Non-cigarette tobacco use and stroke among West Africans: evidence from the SIREN study.

INTRODUCTION: Non-cigarette tobacco (NCT) represents a form of tobacco use with a misperceived significance in chronic disease events. Whether NCT use is sufficient to promote stroke events, especially among Africans, is yet to be understood. This study assessed the relationship between NCT use and stroke among indigenous Africans. METHODS: A total of 7,617 respondents (NCT users: 41 vs. non-NCT: 7576) from the Stroke Investigation Research and Educational Network study were included in the current analysis. NCT use was defined as self-reported use of smoked (cigars or piper) or smokeless (snuff or chewed) tobacco in the past year preceding stroke events. Stroke was defined based on clinical presentation and confirmed with a cranial CT/MRI. Multivariable-adjusted logistic regression was applied to estimate the odds ratio (OR) and 95% confidence interval (CI) for the relationship between NCT and stroke at p<0.05. RESULTS: Out of the 41 (0.54%) who reported NCT use, 27 (65.9%) reported using smokeless NCT. NCT users were older than non-smokers (62.8±15.7 vs 57.7±14.8 years). Overall, NCT use was associated with first-ever stroke (OR: 2.08; 95%CI: 1.02, 4.23) in the entire sample. Notably, smokeless NCT use was independently associated with higher odds of stroke (OR: 2.74; 95%CI: 1.15, 6.54), but smoked NCT use (OR: 0.16; 95%CI: 0.02, 1.63) presented a statistically insignificant association after adjusting for hypertension and other covariates. CONCLUSIONS: NCT use was associated with higher odds of stroke, and public health interventions targeting NCT use might be promising in reducing the burden of stroke among indigenous Africans. IMPLICATIONS: A detailed understanding of the relationship between NCT use and stroke will likely inform well-articulated policy guidance to promote evidence-based recommendations for public health prevention and management of stroke on the African continent.

Are there differences in perceptions, preferences and attitudes towards disclosure of genetic testing for Stroke? A qualitative study among stroke-free SIREN-SIBS genomics study participants.

OBJECTIVE: This study explored perceptions, preferences and attitudes towards disclosure of genetic testing results for stroke among stroke-free controls (and their family members) in the SIREN-SIBS Genomics Study, healthcare providers and policymakers. MATERIALS AND METHODS: We conducted a qualitative thematic analysis of key informant interviews with 61 participants recruited from community advisory boards (30) and health care providers (31) across seven sites in Nigeria and Ghana. RESULTS: Major findings illustrate differences in the knowledge of genetic testing with superior knowledge among health care professionals. Relatives and religious leaders were opined as the best to receive the disclosure as they would be able to break the news to the patient in a culturally sensitive manner to reduce the likely resultant emotional outburst. Poor level of awareness of national guidelines for disclosing genetic results exist. Key facilitating factors for disclosure are education, enabling environment, involvement of religious and community leaders, campaigns, and possible treatment options. Disclosure inhibitors include inadequate information, fear of marital break-up or family displacement, fear of stigmatization, fear of isolation, religious beliefs, health worker attitude, and lack of preparedness to accept results. CONCLUSIONS: These necessitate culturally sensitive interventions for continuing education, increased awareness and sustained engagement to equip all stakeholders in genetic testing disclosure process.

Risk Factor Characterization of Ischemic Stroke Subtypes Among West Africans.

BACKGROUND AND PURPOSE: To identify the qualitative and quantitative contributions of conventional risk factors for occurrence of ischemic stroke and its key pathophysiologic subtypes among West Africans. METHODS: The SIREN (Stroke Investigative Research and Educational Network) is a multicenter, case-control study involving 15 sites in Ghana and Nigeria. Cases include adults aged ≥18 years with ischemic stroke who were etiologically subtyped using the A-S-C-O-D classification into atherosclerosis, small-vessel occlusion, cardiac pathology, other causes, and dissection. Controls were age- and gender-matched stroke-free adults. Detailed evaluations for vascular, lifestyle, and psychosocial factors were performed. We used conditional logistic regression to estimate adjusted odds ratios with 95% CI. RESULTS: There were 2431 ischemic stroke case and stroke-free control pairs with respective mean ages of 62.2±14.0 versus 60.9±13.7 years. There were 1024 (42.1%) small vessel occlusions, 427 (17.6%) large-artery atherosclerosis, 258 (10.6%) cardio-embolic, 3 (0.1%) carotid dissections, and 719 (29.6%) undetermined/other causes. The adjusted odds ratio (95% CI) for the 8 dominant risk factors for ischemic stroke were hypertension, 10.34 (6.91-15.45); dyslipidemia, 5.16 (3.78-7.03); diabetes, 3.44 (2.60-4.56); low green vegetable consumption, 1.89 (1.45-2.46); red meat consumption, 1.89 (1.45-2.46); cardiac disease, 1.88 (1.22-2.90); monthly income $100 or more, 1.72 (1.24-2.39); and psychosocial stress, 1.62 (1.18-2.21). Hypertension, dyslipidemia, diabetes were confluent factors shared by small-vessel, large-vessel and cardio-embolic subtypes. Stroke cases and stroke-free controls had a mean of 5.3±1.5 versus 3.2±1.0 adverse cardio-metabolic risk factors respectively (P<0.0001). CONCLUSIONS: Traditional vascular risk factors demonstrate important differential effect sizes with pathophysiologic, clinical and preventative implications on the occurrence of ischemic stroke among indigenous West Africans.

