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).

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.

Role of hospital leadership in pandemic preparedness: experience at a tertiary hospital in Kenya during the COVID-19 pandemic.

INTRODUCTION: Pandemic preparedness refers to being ready for, responding to and recovering from public health crises, and is integral for health security. Hospital leadership is a critical building block of an effective healthcare system, providing policy, accountability and stewardship in a health crisis. OBJECTIVES AND METHODS: We aimed to describe the leadership and governance structures put in place at the Aga Khan University Hospital, Nairobi, a private not-for-profit tertiary healthcare facility, following the COVID-19 pandemic. We reviewed over 200 hospital documents archived in the COVID-19 repository including those received from the Kenya Ministry of Health, emails, memos, bulletins, meeting minutes, protocols, brochures and flyers. We evaluated and described pandemic preparedness at the hospital under four main themes: (a) leadership, governance and incident management structures; (b) coordination and partnerships; (c) communication strategies; and (d) framework to resolve ethical dilemmas. RESULTS: The hospital expeditiously established three emergency governance structures, namely a task force, an operations team and an implementation team, to direct and implement evidence-based preparedness strategies. Leveraging on partners, the hospital ensured that risk analyses and decisions made: (1) were based on evidence and in line with the national and global guidelines, (2) were supported by community leaders and (3) expedite financing for urgent hospital activities. Communication strategies were put in place to ensure harmonised COVID-19 messaging to the hospital staff, patients, visitors and the public to minimise misinformation or disinformation. An ethical framework was also established to build trust and transparency among the hospital leadership, staff and patients. CONCLUSION: The establishment of a hospital leadership structure is crucial for efficient and effective implementation of pandemic preparedness and response strategies which are evidence based, well resourced and ethical. The role of leadership discussed is applicable to healthcare facilities across low and middle-income countries to develop contextualised pandemic preparedness plans.

Developing and testing a clinical care bundle incorporating caffeine citrate to manage apnoea of prematurity in a resource-constrained setting: a mixed methods clinical feasibility study protocol.

BACKGROUND: Apnoea of prematurity (AOP) is a common condition among preterm infants. Methylxanthines, such as caffeine and aminophylline/theophylline, can help prevent and treat AOP. Due to its physiological benefits and fewer side effects, caffeine citrate is recommended for the prevention and treatment of AOP. However, caffeine citrate is not available in most resource-constrained settings (RCS) due to its high cost. Challenges in RCS using caffeine citrate to prevent AOP include identifying eligible preterm infants where gestational age is not always known and the capability for continuous monitoring of vital signs to readily identify apnoea. We aim to develop an evidence-based care bundle that includes caffeine citrate to prevent and manage AOP in tertiary healthcare facilities in Kenya. METHODS: This protocol details a prospective mixed-methods clinical feasibility study on using caffeine citrate to manage apnoea of prematurity in a single facility tertiary-care newborn unit (NBU) in Nairobi, Kenya. This study will include a 4-month formative research phase followed by the development of an AOP clinical-care-bundle prototype over 2 months. In the subsequent 4 months, implementation and improvement of the clinical-care-bundle prototype will be undertaken. The baseline data will provide contextualised insights on care practices within the NBU that will inform the development of a context-sensitive AOP clinical-care-bundle prototype. The clinical care bundle will be tested and refined further during an implementation phase of the quality improvement initiative using a PDSA framework underpinned by quantitative and qualitative clinical audits and stakeholders' engagement. The quantitative component will include all neonates born at gestation age < 34 weeks and any neonate prescribed aminophylline or caffeine citrate admitted to the NBU during the study period. DISCUSSION: There is a need to develop evidence-based and context-sensitive clinical practice guidelines to standardise and improve the management of AOP in RCS. Concerns requiring resolution in implementing such guidelines include diagnosis of apnoea, optimal timing, dosing and administration of caffeine citrate, standardisation of monitoring devices and alarm limits, and discharge protocols. We aim to provide a feasible standardised clinical care bundle for managing AOP in low and middle-income settings.

