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.

Dietary patterns associated with hypertension among stroke-free indigenous Africans: insights from the Stroke Investigative Research and Educational Network study.

BACKGROUND: The dietary factors associated with the high burden of hypertension among indigenous Africans remain poorly understood. We assessed the relationship between dietary patterns and hypertension among indigenous Africans. METHOD: In this study, 1550 participants with hypertension matched (for age: ±â€Š5 years, sex and ethnicity) with 1550 participants without hypertension were identified from the stroke-free population in the Stroke Investigative Research and Educational Network study in Ghana and Nigeria. Food consumption was assessed using a food frequency questionnaire, and dietary information was summarized using principal component analysis to identify seven dietary patterns. Conditional logistic regression was applied to compute the odds ratio (OR) and 95% confidence interval (CI) for the risk of hypertension by tertiles of dietary patterns adjusting for age, education, income, smoking, alcohol use, physical inactivity, family history of cardiovascular diseases, obesity and salt intake at a two-sided P less than 0.05. RESULTS: Multivariable-adjusted OR [95% confidence interval (CI)] for risk of hypertension by second and third tertiles [using the lowest (first) tertile as reference] of dietary patterns were 0.62 (0.48-0.80), 0.70 (0.54-0.90) for whole grains and fruit drinks; 0.87 (0.68-1.12), 0.83 (0.64-1.08) for fruits; 0.85 (0.65-1.10), 0.97 (0.75-1.26) for vegetables, legumes and potatoes; 0.78 (0.60-1.00), 0.84 (0.65-1.08) for fried foods and sweetened drinks; 1.13 (0.88-1.45), 0.80 (0.62-1.03) for poultry product and organ meat; 1.11 (0.86-1.43), 0.88 (0.68-1.14) for red meat; and 1.14 (0.88-1.48), 1.09 (0.84-1.43) for processed foods ( P  < 0.05). CONCLUSION: A higher adherence to dietary consumption of whole grains and fruits was inversely associated with low odds of hypertension in this population.

Clinical and neuroimaging factors associated with 30-day fatality among indigenous West Africans with spontaneous intracerebral hemorrhage.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is associated with a high case fatality rate in resource-limited settings. The independent predictors of poor outcome after ICH in sub-Saharan Africa remains to be characterized in large epidemiological studies. We aimed to determine factors associated with 30-day fatality among West African patients with ICH. METHODS: The Stroke Investigative Research and Educational Network (SIREN) study is a multicentre, case-control study conducted at 15 sites in Nigeria and Ghana. Adults aged ≥18 years with spontaneous ICH confirmed with neuroimaging. Demographic, cardiovascular risk factors, clinical features and neuroimaging markers of severity were assessed. The independent risk factors for 30-day mortality were determined using a multivariate logistic regression analysis with an adjusted odds ratio (OR) and 95% confidence interval (CI). RESULTS: Among 964 patients with ICH, 590 (61.2%) were males with a mean age (SD) of 54.3(13.6) years and a case fatality of 34.3%. Factors associated with 30-day mortality among ICH patients include: Elevated mean National Institute of Health Stroke Scale(mNIHSS);(OR 1.06; 95% CI 1.02-1.11), aspiration pneumonitis; (OR 7.17; 95% CI 2.82-18.24), ICH volume > 30mls; OR 2.68; 95% CI 1.02-7.00)) low consumption of leafy vegetables (OR 0.36; 95% CI 0.15-0.85). CONCLUSION: This study identified risk and protective factors associated with 30-day mortality among West Africans with spontaneous ICH. These factors should be further investigated in other populations in Africa to enable the development of ICH mortality predictions models among indigenous Africans.

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.

Risk Assessment Score and Chi-Square Automatic Interaction Detection Algorithm for Hypertension Among Africans: Models From the SIREN Study.

