Targeted next-generation sequencing identifies novel variants in candidate genes for Parkinson's disease in Black South African and Nigerian patients.

BACKGROUND: The prevalence of Parkinson's disease (PD) is increasing in sub-Saharan Africa, but little is known about the genetics of PD in these populations. Due to their unique ancestry and diversity, sub-Saharan African populations have the potential to reveal novel insights into the pathobiology of PD. In this study, we aimed to characterise the genetic variation in known and novel PD genes in a group of Black South African and Nigerian patients. METHODS: We recruited 33 Black South African and 14 Nigerian PD patients, and screened them for sequence variants in 751 genes using an Ion AmpliSeq™ Neurological Research panel. We used bcftools to filter variants and annovar software for the annotation. Rare variants were prioritised using MetaLR and MetaSVM prediction scores. The effect of a variant on ATP13A2's protein structure was investigated by molecular modelling. RESULTS: We identified 14,655 rare variants with a minor allele frequency ≤ 0.01, which included 2448 missense variants. Notably, no common pathogenic mutations were identified in these patients. Also, none of the known PD-associated mutations were found highlighting the need for more studies in African populations. Altogether, 54 rare variants in 42 genes were considered deleterious and were prioritized, based on MetaLR and MetaSVM scores, for follow-up studies. Protein modelling showed that the S1004R variant in ATP13A2 possibly alters the conformation of the protein. CONCLUSIONS: We identified several rare variants predicted to be deleterious in sub-Saharan Africa PD patients; however, further studies are required to determine the biological effects of these variants and their possible role in PD. Studies such as these are important to elucidate the genetic aetiology of this disorder in patients of African ancestry.

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.

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.

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.

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.

The social and economic impacts of epilepsy on women in Nigeria.

BACKGROUND: Persons with epilepsy in sub-Saharan Africa experience stigma and social marginalization. There is paucity of data on the social and economic impacts of epilepsy in these patients and in particular, groups like women. We sought to determine the social and economic impacts of epilepsy on Nigerian women and especially how it affects their treatment and outcomes. METHODS: We carried out a cross-sectional survey of 63 women with epilepsy (WWE) and 69 controls matched for age, social status and site of care. A structured questionnaire was used to document information on demographic characteristics, education, employment status, economic status, health care use, personal safety and perceived stigma. The data were collated and analyzed with SPSS version 15. RESULTS: Unemployment, fewer years of formal education, lower marriage rates and higher stigma scores were more frequent among WWE than controls. Physical and sexual abuse with transactional sex was also reported among WWE. We also noted poorer environmental and housing conditions and lower mean personal and household incomes among WWE compared to the control group. CONCLUSION: WWE in this sample from Nigeria have worse social and economic status when compared with women with other non-stigmatized chronic medical conditions.

Addressing antimicrobial resistance in Nigerian hospitals: exploring physicians prescribing behavior, knowledge, and perception of antimicrobial resistance and stewardship programs.

INTRODUCTION: We assessed the knowledge of, attitude toward antimicrobial resistance (AMR) and practice of antimicrobial stewardship (AMS) among physicians in Nigeria to provide future guidance to the Nigerian National Action Plan for AMR. METHODS: A descriptive cross-sectional questionnaire-based study explored the physicians' self-reported practice of antibiotic prescribing, knowledge, attitude, and practice of AMR and components of ASPs. RESULTS: The majority (217; 67.2%) of respondents prescribed antibiotics daily in their clinical practice AMR was recognized as a global and local problem by 308 (95.4%) and 262 (81.1%) respondents, respectively. Only 91 (28.2%) of respondents have ever heard of antibiotic stewardship. The median AMR knowledge score was 40 (19-45)out of 45while that for ASP was 46.0(32-57) out of 60. There was significant statistical difference between the ASP median scores among the medical specialties category (P value <0.0001) More respondents had good knowledge of AMR than ASPs (82.7% versus 36.5%; p < 0.0001). CONCLUSION: Respondents in this study were more knowledgeable about AMR than AMS and its core components.

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

OBJECTIVE: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. METHODS: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. RESULTS: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. CONCLUSIONS: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.

Knowledge, attitudes and practices of West Africans on genetic studies of stroke: Evidence from the SIREN Study.

