Serum markers, obesity and prostate cancer risk: results from the prostate cancer prevention trial

Molecular mechanisms linking obesity to prostate cancer involve steroid hormone and insulin/insulin-like growth factor-1 (IGF-1) pathways. We investigated the association of circulating serum markers (e.g., androgens and IGFs/IGFBPs) with BMI and in modifying the association of obesity with prostate cancer risk. Data and specimens for this nested case-control study are from the Prostate Cancer Prevention Trial, a randomized, placebo-controlled trial of finasteride for prostate cancer prevention. Presence or absence of cancer was determined by prostate biopsy. Serum samples were assayed for sex steroid hormone concentrations and IGF-1 axis analytes. Logistic regression estimated odds ratio and 95% confidence intervals (CIs) for risk of overall, low-grade (Gleason 2–6), and high-grade (Gleason 7–10) cancers. We found significant associations between BMI with serum steroids and IGFs/IGFBPs; the IGF-1 axis significantly associated with several serum steroids. Serum steroid levels did not affect the association of BMI with prostate cancer risk; however, IGFBP2 and IGFs modified the association of obesity with low- and high-grade disease. While serum steroids and IGFs/IGFBPs are associated with BMI, only the IGF-1 axis contributed to obesity-related prostate cancer risk. Understanding the biological mechanisms linking obesity to prostate cancer risk as it relates to circulating serum markers will aid in developing effective prostate cancer prevention strategies and treatments.

Gut microbiota develop towards an adult profile in a sex-specific manner during puberty

Accumulating evidence indicates that gut microbiota may regulate sex-hormone levels in the host, with effects on reproductive health. Very little is known about the development of intestinal microbiota during puberty in humans. To assess the connection between pubertal timing and fecal microbiota, and to assess how fecal microbiota develop during puberty in comparison with adult microbiota, we utilized a Finnish allergy-prevention-trial cohort (Flora). Data collected at 13-year follow-up were compared with adult data from a different Finnish cohort. Among the 13-year-old participants we collected questionnaire information, growth data from school-health-system records and fecal samples from 148 participants. Reference adult fecal samples were received from the Health and Early Life Microbiota (HELMi) cohort (n = 840). Fecal microbiota were analyzed using 16S rRNA gene amplicon sequencing; the data were correlated with pubertal timing and compared with data on adult microbiota. Probiotic intervention in the allergy-prevention-trial cohort was considered as a confounding factor only. The main outcome was composition of the microbiota in relation to pubertal timing (time to/from peak growth velocity) in both sexes separately, and similarity to adult microbiota. In girls, fecal microbiota became more adult-like with pubertal progression (p = 0.009). No such development was observed in boys (p = 0.9). Both sexes showed a trend towards increasing relative abundance of estrogen-metabolizing Clostridia and decreasing Bacteroidia with pubertal development, but this was statistically significant in girls only (p = 0.03). In girls, pubertal timing was associated positively with exposure to cephalosporins prior to the age of 10. Our data support the hypothesis that gut microbiota, particularly members of Ruminococcaceae, may affect pubertal timing, possibly via regulating host sex-hormone levels.Trial registration The registration number for the allergy-prevention-trial cohort: ClinicalTrials.gov, NCT00298337, registered 1 March 2006—Retrospectively registered, https://clinicaltrials.gov/show/NCT00298337. The adult-comparison cohort (HELMi) is NCT03996304.

Stakeholder Insights Into a Systems-Based Suicide Prevention Program Implemented in Regional and Rural Tasmanian Communities

