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BACKGROUND: Lassa fever is endemic in large parts of West Africa. The recommended antiviral treatment is ribavirin. Two treatment regimens are currently endorsed in Nigeria: the "McCormick regimen" based on a study published in 1986 and the "Irrua regimen" constituting a simplified schedule developed at the Irrua Specialist Teaching Hospital, Nigeria. Evidence for the safety and efficacy of ribavirin in Lassa fever patients is poor and pharmacokinetic data for both regimens are lacking. METHODS: Polymerase chain reaction-confirmed Lassa fever patients with mild to moderate disease severity were invited to participate in this prospective, observational pharmacokinetic study. Pharmacokinetics of ribavirin, clinical, virologic, and clinical laboratory parameters were assessed. RESULTS: Using a population pharmacokinetic approach, plasma concentrations of ribavirin were best described by a 3-compartment model. Drug exposure was remarkably consistent between participants. Overall, drug clearance was 28.5% lower in female compared with male participants. Median (5th-95th percentile) time above half maximal inhibitory concentration (IC50) was 37.3% (16.9%-73.1%), 16.7% (8.2%-58.5%), and 9.6% (4.9%-38.4%) on days 1, 7, and 8, respectively. Clinical laboratory parameters indicated reduction of cell damage and development of hemolytic anemia in the course of the treatment period. CONCLUSIONS: This observational study characterizes the pharmacokinetics of ribavirin in the treatment of Lassa fever indicating consistent exposure across patients. Whereas only a short time interval of concentrations above the IC50 implies rather low antiviral efficacy in vivo, the prominent reduction of cell damage markers might point to indirect-potentially anti-inflammatory-effects of ribavirin. The role of ribavirin in the treatment of Lassa fever requires further scrutiny.
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Febre Lassa , Humanos , Masculino , Feminino , Febre Lassa/tratamento farmacológico , Ribavirina/uso terapêutico , Nigéria/epidemiologia , Estudos Prospectivos , Antivirais/uso terapêutico , Hospitais de EnsinoRESUMO
Introduction: Low back pain (LBP) is a prevalent musculoskeletal condition that poses significant public health challenges. However, its epidemiology in Sub-Saharan Africa, especially in rural settings, remains largely unexplored. This study aimed to determine the epidemiology of LBP in a Nigerian Teaching Hospital. Material and methods: This was a retrospective review of the records of all LBP cases seen at the rheumatology clinic from 2018 to 2022 in a Teaching Hospital in South-South Nigeria. The sociodemographic and clinical data, including disability scores, was extracted from the patients' medical records. The data was analyzed using IBM SPSS version 25, and the level of significance was set at p < 0.05. Results: Among 1,580 patients, 319 (20.2%) reported LBP. The mean age was 59.51 ±10.21, and the peak age incidence was 51-60 years. Low back pain was more prevalent in females (61.4%). Work-related factors (47.3%) such as heavy lifting (26.3%), prolonged sitting (19.4%), and poor posture (27.9%) were the prominent risk factors. Sedentary behavior (11.5%) and obesity (16.9%) contributed. Common clinical manifestations included difficulty standing or bending (73%), walking difficulties (67.7%), sleep disturbances (51.4%), and radicular pain (45.8%). Common etiologies were spondylosis (66.5%), spondylolisthesis (22.3%), disc prolapse (19.4%), spinal canal stenosis (15.4%), muscle spasm (12.2%), and tuberculous spondylitis (9.7%). Acute and chronic LBP constituted 12.2% and 79.9% of cases, respectively. In terms of disability, 33.5% had minimal, 44.5% had moderate, 15.4% had severe, and 6.6% had crippling disabilities. Conclusions: Mechanical causes were the most implicated in LBP. Work-related factors and lifestyle choices contribute to the occurrence of LBP. Adjusting posture and lifestyle modification reduces LBP risk. Understanding its epidemiology is crucial for optimizing care and implementing preventive strategies.
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Lassa fever is a viral hemorrhagic fever treated with supportive care and the broad-spectrum antiviral drug ribavirin. The pathophysiology, especially the role of hyperinflammation, of this disease is unknown. We report successful remission of complicated Lassa fever in 2 patients in Nigeria who received the antiinflammatory agent dexamethasone and standard ribavirin.
