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.

Blood culture versus antibiotic use for neonatal inpatients in 61 hospitals implementing with the NEST360 Alliance in Kenya, Malawi, Nigeria, and Tanzania: a cross-sectional study.

BACKGROUND: Thirty million small and sick newborns worldwide require inpatient care each year. Many receive antibiotics for clinically diagnosed infections without blood cultures, the current 'gold standard' for neonatal infection detection. Low neonatal blood culture use hampers appropriate antibiotic use, fuelling antimicrobial resistance (AMR) which threatens newborn survival. This study analysed the gap between blood culture use and antibiotic prescribing in hospitals implementing with Newborn Essential Solutions and Technologies (NEST360) in Kenya, Malawi, Nigeria, and Tanzania. METHODS: Inpatient data from every newborn admission record (July 2019-August 2022) were included to describe hospital-level blood culture use and antibiotic prescription. Health Facility Assessment data informed performance categorisation of hospitals into four tiers: (Tier 1) no laboratory, (Tier 2) laboratory but no microbiology, (Tier 3) neonatal blood culture use < 50% of newborns receiving antibiotics, and (Tier 4) neonatal blood culture use > 50%. RESULTS: A total of 144,146 newborn records from 61 hospitals were analysed. Mean hospital antibiotic prescription was 70% (range = 25-100%), with 6% mean blood culture use (range = 0-56%). Of the 10,575 blood cultures performed, only 24% (95%CI 23-25) had results, with 10% (10-11) positivity. Overall, 40% (24/61) of hospitals performed no blood cultures for newborns. No hospitals were categorised as Tier 1 because all had laboratories. Of Tier 2 hospitals, 87% (20/23) were District hospitals. Most hospitals could do blood cultures (38/61), yet the majority were categorised as Tier 3 (36/61). Only two hospitals performed > 50% blood cultures for newborns on antibiotics (Tier 4). CONCLUSIONS: The two Tier 4 hospitals, with higher use of blood cultures for newborns, underline potential for higher blood culture coverage in other similar hospitals. Understanding why these hospitals are positive outliers requires more research into local barriers and enablers to performing blood cultures. Tier 3 facilities are missing opportunities for infection detection, and quality improvement strategies in neonatal units could increase coverage rapidly. Tier 2 facilities could close coverage gaps, but further laboratory strengthening is required. Closing this culture gap is doable and a priority for advancing locally-driven antibiotic stewardship programmes, preventing AMR, and reducing infection-related newborn deaths.

Variability of respiratory rate measurements in neonates- every minute counts.

BACKGROUND: Respiratory rate is difficult to measure, especially in neonates who have an irregular breathing pattern. The World Health Organisation recommends a one-minute count, but there is limited data to support this length of observation. We sought to evaluate agreement between the respiratory rate (RR) derived from capnography in neonates, over 15 s, 30 s, 120 s and 300 s, against the recommended 60 s. METHODS: Neonates at two hospitals in Nairobi were recruited and had capnograph waveforms recorded using the Masimo Rad 97. A single high quality 5 min epoch was randomly chosen from each subject. For each selected epoch, the mean RR was calculated using a breath-detection algorithm applied to the waveform. The RR in the first 60 s was compared to the mean RR measured over the first 15 s, 30 s, 120 s, full 300 s, and last 60 s. We calculated bias and limits of agreement for each comparison and used Bland-Altman plots for visual comparisons. RESULTS: A total of 306 capnographs were analysed from individual subjects. The subjects had a median gestation age of 39 weeks with slightly more females (52.3%) than males (47.7%). The majority of the population were term neonates (70.1%) with 39 (12.8%) having a primary respiratory pathology. There was poor agreement between all the comparisons based on the limits of agreement [confidence interval], ranging between 11.9 [- 6.79 to 6.23] breaths per minute in the one versus 2 min comparison, and 34.7 [- 17.59 to 20.53] breaths per minute in the first versus last minute comparison. Worsening agreement was observed in plots with higher RRs. CONCLUSIONS: Neonates have high variability of RR, even over a short period of time. A slight degradation in the agreement is noted over periods shorter than 1 min. However, this is smaller than observations done 3 min apart in the same subject. Longer periods of observation also reduce agreement. For device developers, precise synchronization is needed when comparing devices to reduce the impact of RR variation. For clinicians, where possible, continuous or repeated monitoring of neonates would be preferable to one time RR measurements.

