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.

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.

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.

Sociodemographic and behavioural risk factors for obesity among community-dwelling older adults in Ghana and Nigeria: A secondary analysis of data from the SIREN study.

OBJECTIVES: To explore the prevalence and risk factors of obesity among older adults from low- and middle-income countries (LMICs). METHODS: This is a secondary analysis of data obtained from the SIREN study through in-person interviews and measurements from healthy stroke-free older adults (≥60 years). Overweight/obesity was defined as body mass index ≥25 kg/m2. Abdominal obesity was defined as waist-to-hip ratio (WHR) of >0.90 for males and >0.85/females or waist circumference (WC) of >102 cm for males/>88 cm for females. Adjusted odds ratio (aORs) with 95% confidence interval (CIs) of the relationship between obesity and sociodemographic factors were assessed at P < 0.05. RESULTS: Overall, 47.5% of participants were overweight/obese, 76.6% had a larger than recommended WHR, and 54.4% had a larger than recommended WC. Abdominal obesity (WC; aOR: 9.43, CI: 6.99-12.50), being a Nigerian (aOR: 0.55; CI: 0.42-0.72), living in an urban setting (aOR: 1.92; CI: 1.49-2.46), earning >$100/month (aOR: 1.53; CI: 1.19-1.96), and having formal education (aOR: 1.42; CI: 1.08-1.87) were associated with overweight/obesity. CONCLUSION: Living in urban settings, earning a higher income, and having a formal education were associated with a higher odds of obesity among older adults from LMICs.

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.

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.

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.

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.

Carotid and Vertebral Atherosclerosis in West African Stroke Patients: Findings from the Stroke Investigative Research and Education Network.

Background: We evaluated the characteristics of carotid and vertebral atherosclerosis in indigenous West Africans with stroke. Methodology: Of the 3778stroke patients recruited between 01/2014 and 08/2017, 1070 (28.3%) received carotid and vertebral artery evaluation with B-mode Ultrasound. Carotid and vertebral intima-media thickness (IMT) using multiple site technique were measured bilaterally and plaque frequency was determined. Descriptive and comparative analyses between stroke types and vessels were carried out. Results: There were 809 (75.6%) patients with ischemic stroke. The prevalence of intima-media thickening in the study population was 84.0% (898/1070) [95% CI: 81.7-86.1], being higher in the ischemic stroke (688/809, 85.0%) [95% CI: 82.4-87.3] than in the hemorrhagic stroke group (211/261, 80.8%) [95% CI: 75.6-85.2]. Overall prevalence of plaques which was 26.1% [95% CI: 23.5-28.8], was found also to be higher in ischemic than hemorrhagic stroke (29.8%[95% CI: 26.7-33.0] vs. 14.6% [95% CI: 10.8-19.4], p < 0.05). The mean IMT (carotids: 2.01+1.33 mm; vertebrals: 0.96+0.54mm, p<0.001) and prevalence of plaques (carotids: 8.8%; vertebrals: 1.7%,p<0.001) were higher in carotid than vertebral arteries. Age, hypertension, level of formal education, history of smoking, average monthly income, and family histories of hypertension and stroke were associated with intima-media thickening in the carotids (all p< 0.05) in the ischemic stroke patients while family history of hypertension, diabetes mellitus, and level of formal education were independently associated with intima-media thickening in the carotids (all p< 0.05) in the hemorrhagic stroke patients. No CVRF showed an independent association with the presence of plaque in the carotid and vertebral arteries both stroke types. Conclusions: One off our stroke patients in our cohort had atherosclerotic plaques, with ischemic patients being twice as likely to have this burden compared to hemorrhagic patients, and carotid atherosclerosis being five times as frequent as vertebral atherosclerosis.

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.

Unraveling the risk factors for spontaneous intracerebral hemorrhage among West Africans.

