Babatunde L. Salako

Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry.

Adult height is a classic polygenic trait of high heritability (h 2 ∼0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain ∼10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analysis of genome-wide association (GWA) results for adult height in 20,427 individuals of African ancestry with replication in up to 16,436 African Americans. We found two novel height loci (Xp22-rs12393627, P = 3.4×10−12 and 2p14-rs4315565, P = 1.2×10−8). As a group, height associations discovered in European-ancestry samples replicate in individuals of African ancestry (P = 1.7×10−4 for overall replication). Fine-mapping of the European height loci in African-ancestry individuals showed an enrichment of SNPs that are associated with expression of nearby genes when compared to the index European height SNPs (P<0.01). Our results highlight the utility of genetic studies in non-European populations to understand the etiology of complex human diseases and traits.

Traditional herbal preparations and acute renal failure in South West Nigeria

Fifty-three cases (36 men; mean age 30.2 ± 9.5 years) of acute renal failure (ARF) in which traditional herbal preparations were implicated were seen over a 10-year period. The preparations had been taken to treat a febrile illness (38 cases), abdominal upset (seven cases) and for no clear reason (five cases). Vaginal pessaries had been used to induce abortion in two cases and for infertility in one case. The few identified plant materials included leaves and bark of the mango (Mangifera indica), shoots of cashew leaves (Anacardium occidentale), paw-paw leaves (Carica papaya), lime-leaves (Citrus aurantifolia), Solanium erianthum, Morinda lucida leaves and bark, Azadirachta indica leaves. The major presenting features were oliguria or anuria (41); jaundice (39); and anaemia (25). Oliguria occurred 3.5 ± 0.7 days after the ingestion of the herbs. The picture was consistent with acute tubular necrosis in all the cases and the mechanisms were: by intravascular haemolysis (34); hepatotoxicity (5); and presumably direct nephrotoxicity (14). Forty-five patients received dialysis and three deaths were recorded. These cases of ARF could have been prevented by proper education and awareness.

Assessment of Global Kidney Health Care Status

Importance Kidney disease is a substantial worldwide clinical and public health problem, but information about available care is limited. Objective To collect information on the current state of readiness, capacity, and competence for the delivery of kidney care across countries and regions of the world. Design, Setting, and Participants Questionnaire survey administered from May to September 2016 by the International Society of Nephrology (ISN) to 130 ISN-affiliated countries with sampling of key stakeholders (national nephrology society leadership, policy makers, and patient organization representatives) identified by the country and regional nephrology leadership through the ISN. Main Outcomes and Measures Core areas of country capacity and response for kidney care. Results Responses were received from 125 of 130 countries (96%), including 289 of 337 individuals (85.8%, with a median of 2 respondents [interquartile range, 1-3]), representing an estimated 93% (6.8 billion) of the world’s population of 7.3 billion. There was wide variation in country readiness, capacity, and response in terms of service delivery, financing, workforce, information systems, and leadership and governance. Overall, 119 (95%), 95 (76%), and 94 (75%) countries had facilities for hemodialysis, peritoneal dialysis, and kidney transplantation, respectively. In contrast, 33 (94%), 16 (45%), and 12 (34%) countries in Africa had facilities for hemodialysis, peritoneal dialysis, and kidney transplantation, respectively. For chronic kidney disease (CKD) monitoring in primary care, serum creatinine with estimated glomerular filtration rate and proteinuria measurements were reported as always available in only 21 (18%) and 9 (8%) countries, respectively. Hemodialysis, peritoneal dialysis, and transplantation services were funded publicly and free at the point of care delivery in 50 (42%), 48 (51%), and 46 (49%) countries, respectively. The number of nephrologists was variable and was low (<10 per million population) in Africa, the Middle East, South Asia, and Oceania and South East Asia (OSEA) regions. Health information system (renal registry) availability was limited, particularly for acute kidney injury (8 countries [7%]) and nondialysis CKD (9 countries [8%]). International acute kidney injury and CKD guidelines were reportedly accessible in 52 (45%) and 62 (52%) countries, respectively. There was relatively low capacity for clinical studies in developing nations. Conclusions and Relevance This survey demonstrated significant interregional and intraregional variability in the current capacity for kidney care across the world, including important gaps in services and workforce. Assuming the responses accurately reflect the status of kidney care in the respondent countries, the findings may be useful to inform efforts to improve the quality of kidney care worldwide.

