Barriers to and facilitators of effective management of fever episodes in hospitalised Kenyan children with cancer: protocol for convergent mixed methods study.

INTRODUCTION: 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.

Influence of health-insurance on treatment outcome of childhood cancer in Western Kenya.

BACKGROUND: 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.

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.

Background: 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.

An evaluation of the disparities affecting the underdiagnosis of pediatric cancer in Western Kenya.

INTRODUCTION: Western Kenya is home to approximately 24 million people, with 10 million children under the age of 15 years.1 Based on estimates of cancer incidence in similar populations from around the world, approximately 1500 patients should be diagnosed with pediatric cancer each year. This article describes the international collaboration that investigates potential barriers preventing the effective diagnosis of pediatric patients with cancer. METHODS: Here, we describe a multidisciplinary and sequential approach to better evaluate the complex factors affecting the lack of appropriate diagnosis of pediatric cancer in Western Kenya. RESULTS: Internal review at a large tertiary hospital noted 200-250 patients were diagnosed annually, suggesting the remaining 75%-80% of patients go undiagnosed and do not receive treatment. Following our screening process at a local referring hospital, 41 malaria slides demonstrated both morphologic and genetic evidence of leukemia. Knowledge assessments of local providers at referring institutions suggested a lack of education and training as the factors that contribute to lower rates of diagnosis. DISCUSSION: Through a multi-step approach, our teams were better able to isolate potential issues impeding the appropriate and timely diagnosis of pediatric cancer in Kenya.

Outcomes of Wilms tumor treatment in western Kenya.

BACKGROUND/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.

Outcomes of pediatric acute myeloid leukemia treatment in Western Kenya.

BACKGROUND: 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.

Childhood acute lymphoblastic leukemia treatment in an academic hospital in Kenya: Treatment outcomes and health-care providers' perspectives.

BACKGROUND: 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.

Health insurance coverage for vulnerable children: two HIV orphans with Burkitt lymphoma and their quest for health insurance coverage in Kenya.

The United Nations and WHO have summoned governments from low-income and middle-income countries to institute universal health coverage and thereby improve their population's healthcare access and outcomes. Until now, few countries responded favourably to this international plea. The HIV/AIDS epidemic, a major global public health challenge, resulted in over 11 million orphans in sub-Saharan Africa. Extended families have taken responsibility for more than 90% of these children. HIV orphans are likely to be poorer and less healthy. Burkitt lymphoma is the most common childhood cancer in sub-Saharan Africa. If orphans need lifesaving chemotherapy, appointing legal guardians becomes necessary to access health insurance. However, rules and regulations involved may be unclear and costly. This hinders its access for poor families who need it most. Uninsured children risk hospital detention over unpaid medical bills and have lower survival. Our case report depicts the quest for health insurance coverage of two HIV orphans with Burkitt lymphoma in Kenya.

Health-care providers' perspectives on health-insurance access, waiving procedures, and hospital detention practices in Kenya.

BACKGROUND: Patients at Kenyan public hospitals are detained if their families cannot pay their medical bills. Access to health insurance and waiving procedures to prevent detention may be limited. This study explores the perspectives of health-care providers (HCP) on health-insurance access, waiving procedures, and hospital detention practices. PROCEDURE: A self-administered structured questionnaire was completed by 104 HCP (response rate 78%) involved in childhood cancer care. RESULTS: The perspectives of respondents were as follows: all children with cancer should have health insurance according to 96% of HCP. After parents apply for health insurance, it takes too long before treatment costs are covered (67% agree). Patients with childhood cancer without health insurance have a higher chance of abandoning treatment (82% agree). Hospitals should waive bills of all children with cancer when parents have payment difficulties (69% agree). Waiving procedures take too long (75%). Parents are scared by waiving procedures and may decide never to return to the hospital again (68%). Poor families delay visiting the hospital because they fear hospital detention and first seek alternative treatment (92%). When poor families finally come to the hospital, the disease is in advanced stage already (94%). Parents sometimes have to abandon their detained child at the hospital if they cannot pay hospital bills (68%). Detention of children at the hospital if parents cannot pay their medical bills is not approved by 84% of HCP. CONCLUSIONS: HCP acknowledge that access to health insurance needs improvement and that waiving procedures contribute to treatment abandonment. By far, most HCP disapprove of hospital detention practices. These factors warrant urgent attention and adjustment.

Wilms Tumor Treatment Outcomes: Perspectives From a Low-Income Setting.

PURPOSE: 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.

Influence of health insurance status on paediatric non-Hodgkin's lymphoma treatment in Kenya.

OBJECTIVE: 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.