BACKGROUND: It is crucial to assess genomic literacy related to stroke among Africans in preparation for the ethical, legal and societal implications of the genetic revolution which has begun in Africa. OBJECTIVE: To assess the knowledge, attitudes and practices (KAP) of West Africans about stroke genetic studies. METHODS: A comparative cross-sectional study was conducted among stroke patients and stroke-free controls recruited across 15 sites in Ghana and Nigeria. Participants' knowledge of heritability of stroke, willingness to undergo genetic testing and perception of the potential benefits of stroke genetic research were assessed using interviewer-administered questionnaire. Descriptive, frequency distribution and multiple regression analyses were performed. RESULTS: Only 49% of 2029 stroke patients and 57% of 2603 stroke-free individuals knew that stroke was a heritable disorder. Among those who knew, 90% were willing to undergo genetic testing. Knowledge of stroke heritability was associated with having at least post-secondary education (OR 1.51, 1.25-1.81) and a family history of stroke (OR 1.20, 1.03-1.39) while Islamic religion (OR=0.82, CI: 0.72-0.94), being currently unmarried (OR = 0.81, CI: 0.70-0.92), and alcohol use (OR = 0.78, CI: 0.67-0.91) were associated with lower odds of awareness of stroke as a heritable disorder. Willingness to undergo genetic testing for stroke was associated with having a family history of stroke (OR 1.34, 1.03-1.74) but inversely associated with a medical history of high blood pressure (OR = 0.79, 0.65-0.96). CONCLUSION: To further improve knowledge of stroke heritability and willingness to embrace genetic testing for stroke, individuals with less formal education, history of high blood pressure and no family history of stroke require targeted interventions.

Medication adherence and adverse effect profile of antiepileptic drugs in Nigerian patients with epilepsy.

AIM: Medication adherence remains a major challenge among patients with epilepsy (PWE) with the adverse effect profile of antiepileptic drugs (AEDs) as one of its main drivers. METHODS: This was a cross-sectional questionnaire-based study among PWE in selected Nigerian tertiary healthcare facilities using the Morisky Medication Adherence Scale and the Liverpool Adverse Effect Profile (LAEP). RESULTS: 126 PWE from four tertiary healthcare facilities were included in this study comprising of 59 (46.8%) males and 67 (53.2%) females. Carbamazepine (104/70.7%), sodium valproate (23/15.6%) and phenytoin (11/7.5%) were the most commonly prescribed AEDs. Using the Morisky Medication Adherence Scale, 17.2, 38.3 and 44.5% of patients were classified as having high, medium and low adherence, respectively. The mean LAEP score was 23.69 ± 6.07. The most common reported adverse effects among respondents were tiredness (30.4%) and headache (22.5%). CONCLUSION: Medication adherence to AED was poor among patients in this study.

Drug promotional activities in Nigeria: impact on the prescribing patterns and practices of medical practitioners and the implications.

OBJECTIVE: Pharmaceutical companies spend significant amount of resources on promotion influencing the prescribing behavior of physicians. Drug promotion can negatively impact on rational prescribing, which may adversely affect the quality of patient care. However, little is known about these activities in Nigeria as the most populous country in Africa. We therefore aimed to explore the nature of encounters between Nigerian physicians and pharmaceutical sales representatives (PSRs), and how these encounters influence prescribing habits. METHODS: Cross-sectional questionnaire-based study conducted among practicing physicians working in tertiary hospitals in four regions of Nigeria. RESULTS: 176 questionnaires were completed. 154 respondents (87.5%) had medicines promoted to them in the previous three months, with most encounters taking place in outpatients' clinics (60.2%), clinical meetings (46%) and new medicine launches (17.6%). Information about potential adverse effects and drug interactions was provided in 41.5%, and 27.3% of cases, respectively. Food, in the form of lunch or dinner, was the most common form of incentive (70.5%) given to physicians during promotional activities. 61% of physicians felt motivated to prescribe the drug promoted to them, with the quality of information provided being the driving factor. Most physicians (64.8%) would agree to some form of regulation of the relationship between medical doctors and the pharmaceutical industry. CONCLUSION: Interaction between PSRs and physicians is a regular occurrence in Nigeria, influencing prescribing practices. Meals and cheap gifts were the most common items offered to physicians during their encounters with PSRs. The need for some form of regulation by professional organizations and the government was expressed by most respondents to address current concerns.

Knowledge, attitudes and practices related to stroke in Ghana and Nigeria: A SIREN call to action.