A survey of barriers and facilitators to caffeine use for apnoea of prematurity in low- and middle-income countries.

BACKGROUND: Despite its associated benefits which include better long-term pulmonary and neurodevelopmental outcome, the use of caffeine for apnoea of prematurity (AoP) has been limited in low- and middle-income countries (LMIC). AIM: To better understand current caffeine use, the barriers and facilitators to its use and perceptions and practices in LMIC which have a disproportionately high burden of prematurity. METHODS: An anonymous online global survey was conducted, targeting healthcare providers working and training in paediatrics and/or neonatology in LMIC. RESULTS: A total of 181 respondents in 16 LMIC were included in the analysis; most were physicians working in publicly-funded urban tertiary hospitals. Most had received training in the use of caffeine for AoP (77%), reported expertise (70%) and confidence (96%) in its use, and had access to caffeine (65%). Caffeine availability was reported to be the greatest barrier (48%) and the greatest facilitator (37%). Other common barriers included cost (31%), access (7%) and policies or guidelines on caffeine use (7%); other common facilitators included policies or guidelines on caffeine use (11%), access (10%), staff/other providers' acceptance of caffeine as an appropriate treatment (9%) and the availability of staff to administer caffeine (8%). Most (79%) noted that access to caffeine was important, 92% agreed that caffeine improves quality of care, and 95% agreed that caffeine improves patient outcome. CONCLUSION: Improving availability and access to low-cost caffeine will be key to increasing caffeine use in LMIC. ABBREVIATIONS: AoP: Apnoea of Prematurity; LMIC: low- and middle-Income countries; REDCap: Research Electronic Data Capture.

Evaluation of Sibel's Advanced Neonatal Epidermal (ANNE) wireless continuous physiological monitor in Nairobi, Kenya.

BACKGROUND: Neonatal multiparameter continuous physiological monitoring (MCPM) technologies assist with early detection of preventable and treatable causes of neonatal mortality. Evaluating accuracy of novel MCPM technologies is critical for their appropriate use and adoption. METHODS: We prospectively compared the accuracy of Sibel's Advanced Neonatal Epidermal (ANNE) technology with Masimo's Rad-97 pulse CO-oximeter with capnography and Spengler's Tempo Easy reference technologies during four evaluation rounds. We compared accuracy of heart rate (HR), respiratory rate (RR), oxygen saturation (SpO2), and skin temperature using Bland-Altman plots and root-mean-square deviation analyses (RMSD). Sibel's ANNE algorithms were optimized between each round. We created Clarke error grids with zones of 20% to aid with clinical interpretation of HR and RR results. RESULTS: Between November 2019 and August 2020 we collected 320 hours of data from 84 neonates. In the final round, Sibel's ANNE technology demonstrated a normalized bias of 0% for HR and 3.1% for RR, and a non-normalized bias of -0.3% for SpO2 and 0.2°C for temperature. The normalized spread between 95% upper and lower limits-of-agreement (LOA) was 4.7% for HR and 29.3% for RR. RMSD for SpO2 was 1.9% and 1.5°C for temperature. Agreement between Sibel's ANNE technology and the reference technologies met the a priori-defined thresholds for 95% spread of LOA and RMSD. Clarke error grids showed that all HR and RR observations were within a 20% difference. CONCLUSION: Our findings suggest acceptable agreement between Sibel's ANNE and reference technologies. Clinical effectiveness, feasibility, usability, acceptability, and cost-effectiveness investigations are necessary for large-scale implementation.

Qualitative study exploring the feasibility, usability and acceptability of neonatal continuous monitoring technologies at a public tertiary hospital in Nairobi, Kenya.

