Hydroxyurea for secondary stroke prevention in children with sickle cell anemia in Nigeria: a randomized controlled trial.

We tested the hypothesis that fixed oral moderate-dose hydroxyurea (20 mg/kg per day) for initial treatment of secondary stroke prevention results in an 80% relative risk reduction of stroke or death when compared with fixed oral low-dose hydroxyurea (10 mg/kg per day) in a phase 3 double-blind, parallel-group, randomized controlled trial in children with sickle cell anemia (SCA) living in Nigeria. A total of 101 participants were randomly allocated to low-dose (n = 49) and moderate-dose (n = 52) hydroxyurea treatment groups. The median participant follow-up was 1.6 years (interquartile range, 1.0-2.3), with a planned minimum follow-up of 3.0 years. A total of 6 recurrent strokes and 2 deaths vs 5 recurrent strokes and 3 deaths occurred in the low- and moderate-dose groups, respectively. The incidence rate ratio (IRR) of the primary outcome measure of stroke or death in the low- and moderate-dose hydroxyurea treatment groups was 0.98 (95% confidence interval [CI], 0.32-3.00; P = .97). The trial was stopped early owing to no clinical difference in the incidence rates of the primary outcome measure. The incidence rates of recurrent strokes were 7.1 and 6.0 per 100 person-years in the low- and moderate-dose groups, respectively, (IRR, 1.18; 95% CI, 0.30-4.88; P = .74). As a measure of adherence to the oral hydroxyurea therapy, the median percent of returned pills was 3.0% and 2.6% in the low- and moderate-dose groups, respectively. No participant had hydroxyurea therapy stopped for myelosuppression. For children with SCA in low-income settings without access to regular blood transfusion therapy, initial low-dose hydroxyurea is a minimum known efficacious dose for secondary stroke prevention.

Transcranial doppler velocity in iron-deficient Nigerian children with sickle cell anemia.

Oral iron supplementation in iron deficient children with sickle cell anemia and normal transcranial Doppler ultrasound (TCD) velocities does not reduce arterial flow in the middle cerebral artery.

Telemedicine Service Adoption During the COVID-19 Pandemic: Physicians' Experience from Nigeria.

Introduction: Telemedicine practice experiences during the COVID-19 pandemic have not been well documented in resource-constrained settings, such as Nigeria. We set out to assess knowledge, attitude, and factors associated with telemedicine practice during the COVID-19 lockdown, as well as physician experiences in Kano, Nigeria. Methods: We employed a mixed-methods approach, utilizing structured questionnaires administered to 246 physicians, followed by in-depth interviews with a purposive subsample of 20 individuals. The data were analyzed using logistic regression and the framework approach. Results: Overall, 65.0% of the respondents demonstrated moderate to good knowledge of telemedicine. Before COVID, only 47.6% (n = 117) reported practicing telemedicine, compared with 77.2% (n = 190) during the COVID lockdown (p < 0.05). Factors associated with telemedicine practice included having at least 5 years of work experience, working in pediatrics, undergoing senior residency training, receiving formal telemedicine training, possessing good knowledge of telemedicine, and having a positive attitude toward it. The odds of engaging in telemedicine practice were four times higher (adjusted odds ratio = 4.10, 95% confidence interval: 1.79-9.40) for those who practiced it before the pandemic. Challenges identified included knowledge and skill gaps, slow internet connectivity, unstable electricity, and inadequate equipment. Conclusion: To enhance telemedicine practice in resource-limited settings, it is important to focus on strengthening information and communication infrastructure, providing comprehensive clinician training, implementing careful patient selection processes, and improving practice guidelines.

Population health outcomes in Nigeria compared with other west African countries, 1998-2019: a systematic analysis for the Global Burden of Disease Study.

