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Item ‘Addressing HPV vaccine hesitancy: unveiling concerns and building trust’ perspectives of adolescent girls and parents in Kisumu County, Kenya(eCancer Global Foundation, 2024-08-05) Ochomo, Edwin Onyango; Tonui, Philiph; Muthoka, Kapten; Amboka, Sayo; Itsura, Peter; Orang’o, Elkanah Omenge; Rosen, Barry; Loehrer, Patrick; Cu-Uvin, Susan; Medicine, School of MedicineIntroduction: Human papillomavirus (HPV) causes cervical cancer, and HPV vaccination is highly effective in preventing vaccine-targeted HPV infection. However, low HPV vaccination coverage in Kisumu County, Kenya, at about 10% for the first dose, highlights the critical issue of vaccine hesitancy, particularly in low and middle-income countries. Methods: This study explores the concerns, myths and barriers to HPV vaccine uptake among adolescent girls (aged 10-14) enrolled at human immune-deficiency virus comprehensive care clinics and their parents in Kisumu County. Focused group discussions were conducted with 48 participants. Results: Content analysis revealed limited knowledge about the HPV vaccine and widespread misconceptions regarding its safety and efficacy. Financial constraints, injection fears and negative clinic experiences emerged as additional barriers. Conclusion: The findings emphasise the role of effective communication strategies, including engaging parents through written materials and involving them in decision-making, to dispel myths, provide accurate information and encourage HPV vaccination. Collaborative efforts with community stakeholders are crucial to improve vaccine coverage and ultimately reduce the cervical cancer burden.Item Association of Plasma Aflatoxin With Persistent Detection of Oncogenic Human Papillomaviruses in Cervical Samples From Kenyan Women Enrolled in a Longitudinal Study(BMC, 2023-06-06) Tong, Yan; Tonui, Philip; Orang’o, Omenge; Zhang, Jianjun; Maina, Titus; Muthoka, Kapten; Groopman, John; Smith, Joshua; Madeen, Erin; Ermel, Aaron; Loehrer, Patrick; Brown, Darron R.; Biostatistics, School of Public HealthBackground: Cervical cancer is caused by oncogenic human papillomaviruses (HR-HPV) and is common among Kenyan women. Identification of factors that increase HR-HPV persistence is critically important. Kenyan women exposed to aflatoxin have an increased risk of HR-HPV detection in cervical specimens. This analysis was performed to examine associations between aflatoxin and HR-HPV persistence. Methods: Kenyan women were enrolled in a prospective study. The analytical cohort for this analysis included 67 HIV-uninfected women (mean age 34 years) who completed at least two of three annual study visits and had an available blood sample. Plasma aflatoxin was detected using ultra-high pressure liquid chromatography (UHPLC)-isotope dilution mass spectrometry. Annual cervical swabs were tested for HPV (Roche Linear Array). Ordinal logistic regression models were fitted to examine associations of aflatoxin and HPV persistence. Results: Aflatoxin was detected in 59.7% of women and was associated with higher risk of persistent detection of any HPV type (OR = 3.03, 95%CI = 1.08-8.55, P = 0.036), HR-HPV types (OR = 3.63, 95%CI = 1.30-10.13, P = 0.014), and HR-HPV types not included in the 9-valent HPV vaccine (OR = 4.46, 95%CI = 1.13-17.58, P = 0.032). Conclusions: Aflatoxin detection was associated with increased risk of HR-HPV persistence in Kenyan women. Further studies, including mechanistic studies are needed to determine if aflatoxin synergistically interacts with HR-HPV to increase cervical cancer risk.Item Building a Sustainable Comprehensive Multiple Myeloma Program in Western Kenya(American Society of Clinical Oncology, 2021-03) Oduor, Mercy A.; Lotodo, Teresa C.; Vik, Terry A.; Manyega, Kelvin M.; Loehrer, Patrick; Omondi, Austin A.; Oguda, John O.; Asirwa, Fredrick C.; Medicine, School of MedicineDespite improved treatment strategies for multiple myeloma (MM), patient outcomes in low- and middle-income countries remain poor, unlike high-income countries. Scarcity of specialized human resources and diagnostic, treatment, and survivorship infrastructure are some of the barriers that patients