Temple University Health System

Introduction In Kenya prostate cancer (Ca) is the leading cause of cancer related mortality among men. There is lack of data on the social determinants of health and their impact on the stage at diagnosis. Purpose The purpose of this study was to determine prostate cancer stage at diagnosis, and social determinants associated with advanced disease in a Kenyan population. Methods We analyzed data from 170 prostate cancer patients recruited from Kenyatta National Hospital (KNH) and MP Shah Hospital, Nairobi (2022–2024) on patients prospectively recruited in the International Registry for Men with Advanced Prostate Cancer (IRONMAN) and African Cancer Genome Registry (ACGR) registries. Patients included in the study had a histological diagnosis of prostate cancer. All participants completed standardized questionnaires assessing sociodemographic factors, health knowledge, and healthcare access. Clinical and pathological staging data was also collected and multivariable logistic regression used to determine factors associated with metastatic disease at diagnosis. Results The mean age for the participants was 70 years. Most of the participants presented with advanced disease 84.7% ( n = 144). Half of the participants (50%, n = 84) had a Gleason score of 9 and 10 or an ISUP (International Society of Urological Pathology) Grade 5, 36% ( n = 60) had grades 3 and 4 the remaining 14% ( n = 24) had grade 1 and 2. The median PSA was 81 ng/ml (IQR: 26.5–262) and the mean was 402.22 ng/ml (SD:1128.17) with most of the patients 60.5% ( n = 92) having a PSA over 50 ng/ml. The odds of advanced disease were significantly lower among patients with tertiary education compared to primary or no formal education (OR = 0.0.13 95% CI: 0.03–0.56). Patients who were very spiritual had higher odds of advanced disease (OR = 4.51 95% CI: 1.33–15.22). Conclusion Kenyan men in this cohort present predominantly with advanced prostate cancer, influenced by educational status, spirituality and region of residence. There is need for community-based awareness and screening programs for men with low education.

BackgroundThe advent of antiretroviral therapy (ART) has transformed the management of living with HIV into a chronic condition, however, barriers to access persist. Utilization management techniques (UMTs) used by payers to optimize care and resource efficiency often pose challenges for people living with HIV (PLWH) and individuals with increased likelihood of HIV exposure. This study examined the burden of ART-specific UMTs across access pathways in the US, and impact on PLWH, individuals vulnerable to HIV acquisition, and the healthcare system.MethodsA systematic literature review was conducted in MEDLINE®, Embase®, JSTOR, PubMed, and government/non-government HIV management websites focusing on ART-specific UMTs in treatment and pre-exposure prophylaxis (PrEP) of HIV in the US. The search covered publications from the last 10 years and conference abstracts from the last 4 years. Studies that met predefined inclusion criteria, based on the PICOTS framework, were included.ResultsOf 1,863 records, 21 met the study criteria, mostly from the private setting (76%). Prior authorization (PA) was the most common UMT identified (71%), followed by step therapy (5%) and quantity limits (5%) for both HIV treatment and PrEP. For oral HIV PrEP, PAs ranged from 2.3% (Northeast) to 37.3% (South). PA-led rejection rates of up to 21% for HIV PrEP regimens were identified, with formulary restrictions contributing to worse clinical outcomes for HIV treatment and PrEP. While there was a paucity of economic burden data for individuals, formulary restrictions imposed substantial costs to the healthcare system ($2.19 billion higher vs. the open formulary). Provider-based studies reported UMTs substantially impact HIV care, with one study reporting that 76% of providers indicate interference with optimal care, 72% citing UMTs and formularies impede prescribing optimal HIV treatment/PrEP.ConclusionUMT may pose substantial barriers to timely HIV care and prevention. While intended to control costs, they often result in treatment delays, worsening outcomes, and higher expenses. Despite national efforts to eliminate UMTs for HIV treatment and PrEP, access to ART remains unequal. Policy reforms for UMTs may help facilitate equitable access to HIV care, improve health outcomes, and reduce the HIV burden.DisclosuresGirish Prajapati, M.B.B.S., MPH , Merck & Co., Inc.: Employee|Merck & Co., Inc.: Stocks/Bonds (Private Company) Sean P. Fleming, PhD, MSW, Merck & Co., Inc., Rahway, NJ, USA: Employee|Merck & Co., Inc., Rahway, NJ, USA: Stocks/Bonds (Public Company) David E. Koren, PharmD, BCPS, AAHIVP, Gilead Sciences: Advisor/Consultant|Merck Sharp and Dohme: Advisor/Consultant|ViiV Healthcare: Advisor/Consultant Orbit R. Clanton, AOS, Global Community HIV Advocate, Merck & Co., Inc: Advisor/Consultant Harshil Patel, BSc, Merck & Co., Inc: Advisor/Consultant Lucia Perez-Kempner, BPharm, MSc, MBS, Merck & Co., Inc: Advisor/Consultant Astha Jain, M.Pharmacy, Merck & Co., Inc: Advisor/Consultant Sugandh Sharma, M.Sc., Merck & Co., Inc: Advisor/Consultant

A subset of colorectal cancer (CRC) patients displays abnormal DNA methylation patterns (“Outlier Methylation Phenotype” (OMP)) in normal adjacent tissue (NAT). We analyzed the impact of OMP status on epigenetic age and tumor progression using published aging and mitotic clocks and colonic epigenetic clock (EpiAge) developed on controls, with equal representation from Black and Caucasian populations. Three aging clocks (including EpiAge) showed “significantly lower” epigenetic age in CRC. Mitotic clocks suggested significantly fewer stem cell divisions in CRC versus controls. A binomial model using inactive X chromosome CpGs suggested that NAT of CRC patients had fewer stem cells compared with controls. On comparing NAT and tumor methylome, the OMP group showed the fewest epigenetic differences. In conclusion, our study demonstrates that NAT of OMP-CRC patients undergoes epigenetic age deceleration and have fewer epigenetic differences with tumor tissues, suggesting that NAT of OMPs had progressed toward a tumor identity.

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