Decentralized clinical trials for medications to reduce the risk of dementia: Consensus report and guidance.

INTRODUCTION: Recent growth in the functionality and use of technology has prompted an increased interest in the potential for remote or decentralized clinical trials in dementia. There are many potential benefits associated with decentralized medication trials, but we currently lack specific recommendations for their delivery in the dementia field. METHODS: A modified Delphi method engaged an expert panel to develop recommendations for the conduct of decentralized medication trials in dementia prevention. A working group of researchers and clinicians with expertise in dementia trials further refined the recommendations. RESULTS: Overall, the recommendations support the delivery of decentralized trials in dementia prevention provided adequate safety checks and balances are included. A total of 40 recommendations are presented, spanning aspects of decentralized clinical trials, including safety, dispensing, outcome assessment, and data collection. DISCUSSION: These recommendations provide an accessible, pragmatic guide for the design and conduct of remote medication trials for dementia prevention. HIGHLIGHTS: Clinical trials of medication have begun adopting decentralized approaches. Researchers in the field lack guidance on what would be appropriate circumstances and frameworks for what would be appropriate circumstances and frameworks for the use of decentralized trial methods in dementia prevention. The present report provides consensus-based expert recommendations for decentralized clinical trials for dementia prevention.

Extended genome-wide association study employing the African genome resources panel identifies novel susceptibility loci for Alzheimer's disease in individuals of African ancestry.

INTRODUCTION: Despite a two-fold risk, individuals of African ancestry have been underrepresented in Alzheimer's disease (AD) genomics efforts. METHODS: Genome-wide association studies (GWAS) of 2,903 AD cases and 6,265 controls of African ancestry. Within-dataset results were meta-analyzed, followed by functional genomics analyses. RESULTS: A novel AD-risk locus was identified in MPDZ on chromosome (chr) 9p23 (rs141610415, MAF = 0.002, P = 3.68×10-9). Two additional novel common and nine rare loci were identified with suggestive associations (P < 9×10-7). Comparison of association and linkage disequilibrium (LD) patterns between datasets with higher and lower degrees of African ancestry showed differential association patterns at chr12q23.2 (ASCL1), suggesting that this association is modulated by regional origin of local African ancestry. DISCUSSION: These analyses identified novel AD-associated loci in individuals of African ancestry and suggest that degree of African ancestry modulates some associations. Increased sample sets covering as much African genetic diversity as possible will be critical to identify additional loci and deconvolute local genetic ancestry effects. HIGHLIGHTS: Genetic ancestry significantly impacts risk of Alzheimer's Disease (AD). Although individuals of African ancestry are twice as likely to develop AD, they are vastly underrepresented in AD genomics studies. The Alzheimer's Disease Genetics Consortium has previously identified 16 common and rare genetic loci associated with AD in African American individuals. The current analyses significantly expand this effort by increasing the sample size and extending ancestral diversity by including populations from continental Africa. Single variant meta-analysis identified a novel genome-wide significant AD-risk locus in individuals of African ancestry at the MPDZ gene, and 11 additional novel loci with suggestive genome-wide significance at P < 9×10-7. Comparison of African American datasets with samples of higher degree of African ancestry demonstrated differing patterns of association and linkage disequilibrium at one of these loci, suggesting that degree and/or geographic origin of African ancestry modulates the effect at this locus. These findings illustrate the importance of increasing number and ancestral diversity of African ancestry samples in AD genomics studies to fully disentangle the genetic architecture underlying AD, and yield more effective ancestry-informed genetic screening tools and therapeutic interventions.

Towards improving stroke services in Africa: Results from the Africa-UK Stroke Partnership [AUKSP] surveys.

BACKGROUND: The African Stroke Organization (ASO) in partnership with the University of Central Lancashire's Stroke Research Team launched the Africa-UK Stroke Partnership (AUKSP). AUKSP undertook two (stroke expert and hospital Stroke Unit (SU)) on-line surveys mapping existing capacity and capability to deliver African stroke care. METHODS: An on-line expert survey tool was sent to 139 stroke experts in 54 African countries October 2021-March 2022 and the hospital SU survey to 120 hospital SUs (identified from the expert survey) June-October 2022. Both survey tools were prepared according to the World Stroke Organisation's Roadmap for Delivering Quality Stroke Care. Completed responses were exported from Qualtrics into Microsoft excel and were analysed descriptively. RESULTS: Forty-five expert responses and 62 hospital SU responses were analysed, representing 54(87%) public hospitals, 7(11%) private and 1(2%) charitable organization. In both surveys, three main priorities for improvement of stroke services were: a rapid and prompt stroke diagnosis; effective primary and secondary stroke prevention, and acute stroke management. Survey findings suggest that there is a low presence of national stroke surveillance systems and registries, and heterogeneity in availability of diagnostic services, SUs, endovascular treatments, and rehabilitation. CONCLUSION: Significant gaps exist in Africa's capacity and capability to deliver essential elements of effective and quality stroke care. Tackling these challenges requires urgent and sustained multi-stakeholder action including: government, administrators, policy makers and other partners. Our survey findings highlight key priority areas for multi-stakeholder engagement and crafting of a pragmatic, prioritized and context-sensitive African Stroke Action Plan.