OBJECTIVE: To characterize risk factors for spontaneous intracerebral hemorrhage (sICH) occurrence and severity among West Africans. METHODS: The Stroke Investigative Research and Educational Network (SIREN) study is a multicenter case-control study involving 15 sites in Ghana and Nigeria. Patients were adults ≥18 years old with CT-confirmed sICH with age-, sex-, and ethnicity-matched stroke-free community controls. Standard instruments were used to assess vascular, lifestyle, and psychosocial factors. Factors associated with sICH and its severity were assessed using conditional logistic regression to estimate odds ratios (ORs) and population-attributable risks (PARs) with 95% confidence intervals (CIs) for factors. RESULTS: Of 2,944 adjudicated stroke cases, 854 were intracerebral hemorrhage (ICH). Mean age of patients with ICH was 54.7 ± 13.9 years, with a male preponderance (63.1%), and 77.3% were nonlobar. Etiologic subtypes of sICH included hypertension (80.9%), structural vascular anomalies (4.0%), cerebral amyloid angiopathy (0.7%), systemic illnesses (0.5%), medication-related (0.4%), and undetermined (13.7%). Eight factors independently associated with sICH occurrence by decreasing order of PAR with their adjusted OR (95% CI) were hypertension, 66.63 (20.78-213.72); dyslipidemia, 2.95 (1.84-4.74); meat consumption, 1.55 (1.01-2.38); family history of CVD, 2.22 (1.41-3.50); nonconsumption of green vegetables, 3.61 (2.07-6.31); diabetes mellitus, 2.11 (1.29-3.46); stress, 1.68 (1.03-2.77); and current tobacco use, 14.27 (2.09-97.47). Factors associated with severe sICH using an NIH Stroke Scale score >15 with adjusted OR (95% CI) were nonconsumption of leafy green vegetables, 2.03 (1.43-2.88); systolic blood pressure for each mm Hg rise, 1.01 (1.00-1.01); presence of midline shift, 1.54 (1.11-2.13); lobar ICH, 1.72 (1.16-2.55); and supratentorial bleeds, 2.17 (1.06-4.46). CONCLUSIONS: Population-level control of the dominant factors will substantially mitigate the burden of sICH in West Africa.

Normal ultrasonographic dimensions of the gallbladder and common bile duct in neonates

Background: Ultrasound (US) is the first choice of imaging in neonates presenting with persistent jaundice to exclude surgically correctable causes and differentiate obstructive from nonobstructive causes. Previous studies on normal dimensions of gallbladder (GB) and common bile duct (CBD) recruited adults and children spread across a wide age group.Aims: This study aimed to determine GB and CBD normal dimensions in a large homogeneous neonatal population as well as guide decision regarding pre-US fasting in neonates who require GB evaluation.Materials and Methods: Five hundred and twenty-eight healthy newborns were recruited between May 2009 and May 2011. The widest intraluminal anterior-posterior diameters of GB and CBD were measured. Neonatal age in days, sex, birth weight, weight and height, gestational age at delivery, and time interval since last feed recorded.Results: The mean age was 9.56 ± 7.66 days, and 50.6% were males. The mean CBD diameter was 1.16 ± 1.61 mm while the mean GB diameter was 4.42 ± 2.16 mm. GB and CBD were clearly seen and measurable in 297 (55.8%) neonates and 237 (44.38%) neonates, respectively. There was a significant correlation between CBD diameter and GB diameter (P = 0.04) but no correlation with any demographic parameter. GB visualization was not dependent on time interval from last feed.Conclusion: Mean neonatal values for CBD and GB were established, but neonates have a wider range of GB diameters compared with older children, so GB diameter may not be a reliable parameter for neonatal GB pathologies. GB visualization was not dependent on time interval from last feed; hence, a recent feed should not delay emergency scans, especially in ill neonates

Public­private partnerships in Nigerian teaching hospitals: Potential and challenges