with MM, clinicians, and policymakers have to overcome in the former setting. To improve outcomes of patients with MM in Western Kenya, the Academic Model Providing Access to Healthcare (AMPATH) MM Program was set up in 2012. In this article, the program's activities, challenges, and future plans are described distilling important lessons that can be replicated in similar settings. Through the program, training on diagnosis and treatment of MM was offered to healthcare professionals from 35 peripheral health facilities across Western Kenya in 2018 and 2019. Access to antimyeloma drugs including novel agents was secured, and pharmacovigilance systems were developed. Finally, patients were supported to obtain health insurance in addition to receiving peer support through participation in support group meetings. This article provides an implementation blueprint for similar initiatives aimed at increasing access to care for patients with MM in underserved areas.Item Detection and Concentration of Plasma Aflatoxin Is Associated With Detection of Oncogenic Human Papillomavirus in Kenyan Women(Oxford Academic, 2019-09-01) Zhang, Jianjun; Orang’o, Omenge; Tonui, Philip; Tong, Yan; Maina, Titus; Kiptoo, Stephen; Muthoka, Katpen; Groopman, John; Smith, Joshua; Madeen, Erin; Ermel, Aaron; Loehrer, Patrick; Brown, Darron R.; Department of Epidemiology, School of Public HealthAbstract Background Cervical cancer is common in Kenyan women. Cofactors in addition to infection with oncogenic human papillomavirus (HPV) are likely to be important in causing cervical cancer, because only a small percentage of HPV-infected women will develop this malignancy. Kenyan women are exposed to dietary aflatoxin, a potent carcinogen and immunosuppressive agent, which may be such a cofactor. Methods Demographics, behavioral data, plasma, and cervical swabs were collected from 88 human immunodeficiency virus-uninfected Kenyan women without cervical dysplasia. Human papillomavirus detection was compared between women with or without plasma aflatoxin B1-lysine (AFB1-lys) and evaluated in relation to AFB1-lys concentration. Results Valid HPV testing results were available for 86 women (mean age 34.0 years); 49 women (57.0%) had AFB1-lys detected and 37 (43.0%) had none. The AFB1-lys detection was not associated with age, being married, having more than secondary school education, home ownership, living at a walking distance to healthcare ≥60 minutes, number of lifetime sex partners, or age of first sex. The AFB1-lys detection and plasma concentrations were associated with detection of oncogenic HPV types. Conclusions The AFB1-lys positivity and higher plasma AFB1-lys concentrations were associated with higher risk of oncogenic HPV detection in cervical samples from Kenya women. Further studies are needed to determine whether aflatoxin interacts with HPV in a synergistic manner to increase the risk of cervical cancer.Item Expanding Myeloma Training and Care in Western Kenya Through the ECHO Model: The Pilot Phase(American Society of Clinical Oncology, 2024) Oduor, Mercy Atieno; Lotodo, Teresa Cherop; Severance, Tyler; Melly, Beatrice Jepngetich; Omondi, Austin; Ndenga, Indagala; Namaemba, Diana Flora; Oyollo, Yvette; Manyega, Kelvin Mogesa; Morgan, Jennifer; Oguda, John; Loehrer, Patrick; Vik, Terry; Medicine, School of MedicinePurpose: Multiple myeloma (MM) in rural western Kenya is characterized by under and late diagnosis with poor long-term outcomes. Inadequate skilled rural health care teams are partly to blame. The Extension for Community Healthcare Outcomes (ECHO) model attempts to bridge this skills gap by linking rural primary/secondary health care teams (spokes) to myeloma experts in a tertiary care center (hub) in a longitudinal training program. Methods: A hub team comprising myeloma experts and administrators from Moi Teaching and Referral Hospital/Academic Model Providing Access to Healthcare was assembled and spoke sites were recruited from rural health care facilities across western Kenya. A curriculum was developed by incorporating input from spokes on their perceived skills gaps in myeloma. Participants joined sessions remotely through virtual meeting technology. ECHO