Significant Bacteriuria Among Asymptomatic Antenatal Clinic Attendees In Ibadan, Nigeria

Untreated asymptomatic bacteriuria can lead to urinary tract infection (UTI) in pregnancy with devastating maternal and neonatal effects such as prematurity and low birth weight, higher fetal mortality rates and significant maternal morbidity. We carried out a two year (April 2007 to March 2009) cross-sectional epidemiological study to determine the prevalence of significant bacteriuria among asymptomatic antenatal clinic attendees at two antenatal clinics (ANCs) in University College Hospital and Adeoyo Maternity Hospital, both in Ibadan, Nigeria. All consenting ANC attendees without UTI were enrolled in the study. Urine specimens of 5 to 10 ml collected from each subject were examined microscopically for white blood cells, red blood cells and bacteria. The specimens were further cultured on MacConkey agar using a sterile bacteriological loop that delivered 0.002 ml of urine. Colony counts yielding bacterial growth of more than 105/ml of pure isolates were considered significant. Of the 473 subjects studied, 136 had significant bacteriuria, giving a prevalence rate of 28.8%. The highest age specific prevalence (47.8%) was found in the 25–29 year olds while only one (0.7%) was found in the teenage group. A large percentage (64.0%) of subjects with significant bacteriuria had tertiary education, compared with 4.4% who had no formal education but the association was not statistically significant (X2 = 0.47, p = 0.79). The majority (75.8%) of subjects with significant bacteriuria had no previous history of abortion, while 20 (14.7%) had one previous abortion and only three (2.1%) admitted to three previous abortions (X2 = 5.16, p = 0.16). The majority (69.8%) of those with significant bacteriuria presented at second trimester while 38 (28.0%) presented at third trimester (X2 = 6.5, p = 37). Only 22 (4.6%) of the studied subjects presented at first trimester, and 3 (13.7%) of these had significant bacteriuria. The prevalence of asymptomatic bacteriuria is high among this study population. Hence we suggest that advocacy programs be initiated to urge pregnant women to access ANC services early in pregnancy.

Randomized controlled trial of a multipronged intervention to improve blood pressure control among stroke survivors in Nigeria

Rationale Stroke is the second-leading cause of death in low- and middle-income countries, but use of evidence-based therapies for stroke prevention in such countries, especially those in Africa, is extremely poor. This study is designed to enhance the implementation and sustainability of secondary stroke-preventive services following hospital discharge. Aim/Hypothesis The primary study aim is to test whether a Chronic Care Model-based initiative entitled the Tailored Hospital-based Risk reduction to Impede Vascular Events after Stroke (THRIVES) significantly improves blood pressure control after stroke. Design This prospective triple-blind randomized controlled trial will include a cohort of 400 patients with a recent stroke discharged from four medical care facilities in Nigeria. The culturally sensitive, system-appropriate intervention comprises patient report cards, phone text messaging, an educational video, and coordination of posthospitalization care. Study Outcomes The primary outcome is improvement of blood pressure control. Secondary endpoints include control of other stroke risk factors, medication adherence, functional status, and quality of life. We will also perform a cost analysis of THRIVES from the viewpoint of government policy-makers. Discussion We anticipate that a successful intervention will serve as a scalable model of effective postdischarge chronic blood pressure management for stroke in sub-Saharan Africa and possibly for other symptomatic cardiovascular disease entities in the region.

Hepatitis C in sub-saharan Africa: urgent need for attention.

The hepatitis C virus (HCV), which was not recognized as an infectious agent until the 1980s, is responsible for a worldwide epidemic. The World Health Organization estimates global prevalence at 2.8%, with 185 million persons infected. In contrast to hepatitis B, where successful vaccine campaigns have reduced the disease burden, much less progress has been made toward the control of HCV. Phylogenetic studies suggest that HCV originated in Africa and has been endemic in some regions for at least 500–600 years. However, little is known about the epidemiology, transmission, and clinical course of HCV in Africa. With the advent of highly effective anti-HCV agents, there exists great potential to at least curb the global epidemic. For regions such as sub-Saharan Africa, however, this will require a thorough understanding of the regional population-level epidemiology, risk factors, and transmission mechanisms. Only then can effective treatment and prevention strategies be introduced.

Adrenergic Alpha-1 Pathway Is Associated with Hypertension among Nigerians in a Pathway-focused Analysis