INTRODUCTION: Stroke is a prominent cause of death, disability, and dementia in sub-Saharan Africa (SSA). The Stroke Investigative Research and Education Network works collaboratively with stroke survivors and individuals serving as community controls to comprehensively characterize the genomic, sociocultural, economic and behavioral risk factors for stroke in SSA. PURPOSE: In this paper, we aim to: i) explore the attitudes, beliefs, and practices related to stroke in Ghana and Nigeria using the process of qualitative description; and ii) propose actions for future research and community-based participation and education. METHODS: Stroke survivors, their caregivers, health care professionals, and community representatives and faith-based leaders participated in one of twenty-six focus groups, which qualitatively explored community beliefs, attitudes and practices related to stroke in Ghana and Nigeria. Arthur Kleinman's Explanatory Model of Illness and the Social Ecological Model guided the questions and/or thematic analysis of the qualitative data. We hereby describe our focus group methods and analyses of qualitative data, as well as the findings and suggestions for improving stroke outcomes. RESULTS AND DISCUSSION: The major findings illustrate the fears, causes, chief problems, treatment, and recommendations related to stroke through the views of the participants, as well as recommendations for working effectively with the SIREN communities. Findings are compared to SIREN quantitative data and other qualitative studies in Africa. As far as we are aware, this is the first paper to qualitatively explore and contrast community beliefs, attitudes, and practices among stroke survivors and their caregivers, community and faith-based leaders, and health professionals in multiple communities within Nigeria and Ghana.

Biobanking in a Challenging African Environment: Unique Experience from the SIREN Project.

Africa was previously insufficiently represented in the emerging discipline of biobanking despite commendable early efforts. However, with the Human, Heredity, and Health in Africa (H3Africa) initiative, biorepository science has been bolstered, regional biobanks are springing up, and awareness about biobanks is growing on the continent. The Stroke Investigative Research and Educational Network (SIREN) project is a transnational, multicenter, hospital and community-based study involving over 3000 cases and 3000 controls recruited from 16 sites in Ghana and Nigeria. SIREN aims to explore and unravel the genetic and environmental factors that interact to produce the peculiar phenotypic and clinical characteristics of stroke as seen in people of African ancestry and facilitate the development of new diagnostics, therapeutics, and preventative strategies. The aim of this article is to describe our experience with the development of the procedure for collection, processing, storage, and shipment of biological samples (blood, serum, plasma, buffy coat, red cell concentrates, and DNA) and brain imaging across coordinating and participating sites within the SIREN Project. The SIREN network was initiated in 2014 with support and funding from the H3Africa Initiative. The SIREN Biobank currently has 3015 brain images, 92,950 blood fractions (serum, plasma, red cell concentrates, and buffy coat) accrued from 8450 recruited subjects, and quantified and aliquoted good-quality DNA extracts from 6150 study subjects. This represents an invaluable resource for future research with expanding genomic and trans-omic technologies. This will facilitate the involvement of indigenous African samples in cutting-edge stroke genomics and trans-omics research. It is, however, critical to effectively engage African stroke patients and community members who have contributed precious biological materials to the SIREN Biobank to generate appropriate evidence base for dealing with ethical, legal, and social issues of privacy, autonomy, identifiability, biorights, governance issues, and public understanding of stroke biobanking in the context of unique African culture, language, and belief systems.

Interleukin-6 (IL-6) rs1800796 and cyclin dependent kinase inhibitor (CDKN2A/CDKN2B) rs2383207 are associated with ischemic stroke in indigenous West African Men.

BACKGROUND: Inherited genetic variations offer a possible explanation for the observed peculiarities of stroke in sub - Saharan African populations. Interleukin-6 polymorphisms have been previously associated with ischemic stroke in some non-African populations. AIM: Herein we investigated, for the first time, the association of genetic polymorphisms of IL-6, CDKN2A- CDKN2B and other genes with ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study. METHODS: Twenty-three previously identified single nucleotide polymorphisms (SNPs) in 14 genes of relevance to the neurobiology of ischemic stroke were investigated. Logistic regression models adjusting for known cardiovascular disease risk factors were constructed to assess the associations of the 23 SNPs in rigorously phenotyped cases (N=429) of ischemic stroke (Men=198; Women=231) and stroke- free (N=483) controls (Men=236; Women=247). RESULTS: Interleukin-6 (IL6) rs1800796 (C minor allele; frequency: West Africans=8.6%) was significantly associated with ischemic stroke in men (OR=2.006, 95% CI=[1.065, 3.777], p=0.031) with hypertension in the model but not in women. In addition, rs2383207 in CDKN2A/CDKN2B (minor allele A with frequency: West Africans=1.7%) was also associated with ischemic stroke in men (OR=2.550, 95% CI=[1.027, 6.331], p=0.044) with primary covariates in the model, but not in women. Polymorphisms in other genes did not show significant association with ischemic stroke. CONCLUSION: Polymorphisms rs1800796 in IL6 gene and rs2383207 in CDKN2A/CDKN2B gene have significant associations with ischemic stroke in indigenous West African men. CDKN2A/CDKN2B SNP rs2383207 is independently associated with ischemic stroke in indigenous West African men. Further research should focus on the contributions of inflammatory genes and other genetic polymorphisms, as well as the influence of sex on the neurobiology of stroke in people of African ancestry.

