Browsing by Author "Olbara, Gilbert"
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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 Childhood acute lymphoblastic leukemia treatment in an academic hospital in Kenya: Treatment outcomes and health‐care providers’ perspectives(Wiley, 2021-12) Olbara, Gilbert; van der Wijk, Thyra; Njuguna, Festus; Langat, Sandra; Mwangi, Henry; Skiles, Jodi; Vik, Terrry A.; Kaspers, Gertjan J.L.; Mostert, Saskia; Pediatrics, School of MedicineBackground Early deaths and treatment nonadherence are major reasons for low childhood acute lymphoblastic leukemia (ALL) survival in low- and middle-income countries. This study assessed treatment outcomes of children presenting with ALL and evaluated perspectives of health-care providers (HCP) on ALL treatment at a Kenyan academic hospital. Methods This was a combined retrospective medical records and cross-sectional questionnaire study. Treatment outcomes of 136 children diagnosed with ALL between 2010 and 2016 were collected. Questionnaires were completed by 245 HCP (response rate, 86%) between September and October 2016. Results Childhood ALL treatment outcomes were death (30%), progressive or relapsed disease (26%), abandonment (24%), and event-free survival (20%). Of all deaths, 80% were early deaths (prior or during induction), whereas 20% occurred in remission. Probability of event-free survival at three years was 18%. Only 57% of HCP believed childhood ALL can be cured, with more doctors (96%) than other HCP (45%) believing in curability of ALL (P < 0.001). The majority of HCP (96%) thought that experienced doctors should put more time and effort into making parents understand the diagnosis and necessity to complete treatment. According to HCP, reasons for protocol nonadherence included parental financial difficulties (94%) and use of alternative treatment (79%). Conclusions Event-free survival for ALL in Kenya is low. The primary reason for treatment failure is early death from treatment-related complications. More efforts should be directed toward improving supportive care strategies. In the opinion of HCPs, improved communication with parents and supervision of junior staff will improve ALL treatment outcomes.Item Clinical Impact of Project ECHO in Children With Cancer in Western Kenya: A Case Series(American Society of Clinical Oncology, 2024) Olbara, Gilbert; Njuguna, Festus; Etling, Mary Ann; Langat, Sandra; Kipng’etich, Martha; Nessle, Charles N.; Kaspers, Gertjan J. L.; Vik, Terry A.; Severance, Tyler S.; Pediatrics, School of MedicineItem CYP3A5 genotype and its impact on vincristine pharmacokinetics and development of neuropathy in Kenyan children with cancer(Wiley, 2018-03) Skiles, Jodi L.; Chiang, ChienWei; Li, Claire H.; Martin, Steve; Smith, Ellen L.; Olbara, Gilbert; Jones, David R.; Vik, Terry A.; Mostert, Saskia; Abbink, Floor; Kaspers, Gertjan J.; Li, Lang; Njuguna, Festus; Sajdyk, Tammy J.; Renbarger, Jamie L.; Pediatrics, School of MedicineBACKGROUND: Vincristine (VCR) is a critical part of treatment in pediatric malignancies and is associated with dose-dependent peripheral neuropathy (vincristine-induced peripheral neuropathy [VIPN]). Our previous findings show VCR metabolism is regulated by the CYP3A5 gene. Individuals who are low CYP3A5 expressers metabolize VCR slower and experience more severe VIPN as compared to high expressers. Preliminary observations suggest that Caucasians experience more severe VIPN as compared to nonCaucasians. PROCEDURE: Kenyan children with cancer who were undergoing treatment including VCR were recruited for a prospective cohort study. Patients received IV VCR 2 mg/m2 /dose with a maximum dose of 2.5 mg as part of standard treatment protocols. VCR pharmacokinetics (PK) sampling was collected via dried blood spot cards and genotyping was conducted for common functional variants in CYP3A5, multi-drug resistance 1 (MDR1), and microtubule-associated protein tau (MAPT). VIPN was assessed using five neuropathy tools. RESULTS: The majority of subjects (91%) were CYP3A5 high-expresser genotype. CYP3A5 low-expresser genotype subjects had a significantly higher dose and body surface area normalized area under the