Pre-Stroke Depression in Ghana and Nigeria: Prevalence, Predictors and Association With Poststroke Depression.

OBJECTIVES: Depression is a risk factor for stroke. There is a knowledge gap on the predictors of prestroke depression in stroke survivors living in low- and middle-income countries (LMICs). We estimated prevalence and predictors of prestroke depression, as well as its association with poststroke depression (PSD) in the largest study of stroke in Africa. METHODS: We evaluated information collected as part of the Stroke Investigative Research and Education Network (SIREN) study, a multicentre, case-control study conducted at 15 sites in Ghana and Nigeria. Prestroke depression status was ascertained in stroke survivors using a validated self-report tool, while PSD was assessed using a stroke specific screening tool for depression ("HRQOLISP-E"). Independent associations were investigated using complementary log-log regression and binary logit models. RESULTS: Among 1,977 participants, prestroke depression was found in 141 (7.1%). In multivariate analyses, prestroke depression was significantly associated with tachycardia (OR = 2.22, 95% CI = 1.37-3.56) and low consumption of green leafy vegetables (OR = 1.91, 95% CI = 1.12-3.24). Forty-one (29.1%) of the prestroke depression sub-sample developed PSD. However, prestroke depression was not significantly associated with PSD. CONCLUSION: The findings should energize before-the-stroke identification and prioritization of limited treatment resources in LMICs to persons with depression who have multiple, additional, risks of stroke.

Magnitude of diabetic peripheral neuropathy in Saudi Arabia: a systematic review and meta-analysis.

BACKGROUND: Diabetic peripheral neuropathy (DPN), due to its potential for causing morbidity and disability from foot ulcers and amputations, is increasingly becoming a source of concern in Saudi Arabia and worldwide. However, wide variability exists in the prevalence of DPN reported in previous studies in Saudi Arabia, limiting the utility of existing data in national public health policy. Therefore, the aim of this study was to systematically evaluate the magnitude of DPN in patients living with DM in Saudi Arabia in order to inform policymakers during the implementation of appropriate preventive and treatment strategies for DPN. METHODS: PubMed, Google Scholar, African Journals Online, Scopus, Web of Science, Embase, and Wiley Online Library were searched systematically to acquire relevant articles based on preset criteria. We evaluated heterogeneity and publication bias and employed a random-effects model to estimate the pooled prevalence of DPN from the included studies. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in conducting the meta-analysis. Analysis was performed using the STATA Version 12 software. RESULTS: Twelve studies with a total of 4,556 participants living with DM, of whom 2,081 were identified as having DPN were included in the meta-analysis. The overall prevalence of DPN was 39% (95% CI [30%, 49%]). Subgroup analysis based on diagnostic method showed that prevalence estimates for DPN using screening questionnaires and clinical examination were 48% (95% CI [46%, 50%]) and 40% (95% CI: [38%, 42%]), respectively, while the estimated prevalence using nerve conduction studies was 26% (95% CI [15%, 36%]). CONCLUSION: This study showed a high magnitude of DPN in Saudi Arabia (39%), thus highlighting the need for sustained efforts to reduce the prevalence of diabetes mellitus and DPN in the kingdom.

Differential associations between pre-diabetes, diabetes and stroke occurrence among West Africans.

