Search

Objective: To examine associations between work and commute hours with food consumption and test whether neighbourhood type (20-minute neighbourhood (20MN)/non-20MN) moderate associations. Design: Cross-sectional analysis of the Places and Locations for Activity and Nutrition study (ProjectPLAN). Exposures were work hours (not working (0 h), working up to full-time (1–38 h/week), working overtime (> 38 h/week)), and among those employed, combined weekly work and commute hours (continuous). Outcomes were usual consumption of fruit, vegetables, takeaway food, snacks and soft drinks, and number of discretionary food types (takeaway, snacks and soft drinks) consumed weekly. Generalised linear models were fitted to examine associations between each exposure and outcome. The moderating role of neighbourhood type was examined through interaction terms between each exposure and neighbourhood type (20MN/non-20MN). Setting: Melbourne and Adelaide, Australia, 2018–2019. Participants: Adults ≥ 18 years old (n 769). Results: Although all confidence intervals contained the null, overall, patterns suggested non-workers and overtime workers have less healthy food behaviours than up-to-full-time workers. Among those employed, analysis of continuous work and commute hours data suggested longer work and commute hours were positively associated with takeaway consumption (OR = 1·014, 95 % CI 0·999, 1·030, P-value = 0·066). Patterns of better behaviours were observed across most outcomes for those in 20MN than non-20MN. However, differences in associations between work and commute hours with food consumption across neighbourhood type were negligible. Conclusions: Longer work and commute hours may induce poorer food behaviours. There was weak evidence to suggest 20MN moderate associations between work and commute hours with food consumption, although behaviours appeared healthier for those in 20MN.

Background: Genome-wide association studies have identified multiple genetic variants associated with susceptibility to prostate cancer (PrCa). In the two-stage Cancer Genetic Markers of Susceptibility prostate cancer scan, a single-nucleotide polymorphism (SNP), rs10486567, located within intron 2 of JAZF1 gene on chromosome 7p15.2, showed a promising association with PrCa overall (P = 2.14 × 10−6), with a suggestion of stronger association with aggressive disease (P = 1.2 × 10−7).Methods: In the third stage of genome-wide association studies, we genotyped 106 JAZF1 SNPs in 10,286 PrCa cases and 9,135 controls of European ancestry.Results: The strongest association was observed with the initial marker rs10486567, which now achieves genome-wide significance [P = 7.79 × 10−11; ORHET, 1.19 (95% confidence interval, 1.12-1.27); ORHOM, 1.37 (95% confidence interval, 1.20-1.56)]. We did not confirm a previous suggestion of a stronger association of rs10486567 with aggressive disease (P = 1.60 × 10−4 for aggressive cancer, n = 4,597; P = 3.25 × 10−8 for nonaggressive cancer, n = 4,514). Based on a multilocus model with adjustment for rs10486567, no additional independent signals were observed at chromosome 7p15.2. There was no association between PrCa risk and SNPs in JAZF1 previously associated with height (rs849140; P = 0.587), body stature (rs849141, tagged by rs849136; P = 0.171), and risk of type 2 diabetes and systemic lupus erythematosus (rs864745, tagged by rs849142; P = 0.657).Conclusion: rs10486567 remains the most significant marker for PrCa risk within JAZF1 in individuals of European ancestry.Impact: Future studies should identify all variants in high linkage disequilibrium with rs10486567 and evaluate their functional significance for PrCa. Cancer Epidemiol Biomarkers Prev; 19(5); 1349–55. ©2010 AACR.

Background: One of the goals of personalized medicine is to generate individual risk profiles that could identify individuals in the population that exhibit high risk. The discovery of more than two-dozen independent single-nucleotide polymorphism markers in prostate cancer has raised the possibility for such risk stratification. In this study, we evaluated the discriminative and predictive ability for prostate cancer risk models incorporating 25 common prostate cancer genetic markers, family history of prostate cancer, and age.Methods: We fit a series of risk models and estimated their performance in 7,509 prostate cancer cases and 7,652 controls within the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). We also calculated absolute risks based on SEER incidence data.Results: The best risk model (C-statistic = 0.642) included individual genetic markers and family history of prostate cancer. We observed a decreasing trend in discriminative ability with advancing age (P = 0.009), with highest accuracy in men younger than 60 years (C-statistic = 0.679). The absolute ten-year risk for 50-year-old men with a family history ranged from 1.6% (10th percentile of genetic risk) to 6.7% (90th percentile of genetic risk). For men without family history, the risk ranged from 0.8% (10th percentile) to 3.4% (90th percentile).Conclusions: Our results indicate that incorporating genetic information and family history in prostate cancer risk models can be particularly useful for identifying younger men that might benefit from prostate-specific antigen screening.Impact: Although adding genetic risk markers improves model performance, the clinical utility of these genetic risk models is limited. Cancer Epidemiol Biomarkers Prev; 21(3); 437–44. ©2012 AACR.

