Klippel-Feil syndrome presenting as recurrent abdominal pain in a teenager: importance of computed tomography scan in diagnostic workup

Klippel-Feil syndrome (KFS) is a segmentation and cleavage malformation of the cervical spine in the early weeks of foetal development. This is considered as a sporadic genetic abnormality, and is accompanied by multisystem disorders such as a short neck, cardiac disease, renal ectopia and other associated genitourinary syndromes. In this case report, we present the clinical and radiological findings of a 14-year old school boy who was referred to us from a private hospital for abdominopelvic ultrasound to ascertain his cause of recurrent abdominal pains since childhood. We also present the role of computed tomography in detecting multisystemabnormalities during a single hospital visit.Keywords: Recurrent abdominal pains, renal ectopia, multiple cervicothoracic vertebral fusions, Sprengel's scapula

Data_Sheet_1_International collaborative research, systems leadership and education: reflections from academic biomedical researchers in Africa.docx

ScopeAcademic biomedical researchers and educators in African countries navigate complex local, national, and international systems to conduct grant-funded research. To secure funding, collaboration with researchers from high-income countries is often necessary. Existing literature highlights that these global health initiatives are commonly fraught with unequal power dynamics and lead by the foreign partners. Despite these inequalities, African faculty can benefit from these collaborations, fostering the development of their labs and careers. This study delves into reflections on lived experiences from academic biomedical researchers in Africa to better understand the impact of foreign collaborations.MethodsWe designed a qualitative study using the Interpretative Phenomenological Analysis (IPA) method and used Self-determination and Complex Systems Leadership theories to frame this study. Ten academic biomedical researchers in Africa consented to join this study. The participants submitted a four-week series of reflective journals through an online data management platform. Subsequently, IPA methods were employed to analyze the collected journals.ResultsParticipants’ reflections yielded six thematic key findings, encompassing their experiences in international collaborative research. The findings included: foreign dominance within the international macrosystem; resource challenges in their local microsystems; mesosystem dependency from collaborations; scholarly identity within research relationships; collaborative leadership; and the impact of the foreign perspective. From these findings, three implications were drawn suggesting that participants were (1) motivated by scholarly identity found in collaborations; (2) depended on collaborations that were colonialist but beneficial; and (3) created change through leadership at the microsystem level.ImplicationsForeign collaborators and funders in global health education and research should critically consider how implications of this study relate to their collaborative work. Based on our analysis, recommendations for foreign collaborators and funders include prioritizing local leadership and perspectives in education initiatives and research grants; reviewing and leveraging collective leadership; engaging in bidirectional training, and mentoring opportunities; participating in power assessments; and removing publication barriers for researchers in Africa (and low-and middle-income countries). Insights from this study could impact global health research and education in multiple ways including new initiatives in mentorship and training in international collaborations along with increased awareness and correction of colonialism within these collaborations.</p

Association Between Dietary Pattern And Severity Of Pain Crisis In Adolescents With Sickle Cell Anaemia Attending A Tertiary Health Facility In Northwestern Nigeria

Background: Sickle cell anaemia is an inherited chronic disease with clinical manifestations arising from polymerization of haemoglobin leading to the deformity of red blood cells into a sickled shape.Objective: This study assessed the dietary pattern and severity of pain crisis in adolescents with sickle cell anaemia.Methods: The study design was a cross-sectional survey. Fifty consenting participants with a diagnosis of sickle cell anaemia aged 10 to 19 years were enrolled in this study. Severity of pain crisis was evaluated using a modified Wong-Baker's Pain Scale. Food frequency questionnaire was used to obtain food consumption patterns. Data generated was analyzed using Statistical Package for Social Sciences (SPSS) software. Cross tabulation and Chi-square were used to determine relationships between variables and statistical significance was established at p&lt;0.05.Results: All the participants were single with 54 % (n/50) female and 60 % (n/50) of them had at least secondary education. Mean age of participants was 14.3±2.8years. Adolescents who had no pain crisis were 28 % (n/N) while 42 % (n/N), 18 % (n/N) and 12 % (n/N), had mild, moderate and severe pain respectively. Dietary pattern consisted mostly of cereals, roots and tubers, milk and milk products consumed with vegetables being the least consumed. Roots and tubers, milk and milk products showed significant negative relationship with pain severity (p=0.025 and p=0.019 respectively) while meal skipping showed significant positive relationship with severity pain (p=0.034).Conclusion: Poor dietary practices was associated with the severity of pain crisis of the adolescents living with SCA

Single-cell RNA seq analysis of erythroid cells reveals a specific sub-population of stress erythroid progenitors