BACKGROUND: There are limited data from Africa on the burden and associations between pre-diabetes (pre-DM), diabetes mellitus (DM) and stroke occurrence in a region experiencing a profound rise in stroke burden. PURPOSE: To characterize the associations between stroke and dysglycemic status among West Africans. METHODS: The Stroke Investigative Research and Educational Network (SIREN) is a multicenter, case-control study involving 15 sites in Ghana and Nigeria. Cases include adults aged ≥18 years with clinical and radiological evidence of an acute stroke. Controls were age-and-gender matched stroke-free adults. Detailed evaluations for vascular factors were performed. Pre-diabetes was defined as HBA1c of 5.7%-6.4% or Fasting blood glucose (FBG) 5.6-7.0 mmol/L and DM as HBA1c >6.5% or FBG>7.0 mmol/L. We used conditional logistic regression to estimate adjusted odds ratios (aOR) with 95% Confidence Interval. RESULTS: Among 2,935 stroke cases the mean age was 60.0 ± 14.2 years with 55.2% being males. By glycemic status, 931 (31.7%) were euglycemic, 633 (21.6%) had Pre-diabetes and 1371 (46.7%) had DM. Of the age- and sex-matched stroke-free controls 69.2% were euglycemic, 13.3% had pre-DM and 17.5% had DM. Pre-DM [aOR (95% CI): 3.68(2.61-5.21)] and DM [4.29 (3.19-5.74)] were independently associated with stroke. The aOR of Pre-DM for ischemic stroke 3.06 (2.01-4.64)] was lower than 4.82 (3.37-6.89) for DM. However, the aOR of Pre-DM for hemorrhagic stroke 6.81 (95% CI: 3.29 - 14.08)] was higher than 3.36 (1.94-5.86) for DM. Furthermore, the aOR of pre-DM for ischemic stroke subtypes were 9.64 (1.30-71.57) for cardio-embolic stroke, 3.64 (1.80-7.34) for small-vessel occlusive disease and 4.63 (0.80-26.65) for large-vessel disease. CONCLUSION: Pre-DM is strongly and independently associated with stroke in Africans. Improving glycemic control through screening, healthy lifestyle and pharmacotherapy at a population level may be strategic in reducing the rising burden of stroke in Africa.

Legal Implications of Stroke Biobanking and Genomics Research in Sub-Saharan Africa.

Stroke is a major cause of death in Sub-Saharan Africa (SSA) and genetic factors appear to play a part. This has led to stroke biobanking and genomics research in SSA. Existing stroke studies have focused on causes, incidence rates, fatalities and effects. However, scant attention has been paid to the legal issues in stroke biobanking and genomics research in the sub-region. Therefore, this article examines the legal implications of stroke biobanking and genomics research in SSA. The article adopts a textual analysis of primary and secondary sources in law. It reports that there are laws from the perspectives of human right, the common law, and intellectual property. However, there are gaps to be filled. The article therefore argues for legislative intervention. It concludes that pending the time the statute will be enacted, genomics researchers in Africa should adopt the ethical guidelines prepared by Human Heredity and Health in Africa (H3 Africa).

A Novel Afrocentric Stroke Risk Assessment Score: Models from the Siren Study.

BACKGROUND: Stroke risk can be quantified using risk factors whose effect sizes vary by geography and race. No stroke risk assessment tool exists to estimate aggregate stroke risk for indigenous African. OBJECTIVES: To develop Afrocentric risk-scoring models for stroke occurrence. MATERIALS AND METHODS: We evaluated 3533 radiologically confirmed West African stroke cases paired 1:1 with age-, and sex-matched stroke-free controls in the SIREN study. The 7,066 subjects were randomly split into a training and testing set at the ratio of 85:15. Conditional logistic regression models were constructed by including 17 putative factors linked to stroke occurrence using the training set. Significant risk factors were assigned constant and standardized statistical weights based on regression coefficients (ß) to develop an additive risk scoring system on a scale of 0-100%. Using the testing set, Receiver Operating Characteristics (ROC) curves were constructed to obtain a total score to serve as cut-off to discriminate between cases and controls. We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) at this cut-off. RESULTS: For stroke occurrence, we identified 15 traditional vascular factors. Cohen's kappa for validity was maximal at a total risk score of 56% using both statistical weighting approaches to risk quantification and in both datasets. The risk score had a predictive accuracy of 76% (95%CI: 74-79%), sensitivity of 80.3%, specificity of 63.0%, PPV of 68.5% and NPV of 76.2% in the test dataset. For ischemic strokes, 12 risk factors had predictive accuracy of 78% (95%CI: 74-81%). For hemorrhagic strokes, 7 factors had a predictive accuracy of 79% (95%CI: 73-84%). CONCLUSIONS: The SIREN models quantify aggregate stroke risk in indigenous West Africans with good accuracy. Prospective studies are needed to validate this instrument for stroke prevention.

The Nigeria Parkinson Disease Registry: Process, Profile, and Prospects of a Collaborative Project.

