Hydroxyurea Therapy for Neurological and Cognitive Protection in Pediatric Sickle Cell Anemia in Uganda (BRAIN SAFE II): Protocol for a single-arm open label trial.

Background: Children with sickle cell anemia (SCA) in Sub-Saharan Africa are at high risk of sickle cerebrovascular injury (SCVI). Hydroxyurea, a commonly used disease-modifying therapy, may prevent or decrease SCVI for reduced incident stroke, stroke risk and potentially cognitive dysfunction. We aim to test the impact of daily hydroxyurea therapy on these outcomes in Ugandan children with SCA. We hypothesize that hydroxyurea therapy over 36 months will prevent, stabilize or improve these complications of SCA. Methods: The BRAIN SAFE II study is an open-label, single-arm trial of daily hydroxyurea for 270 children with SCA (HbSS) in Uganda, ages 3-9 years. Following baseline assessments, participants began hydroxyurea therapy and clinically followed per local guidelines. Standard hydroxyurea dose is escalated to maximum tolerated dose (MTD). SCVI is assessed by cerebral arterial velocity using Doppler ultrasound, with cognitive function determined by formal neurocognitive testing (primary outcomes). Structural SCVI is assessed by magnetic resonance imaging (MRI) and angiography (MRA) in a sub-sample of 90 participants ages ≥5 years, along with biomarkers of anemia, inflammation and malnutrition (secondary outcomes). At trial midpoint (18 months) and completion (36 months), primary outcomes will be compared to participants' baseline to determine hydroxyurea impact and relationships to secondary outcomes. Conclusion: This open-label, single-arm trial will examine the impact of hydroxyurea on preventing or ameliorating SCA SCVI in children, assessed by reducing incident stroke, stroke risk and neurocognitive dysfunction. Trial results will provide important insight into the role of hydroxyurea therapy on critical manifestations of SCVI in children with SCA.

A paradigm shift in point-of-care imaging in low-income and middle-income countries.

The concept of primary healthcare is now regarded as crucial for enhancing access to healthcare services in low-income and middle-income countries (LMICs). Technological advancements that have made many medical imaging devices smaller, lighter, portable and more affordable, and infrastructure advancements in power supply, Internet connectivity, and artificial intelligence, are all increasing the feasibility of POCI (point-of care imaging) in LMICs. Although providing imaging services at the same time as the clinic visit represents a paradigm shift in the way imaging care is typically provided in high-income countries where patients are typically directed to dedicated imaging centres, a POCI model is often the only way to provide timely access to imaging care for many patients in LIMCs. To address the growing burden of non-communicable diseases such as cancer and heart disease, bringing advanced imaging tools to the POCI will be necessary. Strategies tailored to the countries' specific needs, including training, safety and quality, will be of the utmost importance.

Adult Computed Tomography examinations in Uganda: Towards determining the National Diagnostic Reference Levels.

INTRODUCTION: Diagnostic Reference Levels (DRLs), typically set at the 75th percentile of the dose distribution from surveys conducted across a broad user base using a specified dose-measurement protocol, are recommended for radiological examinations. There is a need to develop and implement DRLs as a standardisation and optimisation tool for the radiological protection of patients at Computed Tomography (CT) facilities. METHODS: This was a retrospective cross-sectional study conducted in seven (7) different CT scan facilities in which participants were recruited by systematic random sampling. The study variables were dose length product (DLP) and volume-weighted CTDI (CTDIvol) for the radiation doses for head, chest, abdomen and lumbar spine CT examinations. The DRLs for CTDIvol and DLP were obtained by calculating the 3rd quartiles of the radiation doses per study site by anatomical region. The national diagnostic reference levels were determined by computation of DRLs using the 75th centile of the median values. RESULTS: A total of 574 patients were examined with an average age of 47.1 years. For CTDIvol estimates; there was a strong positive significant relationship between the CTDIvol and examination mAs (rs = 0.9017, p-value < 0.001), and reference mAs (rs = 0.0.7708, p-value < 0.001). For DLP estimates; there was a moderate positive significant relationships between DLP and total mAs (rs = 0.6812, p-value < 0.001), reference mAs (rs = 0.5493, p-value < 0.001). The DRLs were as follows; for head CT scan - the average median CTDIvol was 56.02 mGy and the DLP was 1260.3 mGy.cm; for Chest CT, the CTDI volume was 7.82 mGy and the DLP was 377.0 mGy.cm; for the abdomen CT, the CTDI volume 12.54 mGy and DLP 1418.3 mGy.cm and for the lumbar spine 19.48 mGy and the DLP was 843 mGy.cm, respectively. CONCLUSION: This study confirmed the need to optimize the CT scan parameters in order to lower the national DRLs. This can be achieved by extensive training of all the CT scan radiographers on optimizing the CT scan acquisition parameters. Continuous dose audits are also advised with new equipment or after every three years to ensure that values out of range are either justified or further investigated.

