ≥500 mL (OR 0.39, P = 0.048) or ≥1 L (OR 0.24, P = 0.009), >200 mL blood loss at presentation (OR 0.17, P = 0.015), increasing time post-delivery (OR 0.84, P = 0.044), retained products of conception (RPOC) on ultrasound (OR 0.024, P = 0.001) and vaginal birth (OR 0.27, P = 0.027). CONCLUSION: Medical management was highly successful. Vaginal birth, MROP, primary PPH, RPOC on ultrasound and increasing time post-delivery were associated with increased need for surgical management.

Factors associated with women's supplemental screening intentions following dense breast notification in an online randomised experimental study.

Controversy surrounding recommendations for supplemental screening (ultrasound and magnetic resonance screening) in women with dense breasts exists, as the long-term benefits from these additional modalities may not outweigh the harms. This study aimed to examine factors associated with supplemental screening intentions following a hypothetical breast density notification in a population of women who have not been routinely notified. Australian women of breast screening age participated in an online randomised experimental study where they were presented with one of two breast density notifications (with or without health literacy-sensitive information) and asked their screening intentions. After adjusting for covariates in multivariable analyses, women in both groups (n = 940) who indicated higher levels of breast cancer worry, had private health insurance, had a family history of breast cancer, and had a greater number of times previously attending mammography screening had higher intentions for supplemental screening. Understanding women's supplemental screening intentions following notification of dense breasts has important implications for health systems with breast screening considering the impacts of widespread notification. Personal, clinical and psychological factors should be considered when discussing both the benefits and harms of supplemental screening with women with dense breasts.

General practitioners' views and experiences of communicating with older people about cancer screening: a qualitative study.

BACKGROUND: Older adults should be supported to make informed decisions about cancer screening. However, it is unknown how general practitioners (GPs) in Australia communicate about cancer screening with older people. AIM: To investigate GPs' views and experiences of communicating about cancer screening (breast, cervical, prostate, and bowel) with older people (≥70 years). DESIGN AND SETTING: Qualitative, semi-structured interviews, Australia. METHOD: Interviews were conducted with GPs practising in Australia (n = 28), recruited through practice-based research networks, primary health networks, social media, and email invitation. Interviews were audio-recorded and analysed thematically using Framework Analysis. RESULTS: Findings across GPs were organized into 3 themes: (i) varied motivation to initiate cancer screening discussions; some GPs reported that they only initiated screening within recommended ages (<75 years), others described initiating discussions beyond recommended ages, and some experienced older patient-initiated discussions; (ii) GPs described the role they played in providing screening information, whereby detailed discussions about the benefits/risks of prostate screening were more likely than other nationally funded screening types (breast, cervical, and bowel); however, some GPs had limited knowledge of recommendations and found it challenging to explain why screening recommendations have upper ages; (iii) GPs reported providing tailored advice and discussion based on personal patient preferences, overall health/function, risk of cancer, and previous screening. CONCLUSIONS: Strategies to support conversations between GPs and older people about the potential benefits and harms of screening in older age and rationale for upper age limits to screening programmes may be helpful. Further research in this area is needed.

Australian General Practitioners' Current Knowledge, Understanding, and Feelings Regarding Breast Density Information and Notification: A Cross-Sectional Study.

BACKGROUND: There is a lack of evidence around Australian general practitioners' (GPs) views of issues surrounding breast density. The current study aimed to quantitatively assess GPs' current knowledge, understanding, and feelings around breast density information and notification. METHODS: This study involved a cross-sectional survey using an online platform to collect quantitative data from Australian GPs. Survey data were analysed with descriptive statistics. RESULTS: A total 60 responses from GPs were analysed. Most (n = 58; 97%) had heard or read about breast density and nearly 90% (n = 52; 87%) have had discussions about breast density with patients. Three-quarters (n = 45; 75%) were supportive of making breast density notification mandatory for patients with dense tissue and a similar proportion (n = 45/58; 78%) felt they need or want more education on breast density. CONCLUSIONS: There is strong support for notifying patients of breast density, and interest in further education and training among the surveyed GPs. As GPs play a central role in cancer prevention and control, their involvement in discussions related to breast density notification, evaluation and appraisal of evidence, development of communication strategies, and participation in ongoing research on the topic will be indispensable.

Australian Women's Intentions and Psychological Outcomes Related to Breast Density Notification and Information: A Randomized Clinical Trial.