PDF file - 169K

PDF file - 71K

Supplementary Table 3 from Refining the Prostate Cancer Genetic Association within the JAZF1 Gene on Chromosome 7p15.2

Supplementary Table 1 from Refining the Prostate Cancer Genetic Association within the JAZF1 Gene on Chromosome 7p15.2

Supplementary Table Legends from Refining the Prostate Cancer Genetic Association within the JAZF1 Gene on Chromosome 7p15.2

PURPOSE For patients with metastatic hormone-sensitive prostate cancer, metastatic burden affects outcome. We examined efficacy and safety from the ARASENS trial for subgroups by disease volume and risk. METHODS Patients with metastatic hormone-sensitive prostate cancer were randomly assigned to darolutamide or placebo plus androgen-deprivation therapy and docetaxel. High-volume disease was defined as visceral metastases and/or ≥ 4 bone metastases with ≥ 1 beyond the vertebral column/pelvis. High-risk disease was defined as ≥ 2 risk factors: Gleason score ≥ 8, ≥ 3 bone lesions, and presence of measurable visceral metastases. RESULTS Of 1,305 patients, 1,005 (77%) had high-volume disease and 912 (70%) had high-risk disease. Darolutamide increased overall survival (OS) versus placebo in patients with high-volume (hazard ratio [HR], 0.69; 95% CI, 0.57 to 0.82), high-risk (HR, 0.71; 95% CI, 0.58 to 0.86), and low-risk disease (HR, 0.62; 95% CI, 0.42 to 0.90), and in the smaller low-volume subgroup, the results were also suggestive of survival benefit (HR, 0.68; 95% CI, 0.41 to 1.13). Darolutamide improved clinically relevant secondary end points of time to castration-resistant prostate cancer and subsequent systemic antineoplastic therapy versus placebo in all disease volume and risk subgroups. Adverse events (AEs) were similar between treatment groups across subgroups. Grade 3 or 4 AEs occurred in 64.9% of darolutamide patients versus 64.2% of placebo patients in the high-volume subgroup and 70.1% versus 61.1% in the low-volume subgroup. Among the most common AEs, many were known toxicities related to docetaxel. CONCLUSION In patients with high-volume and high-risk/low-risk metastatic hormone-sensitive prostate cancer, treatment intensification with darolutamide, androgen-deprivation therapy, and docetaxel increased OS with a similar AE profile in the subgroups, consistent with the overall population. [Media: see text]

ObjectiveTo test the efficacy of theTransform-Us!school- and home-based intervention on children’s physical activity (PA), sedentary behaviour (SB) and cardiometabolic risk factor profiles.MethodsA 30-month 2×2 factorial design cluster randomised controlled trial delivered in 20 primary schools (148 Year 3 classes) in Melbourne, Australia (2010–2012), that used pedagogical and environmental strategies to reduce and break up SB, promote PA or a combined approach, compared with usual practice. Primary outcomes (accelerometry data; n=348) were assessed at baseline, 18 and 30 months. Secondary outcomes included body mass index (BMI) and waist circumference (WC) (n=564), blood pressure (BP) (n=537) and biomarkers (minimum n=206). Generalised linear mixed models estimated the interactive effects of the PA and SB interventions on the outcomes. If there was no interaction, the main effects were assessed.ResultsAt 18 months, there were intervention effects on children’s weekday SB (−27 min, 95% CI: −47.3 to −5.3) for the PA intervention, and on children’s average day PA (5.5 min, 95% CI: 0.1 to 10.8) for the SB intervention. At 30 months, there was an intervention effect for children’s average day SB (−33.3 min, 95% CI: −50.6 and −16.0) for the SB intervention. Children’s BMI (PA and SB groups) and systolic BP (combined group) were lower, and diastolic BP (PA group) was higher. There were positive effects on WC at both time points (SB intervention) and mixed effects on blood parameters.ConclusionsTheTransform-Us!PA and SB interventions show promise as a pragmatic approach for reducing children’s SB and adiposity indicators; but achieving substantial increases in PA remains challenging.Trial registrationISRCTN83725066; ACTRN12609000715279.

Purpose: The global prevalence of overweight remains high; effective strategies that consider patterns of body weight changes to identify periods when adults are susceptible to weight gain are warranted. This systematic review aimed to investigate body weight patterns, and how they were associated with dietary intake and/or dietary behaviours (Prospero CRD42020161977). Methods: Systematic literature search was conducted in the Medline, Embase, and CINAHL databases until November 2020. Observational studies in adults (18 years and over) that reported at least two measurements of weight and dietary intake in a year were included. Risk of bias was conducted using the Evidence Analysis Library by the Academy of Nutrition and Dietetics tool. This review included 16 unique studies after title, abstract, and full-text screening, and findings were narratively synthesised. Results: Of the six studies conducted in the farming populations, five were conducted in countries with two seasons (dry vs. rainy seasons) and all studies observed higher body weight during the dry season (up to 3.1 kg difference between seasons). The remaining study was conducted in a sub-tropical country and did not observe temporal weight patterns. Higher dietary intake was also reported during the dry season in the tropical countries. In non-farming populations (n = 10), temporal patterns were also seen, where higher body weight and adiposity was observed during colder seasons (autumn and winter). However, the opposite was found in a study conducted in Iran, where higher weight was seen in summer. Concurrent with higher body weight, higher energy, fat, carbohydrate and soda consumption, and lower fiber and vegetable intake were observed. Conclusion: Temporal weight and dietary patterns exist, and they were country- and context-specific; these patterns were also related to factors such as activity levels, seasons and occupation. Future interventions should consider temporal patterns in the design and delivery of timely and tailored dietary interventions to promote optimal body weight. Refereed/Peer-reviewed

