Access to essential cancer medicines for children: a comparative mixed-methods analysis of availability, price, and health-system determinants in east Africa.

BACKGROUND: Access to essential childhood cancer medicines is a core determinant of childhood cancer outcomes. Available evidence, although scarce, suggests that access to these medicines is highly variable across countries, particularly in low-income and middle-income countries, where the burden of childhood cancer is greatest. To support evidence-informed national and regional policies for improved childhood cancer outcomes, we aimed to analyse access to essential childhood cancer medicines in four east African countries-Kenya, Rwanda, Tanzania, and Uganda-by determining the availability and price of these medicines and the health system determinants of access. METHODS: In this comparative analysis, we used prospective mixed-method analyses to track and analyse the availability and price of essential childhood cancer medicines, investigate contextual determinants of access to childhood cancer medicines within and across included countries, and assess the potential effects of medicine stockouts on treatment. Eight tertiary care hospitals were included, seven were public sites (Kenyatta National Hospital [KNH; Nairobi, Kenya], Jaramogi Oginga Odinga Referral and Teaching Hospital [JOORTH; Kisumu, Kenya], Moi University Teaching and Referral Hospital [MTRH; Eldoret, Kenya], Bugando Medical Centre [BMC; Mwanza, Tanzania], Muhimbili National Hospital [MNH; Dar es Salaam, Tanzania], Butaro Cancer Centre of Excellence [BCCE; Butaro Sector, Rwanda], and Uganda Cancer Institute [UCI; Kampala, Uganda]) and one was a private site (Aga Khan University Hospital [AKU; Nairobi, Kenya]). We catalogued prices and stockouts for 37 essential drugs from each of the eight study siteson the basis of 52 weeks of prospective data that was collected across sites from May 1, 2020, to Jan 31, 2022. We analysed determinants of medicine access using thematic analysis of academic literature, policy documents, and semi-structured interviews from a purposive sample of health system stakeholders. FINDINGS: Recurrent stockouts of a wide range of cytotoxic and supportive care medicines were observed across sites, with highest mean unavailability in Kenya (JOORTH; 48·5%), Rwanda (BCCE; 39·0%), and Tanzania (BMC; 32·2%). Drugs that had frequent stockouts across at least four sites included methotrexate, bleomycin, etoposide, ifosfamide, oral morphine, and allopurinol. Average median price ratio of medicines at each site was within WHO's internationally accepted threshold for efficient procurement (median price ratio ≤1·5). The effect of stockouts on treatment was noted across most sites, with the greatest potential for treatment interruptions in patients with Hodgkin lymphoma, retinoblastoma, and acute lymphocytic leukaemia. Policy prioritisation of childhood cancers, health financing and coverage, medicine procurement and supply chain management, and health system infrastructure emerged as four prominent determinants of access when the stratified purposive sample of key informants (n=64) across all four countries (Kenya n=19, Rwanda n=15, Tanzania n=13, and Uganda n=17) was interviewed. INTERPRETATION: Access to childhood cancer medicines across east Africa is marked by gaps in availability that have implications for effective treatment delivery for a range of childhood cancers. Our findings provide detailed evidence of barriers to access to childhood cancer medicine at multiple points in the pharmaceutical value chain. These data could inform national and regional policy makers to optimise cancer medicine availability and affordability as part of efforts to improve childhood cancer outcomes specific regions and internationally. FUNDING: American Childhood Cancer Organization, Childhood Cancer International, and the Friends of Cancer Patients Ameera Fund.

Baseline blood count levels increase odds of cytopenia among CML patients in Kenya: a case control study.

