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Browsing by Author "Vik, Terry"
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Item Barriers to and facilitators of effective management of fever episodes in hospitalised Kenyan children with cancer: protocol for convergent mixed methods study(BMJ Publishing, 2023-11-02) Nessle, Charles Nathaniel; Njuguna, Festus; Dettinger, Julia; Koima, Raphael; Nyamusi, Lenah; Kisembe, Evelynn; Kinja, Sarah; Ndung’u, Mercy; Njenga, Dennis; Langat, Sandra; Olbara, Gilbert; Moyer, Cheryl; Vik, Terry; Pediatrics, School of MedicineIntroduction: Febrile neutropenia is an oncological emergency in children with cancer, associated with serious infections and complications. In low-resourced settings, death from infections in children with cancer is 20 times higher than in high-resourced treatment settings, thought to be related to delays in antibiotic administration and management. The barriers to effective management of fever episodes in children with cancer have not previously been described. This convergent mixed-methods study will provide the evidence to develop fever treatment guidelines and to inform their effective implementation in children with cancer at Moi Teaching and Referral Hospital (MTRH), a level 6 referral hospital in western Kenya. Methods and analysis: Prospective data collection of paediatric patients with cancer with new fever episodes admitted to MTRH will be performed during routine treatment. Clinical variables will be collected from 50 fever episodes, including cancer diagnosis and infectious characteristics of the fever episode, and elapsed time from fever onset to various milestones in the management workflow. Semistructured qualitative interviews with healthcare providers (estimated 20 to reach saturation) will explore the barriers to and facilitators of appropriate management of fever episodes in children with cancer. The interview guide was informed by a theoretical framework and Consolidated Framework for Implementation Research. A mixed-methods analysis use of joint display tables and process mapping will link and integrate the two types of data with meta-inferences. Ethics and dissemination: Institutional review board approval was obtained from the MTRH (0004273) and the University of Michigan (HUM0225674), and the study was registered with National Commission for Science Technology and Innovation (P/23/22885). Written consent will be obtained from all participants. Results will be formally shared with local and national policy leadership and local end users, presented at relevant national academic conferences and submitted for publication in a peer-reviewed journal.Item Factors influencing time to diagnosis and treatment among pediatric oncology patients in Kenya(Taylor & Francis, 2016) Njuguna, F.; Martijn, H.; Langat, S.; Musimbi, J.; Muliro, H.; Skiles, Jodi; Vik, Terry; Sitaresmi, M. N.; van de Ven, P. M.; Kaspers, G. J. L.; Mostert, S.; Department of Pediatrics, IU School of MedicineEarly diagnosis and start of treatment are fundamental goals in cancer care. This study determines the time lag and the factors that influence the time to diagnosis and start of treatment. Study participants were parents of childhood cancer patients diagnosed between August 2013 and July 2014 in a hospital in Kenya. Patient, physician, diagnosis, treatment, health care system, and total delay were explored using a questionnaire. Demographic and medical data were collected from the patients' medical records. Parents of 99 childhood cancer patients were interviewed (response rate: 80%). Median total delay was 102 (9–1021) days. Median patient delay (4 days) was significantly shorter than health care system delay (median 87 days; P < .001). Diagnosis delay (median 94 days) was significantly longer than treatment delay (median 6 days; P < .001). days. Lack of health insurance at diagnosis and use of alternative medicine before attending conventional health services were associated with a significantly longer patient delay (P = .041 and P = .017, respectively). The type of cancer had a significant effect on treatment delay (P = .020). The type of health facility attended affected only patient delay (P = .03). Gender, age at diagnosis, stage of disease, parents' education level or income, and distance from hospital did not have a significant effect on the length of any type of delay. Training on childhood cancer should be included in the curricula for medical training institutes. In-service workshops should be held for the health workers already working. Families must be obligated to get health insurance. Families should be encourage to attend conventional health facilities and informed on symptoms of cancer through mass media.