curve than CYP3A5 high-expresser genotype subjects (0.28 ± 0.15 hr·m2 /l vs. 0.15 ± 0.011 hr·m2 /l, P = 0.027). Regardless of which assessment tool was utilized, minimal neuropathy was detected in this cohort. There was no difference in the presence or severity of neuropathy assessed between CYP3A5 high- and low-expresser genotype groups. CONCLUSION: Genetic factors are associated with VCR PK. Due to the minimal neuropathy observed in this cohort, there was no demonstrable association between genetic factors or VCR PK with development of VIPN. Further studies are needed to determine the role of genetic factors in optimizing dosing of VCR for maximal benefit.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 Influence of health-insurance on treatment outcome of childhood cancer in Western Kenya(Springer, 2023-07-15) Langat, Sandra; Njuguna, Festus; Olbara, Gilbert; Martijn, Hugo; Sieben, Cenne; Haverkort, Moniek; Njenga, Dennis; Vik, Terry A.; Kaspers, Gertjan; Mostert, Saskia; Pediatrics, School of MedicineBackground: Few governments in low and middle-income countries (LMIC) have responded favourably to the international plea for Universal Health Coverage. Childhood cancer survival in LMIC is often below 20%. Limited health-insurance coverage may contribute to this poor survival. Our study explores the influence of health-insurance status on childhood cancer treatment outcomes in a Kenyan academic hospital. Methods: This was a retrospective medical records review of all children diagnosed with cancer at Moi Teaching and Referral Hospital between 2010 and 2016. Socio-demographic and clinical data was collected using a structured data collection form. Fisher's exact test, chi-squared test, Kaplan-Meier method, log-rank test and Cox proportional hazard model were used to evaluate relationships between treatment outcomes and patient characteristics. Study was approved by Institutional Research Ethics Committee. Findings: From 2010-2016, 879 children were newly diagnosed with cancer. Among 763 patients whose records were available, 28% abandoned treatment, 23% died and 17% had progressive/relapsed disease resulting in 32% event-free survival. In total 280 patients (37%) had health-insurance at diagnosis. After active enrolment during treatment, total health-insurance registration level reached 579 patients (76%). Treatment outcomes differed by health-insurance status (P < 0.001). The most likely treatment outcome in uninsured patients was death (49%), whereas in those with health-insurance at diagnosis and those who enrolled during treatment it was event-free survival (36% and 41% respectively). Overall survival (P < 0.001) and event-free survival (P < 0.001) were higher for insured versus uninsured patients. The hazard-ratio for treatment failure was 0.30 (95% CI:0.22-0.39; P < 0.001) for patients insured at diagnosis and 0.32 (95% CI:0.24-0.41; P < 0.001) for patients insured during treatment in relation to those without insurance. Interpretation: Our study highlights the need for Universal Health Coverage in LMIC. Children without health-insurance had significantly lower survival. Childhood cancer treatment outcomes can be ameliorated by strategies that improve health-insurance access.Item Non-randomised prospective clinical trial to improve follow-up adherence, survivorship knowledge and late effects documentation at a childhood cancer clinic in Western Kenya: a study protocol(BMJ, 2025-06-10) Lemmen, Jesse; Mageto, Susan; Vik, Terry; Olbara, Gilbert; Kaspers, Gertjan; Njuguna, Festus; Pediatrics, School of MedicineIntroduction: International survivorship guideline consortia have developed strategies to prevent, detect and manage late effects of childhood cancer survivors. However, recommendations do not adequately reflect the everyday reality of paediatric oncology care in low- and middle-income countries. In this study protocol, a survivorship intervention programme, comprising an educational component and a follow-up component, is described. The Educational Programme aims to improve follow-up adherence of childhood cancer survivors through increasing survivorship knowledge of caregivers. The Follow-up Programme aims to map late effects by implementing a follow-up form at the outpatient clinic to be used by trained healthcare providers. Methods and analysis: This non-randomised prospective clinical trial will be performed at a referral hospital in Western Kenya. 