BACKGROUND: Imatinib is the gold standard for the treatment of all phases of Philadelphia positive Chronic Myeloid Leukemia (CML). During treatment, patients may develop cytopenia. We aimed to study the baseline characteristics and factors associated with cytopenia at a Nairobi Hospital. METHODS: This was a retrospective case-control study of patients aged ≥18 years on follow-up at the Glivec International Patient Access Program (GIPAP) clinic from 2007 to 2015. The cases consisted of CML patients on imatinib who developed cytopenia. The controls were CML patients on imatinib who did not develop cytopenia. Baseline socio - demographic, clinical, hematologic, and molecular data were retrieved from patients' files. Chi square or fishers' exact tests were used to analyze for differences between cytopenia and no cytopenia. Binary logistic regressions were employed to identify relationships. Univariate and multivariate analyses were done to identify independent predictors of cytopenia. Odds ratios (OR) were presented including the 95% confidence intervals and respective p values. RESULTS: A total of 201 patients were studied consisting of ninety-four (94) patients with cytopenia and 107 with no cytopenia. Among the entire population, males were 52, and 42% were aged 36-50 years. Sex, age, marital status, occupation and education level were similar between the cytopenia and no cytopenia groups. Among the 201 patients, 70% had symptoms for > 12 months before diagnosis, 78.6% had B symptoms at baseline, 80% had a moderate splenomegaly at baseline. Among patients with cytopenia, 40 and 37.4% developed cytopenia within 3 months and 3-6 months respectively after imatinib initiation. Baseline neutrophilia, neutropenia, anaemia, thrombocytosis, thrombocytopenia was found in 68, 11, 11, 23.5 and 11% respectively. Baseline hemoglobin, neutrophil and platelet level were significantly different between the cytopenia and the no cytopenia group. On univariable analysis, baseline anemia with hb < 7.9 g/dL (p = 0.002), neutropenia (p = 0.001), neutrophilia > 100,000/mm3 (p = 0.002) and thrombocytopenia (p = 0.001) increased the odds of developing cytopenia. On multivariable analysis, baseline anaemia (p value < 0.002), neutropenia (p value < 0.001), thrombocytopenia (p value, < 0.001) and thrombocytosis (p value, 0.033) increased the odds of developing cytopenia. CONCLUSION: Odds of cytopenia were higher in presence of baseline cytopenia and thrombocytosis. Clinicians should have a high index of suspicion for these patients.

Factors associated with 36-month loss to follow-up and mortality outcomes among HIV-infected adults on antiretroviral therapy in Central Kenya.

BACKGROUND: The scale-up of HIV treatment programs has resulted in a reduction in HIV-related morbidity and mortality. However, retention of patients in these programs remains a challenge in sub-Saharan Africa. Understanding factors associated with loss to follow-up (LTFU) and mortality outcomes is therefore important to inform targeted program interventions. METHODS: A retrospective multi-cohort analysis of 23,890 adult patients on ART over 36 months of follow-up in Kenya was done. Multivariate logistic regression analysis was done to assess for factors associated with LTFU and mortality at 6, 12, 24, and 36 months of follow-up. RESULTS: Majority, 67.7%, were female. At 36 months, 27.2% were LTFU and 13.5% had died. Factors associated with mortality at 36 months included older age (51 years and above) using 20-35 years as reference [(adjusted odds ratio [aOR], 1.51, 95% confidence interval (CI) 1.23-1.86, p < 0.001], being male (aOR, 1.59, 95% CI 1.39-1.83, p < 0.001), divorced using married as reference (aOR, 1.86, 95% CI 1.56-2.22, p < 0.001), having a body mass index (BMI) score of less than 18.5 kg/m2 using 18.5-24.9 kg/m2 as reference (aOR = 1.79, 95% CI 1.52-2.11, p < 0.001), and, World Health Organization stage III and IV using stage I as the reference (aOR, 1.94, 95% CI 1.43-2.63 and aOR, 4.24, 95% CI 3.06-5.87, p < 0.001 respectively). Factors associated with LTFU at 36 months included being young between 20 and 35 years (aOR, 1.49, 95% CI 1.40-1.59, p < 0.001) using 36-50 years as reference, being male (aOR, 1.19, 95% CI 1.12-1.27, p < 0.001), and being single or divorced using married as reference (aOR, 1.34, 95% CI 1.23-1.45 and aOR, 1.25, 95% CI 1.15-1.36, p < 0.001 respectively). Patients with baseline BMI of less than 18.5 kg/m2 using normal BMI as reference (aOR, 1.68, 95% CI 1.39-2.02, p < 0.001) were also likely to be LTFU. CONCLUSIONS: Factors associated with LTFU and mortality were generally similar over time. Implementation of programs in similar settings should be tailored to gender, age profiles, nutritional, and, marital status of patients to address LTFU. In addition, programs should focus on the care of older patients to reduce the risk of mortality.

