A Protective Role for Arachidonic Acid Metabolites against Advanced Colorectal Adenoma in a Phase III Trial of Selenium

Oxylipins derived from arachidonic acid (ARA) have been implicated in the development of colorectal adenomas and colorectal cancer. The primary purpose of this work was to determine the relationship between plasma levels of oxylipins and colorectal adenoma characteristics at study entry, as well as with the development of a new adenoma during follow-up within a Phase III adenoma prevention clinical trial with selenium (Sel). Secondarily, we sought to determine whether the selenium intervention influenced plasma oxylipin levels. Four oxylipins were quantified in stored plasma samples from a subset of Sel study subjects (n = 256) at baseline and at 12-months. There were significantly lower odds of an advanced adenoma at baseline with higher prostaglandin E2 (PGE2), with an OR (95% CI) of 0.55 (0.33–0.92), and with 5-hydroxyeicosatetraenoic acid (5-HETE) ((0.53 (0.33–0.94)); and of a large adenoma with higher PGE2 ((0.52 (0.31–0.87)). In contrast, no associations were observed between any oxylipin and the development of a new adenoma during follow-up. Selenium supplementation was associated with a significantly smaller increase in 5-HETE after 12 months compared to the placebo, though no other results were statistically significant. The ARA-derived oxylipins may have a role in the progression of non-advanced adenoma to advanced, but not with the development of a new adenoma.

Application of a composite measure of product adherence, protocol compliance, and semen exposure to a phase III microbicide HIV prevention trial

Background Strict adherence to antiretroviral-based microbicide use is important for effective HIV prevention. We previously developed a composite measure of product adherence, protocol compliance, and semen exposure for determining vaginal use of tenofovir (TFV) 1% gel applicators through biomarkers and residual drug analyses. In this study, we tested the ability of the composite measure in vaginally used TFV gel applicators from a Phase III HIV prevention clinical trial. Methods Used vaginal gel applicators from the FACTS 001 study were swabbed for detection of vaginal bacterial markers (vaginal insertion), semen DNA markers (semen exposure), and residual TFV gel (product use). Results Of 1,098 evaluable TFV and placebo applicators, 80% had detectable vaginal insertion biomarkers and 52% had semen biomarkers. Ninety-nine percent of vaginally inserted applicators TFV applicators had detectable residual TFV as measured by liquid chromatography with tandem mass spectroscopy (LC–MS/MS). Residual TFV levels were also successfully detected using Fourier Transform Infrared (FTIR)-based spectroscopy. Conclusions Vaginal insertion and semen exposure biomarkers were detectable on used TFV 1% gel applicators. Residual TFV on these gel applicators was detectable by LC–MS/MS and FTIR-based spectroscopy, which has potential to be a more convenient and quicker method for detecting drug use. With continual improvements, this composite measure of product adherence, protocol compliance, and semen exposure has potential to assess use of not only TFV gel but also other topical microbicides or products.

Participating in HIV Prevention Clinical Trial: Reasons and Experiences among Female Participants in Antibody Mediated Prevention Study at UNC Project, Lilongwe, Malawi

Aim: The overall aim of the study was to assess the reasons and experiences of participants involved in Antibody Mediated Prevention (AMP) HIV prevention clinical trial at University of North Carolina (UNC) Project, Lilongwe, Malawi. We determined the participants’ reasons for participating in HIV Prevention clinical trials; and the experiences of participants in HIV Prevention clinical trials. Methods: We adopted the qualitative cross-sectional study method. Data were collected using in-depth interviews (IDIs). Purposive sampling was used to select 12 study participants who consented to take part in the study. All participants were the ones taking part in the AMP HIV prevention study at the UNC Project. Data analysis was done concurrently with data collection using content analysis. Results: Individuals were motivated to participate in HIV research due to a range of perceived benefits. These included personal, health, and financial benefits. Participants' research experiences and their continued participation in HIV research were influenced by the research clinic context and the nature of their interactions with research staff. Conclusion: When the clinical trial study participants’ expectations are met through what they experience in the study, the chances of them adhering to the study visits and procedures are high. Even for those who did not have any expectations prior to the study, feeling welcomed and being able to open up to the study staff encouraged their continued participation. In the end, this outweighed the negative comments made by the people in their communities or their friends

Temozolomide in secondary prevention of HER2-positive breast cancer brain metastases

Brain metastases occur in up to 25–55% of patients with metastatic HER2-positive breast cancer. Standard treatment has high rates of recurrence or progression, limiting survival and quality of life in most patients. Temozolomide (TMZ) is known to penetrate the blood–brain barrier and is US FDA approved for treatment of glioblastoma. Our group has demonstrated that low doses of TMZ administered in a prophylactic, metronomic fashion can significantly prevent development of brain metastases in murine models of breast cancer. Based on these findings, we initiated a secondary-prevention clinical trial with oral TMZ given to HER2-positive breast cancer patients with brain metastases after recent local treatment in combination with T-DM1 for systemic control of disease. Primary end point is freedom from new brain metastases at 1 year. (NCT03190967).

Emerging trends in contraceptive use, transitions and preferences among female sex workers screened for an HIV prevention clinical trial in Kisumu, Kenya: a cross-sectional study

Background: Globally about 210 million women conceive annually and 38% of these pregnancies are unintended. Female sex workers (FSWs) are at increased risk of both unintended pregnancy and acquiring HIV, which could lead to adverse sexual and reproductive health (SRH) outcomes. We sought to assess contraceptive use or non-use, preferences and determinants among a cohort of FSWs screened for an HIV prevention clinical trial in Kisumu, Kenya. Methods: A cross sectional study of healthy FSWs referred for possible recruitment into the Antibody Mediated HIV Prevention (AMP) Study was conducted between December 2016 and September 2018. Potentially eligible participants were screened for HIV and data on social-demographic, contraceptive use and other SRH characteristics were collected. Those not on a method recorded their contraceptive preferences. Results: Data on 210 FSWs with a median age of 24.5 years (interquartile range, IQR 22-26) are presented. Of these, 187 (89.1%) had two children or fewer; only 56 (26.7%) had completed secondary or higher education. At the time of the interview, 18 (8.6%) were HIV-infected and 181 (86.2%) were using a modern contraceptive. Implants (48.6%) and depot injections (37.6%) were the most commonly used methods. Most (41.4%) of those not on family planning preferred oral pills. Respondents who had two or more children were three times more likely than their primiparous and nulliparous counterparts to report use of a contraceptive. Use of modern contraception methods did not differ by respondent’s ownership of a medical insurance cover or other occupation. Conclusion: There is high use of modern contraception among FSWs in Kisumu with the majority using subdermal implants. Reproductive health programs should implement targeted SRH interventions for specific populations and risk groups. Effective contraceptive counselling and interventions among FSWs should consider the client’s parity and level of education.