BACKGROUND: Clinical disease registries are useful for quality improvement in care, benchmarking standards, and facilitating research. Collaborative networks established thence can enhance national and international studies by generating more robust samples and credible data and promote knowledge sharing and capacity building. This report describes the methodology, baseline data, and prospects of the Nigeria Parkinson Disease Registry. METHODS: This national registry was established in November 2016. Ethics approval was obtained for all sites. Basic anonymized data for consecutive cases fulfilling the United Kingdom Parkinson's Disease Brain Bank criteria (except the exclusion criterion of affected family members) are registered by participating neurologists via a secure registry website (www.parkinsonnigeria.com) using a minimal common data capture format. RESULTS: The registry had captured 578 participants from 5 of 6 geopolitical zones in Nigeria by July 2019 (72.5% men). Mean age at onset was 60.3 ± 10.7 years; median disease duration (interquartile range) was 36 months (18-60.5 months). Young-onset disease (<50 years) represented 15.2%. A family history was documented in 4.5% and 7.8% with age at onset <50 and ≥ 50, respectively. The most frequent initial symptom was tremor (45.3%). At inclusion, 93.4% were on treatment (54.5% on levodopa monotherapy). Per-capita direct cost for the registry was $3.37. CONCLUSIONS: This is the first published national Parkinson's disease registry in sub-Saharan Africa. The registry will serve as a platform for development of multipronged evidence-based policies and initiatives to improve quality of care of Parkinson's disease and research engagement in Nigeria. © 2020 International Parkinson and Movement Disorder Society.

Prevalence of active epilepsy, lifetime epilepsy prevalence, and burden of epilepsy in Sub-Saharan Africa from meta-analysis of door-to-door population-based surveys.

BACKGROUND: There is marked variation in the prevalence of epilepsy across Sub-Saharan Africa (SSA). In order to accurately estimate the clinical and public health impacts of epilepsy in the region, robust and reliable epidemiological data are required for appropriate estimation of logistical, economical, and social impacts of epilepsy including policy formulation and intervention in the region. OBJECTIVE: We sought to evaluate the prevalence of active epilepsy (AE) and lifetime epilepsy prevalence in SSA using available data collected at community level. METHODS: We carefully searched online databases and identified the required articles using prespecified criteria. Random-effects model (REM) was used to estimate the active and lifetime prevalence from data generated from studies in SSA.. The burden of epilepsy, in terms of the number of people with the disease, was also obtained. Heterogeneity in the analysis was further explored using subgroup analysis and meta-regression techniques. RESULT: A total of 39 and 12 community-based door-to-door surveys addressing AE and lifetime epilepsy, respectively, from different countries of SSA met the inclusion criteria for the study. Random-effects model estimates of overall prevalence of epilepsy were 9 per 1000 persons (95% confidence interval (CI): 8.0-9.9 per 1000 persons) for AE and 16 per 1000 persons (95% CI: 12.3-19.7 per 1000 persons) for lifetime epilepsy. The prevalence was highest in the Central Africa subregion with 30.2 per 1000 persons (95% CI: 6.2 to 66.7 per 1000 persons). The prevalence of AE in the rural settlement was twice that of the urban settlements. About 9,596,551 (95% CI: 8,530,267-10,556,206) people with AE and 17,060,535 (95% CI: 13,115,286-21,005,784) people with lifetime epilepsy live in SSA. CONCLUSION: This study estimates the active (9/1000) and lifetime (16/1000) epilepsy with a remarkable burden of the disease in SSA. However, the prevalence, which is higher in the rural setting, varies within the subregion of SSA.

Differential Impact of Risk Factors on Stroke Occurrence Among Men Versus Women in West Africa.

