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| 2. |
- Abe, O, et al.
(author)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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In: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Journal article (peer-reviewed)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 6. |
- Jaffee, E. M., et al.
(author)
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Future cancer research priorities in the USA: a Lancet Oncology Commission
- 2017
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In: Lancet Oncology. - 1470-2045. ; 18:11
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Research review (peer-reviewed)abstract
- We are in the midst of a technological revolution that is providing new insights into human biology and cancer. In this era of big data, we are amassing large amounts of information that is transforming how we approach cancer treatment and prevention. Enactment of the Cancer Moonshot within the 21st Century Cures Act in the USA arrived at a propitious moment in the advancement of knowledge, providing nearly US$ 2 billion of funding for cancer research and precision medicine. In 2016, the Blue Ribbon Panel (BRP) set out a roadmap of recommendations designed to exploit new advances in cancer diagnosis, prevention, and treatment. Those recommendations provided a high-level view of how to accelerate the conversion of new scientific discoveries into effective treatments and prevention for cancer. The US National Cancer Institute is already implementing some of those recommendations. As experts in the priority areas identified by the BRP, we bolster those recommendations to implement this important scientific roadmap. In this Commission, we examine the BRP recommendations in greater detail and expand the discussion to include additional priority areas, including surgical oncology, radiation oncology, imaging, health systems and health disparities, regulation and financing, population science, and oncopolicy. We prioritise areas of research in the USA that we believe would accelerate efforts to benefit patients with cancer. Finally, we hope the recommendations in this report will facilitate new international collaborations to further enhance global efforts in cancer control.
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| 8. |
- Leddy, Anna M., et al.
(author)
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Community collective efficacy is associated with reduced physical intimate partner violence (IPV) incidence in the rural province of Mpumalanga, South Africa : findings from HPTN 068
- 2019
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In: Journal of Epidemiology and Community Health. - : BMJ Publishing Group Ltd. - 0143-005X .- 1470-2738. ; 73:2, s. 176-181
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Journal article (peer-reviewed)abstract
- Background Intimate partner violence (IPV) is a human rights violation and is associated with a variety of adverse physical and mental health outcomes. Collective efficacy, defined as mutual trust among community members and willingness to intervene on the behalf of the common good, has been associated with reduced neighbourhood violence. Limited research has explored whether community collective efficacy is associated with reduced incidence of IPV. This is of particular interest among adolescent girls and young women (AGYW) in sub-Saharan Africa, where the burden of HIV is greatest and IPV is common. Methods We collected longitudinal data among 2533 AGYW (ages 13-20) enrolled in the HPTN 068 cohort in Mpumalanga province, South Africa between 2011 and 2016. We included participants from 26 villages where community surveys were collected during the HPTN 068 study. Collective efficacy was measured at the village level via two population-based cross-sectional surveys in 2012 and 2014. Multivariable Poisson generalised estimating equation regression models estimated the relative risk ratio (RR) between village collective efficacy scores and subsequent physical IPV 12 month incidence, adjusting for village-level clustering and covariates. Results Thirty-eight per cent of the cohort (n=950) reported at least one episode of recent physical IPV during follow-up. For every SD higher level of collective efficacy, there was a 6% lower level of physical IPV incidence (adjusted RR: 0.94; 95% CI 0.89 to 0.98) among AGYW after adjusting for covariates. Conclusions Community-level interventions that foster the development of collective efficacy may reduce IPV among AGYW.
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| 9. |
- Lippman, Sheri A., et al.