BACKGROUND: This study aimed to develop a risk-scoring model for hypertension among Africans. METHODS: In this study, 4413 stroke-free controls were used to develop the risk-scoring model for hypertension. Logistic regression models were applied to 13 risk factors. We randomly split the dataset into training and testing data at a ratio of 80:20. Constant and standardized weights were assigned to factors significantly associated with hypertension in the regression model to develop a probability risk score on a scale of 0 to 1 using a logistic regression model. The model accuracy was assessed to estimate the cutoff score for discriminating hypertensives. RESULTS: Mean age was 59.9±13.3 years, 56.0% were hypertensives, and 8 factors, including diabetes, age ≥65 years, higher waist circumference, (BMI) ≥30 kg/m2, lack of formal education, living in urban residence, family history of cardiovascular diseases, and dyslipidemia use were associated with hypertension. Cohen κ was maximal at ≥0.28, and a total probability risk score of ≥0.60 was adopted for both statistical weighting for risk quantification of hypertension in both datasets. The probability risk score presented a good performance-receiver operating characteristic: 64% (95% CI, 61.0-68.0), a sensitivity of 55.1%, specificity of 71.5%, positive predicted value of 70.9%, and negative predicted value of 55.8%, in the test dataset. Similarly, decision tree had a predictive accuracy of 67.7% (95% CI, 66.1-69.3) for the training set and 64.6% (95% CI, 61.0-68.0) for the testing dataset. CONCLUSIONS: The novel risk-scoring model discriminated hypertensives with good accuracy and will be helpful in the early identification of community-based Africans vulnerable to hypertension for its primary prevention.

Research participants' perception of ethical issues in stroke genomics and neurobiobanking research in Africa.

Background: There is a growing interest in stroke genomics and neurobiobanking research in Africa. These raise several ethical issues, such as consent, re-use, data sharing, storage, and incidental result of biological samples. Despite the availability of ethical guidelines developed for research in Africa, there is paucity of information on how the research participants' perspectives could guide the research community on ethical issues in stroke genomics and neurobiobanking research. To explore African research participants' perspectives on these issues, a study was conducted at existing Stroke Investigation Research and Education Network (SIREN) sites in Nigeria and Ghana. Method: Using an exploratory design, twenty-eight Focus Group Discussions (FGDs) sessions were conducted with stroke survivors (n=7), caregivers(n=7), stroke - free controls(n=7), and Community Advisory Board members(n=7). Data were collected using an interview guide. Interviews were conducted in English and indigenous languages of the community, audio recorded, and transcribed verbatim. Data were analyzed using NVivo (March, 2020) Software. Result: Results revealed that stroke genomics and neurobiobanking research in Africa require researchers' direct attention to ethical issues. Concerns were raised about understanding, disclosure and absence of coercion as components of true autonomous decision making in research participation. Participants argued that the risk and benefits attached to participation should be disclosed at the time of recruitment. Fears around data sharing were voiced as adherence to the principle of privacy and confidentiality were of paramount importance to participants. The preference was to receive the results of incidental findings with no stigma attached from society. Conclusion: Research participants' perspectives are a vital aspect of community engagement in stroke genomics and neurobiobanking research. Findings from this study suggest that research participants are interested in these fields of research in Africa if their concerns about ethical issues are appropriately addressed within the research framework.

Family Needs Assessment of Patients with Cerebral Palsy Attending Two Hospitals in Accra, Ghana.

BACKGROUND: The family represents the most essential and supportive environment for children with cerebral palsy (CP). To improve children's outcomes, it is crucial to consider the needs of families in order to offer family-centered care, which tailors services to these needs. OBJECTIVE: We conducted a needs assessment to identify the family needs of patients with CP attending two hospitals in Accra. METHODS: The study was a cross-sectional study involving primary caregivers of children with CP attending neurodevelopmental clinics. Structured questionnaires were used to collect data spanning an 8-month period. The data were summarized, and statistical inference was made. RESULTS: Service needs identified were childcare, counseling, support groups, financial assistance, and recreational facilities. Information needs included adult education, job training/employment opportunities, education, health and social programs, knowledge about child development, and management of behavioral and feeding/nutrition problems. Reducing extensive travel time was desirable to improve access to healthcare. With the increasing severity of symptoms came the need for improved accessibility in the home to reduce the child's hardship, as well as assistive devices, recreational facilities, and respite for the caregiver(s). CONCLUSION: Families of children with CP have information, service, and access needs related to their disease severity and family context.

Determinants of First-Ever Stroke Severity in West Africans: Evidence From the SIREN Study.