Background: Public­private partnership (PPP) has become a popular model used by public sector organizations that are usually under-funded by their respective governments to render services in fulfillment of their egalitarian responsibilities and goals. Lately, the health sector has been a recipient of such initiatives and the trend is growing. However, the successful delivery of services to patients is sometimes hampered because of difficulties encountered in both the development and interpretation of clauses contained in agreements including Memoranda of Understanding between the parties. The anticipated outcomes and impact often remain elusive due to the tensions encountered during implementation.Aim and Objective: The aim of this study was to determine the current operational status as well as explore potential benefits and challenges of the use of the PPP model in radiology departments of selected teaching hospitals within three South-Western States of Nigeria (Lagos, Ogun, and Oyo). It is hoped that the study findings would provide useful data needed for improvement of the PPP model as it is being currently practiced.Materials and Methods: This was a qualitative study in which 138 closed- and open-ended questionnaires were administered to all cadres of staff in radiology departments of the selected hospitals teaching hospitals within three South-Western States of Nigeria (Lagos, Ogun, and Oyo).Results: There was a 100% response from the participants. The age range of the participants was 25­65 years. Study findings showed that almost all radiological equipment can be acquired through PPP. There was improved service delivery and residency training with PPP. Jurisdictional conflict was the greatest challenge.Conclusion: PPP is a viable option that should be encouraged by government for the purchase of equipment in hospitals

Arsenicosis in bladder pathology and schistosomiasis in Eggua, Nigeria.

Background: Chronic schistosomiasis and arsenic exposure through drinking water are some of the risk factors for bladder cancer. To determine the association of schistosomiasis and arsenicosis with bladder pathologies, 122 individuals from Eggua in southwest Nigeria were recruited for this study. Methods: Prevalence of schistosomiasis was determined by urine microscopy and PCR. Total urinary arsenic concentration and arsenic levels in three different water sources in the community were assessed by flame atomic absorption spectrometry. Bladder pathologies were investigated by ultrasonography. The data collected were evaluated with chi-square (χ2) and ANOVA tests to examine the relationships among demographic factors, infection, bladder pathologies and urinary arsenic concentrations. Results: The prevalence and mean intensity of schistosomiasis were 21.3% and 20.7 eggs/10 mL urine, respectively. Arsenic concentration in two of the water sources, River Yewa (0.46 mg/L) and borehole (0.52 mg/L), were above the WHO standard (0.01 mg/L); and the mean concentration in urine samples, 1.17 mg/L, was also above the WHO standard (0.2 mg/L). There was no evidence of an association between bladder pathology and arsenicosis, or between schistosomiasis associated-bladder pathology and arsenicosis (p=0.66). Conclusions: Arsenicosis is a public health concern in the study population. At the moment no clear roles are envisaged for it in the development of bladder pathologies or urinary schistosomiasis-associated bladder pathologies in Eggua.

Metabolite profiling for biomarkers in Schistosoma haematobium infection and associated bladder pathologies.

BACKGROUND: Metabolic fingerprinting analysis can offer insights into underlying reactions in a biological system; hence it is crucial to the understanding of disease pathogenesis and could provide useful tools for discovering biomarkers. We sought to examine the urine and plasma metabolome in individuals affected by urogenital schistosomiasis and its associated-bladder pathologies. METHODOLOGY: Blood and midstream urine were obtained from volunteers who matched our inclusion criteria among residents from Eggua, southwestern Nigeria. Samples were screened by urinalysis, microscopy, PCR and ultrasonography, and categorised as advanced (urogenital schistosomiasis associated-bladder pathologies), infection-only (urogenital schistosomiasis alone) and controls (no infection and no pathology). Metabolites were extracted and data acquired with ultra high-performance liquid chromatography coupled with Thermo Q-Exactive orbitrap HRMS. Data was analysed with MetaboAnalyst, Workflow4Metabolomics, HMDB, LipidMaps and other bioinformatics tools, with univariate and multivariate statistics for metabolite selection. PRINCIPAL FINDINGS: There were low levels of host sex steroids, and high levels of several benzenoids, catechols and lipids (including ganglioside, phosphatidylcholine and phosphatidylethanolamine), in infection-only and advanced cases (FDR<0.05, VIP>2, delta>2.0). Metabolites involved in biochemical pathways related to chorismate production were abundant in controls, while those related to choline and sphingolipid metabolism were upregulated in advanced cases (FDR<0.05). Some of these human host and Schistosoma haematobium molecules, including catechol estrogens, were good markers to distinguish infection-only and advanced cases. CONCLUSIONS: Altered glycerophospholipid and sphingolipid metabolism could be key factors promoting the development of bladder pathologies and tumours during urogenital schistosomiasis.

Correction: The microbiome in urogenital schistosomiasis and induced bladder pathologies.

[This corrects the article DOI: 10.1371/journal.pntd.0005826.].

