HIV self-screening distribution preferences and experiences among men who have sex with men in Mpumalanga Province: Informing policy for South Africa.

Current research suggests that HIV self-screening (HIVSS) is a feasible and acceptable approach to increase HIV testing among men who have sex with men (MSM). However, few data are available to shape policy around dissemination and implementation. Gaps in knowledge include preferences for distribution of HIVSS kits, potential social harms and benefits of their use, and how much test users would be willing to pay for the kits. The aim was to inform policy recommendations to optimise distribution of HIVSS kits to MSM in South Africa (SA), where there is a high HIV incidence and unmet testing needs. MSM in the high-HIV-prevalence Gert Sibande and Ehlanzeni districts of Mpumalanga Province, SA, were enrolled between October 2015 and May 2017. Participants were provided with their choice of blood or oral fluid HIVSS test kits, receiving 5 kits at enrolment and 4 additional kits at the 3-month follow-up visit. Questionnaires were administered at enrolment, 3 months and 6 months. We analysed participants' reported social benefits and harms, and their preferences for kit distribution and pricing. Among 127 MSM screened and enrolled, 114 responded to follow-up questionnaires regarding distribution preferences, 49.3% preferred to acquire HIVSS kits at a community-based organisation (CBO) and 42.7% at a clinic, with 8% preferring a pharmacy. Participants with higher education preferred CBO sites for distribution; in other respects preferences were similar by demographic characteristics. Reported social benefits were common, including knowing one's status, prevention knowledge gained and improved communication with partners. Despite ubiquitous interest in using the kits, the majority of MSM could not afford to purchase test kits. SA guidelines have integrated HIVSS into HIV and testing policy, but little has been published regarding distribution channels of the kits for MSM and other key populations. There is a partnership between the National Department of Health and CBOs that specialise in key population programming to ensure MSM and other populations with unmet testing needs can access affordable test kits. We observed no social harms, and there were multiple social benefits. Consequently, we recommend immediate free or low-cost distribution of HIVSS kits to MSM through community-based initiatives. Future research should continue to assess optimised linkage to care.

Clinical and economic impact of multiple gated acquisition scan monitoring during anthracycline therapy.

The clinical and economic impacts of monitoring cardiac function in patients given doxorubicin have yet to be determined, especially in relation to patient age, cumulative doxorubicin dose, and the relative efficacies of doxorubicin-based vs alternative regimens. We developed a decision analysis model that includes these factors to estimate the incremental survival benefit and cost-effectiveness of using multiple gated acquisition scans to measure left-ventricular ejection fraction before and during doxorubicin chemotherapy. Probability distributions for the incidences of abnormal left-ventricular ejection fraction findings and congestive heart failure were derived from a retrospective review of 227 consecutive cases at The University of Michigan Medical Center and published findings. Multiple gated acquisition-scan monitoring minimally improved the probability of 5-year survival (<1.5% in the base--case scenario). For patients who received up to 350 mg m(-2) of doxorubicin, multiple gated acquisition-scan screening had an incremental cost of $425 402 per life saved for patients between the ages of 15--39. This incremental cost markedly decreased to $138 191, for patients between the ages of 40--59, and to $86 829 for patients older than 60 years. The small gain in 5-year survival probability secondary to multiple gated acquisition scan monitoring doubled for all age groups when the average cumulative dose for doxorubicin reached 500 mg m(-2). Variations in the cure rate differences between the doxorubicin and alternative regimens had insignificant effects on the improvement in 5-year survival rates from multiple gated acquisition-scan screening. The use of multiple gated acquisition scans for pretreatment screening appears to be more cost-effective for patients who are 40 years or older, when cumulative doxorubicin dose is 350 mg m(-2) or less.

Executive Summary of the National Cancer Institute Workshop: Highlights and recommendations.