Prevalence and Prognostic Features of ECG Abnormalities in Acute Stroke: Findings From the SIREN Study Among Africans.

BACKGROUND: Africa has a growing burden of stroke with associated high morbidity and a 3-year fatality rate of 84%. Cardiac disease contributes to stroke occurrence and outcomes, but the precise relationship of abnormalities as noted on a cheap and widely available test, the electrocardiogram (ECG), and acute stroke outcomes have not been previously characterized in Africans. OBJECTIVES: The study assessed the prevalence and prognoses of various ECG abnormalities among African acute stroke patients encountered in a multisite, cross-national epidemiologic study. METHODS: We included 890 patients from Nigeria and Ghana with acute stroke who had 12-lead ECG recording within first 24 h of admission and stroke classified based on brain computed tomography scan or magnetic resonance imaging. Stroke severity at baseline was assessed using the Stroke Levity Scale (SLS), whereas 1-month outcome was assessed using the modified Rankin Scale (mRS). RESULTS: Patients' mean age was 58.4 ± 13.4 years, 490 were men (55%) and 400 were women (45%), 65.5% had ischemic stroke, and 85.4% had at least 1 ECG abnormality. Women were significantly more likely to have atrial fibrillation, or left ventricular hypertrophy with or without strain pattern. Compared to ischemic stroke patients, hemorrhagic stroke patients were less likely to have atrial fibrillation (1.0% vs. 6.7%; p = 0.002), but more likely to have left ventricular hypertrophy (64.4% vs. 51.4%; p = 0.004). Odds of severe disability or death at 1 month were higher with severe stroke (AOR: 2.25; 95% confidence interval: 1.44 to 3.50), or atrial enlargement (AOR: 1.45; 95% confidence interval: 1.04 to 2.02). CONCLUSIONS: About 4 in 5 acute stroke patients in this African cohort had evidence of a baseline ECG abnormality, but presence of any atrial enlargement was the only independent ECG predictor of death or disability.

The prescribing of generic medicines in Nigeria: knowledge, perceptions and attitudes of physicians.

Generic medicines have the same efficacy and safety as originators at lower prices; however, there are concerns with their utilization in Nigeria. Objective was to evaluate physicians' understanding and perception of generics. A questionnaire was administered among physicians working in tertiary healthcare facilities in four geo-political regions of Nigeria. Questionnaire response was 74.3% (191/257) among mainly males (85.9%). The mean knowledge score regarding generics was 5.3 (maximum of 9) with 36.6%, 36.1% and 27.2% having poor, average and good knowledge respectively. Cross-tabulation showed statistical significance (p = 0.047) with the duration of practice but not with position, subspecialty or sex. The majority of respondents did not believe that generic medicines are of lower quality than branded medicines. Therapeutic failure was a major concern in 82.7%, potentially discouraging the prescribing of generics, and a majority (63.9%) did not support generic substitution by pharmacists. Knowledge gaps were identified especially with the perception of generics, which need to be addressed.

Cognitive function in patients with newly diagnosed HIV infection in a tertiary health facility in south - west Nigeria: Assessment using computer-assisted neuropsychological test battery.

INTRODUCTION: Cognitive dysfunction is common among patients with human immunodeficiency virus (HIV) infection however there are few reports from sub-Saharan Africa. METHODS: We studied fifty seropositive patients with human immunodeficiency virus (HIV) infection along with fifty matched seronegative control. Medical history taking and general physical and neurological examinations were done for all study participants. Laboratory evaluations and chest X-ray were done for all the patients. The cognitive function was done with the aid of 'Fepsy' automated test battery for all the study participants. The data was analyzed with statistical package for social sciences software version 21.0 (SPSS Chicago IL). RESULT: About 70% of the HIV patients were in advanced disease stage. The auditory and visual reaction times, binary choice reaction times, and computerized visual scanning task time were more prolonged in the HIV group (p < 0.05). There were also increased memory accuracy and binary choice task accuracy in the HIV group (p < 0.05). However the vigilance task performance was similar between the two groups (p > 0.05). Among the patients with HIV infection, the presence of anemia and central nervous system toxoplasmosis infection was associated with prolonged auditory and visual reaction times. CONCLUSION: There was a high rate of cognitive dysfunction in patients with HIV infection in this study.