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Febre Lassa , Antivirais/uso terapêutico , Dexametasona/uso terapêutico , Humanos , Febre Lassa/diagnóstico , Febre Lassa/tratamento farmacológico , Vírus Lassa/genética , Ribavirina/uso terapêuticoRESUMO
INTRODUCTION: Coronavirus disease 2019 (COVID-19), a highly transmissible viral infection has spread worldwide causing exponential increase in morbidity and mortality. But so far, there is limited information available to describe the presenting characteristics, outcomes and treatment modalities of COVID-19 patients in Nigeria. This study aimed to describe the demographic and clinical characteristics, underlying comorbidities, treatment modalities and outcomes of patients isolated and treated in a repurposed COVID-19 isolation and treatment centre in Abuja, Nigeria. MATERIALS AND METHODS: A retrospective study which reviewed the medical records of 300 confirmed COVID-19 patients isolated and treated according to the World Health Organisation and Nigeria Centre for Disease Control guidelines between 22nd July and 26th October, 2020 in ThisDay Dome Isolation and Treatment Centre. Data collected from the medical records include demographics, clinical features, treatment measures and outcomes. RESULTS: Out of 300 patients studied, 61.0% were male. The mean age of the participants was 38.2 ± 14.7. Less than half of the patients (40.3%) had one or more underlying comorbidities with hypertension the most common co-morbidity. Majority (62%) of patients were mildly symptomatic, 33% were asymptomatic while only 2% were severely symptomatic. The most common presenting symptoms include cough 34.0%, fever 30.3%, anosmia 28.7% and dysgeusia 22.7%. Older age (P < 0.001), tertiary education and the presence of underlying comorbidity (P < 0.001) were significantly associated with symptomatic presentation of COVID-19. The median duration of time between positive laboratory testing and presentation for treatment was 5 days (0-29). All patients were treated with a combination of Ivermectin, Azithromycin, Zinc and Vitamin C with no recorded death. The median length of stay at facility was 9 days. CONCLUSION: Close attention should be given to patients with co-morbidities as an inefficient management of such co-morbidities could lead to mortalities which may not be directly attributable to COVID-19.
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COVID-19 , Idoso , Comorbidade , Humanos , Masculino , Nigéria , Estudos Retrospectivos , SARS-CoV-2RESUMO
OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disorder with a poorly understood aetiology. It predominantly affects females and has a variety of clinical manifestations. In Nigeria, there are limited data on the prevalence and burden of the disease. This study aimed to determine the clinical and laboratory profiles of SLE patients seen in a new rheumatology clinic in South-South Nigeria. MATERIAL AND METHODS: This was a retrospective cross-sectional study conducted over five years (January 2016 to December 2020). The case files of patients that satisfied the diagnosis of SLE were reviewed. The diagnosis was based on the 1997 update of the American College of Rheumatology revised criteria for the classification of SLE. The sociodemographic, clinical, and immunological data were extracted from case records. Data analysis was carried out using IBM SPSS statistics® 2012 version 21.0. RESULTS: Fifty-two patients were diagnosed with SLE, giving a frequency of 4.7%. Forty-seven (90.4%) of the study participants were females, with a female-to-male ratio of 9.4 : 1. The mean age of the study group was 28.42 years. The mean duration of disease before diagnosis was 4.04 months with a range of 1-15 months. The patients had various organ system manifestations, with polyarthritis being the commonest (86.5%). Others included mucocutaneous (78.8%), haematological (69.2%), serositis (40.4%), renal (38.5%), and neurological (25%) manifestations. Antinuclear antibody (ANA) assay and anti-double-stranded DNA were positive in 100% and 69.2% of patients, respectively. All patients were placed on steroids, and 96.2% had hydroxychloroquine. None of the patients were on biologic disease-modifying antirheumatic drugs. CONCLUSIONS: This study's results are consistent with data from other African countries. To fully understand the burden and epidemiology of SLE in Nigeria, a larger prospective study is needed.