Importance: Whether the benefits of notifying women about breast density outweigh the potential harms to inform current and future mammogram screening practice remains unknown. Objective: To assess the effect of mammographic breast density notification and information provision on women's intention to seek supplemental screening and psychological outcomes. Design, Setting, and Participants: A 3-arm online randomized clinical trial was conducted from August 10 to 31, 2021. Data analysis was conducted from September 1 to October 20, 2021. Participants included Australian residents identifying as female, aged between 40 and 74 years, with no history of breast cancer who were residing in jurisdictions without existing breast density notification with screening mammograms. Interventions: Women were randomized to receive 1 of the following hypothetical breast screening test result letters: screening mammogram result letter without breast density messaging (control), screening mammogram result letter with breast density messaging and an existing density information letter taken from a screening service in Australia (intervention 1), and screening mammogram result letter with breast density messaging and a health literacy-sensitive version of the letter adapted for people with lower health literacy (intervention 2). Main Outcomes and Measures: Primary outcomes were intention to seek supplemental screening; feeling anxious (uneasy, worried, or nervous), informed, or confused; and having breast cancer worry. Results: A total of 1420 Australian women were randomized and included in the final analysis. The largest group consisted of 603 women aged 60 to 74 years (42.5%). Compared with the control cohort (n = 480), women who received density notification via intervention 1 (n = 470) and intervention 2 (n = 470) reported a significantly higher intention to seek supplemental screening (0.8% vs 15.6% and 14.2%; P < .001) and feeling anxious (14.2% vs 49.4% and 48.5%; P < .001), confusion (7.8% vs 24.0% and 23.6%; P < .001), and worry about breast cancer (quite/very worried: 6.9% vs 17.2% and 15.5%; P < .001). There were no statistically significant differences in these outcomes between the 2 intervention groups. Conclusions and Relevance: In this randomized clinical trial, breast density notification and information integrated with screening mammogram results increased women's intention to seek supplemental screening and made women feel anxious, confused, or worried about breast cancer. These findings have relevance and implications for mammogram screening services and policy makers considering whether and, if so, how best to implement widespread notification of breast density as part of mammography screening. Trial Registration: ACTRN12621000253808.

Patient-Reported Factors Associated With Older Adults' Cancer Screening Decision-making: A Systematic Review.

Importance: Decisions for older adults (aged ≥65 years) and their clinicians about whether to continue to screen for cancer are not easy. Many older adults who are frail or have limited life expectancy or comorbidities continue to be screened for cancer despite guidelines suggesting they should not; furthermore, many older adults have limited knowledge of the potential harms of continuing to be screened. Objective: To summarize the patient-reported factors associated with older adults' decisions regarding screening for breast, prostate, colorectal, and cervical cancer. Evidence Review: Studies were identified by searching databases from January 2000 to June 2020 and were independently assessed for inclusion by 2 authors. Data extraction and risk of bias assessment were independently conducted by 2 authors, and then all decisions were cross-checked and discussed where necessary. Data analysis was performed from September to December 2020. Findings: The search yielded 2475 records, of which 21 unique studies were included. Nine studies were quantitative, 8 were qualitative, and 4 used mixed method designs. Of the 21 studies, 17 were conducted in the US, and 10 of 21 assessed breast cancer screening decisions only. Factors associated with decision-making were synthesized into 5 categories: demographic, health and clinical, psychological, physician, and social and system. Commonly identified factors associated with the decision to undergo screening included personal or family history of cancer, positive screening attitudes, routine or habit, to gain knowledge, friends, and a physician's recommendation. Factors associated with the decision to forgo screening included being older, negative screening attitudes, and desire not to know about cancer. Some factors had varying associations, including insurance coverage, living in a nursing home, prior screening experience, health problems, limited life expectancy, perceived cancer risk, risks of screening, family, and a physician's recommendation to stop. Conclusions and Relevance: Although guidelines suggest incorporating life expectancy and health status to inform older adults' cancer screening decisions, older adults' ingrained beliefs about screening may run counter to these concepts. Communication strategies are needed that support older adults to make informed cancer screening decisions by addressing underlying screening beliefs in context with their perceived and actual risk of developing cancer.

Preferences for More or Less Health Care and Association With Health Literacy of Men Eligible for Prostate-Specific Antigen Screening in Australia.