Background Baseline stroke severity is probably partly responsible for poor stroke outcomes in sub-Saharan Africa. However, there is a paucity of information on determinants of stroke severity among indigenous Africans. We sought to identify the factors associated with stroke severity among West Africans in the SIREN (Stroke Investigative Research and Educational Networks) study. Methods and Results Stroke was diagnosed clinically and confirmed with brain neuroimaging. Severe stroke was defined as a Stroke Levity Scale score of ≤5. A multivariate logistic regression model was constructed to identify factors associated with stroke severity at 95% CI and a nominal cutoff of 5% type 1 error. A total of 3660 stroke cases were included. Overall, 50.7%% had severe stroke, including 47.6% of all ischemic strokes and 56.1% of intracerebral hemorrhage. Factors independently associated with severe stroke were meat consumption (adjusted odds ratio [aOR], 1.97 [95% CI, 1.43-2.73]), low vegetable consumption (aOR, 2.45 [95% CI, 1.93-3.12]), and lesion volume, with an aOR of 1.67 (95% CI, 1.03-2.72) for lesion volume of 10 to 30 cm3 and aOR of 3.88 (95% CI, 1.93-7.81) for lesion volume >30 cm3. Severe ischemic stroke was independently associated with total anterior circulation infarction (aOR, 3.1 [95% CI, 1.5-6.9]), posterior circulation infarction (aOR, 2.2 [95% CI, 1.1-4.2]), and partial anterior circulation infarction (aOR, 2.0 [95% CI, 1.2-3.3]) compared with lacunar stroke. Increasing age (aOR, 2.6 [95% CI, 1.3-5.2]) and lesion volume >30 cm3 (aOR, 6.2 [95% CI, 2.0-19.3]) were independently associated with severe intracerebral hemorrhage. Conclusions Severe stroke is common among indigenous West Africans, where modifiable dietary factors are independently associated with it. These factors could be targeted to reduce the burden of severe stroke.

Patient-level and system-level determinants of stroke fatality across 16 large hospitals in Ghana and Nigeria: a prospective cohort study.

BACKGROUND: Every minute, six indigenous Africans develop new strokes. Patient-level and system-level contributors to early stroke fatality in this region are yet to be delineated. We aimed to identify and quantify the contributions of patient-level and system-level determinants of inpatient stroke fatality across 16 hospitals in Ghana and Nigeria. METHODS: The Stroke Investigative Research and Educational Network (SIREN) is a multicentre study involving 16 sites in Ghana and Nigeria. Cases include adults (aged ≥18 years) with clinical and radiological evidence of an acute stroke. Data on stroke services and resources available at each study site were collected and analysed as system-level factors. A host of demographic and clinical variables of cases were analysed as patient-level factors. A mixed effect log-binomial model including both patient-level and system-level covariates was fitted. Results are presented as adjusted risk ratios (aRRs) with respective 95% CIs. FINDINGS: Overall, 814 (21·8%) of the 3739 patients admitted with stroke died as inpatients: 476 (18·1%) of 2635 with ischaemic stroke and 338 (30·6%) of 1104 with intracerebral haemorrhage. The variability in the odds of stroke fatality that could be attributed to the system-level factors across study sites assessed using model intracluster correlation coefficient was substantial at 7·3% (above a 5% threshold). Stroke units were available at only five of 16 centres. The aRRs of six patient-level factors associated with stroke fatality were: low vegetable consumption, 1·19 (95% CI 1·07-1·33); systolic blood pressure, 1·02 (1·01-1·04) for each 10 mm Hg rise; stroke lesion volume more than 30 cm3, 1·48 (1·22-1·79); National Institutes of Health Stroke Scale (NIHSS) score, 1·20 (1·13-1·26) for each 5-unit rise; elevated intracranial pressure, 1·75 (1·31-2·33); and aspiration pneumonia, 1·79 (1·16-2·77). INTERPRETATION: Studies are needed to assess the efficacy of interventions targeting patient-level factors such as aspiration pneumonia in reducing acute stroke fatality in this region. Policy directives to improve stroke unit access are warranted. FUNDING: US National Institutes of Health. TRANSLATIONS: For the Twi, Yoruba and Hausa translations of the abstract see Supplementary Materials section.

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.

Capacity-Building for Stroke Genomic Research Data Collection: The African Neurobiobank Ethical, Legal, and Social Implications Project Experience.