sessions consisted of a spoke-led case presentation with guided discussion followed by an expert-led lecture. An end-of-program survey was used to evaluate participant satisfaction, knowledge, and practice patterns. Results: A total of eight sessions were conducted between April and November 2021 with a median of 40 attendees per session drawn from diverse health care disciplines. Twenty-four spoke sites were identified from 15 counties across western Kenya. The majority of attendees reported satisfaction with the ECHO program (25 of 29) and improvement in their myeloma knowledge (24 of 29). There were 74 new myeloma diagnoses made at the hub site in 2021, representing a 35% increase from the previous 3-year average despite the COVID-19 pandemic that suppressed health care access globally. Recommendations: The pilot ECHO model was successfully implemented in myeloma training for rural-based health care teams. Key attributes included collaborative curriculum development, interactive case-based bidirectional learning, and multidisciplinary engagement.Item Improvement of diagnosis in children with Burkitt lymphoma in Kenya: feasibility study for the implementation of fluorescence in situ hybridisation testing for MYC and the MYC/IGH translocation(eCancer, 2023-02-08) Vance, Gail H.; Lotodo, Teresa; Kigen, Nicholas; Stohler, Ryan; Choi, Haki; Njuguna, Festus; Moormann, Ann M.; Kirwa, Erastus; Langat, Sandra; Loehrer, Patrick; Vik, Terry; Medical and Molecular Genetics, School of MedicineBackground: Indiana University (IU) initiated fluorescence in situ hybridisation (FISH) methodology for Burkitt Lymphoma (BL) to advance the accuracy and speed of diagnosis in the AMPATH Reference Laboratory at Moi Teaching and Referral Hospital (MTRH) in Eldoret, Kenya. Standard diagnostic testing for BL at MTRH includes morphology of the biopsy specimen or aspirate and limited immunohistochemistry panels. Methods: Tumour specimens from 19 children enrolled from 2016 to 2018 in a prospective study to improve the diagnosis and staging of children with suspected BL were evaluated. Touch preps from biopsy specimens or smears from fine needle aspiration were collected, stained with Giemsa and/or H&E and reviewed by pathologists to render a provisional diagnosis. Unstained slides were stored and later processed for FISH. Duplicate slides were split between two laboratories for analysis. Flow cytometry results were available for all specimens. Results from the newly established FISH laboratory in Eldoret, Kenya were cross-validated in Indianapolis, Indiana. Results: Concordance studies found 18 of 19 (95%) of specimens studied yielded analysable FISH results for one or both probe sets (MYC and MYC/IGH) in both locations. There was 94% (17/18) concordance of results between the two FISH laboratories. FISH results were 100% concordant for the 16 specimens with a histopathological diagnosis of BL and two of three non-BL cases (one case no result in IU FISH lab). FISH was similarly concordant with flow cytometry for specimens with positive flow results with the exception of a nasopharyngeal tumour with positive flow results for CD10 and CD20 but was negative by FISH. The modal turn-around time for FISH testing on retrospective study specimens performed in Kenya ranged between 24 and 72 hours. Conclusion: FISH testing was established, and a pilot study performed, to assess the feasibility of FISH as a diagnostic tool for the determination of BL in a Kenyan paediatric population. This study supports FISH in limited resource settings to improve the accuracy and speed of diagnosis of BL in Africa.Item A Randomized Trial of Two Print Interventions to Increase Colon Cancer Screening Among First-Degree Relatives(2008-05) Rawl, Susan M.; Champion, Victoria L.; Scott, Linda L; Zhou, Honghong; Monahan, Patrick; Ding, Yan; Loehrer, Patrick; Skinner, Celette SuggFirst-degree relatives (FDRs) of people diagnosed with colorectal cancer (CRC) have a two- to threefold increased risk of developing the same disease. Tailored print interventions based on behavior change theories have demonstrated considerable promise in facilitating health-promoting behaviors. This study compared the impact of two