BACKGROUND: Population-level health and mortality data are crucial for evidence-informed policy but scarce in Nigeria. To fill this gap, we undertook a comprehensive assessment of the burden of disease in Nigeria and compared outcomes to other west African countries. METHODS: In this systematic analysis, using data and results of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, we analysed patterns of mortality, years of life lost (YLLs), years lived with disability (YLDs), life expectancy, healthy life expectancy (HALE), and health system coverage for Nigeria and 15 other west African countries by gender in 1998 and 2019. Estimates of all-age and age-standardised disability-adjusted life-years for 369 diseases and injuries and 87 risk factors are presented for Nigeria. Health expenditure per person and gross domestic product were extracted from the World Bank repository. FINDINGS: Between 1998 and 2019, life expectancy and HALE increased in Nigeria by 18% to 64·3 years (95% uncertainty interval [UI] 62·2-66·6), mortality reduced for all age groups for both male and female individuals, and health expenditure per person increased from the 11th to third highest in west Africa by 2018 (US$18·6 in 2001 to $83·75 in 2018). Nonetheless, relative outcomes remained poor; Nigeria ranked sixth in west Africa for age-standardised mortality, seventh for HALE, tenth for YLLs, 12th for health system coverage, and 14th for YLDs in 2019. Malaria (5176·3 YLLs per 100 000 people, 95% UI 2464·0-9591·1) and neonatal disorders (4818·8 YLLs per 100 000, 3865·9-6064·2) were the leading causes of YLLs in Nigeria in 2019. Nigeria had the fourth-highest under-five mortality rate for male individuals (2491·8 deaths per 100 000, 95% UI 1986·1-3140·1) and female individuals (2117·7 deaths per 100 000, 1756·7-2569·1), but among the lowest mortality for men older than 55 years. There was evidence of a growing non-communicable disease burden facing older Nigerians. INTERPRETATION: Health outcomes remain poor in Nigeria despite higher expenditure since 2001. Better outcomes in countries with equivalent or lower health expenditure suggest health system strengthening and targeted intervention to address unsafe water sources, poor sanitation, malnutrition, and exposure to air pollution could substantially improve population health. FUNDING: The Bill & Melinda Gates Foundation.

Improvised bubble continuous positive airway pressure ventilation use in neonates in resource-limited settings: a systematic review and meta-analysis.

OBJECTIVES: In the face of limited fiscal and technical resources, improvised methods have been used to provide effective and sustainable ventilatory support in low-resource settings to reduce neonatal mortality associated with respiratory complications. This study assessed the use of improvised bubble continuous positive airway pressure (ibCPAP) ventilation among neonates with respiratory complications and determined its effect on neonatal outcomes in low- and middle-income countries (LMICs). CONTENT: Hospital-based studies conducted between 2010 and 2020 in LMICs were reviewed. Rayyan® software for systematic review was used for screening and article selection. We used Stata® Statacorp Texas USA software to estimate pooled prevalence, proportion estimates, weighted mean differences and 95% Confidence Interval (CI), using the random effects model. SUMMARY: A total of 193 articles were generated and 125 were reviewed. Thirteen articles with 806 neonates on ibCPAP ventilation were included. The pooled prevalence of ibCPAP use was 7.0% (95% CI: 3.0%-13.0%). There was a significant difference in mean oxygen saturation before and after ibCPAP use (-1.34% [95% CI: -1.65% to -1.02%, p<0.01). The duration of oxygen requirement among neonates on ibCPAP was 6.5 hours less than controls (0.27 days [95%CI: -0.49 to -0.05, p<0.01). OUTLOOK: IbCPAP had no effect on the respiratory rate, duration of admission, mortality and survival. IbCPAP use in LMIC hospitals is low and its use improved oxygen saturation and duration on oxygen among the neonates, but had no impact on length of stay, respiratory rate, mortality or survival.

Magnetic Bead Processing Enables Sensitive Ligation-Based Detection of HIV Drug Resistance Mutations.

HIV develops single nucleotide polymorphisms (SNPs), some of which lead to drug resistance mutations (DRMs) that prevent therapeutic viral suppression. Genomic sequencing enables healthcare professionals to select effective combination antiretroviral therapy (ART) to achieve and maintain viral suppression. However, sequencing technologies, which are resource-intensive, are limited in their availability. This report describes the first step toward a highly specific ligation-based SNP discrimination method with endpoint PCR detection, which is more suitable for resource-limited clinics. The approach is based on magnetic bead processing to maximize reaction product transfer and minimize the carryover of incompatible buffer for three consecutive enzymatic reactions─reverse transcription (RT), oligonucleotide ligation assay (OLA), and PCR. The method improved PCR detection following RT → OLA by 8.06 cycles (∼250-fold) compared to direct pipette processing and detected between 103 and 104 RNA copies per reaction. In studies with synthesized nucleic acids based on the well-studied HIV mutation, K103N, the assay successfully differentiated between wild-type and mutant for RNA targets with high specificity. With further development, this design provides a pathway for SNP detection with more accessible PCR instrumentation and is a step toward a self-contained processing approach that incorporates the SNP specificity of the ligation reaction for more effective clinical management of DRMs in resource-constrained settings.