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BACKGROUND: Clinical disease registries are useful for quality improvement in care, benchmarking standards, and facilitating research. Collaborative networks established thence can enhance national and international studies by generating more robust samples and credible data and promote knowledge sharing and capacity building. This report describes the methodology, baseline data, and prospects of the Nigeria Parkinson Disease Registry. METHODS: This national registry was established in November 2016. Ethics approval was obtained for all sites. Basic anonymized data for consecutive cases fulfilling the United Kingdom Parkinson's Disease Brain Bank criteria (except the exclusion criterion of affected family members) are registered by participating neurologists via a secure registry website (www.parkinsonnigeria.com) using a minimal common data capture format. RESULTS: The registry had captured 578 participants from 5 of 6 geopolitical zones in Nigeria by July 2019 (72.5% men). Mean age at onset was 60.3 ± 10.7 years; median disease duration (interquartile range) was 36 months (18-60.5 months). Young-onset disease (<50 years) represented 15.2%. A family history was documented in 4.5% and 7.8% with age at onset <50 and ≥ 50, respectively. The most frequent initial symptom was tremor (45.3%). At inclusion, 93.4% were on treatment (54.5% on levodopa monotherapy). Per-capita direct cost for the registry was $3.37. CONCLUSIONS: This is the first published national Parkinson's disease registry in sub-Saharan Africa. The registry will serve as a platform for development of multipronged evidence-based policies and initiatives to improve quality of care of Parkinson's disease and research engagement in Nigeria. © 2020 International Parkinson and Movement Disorder Society.
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Doença de Parkinson , África Subsaariana , Feminino , Humanos , Masculino , Nigéria/epidemiologia , Doença de Parkinson/epidemiologia , Sistema de Registros , Reino UnidoRESUMO
Neurocysticercosis (NCC) is a common parasitic brain infestation caused by the ingestion of Taenia solium eggs, predominantly in developing countries. In this report, we presented the case of a 44-year-old woman who exhibited stroke symptoms and had a decade-long history of recurrent headaches and epilepsy. At presentation, a non-contrast computed tomography scan of the brain was performed and revealed hypodense oval lesions and calcified cysts in both cerebral hemispheres, strongly indicative of NCC. The patient responded positively to treatment with dexamethasone, albendazole, and carbamazepine. This case study underscores the importance of neuroimaging in investigating patients with neurological conditions like epilepsy, especially in developing countries. Early diagnosis and effective treatment are crucial in preventing and controlling NCC, reducing its impact on public health.
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Objectives: This research intended to examine the demographic and clinical attributes of stroke admissions in a rural Nigerian hospital. Materials and Methods: A retrospective analysis of stroke admissions was conducted over 1 year. All necessary data were obtained from patients' records and SPSS was employed for data analysis. P < 0.05 was deemed significant. Results: There were 52 stroke cases, accounting for 5.9% of medical admissions. The patients' mean age was 62.81 ± 12.71 years, while females constituted 51.9% of cases. Common risk factors included hypertension (76.9%), hyperlipidemia (38.5%), alcohol (26.9%), and diabetes mellitus (26.9%). Clinical manifestations included hemiparesis/plegia (84.6%), altered consciousness (63.5%), slurred speech (61.5%), cranial nerve deficit (61.5%), aphasia (42.3%), and headache (34.6%). Ischemic stroke (71.2%) predominated over hemorrhagic stroke (28.8%). The average hospitalization duration was 17.62 ± 8.91 days, and the mean onset to arrival time was 121.31 ± 136.06 h. Discharge and mortality rates were 82.7% and 13.5%, respectively. The association between stroke subtypes and mortality was significant (P = 0.001). Conclusion: Stroke constitutes a significant portion of medical admissions in Nigeria, with ischemic stroke being more prevalent. High mortality rates underscore the urgent need to manage risk factors to prevent stroke.
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Lassa fever is a viral haemorrhagic fever belonging to the arenaviridae family that is well known to be endemic to West Africa. The clinical presentation of the disease ranges from asymptomatic to fulminant illness. Lymphadenopathy a clinical manifestation of inflammation, infection, or malignancy has not been widely reported in Lassa fever disease. We report two cases of Lassa fever disease presenting with lymphadenopathy.
Enlargement of lymph nodes, is a common symptom of many infections, however it is not commonly mentioned in patients with Lassa fever, a viral hemorrhagic fever that is endemic in West Africa. However, recent research suggests that lymphadenopathy may be underreported in Lassa fever patients. This new finding could have important implications for the diagnosis and treatment of the disease, as well as for our understanding of how it spreads.