Background: The fields of stroke genomics, biobanking, and precision medicine are rapidly expanding in sub-Saharan Africa. However, the ethical, legal, and social implications (ELSI) of emerging neurobiobanking and genomic data resources are unclear in an emerging African scientific landscape with unique cultural, linguistic, and belief systems. Objective: This article documents capacity-building experiences of researchers during the development, pretesting, and validation of data collection instruments of the African Neurobiobank for Precision Stroke Medicine-(ELSI) Project. Methods: The African Neurobiobank for Precision Stroke Medicine-ELSI project is a transnational, multicenter project implemented across seven sites in Ghana and Nigeria. Guided by the Community-Based Participatory Research framework, we conducted three workshops with key stakeholders to review the study protocol, ensure uniformity in implementation; pretest, harmonize, and integrate context-specific feedback to ensure validity and adaptability of data collection instruments. Workshop impact was assessed using an open-ended questionnaire, which included questions on experience with participation in any of the workshops, building capacity in Genetic and Genomic Research (GGR), level of preparedness toward GGR, the genomic mini-dictionary developed by the team, and its impact in enhancing understanding in GGR. Data were analyzed qualitatively using a thematic framework approach. Results: Findings revealed the usefulness of the workshop in improving participants' knowledge and capacity toward GGR implementation. It further identified local, context-specific concerns regarding quality data collection, the need to develop culturally acceptable, genomic/biobanking data collection tools, and a mini-dictionary. Participants-reported perceptions were that the mini-dictionary enhanced understanding, participation, and data collection in GGR. Overall, participants reported increased preparedness and interest in participating in GGR. Conclusion: Capacity-building is a necessary step toward ELSI-related genomic research implementation in African countries where scholarship of ELSI of genomics research is emerging. Our findings may be useful to the design and implementation of ELSI-GGR projects in other African countries.

Dietary patterns associated with stroke among West Africans: A case-control study.

BACKGROUND: The relationship of diet with stroke risk among Africans is not well understood. AIM: The aim of this study was to investigate the association between dietary patterns and stroke risk among West Africans. METHODS: In this multi-center case-control study, 3684 stroke patients matched (for age and sex) with 3684 healthy controls were recruited from Nigeria and Ghana. Food consumption was assessed using a food frequency questionnaire, and dietary patterns were summarized using principal component analysis. Stroke was defined using predefined criteria primarily on clinical evaluation following standard guidelines. Conditional logistic regression was applied to compute odds ratio (OR) and 95% confidence interval (CI) for stroke risk by tertiles of dietary patterns adjusting for relevant confounders. RESULTS: Overall, mean age was 59.0 ± 13.9 years, and 3992 (54.2%) were males. Seven dietary patterns were identified. Multivariable-adjusted OR (95% CI) for risk of stroke by second and third tertiles (using the lowest and first tertile as reference) of dietary patterns was 1.65 (1.43, 1.90) and 1.74 (1.51, 2.02), for "poultry product and organ meat"; 1.69 (1.47, 1.96) and 1.51 (1.31, 1.75) for "red meat"; 1.07 (0.92, 1.23) and 1.21 (1.04, 1.40) for "fried foods and sweetened drinks"; 0.69 (0.60, 0.80) and 0.45 (0.39, 0.53) for "vegetables"; 0.84 (0.72, 0.97) and 0.81 (0.70, 0.93) for "whole-grain and fruit drinks"; and 0.97 (0.84, 1.12) and 0.85 (0.73, 0.98) for "fruits" respectively (p < 0.05). CONCLUSION: These data suggest that plant-based diets are associated with a lower risk of stroke and might be a beneficial dietary recommendation for the primary prevention of stroke among Africans.

Secondhand smoke exposure is independently associated with stroke among non-smoking adults in West Africa.

BACKGROUND: Stroke is a leading cause of disability and mortality worldwide, but little is known about the contribution of secondhand smoke exposure (SHSE) to stroke epidemiology among indigenous Africans. OBJECTIVE: To evaluate the association of SHSE with stroke among indigenous Africans. METHODS: We analyzed the relationship of SHSE with stroke among 2990 case-control pairs of adults who had never smoked (identified in the SIREN study) using conditional logistic regression at a two-sided P < 0.05. RESULTS: Multivariable-adjusted odds ratio and 95% confidence interval; 1.25 (1.04, 1.50; P = 0.02) revealed SHSE was positively associated with stroke independent of stroke subtypes. CONCLUSION: Culturally relevant primary prevention strategies targeted at SHSE might be promising in preventing stroke among Africans.

Biological sample donation and informed consent for neurobiobanking: Evidence from a community survey in Ghana and Nigeria.