Background Diabetes mellitus represents a substantial global health challenge, with prevalence rising in low- and middle-income countries (LMICs). Although diabetes is known to follow a socioeconomic gradient, patterns in LMICs are unclear. This study examined associations between education and diabetes, and diabetes self-management behaviours, in six LMICs. Methods Cross-sectional data for 31,780 participants from China, Ghana, India, Mexico, Russia, and South Africa from the World Health Organization Study on Global AGEing and adult health (SAGE) study were used. Participants aged ≥50 years completed face-to-face interviews between 2007 and 2010. Participants self-reported diabetes diagnosis, physical activity, sedentary time, fruit and vegetable consumption, any special diet/program for diabetes, whether they were taking insulin for diabetes and number of years of education. Height, weight, waist, and hip circumference were measured. Country-specific survey-weighted log-binomial regression models were fitted to examine associations between the number of years of education and self-reported diabetes diagnosis (primary analysis). In secondary analyses, among those with a self-reported diabetes diagnosis, generalised linear regression models were fitted to examine associations between education and i) physical activity, ii) sedentary time, iii) fruit and vegetable consumption, iv) special diet for diabetes, v) taking insulin, vi) BMI, vii) waist circumference and viii) hip circumference. Results There was strong evidence of an association between years of education and diabetes diagnosis in Ghana (RR = 1.09, 95% CI: 1.06–1.13) and India (RR = 1.09, 95% CI: 1.07–1.12) only. In India, greater years of education was associated with higher leisure physical activity, fruit and vegetable intake, rates following a special diet or taking insulin, but also higher mean BMI, waist and hip circumference. Relationships between education and self-management behaviours were rarely seen in the other countries. Conclusions Associations between education and diabetes, and behavioural self-management (India only) was more evident in the two least developed (Ghana and India) of the WHO SAGE countries, indicating increasing diabetes diagnosis with greater numbers of years of education. The lack of gradients elsewhere may reflect shifting risk from higher to lower educated populations. While there was some suggestion that self-management behaviours were greater with increased education in India, this was not observed in the other countries.

Background The amount of time children spend outside of their home environment has increased over the past decades. Therefore, the quality of the health behaviour environments where young children spend time is likely to impact their health behaviour opportunities. The aim of this study was to describe the proportion of mothers who consider it possible to make changes in their local communities to increase opportunities for children to eat healthily, be physically active, and limit screen time exposure, as well as the proportion who have attempted to do so. The characteristics of mothers with differing advocacy beliefs and intentions were explored. Methods Cross-sectional data collected using questionnaires from 307 mothers who participated in the 3.5-year follow-up of the INFANT cluster-randomized controlled trial were used. Frequencies were used to assess the number of mothers who thought it possible to bring about change in their local communities and for the those who had attempted to do so. Binary logistic regression analyses were used to compare sociodemographic characteristics of mothers with differing responses. Results Most mothers thought it was possible to bring about change in their local community with regards to providing more opportunities for their child to eat healthily (83.7%), be physically active (90.9%) as well as limit exposure to screen time (63.5%). However, less than 19% and 11% of mothers have thought about or tried to bring about change in their child’s childcare centre or local community, respectively. No sociodemographic differences were found between the mothers who thought it was possible to bring about actioning change (p-values > 0.1) or for those that have thought about change (p-values > 0.1). Conclusion As children are continuously being exposed to obesogenic environments future quantitative and qualitative studies are needed to describe how to promote parental advocacy and engagement, in order to provide children with environments that support healthy lifestyle behaviours.

The amount of time children spend outside of their home environment has increased over the past decades. Therefore, the quality of the health behaviour environments where young children spend time is likely to impact their health behaviour opportunities. The aim of this study was to describe the proportion of mothers who consider it possible to make changes in their local communities to increase opportunities for children to eat healthily, be physically active, and limit screen time exposure, as well as the proportion who have attempted to do so. The characteristics of mothers with differing advocacy beliefs and intentions were explored.Cross-sectional data collected using questionnaires from 307 mothers who participated in the 3.5-year follow-up of the INFANT cluster-randomized controlled trial were used. Frequencies were used to assess the number of mothers who thought it possible to bring about change in their local communities and for the those who had attempted to do so. Binary logistic regression analyses were used to compare sociodemographic characteristics of mothers with differing responses.Most mothers thought it was possible to bring about change in their local community with regards to providing more opportunities for their child to eat healthily (83.7%), be physically active (90.9%) as well as limit exposure to screen time (63.5%). However, less than 19% and 11% of mothers have thought about or tried to bring about change in their child's childcare centre or local community, respectively. No sociodemographic differences were found between the mothers who thought it was possible to bring about actioning change (p-values 0.1) or for those that have thought about change (p-values 0.1).As children are continuously being exposed to obesogenic environments future quantitative and qualitative studies are needed to describe how to promote parental advocacy and engagement, in order to provide children with environments that support healthy lifestyle behaviours.