(author)
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Village community mobilization is associated with reduced HIV incidence in young South African women participating in the HPTN 068 study cohort
- 2018
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In: Journal of the International AIDS Society. - : John Wiley & Sons. - 1758-2652. ; 21:S7
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Journal article (peer-reviewed)abstract
- Introduction: Adolescent girls and young women (AGYW) in South Africa bear a disproportionate burden of HIV. Community mobilization (CM), defined as community members taking collective action to achieve a common goal related to health, equity and rights, has been associated with increased HIV testing and condom use and has been called a ‘critical enabler’ for addressing the HIV epidemic. However, limited research has examined whether CM is associated with HIV incidence among AGYW.Methods: We examine the association of CM with incident HIV among AGYW (ages 13 to 21) enrolled in the HPTN 068 cohort in the Agincourt Health and socio‐Demographic Surveillance System, South Africa. This analysis includes 2292 participants residing in 26 villages where cross‐sectional, population‐based surveys were conducted to measure CM among 18‐ to 35‐year‐old residents in 2012 and 2014. HPTN 068 participants completed up to five annual visits that included an HIV test (2011 to 2016). Household‐level data were collected from AGYW parents/guardians and census data is updated annually. Mean village‐level CM scores were created using a validated community mobilization measure with seven components (social cohesion, social control, critical consciousness, shared concerns, organizations and networks, leadership and collective action). We used pooled generalized estimating equation regression with a Poisson distribution to estimate risk ratios (RR) for the association of village‐level CM score and CM components with incident HIV infection, accounting for village‐level clustering and adjusting for key covariates.Results: There were 194 incident infections over the follow‐up period. For every additional standard deviation of village‐level CM there was 12% lower HIV incidence (RR: 0.88, 95% CI: 0.79, 0.98) after adjusting for individual, household and community characteristics. CM components associated with lower HIV incidence included critical consciousness (RR: 0.88; CI: 0.79, 0.97) and leadership (RR: 0.87; CI: 0.79, 0.95); while not statistically significant, social cohesion (RR: 0.91; CI: 0.81, 1.01), shared concerns (RR: 0.90; CI: 0.81, 1.00), and organizations and networks (RR: 0.91; CI: 0.79, 1.03) may also play a protective role.Conclusions: These results suggest that having strong community social resources will reduce AGYW's risk of HIV acquisition. Work to mobilize communities, focusing on building social cohesion, shared concerns, critical consciousness, and effective and accountable leadership, can fortify prevention programming for AGYW.
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| 10. |
- MacPhail, Catherine, et al.
(author)
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Process elements contributing to community mobilization for HIV risk reduction and gender equality in rural South Africa
- 2019
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 14:12
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Journal article (peer-reviewed)abstract
- Community mobilization has been recognized as a critical enabler for HIV prevention and is employed for challenging gender inequalities. We worked together with community partners to implement the 'One Man Can' intervention in rural Mpumalanga, South Africa to promote gender equality and HIV risk reduction. During the intervention, we conducted longitudinal qualitative interviews and focus group discussions with community mobilizers (n = 26), volunteer community action team members (n = 22) and community members (n = 52) to explore their experience of being part of the intervention and their experiences of change associated with the intervention. The objective of the study was to examine processes of change in community mobilization for gender equity and HIV prevention. Our analysis showed that over time, participants referred to three key elements of their engagement with the intervention: developing respect for others; inter-personal communication; and empathy. These elements were viewed as assisting them in adopting a 'better life' and associated with behaviour change in the intervention's main focus areas of promoting gender equality and HIV risk reduction behaviours. We discuss how these concepts relate to the essential domains contained within our theoretical framework of community mobilization-specifically critical consciousness, shared concerns and social cohesion -, as demonstrated in this community. We interpret the focus on these key elements as significant indicators of communities engaging with the community mobilization process and initiating movement towards structural changes for HIV prevention.
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| 11. |
- Pettifor, Audrey, et al.