An Africa point of view on quality and safety in imaging.

Africa has seen an upsurge in diagnostic imaging utilization, with benefits of efficient and accurate diagnosis, but these could easily be offset by undesirable effects attributed to unjustified, unoptimized imaging and poor quality examinations. This paper aims to present Africa's position regarding quality and safety in imaging, give reasons for the rising interest in quality and safety, define quality and safety from an African context, list drivers for quality and safety in Africa, discuss the impact of COVID-19 on quality and safety, and review Africa's progress using the Bonn Call for Action framework while proposing a way forward for imaging quality and safety in Africa. In spite of a healthcare setting characterized by meagre financial, human and technology resources, a rapidly widening disease-burden spectrum, growing proportion of non-communicable diseases and resurgence of tropical and global infections, Africa has over the last ten years made significant strides in quality and safety for imaging. These include raising radiation-safety awareness, interest and application of evidence-based radiation safety recommendations and guidance tools, establishing facility and national diagnostic reference levels (DRLs) and strengthening end-user education and training. Major challenges are: limited human resource, low prioritization of imaging in relation to other health services, low level of integration of imaging into the entire health service delivery, insufficient awareness for radiation safety awareness, a radiation safety culture which is emerging, insufficient facilities and opportunities for education and training. Solutions to these challenges should target the entire hierarchy of health service delivery from prioritization, policy, planning, processes to procedures.

Middle cerebral arterial flow redistribution is an indicator for intrauterine fetal compromise in late pregnancy in low-resource settings: A prospective cohort study.

OBJECTIVE: We aimed to determine the prevalence of abnormal umbilical artery (UA), uterine artery (UtA), middle cerebral artery (MCA) and cerebroplacental ratio (CPR) Doppler, and their relationship with adverse perinatal outcomes in women undergoing routine antenatal care in the third trimester. DESIGN: Prospective cohort. SETTING: Kagadi Hospital, Uganda. POPULATION: Non-anomalous singleton pregnancies. METHODS: Women underwent an early dating ultrasound and a third-trimester Doppler scan between 32 and 40 weeks of gestation, from 2018 to 2020. We handled missing data using multiple imputation and analysed the data using descriptive methods and a binary logistic regression model. MAIN OUTCOME MEASURES: Composite adverse perinatal outcome (CAPO), perinatal death and stillbirth. RESULTS: We included 995 women. The mean gestational age at Doppler scan was 36.9 weeks (SD 1.02 weeks) and 88.9% of the women gave birth in a health facility. About 4.4% and 5.6% of the UA pulsatility index (PI) and UtA PI were above the 95th percentile, whereas 16.4% and 10.4% of the MCA PI and CPR were below the fifth percentile, respectively. Low CPR was strongly associated with stillbirth (OR 4.82, 95% CI 1.09-21.30). CPR and MCA PI below the fifth percentile were independently associated with CAPO; the association with MCA PI was stronger in small-for-gestational-age neonates (OR 3.75, 95% CI 1.18-11.88). CONCLUSION: In late gestation, abnormal UA PI was rare. Fetuses with cerebral blood flow redistribution were at increased risk of stillbirth and perinatal complications. Further studies examining the predictive accuracy and effectiveness of antenatal Doppler ultrasound screening in reducing the risk of perinatal deaths in low- and middle-income countries are warranted. TWEETABLE ABSTRACT: Blood flow redistribution to the fetal brain is strongly associated with stillbirths in low-resource settings.

Prognostic accuracy of antenatal Doppler ultrasound for adverse perinatal outcomes in low-income and middle-income countries: a systematic review.