BACKGROUND People of low socioeconomic position such as those on a low income are disproportionately affected by diabetes, and by unhealthy eating patterns that contribute to poor disease self-management and prognosis. Digitally-delivered interventions have the potential to address some of the barriers to healthy eating experienced by this group. However, little is known about their effectiveness among underserved populations. OBJECTIVE This systematic review was conducted to assess the effectiveness of digitally-delivered interventions for improving nutrition behaviours and nutrition‐related health outcomes among underserved people with type 2 diabetes (T2D). METHODS MEDLINE complete, Global Health, EMBASE, CINAHL complete, Informit Health, IEEE Xplore, Applied science and technology source were searched for digitally-delivered nutrition intervention for disadvantaged people with T2D, published between 1990 and 2022. Two reviewers independently assessed studies for eligibility and determined study quality, using the Cochrane Risk of Bias Assessment Tool. The Behavioural Change Technique Taxonomy V1 (BCTTv1) was used to identify BCTs used in the design of interventions. RESULTS Ten out of 2434 identified records met eligibility criteria and were included, comprising 947 participants. Two digital platforms, web and messaging services (SMS or MMS) were used to deliver interventions. Significant improvements in dietary behaviours were reported in five out of 10 studies, representing improvements in healthier food choices, or increases in dietary knowledge and skills or self-efficacy. Seven studies examined changes in blood glucose level, of which four achieved significant decreases in HbA1C level ranging from 0.3% to 1.8%. The most frequently identified BCTs across all studies were “Instruction on how to perform the behaviour”, “information about health consequences” and “social support”. CONCLUSIONS This review provided some support for the efficacy of digitally-delivered interventions on improving healthy eating behaviours of disadvantaged people with T2D, an essential dietary prerequisite for changes in clinical metabolic parameters. Further research is needed into how underserved people with T2D may benefit more from digital approaches and to find the specific features of effective digital interventions for supporting healthy behaviours amongst disadvantaged populations.

Tumour dependency on specific metabolic signals has been demonstrated and often guided numerous therapeutic approaches. We identify melanoma addiction to the mitochondrial protein glutaryl-CoA dehydrogenase (GCDH), which functions in lysine metabolism and controls protein glutarylation. GCDH knockdown induced cell death programmes in melanoma cells, an activity blocked by inhibition of the upstream lysine catabolism enzyme DHTKD1. The transcription factor NRF2 mediates GCDH-dependent melanoma cell death programmes. Mechanistically, GCDH knockdown induces NRF2 glutarylation, increasing its stability and DNA binding activity, with a concomitant transcriptional upregulation of ATF4, ATF3, DDIT3 and CHAC1, resulting in cell death. In vivo, inducible inactivation of GCDH effectively inhibited melanoma tumour growth. Correspondingly, reduced GCDH expression correlated with improved survival of patients with melanoma. These findings identify melanoma cell addiction to GCDH, limiting apoptotic signalling by controlling NRF2 glutarylation. Inhibiting the GCDH pathway could thus represent a therapeutic approach to treat melanoma.

The introduction of magnetic resonance (MR) linear accelerators (MR-Linac) marks the beginning of a new era in radiotherapy. MR-Linac systems are currently being operated by teams of radiation therapists (RTs), radiation oncology medical physicists (ROMPs) and radiation oncologists (ROs) due to the diverse and complex tasks required to deliver treatment. This is resource-intensive and logistically challenging. RT-led service delivery at the treatment console is paramount to simplify the process and make the best use of this technology for suitable patients with commonly treated anatomical sites. This article will discuss the experiences of our department in developing and implementing an RT-led workflow on the 1.5 T MR-Linac.