Background and Purpose- The interplay between sex and the dominant risk factors for stroke occurrence in sub-Saharan Africa has not been clearly delineated. We compared the effect sizes of risk factors of stroke by sex among West Africans. Methods- SIREN study (Stroke Investigative Research and Educational Networks) is a case-control study conducted at 15 sites in Ghana and Nigeria. Cases were adults aged >18 years with computerized tomography/magnetic resonance imaging confirmed stroke, and controls were age- and sex-matched stroke-free adults. Comprehensive evaluation for vascular, lifestyle, and psychosocial factors was performed using validated tools. We used conditional logistic regression to estimate odds ratios and reported risk factor specific and composite population attributable risks with 95% CIs. Results- Of the 2118 stroke cases, 1193 (56.3%) were males. The mean±SD age of males was 58.1±13.2 versus 60.15±14.53 years among females. Shared modifiable risk factors for stroke with adjusted odds ratios (95% CI) among females versus males, respectively, were hypertension [29.95 (12.49-71.77) versus 16.1 0(9.19-28.19)], dyslipidemia [2.08 (1.42-3.06) versus 1.83 (1.29-2.59)], diabetes mellitus [3.18 (2.11-4.78) versus 2.19 (1.53-3.15)], stress [2.34 (1.48-3.67) versus 1.61 (1.07-2.43)], and low consumption of green leafy vegetables [2.92 (1.89-4.50) versus 2.00 (1.33-3.00)]. However, salt intake and income were significantly different between males and females. Six modifiable factors had a combined population attributable risk of 99.1% (98.3%-99.6%) among females with 9 factors accounting for 97.2% (94.9%-98.7%) among males. Hemorrhagic stroke was more common among males (36.0%) than among females (27.6%), but stroke was less severe among males than females. Conclusions- Overall, risk factors for stroke occurrence are commonly shared by both sexes in West Africa favoring concerted interventions for stroke prevention in the region.

Prevalence and burden of epilepsy in Nigeria: A systematic review and meta-analysis of community-based door-to-door surveys.

BACKGROUND: Studies on prevalence of epilepsy in Nigeria yielded figures ranging between 3.1 and 37 per 1000, giving one of the widest variations in prevalence of epilepsy world over. In order to accurately estimate clinical and public health impacts of epilepsy in Nigeria, robust and reliable epidemiological data are required for an appropriate estimation of logistical, economical, and social impacts of epilepsy. OBJECTIVE: The objectives of the study were to determine, using meta-analysis, the prevalence of epilepsy by pooling data from community-based door-to-door surveys conducted in various parts of Nigeria, explore the existing variation in prevalence of epilepsy in Nigeria along geopolitical regions and settlement setting of the country, and then evaluate the burden of epilepsy in Nigeria. METHODS: Prevalence estimates were derived from a random effects meta-analysis of observational studies reporting the prevalence of epilepsy in Nigeria. The derived estimate for the prevalence of epilepsy was applied to the total populations in Nigeria to give an estimated burden of epilepsy in Nigeria. RESULT: Nine community-based door-to-door surveys, with quality data from different regions in Nigeria, were included. I-squared (I2) heterogeneity was 88.5%. Random effects model (REM) estimate of overall prevalence of epilepsy from the studies was 8 per 1000 (95% confidence interval (95% CI): 6-10). The prevalence was highest (11 per 1000) in the south western part of the country. It was also higher among the rural (15 per 1000 people) than the urban (6 per 1000) dwellers. The burden of epilepsy in Nigeria, based on the prevalence estimate was 1,280,000 persons (95% CI: 960,000-1,600,000 persons). CONCLUSION: In Nigeria, the estimated prevalence of epilepsy is 8 per 1000 people indicating a substantial burden of the disease in the country.

Stroke Among Young West Africans: Evidence From the SIREN (Stroke Investigative Research and Educational Network) Large Multisite Case-Control Study.

BACKGROUND AND PURPOSE: Stroke in lower and middle-income countries affects a young and productive age group. Data on factors associated with stroke in the young are sorely lacking from lower and middle-income countries. Our objective is to characterize the nature of stroke and its risk factors among young West Africans aged <50 years old. METHODS: The SIREN (Stroke Investigative Research and Educational Network) is a multicenter, case-control study involving 15 sites in Nigeria and Ghana. Cases included adults aged ≥18 years with computed tomography/magnetic resonance imaging-confirmed stroke. Controls were age-and gender-matched stroke-free adults recruited from the communities in catchment areas of cases. Comprehensive evaluation for vascular, lifestyle, and psychosocial factors was performed. We used conditional logistic regression to estimate odds ratios and population attributable risks with 95% confidence intervals. RESULTS: Five hundred fifteen (24.3%) out of 2118 cases enrolled were <50 years old. Among subjects <50 years old, hemorrhagic stroke proportion was 270 (52.5%) versus 245 (47.5%) for ischemic strokes. Etiologic subtypes of ischemic strokes included large artery atherosclerosis (40.0%), small vessel disease (28.6%), cardioembolism (11.0%), and undetermined (20.4%). Hypertension (91.7%), structural lesions (3.4%), and others (4.9%) were causally associated with hemorrhagic stroke. Six topmost modifiable factors associated with stroke in descending order of population attributable risk (95% confidence interval) were hypertension: 88.7% (82.5%-94.8%), dyslipidemia: 48.2% (30.6%-65.9%), diabetes mellitus: 22.6% (18.7%-26.5%), low green vegetable consumption: 18.2% (-6.8%-43.2%), stress: 14.5% (4.9%-24.1%), and cardiac disease: 8.4% (5.8%-11.1%). CONCLUSIONS: The high and rising burden of stroke among young Africans should be curtailed via aggressive, population-wide vascular risk factor control.