Importance: Understanding personal factors that influence diverse responses to health care information, such as preferences for more or less health care, might be beneficial to more effective communication and better involvement in health care choices. Objective: To determine whether individuals' preferences for more or less health care are associated with informed choice and understanding of overdiagnosis in routine prostate cancer screening and to examine associations among preferences, educational status, and health literacy. Design, Setting, and Participants: This survey study included a community-based sample of men in Australia aged 45 to 60 years eligible for prostate-specific antigen (PSA) screening, recruited via an international social research company. Survey data were collected online from June 27 to July 26, 2018. Data were analyzed in April 2020. Exposures: Participants were randomized to 1 of 2 versions of an online decision aid (full-length or abbreviated) about PSA screening and completed an online survey that included a measure of preference for more or less health care, the Medical Maximizer-Minimizer Scale (MMS), in which higher score indicates preference for more health care. Main Outcomes and Measures: The primary outcome was informed choice; knowledge, attitudes, and intentions about screening for prostate cancer were also measured. Results: Of 3722 participants who began the survey, 2993 (80.4%) completed it (mean [SD] age, 52.15 [6.65] years). Stronger preferences for more heath care were observed in those without tertiary education (mean difference, 0.15; 95% CI, 0.09-0.22; P < .001) and with inadequate health literacy (mean difference, 0.16; 95% CI, 0.09-0.22; P < .001). After controlling for health and demographic variables, a 1-unit increase in MMS score was associated with reduced relative risk (RR) of making an informed choice (RR, 0.78; 95% CI, 0.74-0.82; P < .001) and of having adequate conceptual knowledge (RR, 0.87; 95% CI, 0.84-0.90; P < .001), correct numerical knowledge (RR, 0.93; 95% CI, 0.89-0.97; P = .001), and correct understanding of overdiagnosis (RR, 0.84; 95% CI, 0.79-0.90; P < .001). A 1-unit increase in MMS score was associated with a more positive attitude toward screening (RR, 1.18; 95% CI, 1.15-1.21; P < .001) and more positive intention to screen (RR, 1.20; 95% CI, 1.16-1.25; P < .001) after adjusting for control variables. Conclusions and Relevance: This survey study examined associations between preferences for more or less health care and knowledge about overdiagnosis and informed choice among men in Australia. These results may motivate clinicians to elicit individual patient preferences to facilitate tailored discussions with patients about low-value care, such as prostate cancer screening, for which benefit is uncertain.

Psychosocial and clinical predictors of continued cancer screening in older adults.

OBJECTIVE: Many older adults (aged 75+) continue cancer screening despite guidelines suggesting they should not. Using mixed-methods, we examined psychosocial and clinical factors associated with continued breast/prostate screening. METHODS: We conducted an online, scenario-based, randomized study in Australia with participants aged 65+ years. The primary outcome was screening intention (10-point scale, dichotomized: low (1-5) and high (6-10)). We also measured demographic, psychosocial, and age-related clinical variables. Participants provided reason/s for their screening intentions in free-text. RESULTS: 271 eligible participants completed the survey (aged 65-90 years, 71% adequate health literacy). Those who reported higher cancer anxiety, were men, screened more recently, had family history of breast/prostate cancer and were independent in activities of daily living, were more likely to intend to continue screening. Commonly reported reasons for intending to continue screening were grouped into six themes: routine adherence, the value of knowing, positive screening attitudes, perceived susceptibility, benefits focus, and needing reassurance. CONCLUSIONS: Psychosocial factors may drive continued cancer screening in older adults and undermine efforts to promote informed decision-making. PRACTICE IMPLICATIONS: When communicating benefits and harms of cancer screening to older adults, both clinical and psychosocial factors should be discussed to support informed decision-making.

Regulation of the Acute Sickness Response by the P2RX7 Receptor.

BACKGROUND: The acute sickness response to infection is a stereotyped set of illness manifestations initiated by proinflammatory signals in the periphery but mediated centrally. P2RX7 is a highly polymorphic gene encoding an ATP-gated cationic pore, widely expressed on immune cells and the brain, and regulating the NLRP3 inflammasome, as well as diverse neural functions. METHODS: Associations between P2RX7 genotype, pore activity, and illness manifestations were examined in a cohort with acute viral and bacterial infections (n = 484). Genotyping of 12 P2RX7 function-modifying single-nucleotide polymorphisms (SNPs) was used to identify haplotypes and diplotypes. Leucocyte pore activity was measured by uptake of the fluorescent dye, YO-PRO-1, and by ATP-induced interleukin-1ß (IL-1ß) release. Associations were sought with scores describing the symptom domains, or endophenotypes, derived from principal components analysis. RESULTS: Among the 12 SNPs, a 4-SNP haplotype block with 5 variants was found in 99.5% of the subjects. These haplotypes and diplotypes were closely associated with variations in pore activity and IL-1ß production. Homozygous diplotypes were associated with overall illness severity as well as fatigue, pain, and mood disturbances. CONCLUSIONS: P2RX7 signaling plays a significant role in the acute sickness response to infection, likely acting in both the immune system and the brain.