Prostate cancer chemoprevention represents a relatively new and promising strategy for reducing the immense public health burden of this devastating cancer of men in the United States and Western societies. Chemoprevention is defined as the administration of agents (drugs, biologics, and natural products) that modulate (inhibit) one or more steps in the multistage carcinogenesis process culminating in invasive adenocarcinoma of the prostate. In 2000, there were an estimated 170,000 new cases of prostate cancer and 31,000 deaths in the United States. During the past decade, the National Cancer Institute (NCI) organized the chemoprevention research program and began testing the first generation of promising agents (eg, 4-(hydroxy)-fenretinide [4-HPR], difluoromethylornithine [DFMO], antiandrogens) in high-risk cohorts and launched the first-large scale US phase 3 primary prevention trial, known as Prostate Cancer Prevention Trial (PCPT-1), in 18,000 average-risk men (age more than 55 years and prostate-specific antigen [PSA] less than 3 ng/mL) treated for 7 years with finasteride or placebo. In the summer of 1998, the NCI Prostate Cancer Progress Review Group (PRG) Report to the director of NCI was published in response to the leadership of the prostate cancer advocacy community in conjunction with Congress. To further elucidate and address critical issues identified in this report and to develop a research agenda for the newly created Prostate and Urologic Cancer Research Group in the Division of Cancer Prevention at NCI, the NCI organized the workshop "New Clinical Trial Strategies for Prostate Cancer Chemoprevention." The major objectives were to promote understanding and cooperation among the NCI, US Food and Drug Administration (FDA), academia, pharmaceutical industry, and the public regarding new opportunities for clinical prevention trials for prostate cancer. The workshop was divided into three concurrent breakout panels and a fourth joint integrative panel. The workshop addressed multiple key areas identified in the PRG report in the following panels: (1) Molecular Targets and Promising Agents in Clinical Development; (2) Intermediate Endpoint Biomarkers for Prevention Trials; (3) High-Risk Study Populations for Prevention Trials, and (4) Preventive Clinical Trial Designs and Regulatory Issues. Expert panelists were drawn from leading academic, pharmaceutical, and government scientists in basic research and clinical investigation. Key pharmaceutical, biotechnology, academic, and National Institutes of Health scientists presented overviews of their new agents and products in clinical development (representing the next generation of promising agents). Senior FDA physicians from the Center for Drugs and Center for Biologics presented on current standards for new drug and biologic approval for chemoprevention efficacy. Some of the key topics included recent advances in the state of knowledge of promising agents in the clinic based on molecular targets as well as bottlenecks in drug development for pharmaceutical sponsors; strategic modulable biomarkers that can serve as primary endpoints in phase 1/2 trials to assess preventive efficacy; high-risk cohorts with precancer (high-grade prostatic intraepithelial neoplasia) and representative clinical trial designs that are ready for immediate translation into efficient prevention trials, such as Bayesian sequential monitoring for early assessment of biologic activity and factorial designs for assessment of multiagent combinations. Finally, each expert panel generated recommendations for areas of future research emphasizing opportunities and infrastructure needs.

Frequent microsatellite alterations at chromosomes 9p21 and 3p14 in oral premalignant lesions and their value in cancer risk assessment.

To better understand genetic alterations in oral premalignant lesions, we examined 84 oral leukoplakia samples from 37 patients who had been enrolled in a chemoprevention trial. The samples were analyzed for two microsatellite markers located at chromosomes 9p21 and 3p14. Loss of heterozygosity (LOH) at either or both loci was identified in 19 of the 37 (51%) patients. Of these 19 patients, seven (37%) have developed head and neck squamous cell carcinoma (HNSCC) while only one of 18 (6%) of patients without LOH developed HNSCC. Our data suggest that clonal genetic alterations are common in oral premalignant lesions; that multiple genetic alterations have already occurred in oral premalignant lesions, allowing at least a focal clonal expansion; and that losses of the 9p21 and 3p14 regions may be related to early processes of tumorigenesis in HNSCC. These genetic alterations in premalignant tissues may serve as markers for cancer risk assessment.

A quantitatively scored cancer-risk assessment tool: its development and use.

Achievement of NIH and ACS goals for reduction in cancer mortality will require increased efforts directed at risk reduction and early detection in the general population. Primary care providers will play a major role. This paper describes the development and use of a quantitative cancer-risk appraisal tool designed to promote cancer prevention and screening and provide a framework for advancing education on these critical issues at all levels of medical training, to assist physicians in risk identification and patient counseling. The risk assessment questionnaire is close-ended and easily completed by the patient within 10 to 15 minutes. The IBM-compatible format permits easy quantitation by laser scanning and computer analysis. This program quantitates risks arising from interacting independent factors and estimates the effects of primary prevention interventions. Program output includes age- and sex-specific ACS screening guidelines and discussion of intensified screening measures in high-risk subjects.