Stroke in Indigenous Africans, African Americans, and European Americans: Interplay of Racial and Geographic Factors.

BACKGROUND AND PURPOSE: The relative contributions of racial and geographic factors to higher risk of stroke in people of African ancestry have not been unraveled. We compared stroke type and contributions of vascular risk factors among indigenous Africans (IA), African Americans (AA), and European Americans (EA). METHODS: SIREN (Stroke Investigative Research and Educational Network) is a large multinational case-control study in West Africa-the ancestral home of 71% AA-whereas REGARDS (Reasons for Geographic and Racial Differences in Stroke) is a cohort study including AA and EA in the United States. Using harmonized assessments and standard definitions, we compared data on stroke type and established risk factors for stroke in acute stroke cases aged ≥55 years in both studies. RESULTS: There were 811 IA, 452 AA, and 665 EA stroke subjects, with mean age of 68.0±9.3, 73.0±8.3, and 76.0±8.3 years, respectively (P<0.0001). Hemorrhagic stroke was more frequent among IA (27%) compared with AA (8%) and EA (5.4%; P<0.001). Lacunar strokes were more prevalent in IA (47.1%), followed by AA (35.1%) and then EA (21.0%; P<0.0001). The frequency of hypertension in decreasing order was IA (92.8%), followed by AA (82.5%) and then EA (64.2%; P<0.0001) and similarly for diabetes mellitus IA (38.3%), AA (36.8%), and EA (21.0%; P<0.0001). Premorbid sedentary lifestyle was similar in AA (37.7%) and EA (34.0%) but lower frequency in IA (8.0%). CONCLUSIONS: Environmental risk factors such as sedentary lifestyle may contribute to the higher proportion of ischemic stroke in AA compared with IA, whereas racial factors may contribute to the higher proportion of hypertension and diabetes mellitus among stroke subjects of African ancestry.

Economic evaluation of childhood epilepsy in a resource-challenged setting: A preliminary survey.

BACKGROUND: Considerable disease variability exists between patients with epilepsy, and the societal costs for epilepsy care are overall high, because of high frequency in the general population especially in children from developing countries. MATERIALS AND METHODS: A cross-sectional study where children with established diagnosis of epilepsy were interviewed using a semi-structured questionnaire. Prevalence-based costs were stratified by patients' sociodemographic characteristics and socioeconomic scores (SES). The 'bottom-up' and 'human capital' approaches were used to generate estimates on the direct and indirect (productivity losses) costs of epilepsy, respectively. All estimates of the financial burden of epilepsy were analyzed from the 'societal perspective' using IBM SPSS statistics software, version 20.0. RESULTS: The study had 103 enrollees with most in the age group of 0-5years (45.6%). Majority (61.3%) belong to the low socioeconomic class (Ogunlesi SES class IV and V) and reside (80.6%) in an urban setting. The total direct and indirect costs per month were ₦2,149,965.00 ($8497.88) and ₦363,187.80 ($1435.52), respectively. The cost of care per patient per annum was ₦292,794.50 ($1157.29), and the total cost for all the patients per year was ₦30,157,833.60 ($119,200.92). Investigative procedures are the principal cost drivers (₦15,861.17 or $18.15) comprising approximately 58.7% of the total direct costs per patient. CONCLUSIONS: Cost of investigations contributed immensely to the total direct cost of care in our study. With the present economic situation in the country, out-of-pocket payments may contribute significantly to catastrophic expenditures and worsening of secondary treatment gap in children with epilepsy.

Development and Reliability of a User-Friendly Multicenter Phenotyping Application for Hemorrhagic and Ischemic Stroke.