(author)
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Community mobilization to modify harmful gender norms and reduce HIV risk : results from a community cluster randomized trial in South Africa
- 2018
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In: Journal of the International AIDS Society. - : John Wiley & Sons. - 1758-2652. ; 21:7
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Journal article (peer-reviewed)abstract
- Introduction: Community mobilization (CM) is increasingly recognized as critical to generating changes in social norms and behaviours needed to achieve reductions in HIV. We conducted a CM intervention to modify negative gender norms, particularly among men, in order to reduce associated HIV risk.Methods: Twenty two villages in the Agincourt Health and Socio-Demographic Surveillance Site in rural Mpumalanga, South Africa were randomized to either a theory-based, gender transformative, CM intervention or no intervention. Two cross-sectional, population-based surveys were conducted in 2012 (pre-intervention, n = 600 women; n = 581 men) and 2014 (pos-tintervention, n = 600 women; n = 575 men) among adults ages 18 to 35 years. We used an intent-to-treat (ITT) approach using survey regression cluster-adjusted standard errors to determine the intervention effect by trial arm on gender norms, measured using the Gender Equitable Mens Scale (GEMS), and secondary behavioural outcomes.Results: Among men, there was a significant 2.7 point increase (Beta Coefficient 95% CI: 0.62, 4.78, p = 0.01) in GEMS between those in intervention compared to control communities. We did not observe a significant difference in GEMS scores for women by trial arm. Among men and women in intervention communities, we did not observe significant differences in perpetration of intimate partner violence (IPV), condom use at last sex or hazardous drinking compared to control communities. The number of sex partners in the past 12 months (AOR 0.29, 95% CI 0.11 to 0.77) were significantly lower in women in intervention communities compared to control communities and IPV victimization was lower among women in intervention communities, but the reduction was not statistically significant (AOR 0.53, 95% CI 0.24 to 1.16).Conclusion: Community mobilization can reduce negative gender norms among men and has the potential to create environments that are more supportive of preventing IPV and reducing HIV risk behaviour. Nevertheless, we did not observe that changes in attitudes towards gender norms resulted in desired changes in risk behaviours suggesting that more time may be necessary to change behaviour or that the intervention may need to address behaviours more directly.
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| 12. |
- Leddy, Anna M., et al.
(author)
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Emotional Violence is Associated with Increased HIV Risk Behavior Among South African Adolescent Girls and Young Women in the HPTN 068 Cohort
- 2022
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In: Aids and Behavior. - : Springer. - 1090-7165 .- 1573-3254. ; 26:6, s. 1863-1870
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Journal article (peer-reviewed)abstract
- Limited research has explored how emotional intimate partner violence (IPV) shapes HIV risk behaviors. Using cross-sectional data from the HPTN 068 post-trial visit (N = 1942), we assessed the association between emotional IPV and its sub-domains (verbal abuse and threats) with condomless sex, transactional sex, and frequent alcohol use among young women in South Africa. In adjusted multivariable logistic regression models, any emotional IPV and verbal IPV were associated with increased odds of condomless sex (aOR: 1.47; 95% CI: 1.15, 1.87; and aOR: 1.48; 95% CI: 1.15, 1.89), transactional sex (aOR: 2.32; 95% CI: 1.74, 3.08; and aOR: 2.02; 95% CI: 1.51, 2.71) and alcohol use (aOR: 1.88; 95% CI: 1.39, 2.53; and aOR: 1.87; 95% CI: 1.37, 2.55). Threats were associated with transactional sex (aOR: 3.67; 95% CI: 2.62, 5.14). Future research should examine this relationship over-time and HIV prevention programs should consider and address emotional IPV.
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| 13. |
- Leddy, Anna M., et al.
(author)
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Examining Mediators of the Relationship Between Community Mobilization and HIV Incidence Among Young South African Women Participating in the HPTN 068 Study Cohort
- 2022
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In: Aids and Behavior. - : Springer. - 1090-7165 .- 1573-3254. ; 26:5, s. 1347-1354
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Journal article (peer-reviewed)abstract
- We previously demonstrated that village community mobilization (CM) was associated with reduced HIV incidence among adolescent girls and young women (AGYW) in South Africa. Little remains known about the mechanisms linking CM to HIV incidence. Using longitudinal data from 2292 AGYW in the HPTN 068 cohort (2011–2017), we examined whether school attendance, pro-social engagement, and hope for the future mediated the relationship between CM and HIV incidence. CM was measured at the village-level via two population-based surveys (2012 and 2014). Mediators and incident HIV infection were measured through HPTN 068 surveys and HIV testing. Mediation analyses were conducted using Mplus 8.5, adjusting for village-level clustering and covariates. Hope for the future mediated the relationship between CM and HIV incidence (indirect effect-RR 0.98, bias-corrected 95% CI 0.96, 0.99). Pro-social engagement and school attendance did not demonstrate indirect effects. CM reduces AGYW’s HIV acquisition risk, in part, by engendering hope.
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| 14. |
- Lippman, Sheri A, et al.