OBJECTIVES: This systematic review examined available literature on the prognostic accuracy of Doppler ultrasound for adverse perinatal outcomes in low/middle-income countries (LMIC). DESIGN: We searched PubMed, Embase, Cochrane Library and Scopus from inception to April 2020. SETTING: Observational or interventional studies from LMICs. PARTICIPANTS: Singleton pregnancies of any risk profile. INTERVENTIONS: Umbilical artery (UA), middle cerebral artery (MCA), cerebroplacental ratio (CPR), uterine artery (UtA), fetal descending aorta (FDA), ductus venosus, umbilical vein and inferior vena cava. PRIMARY AND SECONDARY OUTCOME MEASURES: Perinatal death, stillbirth, neonatal death, expedited delivery for fetal distress, meconium-stained amniotic fluid, low birth weight, fetal growth restriction, admission to neonatal intensive care unit, neonatal acidosis, Apgar scores, preterm birth, fetal anaemia, respiratory distress syndrome, length of hospital stay, birth asphyxia and composite adverse perinatal outcomes (CAPO). RESULTS: We identified 2825 records, and 30 (including 4977 women) from Africa (40.0%, n=12), Asia (56.7%, n=17) and South America (3.3%, n=01) were included. Many individual studies reported associations and promising predictive values of UA Doppler for various adverse perinatal outcomes mostly in high-risk pregnancies, and moderate to high predictive values of MCA, CPR and UtA Dopplers for CAPO. A few studies suggested that the MCA and FDA may be potent predictors of fetal anaemia. No randomised clinical trial (RCT) was found. Most studies were of suboptimal quality, poorly powered and characterised by wide variations in outcome classifications, the timing for the Doppler tests and study populations. CONCLUSION: Local evidence to guide how antenatal Doppler ultrasound should be used in LMIC is lacking. Well-designed studies, preferably RCTs, are required. Standardisation of practice and classification of perinatal outcomes across countries, following the international standards, is imperative. PROSPERO REGISTRATION NUMBER: CRD42019128546.

Antenatal Doppler ultrasound implementation in a rural sub-Saharan African setting: exploring the perspectives of women and healthcare providers.

BACKGROUND: The World Health Organization recommends research to evaluate the effects of a single third trimester Doppler ultrasound examination on preventable deaths in unselected-risk pregnancies, particularly in low- and middle-income countries (LMICs) where the evidence base is scarce. While evaluating such technologies, researchers often ignore women and health care provider perspectives. This study explored the views and experiences of women and healthcare providers regarding the use of advanced ultrasound technology to optimize the health of mothers and their babies in a rural community in mid-western Uganda. METHODS: We enrolled 53 mothers and 10 healthcare providers, and captured data on their perceptions, barriers, and facilitators to the use of Doppler ultrasound technology using focus group discussions, semi-structured interviews and observations. Using qualitative content analysis, we inductively coded the transcripts in ATLAS.ti 8.0, detecting emerging themes. RESULTS: Women were afraid that ultrasound would harm them or their fetuses and many of them had never seen an ultrasound scan. The majority of the women found their partners supportive to attend antenatal care and use ultrasound services. Healthcare providers in Kagadi Hospital were unfamiliar with Doppler technology and using it to guide clinical decisions. Other barriers to the implementation of Doppler ultrasound included shortage of trained local staff, insufficient equipment, long distance to and from the hospital, and frequent power cuts. CONCLUSIONS: We found limited exposure to Doppler ultrasound technology among women and healthcare providers in mid-western Uganda. Engaging male partners may potentially influence the likelihood of accepting and using it to improve the health of women and their fetuses while wide spread myths and misconceptions about it may be changed by community engagement. Healthcare workers experienced difficulties in offering follow-up care to mothers detected with complications and Doppler ultrasound required a high level of training. While introducing advanced ultrasound machines to weak health systems, it is important to adequately train healthcare providers to avoid inappropriate interventions based on misinterpretation of the findings, consider where it is likely to be most beneficial, and embed it with realistic clinical practice guidelines.

Globally, nearly three million babies are stillborn every year, but most especially in low- and middle-income countries like Uganda. One of the factors contributing to a high number of stillbirths in low-income countries is the difficulty in identifying complications and accessing high quality care during pregnancy. Although antenatal Doppler scans are being widely used to diagnose complications in high-risk pregnancies in developed countries, studies evaluating it in LMICs are needed before it is implemented on a wide scale. We engaged 53 mothers, eight health workers from a hospital and two healthcare managers from a local government in Uganda to attain their opinions about Doppler ultrasound. We found that spousal involvement may promote acceptance and use of ultrasound services. However, the health workers did not have adequate knowledge about Doppler technology and using it for the benefit of mothers and the mothers feared that ultrasound procedures might harm them or their unborn babies. Making matters worse, the hospital faced frequent power cuts that affected the use of the equipment. Further, mothers must cover a long distance to access the hospital and its services. To reduce the number of babies dying during pregnancy or a few days after birth in Uganda and similar low-resource settings using Doppler technology, it is essential to strengthen the health systems. Starting with the training of healthcare providers to equipping and stabilizing power supply in health facilities, and educating the public about critical health procedures to break myths and misconceptions.

Integrating Ultrasound Teaching into Preclinical Problem-based Learning.