HIV self-testing and repeat testing in pregnancy and postpartum in Northern Nigeria.

OBJECTIVE: Incident HIV infections in pregnant and breastfeeding mothers pose significant challenges to prevention of mother-to-child HIV transmission efforts in sub-Saharan Africa. We identified the predictors of willingness to self-test for HIV when retesting in pregnancy and postpartum among antenatal clients in a tertiary hospital in Northern Nigeria. METHODS: Structured and validated questionnaires were administered to a cross section of antenatal attendees (n = 370) in March 2021. Willingness to self-test and adjusted odds ratios of potential predictors were generated from logistic regression models. RESULTS: Of the 317 respondents who agreed to repeat HIV test during pregnancy, 29.3% (n = 93) were willing to self-test. Similarly, of those (n = 350) willing to retest after delivery, 27.4% (n = 96) were willing to self-test. Willingness to self-test during pregnancy was higher among respondents who were multiparous (2-4 births) (adjusted odds ratio, aOR = 2.40, 95% confidence interval CI, 1.14-6.43), employed (aOR = 1.49, 95% CI, 1.13-4.53) and those with at least secondary education (aOR = 2.96, 95% CI, 1.43-11.47). In contrast, willingness to self-test was lower among those who were unaware of the husband's HIV status (aOR = 0.05, 95% CI, 0.02-0.13). Willingness to self-test after delivery was higher among respondents who were married (aOR = 15.41, 95% CI, 3.04-78.2), multiparous (aOR = 2.01, 95% CI, 1.27-5.63), employed (aOR = 1.59, 95% CI, 1.08-2.35) and had at least to secondary education (aOR = 6.12, 95% CI, 1.36-27.47). In contrast, willingness to self-test postpartum was lower among those who booked late (≥29 weeks) (aOR = 0.11, 95% CI, 0.022-0.52), those who were unaware of the risk of HIV transmission during breastfeeding (aOR = 0.29, 95% CI, 0.12-0.68) and participants who were unaware of the husband's HIV status (aOR = 0.076, 95% CI, 0.03-0.19). CONCLUSION: Willingness to self-test for HIV in pregnancy and postpartum was low in this population and was influenced by risk perception, socio-demographic and obstetric attributes. Communication interventions and training of potential mentor mothers among early adopters could improve self-testing in this group and similar settings.

Etiology of Persistent Microalbuminuria in Nigeria (P_MICRO study): protocol and study design.

BACKGROUND: Microalbuminuria is an independent risk factor for cardiovascular and kidney disease and a predictor of end organ damage, both in the general population and in persons with HIV (PWH). Microalbuminuria is also an important risk factor for mortality in PWH treated with antiretroviral therapy (ART). In the ongoing Renal Risk Reduction (R3) study in Nigeria, we identified a high prevalence of microalbuminuria confirmed by two measurements 4-8 weeks apart in ART-experienced, virologically suppressed PWH. Although Stage 1 or 2 hypertension and exposure to potentially nephrotoxic antiretroviral medications were common in R3 participants, other traditional risk factors for albuminuria and kidney disease, including diabetes, APOL1 high-risk genotype, and smoking were rare. Co-infection with endemic pathogens may also be significant contributors to albuminuria, but co-infections were not evaluated in the R3 study population. METHODS: In Aim 1, we will cross-sectionally compare the prevalence of albuminuria and established kidney disease risk factors in a cohort of PWH to age- and sex-matched HIV-negative adults presenting for routine care at the Aminu Kano Teaching Hospital in Kano, Nigeria. We will leverage stored specimens from 2500 R3 participants and enroll an additional 500 PLWH recently initiated on ART (≤ 24 months) and 750 age- and sex-matched HIV-negative adults to determine the contribution of HIV, hypertension, and other comorbid medical conditions to prevalent albuminuria. In Aim 2, we will follow a cohort of 1000 HIV-positive, ART-treated and 500 HIV-negative normoalbuminuric adults for 30 months to evaluate the incidence and predictors of albuminuria. DISCUSSION: The findings from this study will support the development of interventions to prevent or address microalbuminuria in PWH to reduce kidney and cardiovascular morbidity and mortality. Such interventions might include more intensive monitoring and treatment of traditional risk factors, the provision of renin-angiotensin aldosterone system or sodium-glucose cotransporter-2 inhibitors, consideration of changes in ART regimen, and screening and treatment for relevant co-infections.