Introduction The treatment of burn patients using amphetamines is challenging for hemodynamic and behavioral reasons. In addition, recent amphetamine use may also pose intraoperative risks. Due to insufficient literature to guide the safety and timing of operative care, wide practice variation exists in the operative timing for this patient population. We hypothesize that burn excision without negative amphetamine toxicology is safe. Methods We queried the operative and electronic health records of amphetamine-positive patients treated from 2017-2022 at two ABA verified burn centers. The practice guideline at Center A obtains admission toxicology only and proceeds with surgery based on hemodynamic status and operative urgency, whereas Center B sends daily toxicology until a negative test results. The primary safety outcome was the use of vasoactive agents during the index operation. This risk was modeled via logistic regression and adjusted for injury severity and hospital day for index operation. Secondary outcomes included death and inpatient complications. Results A total of 270 patients were identified during the study period. Mean age was 45.5 years (SD 12.9 years), median TBSA was 9.2% and the majority were male (76.7%). There were no significant differences in injury size, age, or male/female proportion between the two sites. Whereas Center A only tested once on admission, Center B obtained a median of 4 toxicology screens prior to surgery. There were no difference in mean induction systolic blood pressure between the 2 sites, although Center A had more patients who had SBP< 95 or >160mmHg on induction (one-way ANOVA p=0.596). The adjusted OR of requiring vasoactive support during surgery was not associated with negative toxicology status (p=0.821). A larger injury size (%TBSA >20) conferred a significant higher risk of vasoactive support (adj. OR 13.42 [3.90 – 46.23], p< 0.001). Clinical outcomes at the 2 sites were similar in the terms of mortality, number of operations, stroke, and hospital length of stay. Conclusions Comparison between 2 ABA verified burn centers identifies a significant variation in practice with regards to serial amphetamine screenings prior to burn surgery. This study indicates that negative toxicology does not impact intraoperative anesthesia management nor subsequent burn clinical outcomes. Applicability of Research to Practice Serial toxicology tests are unnecessary to guide operative timing of burn patients with amphetamine use.

We assessed willingness to use HIV pre-exposure prophylaxis (PrEP) and current PrEP use among gay and bisexual men (GBM) in Australia.National, online cross-sectional surveys of GBM were conducted in 2013, 2015, 2017, and 2019. Willingness to use PrEP was measured on a previously validated scale. Trends and associations with key measures were analyzed using multivariate logistic regression.During 2013-2019, 4908 surveys were completed. Among HIV-negative and untested men not currently using PrEP, willingness to use PrEP increased from 23.0% in 2013 to 36.5% in 2017 (P0.001) but then plateaued at 32% in 2019 (P = 0.13). The proportion of current PrEP users increased significantly from 2.5% in 2015 to 38.5% in 2019 (P0.001). In 2019, factors independently associated with being a current PrEP user (compared with non-PrEP users who were willing to use PrEP) included having subsidized health care (Medicare), knowing HIV-positive people, being recently diagnosed with an STI other than HIV, having higher numbers of recent male sexual partners, recent condomless sex with casual and regular partners, and frequent PrEP sorting.Willingness to use PrEP has plateaued as its use has rapidly increased among GBM in Australia. PrEP use is concentrated among more sexually active men with access to subsidized health care. Free or low cost access schemes may facilitate broader access among GBM who want or need PrEP but lack access to subsidized health care.

We explored the association of prostate cryotherapy and immunomodulation with granulocyte-macrophage colony-stimulating factor (GMCSF) in the generation of detectable tumor-specific T- and B-cell responses in men with prostate cancer. A randomized pilot study of patients assigned to either cryotherapy alone (Control group) or in combination with GMCSF (Treatment group). The impact of therapy on the development of T- and B-cell responses against tumor-related antigens was studied using enzyme-linked immune absorbent spot (ELISpot) and protein microarray panels (Sematrix) assays, respectively. Fold changes in response to treatment were calculated by normalization of post-treatment ELISpot values against the mean pre-cryoablation response. Student t tests between treatment and control groups at 4 weeks and 12 weeks across all the antigens were performed. A total of 20 patients were randomized to either control or treatment arm. At 4 weeks after cryotherapy, the treatment group demonstrated an average fold change in cancer antigen-related antibodies of 2.8% above their mean baseline values, whereas controls averaged an 18% change below mean baseline (p

We have tracked belief in the effectiveness of HIV treatment as prevention (TasP) among Australian gay and bisexual men (GBM) since 2013. National, online cross-sectional surveys of GBM were conducted every 2 years during 2013–2019. Trends and associations were analyzed using multivariate logistic regression. Data from 4,903 survey responses were included. Belief that HIV treatment prevents transmission increased from 2.6% in 2013 to 34.6% in 2019. Belief in the effectiveness of TasP was consistently higher among HIV-positive participants than other participants. In 2019, higher levels of belief in TasP were independently associated with university education, being HIV-positive, using pre-exposure prophylaxis, knowing more HIV-positive people, being recently diagnosed with a sexually transmitted infection (STI) and use of post-exposure prophylaxis. Belief that HIV treatment prevents transmission has increased substantially among Australian GBM, but remains concentrated among HIV-positive GBM, those who know HIV-positive people, and GBM who use antiretroviral-based prevention.