OBJECTIVES: The aim is to provide students in the preclinical with ultrasound image interpretation skills. Research question: Are students in smaller groups with access to a combination of lectures and hands-on patient contact most likely to have better ultrasound image interpretation skills, than students in larger groups with only interactive didactic lectures? METHODOLOGY: First-year students at the preclinical Program of the College of Medicine, participated in two 2-h introductory interactive ultrasound sessions. The study comprised two cohorts: 2012/2013 students, who were offered large group teaching (LGT) sessions (control group), and 2013/2014 students, who received the intervention in small group learning problem-based learning (PBL) sessions (experimental group). The overall learning objectives were identical for both groups. The success of the module was evaluated using pre- and post-tests as well as students' feedback. RESULTS: The students in the experimental group showed significantly higher scores in interpretations of images than those in the control group. The experimental group showed achievement of learning outcomes along with higher levels of satisfaction with the module compared to the latter. CONCLUSION: Posttest knowledge of the basics of ultrasound improved significantly over the pretest in the experimental group. In addition, students' overall satisfaction of the ultrasound module was shown to be higher for the PBL compared to the LGT groups. Small groups in an interactive and PBL setting along with opportunities for hands-on practice and simultaneous visualization of findings on a high definition screen should enhance preclinical student learning of the basics of ultrasound. Despite the potential of ultrasound as a clinical, teaching and learning tool for students in the preclinical years, standardized recommendations have yet to be created regarding its integration into the curricula within academic institutions and clinical medicine. The interactive and PBL is here to stay at the college of medicine. Further research would be carried out to see if this trend persists in the upcoming vertical system-based curriculum of the college of medicine.

Impact of Introducing Routine Antenatal Ultrasound Services on Reproductive Health Indicators in Mpigi District, Central Uganda.

The preponderance of global maternal and neonatal deaths occurs in low-resource countries. The risk factors that lead to these deaths are often detectable with ultrasound (US) and potentially preventable. We assessed the impact of performing US scanning during antenatal care (ANC) on reproductive health service utilization in a rural Ugandan district. This pragmatic comparative study was conducted in 2 constituencies of Mpigi district in Uganda. In the 5 intervention sites located in the Mawokota North constituency, facility midwives were trained in limited obstetric US scanning. They were equipped with solar-powered portable US machines and redeployed to offer US scanning as an integral component of ANC. The 5 control sites in the Mawokota South constituency offered the same ANC services without US scanning. We compared the difference in the first and fourth ANC attendance, facility deliveries, and referral of obstetric complications in the intervention and the control sites before and after the introduction of US. There was a 32% increase in the first ANC attendance at the intervention sites compared with 7.4% in the controls sites (P < 0.001). In the intervention sites, the fourth antenatal attendance increased by 147% compared with 0.6% decline in the control sites (P < 0.001). Referrals of high-risk pregnancies increased by 40.7% in the intervention sites compared with 25% in the control site. The number of births at the interventional sites increased by 34.1% compared with 29.5% in the control sites. Integration of limited obstetric US into routine ANC visits is associated with an increase in ANC attendance.

Assessing the performance of medical personnel involved in the diagnostic imaging processes in mulago hospital, kampala, Uganda.

OBJECTIVES: Uganda, has limited health resources and improving performance of personnel involved in imaging is necessary for efficiency. The objectives of the study were to develop and pilot imaging user performance indices, document non-tangible aspects of performance, and propose ways of improving performance. MATERIALS AND METHODS: This was a cross-sectional survey employing triangulation methodology, conducted in Mulago National Referral Hospital over a period of 3 years from 2005 to 2008. The qualitative study used in-depth interviews, focus group discussions, and self-administered questionnaires, to explore clinicians' and radiologists' performancerelated views. RESULTS: THE STUDY CAME UP WITH FOLLOWING INDICES: appropriate service utilization (ASU), appropriateness of clinician's nonimaging decisions (ANID), and clinical utilization of imaging results (CUI). The ASU, ANID, and CUI were: 94%, 80%, and 97%, respectively. The clinician's requisitioning validity was high (positive likelihood ratio of 10.6) contrasting with a poor validity for detecting those patients not needing imaging (negative likelihood ratio of 0.16). Some requisitions were inappropriate and some requisition and reports lacked detail, clarity, and precision. CONCLUSION: Clinicians perform well at imaging requisition-decisions but there are issues in imaging requisitioning and reporting that need to be addressed to improve performance.

Training for rural radiology and imaging in sub-saharan Africa: addressing the mismatch between services and population.