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BACKGROUND: Managing Lassa fever (LF) patients is challenging because of the complexity of this life-threatening infectious disease, the necessary isolation measures, and the limited resources in countries where it is endemic. Point-of-care ultrasonography (POCUS) is a promising low-cost imaging technique that may help in guiding the management of patients. METHODS: We conducted this observational study at the Irrua Specialist Teaching Hospital in Nigeria. We developed a POCUS protocol, trained local physicians who applied the protocol to LF patients and recorded and interpreted the clips. These were then independently re-evaluated by an external expert, and associations with clinical, laboratory and virological data were analyzed. FINDINGS: We developed the POCUS protocol based on existing literature and expert opinion and trained two clinicians, who then used POCUS to examine 46 patients. We observed at least one pathological finding in 29 (63%) patients. Ascites was found in 14 (30%), pericardial effusion in 10 (22%), pleural effusion in 5 (11%), and polyserositis in 7 (15%) patients, respectively. Eight patients (17%) showed hyperechoic kidneys. Seven patients succumbed to the disease while 39 patients survived, resulting in a fatality rate of 15%. Pleural effusions and hyper-echoic kidneys were associated with increased mortality. INTERPRETATION: In acute LF, a newly established POCUS protocol readily identified a high prevalence of clinically relevant pathological findings. The assessment by POCUS required minimal resources and training; the detected pathologies such as pleural effusions and kidney injury may help to guide the clinical management of the most at-risk LF patients.
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Febre Lassa , Médicos , Derrame Pleural , Humanos , Febre Lassa/diagnóstico por imagem , Sistemas Automatizados de Assistência Junto ao Leito , Ultrassonografia/métodosRESUMO
INTRODUCTION: The association between MAPT and PD risk may be subject to ethnic variability even within populations of similar geographical origin. Data on MAPT haplotype frequencies, and its association with PD risk in black Africans are lacking. We aimed to determine the frequencies of MAPT haplotypes and their role as risk factors for PD and age at onset in Nigerians. METHODS: The haplotype and genotype frequencies of MAPT rs1052553 were analysed in 907 individuals with PD and 1022 age-matched healthy controls from the Nigeria Parkinson's Disease Research network cohort. Clinical data related to PD included age at study, age at onset (AAO), and disease duration. RESULTS: The frequency of the H1 haplotype was 98.7% in PD, and 99.1% in controls (p = 0.19). The H2 haplotype was present in - 1.3% of PD and 0.9% of controls (p = 0.24). The most frequent MAPT genotype was H1H1 (PD - 97.5%, controls - 98.2%). The H1 haplotype was not associated with PD risk after accounting for gender and AAO (Odds ratio for H1/H1 vs H1/H2 and H2/H2: 0.68 (95% CI:0.39-1.28); p = 0.23). CONCLUSIONS: Our findings support previous studies that report a low frequency of the MAPT H2 haplotype in black ancestry Africans but document its occurrence in Nigerians. The MAPT H1 haplotype was not associated with an increased risk or age at onset of PD in this cohort.
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Doença de Parkinson , Humanos , População Africana , Idade de Início , Alelos , Demografia , Predisposição Genética para Doença/genética , Genótipo , Haplótipos , Doença de Parkinson/epidemiologia , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único , Proteínas tau/genéticaRESUMO
Background: The microtubule-associated protein tau ( MAPT ) gene is critical because of its putative role in the causal pathway of neurodegenerative diseases including Parkinson's disease (PD). However, there is a lack of clarity regarding the link between the main H1 haplotype and risk of PD. Inconsistencies in reported association may be driven by genetic variability in the populations studied to date. Data on MAPT haplotype frequencies in the general population and association studies exploring the role of MAPT haplotypes in conferring PD risk in black Africans are lacking. Objectives: To determine the frequencies of MAPT haplotypes and explore the role of the H1 haplotype as a risk factor for PD risk and age at onset in Nigerian Africans. Methods: The haplotype and genotype frequencies of MAPT rs1052553 were analysed using PCR-based KASP™ in 907 individuals with PD and 1,022 age-matched neurologically normal controls from the Nigeria Parkinson's Disease Research (NPDR) network cohort. Clinical data related to PD included age at study, age at onset, and disease duration. Results: The frequency of the main MAPT H1 haplotype in this cohort was 98.7% in individuals with PD, and 99.1% in healthy controls (p=0.19). The H2 haplotype was present in 41/1929 (2.1%) of the cohort (PD - 1.3%; Controls - 0.9%; p=0.24). The most frequent MAPT genotype was H1H1 (PD - 97.5%, controls - 98.2%). The H1 haplotype was not associated with PD risk after accounting for gender and age at onset (Odds ratio for H1/H1 vs H1/H2 and H2/H2: 0.68 (95% CI:0.39-1.28); p=0.23). Conclusions: Our findings support previous studies that report a low frequency of the MAPT H2 haplotype in black ancestry Africans, but document its occurrence in the Nigerian population (2.1%). In this cohort of black Africans with PD, the MAPT H1 haplotype was not associated with an increased risk or age at onset of PD.