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 Influence of health insurance status on paediatric non-Hodgkin's lymphoma treatment in Kenya(BMJ Publishing Group, 2017-08-11) Martijn, Hugo A.; Njuguna, Festus; Olbara, Gilbert; Langat, Sandra; Skiles, Jodi; Martin, Stephen; Vik, Terry; Ven, Peter M. van de; Kaspers, Gertjan JL; Mostert, Saskia; Pediatrics, School of MedicineObjective: Non-Hodgkin's lymphoma (NHL) is the most common childhood malignancy in sub-Saharan Africa. Survival rates for NHL are higher than 80% in high-income countries.This study explores treatment outcomes of children with NHL in Kenya, a sub-Saharan low-income country, and the association between health insurance status at diagnosis and treatment outcomes. Design: This was a retrospective medical records study. All children diagnosed with NHL in 2010, 2011 and 2012 were included. Data on treatment outcomes and health insurance status at diagnosis were collected. Results: Of all 63 patients with NHL, 35% abandoned treatment, 22% had progressive or relapsed disease, 14% died and 29% had event-free survival. Most patients (73%) had no health insurance at diagnosis. Treatment outcomes in children with or without health insurance at diagnosis differed significantly (p=0.005). The most likely treatment outcome in children with health insurance at diagnosis was event-free survival (53%), whereas in children without health insurance at diagnosis it was abandonment of treatment (44%). Crude HR for treatment failure was 3.1 (95% CI 1.41 to 6.60, p=0.005) for uninsured versus insured children. The event-free survival estimate was significantly higher in children with health insurance at diagnosis than in patients without health insurance at diagnosis (p=0.003). Stage of disease at diagnosis was identified as a confounder of this association (adjusted HR=2.4, 95% CI 0.95 to 6.12, p=0.063). Conclusions: Survival of children with NHL in Kenya is much lower compared with high-income countries. Abandonment of treatment is the most common cause of treatment failure. Health insurance at diagnosis was associated with better treatment outcomes and survival.Item Model-Based Individualized Treatment of Chemotherapeutics: Bayesian Population Modeling and Dose Optimization(Public Library of Science, 2015) Jayachandran, Devaraj; Laínez-Aguirre, José; Rundell, Ann; Vik, Terry; Hannemann, Robert; Reklaitis, Gintaras; Ramkrishna, Doraiswami; Department of Pediatrics, IU School of Medicine6-Mercaptopurine (6-MP) is one of the key drugs in the treatment of many pediatric cancers, auto immune diseases and inflammatory bowel disease. 6-MP is a prodrug, converted to an active metabolite 6-thioguanine nucleotide (6-TGN) through enzymatic reaction involving thiopurine methyltransferase (TPMT). Pharmacogenomic variation observed in the TPMT enzyme produces a significant variation in drug response among the patient population. Despite 6-MP's widespread use and observed variation in treatment response, efforts at quantitative optimization of dose regimens for individual patients are limited. In addition, research efforts devoted on pharmacogenomics to predict clinical responses are proving far from ideal. In this work, we present a Bayesian population modeling approach to develop a pharmacological model for 6-MP metabolism in humans. In the face of scarcity of data in clinical settings, a global sensitivity analysis based model reduction approach is used to minimize the parameter space. For accurate estimation of sensitive parameters, robust optimal experimental design based on D-optimality criteria was exploited. With the patient-specific model, a model predictive control algorithm is used to optimize the dose scheduling with the objective of maintaining the 6-TGN concentration within its therapeutic window. More importantly, for the first time, we show how the incorporation of information from different levels of biological chain-of response (i.e. gene expression-enzyme phenotype-drug phenotype) plays a critical role in determining the uncertainty in predicting therapeutic target. The model and the control approach can be utilized in the clinical setting to individualize 6-MP dosing based on the patient's ability to metabolize the drug instead of the traditional standard-dose-for-all approach.Item Wilms Tumor Treatment Outcomes: Perspectives From a Low-Income Setting(American Society of Clinical Oncology, 2016-12-21) Njuguna, Festus; Martijn, Hugo A.; Kuremu, Robert Tenge; Saula, Peter; Kirtika, Patel; Olbara, Gilbert; Langat, Sandra; Martin, Steve; Skiles, Jodi; Vik, Terry; Kaspers, Gertjan J.L.; Mostert, Saskia; Medicine, School of MedicinePurpose Wilms tumor is the commonest renal malignancy in childhood. Survival in high-income countries is approximately 90%, whereas in low-income countries, it is less than 50%. This study assessed treatment outcomes of patients with Wilms tumor at a Kenyan academic hospital. Patients and Methods We conducted a retrospective medical record review of all children diagnosed with Wilms tumor between 2010 and 2012. Data on treatment outcomes and various sociodemographic and clinical characteristics were collected. Results Of the 39 patients with Wilms tumor, 41% had event-free survival, 31% abandoned treatment, 23% died, and 5% had progressive or relapsed disease. Most patients presented at an advanced stage: stage I (0%), II (7%), III (43%), IV (40%), or V (10%). The most likely treatment outcome in patients with low-stage (I to III) disease was event-free survival (67%), whereas in those with high-stage (IV to V) disease, it was death (40%). No deaths or instances of progressive or relapsed disease were recorded among patients with low-stage disease; their only reason for treatment failure was abandonment of treatment. Stage of disease significantly affected treatment outcomes (P = .014) and event-free survival estimates (P < .001). Age at diagnosis, sex, duration of symptoms, distance to hospital, and health insurance status did not statistically significantly influence treatment outcomes or event-free survival estimates. Conclusion Survival of patients with Wilms tumor in Kenya is lower compared with that in high-income countries. Treatment abandonment is the most common cause of treatment failure. Stage of disease at diagnosis statistically significantly affects treatment outcomes and survival.