Active surveillance as a management option for cervical intraepithelial neoplasia 2: An online experimental study.

OBJECTIVE: To investigate framing of active surveillance as a management option for cervical intraepithelial neoplasia (CIN)2 in women of childbearing age. METHODS: We conducted a between-subjects factorial (2 × 2) randomised experiment. Women aged 25-40 living in Australia were presented with the same hypothetical pathway of testing human papillomavirus (HPV)-positive, high-grade cytology and a diagnosis of CIN2, through an online survey. They were randomised to one of four groups to evaluate the effects of (i) framing (method of explaining resolution of abnormal cells) and (ii) inclusion of an overtreatment statement (included versus not). Primary outcome was management choice following the scenario: active surveillance or surgery. RESULTS: 1638 women were randomised. Overall, preference for active surveillance was high (78.9%; n = 1293/1638). There was no effect of framing or providing overtreatment information, or their interaction, on management choice. After adjusting for intervention received, age, education, and other model covariates, participants were more likely to choose active surveillance over surgery if they had not already had children, had plans for children in the future, had no family history of cancer, had no history of endometriosis, had adequate health literacy, and more trust in their GP. Participants were less likely to choose active surveillance over surgery if they were more predisposed to seek health care for minor problems. CONCLUSIONS: Although we found no framing effect across the four conditions, we found a high level of preference for active surveillance with associations of increased preference that accord with the desire to minimise potential risks of CIN2 treatment on obstetric outcomes. These are valuable data for future clinical trials of active surveillance for management of CIN2 in younger women of childbearing age. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12618002043213, 20/12/2018, prior to participant enrolment).

Effects of health literacy, screening, and participant choice on action plans for reducing unhealthy snacking in Australia: A randomised controlled trial.

BACKGROUND: Low health literacy is associated with poorer health outcomes. A key strategy to address health literacy is a universal precautions approach, which recommends using health-literate design for all health interventions, not just those targeting people with low health literacy. This approach has advantages: Health literacy assessment and tailoring are not required. However, action plans may be more effective when tailored by health literacy. This study evaluated the impact of health literacy and action plan type on unhealthy snacking for people who have high BMI or type 2 diabetes (Aim 1) and the most effective method of action plan allocation (Aim 2). METHODS AND FINDINGS: We performed a 2-stage randomised controlled trial in Australia between 14 February and 6 June 2019. In total, 1,769 participants (mean age: 49.8 years [SD = 11.7]; 56.1% female [n = 992]; mean BMI: 32.9 kg/m2 [SD = 8.7]; 29.6% self-reported type 2 diabetes [n = 523]) were randomised to 1 of 3 allocation methods (random, health literacy screening, or participant selection) and 1 of 2 action plans to reduce unhealthy snacking (standard versus literacy-sensitive). Regression analysis evaluated the impact of health literacy (Newest Vital Sign [NVS]), allocation method, and action plan on reduction in self-reported serves of unhealthy snacks (primary outcome) at 4-week follow-up. Secondary outcomes were perceived extent of unhealthy snacking, difficulty using the plans, habit strength, and action control. Analyses controlled for age, level of education, language spoken at home, diabetes status, baseline habit strength, and baseline self-reported serves of unhealthy snacks. Average NVS score was 3.6 out of 6 (SD = 2.0). Participants reported consuming 25.0 serves of snacks on average per week at baseline (SD = 28.0). Regarding Aim 1, 398 participants in the random allocation arm completed follow-up (67.7%). On average, people scoring 1 SD below the mean for health literacy consumed 10.0 fewer serves per week using the literacy-sensitive action plan compared to the standard action plan (95% CI: 0.05 to 19.5; p = 0.039), whereas those scoring 1 SD above the mean consumed 3.0 fewer serves using the standard action plan compared to the literacy-sensitive action plan (95% CI: -6.3 to 12.2; p = 0.529), although this difference did not reach statistical significance. In addition, we observed a non-significant action plan × health literacy (NVS) interaction (b = -3.25; 95% CI: -6.55 to 0.05; p = 0.054). Regarding Aim 2, 1,177 participants across the 3 allocation method arms completed follow-up (66.5%). There was no effect of allocation method on reduction of unhealthy snacking, including no effect of health literacy screening compared to participant selection (b = 1.79; 95% CI: -0.16 to 3.73; p = 0.067). Key limitations include low-moderate retention, use of a single-occasion self-reported primary outcome, and reporting of a number of extreme, yet plausible, snacking scores, which rendered interpretation more challenging. Adverse events were not assessed. CONCLUSIONS: In our study we observed nominal improvements in effectiveness of action plans tailored to health literacy; however, these improvements did not reach statistical significance, and the costs associated with such strategies compared with universal precautions need further investigation. This study highlights the importance of considering differential effects of health literacy on intervention effectiveness. TRIAL REGISTRATION: Australia and New Zealand Clinical Trial Registry ACTRN12618001409268.