Background The pathway-focused association approach offers a hypothesis driven alternative to the agnostic genome-wide association study. Here we apply the pathway-focused approach to an association study of hypertension, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in 1614 Nigerians with genome-wide data. Methods and Results Testing of 28 pathways with biological relevance to hypertension, selected a priori, containing a total of 101 unique genes and 4,349 unique single-nucleotide polymorphisms (SNPs) showed an association for the adrenergic alpha 1 (ADRA1) receptor pathway with hypertension (p<0.0009) and diastolic blood pressure (p<0.0007). Within the ADRA1 pathway, the genes PNMT (hypertension Pgene<0.004, DBP Pgene<0.004, and SBP Pgene<0.009, and ADRA1B (hypertension Pgene<0.005, DBP Pgene<0.02, and SBP Pgene<0.02) displayed the strongest associations. Neither ADRA1B nor PNMT could be the sole mediator of the observed pathway association as the ADRA1 pathway remained significant after removing ADRA1B, and other pathways involving PNMT did not reach pathway significance. Conclusions We conclude that multiple variants in several genes in the ADRA1 pathway led to associations with hypertension and DBP. SNPs in ADRA1B and PNMT have not previously been linked to hypertension in a genome-wide association study, but both genes have shown associations with hypertension through linkage or model organism studies. The identification of moderately significant (10−2>p>10−5) SNPs offers a novel method for detecting the “missing heritability” of hypertension. These findings warrant further studies in similar and other populations to assess the generalizability of our results, and illustrate the potential of the pathway-focused approach to investigate genetic variation in hypertension.

Association between Electrocardiographic Left Ventricular Hypertrophy with Strain Pattern and Left Ventricular Structure and Function

Background and Purpose: Electrocardiographic left ventricular hypertrophy (LVH) with strain pattern has been documented as a marker for LVH. Its presence on the ECG of hypertensive patients is associated with poor prognosis. The study was carried out to assess the association of the electrocardiographic strain with left ventricular mass (LVM) and function in hypertensive Nigerians. Material and Methods: ECG as well as echocardiograms were performed in 64 hypertensive patients with ECG-LVH and strain pattern, 65 patients with ECG-LVH by Sokolow-Lyon (SL) voltage criteria and 62 normal controls. Results: The study showed that electrocardiographic left ventricular (LV) strain pattern is associated with dilated left atrium, larger LV internal dimensions and greater absolute and indexed LVM in hypertensive Nigerians compared with ECG-LVH by SL voltage criteria alone or normal controls. Conclusion: The findings of this study support the fact that the ECG strain pattern is associated with increased LVM and an increased risk of developing abnormal LV geometry.

Self-Reported Quality of Life Before and After Aerobic Exercise Training in Individuals with Hypertension: A Randomised-Controlled Trial

BACKGROUND The Effects of Aerobic Exercise Training (AET) on self-reported Quality of Life (QoL) in people with hypertension have been previously documented. However, data on black populations, especially from Africa, seem not to be available. This study investigated the effects of AET on QoL and exercise capacity in Nigerians on treatment for essential hypertension. METHOD This randomised-controlled trial involved newly diagnosed individuals, with mild-to-moderate essential hypertension randomly assigned to antihypertensive drugs (ADs) alone (control: n = 60) and AET+ADs (exercise: n = 60) groups. The study lasted for 12 weeks. QoL was measured using the World Health Organization QoL Short Form (WHOQoL-BREF) and exercise capacity was assessed using the Rockport Fitness Walk Test pre- and post-study. RESULTS Physical health, psychological health, and social relationships domains of QoL improved significantly in the exercise and control groups post-intervention. The environment domain of QoL and exercise capacity improved significantly in only the exercise group. There were larger improvements in the physical health, psychological health, and environment domains of QoL, and exercise capacity in the exercise group. CONCLUSION Aerobic exercise improves QoL and exercise capacity in individuals with essential hypertension.

Factors Associated with Medication Nonadherence among Hypertensives in Ghana and Nigeria

Background. Blood pressure (BP) control is poor among hypertensives in many parts of sub-Saharan Africa. A potentially modifiable factor for control of BP is medication nonadherence (MNA); our study therefore aimed to determine factors associated with MNA among hypertensives in Ghana and Nigeria. Methodology. We conducted a multicenter cross-sectional study. Patients were recruited from Korle-Bu Hospital (n = 120), Ghana; and University of Port Harcourt Teaching Hospital, (n = 73) Apapa General Hospital Lagos (n = 79) and University College Hospital Ibadan (n = 85), Nigeria. Results. 357 hypertensive patients (42.6% males) participated. MNA was found in 66.7%. Adherence showed correlation with depression (r = −0.208, P < 0.001), concern about medications (r = −0.0347, P = 0.002), and knowledge of hypertension (r = 0.14, P = 0.006). MNA was associated with formal education (P = 0.001) and use of herbal preparation (P = 0.014). MNA was found in 61.7% of uninsured participants versus 73.1% of insured participants (P = 0.032). Poor BP control was observed in 69.7% and there was significant association between MNA and poor BP control (P = 0.006). Conclusion. MNA is high among hypertensives in Ghana and Nigeria and is associated with depression, concern about hypertensive medications, formal education, and use of herbal preparations. The negative association between health insurance and MNA suggests interplay of other factors and needs further investigation.