(author)
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A community mobilisation intervention to improve engagement in HIV testing, linkage to care, and retention in care in South Africa : a cluster-randomised controlled trial
- 2022
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In: The Lancet HIV. - : Elsevier. - 2405-4704 .- 2352-3018. ; 9:9, s. e617-e626
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Journal article (peer-reviewed)abstract
- Background: Community mobilisation, engaging communities in a process to collectively enact change, could improve HIV testing and care engagement. In South Africa, current rates fall below those needed for epidemic control. We assessed whether community mobilisation increased HIV testing, linkage to care, and retention in care over time in intervention relative to control communities.Methods: We conducted a cluster-randomised controlled trial in villages in the Agincourt sub-district of the rural Mpumalanga Province in South Africa. 15 villages were randomly assigned to either a community mobilisation intervention engaging residents to address social barriers to HIV testing and treatment (intervention arm) or to a control arm using balanced randomisation. Villages were eligible if they had been fully enumerated in 2014, had not been included in previous mobilisation activities, and included over 500 permanent adult residents aged 18–49 years. Primary outcomes included quarterly rates of HIV testing, linkage to care, and retention in care documented from health facility records among residents of the intervention and control communities over the 3-year study period. Intention-to-treat analyses employed generalised estimating equations stratified by sex. This trial is registered with ClinicalTrials.gov, NCT02197793.Findings: Between Aug 1, 2015, and July 31, 2018, residents in eight intervention communities (n=20 544 residents) and seven control communities (n=17 848) contributed data; 92 residents contributed to both arms. Among men, HIV testing increased quarterly by 12·1% (relative change [RC] 1·121, 95% CI 1·099 to 1·143, p<0·0001) in the intervention communities and 9·5% (1·095, 1·075 to 1·114, p=0·011) in the control communities; although increases in testing were greater in the intervention villages, differences did not reach significance (exponentiated interaction coefficient 1·024, 95% CI 0·997 to 1·052, p=0·078). Among women, HIV testing increased quarterly by 10·6% (RC 1·106, 95% CI 1·097 to 1·114, p<0·0001) in the intervention communities and 9·3% (1·093, 1·084 to 1·102, p=0·053) in the control communities; increases were greater in intervention communities (exponentiated interaction coefficient 1·012, 95% CI 1·001 to 1·023, p=0·043). Quarterly linkage increased significantly among women in the intervention communities (RC 1·013, 95% CI 1·002 to 1·023, p=0·018) only. Quarterly linkage fell among men in both arms, but decreased significantly among men in the control communities (0·977, 0·954 to 1·002, p=0·043). Quarterly retention fell among women in both arms; however, reductions were tempered among women in the intervention communities (exponentiated interaction coefficient 1·003, 95% CI <1·000 to 1·006, p=0·062). Retention fell significantly among men in both arms with difference in rates of decline.Interpretation: Community mobilisation was associated with modest improvements in select trial outcomes. The sum of these incremental, quarterly improvements achieved by addressing social barriers to HIV care engagement can impact epidemic control. However, achieving optimal impacts will probably require integrated efforts addressing both social barriers through community mobilisation and provision of improved service delivery.
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| 15. |
- Lippman, Sheri A., et al.
(author)
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Evaluation of the Tsima community mobilization intervention to improve engagement in HIV testing and care in South Africa : study protocol for a cluster randomized trial
- 2017
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In: Implementation Science. - : BIOMED CENTRAL LTD. - 1748-5908. ; 12:9
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Journal article (peer-reviewed)abstract
- Background: HIV transmission can be decreased substantially by reducing the burden of undiagnosed HIV infection and expanding early and consistent use of antiretroviral therapy (ART). Treatment as prevention (TasP) has been proposed as key to ending the HIV epidemic. To activate TasP in high prevalence countries, like South Africa, communities must be motivated to know their status, engage in care, and remain in care. Community mobilization (CM) has the potential to significantly increase uptake testing, linkage to and retention in care by addressing the primary social barriers to engagement with HIV care-including poor understanding of HIV care; fear and stigma associated with infection, clinic attendance and disclosure; lack of social support; and gender norms that deter men from accessing care. Methods/design: Using a cluster randomized trial design, we are implementing a 3-year-theory-based CM intervention and comparing gains in HIV testing, linkage, and retention in care among individuals residing in 8 intervention communities to that of individuals residing in 7 control communities. Eligible communities include 15 villages within a health and demographic surveillance site (HDSS) in rural Mpumalanga, South Africa, that were not exposed to previous CM efforts. CM activities conducted in the 8 intervention villages map onto six mobilization domains that comprise the key components for community mobilization around HIV prevention. To evaluate the intervention, we will link a clinic-based electronic clinical tracking system in all area clinics to the HDSS longitudinal census data, thus creating an open, population-based cohort with over 30,000 18-49-year-old residents. We will estimate the marginal effect of the intervention on individual outcomes using generalized estimating equations. In addition, we will evaluate CM processes by conducting baseline and endline surveys among a random sample of 1200 community residents at each time point to monitor intervention exposure and community level change using validated measures of CM. Discussion: Given the known importance of community social factors with regard to uptake of testing and HIV care, and the lack of rigorously evaluated community-level interventions effective in improving testing uptake, linkage and retention, the proposed study will yield much needed data to understand the potential of CM to improve the prevention and care cascade. Further, our work in developing a CM framework and domain measures will permit validation of a CM conceptual framework and process, which should prove valuable for community programming in Africa.