The microbiome in urogenital schistosomiasis and induced bladder pathologies.

BACKGROUND: Human schistosomiasis is a highly prevalent neglected tropical disease (NTD) caused by Schistosoma species. Research on the molecular mechanisms influencing the outcomes of bladder infection by Schistosoma haematobium is urgently needed to develop new diagnostics, therapeutics and infection prevention strategies. The objective of the research study was to determine the microbiome features and changes in urine during urogenital schistosomiasis and induced bladder pathologies. METHODOLOGY: Seventy participants from Eggua, southwestern Nigeria provided morning urine samples and were screened for urogenital schistosomiasis infection and bladder pathologies in a cross-sectional study. Highthroughput NGS sequencing was carried out, targeting the 16S V3 region. Filtered reads were processed and analyzed in a bioinformatics pipeline. PRINCIPAL FINDINGS: The study participants (36 males and 34 females, between ages 15 and 65) were categorized into four groups according to status of schistosomiasis infection and bladder pathology. Data analytics of the next-generation sequencing reads revealed that Proteobacteria and Firmicutes dominated and had influence on microbiome structure of both non-infected persons and persons with urogenital schistosomiasis. Furthermore, gender and age influenced taxa abundance independent of infection or bladder pathology. Several taxa distinguished urogenital schistosomiasis induced bladder pathologies from urogenital schistosomiasis infection alone and from healthy persons, including known immune-stimulatory taxa such as Fusobacterium, Sphingobacterium and Enterococcus. Some of these significant taxa, especially Sphingobacterium were projected as markers of infection, while several genera including potentially beneficial taxa such as Trabulsiella and Weissella, were markers of the non-infected. Finally, expected changes in protein functional categories were observed to relate to cellular maintenance and lipid metabolism. CONCLUSION: The urinary microbiome is a factor to be considered in developing biomarkers, diagnostic tools, and new treatment for urogenital schistosomiasis and induced bladder pathologies.

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.

Exploring Overlaps Between the Genomic and Environmental Determinants of LVH and Stroke: A Multicenter Study in West Africa.

BACKGROUND: Whether left ventricular hypertrophy (LVH) is determined by similar genomic and environmental risk factors with stroke, or is simply an intermediate stroke marker, is unknown. OBJECTIVES: We present a research plan and preliminary findings to explore the overlap in the genomic and environmental determinants of LVH and stroke among Africans participating in the SIREN (Stroke Investigative Research and Education Network) study. METHODS: SIREN is a transnational, multicenter study involving acute stroke patients and age-, ethnicity-, and sex-matched control subjects recruited from 9 sites in Ghana and Nigeria. Genomic and environmental risk factors and other relevant phenotypes for stroke and LVH are being collected and compared using standard techniques. RESULTS: This preliminary analysis included only 725 stroke patients (mean age 59.1 ± 13.2 years; 54.3% male). Fifty-five percent of the stroke subjects had LVH with greater proportion among women (51.6% vs. 48.4%; p < 0.001). Those with LVH were younger (57.9 ± 12.8 vs. 60.6 ± 13.4; p = 0.006) and had higher mean systolic and diastolic blood pressure (167.1/99.5 mm Hg vs 151.7/90.6 mm Hg; p < 0.001). Uncontrolled blood pressure at presentation was prevalent in subjects with LVH (76.2% vs. 57.7%; p < 0.001). Significant independent predictors of LVH were age <45 years (adjusted odds ratio [AOR]: 1.91; 95% confidence interval [CI]: 1.14 to 3.19), female sex (AOR: 2.01; 95% CI: 1.44 to 2.81), and diastolic blood pressure > 90 mm Hg (AOR: 2.10; 95% CI: 1.39 to 3.19; p < 0.001). CONCLUSIONS: The prevalence of LVH was high among stroke patients especially the younger ones, suggesting a genetic component to LVH. Hypertension was a major modifiable risk factor for stroke as well as LVH. It is envisaged that the SIREN project will elucidate polygenic overlap (if present) between LVH and stroke among Africans, thereby defining the role of LVH as a putative intermediate cardiovascular phenotype and therapeutic target to inform interventions to reduce stroke risk in populations of African ancestry.