mailed print interventions on CRC screening outcomes among FDRs. Methods This randomized trial compared effects of two mailed print interventions – one tailored and one nontailored – on participation in CRC screening among FDRs of CRC survivors. Data collected via phone interviews from 140 FDRs at baseline, 1 week post-intervention, and 3 months post-intervention. Results At 3 months, both the tailored and nontailored interventions yielded modest but statistically insignificant increases in adherence to any CRC screening test (14% vs. 21%, respectively; p = 0.30). While there were no main effects for tailored versus nontailored interventions, there were significant interactions that showed that the tailored print intervention had significantly greater effects on forward stage movement for CRC screening depending on stage of adoption at baseline, race, and objective CRC risk. Receipt of the tailored intervention was 2.5 times more likely to move baseline precontemplators and contemplators forward in stage of adoption for colonoscopy (95% CI: 1.10–5.68) and was three times more likely to move Caucasians forward in stage of adoption for FOBT (95% CI: 1.00–9.07). In addition, the tailored intervention was 7.7 times more likely to move people at average risk forward in stage of adoption for colonoscopy (95% CI: 1.25–47.75). Conclusion The tailored print intervention was more effective at moving Caucasians, those in precontemplation and contemplation at baseline, and those at average risk forward in their stage of adoption for CRC screening. Practice implications Both tailored and nontailored print interventions showed moderate effects for increasing CRC screening participation. Tailored print interventions may be more effective for certain subgroups.Item Reducing Geographic Barriers for Breast Cancer Diagnosis(American Society of Clinical Oncology, 2022-05-05) Adaniya, Emily; Bhatia, Manisha; Kiptoo, Stephen; Wabende, Lucy Najala; Kisilu, Nicholas; Kibiwot, Silvanus; Jepkirui, Sally; Awuor, Dorice Adhiambo; Loehrer, Patrick; Hunter-Squires, Joanna; Busakhala, Naftali; Medicine, School of MedicinePurpose: Increasing travel times to the nearest diagnostic facilities and cancer centers are correlated with decreasing prevalence of breast cancer diagnosis and increasing stage of cancer at diagnosis. Moi Teaching and Referral Hospital (MTRH), in Uasin Gishu County, houses the only public cancer center in western Kenya. A MTRH program, the Academic Model Providing Access to Healthcare Breast and Cervical Cancer Control Program (ABCCCP) hosted health fair breast cancer screening events and mentored nurses at local health facilities to complete clinical breast exams (CBEs). The objective is to understand the effect of the ABCCCP in reducing geographic barriers for breast cancer screening/early diagnosis. Methods: This is a retrospective review of the 61,392 patients who underwent breast cancer screening at a ministry of health facility in western Kenya from 2017-2021. ABCCCP hosted health fairs targeted at communities and mentored nurses at health facilities to complete clinical breast exams (CBEs) to target individual patients. Facility distances from MTRH were mapped via Google Maps. Descriptive analyses were performed to a significance of α < 0.05. Results: Two-thirds of the screening/early diagnosis CBEs occurred in five of the 22 counties in western Kenya: Busia, Uasin Gishu, Trans-Nzoia, Bungoma, and Kakamega. However, these five counties only had 25% of all ABCCCP screening sites in western Kenya. Only Uasin Gishu and Kakamega provided chemotherapy while Busia and Trans-Nzoia had additional programming promoting preventative healthcare through integration of community health volunteers. In these five counties, no association between the distance of the ministry of health facilities from MTRH and number of CBEs completed existed. Conclusion: ABCCCP programming reduced some geographic disparities in breast cancer screening/diagnosis in the top five counties. It may be result of the number of mentored nurses and health fair events. Further work should be completed to understand if a relationship between geographic distance from MTRH and the stage and treatment