OBJECTIVE: To assess the feasibility, usability and acceptability of two non-invasive, multiparameter, continuous physiological monitoring (MCPM) technologies for use in neonates within a resource-constrained healthcare setting in sub-Saharan Africa. DESIGN: A qualitative study using in-depth interviews and direct observations to describe healthcare professional and caregiver perspectives and experiences with investigational MCPM technologies from EarlySense and Sibel compared with selected reference technologies. SETTING: Pumwani Maternity Hospital is a public, high-volume, tertiary hospital in Nairobi, Kenya. PARTICIPANTS: In-depth interviews were conducted with five healthcare administrators, 12 healthcare providers and 10 caregivers. Direct observations were made of healthcare providers using the technologies on 12 neonates overall. RESULTS: Design factors like non-invasiveness, portability, ease-of-use and ability to measure multiple vital signs concurrently emerged as key themes supporting the usability and acceptability of the investigational technologies. However, respondents also reported feasibility challenges to implementation, including overcrowding in the neonatal unit, lack of reliable access to electricity and computers, and concerns about cost and maintenance needs. To improve acceptability, respondents highlighted the need for adequate staffing to appropriately engage caregivers and dispel misconceptions about the technologies. CONCLUSION: Study participants were positive about the usefulness of the investigational technologies to strengthen clinical care quality and identification of at-risk neonates for better access to timely interventions. These technologies have the potential to improve equity of access to appropriate healthcare services and neonatal outcomes in sub-Saharan African healthcare facilities. However, health system strengthening is also critical to support sustainable uptake of technologies into routine care. TRIAL REGISTRATION NUMBER: NCT03920761.

Clinical feasibility of a contactless multiparameter continuous monitoring technology for neonates in a large public maternity hospital in Nairobi, Kenya.

Multiparameter continuous physiological monitoring (MCPM) technologies are critical in the clinical management of high-risk neonates; yet, these technologies are frequently unavailable in many African healthcare facilities. We conducted a prospective clinical feasibility study of EarlySense's novel under-mattress MCPM technology in neonates at Pumwani Maternity Hospital in Nairobi, Kenya. To assess feasibility, we compared the performance of EarlySense's technology to Masimo's Rad-97 pulse CO-oximeter with capnography technology for heart rate (HR) and respiratory rate (RR) measurements using up-time, clinical event detection performance, and accuracy. Between September 15 and December 15, 2020, we collected and analyzed 470 hours of EarlySense data from 109 enrolled neonates. EarlySense's technology's up-time per neonate was 2.9 (range 0.8, 5.3) hours for HR and 2.1 (range 0.9, 4.0) hours for RR. The difference compared to the reference was a median of 0.6 (range 0.1, 3.1) hours for HR and 0.8 (range 0.1, 2.9) hours for RR. EarlySense's technology identified high HR and RR events with high sensitivity (HR 81%; RR 83%) and specificity (HR 99%; RR 83%), but was less sensitive for low HR and RR (HR 0%; RR 14%) although maintained specificity (HR 100%; RR 95%). There was a greater number of false negative and false positive RR events than false negative and false positive HR events. The normalized spread of limits of agreement was 9.6% for HR and 28.6% for RR, which met the a priori-identified limit of 30%. EarlySense's MCPM technology was clinically feasible as demonstrated by high percentage of up-time, strong clinical event detection performance, and agreement of HR and RR measurements compared to the reference technology. Studies in critically ill neonates, assessing barriers and facilitators to adoption, and costing analyses will be key to the technology's development and potential uptake and scale-up.

Evaluation of a contactless neonatal physiological monitor in Nairobi, Kenya.

BACKGROUND: Globally, 2.5 million neonates died in 2018, accounting for 46% of under-5 deaths. Multiparameter continuous physiological monitoring (MCPM) of neonates allows for early detection and treatment of life-threatening health problems. However, neonatal monitoring technology is largely unavailable in low-resource settings. METHODS: In four evaluation rounds, we prospectively compared the accuracy of the EarlySense under-mattress device to the Masimo Rad-97 pulse CO-oximeter with capnography reference device for heart rate (HR) and respiratory rate (RR) measurements in neonates in Kenya. EarlySense algorithm optimisations were made between evaluation rounds. In each evaluation round, we compared 200 randomly selected epochs of data using Bland-Altman plots and generated Clarke error grids with zones of 20% to aid in clinical interpretation. RESULTS: Between 9 July 2019 and 8 January 2020, we collected 280 hours of MCPM data from 76 enrolled neonates. At the final evaluation round, the EarlySense MCPM device demonstrated a bias of -0.8 beats/minute for HR and 1.6 breaths/minute for RR, and normalised spread between the 95% upper and lower limits of agreement of 6.2% for HR and 27.3% for RR. Agreement between the two MCPM devices met the a priori-defined threshold of 30%. The Clarke error grids showed that all observations for HR and 197/200 for RR were within a 20% difference. CONCLUSION: Our research indicates that there is acceptable agreement between the EarlySense and Masimo MCPM devices in the context of large within-subject variability; however, further studies establishing cost-effectiveness and clinical effectiveness are needed before large-scale implementation of the EarlySense MCPM device in neonates. TRIAL REGISTRATION NUMBER: NCT03920761.