Secondary prevention of rheumatic heart disease in Ethiopia: a multicenter study.

BACKGROUND: Ethiopia has a high acute rheumatic fever (ARF) and rheumatic heart disease (RHD) prevalence, and to our knowledge, there are no data on the status of secondary prevention in children with RHD. This study describes the status of secondary RHD prevention. METHODS: A multicenter, prospective study was performed on children aged 5-17 years with RHD in Ethiopia. Good adherence was defined as at least 80% completion of benzathine penicillin (BPG) or oral Amoxicillin within the previous year. The primary outcome measure was adherence to prophylaxis, expressed as a proportion. Socio-demographics, severity of RHD, and ARF recurrence were evaluated. RESULTS: A total of 337 children with a mean age of 12.9 ± 2.6 years were included. The majority (73%) had severe aortic/mitral disease. Participants were on BPG (80%) or Amoxicillin (20%) prophylaxis. Female sex (P = 0.04) use of BPG (0.03) and shorter mean duration of prophylaxis in months (48.5 ± 31.5 vs. 60.7 ± 33, respectively, P < 0.008) predicted good adherence. Running out of medications (35%), interrupted follow-up (27%), and the COVID-19 pandemic (26%) were the most common reasons for missing prophylaxis. Recurrence of ARF was higher in participants on Amoxicillin compared with BPG (40% vs. 16%, P < 0.001) and in those with poor adherence compared with good adherence (36.8% vs. 17.9%, respectively, P = 0.005). Type and duration of prophylaxis (OR 0.5, CI = 0.24, 0.9, P = 0.02; OR = 1.1, CI = 1.1, 1.2, P = 0.04, respectively), and sex (OR = 1.9, CI = 1.1, 3.4, P = 0.03) were independent predictors of poor adherence. CONCLUSION: Poor adherence is prevalent in Ethiopian children living with RHD. Amoxicillin is a suboptimal option for prophylaxis as its use is associated with lower adherence and a higher rate of ARF recurrence.

Establishing Sickle Cell Disease Stroke Prevention Teams in Africa is Feasible: Program Evaluation Using the RE-AIM Framework.

We used the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to evaluate a Stroke Prevention Team's readiness to prevent strokes in children with sickle cell anemia living in northern Nigeria. The NIH sponsored Stroke Prevention Trial in Nigeria included a goal of a sustainable stroke prevention program. The program's 1-year reach for transcranial Doppler screening was 14.7% (4710/32,000) of which 6.0% (281/4710) had abnormal velocities (≥200 cm/s). All participants with abnormal transcranial Doppler velocities were started on hydroxyurea (effectiveness). The leaders of all 5 hospitals agreed to adopt the program. After 1 year, program-implementation and maintenance rates were 100%, demonstrating the program's feasibility and short-term sustainability.

Perinatal factors associated with admission to neonatal intensive care unit following cesarean delivery in Kano, northern Nigeria.