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Background: Understanding the genetic mechanisms underlying diseases in ancestrally diverse populations is a critical step towards the realization of the global application of precision medicine. The African and African admixed populations enable mapping of complex traits given their greater levels of genetic diversity, extensive population substructure, and distinct linkage disequilibrium patterns. Methods: Here we perform a comprehensive genome-wide assessment of Parkinson's disease (PD) in 197,918 individuals (1,488 cases; 196,430 controls) of African and African admixed ancestry, characterizing population-specific risk, differential haplotype structure and admixture, coding and structural genetic variation and polygenic risk profiling. Findings: We identified a novel common risk factor for PD and age at onset at the GBA1 locus (risk, rs3115534-G; OR=1.58, 95% CI = 1.37 - 1.80, P=2.397E-14; age at onset, BETA =-2.004, SE =0.57, P = 0.0005), that was found to be rare in non-African/African admixed populations. Downstream short- and long-read whole genome sequencing analyses did not reveal any coding or structural variant underlying the GWAS signal. However, we identified that this signal mediates PD risk via expression quantitative trait locus (eQTL) mechanisms. While previously identified GBA1 associated disease risk variants are coding mutations, here we suggest a novel functional mechanism consistent with a trend in decreasing glucocerebrosidase activity levels. Given the high population frequency of the underlying signal and the phenotypic characteristics of the homozygous carriers, we hypothesize that this variant may not cause Gaucher disease. Additionally, the prevalence of Gaucher's disease in Africa is low. Interpretation: The present study identifies a novel African-ancestry genetic risk factor in GBA1 as a major mechanistic basis of PD in the African and African admixed populations. This striking result contrasts to previous work in Northern European populations, both in terms of mechanism and attributable risk. This finding highlights the importance of understanding population-specific genetic risk in complex diseases, a particularly crucial point as the field moves toward precision medicine in PD clinical trials and while recognizing the need for equitable inclusion of ancestrally diverse groups in such trials. Given the distinctive genetics of these underrepresented populations, their inclusion represents a valuable step towards insights into novel genetic determinants underlying PD etiology. This opens new avenues towards RNA-based and other therapeutic strategies aimed at reducing lifetime risk. Evidence Before this Study: Our current understanding of Parkinson's disease (PD) is disproportionately based on studying populations of European ancestry, leading to a significant gap in our knowledge about the genetics, clinical characteristics, and pathophysiology in underrepresented populations. This is particularly notable in individuals of African and African admixed ancestries. Over the last two decades, we have witnessed a revolution in the research area of complex genetic diseases. In the PD field, large-scale genome-wide association studies in the European, Asian, and Latin American populations have identified multiple risk loci associated with disease. These include 78 loci and 90 independent signals associated with PD risk in the European population, nine replicated loci and two novel population-specific signals in the Asian population, and a total of 11 novel loci recently nominated through multi-ancestry GWAS efforts.Nevertheless, the African and African admixed populations remain completely unexplored in the context of PD genetics. Added Value of this Study: To address the lack of diversity in our research field, this study aimed to conduct the first genome-wide assessment of PD genetics in the African and African admixed populations. Here, we identified a genetic risk factor linked to PD etiology, dissected African-specific differences in risk and age at onset, characterized known genetic risk factors, and highlighted the utility of the African and African admixed risk haplotype substructure for future fine-mapping efforts. We identified a novel disease mechanism via expression changes consistent with decreased GBA1 activity levels. Future large scale single cell expression studies should investigate the neuronal populations in which expression differences are most prominent. This novel mechanism may hold promise for future efficient RNA-based therapeutic strategies such as antisense oligonucleotides or short interfering RNAs aimed at preventing and decreasing disease risk. We envisage that these data generated under the umbrella of the Global Parkinson's Genetics Program (GP2) will shed light on the molecular mechanisms involved in the disease process and might pave the way for future clinical trials and therapeutic interventions. This work represents a valuable resource in an underserved population, supporting pioneering research within GP2 and beyond. Deciphering causal and genetic risk factors in all these ancestries will help determine whether interventions, potential targets for disease modifying treatment, and prevention strategies that are being studied in the European populations are relevant to the African and African admixed populations. Implications of all the Available Evidence: We nominate a novel signal impacting GBA1 as the major genetic risk factor for PD in the African and African admixed populations. The present study could inform future GBA1 clinical trials, improving patient stratification. In this regard, genetic testing can help to design trials likely to provide meaningful and actionable answers. It is our hope that these findings may ultimately have clinical utility for this underrepresented population.