Social domains of poor mental health: A qualitative pilot study of community stakeholders' understanding and demarcation of mental illness and its interpretations in rural Nigeria.

Background and Aims: Although previous studies on mental health/illness in Nigeria have explored knowledge and attitude of community members using quantitative approaches, few studies have engaged stakeholders within rural communities on the issue of mental illness using qualitative approaches. Community stakeholders play a critical role in influencing health behaviors. The objective of this pilot study was to explore community stakeholders' understanding and demarcation of mental illness, and its interpretations in a rural Nigerian town. This is with the aim of shaping stakeholders understanding of people when they experience mental distress within the community. Methods: The study was conducted in Ijebu-Igbo town of Ogun State in south-west Nigeria. In-depth interviews were conducted among two religious' leaders: a Pastor and an Imam, a traditional healer, a medical doctor, and a registered nurse, and a focus group discussion was held in a church with members of its advisory committee. Results: The findings showed that community stakeholders gave multiple interpretations of mental illness and many attribute mental illness to spiritual attack, ancestral curse, anger of the gods, and personal affliction (Ogun-Afowofa). This has been categorized as familial and individual attributes in this study which is part of the main themes derived. The study findings also show that the understanding of community members regarding the root causes of mental illness is somewhat vague based on their poor knowledge of mental illness. This is because of the various interpretations they gave to explain mental health is based on their cultural orientation, socialization, and belief system, and not based on any medical knowledge. Conclusion: This pilot study was conducted to justify the main study. There is therefore a need for health education interventions to enlighten and educate community stakeholders with requisite knowledge for better understanding and interpretation of mental illness. Also, through mental health education interventions, community members will gain clarity on what mental health is and what it is not.

Implementing genetic testing in diabetes: Knowledge, perceptions of healthcare professionals, and barriers in a developing country.

INTRODUCTION: Maturity-Onset Diabetes of the Young (MODY) is an unusual type of diabetes often missed in clinical practice, especially in Africa. Treatment decisions for MODY depend on a precise diagnosis, only made by genetic testing. We aimed to determine MODY knowledge among Nigerian healthcare professionals (HCPs), their perceptions, and barriers to the implementation of genetic testing in diabetes patients. METHODS: A cross-sectional survey was conducted among doctors and nurses in three levels of public and private healthcare institutions in Ibadan, Nigeria, from December 2018 to June 2019. In all, 70% and 30% of a total 415 participants were recruited from public and private centers, respectively. HCPs were recruited in a 60:40% ratio, respectively. A 51-item instrument was used to assess MODY knowledge, perceptions of HCPs, and barriers to the implementation of genetic testing in diabetes patients. RESULTS: In the survey, 43.4% self-rated their current MODY knowledge to be at least moderate. About 68%, 73% and 86%, respectively, correctly answered 3 of 5 questions on basic genetics' knowledge. However, only 1 of 7 MODY-specific questions was answered correctly by 72.7% of the respondents. The mean basic genetics and MODY-specific knowledge scores were 2.6/5 (SD=1.0) and 1.8/9 (SD=1.3), respectively. Multiple linear regression showed higher mean scores among those aged 30-49 years, those with degrees and fellowships (except PhD), and general practitioners; 360 (80.0%) perceived that genetic testing plays a central role in diabetes care. Barriers to genetic testing were lack of access to testing facilities, guidance on the use of and updates/educational materials on genetic testing (82.7%, 62.1% and 50.3%, respectively). CONCLUSIONS: The level of MODY awareness and knowledge among Nigerian HCPs is unacceptably low with a lack of access to genetic testing facilities. These can hinder the implementation of precision diabetes medicine. Increased awareness, provision of decision support aids, and genetic testing facilities are urgently needed.

Prevalence and Patterns of Seizure-related Injuries: A Study of People Living with Epilepsy Found in a Community-based Door-to-door Survey in Southeast Nigeria.