patterns of these patients is also reduced by ABCCCP.Item The subgroups of the phase III RECOURSE trial of trifluridine/tipiracil (TAS-102) versus placebo with best supportive care in patients with metastatic colorectal cancer(Elsevier, 2017-12-01) Cutsem, Eric Van; Mayer, Robert J.; Laurent, Stéphanie; Winkler, Robert; Grávalos, Cristina; Benavides, Manuel; Longo-Munoz, Federico; Portales, Fabienne; Ciardiello, Fortunato; Siena, Salvatore; Yamaguchi, Kensei; Muro, Kei; Denda, Tadamichi; Tsuji, Yasushi; Makris, Lukas; Loehrer, Patrick; Lenz, Heinz-Josef; Ohtsu, Atsushi; Medicine, School of MedicineBackground: In the phase III RECOURSE trial, trifluridine/tipiracil (TAS-102) extended overall survival (OS) and progression-free survival (PFS) with an acceptable toxicity profile in patients with metastatic colorectal cancer refractory or intolerant to standard therapies. The present analysis investigated the efficacy and safety of trifluridine/tipiracil in RECOURSE subgroups. Methods: Primary and key secondary end-points were evaluated using a Cox proportional hazards model in prespecified subgroups, including geographical subregion (United States of America [USA], European Union [EU], Japan), age (<65 years, ≥65 years) and v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homologue (KRAS) status (wild type, mutant). Safety and tolerability were reported with descriptive statistics. Results: Eight-hundred patients were enrolled: USA, n = 99; EU, n = 403; Japan, n = 266. Patients aged ≥65 years and those with mutant KRAS tumours comprised 44% and 51% of all patients in the subregions, respectively. Final OS analysis (including 89% of events, compared with 72% in the initial analysis) confirmed the survival benefit associated with trifluridine/tipiracil, with a hazard ratio (HR) of 0.69 (95% confidence interval [CI] 0.59–0.81; P = 0.0001). Median OS in the three regions was 6.5–7.8 months in the trifluridine/tipiracil arm and 4.3–6.7 months in the placebo arm (USA: HR 0.56; 95% CI 0.34–0.94; P = 0.0277; EU: HR 0.62; 95% CI 0.48–0.80; P = 0.0002; Japan: HR 0.75; 95% CI 0.57–1.00; P = 0.0470). Median PFS was 2.0–2.8 months for trifluridine/tipiracil and 1.7–1.8 months for placebo; HRs favoured trifluridine/tipiracil in all regions. Similar clinical benefits of trifluridine/tipiracil were observed in elderly patients and in those with mutant KRAS tumours. There were no marked differences among subregions in terms of safety and tolerability. Conclusions: Trifluridine/tipiracil was effective in all subgroups, regardless of age, geographical origin or KRAS status.Item Thymic Carcinomas and Second Malignancies: A Single-Center Review(MDPI, 2021-05-19) Badve, Sunil S.; Dougherty, Rachel; Balatico, Michael; Kesler, Kenneth A.; Loehrer, Patrick; Gökmen-Polar, Yesim; Surgery, School of MedicineThymic carcinomas account for less than 0.01% of new cancer diagnoses annually and are more aggressive than thymomas. Autoimmune disorders have been associated with thymomas and only recently with thymic carcinomas. Second malignancies are well described after thymomas. The aim of this study was to analyze the incidence of second malignancies in patients with thymic carcinomas. All cases of thymic carcinomas were identified from the pathology archives of Indiana University. Histological materials were reviewed and further correlated with clinical data to identify incidence of second cancers in patients with thymic carcinomas. Histological material was available for review in 92 cases of thymic carcinoma. Clinical data were available for 85 patients. Fourteen of these (16.5%) patients had a second malignancy; these included small cell lung carcinoma, "testicular cancer", embryonal carcinoma, seminoma, breast carcinoma (two cases), prostatic adenocarcinoma, Hodgkin's lymphoma, thyroid carcinoma, bladder carcinoma (two cases), renal cell carcinoma, and melanoma. The latter could precede, be concurrent with, or follow the diagnosis thymic carcinoma. The incidence of second cancers in patients with thymic carcinomas is similar to that reported for thymomas. Abnormalities in immunological surveillance may be responsible for this high incidence of second malignancies in thymic tumors.