OBJECTIVES: Cesarean section is the most common obstetric surgical procedure, with associated risks for adverse neonatal outcomes. The interplay of perinatal factors associated with neonatal admissions following cesarean delivery remains poorly understood in developing countries. We examined how perinatal and facility-based factors affect Neonatal Intensive Care Unit (NICU) admission after cesarean delivery in northern Nigeria. METHODS: A prospective cohort study involving 200 women undergoing cesarean section were consecutively enrolled with subsequent follow-up of their infants in the post-natal period. Data were abstracted from the medical record using an interviewer-administered questionnaire. The primary outcomes were NICU admission and intrauterine or early neonatal deaths. Binary logistic regression modelling was used to identify variables independently associated with the outcomes. RESULTS: Over the study period (six months), there were 200 cesarean sections. A total of 30 (15.0%) neonates were admitted into the NICU following the procedure. No stillbirths or early neonatal deaths were recorded. NICU admission was associated with gestational age (preterm vs. term [adjusted odds ratio, aOR: 18.9, 95% confidence interval (CI): 4.0-90.4]), birth weight (small vs. appropriate [aOR: 6.7, 95% CI 1.9-22.7] and large vs. appropriate birth weight [aOR: 20.3, 95% CI 2.9-143.7]) and the number of indications for cesarean section (≥2 vs. one [aOR: 0.2, 95% 0.1-0.8]). CONCLUSIONS: Prematurity, small and large for gestational age neonates; and indications for cesarean section were associated with increased likelihood of neonatal admission following cesarean delivery. These findings could inform ongoing quality enhancement initiatives to improve NICU admission outcomes at the study site, and other similar settings.

Strengthening research capacity through an intensive training program for biomedical investigators from low- and middle-income countries: the Vanderbilt Institute for Research Development and Ethics (VIRDE).

BACKGROUND: Capacity strengthening initiatives aimed at increasing research knowledge and skills of investigators in low- and middle-income countries (LMICs) have been implemented over the last several decades. With increased capacity, local investigators will have greater leadership in defining research priorities and impact policy change to help improve health outcomes. Evaluations of models of capacity strengthening programs are often limited to short-term impact. Noting the limitations of traditional output-based evaluations, we utilized a broader framework to evaluate the long-term impact of the Vanderbilt Institute in Research Development and Ethics (VIRDE), a decade-old intensive grant development practicum specifically tailored for investigators from LMICs. METHODS: To assess the impact of VIRDE on the research careers of alumni over the past 10 years, we surveyed alumni on research engagement, grant productivity, career trajectory, and knowledge gained in grant writing. Descriptive statistics, including means and total counts, and paired sample t-tests were used to analyze the data. RESULTS: Forty-six of 58 alumni completed the survey. All respondents returned to their home countries and are currently engaged in research. Post-VIRDE grant writing knowledge ratings were significantly greater than pre-VIRDE. The number of respondents submitting grants post-VIRDE was 2.6 times higher than before the program. Eighty-three percent of respondents submitted a total of 147 grants post-VIRDE, of which 45.6% were awarded. Respondents acknowledged VIRDE's positive impact on career growth and leadership, with 88% advancing in career stage. CONCLUSIONS: Gains in grant writing knowledge and grant productivity suggest that VIRDE scholars built skills and confidence in grant writing during the program. A substantial proportion of respondents have advanced in their careers and continue to work in academia in their country of origin. Results show a sustained impact on the research careers of VIRDE alumni. The broader framework for research capacity strengthening resulted in an expansive assessment of the VIRDE program and alumni, illuminating successful program elements and implications that can inform similar capacity strengthening programs.

Correlates of human papillomavirus vaccine knowledge and acceptability among medical and allied health students in Northern Nigeria.

Prior to its planned introduction, we investigated predictors of baseline knowledge and acceptability of HPV vaccination among medical and allied health care students in Kano, northern Nigeria. A total of 410 medical, dental and allied health students completed structured validated questionnaires. Knowledge scores and acceptability of HPV vaccine were determined and adjusted odds ratios (AOR) for predictors of HPV knowledge and acceptability were derived from multivariate logistic regression models. Overall, 3.7% (n = 15), 30.7% (n = 126) and 65.6% (n = 269) of respondents had good, moderate, and poor knowledge of HPV, respectively. The majority 334 (81.5%) were willing to accept the HPV vaccine, but only 18 (4.4%) had received at least one dose of the vaccine. Knowledge of HPV was better among females, younger (<20 years) medical students, students at higher levels of study, sexually experienced students, and condom users. HPV vaccine acceptance was higher among female students in the faculty of allied health with a family history of cervical cancer and good or moderate knowledge of HPV. In conclusion, most students were willing to receive HPV vaccination, despite their sub-optimal level of knowledge and low vaccine uptake. We recommend piloting the HPV vaccine in health colleges and recruiting early adopters as peer educators and advocates.IMPACT STATEMENTWhat is already known on this subject? Human Papilloma Virus (HPV) vaccine has been introduced in over 80 countries in the past decade, but evidence suggests low awareness of HPV infection and the vaccine, especially in developing countries. Nigeria proposes to introduce the HPV vaccine as part of the routine immunisation program in early 2021.What do the results of this study add? The majority of medical and allied health students in Kano, Nigeria, were willing to receive HPV vaccination, despite their sub-optimal level of knowledge and low vaccine uptake. Vaccine acceptance was predicted by the respondent's sex, course of study, family history of cervical cancer and knowledge of HPV.What are the implications of these findings for clinical practice and/or further research? The findings could inform program implementation and evaluation as HPV vaccine uptake is scaled up across Africa.