Decentralizing cancer care in sub-Saharan Africa through an integrated regional cancer centre model: The case of Kenya.

For 50 years, comprehensive cancer treatment services were provided at one public hospital and a few private facilities in the capital city. In 2019, the services were decentralized to new national and regional centers to increase service accessibility using an integration model. This study aimed to analyze the status of the utilization of services at regional cancer centers. We analyzed data from the district health information system, focusing on patient demographics, visit type, cancer stage, and the type of treatment provided. For comparison, a trend analysis of new cancer cases recorded at the main national referral hospital between 2011-2021 was also conducted. We conducted a descriptive analysis of the variables of interest; the median was used to summarize continuous variables and percentages were used for categorical variables. A total of 29,321 patients visited the regional centers in 2021; the median age was 57 years (IQR 44-68) and 57.3% (16,815) were female. Visits to regional centres represented 38.8% (29,321/75,501) of all visits to public cancer centers; new visits accounted for 16.4% (4814/29321), and the rest were follow-up visits. Most patients (71%) had an advanced disease. The proportion of male patients with advanced-stage cancer was significantly higher than that of female patients (74% vs. 69%, P<0.001). Of the 15,275 patients who received treatment at regional centers, 69.1% (10,550) received chemotherapy.The increased patient visits show good service uptake at the regional centers, implying improved access. These findings can inform policies that will guide future expansion and service improvement. We recommend optimizing cancer service delivery at regional centers across the care continuum to improve patient outcomes.

Factors Associated with Treatment Outcomes Among Children and Adolescents Living with HIV Receiving Antiretroviral Therapy in Central Kenya.

Expanded access to HIV treatment services has improved outcomes for children and adolescents living with HIV in Kenya. Minimal data are available on these outcomes. We describe temporal trends in outcomes for children and adolescents initiating antiretroviral therapy (ART) from 2004 to 2014 at sites supported by Centre for Health Solutions-Kenya, in central Kenya. We retrospectively analyzed data from children 0-9 years of age (n = 3,519) and adolescents 10-19 years of age (n = 1,663) living with HIV, who newly initiated ART at 47 health facilities in central Kenya. Year cohorts were analyzed from the Comprehensive Patient Application Database (CPAD) and International Quality Care (IQCare) electronic medical databases, including temporal trends in outcomes and associated factors using multivariable competing risk regression analysis. There were more girls (2,453 [52.7%]) than boys, with most enrolled at World Health Organization (WHO) stage II (1,813 [37.7%]) or III disease (1,694 [35.1%]). Most of the children and adolescents (4,431 [96.4%]) did not have tuberculosis (TB) symptoms. Cumulative lost to follow-up (LTFU) incidence at 6, 12, 24, and 36 months were 5.0%, 9.9%, 22.9%, and 33.1%, respectively. Cumulative mortality incidence at 6, 12, 24, and 36 months were 0.7%, 1.0%, 1.2%, and 1.5%, respectively. The incidence of LTFU was higher among female children and adolescents, those initiated on tenofovir-based regimens, and those with presumptive TB symptoms. Mortality risk was higher among those with WHO stage III or IV disease, and children and adolescents on TB treatment or who had presumptive TB. Enrollment occurred at a young age and pediatric-friendly ART regimens were initiated at earlier WHO stages implying effective early infant diagnosis and treatment for all strategies, resulting in improved treatment outcomes. The higher retention rates in recent years as well as the lower retention after many years of follow-up underscore the importance of implementing longitudinal follow-up strategies targeting this population.

Characteristics and Treatment Response of Patients with HIV Associated Kaposi's Sarcoma in Central Kenya.