Assessment of neonatal respiratory rate variability.

Accurate measurement of respiratory rate (RR) in neonates is challenging due to high neonatal RR variability (RRV). There is growing evidence that RRV measurement could inform and guide neonatal care. We sought to quantify neonatal RRV during a clinical study in which we compared multiparameter continuous physiological monitoring (MCPM) devices. Measurements of capnography-recorded exhaled carbon dioxide across 60-s epochs were collected from neonates admitted to the neonatal unit at Aga Khan University-Nairobi hospital. Breaths were manually counted from capnograms and using an automated signal detection algorithm which also calculated mean and median RR for each epoch. Outcome measures were between- and within-neonate RRV, between- and within-epoch RRV, and 95% limits of agreement, bias, and root-mean-square deviation. Twenty-seven neonates were included, with 130 epochs analysed. Mean manual breath count (MBC) was 48 breaths per minute. Median RRV ranged from 11.5% (interquartile range (IQR) 6.8-18.9%) to 28.1% (IQR 23.5-36.7%). Bias and limits of agreement for MBC vs algorithm-derived breath count, MBC vs algorithm-derived median breath rate, MBC vs algorithm-derived mean breath rate were - 0.5 (- 2.7, 1.66), - 3.16 (- 12.12, 5.8), and - 3.99 (- 11.3, 3.32), respectively. The marked RRV highlights the challenge of performing accurate RR measurements in neonates. More research is required to optimize the use of RRV to improve care. When evaluating MCPM devices, accuracy thresholds should be less stringent in newborns due to increased RRV. Lastly, median RR, which discounts the impact of extreme outliers, may be more reflective of the underlying physiological control of breathing.

Multiparameter Continuous Physiological Monitoring Technologies in Neonates Among Health Care Providers and Caregivers at a Private Tertiary Hospital in Nairobi, Kenya: Feasibility, Usability, and Acceptability Study.

BACKGROUND: Continuous physiological monitoring technologies are important for strengthening hospital care for neonates, particularly in resource-constrained settings, and understanding user perspectives is critical for informing medical technology design, development, and optimization. OBJECTIVE: This study aims to assess the feasibility, usability, and acceptability of 2 noninvasive, multiparameter, continuous physiological monitoring technologies for use in neonates in an African health care setting. METHODS: We assessed 2 investigational technologies from EarlySense and Sibel, compared with the reference Masimo Rad-97 technology through in-depth interviews and direct observations. A purposive sample of health care administrators, health care providers, and caregivers at Aga Khan University Hospital, a tertiary, private hospital in Nairobi, Kenya, were included. Data were analyzed using a thematic approach in NVivo 12 software. RESULTS: Between July and August 2020, we interviewed 12 health care providers, 5 health care administrators, and 10 caregivers and observed the monitoring of 12 neonates. Staffing and maintenance of training in neonatal units are important feasibility considerations, and simple training requirements support the feasibility of the investigational technologies. Key usability characteristics included ease of use, wireless features, and reduced number of attachments connecting the neonate to the monitoring technology, which health care providers considered to increase the efficiency of care. The main factors supporting acceptability included caregiver-highlighted perceptions of neonate comfort and health care respondent technology familiarity. Concerns about the side effects of wireless connections, electromagnetic fields, and mistrust of unfamiliar technologies have emerged as possible acceptability barriers to investigational technologies. CONCLUSIONS: Overall, respondents considered the investigational technologies feasible, usable, and acceptable for the care of neonates at this health care facility. Our findings highlight the potential of different multiparameter continuous physiological monitoring technologies for use in different neonatal care settings. Simple and user-friendly technologies may help to bridge gaps in current care where there are many neonates; however, challenges in maintaining training and ensuring feasibility within resource-constrained health care settings warrant further research. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-035184.

Serum Procalcitonin Levels in Children with Clinical Syndromes for Targeting Antibiotic Use at an Emergency Department of a Kenyan Hospital.