Background Risk stratification in men with suspicion of prostate cancer (PCa) requires reliable diagnostic tests, not only to identify high-grade PCa, also to minimize the overdetection of low-grade PCa, and reduction of “unnecessary” prostate MRIs and biopsies. This study aimed to evaluate the SelectMDx test to detect high-grade PCa in biopsy-naïve men. Subsequently, to assess combinations of SelectMDx test and multi-parametric (mp) MRI and its potential impact on patient selection for prostate biopsy. Methods This prospective multicenter diagnostic study included 599 biopsy-naïve patients with prostate-specific antigen level ≥3 ng/ml. All patients underwent a SelectMDx test and mpMRI before systematic transrectal ultrasound-guided biopsy (TRUSGB). Patients with a suspicious mpMRI also had an in-bore MR-guided biopsy (MRGB). Histopathologic outcome of TRUSGB and MRGB was used as reference standard. High-grade PCa was defined as ISUP Grade Group (GG) ≥ 2. The primary outcome was the detection rates of low- and high-grade PCa and number of biopsies avoided in four strategies, i.e., (1) SelectMDx test-only, (2) mpMRI-only, (3) SelectMDx test followed by mpMRI when SelectMDx test was positive (conditional strategy), and (4) SelectMDx test and mpMRI in all (joint strategy). A positive SelectMDx test outcome was a risk score of ≥−2.8. Decision curve analysis (DCA) was performed to assess clinical utility. Results Prevalence of high-grade PCa was 31% (183/599). Thirty-eight percent (227/599) of patients had negative SelectMDx test in whom biopsy could be avoided. Low-grade PCa was not detected in 35% (48/138) with missing 10% (18/183) high-grade PCa. Yet, mpMRI-only could avoid 49% of biopsies, not detecting 4.9% (9/183) of high-grade PCa. The conditional strategy reduces the number of mpMRIs by 38% (227/599), avoiding biopsy in 60% (357/599) and missing 13% (24/183) high-grade PCa. Low-grade PCa was not detected in 58% (80/138). DCA showed the highest net benefit for the mpMRI-only strategy, followed by the conditional strategy at-risk thresholds >10%. Conclusions SelectMDx test as a risk stratification tool for biopsy-naïve men avoids unnecessary biopsies in 38%, minimizes low-grade PCa detection, and misses only 10% high-grade PCa. Yet, using mpMRI in all patients had the highest net benefit, avoiding biopsy in 49% and missing 4.9% of high-risk PCa. However, if mpMRI availability is limited or expensive, using mpMRI-only in SelectMDx test positive patients is a good alternative strategy.

Around 40% of the world’s population is currently without access to the Internet. The digital divide is due to the high cost of provisioning these services and the low return on investment for network operators. We propose using 5G network slicing with multi-tenancy (also known as neutral host networks (NHN)) for macro-cells and small cells in rural areas to reduce the costs. This paper investigates the techno-economic feasibility of using rural 5G NHN to minimise the digital divide. A generic model is developed to analyse the techno-economic analysis of 5G NHN deployment around the world, with a special focus on rural areas where no MNO is interested in providing services. To understand the application, it is applied to the Indian scenario. First, a discussion on existing infrastructure, competition and statistics for Indian telecommunications is presented. Next, the technical requirements are analysed using the key performance indicators (KPI) required for the rural 5G NHN for the Indian scenario. The study also analyses the relationship between coverage, investment in the network, the number of subscribers, investment time, demand, the investment per user and sensitivity analysis to understand the feasibility of the proposed solution for Indian villages with different input conditions. Later, a case study is carried out based on the proposed approach, along with coverage modelling for a few Indian villages having different topologies. The results show that 5G NHN using network slicing can significantly reduce the total investment required for providing 5G services in rural areas. Furthermore, the study shows that rural 5G NHN is a viable investment and a key enabler for Internet connectivity for villages with 10-year investment, having a subscribers’ base as low as 100 with a customer growth rate of 7%.

15 Background: In ARASENS (NCT02799602), DARO plus ADT and DOC significantly reduced the risk of death by 32.5% (HR 0.68; 95% CI: 0.57–0.80; P

148 Background: In ARASENS (NCT02799602), DARO in combination with ADT and DOC significantly reduced the risk of death by 32.5% (HR 0.68; 95% CI 0.57–0.80; P2 q21d for 6 cycles). The effect of DARO on DOC PK was assessed by noncompartmental analysis from the first 25 patients with dense PK data and by population PK (PopPK) for all patients. DARO PK from ARASENS were compared with PK data from ARAMIS (NCT02200614; without DOC) to evaluate the impact of DOC on DARO PK. Results: Of 1306 randomized patients, 1305 were included in the full analysis set (DARO, n=651; PBO, n=654). The median treatment duration was longer with DARO vs PBO (41.0 vs 16.7 months) and more DARO-treated patients (45.9% vs 19.1%) were still receiving treatment at primary analysis cutoff (Oct 25, 2021). Almost all patients completed 6 cycles of DOC in both groups (DARO, 87.6%; PBO, 85.5%). The proportion of patients requiring DOC dose modification (interrupted/delayed or reduced) was similar between groups (DARO, 60.0%; PBO, 62.9%). TEAEs led to discontinuation/reduction of DOC in 8.0%/19.9% of DARO patients and 10.3%/19.5% of PBO patients. PopPK analysis indicated that DOC PK in ARASENS was generally consistent with that in the literature. A slight numeric increase in DOC exposure was observed in the DARO + DOC + ADT arm, with 15% higher maximum plasma concentration (geometric mean, 1.93 vs 1.68 µg/mL) and 6% higher area under the concentration-time curve (AUC0-tlast within an 8-hour sampling interval, 2.10 vs 1.99 µg·h/mL) vs PBO + DOC + ADT. This small numeric increase is likely not clinically relevant given the variability in DOC exposure (coefficient of variation, 23%–54%). PK meta-analysis of ARASENS and, which considered patients’ intrinsic characteristics as covariates (eg, age, body weight, region), indicated a 10% lower AUC0-12ss of DARO in patients receiving DOC vs those not receiving DOC, which is not considered clinically relevant. Conclusions: The combination of DARO + DOC + ADT increases overall survival with similar overall incidence of TEAEs and no observed drug-drug interactions between DARO and DOC. DARO can be effectively and safely administered with DOC in patients with mHSPC without clinically relevant changes in PK of DARO or DOC. Clinical trial information: NCT02799602 .