INTRODUCTION: Genomic research and neurobiobanking are expanding globally. Empirical evidence on the level of awareness and willingness to donate/share biological samples towards the expansion of neurobiobanking in sub-Saharan Africa is lacking. AIMS: To ascertain the awareness, perspectives and predictors regarding biological sample donation, sharing and informed consent preferences among community members in Ghana and Nigeria. METHODS: A questionnaire cross-sectional survey was conducted among randomly selected community members from seven communities in Ghana and Nigeria. RESULTS: Of the 1015 respondents with mean age 39.3 years (SD 19.5), about a third had heard of blood donation (37.2%, M: 42.4%, F: 32.0%, p = 0.001) and a quarter were aware of blood sample storage for research (24.5%; M: 29.7%, F: 19.4%, p = 0.151). Two out of ten were willing to donate brain after death (18.8%, M: 22.6%, F: 15.0%, p<0.001). Main reasons for unwillingness to donate brain were; to go back to God complete (46.6%) and lack of knowledge related to brain donation (32.7%). Only a third of the participants were aware of informed consent (31.7%; M: 35.9%, F: 27.5%, p<0.001). Predictors of positive attitude towards biobanking and informed consent were being married, tertiary level education, student status, and belonging to select ethnic groups. CONCLUSION: There is a greater need for research attention in the area of brain banking and informed consent. Improved context-sensitive public education on neurobiobanking and informed consent, in line with the sociocultural diversities, is recommended within the African sub region.

Determinants of metabolic syndrome and its prognostic implications among stroke patients in Africa: Findings from the Stroke Investigative Research and Educational Network (SIREN) study.

BACKGROUND: The prognostic implications of metabolic syndrome (METS) among African stroke patients are poorly understood. This study aimed to investigate the determinants of METS and its prognostic implications among Africans with newly diagnosed stroke in the SIREN study. METHODS: We included stroke cases (adults aged >18 years with CT/MRI confirmed stroke). The validated tools comprehensively evaluated vascular, lifestyle, and psychosocial factors. We used logistic regression to estimate adjusted odds ratios (OR) with 95% CIs for the association between METS and risk factors. We also computed the prediction power of the domain of covariates in a sequential manner using the area under the receiver operating curve (ROC) curve. RESULTS: Among 3998 stroke subjects enrolled in the study, 76.8% had METS by at least one of the clinical definitions. Factors associated with METS were age > 50 years (OR- 1.46, CI-1.19-1.80), male gender (OR 4.06, CI- 3.28-5.03), income >100USD (OR1.42, CI-1.17-1.71), stress (OR1.46, CI-1.14-1.87), family history of diabetes mellitus (OR1.38, CI-1.06-1.78), and cardiac disease (OR1.42, CI-1.18-1.65). Stroke severity was higher among those with METS (SLS = 5.8 ± 4.3) compared with those without METS (6.2 ± 4.5) at p = 0.037. METS was associated with higher odds (aOR 1.31, CI-1.08-1.58) of one-month fatality after adjusting for stroke severity, age > 50 years, and average monthly income >100USD. CONCLUSION: METS is very common among African stroke patients and is associated with stroke severity and worse one-month fatality. Lifestyle interventions may prevent METS and attenuate its impact on stroke occurrence and outcomes.

Home-Based Remedies to Prevent COVID-19-Associated Risk of Infection, Admission, Severe Disease, and Death: A Nested Case-Control Study.

Objective: This study aimed at determining the various types of home-based remedies, mode of administration, prevalence of use, and their relevance in reducing the risk of infection, hospital admission, severe disease, and death. Methods: The study design is an open cohort of all participants who presented for testing for COVID-19 at the Infectious Disease Treatment Centre (Tamale) and were followed up for a period of six weeks. A nested case-control study was designed. Numerical data were analysed using STATA version 14, and qualitative data were thematically analysed. Results: A total of 882 participants made up of 358 (40.6%) cases and 524 (59.4%) unmatched controls took part in the study. The prevalence of usage of home-based remedies to prevent COVID-19 was 29.6% (n = 261). These include drinks (34.1% (n = 100)), changes in eating habits/food (33.8% (n = 99)), physical exercise (18.8% (n = 55)), steam inhalation (9.9% (n = 29)), herbal baths (2.7% (n = 8)), and gurgle (0.7 (n = 2)). Participants who practiced any form of home-based therapy were protected from SARS-CoV-2 infection (OR = 0.28 (0.20-0.39)), severe/critical COVID-19 (OR = 0.15 (0.05-0.48)), hospital admission (OR = 0.15 (0.06-0.38)), and death (OR = 0.31 (0.07-1.38)). Analysis of the various subgroups of the home-based therapies, however, demonstrated that not all the home-based remedies were effective. Steam inhalation and herbal baths were associated with 26.6 (95% CI = 6.10-116.24) and 2.7 (95% CI = 0.49-14.78) times increased risk of infection, respectively. However, change in diet (AOR = 0.01 (0.00-0.13)) and physical exercise (AOR = 0.02 (0.00-0.26)) remained significantly associated with a reduced risk of infection. We described results of thematic content analysis regarding the common ingredients in the drinks, diets, and other home-based methods administered. Conclusion: Almost a third of persons presenting for COVID-19 test were involved in some form of home-based remedy to prevent COVID-19. Steam inhalation and herbal baths increased risk of COVID-19 infection, while physical exercise and dietary changes were protective against COVID-19 infection and hospital admission. Future protocols might consider inclusion of physical activity and dietary changes based on demonstrated health gains.