Contribution of psychosocial factors to socioeconomic inequalities in mortality among older Australian men: a population-based cohort study.

BACKGROUND: Among older people, the extent to which psychosocial factors explain socioeconomic inequalities in mortality is debated. We aimed to investigate the potential mediating effect of psychosocial factors on socioeconomic inequalities in mortality. METHODS: We used data from a prospective population-based cohort (the Concord Health and Ageing in Men Project; baseline recruitment in 2005-2007), in Sydney, Australia. The main outcomes were all-cause and cause-specific mortality. Socioeconomic status (SES; educational attainment, occupational position, source of income, housing tenure, and a cumulative SES score) was assessed at baseline. Measures of structural and functional social support, as well as depressive and anxiety symptoms were assessed three times during follow-ups. Associations were quantified using Cox regression. Mediation was calculated using "change-in-estimate method". RESULTS: 1522 men (mean age at baseline: 77·4 ± 5·5 years) were included in the analyses with a mean (SD) follow-up time of 9·0 (3·6) years for all-cause and 8·0 (2·8) years for cause-specific mortality. At baseline, psychosocial measures displayed marked social patterning. Being unmarried, living alone, low social interactions, and elevated depressive symptoms were associated with higher risk of all-cause and cardiovascular disease (CVD) mortality. Psychosocial factors explained 35% of SES inequalities in all-cause mortality, 29% in CVD mortality, 12% in cancer mortality, and 39% in non-CVD, non-cancer mortality. CONCLUSION: Psychosocial factors may account for up to one-third of SES inequalities in deaths from all and specific causes (except cancer mortality). Our findings suggest that interventional studies targeting social relationships and/or psychological distress in older men aiming to reduce socioeconomic inequalities in mortality are warranted.

Socioeconomic status, health-related behaviours, and death among older people: the Concord health and aging in men project prospective cohort study.

BACKGROUND: Conflicting evidence exists regarding the association of socioeconomic status (SES) with mortality among older people and little is known about the mechanisms underlying this association. We investigated the association of SES with mortality among older Australian men. We also investigated potential mediating effects of health-related behaviours in SES-mortality associations. METHODS: We used data from a prospective population-based cohort (the Concord Health and Aging in Men Project), in Sydney, Australia. The main outcomes were all-cause and cause-specific mortality. Educational attainment, occupational position, source of income, housing tenure, and a cumulative SES score were assessed at baseline. Longitudinally assessed alcohol consumption, smoking, physical activity, and body mass index were investigated as potential mediators. Associations were quantified using Cox regression. RESULTS: We evaluated 1527 men (mean age: 77.4 ± 5.5 years). During a mean follow-up time of 9.0 years, 783 deaths occurred. For deaths from all causes, the adjusted hazard ratio (HR) for the lowest tertile of cumulative SES score versus the highest tertile was 1.44 (95% CI 1.21 to 1.70); the corresponding sub-HRs were 1.35 (0.96 to 1.89) for cardiovascular disease (CVD) mortality; 1.58 (1.15 to 2.18) for cancer mortality, and 1.86 (1.36 to 2.56) for non-CVD, non-cancer mortality. SES-mortality associations were attenuated by 11-25% after adjustment for mediating health-related behaviours. CONCLUSION: Low SES is associated with increased mortality in older Australian men and health-related behaviours accounted for less than one-fourth of these associations. Further research is needed to fully understand the mechanisms underlying SES inequalities in mortality among older people.