Serum procalcitonin (PCT) was measured in 228 children aged 1 month to 15 years at an emergency department of a hospital located in an area without local malaria transmission in children with suspected infections; 21% (49) children had a clinical syndrome for suspected bacterial infections (Syndrome+ve). In children with Syndrome+ve criteria, 27/49 (55.1%) had PCT ≥0.5 µg/l but only 59/179 (32.9%) of those Syndrome-ve had abnormal PCT, χ2 = 8.0, p = 0.005; positive likelihood ratio = 2.0 [95% confidence interval (CI) 1.2-3.3]; negative likelihood ratio = 0.8 (95% CI 0.7-1.0). In patients with pneumonia, 9/15 (60%) with severe pneumonia had PCT ≥0.5 µg/l compared to 11/21 (52.4%) with non-severe pneumonia, χ2 = 0.2, p = 0.65. Children with clinical signs of pneumonia or clinical signs suggestive of bacterial infections fulfilling clinical syndromic definitions for suspected bacterial infections commonly have elevated PCT level. PCT levels are associated with disease severity and antibiotic trials guided by PCT levels may be needed where cultures are not available.

Factors influencing choice of skilled birth attendance at ANC: evidence from the Kenya demographic health survey.

BACKGROUND: In Kenya, skilled attendance at delivery is well below the international target of 90% and the maternal mortality ratio is high at 362 (CI 254-471) per 100,000 live births despite various interventions. The preventative role of skilled attendance at delivery makes it a benchmark indicator for safe motherhood. METHODS: Maternal health data from the Service Provision Assessment Survey, a subset of the 2010 Kenya Demographic Health Survey was analyzed. Logistic regression models were employed using likelihood ratio test to explore association between choice of skilled attendance and predictor variables. RESULTS: Overall, 94.8% of women are likely to seek skilled attendance at delivery. Cost, education level, number of antenatal visits and sex of provider were strongly associated with client's intention to deliver with a skilled birth attendant at delivery. Women who reported having enough money set aside for delivery were 4.34 (p < 0.002, 95% CI: 1.73; 10.87) times more likely to seek skilled attendance. Those with primary education and above were 6.6 times more likely to seek skilled attendance than those with no formal education (p < 0.001, 95% CI: 3.66; 11.95). Women with four or more antenatal visits were 5.95 (p < 0.018, 95% CI: 1.35; 26.18) times more likely to seek skilled attendance. Compared to men, female providers impacted more on the client's plan (OR = 2.02 (p < 0.014, 95% CI: 1.35; 3.53). CONCLUSION: Interventions aimed at improving skilled attendance at delivery should include promotion of formal education of women and financial preparation for delivery. Whenever circumstances permit, women should be allowed to choose gender of preferred professional attendant at delivery.

Effect of provision of an integrated neonatal survival kit and early cognitive stimulation package by community health workers on developmental outcomes of infants in Kwale County, Kenya: study protocol for a cluster randomized trial.

BACKGROUND: Each year, more than 200 million children under the age of 5 years, almost all in low- and middle-income countries (LMICs), fail to achieve their developmental potential. Risk factors for compromised development often coexist and include inadequate cognitive stimulation, poverty, nutritional deficiencies, infection and complications of being born low birthweight and/or premature. Moreover, many of these risk factors are closely associated with newborn morbidity and mortality. As compromised development has significant implications on human capital, inexpensive and scalable interventions are urgently needed to promote neurodevelopment and reduce risk factors for impaired development. METHOD/DESIGN: This cluster randomized trial aims at evaluating the impact of volunteer community health workers delivering either an integrated neonatal survival kit, an early stimulation package, or a combination of both interventions, to pregnant women during their third trimester of pregnancy, compared to the current standard of care in Kwale County, Kenya. The neonatal survival kit comprises a clean delivery kit (sterile blade, cord clamp, clean plastic sheet, surgical gloves and hand soap), sunflower oil emollient, chlorhexidine, ThermoSpot(TM), Mylar infant sleeve, and a reusable instant heater. Community health workers are also equipped with a portable hand-held electric scale. The early cognitive stimulation package focuses on enhancing caregiver practices by teaching caregivers three key messages that comprise combining a gentle touch with making eye contact and talking to children, responsive feeding and caregiving, and singing. The primary outcome measure is child development at 12 months of age assessed with the Protocol for Child Monitoring (Infant and Toddler version). The main secondary outcome is newborn mortality. DISCUSSION: This study will provide evidence on effectiveness of delivering an innovative neonatal survival kit and/or early stimulation package to pregnant women in Kwale County, Kenya. Study findings will help inform policy on the most appropriate interventions for promoting healthy brain development and reduction of newborn morbidity and mortality in Kenya and other similar settings. TRIAL REGISTRATION: ClinicalTrial.gov NCT02208960 (August 1, 2014).