CONTEXT: Epileptic seizures and the unpredictable falls resulting from epileptic seizures predispose the people living with epilepsy (PLWE) to various physical injuries as well as postictal cognitive and behavioral changes. AIMS: The aim of the study was to determine the frequency and patterns of seizure-related physical injuries, postictal cognitive impairments, and behavioral changes. SETTINGS AND DESIGN: This was a cross-sectional descriptive study in a Southeast Nigeria local government area. SUBJECTS AND METHODS: PLWE identified during a two-phase door-to-door survey and their caregivers were interviewed using a semi-structured questionnaire. STATISTICAL ANALYSIS USED: The Statistical Package for the Social Sciences version 22.0 was used. RESULTS: There were 56 cases of active convulsive seizures comprising 33 (58.9%) males and 23 (41.1%) females, with a mean age of 32.9 ± 14.2. The lifetime prevalence of seizure-related physical injuries, postictal behavioral changes, and postictal cognitive impairments was 9.8 per 1000 (95% confidence interval [CI]: 9.1-10.0), 8.4 per 1000 (95% CI: 7.2-9.2), and 6.3 per 1000 (95% CI: 4.9-7.5), respectively. Skin/soft-tissue injuries and tongue laceration were the most frequent physical injuries found in 66.1% (n = 37/56) and 60.7% (n = 34/56) of cases, respectively. The frequency of soft-tissue injuries was significantly higher (χ2 = 5.038; P = 0.0248) in the females 78.3% (n = 18/23) than the males 48.5% (n = 16/33). About a third of the females 39.1% had burn injuries compared to 18.1% of the males. CONCLUSIONS: Seizure-related injuries are common and have the tendency to increase the burden of epilepsy and epilepsy-related stigma from deformities and the chronic disfiguring scars resulting from such injuries.

Résumé Contexte:Les crises d'épilepsie et les chutes imprévisibles résultant des crises d'épilepsie prédisposent les personnes vivant avec l'épilepsie (PLWE) à diverses blessures physiques ainsi que des changements cognitifs et comportementaux post-critiquesObjectifs:Le but de l'étude était de déterminer la fréquence et les caractéristiques des blessures physiques liées aux crises, des déficiences cognitives post-critiques et des changements de comportement. Paramètres et conception: il s'agissait d'une étude descriptive transversale dans une zone de gouvernement local du sud-est du Nigeria. Sujets et méthodes: PLWE identifiées lors d'une enquête porte-à-porte en deux phases et leurs soignants ont été interrogés à l'aide d'un questionnaire semi-structuré. Analyse statistique utilisée: Le progiciel statistique pour les sciences sociales version 22.0 a été utiliséRésultats:Il y a eu 56 cas de crises convulsives actives comprenant 33 (58,9 %) hommes et 23 (41,1 %) femmes, avec un âge moyen de 32,9 ± 14,2 ans. La prévalence au cours de la vie des blessures physiques, des changements de comportement post-critiques et des troubles cognitifs post-critiques liés aux crises était de 9,8 pour 1 000 (95 % intervalle de confiance [IC]: 9,1 à 10,0), 8,4 pour 1 000 (IC à 95 %: 7,2 à 9,2) et 6,3 pour 1 000 (IC à 95 %: 4,9 à 7,5), respectivement. Blessures de la peau/des tissus mous et les lacérations de la langue étaient les blessures physiques les plus fréquentes trouvées dans 66,1 % (n = 37/56) et 60,7 % (n = 34/56) des cas, respectivement. La fréquence de les blessures des tissus mous étaient significativement plus élevées (χ2 = 5,038; P = 0,0248) chez les femmes 78,3 % (n = 18/23) que chez les hommes 48,5 % (n = 16/33). Environ un tiers Parmi les femmes, 39,1 % avaient des brûlures, contre 18,1 % des hommesConclusions:Les blessures liées aux convulsions sont fréquentes et ont tendance à accroître le fardeau de l'épilepsie et de la stigmatisation liée à l'épilepsie due aux malformations et aux cicatrices défigurantes chroniques résultant de telles blessures.

Variations in the prevalence of atrial fibrillation, and in the strength of its association with ischemic stroke, in countries with different income levels: INTERSTROKE case-control study.

BACKGROUND: The contribution of atrial fibrillation (AF) to the etiology and burden of stroke may vary by country income level. AIMS: We examined differences in the prevalence of AF and described variations in the magnitude of the association between AF and ischemic stroke by country income level. METHODS: In the INTERSTROKE case-control study, participants with acute first ischemic stroke were recruited across 32 countries. We included 10,363 ischemic stroke cases and 10,333 community or hospital controls who were matched for age, sex, and center. Participants were grouped into high-income (HIC), upper-middle-income (subdivided into two groups-UMIC-1 and UMIC-2), and lower-middle-income (LMIC) countries, based on gross national income. We evaluated the risk factors for AF overall and by country income level, and evaluated the association of AF with ischemic stroke. RESULTS: AF was documented in 11.9% (n = 1235) of cases and 3.2% (n = 328) of controls. Compared to HIC, the prevalence of AF was significantly lower in UMIC-2 (aOR 0.35, 95% CI 0.29-0.41) and LMIC (aOR 0.50, 95% CI 0.41-0.60) on multivariable analysis. Hypertension, female sex, valvular heart disease, and alcohol intake were stronger risk factors for AF in lower-income countries, and obesity a stronger risk factor in higher-income countries. The magnitude of association between AF and ischemic stroke was significantly higher in lower-income countries compared to higher-income countries. The population attributable fraction for AF and stroke varied by region and was 15.7% (95% CI 13.7-17.8) in HIC, 14.6% (95% CI 12.3-17.1) in UMIC-1, 5.7% (95% CI 4.9-6.7) in UMIC-2, and 6.3% (95% CI 5.3-7.3) in LMIC. CONCLUSION: Risk factors for AF vary by country income level. AF contributes to stroke burden to a greater extent in higher-income countries than in lower-income countries, due to a higher prevalence and despite a lower magnitude of odds ratio.