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| 16. |
- Stoner, Marie C.D., et al.
(author)
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Modeling Combination Interventions to Prevent Human Immunodeficiency Virus in Adolescent Girls and Young Women in South Africa (HIV Prevention Trials Network 068)
- 2021
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In: Clinical Infectious Diseases. - : Oxford University Press. - 1058-4838 .- 1537-6591. ; 73:7, s. e1911-e1918
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Journal article (peer-reviewed)abstract
- BACKGROUND: Combination interventions may be an effective way to prevent human immunodeficiency virus (HIV) in adolescent girls and young women. However, current studies are not designed to understand which specific interventions and combinations will be most effective. We estimate the possible impacts of interventions on a combination of factors associated with HIV.METHODS: We used the g-formula to model interventions on combinations of HIV risk factors to identify those that would prevent the most incident HIV infections, including low school attendance, intimate partner violence, depression, transactional sex, and age-disparate partnerships. We used data from the HIV Prevention Trials Network (HPTN) 068 study in rural South Africa from 2011 to 2017. We estimated HIV incidence under a potential intervention that reduced each risk factor and compared this to HIV incidence under the current distribution of these risk factors.RESULTS: Although many factors had strong associations with HIV, potential intervention estimates did not always suggest large reductions in HIV incidence because the prevalence of risk factors was low. When modeling combination effects, an intervention to increase schooling, decrease depression, and decease transactional sex showed the largest reduction in incident infection (risk difference, -1.4%; 95% confidence interval [CI], -2.7% to -.2%), but an intervention on only transactional sex and depression still reduced HIV incidence by -1.3% (95% CI, -2.6% to -.2%).CONCLUSIONS: To achieve the largest reductions in HIV, both prevalence of the risk factor and strength of association with HIV must be considered. Additionally, intervening on more risk factors may not necessarily result in larger reductions in HIV incidence.
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| 17. |
- Treves-Kagan, Sarah, et al.
(author)
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Gender, HIV Testing and Stigma : The Association of HIV Testing Behaviors and Community-Level and Individual-Level Stigma in Rural South Africa Differ for Men and Women
- 2017
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In: Aids and Behavior. - : Springer. - 1090-7165 .- 1573-3254. ; 21:9, s. 2579-2588
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Journal article (peer-reviewed)abstract
- Stigma remains a significant barrier to HIV testing in South Africa. Despite being a social construct, most HIV-stigma research focuses on individuals; further the intersection of gender, testing and stigma is yet to be fully explored. We examined the relationship between anticipated stigma at individual and community levels and recent testing using a population-based sample (n = 1126) in Mpumalanga, South Africa. We used multi-level regression to estimate the potential effect of reducing community-level stigma on testing uptake using the g-computation algorithm. Men tested less frequently (OR 0.22, 95% CI 0.14-0.33) and reported more anticipated stigma (OR 5.1, 95% CI 2.6-10.1) than women. For men only, testing was higher among those reporting no stigma versus some (OR 1.40, 95% CI 0.97-2.03; p = 0.07). For women only, each percentage point reduction in community-level stigma, the likelihood of testing increased by 3% (p < 0.01). Programming should consider stigma reduction in the context of social norms and gender to tailor activities appropriately.
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