Purpose: Emerging evidence indicates that systems-based suicide prevention programs can help optimise suicide prevention activities, with the National Suicide Prevention Trial using these approaches in regional and community contexts throughout Australia. The Tasmanian arm of the Trial adopted the LifeSpan systems framework to deliver suicide prevention activities across three distinct geographical areas, focusing on high-risk populations of men aged 40-64 and people 65 and over. The University of Tasmania’s Centre for Rural Health undertook a local-level evaluation of the Trial in Tasmania.Aims: To explore key stakeholder perceptions of the implementation of a systems-based suicide prevention program in regional and rural communities in Tasmania, Australia.Method: Focus groups and interviews with 46 participants, comprising Working Group members (n=25), Tasmania’s Primary Health Network employees (n=7), and other key stakeholders (n=14), with the majority (53.3%) reporting a lived experience of suicide. Thematic analysis was used to explore data and study aims.Results: Key themes centred on how the National Suicide Prevention Trial was understood and established in Tasmania; Working Group governance structures and processes; communication and engagement processes; reaching priority population groups; the LifeSpan model and activity development; and the effectiveness and sustainability of activities.Discussion: Findings showed communities were wary of suicide and wanted to engage to take action and the Trial provided the resources and coordination to do so. Perceived limitations implementing the Trial included varied involvement of key stakeholders, and lack of role clarity within Working Groups. Barriers delivering activities to the priority population groups suggested a strict adherence to the Lifespan model was challenging. Working Groups embraced a pragmatic approach, preferring activities that best utilised available capital and resources to meet perceived needs within communities. While a focus on effectiveness and sustainability of activities was seen as important, barriers at the community-level, i.e. nobody to run them, hindered these efforts. Analysis of stakeholder perceptions provides crucial insights for guiding future community-based suicide prevention efforts in regional and rural areas, and with high-risk groups.

Women’s sexual scripting in the context of universal access to antiretroviral treatment—findings from the HPTN 071 (PopART) trial in South Africa

Background HIV treatment-based prevention modalities present new opportunities for women to make decisions around sex, intimacy, and prevention. The Universal test and treat (UTT) strategy, where widespread HIV testing is implemented and all people with HIV can access treatment, has the potential to change how sex is understood and HIV prevention incorporated into sexual relationships. We use the frame of sexual scripting to explore how women attribute meaning to sex relative to UTT in an HIV prevention trial setting. Exploring women’s sexual narratives, we explored how HIV prevention feature in the sexual scripts for women who had access to UTT in South Africa (prior to treatment guideline changes) and increased HIV prevention messaging, compared to places without widespread access to HIV testing and immediate access to treatment. Methods We employed a two-phased thematic analysis to explore longitudinal qualitative data collected from 71 women (18–35 years old) between 2016 and 2018 as part of an HIV prevention trial in the Western Cape Province, South Africa. Of the participants, 58/71 (82%) were from intervention communities while 13/71 (18%) lived in control communities without access to UTT. Twenty participants self-disclosed that they were living with HIV. Results We found no narrative differences between women who had access to UTT and those who did not. HIV and HIV prevention, including treatment-based prevention modalities, were largely absent from women’s thinking about sex. In their scripts, women idealised romantic sex, positioned sex as ‘about relationships’, and described risky sex as ‘other’. When women were confronted by HIV risk (for example, when a partner disclosed his HIV-positive status) this created a point of disjuncture between this new perception of risk and their accepted relationship scripts. Conclusion These findings suggest that HIV-negative women did not include their partners’ use of antiretroviral therapy in their sexual partnership choices. For these women, the preventive benefits of UTT are experienced passively—through community-wide viral suppression—rather than through their own behaviour change explicitly related to the availability of treatment as prevention. We propose that prevention-based modalities should be made available and supported and framed as an intervention to promote relationship well-being.

Validation of the European Drug Addiction Prevention Trial Questionnaire (EU-Dap) for substance use screening and to assess risk and protective factors among early adolescents in Chile

Background Substance use is highly prevalent among Chilean adolescents, and the damage it causes at the neurobiological, psychological, and social levels is known. However, there are no validated screening instruments that also assess risk and protective factors for this population in Chile, which is essential for evaluating future prevention interventions. Objective To determine the psychometric properties of the European Drug Addiction Prevention Trial Questionnaire (EU-Dap) questionnaire. Methods A cross-sectional study was carried out in 13 schools in the city of Santiago de Chile. The sample included 2261 adolescents ranging from 10 to 14 years old. Linguistic and cultural adaptation was assessed using focus groups with adolescents, the construct validity was evaluated using confirmatory factor analysis, and measures of its reliability were also determined. Furthermore, the associations regarding risk and protective factors with substance use were explored. Results Substance use questions were well understood and seemed to adequately capture the consumption of different drugs. Regarding the subscales of risk and protective factors, the analyses showed that most subscales had good psychometric properties, and few needed some degree of improvement (e.g., some items were removed). After the changes, most final subscales had good or adequate goodness of fit adjustments and good or acceptable internal consistency. Finally, the main associated factors with the substance use outcomes were: future substance use and school bonding for tobacco use; negative beliefs about alcohol, future substance use, school bonding and refusal skills for alcohol use; and negative beliefs about marihuana, positive attitudes towards drugs, risk perception, and substance abuse index for marihuana use. Normative beliefs increased the risk for all substances use. Conclusions The current findings suggest that the EU-Dap is a valid and reliable instrument, and it may help to evaluate the effectiveness of drug use prevention interventions.