Background Healthy eating is a key element of type 2 diabetes (T2D) self-management. Digital interventions offer new avenues to reach broad audiences to promote healthy eating behaviors. However, acceptance of these interventions by socioeconomically disadvantaged people (eg, those with lower levels of education and income or from ethnic minority groups) has not yet been fully evaluated. Objective This study aimed to investigate the acceptability and usability of EatSmart, a 12-week web-based and mobile-delivered healthy eating behavior change support program, from the perspective of intervention participants living with T2D and health care providers (HCPs) involved in diabetes care. Methods This study used a qualitative descriptive design. Overall, 60 disadvantaged adults with T2D, as determined by receipt of either a HealthCare Card or a pension or benefit as the main source of income, were recruited. Data from participants regarding their experiences with and perceptions of the program and longer-term maintenance of any behavior or attitudinal changes were collected through a web-based self-report survey with open-ended questions administered 12 weeks after baseline (54/60, 90%) and semistructured telephone interviews administered 36 weeks after baseline (16/60, 27%). Supplementary semistructured interviews with 6 HCPs involved in diabetes care (endocrinologists, accredited practicing dietitians, and diabetes nurse educators) were also conducted 36 weeks after baseline. These interviews aimed to understand HCPs’ views on successful and unsuccessful elements of EatSmart as a technology-delivered intervention; any concerns or barriers regarding the use of these types of interventions; and feedback from their interactions with patients on the intervention’s content, impact, or observed benefits. All data from the surveys and interviews were pooled and thematically analyzed. Results In total, 5 key themes emerged from the data: program impact on food-related behaviors and routines, satisfaction with the program, reasons for low engagement and suggestions for future programs, benefits and challenges of digital interventions, and cultural considerations. Results showed that EatSmart was acceptable to participants and contributed positively to improving food-related behaviors. Most participants (27/43, 63%) mentioned that they enjoyed their experience with EatSmart and expressed high satisfaction with its content and delivery. The educational and motivational content was considered the most useful part of the program. Benefits discussed by intervention participants included gaining health knowledge and skills, positive changes in their food purchasing and cooking, and eating greater quantities and varieties of fruits and vegetables. HCPs also described the intervention as beneficial and persuasive for the target audience and had specific suggestions for future tailoring of such programs. Conclusions The findings suggested that this digitally delivered intervention with supportive educational modules and SMS text messages was generally appealing for both participants and HCPs. This intervention medium shows promise and could feasibly be rolled out on a broader scale to augment usual diabetes care. International Registered Report Identifier (IRRID) RR2-10.2196/19488

Introduction: Blacks/African-Americans (B/AAs) are disproportionately affected by prostate cancer, with higher incidence and mortality rates versus other racial/ethnic groups. Darolutamide (DARO) is a structurally distinct and highly potent androgen receptor inhibitor. In the ARASENS trial (NCT02799602), DARO in combination with androgen-deprivation therapy (ADT) and docetaxel significantly reduced the risk of death by 32.5% (HR, 0.68; 95% CI 0.57–0.80; P Citation Format: Neal D. Shore, Maha H.A. Hussain, Fred Saad, Karim Fizazi, Cora N. Sternberg, E. David Crawford, Bertrand Tombal, Luke Nordquist, Michael Cookson, Jay Jhaveri, Silke Thiele, Shankar Srinivasan, Jorge Ortiz, Matthew R. Smith. Efficacy and safety of darolutamide in combination with androgen-deprivation therapy (ADT) and docetaxel in Black/African-American patients from the phase 3 ARASENS trial [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B131.

No abstract available.