The objectives of this review are to outline the needs, challenges, and training interventions for rural radiology (RR) training in Sub-Saharan Africa (SSA). Rural radiology may be defined as imaging requirements of the rural communities. In SSA, over 80% of the population is rural. The literature was reviewed to determine the need for imaging in rural Africa, the challenges, and training interventions. Up to 50% of the patients in the rural health facilities in Uganda may require imaging, largely ultrasound and plain radiography. In Uganda, imaging is performed, on an average, in 50% of the deserving patients in the urban areas, compared to 10-13 % in the rural areas. Imaging has been shown to increase the utilization of facility-based rural health services and to impact management decisions. The challenges in the rural areas are different from those in the urban areas. These are related to disease spectrum, human resource, and socio-economic, socio-cultural, infrastructural, and academic disparities. Countries in Sub-Saharan Africa, for which information on training intervention was available, included: Uganda, Kenya, Tanzania, Rwanda, Zambia, Ghana, Malawi, and Sudan. Favorable national policies had been instrumental in implementing these interventions. The interventions had been made by public, private-for-profit (PFP), private-not-for profit (PNFP), local, and international academic institutions, personal initiatives, and professional societies. Ultrasound and plain radiography were the main focus. Despite these efforts, there were still gross disparities in the RR services for SSA. In conclusion, there have been training interventions targeted toward RR in Africa. However, gross disparities in RR provision persist, requiring an effective policy, plus a more organized, focused, and sustainable approach, by the stakeholders.

Assessing the performance of imaging health systems in five selected hospitals in Uganda.

OBJECTIVES: The first objective of the study was to develop an index termed as the 'Imaging Coverage' (IC), for measuring the performance of the imaging health systems. This index together with the Hospital-Based Utilization (HBU) would then be calculated for five Ugandan hospitals. Second, was to relate the financial resources and existing health policy to the performance of the imaging systems. MATERIALS AND METHODS: This was a cross-sectional survey employing the triangulation methodology, conducted in Mulago National Referral Hospital. The qualitative study used cluster sampling, in-depth interviews, focus group discussions, and self-administered questionnaires to explore the non-measurable aspects of the imaging systems' performances. RESULTS: The IC developed and tested as an index for the imaging system's performance was 36%. General X-rays had the best IC followed by ultrasound. The Hospital-Based Utilization for the five selected hospitals was 186 per thousand and was the highest for general radiography followed by ultrasound. CONCLUSION: The IC for the five selected hospitals was 36% and the HBU was 186 per thousand, reflecting low performance levels, largely attributable to inadequate funding. There were shortfalls in imaging requisitions and inefficiencies in the imaging systems, financing, and health policy. Although the proportion of inappropriate imaging was small, reducing this inappropriateness even further would lead to a significant total saving, which could be channeled into investigating more patients. Financial resources stood out as the major limitation in attaining the desired performance and there is a need to increase budget funding so as to improve the performance of the imaging health systems.

Assessing the Diagnostic Imaging needs for Five Selected Hospitals in Uganda.

INTRODUCTION: Uganda has limited health resources. It is important to measure the need for imaging in order to set policy and plan for imaging services. OBJECTIVES: The first specific objective was to develop and apply four imaging needs indices on a case study basis, in five selected Ugandan hospitals. The indices were: Imaging Load (IL), Imaging Burden (IB), Type Specific Imaging Burden (TSIB), and Disease Specific Imaging Burden (DSIB). The second objective was to explore the perceptions of the patient, referring clinician, and radiologist regarding the values, meaning, and objective of imaging in patient care. MATERIALS AND METHODS: This was a cross-sectional survey employing triangulation methodology, conducted in 5 Ugandan hospitals over a period of 3 years during 2005 - 2008. The subjects were divided into four clusters: Obstetrics and gynecology (obs/gynae), surgery, internal medicine, and pediatrics. For the quantitative component of the study, data from case notes was used to calculate the indices. The qualitative component explored the non-measurable aspects of imaging needs from the clinician's, radiologist's, and patient's perspective. RESULTS: A total of 1961 patient case notes were studied. The IB was 460 per 1000 hospital patients per year. The highest TSIB was for ultrasound at 232 per 1000 hospital patients per year, followed by 191 patients for general X-ray. The majority of the patients interviewed had special desires, expectations, and misconceptions. CONCLUSIONS: There is a high IB of 460 per thousand patient populations per year, mainly due to ultrasound. The majority of the patients have perceptions, misconceptions, beliefs, and values which influence the need for imaging. There is a need to address the medical and non-tangible imaging needs of the patient and to counteract imaging-related misconceptions and over-expectations. Public awareness of the value, capabilities, limitations, and adverse effects of various imaging modalities need to be addressed to ensure that the patients make informed imaging choices and readily avail themselves of interventions in situations when imaging is crucial, for example in suspected high-risk pregnancy.