Challenges in recruiting children to a multidrug-resistant TB prevention trial

BACKGROUND: Recruitment to randomised clinical trials can be challenging and slow recruitment has serious consequences. This study aimed to summarise and reflect on the challenges in enrolling young children to a multidrug-resistant TB (MDR-TB) prevention trial in South Africa.METHODS: Recruitment to the Tuberculosis Child Multidrug-resistant Preventive Therapy Trial (TB-CHAMP) was tracked using an electronic recruiting platform, which was used to generate a recruiting flow diagram. Structured personnel questionnaires, meeting minutes and workshop notes were thematically analysed to elucidate barriers and solutions.RESULT: Of 3,682 (85.3%) adult rifampicin (RIF) resistant index cases with pre-screening outcomes, 1597 (43.4%) reported having no children under 5 years in the household and 562 (15.3%) were RIF-monoresistant. More than nine index cases were pre-screened for each child enrolled. Numerous barriers to recruitment were identified. Thorough recruitment planning, customised tracking data systems, a dedicated recruiting team with strong leadership, adequate resources to recruit across large geographic areas, and excellent relationships with routine TB services emerged as key factors to ensure successful recruitment.CONCLUSION: Recruitment of children into MDR-TB prevention trials can be difficult. Several MDR-TB prevention trials are underway, and lessons learnt from TB-CHAMP will be relevant to these and other TB prevention studies.

Preference-weighted quality of life: Findings from the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

144 Background: The differences in preference-weighted health-related quality of life (HRQOL) among racial and ethnic groups have been previously reported. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) enrolled 35,533 men aged 50 years and older, among whom 20% were minorities. HRQOL, using the SF-36V, was examined for a subset of participants. Using these survey data, we examined the preference-weighted HRQOL differences across the racial/ethnic categories included in SELECT. Methods: SELECT participants who completed the SF-36V at baseline, and subsequently in at least one of years 1, 3, and 5 were included. We used the SF-6D to calculate an HRQOL score ranging between 0 (worst possible) and 1 (best possible) for every participant using data from the SF-36V. We modeled the association of race/ethnicity with SF-6D scores using a linear mixed model adjusting for demographic and clinical characteristics. Results: At baseline, 9,691 men were eligible for analysis. Hispanic and non-Hispanic white participants had higher unadjusted mean SF-6D scores than non-Hispanic Black participants at baseline and every subsequent time point (p<0.05; Table). Non-Hispanic white participants had lower mean scores than Hispanic participants at every time point after baseline. After adjusting for demographic and clinical characteristics there are statistically significant differences in HRQOL among all three groups. In particular, Hispanic participants had higher scores than white participants by.074 (p<.001),.076 (p<.001), and.039 (p<.001) in years 1, 3, and 5 after baseline. Conversely, compared to non-Hispanic White participants, non-Hispanic Black participants had lower scores by.009 (p=.004) and.008 (p=.02) in years 1 and 3 after baseline. Conclusions: In this sample of men enrolled in a prostate cancer chemoprevention trial, preference-weighted HRQOL using the SF-6D was higher for Hispanic men than for white and Black men, and lower for Black men than for white men. Understanding how individuals belonging to different racial and/or ethnic categories view their own HRQOL is necessary not only for delivering culturally competent care but also for conducting accurate cost effectiveness analyses of new interventions and programs. Further research that includes a sample with women, reports on more categories of race/ethnicity, and explores underlying potential cultural and social differences is necessary. [Table: see text]