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.

Registration status, mercury exposure biomarkers, and neuropsychological assessment of artisanal and small-scale gold miners (ASGM) from the Western Region of Ghana.

The artisanal and small-scale gold mining (ASGM) sector is estimated to be the largest anthropogenic source of mercury pollution worldwide, and not surprisingly human exposures in this sector are amongst the highest of all population groups. While formalization of the sector has been proposed as a solution to help improve health and safety within ASGM sites, there are few empirical studies in support of this notion. The objective of this study was to assess if individuals working in ASGM sites that are registered have reduced mercury exposures and better neuropsychological scores than workers from unregistered sites. To achieve this objective, we studied biological samples (urine, hair) and survey data from a study of 404 ASGM workers (of which, 295 worked in registered ASGM sites) conducted in Tarkwa (Ghana) in 2014. Between miners working in registered and unregistered sites, there were few differences in socio-demographic characteristics. Median urinary mercury concentration (specific gravity-corrected) among those from unregistered mines was nearly 3-fold higher than those from the registered mines (18.5 versus 6.6 µg/L), and in the overall population the median concentration was 10.0 µg/L, and ranged from 0.3 to 2499 µg/L. Mercury biomarkers varied across ASGM work categories (e.g., those who burned or amalgamated had the highest) and users of personal protective equipment. Nearly 30% of the study population indicated having some challenges concerning, for example, reduced appetite, hair loss, or excess salivation. Ataxia and rigidity of gait were absent in most of the participants, and for those with slight, moderate, or marked responses, there were no differences between miners from registered and unregistered sites, across work groups, as well as in reference to mercury biomarker measures. For the pencil tapping, Frostig, matchbox, and Wechsler tests, no striking differences were found though a correlation was found between urinary mercury levels and matchbox scores among those who amalgamate and burn, and scores were similar to past studies using the same tests in ASGM sites. We believe this is the first study to compare mercury exposures and neuropsychological test results between miners from registered and unregistered ASGM sites. In doing so, the research findings provide the necessary evidence for stakeholders and parties of the Minamata Convention considering various response options to help fulfill their obligations.

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.

Frequency and factors associated with post-stroke seizures in a large multicenter study in West Africa.

BACKGROUND: Post-stroke seizures (PSS) are associated with significant morbidity and mortality across the globe. There is a paucity of data on PSS in Africa. PURPOSE: To assess the frequency and factors associated with PSS by stroke types across 15 hospitals in Nigeria and Ghana. METHODS: We analyzed data on all stroke cases recruited into the Stroke Investigative Research and Educational Network (SIREN). We included adults aged ≥18 years with radiologically confirmed ischemic stroke (IS) or intracerebral hemorrhage (ICH). PSS were defined as acute symptomatic seizures occurring at stroke onset and/or during acute hospitalization up until discharge. We used logistic regression to estimate adjusted odds ratios (aOR) with 95% Confidence Interval. RESULTS: Among 3344 stroke patients, 499 (14.9%) had PSS (95% CI: 13.7-16.2%). The mean duration of admission in days for those with PSS vs no PSS was 17.4 ± 28.6 vs 15.9 ± 24.7, p = 0.72. There were 294(14.1%) PSS among 2091 ischemic strokes and 159(17.7%) among 897 with ICH, p = 0.01. The factors associated with PSS occurrence were age < 50 years, aOR of 1.59 (1.08-2.33), National Institute of Health Stroke Score (NIHSS), 1.29 (1.16-1.42) for each 5 units rise and white cell count 1.07 (1.01-1.13) for each 10^3 mm3 rise. Factors associated with PSS in ischemic were NIHSS score, aOR of 1.17 (1.04-1.31) and infarct volume of 10-30 cm3 aOR of 2.17(1.37-3.45). Among ICH, associated factors were alcohol use 5.91 (2.11-16.55) and lobar bleeds 2.22 (1.03-4.82). CONCLUSION: The burden of PSS among this sample of west Africans is substantial and may contribute to poor outcomes of stroke in this region. Further longitudinal studies are required to understand the impact on morbidity and mortality arising from PSS in Africa.