Apolipoprotein-1 risk variants and associated kidney phenotypes in an adult HIV cohort in Nigeria.

HIV-positive adults are at risk for various kidney diseases, and apolipoprotein 1 (APOL1) high-risk genotypes increase this risk. This study aimed to determine the prevalence and ethnic distribution of APOL1 risk genotypes among a cohort of HIV-positive Nigerian adults and explore the relationship between APOL1 risk variant status with albuminuria and estimated glomerular filtration rate (eGFR). We conducted a cross-sectional study among 2 458 persons living with HIV who attended an HIV clinic in northern Nigeria and had received antiretroviral therapy for a minimum of six months. We collected two urine samples four-eight weeks apart to measure albumin excretion, and blood samples to measure eGFR and determine APOL1 genotype. The frequency of APOL1 high-risk genotype was 6.2%, which varied by ethnic group: Hausa/Fulani (2.1%), Igbo (49.1%), and Yoruba (14.5%). The prevalence of microalbuminuria (urine/albumin creatinine ratio 30- 300 mg/g) was 37%, and prevalence of macroalbuminuria (urine/albumin creatinine ratio over 300 mg/g) was 3%. The odds of microalbuminuria and macroalbuminuria were higher for participants with the APOL1 high-risk genotype compared to those carrying the low-risk genotype ([adjusted odds ratio 1.97, 95% confidence interval 1.37-2.82] and [3.96, 1.95-8.02] respectively). APOL1 high-risk genotype participants were at higher risk of having both an eGFR under 60 ml/min/1.73m2 and urine/albumin creatinine ratio over 300 mg/g (5.56, 1.57-19.69). Thus, we found a high proportion of HIV-positive, antiretroviral therapy-experienced, and largely virologically suppressed adults had microalbuminuria. Hence, although the high-risk APOL1 genotype was less prevalent than expected, it was strongly associated with some level of albuminuria.

Strategies for Successful Clinical Trial Recruitment of People Living with HIV in Low- and Middle-Income Countries: Lessons Learned and Implementation Implications from the Nigeria Renal Risk Reduction (R3) Trial.

PURPOSE OF REVIEW: Clinical trials represent a bedrock for measuring efficacy of interventions in biomedical research, but recruitment into clinical trials remains a challenge. Few data have focused on recruitment strategies from the perspective of clinical trial teams, especially in low- and middle-income countries (LMIC), where HIV is most prevalent. RECENT FINDINGS: We summarized data from the literature and our experience with recruitment for the Renal Risk Reduction trial, aimed at reducing risk of kidney complications among people living with HIV in Nigeria. Using an implementation science framework, we identified strategies that contributed to successful clinical trial recruitment. For strategies that could not be categorized by this framework, we summarized key features according to selected action, actor, target, context, and time. We identified how these identified strategies could map to subsequent implementation outcomes at the patient and provider/health system level, as well as capacity-building efforts to meet needs identified by LMIC partners, which is a priority for success. Our experience highlights the importance of considering implementation outcomes, and the strategies necessary to achieve those outcomes early, in the planning and execution of clinical trials. Clinical trial recruitment can be optimized via methodologies grounded in implementation science.

Pregnancy outcomes among Asian Americans of advanced maternal age, 1992-2018.