Clinical feasibility of an advanced neonatal epidermal multiparameter continuous monitoring technology in a large public maternity hospital in Nairobi, Kenya.

Clinically feasible multiparameter continuous physiological monitoring technologies are needed for use in resource-constrained African healthcare facilities to allow for early detection of critical events and timely intervention for major morbidities in high-risk neonates. We conducted a prospective clinical feasibility study of a novel multiparameter continuous physiological monitoring technology in neonates at Pumwani Maternity Hospital in Nairobi, Kenya. To assess feasibility, we compared the performance of Sibel's Advanced Neonatal Epidermal (ANNE) technology to reference technologies, including Masimo's Rad-97 pulse CO-oximeter with capnography technology for heart rate (HR), respiratory rate (RR), and oxygen saturation (SpO2) measurements and Spengler's Tempo Easy non-contact infrared thermometer for temperature measurements. We evaluated key performance criteria such as up-time, clinical event detection performance, and the agreement of measurements compared to those from the reference technologies in an uncontrolled, real-world setting. Between September 15 and December 15, 2020, we collected and analyzed 503 h of ANNE data from 109 enrolled neonates. ANNE's up-time was 42 (11%) h more for HR, 77 (25%) h more for RR, and 6 (2%) h less for SpO2 compared to the Rad-97. However, ANNE's ratio of up-time to total attached time was less than Rad-97's for HR (0.79 vs 0.86), RR (0.68 vs. 0.79), and SpO2 (0.69 vs 0.86). ANNE demonstrated adequate performance in identifying high and low HR and RR and high temperature events; however, showed relatively poor performance for low SpO2 events. The normalized spread of limits of agreement were 8.4% for HR and 52.2% for RR and the normalized root-mean-square deviation was 4.4% for SpO2. Temperature agreement showed a spread of limits of agreement of 2.8 °C. The a priori-identified optimal limits were met for HR and temperature but not for RR or SpO2. ANNE was clinically feasible for HR and temperature but not RR and SpO2 as demonstrated by the technology's up-time, clinical event detection performance, and the agreement of measurements compared to those from the reference technologies.

Prevalence of vitamin D deficiency in exclusively breastfed infants at a tertiary healthcare facility in Nairobi, Kenya.

OBJECTIVE: To determine the prevalence of vitamin D deficiency (VDD) in exclusively breastfed infants at the Aga Khan University Hospital Nairobi, Kenya (AKUHN). The relationships between 25-hydroxyvitamin D; 25OHD, parathyroid hormone (PTH), maternal vitamin D supplementation, and sunlight exposure were also determined. METHODS: Blood from 98 infants was assayed for 25OHD, calcium, phosphate, and PTH. Socio-demographic and clinical characteristics were analyzed using descriptive statistics and inferential analysis (p < 0.05). RESULTS: The prevalence of VDD (25OHD <12 ng/mL), vitamin D insufficiency (VDI, 25OHD 12-20 ng/mL) and vitamin D sufficiency (VDS, 25OHD >20 ng/mL) was 11.2% (95% CI 8.0%-14.4%), 12.2% (95% CI 8.9%-15.5%), and 76.5% (95% CI 72.3%-80.8%) respectively. There was no difference in the mean age, head circumference, length, or weight of infants in VDD, VDI, and VDS groups. PTH was elevated when 25OHD was <12 ng/mL and normal when 25OHD was between 12-20 ng/mL. 25OHD and PTH were normal in infants whose mothers received vitamin D supplements. Infants who received <30 minutes/day of exposure to sunlight were 5 times more likely to have VDI than infants who received ≥30 minutes/day (p = 0.042). CONCLUSION: The prevalence of VDD in exclusively breastfed infants at AKUHN is low. The current national policy that recommends exclusive breastfeeding of infants in the first 6 months of life appears to be effective in staving off vitamin D deficiency but those infants with < 30 minutes sunlight exposure may benefit from low dose supplemental vitamin D during times of low sunlight exposure.