ABSTRACTBackground : Erythroid cells play important roles in hemostasis and disease. However, there is still significant knowledge gap regarding stress erythropoiesis.Methods : Two single-cell RNAseq datasets of erythroid cells on GEO with accession numbers GSE149938 and GSE184916 were obtained. The datasets from two sources, bone marrow and peripheral blood were analyzed using Seurat v4.1.1, and other tools in R. QC metrics were performed, data were normalized and scaled. Principal components that capture the variation of the data were determined. In clustering the cells, KNN graph was constructed and Louvain algorithm was applied to optimize the standard modularity function. Clusters were defined via differential expression of features.Results We identified 9 different cell types, with a particular cluster representing the stress erythroids. The clusters showed differentially expressed genes as observed from the gene signature plot. The stress erythroid cluster differentially expressed some genes including ALAS2, HEMGN, and GUK1.Conclusion The erythroid population was found to be heterogeneous, with a distinct sub-cell type constituting the stress erythroids; this may have important implications for our knowledge of steady-state and stress erythropoiesis, and the markers found in this cluster may prove useful for future research into the dynamics of stress erythroid progenitor cell differentiation

Primary prevention of stroke in children with sickle cell anemia in Nigeria: Protocol for a mixed methods implementation study in a community hospital

BACKGROUND: In Nigeria, approximately 150,000 children with sickle cell anemia (SCA) are born annually, accounting for more than half of all SCA births worldwide. Without intervention, about 11% of children with SCA will develop a stroke before their 20th birthday. Evidence-based practices for primary stroke prevention include screening for abnormal transcranial Doppler (TCD) measurements coupled with regular blood transfusion therapy for at least one year, followed by hydroxyurea (HU) therapy indefinitely. In high-resource countries, this strategy contributes to a 92% decrease in stroke incidence rates. In 2016, as part of a capacity building objective of the Stroke Prevention Trial in Nigeria (1R01NS094041: SPRING), TCD screening was adopted as standard care at Barau Dikko Teaching Hospital in Kaduna. However, with just 70 radiologists and only 3 certified in TCD screening in the state, just 5.49% (1101/20,040) of eligible children with SCA were screened. Thus, there is a need to explore alternate implementation strategies to ensure children with SCA receive standard care TCD screening to decrease stroke incidence. OBJECTIVE: This protocol describes a study to create a stroke prevention program in a community hospital in Kaduna through task shifting TCD screening to nurses and training medical officers to initiate and monitor HU utilization for stroke prevention. METHODS: This study will be conducted at 2 sites (teaching hospital and community hospital) over a period of 3 years (November 2020 to November 2023), in 3 phases using both quasi-experimental and effectiveness-implementation study designs. In the needs assessment phase, focus groups and structured interviews will be conducted with health care providers and hospital administrators to identify barriers and facilitators to evidence-based stroke prevention practices. Results from the needs assessment will inform intervention strategies and a process plan to fit the needs of the community hospital. In the capacity building phase, nurses and medical officers at the community hospital will be trained on TCD screening and HU initiation and monitoring. In the implementation phase, children with SCA aged 2-16 years will be recruited into a nonrandomized single-arm prospective trial to determine the feasibility of initiating a task-shifted stroke prevention program by recording recruitment, retention, and adherence rates. The Reach and Effectiveness components of the RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) framework will be used to evaluate implementation outcomes between the community and teaching hospitals. RESULTS: The needs assessment phase of the study was completed in February 2021. Manuscript on findings is currently in preparation. Capacity building is ongoing with TCD training and sickle cell disease and stroke education sessions for nurses and doctors in the community hospital. Recruitment for the implementation trial is expected to commence in July 2022. CONCLUSIONS: This study proposes a structured, theory-driven approach to create a stroke prevention program in a community hospital in Kaduna, Nigeria, to decrease stroke incidence among children with SCA. Results will provide preliminary data for a definitive randomized clinical trial in implementation science. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/37927

World Health Organization’s Growth Reference Overestimates the Prevalence of Severe Malnutrition in Children with Sickle Cell Anemia in Africa

Anthropometric indices are widely used to assess the health and nutritional status of children. We tested the hypothesis that the 2007 World Health Organization (WHO) reference for assessment of malnutrition in children with sickle cell anemia (SCA) overestimates the prevalence of severe malnutrition when compared to a previously constructed SCA-specific reference. We applied the WHO and SCA-specific references to children with SCA aged 5&ndash;12 years living in northern Nigeria (Primary Prevention of Stroke in Children with SCA in sub-Saharan Africa (SPRING) trial) to determine the difference in prevalence of severe malnutrition defined as body mass index (BMI) Z-score &lt;&minus;3 and whether severe malnutrition was associated with lower mean hemoglobin levels or abnormal transcranial Doppler measurements (&gt;200 cm/s). A total of 799 children were included in the final analysis (median age 8.2 years (interquartile range (IQR) 6.4&ndash;10.4)). The application of the WHO reference resulted in lower mean BMI than the SCA-specific reference (&minus;2.3 versus &minus;1.2; p &lt; 0.001, respectively). The use of the WHO reference when compared to the SCA-specific reference population also resulted in a higher prevalence of severe malnutrition (28.6% vs. 6.4%; p &lt; 0.001). The WHO reference significantly overestimates the prevalence of severe malnutrition in children with SCA when compared to an SCA-specific reference. Regardless of the reference population, severe malnutrition was not associated with lower mean hemoglobin levels or abnormal transcranial Doppler (TCD) measurements