100 caregivers of children diagnosed with cancer, who will complete treatment within 2 months, will be enrolled and followed for 24 months after completion of treatment. A caregiver control group receiving usual care will be recruited, and sequentially, caregivers will be included in an intervention group to attend an educational group session where they receive educational materials (video, booklet and Survivorship Card). Primary study outcome will be survivors' follow-up adherence. Survivors will be considered lost to follow-up after they miss a scheduled appointment and do not revisit the clinic for more than 6 months. Mixed models regression analyses will be performed to determine intervention effects on follow-up adherence and on caregiver survivorship knowledge uptake. Additionally, healthcare providers will be trained on follow-up care, whereafter a form will be introduced at the outpatient clinic to document late effects in paediatric survivors attending the clinic for the period of a year. Secondary outcomes will be late effects prevalence as documented in the follow-up form and caregiver and healthcare provider survivorship knowledge uptake. Implementation measures (reach, potential effectiveness, adoption, satisfaction and maintenance) will be evaluated for both programmes. Ethics and dissemination: The Institutional Research and Ethics Committee has approved the study protocol. Findings will also be shared with governmental and non-governmental organisations that support children with cancer in Kenya to inform their target audiences and guide their policy development.Lessons learnt from this study could inform healthcare providers and policy makers on how to shape survivorship programmes in the Kenyan context and possibly implement similar programmes in other centres in Sub-Saharan Africa.Item Outcomes of pediatric acute myeloid leukemia treatment in Western Kenya(Wiley, 2022) van Weelderen, Romy E.; Njuguna, Festus; Klein, Kim; Mostert, Saskia; Langat, Sandra; Vik, Terry A.; Olbara, Gilbert; Kipng'etich, Martha; Kaspers, Gertjan J.L.; Pediatrics, School of MedicineBackground: Pediatric acute myeloid leukemia (AML) is a challenging disease to treat in low- and middle-income countries (LMICs). Literature suggests that survival in LMICs is poorer compared with survival in high-income countries (HICs). Aims: This study evaluates the outcomes of Kenyan children with AML and the impact of sociodemographic and clinical characteristics on outcome. Methods and results: A retrospective medical records study was performed at Moi Teaching and Referral Hospital (MTRH) in Eldoret, Kenya, between January 2010 and December 2018. Sociodemographic and clinical characteristics, and treatment outcomes were evaluated. Chemotherapy included two "3 + 7" induction courses with doxorubicin and cytarabine and two "3 + 5" consolidation courses with etoposide and cytarabine. Supportive care included antimicrobial prophylaxis with cotrimoxazole and fluconazole, and blood products, if available. Seventy-three children with AML were included. The median duration of symptoms before admission at MTRH was 1 month. The median time from admission at MTRH to diagnosis was 6 days and to the start of AML treatment 16 days. Out of the 55 children who were started on chemotherapy, 18 (33%) achieved complete remission, of whom 10 (56%) relapsed. The abandonment rate was 22% and the early death rate was 46%. The 2-year probabilities of event-free survival and overall survival were 4% and 7%, respectively. None of the sociodemographic and clinical characteristics were significantly associated with outcome. Conclusion: Survival of Kenyan children with AML is dismal and considerably lower compared with survival in HICs. Strategies to improve survival should be put in place including better supportive care, optimization of the treatment protocol, and reduction of the abandonment rate and time lag to diagnosis with sooner start of treatment.Item Outcomes of Wilms