BACKGROUND: Annotation and Image Markup on ClearCanvas Enriched Stroke-phenotyping Software (ACCESS) is a novel stand-alone computer software application that allows the creation of simple standardized annotations for reporting brain images of all stroke types. We developed the ACCESS application and determined its inter-rater and intra-rater reliability in the Stroke Investigative Research and Educational Network (SIREN) study to assess its suitability for multicenter studies. METHODS: One hundred randomly selected stroke imaging reports from 5 SIREN sites were re-evaluated by 4 trained independent raters to determine the inter-rater reliability of the ACCESS (version 12.0) software for stroke phenotyping. To determine intra-rater reliability, 6 raters reviewed the same cases previously reported by them after a month of interval. Ischemic stroke was classified using the Oxfordshire Community Stroke Project (OCSP), Trial of Org 10172 in Acute Stroke Treatment (TOAST), and Atherosclerosis, Small-vessel disease, Cardiac source, Other cause (ASCO) protocols, while hemorrhagic stroke was classified using the Structural lesion, Medication, Amyloid angiopathy, Systemic disease, Hypertensive angiopathy and Undetermined (SMASH-U) protocol in ACCESS. Agreement among raters was measured with Cohen's kappa statistics. RESULTS: For primary stroke type, inter-rater agreement was .98 (95% confidence interval [CI], .94-1.00), while intra-rater agreement was 1.00 (95% CI, 1.00). For OCSP subtypes, inter-rater agreement was .97 (95% CI, .92-1.00) for the partial anterior circulation infarcts, .92 (95% CI, .76-1.00) for the total anterior circulation infarcts, and excellent for both lacunar infarcts and posterior circulation infarcts. Intra-rater agreement was .97 (.90-1.00), while inter-rater agreement was .93 (95% CI, .84-1.00) for TOAST subtypes. Inter-rater agreement ranged between .78 (cardioembolic) and .91 (large artery atherosclerotic) for ASCO subtypes and was .80 (95% CI, .56-1.00) for SMASH-U subtypes. CONCLUSION: The ACCESS application facilitates a concordant and reproducible classification of stroke subtypes by multiple investigators, making it suitable for clinical use and multicenter research.

Multilingual Validation of the Questionnaire for Verifying Stroke-Free Status in West Africa.

BACKGROUND AND PURPOSE: The Questionnaire for Verifying Stroke-Free Status (QVSFS), a method for verifying stroke-free status in participants of clinical, epidemiological, and genetic studies, has not been validated in low-income settings where populations have limited knowledge of stroke symptoms. We aimed to validate QVSFS in 3 languages, Yoruba, Hausa and Akan, for ascertainment of stroke-free status of control subjects enrolled in an on-going stroke epidemiological study in West Africa. METHODS: Data were collected using a cross-sectional study design where 384 participants were consecutively recruited from neurology and general medicine clinics of 5 tertiary referral hospitals in Nigeria and Ghana. Ascertainment of stroke status was by neurologists using structured neurological examination, review of case records, and neuroimaging (gold standard). Relative performance of QVSFS without and with pictures of stroke symptoms (pictograms) was assessed using sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: The overall median age of the study participants was 54 years and 48.4% were males. Of 165 stroke cases identified by gold standard, 98% were determined to have had stroke, whereas of 219 without stroke 87% were determined to be stroke-free by QVSFS. Negative predictive value of the QVSFS across the 3 languages was 0.97 (range, 0.93-1.00), sensitivity, specificity, and positive predictive value were 0.98, 0.82, and 0.80, respectively. Agreement between the questionnaire with and without the pictogram was excellent/strong with Cohen k=0.92. CONCLUSIONS: QVSFS is a valid tool for verifying stroke-free status across culturally diverse populations in West Africa.

Phenotyping Stroke in Sub-Saharan Africa: Stroke Investigative Research and Education Network (SIREN) Phenomics Protocol.

BACKGROUND: As the second leading cause of death and the leading cause of adult-onset disability, stroke is a major public health concern particularly pertinent in Sub-Saharan Africa (SSA), where nearly 80% of all global stroke mortalities occur, and stroke burden is projected to increase in the coming decades. However, traditional and emerging risk factors for stroke in SSA have not been well characterized, thus limiting efforts at curbing its devastating toll. The Stroke Investigative Research and Education Network (SIREN) project is aimed at comprehensively evaluating the key environmental and genomic risk factors for stroke (and its subtypes) in SSA while simultaneously building capacities in phenomics, biobanking, genomics, biostatistics, and bioinformatics for brain research. METHODS: SIREN is a transnational, multicentre, hospital and community-based study involving 3,000 cases and 3,000 controls recruited from 8 sites in Ghana and Nigeria. Cases will be hospital-based patients with first stroke within 10 days of onset in whom neurovascular imaging will be performed. Etiological and topographical stroke subtypes will be documented for all cases. Controls will be hospital- and community-based participants, matched to cases on the basis of gender, ethnicity, and age (±5 years). Information will be collected on known and proposed emerging risk factors for stroke. STUDY SIGNIFICANCE: SIREN is the largest study of stroke in Africa to date. It is anticipated that it will shed light on the phenotypic characteristics and risk factors of stroke and ultimately provide evidence base for strategic interventions to curtail the burgeoning burden of stroke on the sub-continent.