Capacity building for primary stroke prevention teams in children living with sickle cell anemia in Africa

BackgroundNigeria has the highest proportion of children with sickle cell anemia (SCA) globally; an estimated 150,000 infants with SCA are born annually. Primary stroke prevention in children with SCA must include Nigeria. We describe capacity-building strategies in conjunction with two National Institutes of Health–funded primary stroke prevention trials (a feasibility trial and phase III randomized controlled trial) with initial hydroxyurea treatment for children with SCA and abnormal transcranial Doppler (TCD) velocities in Nigeria. We anticipated challenges to conducting clinical trials in a low-resource setting with a local team that had not previously been involved in clinical research and sought a sustainable strategy for primary stroke prevention.MethodsThis is a descriptive, prospective study of challenges, solutions, and research teams in two trials that enrolled a total of 679 children with SCA.ResultsAs part of the capacity-building component of the trials, over eight years, 23 research personnel (physicians, nurses, research coordinators, a statistician, and a pharmacist) completed a one-month research governance and ethics training program at Vanderbilt University Medical Center, USA. A lead research coordinator for each site completed the Society of Clinical Research Professionals certification. TCD machines were donated; radiologists and nonradiologists were trained and certified to perform TCD. A scalable E-prescription was implemented to track hydroxyurea treatment. We worked with regional government officials to support ongoing TCD-based screening and funding for hydroxyurea for children with SCA at a high risk of stroke.ConclusionsOur trials and capacity building demonstrate a sustainable strategy to initiate and maintain pediatric SCA primary stroke prevention programs in Africa.<br/

Hydroxyurea for primary stroke prevention in children with sickle cell anaemia in Nigeria (SPRING): a double-blind, multicentre, randomised, phase 3 trial

Background: In high-income countries, standard care for primary stroke prevention in children with sickle cell anaemia and abnormal transcranial Doppler velocities results in a 92% relative risk reduction of strokes but mandates initial monthly blood transfusion. In Africa, where regular blood transfusion is not feasible for most children, we tested the hypothesis that initial moderate-dose compared with low-dose hydroxyurea decreases the incidence of strokes for children with abnormal transcranial Doppler velocities.Methods: SPRING is a double-blind, parallel-group, randomised, controlled, phase 3 trial of children aged 5-12 years with sickle cell anaemia with abnormal transcranial Doppler velocities conducted at three teaching hospitals in Nigeria. For randomisation, we used a permuted block allocation scheme with block sizes of four, stratified by sex and site. Allocation was concealed from all but the pharmacists and statisticians. Participants were assigned in a 1:1 ratio to low-dose (10 mg/kg per day) or moderate-dose (20 mg/kg per day) oral hydroxyurea taken once daily with monthly clinical evaluation and laboratory monitoring. The primary outcome was initial stroke or transient ischaemic attack, centrally adjudicated. The secondary outcome was all-cause hospitalisation. We used the intention-to-treat population for data analysis. The trial was stopped early for futility after a planned minimum follow-up of 3·0 years to follow-up for participants. This trial was registered with ClinicalTrials.gov, number NCT02560935.FINDINGS: Between Aug 2, 2016, and June 14, 2018, 220 participants (median age 7·2 years [IQR 5·5-8·9]; 114 [52%] female) were randomly allocated and followed for a median of 2·4 years (IQR 2·0-2·8). All participants were Nigerian and were from the following ethnic groups: 179 (82%) people were Hausa, 25 (11%) were Fulani, and 16 (7%) identified as another ethnicity. In the low-dose hydroxyurea group, three (3%) of 109 participants had strokes, with an incidence rate of 1·19 per 100 person-years and in the moderate-dose hydroxyurea group five (5%) of 111 had strokes with an incidence rate of 1·92 per 100 person-years (incidence rate ratio 0·62 [95% CI 0·10-3·20], p=0·77). The incidence rate ratio of hospitalisation for any reason was 1·71 (95% CI 1·15-2·57, p=0·0071), with higher incidence rates per 100 person-years in the low-dose group versus the moderate-dose group (27·43 vs 16·08). No participant had hydroxyurea treatment stopped for myelosuppression.Interpretation: Compared with low-dose hydroxyurea therapy, participants treated with moderate-dose hydroxyurea had no difference in the stroke incidence rate. However, secondary analyses suggest that the moderate-dose group could lower incidence rates for all-cause hospitalisations. These findings provide an evidence-based guideline for the use of low-dose hydroxyurea therapy for children with sickle cell anaemia at risk of stroke.Funding: National Institute of Neurological Disorders and Stroke