AIM: The trend of delayed childbearing has implications for the increasing national burden of adverse perinatal outcomes across vulnerable racial-ethnic groups. The objective of this study was to investigate age-adjusted risk for adverse maternal-fetal outcomes among Asian Americans of advanced maternal age (≥35 years). METHODS: This was a retrospective cohort study using the 1992-2018 Natality data files. We calculated the prevalence of maternal-fetal outcomes: maternal diabetes, hypertensive disorders of pregnancy (HDP), C-section, small-for-gestational age (SGA), large-for-gestational age (LGA), and preterm birth. Adjusted binomial logistic regression was created to evaluate the association between maternal race/ethnicity and each of the maternal-fetal outcomes. RESULTS: Compared with non-Hispanic Whites, Asian American women had reduced odds of diabetes, HDP, and LGA babies and increased odds of preterm birth, C-section delivery, and SGA, irrespective of the advanced maternal age group. The odds of developing specific adverse outcomes by advanced maternal age varied by Asian American ethnic subgrouping. DISCUSSION: The risk of maternal-fetal outcomes varied among the ethnic subgroups of Asian Americans in the United States. Future studies should explore the sociocultural and environmental nuances that might explain these differences.

The V-BRCH Project: building clinical trial research capacity for HIV and noncommunicable diseases in Nigeria.

Antiretroviral therapy has turned HIV into a chronic condition, with morbidity from HIV-associated noncommunicable diseases (NCDs) becoming more common as HIV-infected individuals live longer. In Nigeria, the additional challenge of an under-capacitated health system highlights the need for skilled clinical investigators who can generate evidence to tackle the double burden of HIV and NCDs. The Vanderbilt-Nigeria Building Research Capacity in HIV and Non-communicable Diseases (V-BRCH) programme is a training platform to create a cohort of skilled Nigerian investigators with the capacity to lead independent clinical trial research focused on the intersection of HIV and NCDs. V-BRCH will solidify an atmosphere of continuous mentoring and skills acquisition for physician faculty at the Aminu Kano Teaching Hospital via short- and medium-term learning opportunities, paired mentoring arrangements, and mentored research projects. Trainees will attend an annual faculty enrichment programme in Nashville, in addition to on-site workshops in Nigeria on HIV-associated NCD epidemiology, clinical trials methodology, evidence synthesis, qualitative research methods, stakeholder engagement, knowledge translation, and grant writing. Research-oriented junior faculty will undergo focused training in clinical trials administration and regulatory oversight. Scholars will share best practices through mentoring panels, regular 'Works in Progress' meetings, and monthly career development seminars. Competitive seed grants will be provided to mentor-mentee teams to promote targeted in-country pilot studies focused on HIV-associated NCDs. For long-term training, physician scientists will be supported to undergo enhanced Master of Public Health (MPH) training at Bayero University in Nigeria and Master of Science in Clinical Investigation (MSCI) training at Vanderbilt. Short-term regional courses, staff development workshops, and MPH curriculum refinement will help to strengthen institutional capacity in HIV-associated NCD clinical trial research. V-BRCH will create a cohort of skilled Nigerian scientists who will be able to compete for independent funding and design and implement high quality research that will generate evidence to inform policy and practice and lead to improved outcomes for Nigerians impacted by HIV-associated NCDs.

Primary prevention of stroke in children with sickle cell anemia in sub-Saharan Africa: rationale and design of phase III randomized clinical trial.

Strokes in children with sickle cell anemia (SCA) are associated with significant morbidity and premature death. Primary stroke prevention in children with SCA involves screening for abnormal transcranial Doppler (TCD) velocity coupled with regular blood transfusion therapy for children with abnormal velocities, for at least one year. However, in Africa, where the majority of children with SCA live, regular blood transfusions are not feasible due to inadequate supply of safe blood, cost, and the reluctance of caregivers to accept transfusion therapy for their children. We describe the Primary Prevention of Stroke in Children with Sickle Cell Disease in Nigeria Trial [StrokePreventioninNigeria (SPRING) trial, NCT02560935], a three-center double-blinded randomized controlled Phase III clinical trial to 1) determine the efficacy of moderate fixed-dose (20 mg/kg/day) versus low fixed-dose (10 mg/kg/day) hydroxyurea therapy for primary stroke prevention; 2) determine the efficacy of moderate fixed-dose hydroxyurea for decreasing the incidence of all cause-hospitalization (pain, acute chest syndrome, infection, other) compared to low fixed-dose hydroxyurea. We will test the primary hypothesis that there will be a 66% relative risk reduction of strokes in children with SCA and abnormal TCD measurements, randomly allocated, for a minimum of three years to receive moderate fixed-dose versus low fixed-dose hydroxyurea (total n = 220). The results of this trial will advance the care of children with SCA in sub-Saharan Africa, while improving research capacity for future studies to prevent strokes in children with SCA.