Introduction: Kaposi's sarcoma (KS) is the most common HIV-associated malignancy in Sub Saharan Africa. In 2018, it was the 7th most common cancer and the 10th most common cause of cancer death in Kenya. This study aimed to describe the baseline and clinical characteristics and treatment response observed following combined antiretroviral treatment (ART) and chemotherapy in KS patients. Methods: This was a descriptive analysis of patients aged ≥15 years treated for KS and HIV at 11 treatment hubs in Central Kenya between 2011 and 2014. Data on baseline and clinical characteristics, ART and chemotherapy regimens as well as treatment responses were collected from patient files and KS registers. Results: A total of 95 patients presenting with clinically suspected KS with no history of prior treatment with chemotherapy were reviewed. All had histological diagnostic samples taken with 67 (71%) having confirmed KS. All were on ART, either newly initiated or continuing on ART, and 63 of the 67 (94.0%) confirmed to have KS received chemotherapy. Among the 67 patients with confirmed KS, mean age was 37.2 years (± 13.2) and 40 (59.7%) were male. More than 80% had normal baseline and follow-up BMI, and 34 (50.7%) were on a TDF-based regimen, 52 (77.6%) were treated with the Adriamycin, bleomycin and vinblastine protocol, and 55 (82.1%) had KS diagnosis before HIV diagnosis. All 67 patients had mucocutaneous lesions. Complete, partial response and stable disease occurred in 27 (40.3%), 10 (14.9%) and 7 (10.4%), respectively, 11 (16.4%) defaulted care during treatment, six patients died during treatment, four patients died before treatment while two patients had progressive disease during chemotherapy. Conclusion: The diagnosis of KS preceded HIV in the majority of cases reviewed, with histology helpful to reduce misdiagnosis. Patients generally complied with their chemotherapy, with overall good response rate for this intervention implemented at primary health-care facilities.

Cytopenia among CML Patients on Imatinib in Kenya: Types, Grades, and Time Course.

BACKGROUND: Imatinib mesylate is the gold standard for the treatment of all phases of Philadelphia-positive chronic myeloid leukemia. Patients on imatinib treatment may develop cytopenia due to drug toxicity. This study aimed to determine the types, grades, and time course of cytopenia in CML patients on imatinib at a Nairobi hospital. METHODS: This was a cross-sectional descriptive study of adult patients aged ≥18 years followed up at the Glivec International Patient Access Program (GIPAP) clinic from 2007 to 2015. Patients who developed cytopenia within 12 months of initiating imatinib were eligible. Clinical and hematologic data were retrieved from the patients' charts and entered into a study proforma. Measures of central tendency such as mean, median, mode, standard deviation, and variance were used for analysis. RESULTS: Sixty three percent (63.6%) of the 94 patients developed a monocytopenia, with anemia seen in 34%, neutropenia in 27.6%, and thrombocytopenia in 8% of the 94 patients. Anemia plus neutropenia was the most common bicytopenia at 12.7%. Pancytopenia was seen in only 5 of the 94 patients. Most of the cytopenia was grades 2 and 3. Anemia was present at baseline while neutropenia and thrombocytopenia developed within 12 months of imatinib initiation. Anemia resolved during the first 12 months of therapy while neutropenia and thrombocytopenia resolved within 24-36 months of treatment. CONCLUSION: Monocytopenia, especially anemia, was the most common type of cytopenia. The cytopenia was predominantly grade 2, developed in majority of the patients within 6 months after imatinib initiation, and had resolved by 24-36 months after imatinib initiation.

Prevalence and Predictors of Cisplatin-Induced Peripheral Neuropathy at the Kenyatta National Hospital.

PURPOSE: To determine the prevalence, predictors, and/or risk factors of chemotherapy-induced peripheral neuropathy in patients undergoing chemotherapy with cisplatin at Kenyatta National Hospital, Nairobi, Kenya. METHODS: This was a cross-sectional analysis of patients who underwent chemotherapy with cisplatin for at least 2 months at Kenyatta National Hospital oncology units. Peripheral neuropathy was determined by history and physical examination per the protocol. Data are presented in tables. Descriptive inferential statistics such as means, medians, and proportions were determined where applicable. RESULTS: We recruited 67 patients who were undergoing chemotherapy with cisplatin. Fifty-six patients (83.6%) had peripheral neuropathy. Forty-five patients (81%) had mild-grade (grades 1 and 2) peripheral neuropathy. Only two patients (3.1%) had grade 4 neuropathy. Almost all patients who were overweight or obese developed peripheral neuropathy. CONCLUSION: Peripheral neuropathy among patients receiving cisplatin is quite prevalent at Kenyatta National Hospital (83.6% prevalence rate). However, most of the patients had a mild grade of neuropathy, which is largely consistent with literature elsewhere.