Identification of thresholds for accuracy comparisons of heart rate and respiratory rate in neonates.

Background: Heart rate (HR) and respiratory rate (RR) can be challenging to measure accurately and reliably in neonates. The introduction of innovative, non-invasive measurement technologies suitable for resource-constrained settings is limited by the lack of appropriate clinical thresholds for accuracy comparison studies. Methods: We collected measurements of photoplethysmography-recorded HR and capnography-recorded exhaled carbon dioxide across multiple 60-second epochs (observations) in enrolled neonates admitted to the neonatal care unit at Aga Khan University Hospital in Nairobi, Kenya. Trained study nurses manually recorded HR, and the study team manually counted individual breaths from capnograms. For comparison, HR and RR also were measured using an automated signal detection algorithm. Clinical measurements were analyzed for repeatability. Results: A total of 297 epochs across 35 neonates were recorded. Manual HR showed a bias of -2.4 (-1.8%) and a spread between the 95% limits of agreement (LOA) of 40.3 (29.6%) compared to the algorithm-derived median HR. Manual RR showed a bias of -3.2 (-6.6%) and a spread between the 95% LOA of 17.9 (37.3%) compared to the algorithm-derived median RR, and a bias of -0.5 (1.1%) and a spread between the 95% LOA of 4.4 (9.1%) compared to the algorithm-derived RR count. Manual HR and RR showed repeatability of 0.6 (interquartile range (IQR) 0.5-0.7), and 0.7 (IQR 0.5-0.8), respectively. Conclusions: Appropriate clinical thresholds should be selected a priori when performing accuracy comparisons for HR and RR. Automated measurement technologies typically use median values rather than counts, which significantly impacts accuracy. A wider spread between the LOA, as much as 30%, should be considered to account for the observed physiological nuances and within- and between-neonate variability and different averaging methods. Wider adoption of thresholds by data standards organizations and technology developers and manufacturers will increase the robustness of clinical comparison studies.

Evaluation of non-invasive continuous physiological monitoring devices for neonates in Nairobi, Kenya: a research protocol.

INTRODUCTION: Continuous physiological monitoring devices are often not available for monitoring high-risk neonates in low-resource settings. Easy-to-use, non-invasive, multiparameter, continuous physiological monitoring devices could be instrumental in providing appropriate care and improving outcomes for high-risk neonates in these low-resource settings. METHODS AND ANALYSIS: The purpose of this prospective, observational, facility-based evaluation is to provide evidence to establish whether two existing non-invasive, multiparameter, continuous physiological monitoring devices developed by device developers, EarlySense and Sibel, can accurately and reliably measure vital signs in neonates (when compared with verified reference devices). We will also assess the feasibility, usability and acceptability of these devices for use in neonates in low-resource settings in Africa. Up to 500 neonates are enrolled in two phases: (1) a verification and accuracy evaluation phase at Aga Khan University-Nairobi and (2) a clinical feasibility evaluation phase at Pumwani Maternity Hospital in Nairobi, Kenya. Both quantitative and qualitative data are collected and analysed. Agreement between the investigational and reference devices is determined using a priori-defined accuracy thresholds. ETHICS AND DISSEMINATION: This trial was approved by the Aga Khan University Nairobi Research Ethics Committee and the Western Institutional Review Board. We plan to disseminate research results in peer-reviewed journals and international conferences. TRIAL REGISTRATION NUMBER: NCT03920761.