Low educational level of head of household, as a proxy for poverty, is associated with severe anaemia among children with sickle cell disease living in a low-resource setting: evidence from the SPRING trial.

Severe anaemia, defined as haemoglobin level < 6·0 g/dl, is an independent risk factor for death in individuals with sickle cell disease living in resource-limited settings. We conducted a cross-sectional study of 941 children with sickle cell anaemia, who had been defined as phenotype HbSS or HbSß0 thalassaemia, aged five to 12 years, and were screened for enrollment into a large primary stroke prevention trial in Nigeria (SPRING; NCT02560935). The main aim of the study was to determine the prevalence and risk factors for severe anaemia. We found severe anaemia to be present in 3·9% (37 of 941) of the SPRING study participants. Severe anaemia was significantly associated with the lower educational level of the head of the household (P = 0·003), as a proxy for poverty, and a greater number of children per room in the household (P = 0·004). Body mass index was not associated with severe anaemia. The etiology of severe anaemia in children living with sickle cell anaemia in Nigeria is likely to be multifactorial with an interplay between an individual's disease severity and other socio-economic factors related to poverty.

Correlating maternal iodine status with neonatal thyroid function in two hospital populations in Ghana: a multicenter cross-sectional pilot study.

BACKGROUND: Congenital hypothyroidism is a common, yet easily treatable cause of poor growth and intellectual disability. Newborn screening programs play an important role in the early detection and treatment of congenital hypothyroidism. However, an estimated 71% of children are born in countries such as Ghana, which does not have a screening program. Iodine deficiency, a common cause of congenital hypothyroidism, is present in the Ghanaian population. Mild to moderate maternal iodine deficiency may negatively impact cognitive function in children. A structured approach to examine the association between maternal iodine levels and infant thyroid function may have important ramifications on our understanding of congenital hypothyroidism in Ghana. We investigated the hypothesis that maternal iodine deficiency impacts infant thyroid function, using Thyroid Stimulating Hormone (TSH) as a marker of thyroid function. We also explored potential opportunities and barriers to newborn screening for congenital hypothyroidism in Ghana. METHODS: This was a cross-sectional, multicenter pilot study of 250 women and their neonates recruited from post-natal clinics in Accra and Tamale, Ghana. We compared maternal urine iodine concentration and infant TSH, as well as maternal sociodemographic and nutrition information. Regression models were used to model the relationship between variables. RESULTS: Median infant TSH was 4.7 µIU/ml (95% CI: 3.9-5.5) in Accra. In Tamale, the median infant TSH was 3.5 µIU/ml (95%CI: 3.3 to 3.6) (Δ: 1.3 µIU/ml, 95% CI: 0.5-2.1, p = 0.002). Median maternal urine iodine concentrations were 141.0 µg/L (95% CI: 115.7 to 166.3) and 142.5 µg/L (95% CI: 125.1 to 160.0) in Accra and Tamale, respectively (Δ: - 1.5 µIU/ml, 95% CI: - 32.2 - 29.2, p = 0.925). There was a weakly positive correlation between maternal urine iodine and infant TSH (rho 0.1, p = 0.02). Almost one-third (30%) of women in both locations had biochemical evidence of iodine deficiency. Mothers with any formal education were more likely to have higher iodine levels than their counterparts who had no formal education (coefficient 0.31, p = 0.006). CONCLUSIONS: Maternal iodine deficiency is prevalent in Ghana and is correlated to infant thyroid function. We recommend studies with larger sample sizes to assess the true scope of this relationship.