Clinical and epidemiological profiles of pediatric COVID-19 in two private Kenyan hospitals.

Introduction: COVID-19 infection has attracted global attention with limited published data on the burden in African children. Methods: hospital-based longitudinal survey in children with COVID-19 infection, aged 0-18 years admitted between August 2020 and December 2021. The main objective of the study was to describe socio-demographic, clinical and diagnostic manifestations of COVID-19 infection in children. Results: the study enrolled 85 children. Median age was 5•1 years (IQR = 1•3 - 12•4) with equal gender distribution. Under five years were 52•9%. Average length of hospital stay among non-severe cases was three days (IQR=2•0-5•0). No deaths were reported. Fifteen patients (18•7%) were asymptomatic. The most common presenting symptoms were fever (51•8%), vomiting (36•5%), cough (27•1%), diarrhea (20•0%), nasal congestion (14•1%) and fast breathing (12•9%). Two patients presented in shock and features consistent with Multisystemic Inflammatory Syndrome in Childhood (MIS-C). Procalcitonin and C-reactive proteins were elevated in 76•9% and 45•8% respectively. Majority (n=80) had white cell counts within normal range and none had bacterial pathogens isolated from blood (n=63). Liver and Renal function tests were within the normal range in the majority of those tested (n=24 and n=64 respectively). Three of the five patients with elevated platelet count (>500 x109/L) had clinical diagnosis of MIS-C. Eight of 20 patients subjected to imaging had radiological features of bilateral ground glass opacifications while six of nine patients who presented with cardiovascular compromise had mild to moderate ventricular dysfunction on echocardiography. Conclusion: our study suggests that children in the African setting manifest a mild form of the COVID-19 infection with low mortality.

Prevalence of non-alcoholic fatty liver disease in overweight and obese children seeking ambulatory healthcare in Nairobi, Kenya.

BACKGROUND: While linked to obesity and associated with an increased cardiovascular morbidity, non-alcoholic fatty liver disease (NAFLD) is an often-asymptomatic cause of chronic liver disease in children. Early detection provides opportunity for interventions to curb progression. Childhood obesity is on the rise in low/middle-income countries, but cause-specific mortality data associated with liver disease are scanty. Establishing the prevalence of NAFLD in overweight and obese Kenyan children would guide in public health policies aimed at early screening and intervention. OBJECTIVES: To investigate prevalence of NAFLD in overweight and obese children aged 6-18 years using liver ultrasonography. METHODOLOGY: This was a cross-sectional survey. After obtaining informed consent, a questionnaire was administered, and blood pressure (BP) measured. Liver ultrasonography was performed to assess fatty changes. Categorical variables were analysed using frequency and percentages. χ2 test and multiple logistic regression model were used to determine relationship between exposure and outcome variables. RESULTS: Prevalence of NAFLD was 26.2% (27/103, 95% CI=18.0% to 35.8%). There was no association between sex and NAFLD (OR1.13, p=0.82; 95% CI=0.4 to 3.2). Obese children were four times more likely to have NAFLD compared with overweight children (OR=4.52, p=0.02; 95% CI=1.4 to 19.0). About 40.8% (n=41) had elevated BP, but there was no association with NAFLD (OR=2.06; p=0.27; 95% CI=0.6 to 7.6). Older children (13-18 years) were more likely to have NAFLD (OR 4.42; p=0.03; 95% CI=1.2 to 17.9). CONCLUSION: Prevalence of NAFLD was high in overweight and obese school children in Nairobi. Further studies are needed to identify modifiable risk factors to arrest progression and prevent sequelae.