Population normative data for three cognitive screening tools for older adults in sub-Saharan Africa / Dados normativos populacionais para três instrumentos de triagem cognitiva para idosos na áfrica subsaariana

ABSTRACT In sub-Saharan Africa (SSA),cognitive screening is complicated by both cultural and educational factors, and the existing normative values may not be applicable. The Identification of Dementia in Elderly Africans (IDEA) cognitive screen is a low-literacy measure with good diagnostic accuracy for dementia. Objective: The aim of this study is to report normative values for IDEA and other simple measures [i.e., categorical verbal fluency, the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) 10-word list] in representative community-dwelling older adults in SSA. Methods: Individuals aged ≥60 years resident in 12 representative villages in Kilimanjaro, Tanzania and individuals aged ≥65 years resident within three communities in Akinyele Local Government Area, Oyo State, Nigeria underwent cognitive screening. The normative data were generated by the categories of age, sex, and education. Results: A total of 3,011 people in Tanzania (i.e., 57.3% females and 26.4% uneducated) and 1,117 in Nigeria (i.e., 60.3% females and 64.5% uneducated) were screened. Individuals with higher age, lower education, and female gender obtained lower scores. The 50th decile values for IDEA were 13 (60-64 years) vs. 8/9 (above 85 years), 10-11 uneducated vs. 13 primary educated, and 11/12 in females vs. 13 in males. The normative values for 10-word list delayed recall and categorical verbal fluency varied with education [i.e., delayed recall mean 2.8 [standard deviation (SD) 1.7] uneducated vs. 4.2 (SD 1.2) secondary educated; verbal fluency mean 9.2 (SD 4.8) uneducated vs. 12.2 (SD 4.3) secondary educated], substantially lower than published high-income country values. Conclusions: The cut-off values for commonly used cognitive screening items should be adjusted to suit local normative values, particularly where there are lower levels of education.

RESUMO Na África Subsaariana (ASS), a triagem cognitiva é complicada por fatores culturais e educacionais, além dos valores normativos existentes poderem não ser aplicáveis. O rastreio cognitivo Identification of Dementia in Elderly Africans (IDEA) é uma medida para níveis baixos de alfabetização com boa acurácia diagnóstica para demência. Objetivo: Relatar os valores normativos para a IDEA e outras medidas simples (fluência verbal categórica, a lista de 10 palavras do Consortium to Establish a Registry for Alzheimer's Disease (CERAD) em idosos residentes na comunidade, representativos da ASS. Métodos: Indivíduos com idade ≥60 residentes em 12 comunidades representativas em Kilimanjaro, Tanzânia e indivíduos com idade ≥65 anos residentes em três comunidades na área governamental de Akinyele, Estado de Oyo, Nigéria, foram submetidos à triagem cognitiva. Os dados normativos foram gerados por faixas etárias, sexo e escolaridade. Resultados: Um total de 3.011 pessoas na Tanzânia (57,3% mulheres, 26,4% sem educação) e 1.117 na Nigéria (60,3% mulheres, 64,5% sem educação) foram examinadas. Os indivíduos com idade mais alta, menor escolaridade e mulheres obtiveram escores mais baixos. Os valores do percentil 50 para a IDEA foram 13 (60-64 anos) vs. 8/9 (85+ anos), 10-11 para analfabetos vs. 13 com educação primária e 11/12 em mulheres vs. 13 em homens. Os valores normativos para a evocação tardia da lista de 10 palavras e a fluência verbal categórica variaram com a educação (evocação tardia 2,8 (SD 1,7) para os sem educação, vs. 4,2 (SD 1,2) para com educação secundária; fluência verbal 9,2 (DP 4,8) para os sem educação vs. 12,2 (SD 4.3) para os com ensino médio, substancialmente inferior aos valores publicados em países de alta renda. Conclusões: Os valores de corte para testes de triagem cognitiva comumente usados devem ser ajustados para se adequar aos valores normativos locais, particularmente em níveis baixos de educação.