BACKGROUND Healthy eating is a key element of type 2 diabetes (T2D) self-management. Digital interventions offer new avenues to reach broad audiences to promote healthy eating behaviours. However, the acceptance of these interventions by socioeconomically disadvantaged people such as those with lower levels of education, lower income, or ethnic minority groups, has not yet been fully evaluated. OBJECTIVE The objective of this study was to investigate the acceptability and usability of EatSmart, a 12-week, web-based and mobile-delivered healthy eating behaviour change support program, from the perspective of both the intervention participants living with T2D, and Health Care Providers (HCPs) involved with diabetes care. METHODS This study employed a qualitative descriptive design. Sixty disadvantaged adults with T2D, as determined by receipt of either a HealthCare Card or a pension/benefit as the main source of income, were recruited to participate in the program. Data from participants regarding their experiences with and perceptions of the program and longer-term maintenance of any behavioural or attitudinal changes were collected through an online self-report survey with open ended questions administered 12-weeks post-baseline (n=54), and semi-structured telephone interviews administered at 36-weeks post-baseline (n=16). Supplementary semi-structured interviews with six HCPs involved with diabetes care (including endocrinologists, accredited practicing dietitians, and diabetes nurse educators) were also conducted at 36-weeks post-baseline. These interviews aimed to understand providers’ views about successful and unsuccessful elements of EatSmart as a technology-delivered intervention, any concerns or barriers regarding use of these type of interventions, and feedback from their interactions with patients about the intervention’s content, impact, or observed benefits. All data from surveys and interviews were pooled and thematically analysed. RESULTS Our data showed that EatSmart was acceptable to participants and contributed positively to improve food-related behaviours. Most participants mentioned that they enjoyed their experience with EatSmart and expressed high satisfaction with its content and delivery. The educational and motivational content was seen as the most useful parts of the program. Benefits discussed by intervention participants included gaining health knowledge and skills; positive changes in their food purchasing and cooking; and in eating greater quantities and varieties of fruits and vegetables. HCPs also described the intervention as beneficial and persuasive for the target audience and had specific suggestions for future tailoring of such programs. CONCLUSIONS The findings suggested that this digitally-delivered intervention with its supportive educational modules and text messages was generally appealing for both participants and HCPs. This intervention medium shows promise and could feasibly be rolled out on a broader scale to augment usual diabetes care. CLINICALTRIAL Australian New Zealand Clinical Trials Registry, ACTRN12619001111167; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12619001111167 INTERNATIONAL REGISTERED REPORT RR2-10.2196/19488

ObjectivesWork hours and commute time are key contributors to time scarcity, with potential detrimental implications for healthy eating. This study examined (1) associations between work and commute hours with food practices and (2) within-individual associations between changes in work and commute hours with changes in food practices.DesignLongitudinal studySettingAustraliaParticipantsData were from 14 807 respondents in waves 7 (2007), 9 (2009), 13 (2013) and 17 (2017) of the Household, Income and Labour Dynamics in Australia Survey. The sample for this analysis included individuals who were in paid employment in at least one of the four waves.Primary and secondary outcome measuresOutcomes included frequency of out-of-home food purchasing for breakfast, lunch, dinner and all three summed eating occasions, and fruit and vegetables consumption.ResultsResults indicated the longer individuals spent working and commuting, the more likely they were to purchase out-of-home foods (frequency of total out-of-home food purchasing: incidence rate ratio (IRR)=1.007 (95% CI 1.007 to 1.008)), and the less they consumed fruit and vegetables, although reductions in fruit and vegetables servings were minimal (fruit: β=−0.002 (95% CI −0.003 to –0.001), vegetables: β=−0.002 (95% CI −0.003 to –0.001)). Similar results regarding associations with out-of-home food purchasing were observed when examining within-individual changes (IRR=1.006 (95% CI 1.005 to 1.007)).ConclusionsResults suggest employment-related time demands push towards more frequent out-of-home food purchasing. In the long term, this may have negative health consequences as out-of-home foods tend to be less healthy than home-prepared foods.

Men treated with androgen deprivation therapy for rising PSA after failed local therapy will often develop castrate resistance, and the appearance of metastases predicts a poor prognosis. Thus, researchers have long sought to prolong the onset of metastasis in patients with nonmetastatic castration-resistant prostate cancer (CRPC). Until 2018, patients in this group had no FDA-approved treatment options. They were typically managed with androgen-deprivation therapy (ADT) to maintain castrate systemic testosterone levels and given approved therapies for metastatic CRPC once metastases appeared. However, third-generation androgen receptor inhibitors (ARIs) have dramatically changed the treatment paradigm, having shown the ability to extend metastasis-free survival (MFS) significantly over ADT alone in Phase 3 trials. The newest of these, darolutamide, prolonged MFS 22 months over placebo while also improving a host of secondary and exploratory endpoints such as overall survival (OS), prostate-specific antigen (PSA) progression and time to pain progression, chemotherapy initiation, and symptomatic skeletal events. Among third-generation ARIs, darolutamide is unique in that it incorporates two pharmacologically active diastereomers and has demonstrated resistance to all known androgen receptor (AR) mutations. Additionally, patients taking darolutamide appear to experience comparatively few central nervous system-related adverse events (AEs) such as fatigue and falls, and no increases in seizures have been reported in the drug’s clinical or preclinical development. Various authors attribute the low incidence of CNS-related AEs to darolutamide’s minimal penetration of the blood–brain barrier (BBB). Other side effects ranging from hot flashes to hypothyroidism also occurred at rates similar to those of the placebo arm in Phase 3. As ADT in itself raises cardiovascular risk, the cardiovascular safety of third-generation antiandrogens as a category warrants continued scrutiny. In total, however, published data suggest that darolutamide provides a reasonable option for patients with nonmetastatic CRPC. Ongoing research will determine darolutamide’s potential role in additional disease states such as localized and castration-sensitive PCa.