tumor treatment in western Kenya(Wiley, 2022-04) Uittenboogaard, Aniek; Njuguna, Festus; Mostert, Saskia; Langat, Sandra; van de Velde, Mirjam E.; Olbara, Gilbert; Vik, Terry A.; Kaspers, Gertjan J. L.; Pediatrics, School of MedicineBackground/objectives Wilms tumor (WT) is a curable type of cancer with 5-year survival rates of over 90% in high-income countries, whereas this is less than 50% in low- and middle-income countries. We assessed treatment outcomes of children with WT treated at a large Kenyan teaching and referral hospital. Design/methods We conducted a retrospective record review of children diagnosed with WT between 2013 and 2016. Treatment protocol consisted of 6 weeks of preoperative chemotherapy and surgery, and 4–18 weeks of postoperative chemotherapy depending on disease stage. Probability of event-free survival (pEFS) and overall survival (pOS) was assessed using Kaplan–Meier method with Cox regression analysis. Competing events were analyzed with cumulative incidences and Fine–Gray regression analysis. Results Of the 92 diagnosed patients, 69% presented with high-stage disease. Two-year observed EFS and OS were, respectively, 43.5% and 67%. Twenty-seven percent of children died, 19% abandoned treatment, and 11% suffered from progressive or relapsed disease. Patients who were diagnosed in 2015–2016 compared to 2013–2014 showed higher pEFS. They less often had progressive or relapsed disease (p = .015) and borderline significant less often abandonment of treatment (p = .09). Twenty-nine children received radiotherapy, and 2-year pEFS in this group was 86%. Conclusion Outcome of children with WT improved over the years despite advanced stage at presentation. Survival probabilities of patients receiving comprehensive therapy including radiation are approaching those of patients in high-income countries. Additional improvement could be achieved by ensuring that patients receive all required treatment and working on earlier diagnosis strategies.Item Severe outcomes and risk factors of non-neutropenic fever episodes in hospitalized children with cancer in Kenya(Frontiers Media, 2025-05-12) Kipchumba, Samuel; Busby, Kenneth; Njenga, Dennis; Dettinger, Julia; Nyamusi, Lenah; Langat, Sandra; Olbara, Gilbert; Moyer, Cheryl A.; Vik, Terry A.; Nessle, C. Nathan; Njuguna, Festus; Pediatrics, School of MedicineIntroduction: Compared to febrile neutropenia (FN), non-neutropenic fever (NNF) episodes in children with cancer have not been associated with severe outcomes. Risk factors for severe outcomes in FN and NNF episodes in children with cancer from low-middle-income countries (LMIC) are incompletely described. Methods: A prospective, observational cohort study was conducted at a tertiary public referral hospital in western Kenya. Inclusion criteria were age ≤14 years, cancer diagnosis, hospitalized, fever >38.5°C or persistently >38°C. Neutropenia was an absolute count (ANC) <500 K/µL. Severe outcomes were BSI or death. Statistical analysis detected significance between groups and a univariate analysis was conducted. Results: Of the 99 fevers, 54.5% were NNF episodes. Over 66% of NNF episodes were in patients with solid tumors. More severe outcomes were observed in NNF episodes compared to FN [BSI: 7.4% (4/54) vs. 4.4% (2/45); death: 7.4% (4/54) vs. 4.4% (2/45)], yet no deaths occurred in episodes with BSI. Acute leukemia not in remission (OR= 8.67, 95% CI [CI: 2.3-32.62]; p= 0.002) and concern for disease relapse (OR= 14.17, 95% CI [2.08-96.3]; p= 0.012) were significantly associated severe outcomes. Time to antibiotic administration (9 hours) did not differ by ANC. Under half (45.5%) of fever episodes had a blood culture ordered, with 93.9% obtained after administration of antibiotics. Discussion: Non-neutropenic fever episodes had more severe outcomes. Prompt fever management is recommended in all children with cancer treated in an LMIC setting. Pediatric oncology treatment centers in LMICs should rigorously evaluate their fever management clinical practice. Clinical risk factors were identified, but a risk-stratified approach in an LMIC setting is not recommended. Urgent attention is needed to identify areas of clinical improvement.