Intellectual Impairment in Patients with Newly Diagnosed HIV Infection in Southwestern Nigeria.

Neurocognitive impairment is a detrimental complication of HIV infection. Here, we characterized the intellectual performance of patients with newly diagnosed HIV infection in southwestern Nigeria. We conducted a prospective study at Owo Federal Medical Center by using the adapted Wechsler Adult Intelligence Scale (WAIS). The raw scores were converted to standardized scores (z-scores) and correlated with clinical and laboratory findings. Fifty-eight HIV positive patients were recruited; 72% were in WHO stages 3 and 4. We detected a high rate of intellectual impairment in HIV positive patients and controls (63.8% and 10%, resp.; P < 0.001). HIV positive patients performed worse throughout the subtests of both verbal and performance intelligence quotients. Presence of opportunistic infections was associated with worse performance in the similarities and digit symbol tests and performance and full scale scores. Lower body weight correlated with poor performance in different WAIS subtests. The high rate of advanced disease stage warrants measures aimed at earlier diagnosis and treatment. Assessment of neurocognitive performance at diagnosis may offer the opportunity to improve functioning in daily life and counteract disease progression.

Sleep disturbances among patients with epilepsy in Nigeria.

BACKGROUND: There is a complex inter-relationship between sleep disorders and epilepsy, and there are few studies in Nigeria on sleep disorders in epilepsy. This study was carried out to determine the prevalence, pattern and predictors of sleep disturbances among persons with epilepsy (PWE). MATERIALS AND METHODS: This was a multi-center, cross-sectional study of 124 PWE in Nigeria. A questionnaire was used to collect data on social and demographic variables, epilepsy- related variables and sleep disturbances in PWE. Exclusion criteria were mental retardation, and use of sedative drugs. The data was analyzed using Statistical Package for Social Sciences version 11.0 and P < 0.05 was considered as significant. RESULTS: There were 77 males and 47 females with a mean age of 33.4 ± 13.1 years. The mean age of seizure onset was 23.7 ± 14.6 years, while the mean duration of epilepsy was 9.5 ± 9.4 years. The commonest type of epilepsy was secondarily generalized tonic-clonic seizures (62%). The prevalence of sleep disorders in PWE was 82%. Parasomnias occurred in 46%, followed by obstructive sleep apnea in 23%, insomnia (19%) excessive daytime sleepiness (EDS) (17%), and restless leg syndrome (11%). None of the socio-demographic or epilepsy- related variables was predictive of EDS or parasomnias in PWE (P > 0.05). CONCLUSION: There is a high frequency of sleep disorders among PWE. Clinicians should screen PWE for sleep disturbances.

Cognitive functions in patients with liver cirrhosis: assessment using community screening interview for dementia.

INTRODUCTION: Neurocognitive dysfunction is common in patients with liver cirrhosis who have no evidence of overt hepatic encephalopathy and is usually associated with impairment of activities of daily living in the patients. MATERIALS AND METHODS: Forty patients with liver cirrhosis without overt hepatic encephalopathy were studied along with forty-one healthy controls. Blood samples were taken from the patients for liver function tests and Hepatitis B and C screening. Liver disease severity was graded using the Child-Pugh scoring system. Community Screening Interview for the Dementia (CSID) questionnaire was administered to all subjects. The CSID questionnaire assesses the cognitive functions of the subjects in the domains of language, memory, orientation, attention/calculation, and praxis. The data were collated and analyzed with the aid of SPSS 15.0 software for frequency, means, and comparison of means using Student's t-test and one-way ANOVA. Significant level was put at P< 0.05. RESULTS: The mean age ± SD of the patients was 46.15 ± 15.31 years and the controls was 45.66 ± 11.54 years. There were 30 males and 10 females in the patients group while the control had has 26 males and 15 females. Majority of the patients had secondary level of education. Nine out of 40 patients (23%) had abnormally low total CSID score. The patients with liver cirrhosis performed poorly in the domains of language, memory, attention/calculation, and praxis. There was no difference in the orientation scores between the patients and the normal controls. The type of Hepatitis virus infection, serum liver enzyme, serum albumin, serum bilirubin, prothrombin time and Child Pugh class of the patients did not influence cognitive performance in the patients. CONCLUSION: Patients with liver cirrhosis have significant cognitive impairment compared with controls and liver function tests/ clinical parameters in the patients did not correlate with their cognitive functions.