Factors associated with frequency of fruit and vegetable consumption among selected sub-Saharan African populations: evidence from the Cardiovascular H3Africa Innovation Resource Project.

BACKGROUND: Frequent fruit and vegetable consumption is considered a promising dietary behaviour that protects health. However, most existing studies about the factors associated with this phenomenon among Africans are based on single-country reports, apart from one meta-regression combining smaller studies. This study harmonized large datasets and assessed factors associated with the frequency of fruit and vegetable consumption in this population. METHODS: Individual-level data on sociodemographics, lifestyle and diet from 20 443 participants across five African countries (Burkina Faso, Ghana, Kenya, South Africa and Nigeria), from the Stroke Investigative Research and Educational Network (SIREN) and Africa Wits-INDEPTH partnership for Genomic Research (AWI-Gen) studies, were harmonized. Total frequency of fruit and vegetable consumption (in portions/week) was classified as 'low' (≤6), 'moderate' (7-14) and 'high' (≥15). Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of factors associated with the total frequency of fruit and vegetable consumption (using 'low' consumption as the reference) were estimated using multinomial regression models. RESULTS: Mean age of participants was 54.3 ± 11.8 years, 10 641 (52.1%) were female, and the median (interquartile range) frequency of total fruit and vegetable consumption was 10.0 (4.0, 21.0) portions/week. Participants with a family history of cardiovascular disease [moderate (aOR, 0.92; 95% CI, 0.85, 1.00) and high (aOR, 0.85; 95% CI, 0.78, 0.92)], current smokers [moderate (aOR, 0.83; 95% CI, 0.74, 0.94) and high (aOR, 0.78; 95% CI, 0.69, 0.88)], current alcohol users [moderate (aOR, 0.92; 95% CI, 0.85, 1.00) and high (aOR, 0.82; 95% CI, 0.76, 0.89)] and physically inactive participants [moderate (aOR, 0.85; 95% CI, 0.75, 0.96) and high (aOR, 0.80; 95% CI, 0.70, 0.90)] were less likely to consume fruits and vegetables frequently. CONCLUSION: Africans with lifestyle risk factors for cardiovascular disease were less likely to consume fruit and vegetables frequently.

Novel functional insights into ischemic stroke biology provided by the first genome-wide association study of stroke in indigenous Africans.

BACKGROUND: African ancestry populations have the highest burden of stroke worldwide, yet the genetic basis of stroke in these populations is obscure. The Stroke Investigative Research and Educational Network (SIREN) is a multicenter study involving 16 sites in West Africa. We conducted the first-ever genome-wide association study (GWAS) of stroke in indigenous Africans. METHODS: Cases were consecutively recruited consenting adults (aged > 18 years) with neuroimaging-confirmed ischemic stroke. Stroke-free controls were ascertained using a locally validated Questionnaire for Verifying Stroke-Free Status. DNA genotyping with the H3Africa array was performed, and following initial quality control, GWAS datasets were imputed into the NIH Trans-Omics for Precision Medicine (TOPMed) release2 from BioData Catalyst. Furthermore, we performed fine-mapping, trans-ethnic meta-analysis, and in silico functional characterization to identify likely causal variants with a functional interpretation. RESULTS: We observed genome-wide significant (P-value < 5.0E-8) SNPs associations near AADACL2 and miRNA (MIR5186) genes in chromosome 3 after adjusting for hypertension, diabetes, dyslipidemia, and cardiac status in the base model as covariates. SNPs near the miRNA (MIR4458) gene in chromosome 5 were also associated with stroke (P-value < 1.0E-6). The putative genes near AADACL2, MIR5186, and MIR4458 genes were protective and novel. SNPs associations with stroke in chromosome 2 were more than 77 kb from the closest gene LINC01854 and SNPs in chromosome 7 were more than 116 kb to the closest gene LINC01446 (P-value < 1.0E-6). In addition, we observed SNPs in genes STXBP5-AS1 (chromosome 6), GALTN9 (chromosome 12), FANCA (chromosome 16), and DLGAP1 (chromosome 18) (P-value < 1.0E-6). Both genomic regions near genes AADACL2 and MIR4458 remained significant following fine mapping. CONCLUSIONS: Our findings identify potential roles of regulatory miRNA, intergenic non-coding DNA, and intronic non-coding RNA in the biology of ischemic stroke. These findings reveal new molecular targets that promise to help close the current gaps in accurate African ancestry-based genetic stroke's risk prediction and development of new targeted interventions to prevent or treat stroke.