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BACKGROUND: An understanding of the genetic mechanisms underlying diseases in ancestrally diverse populations is an important step towards development of targeted treatments. Research in African and African admixed populations can enable mapping of complex traits, because of their genetic diversity, extensive population substructure, and distinct linkage disequilibrium patterns. We aimed to do a comprehensive genome-wide assessment in African and African admixed individuals to better understand the genetic architecture of Parkinson's disease in these underserved populations. METHODS: We performed a genome-wide association study (GWAS) in people of African and African admixed ancestry with and without Parkinson's disease. Individuals were included from several cohorts that were available as a part of the Global Parkinson's Genetics Program, the International Parkinson's Disease Genomics Consortium Africa, and 23andMe. A diagnosis of Parkinson's disease was confirmed clinically by a movement disorder specialist for every individual in each cohort, except for 23andMe, in which it was self-reported based on clinical diagnosis. We characterised ancestry-specific risk, differential haplotype structure and admixture, coding and structural genetic variation, and enzymatic activity. FINDINGS: We included 197â918 individuals (1488 cases and 196â430 controls) in our genome-wide analysis. We identified a novel common risk factor for Parkinson's disease (overall meta-analysis odds ratio for risk of Parkinson's disease 1·58 [95% CI 1·37-1·80], p=2·397â×â10-14) and age at onset at the GBA1 locus, rs3115534-G (age at onset ß=-2·00 [SE=0·57], p=0·0005, for African ancestry; and ß=-4·15 [0·58], p=0·015, for African admixed ancestry), which was rare in non-African or non-African admixed populations. Downstream short-read and long-read whole-genome sequencing analyses did not reveal any coding or structural variant underlying the GWAS signal. The identified signal seems to be associated with decreased glucocerebrosidase activity. INTERPRETATION: Our study identified a novel genetic risk factor in GBA1 in people of African ancestry, which has not been seen in European populations, and it could be a major mechanistic basis of Parkinson's disease in African populations. This population-specific variant exerts substantial risk on Parkinson's disease as compared with common variation identified through GWAS and it was found to be present in 39% of the cases assessed in this study. This finding highlights the importance of understanding ancestry-specific genetic risk in complex diseases, a particularly crucial point as the Parkinson's disease field moves towards targeted treatments in clinical trials. The distinctive genetics of African populations highlights the need for equitable inclusion of ancestrally diverse groups in future trials, which will be a valuable step towards gaining insights into novel genetic determinants underlying the causes of Parkinson's disease. This finding opens new avenues towards RNA-based and other therapeutic strategies aimed at reducing lifetime risk of Parkinson's disease. FUNDING: The Global Parkinson's Genetics Program, which is funded by the Aligning Science Across Parkinson's initiative, and The Michael J Fox Foundation for Parkinson's Research.
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População Africana , Doença de Parkinson , Humanos , População Negra/genética , Loci Gênicos , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Desequilíbrio de Ligação , Doença de Parkinson/etnologia , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único/genética , População Africana/genéticaRESUMO
BACKGROUND: Only one recommendation currently exists for the treatment of Lassa fever (LF), which is ribavirin administered in conjunction with supportive care. This recommendation is primarily based on evidence generated from a single clinical trial that was conducted more than 30 years ago-the methodology and results of which have recently come under scrutiny. The requirement for novel therapeutics and reassessment of ribavirin is therefore urgent. However, a significant amount of work now needs to be undertaken to ensure that future trials for LF can be conducted consistently and reliably to facilitate the efficient generation of evidence. METHODOLOGY: We convened a consultation group to establish the position of clinicians and researchers on the core components of future trials. A Core Eligibility Criteria (CEC), Core Case Definition (CCD), Core Outcome Set (COS) and Core Data Variables (CDV) were developed through the process of a multi-stakeholder consultation that took place using a modified-Delphi methodology. RESULTS: A consensus position was achieved for each aspect of the framework, which accounts for the inclusion of pregnant women and children in future LF clinical trials. The framework consists of 8 core criteria, as well as additional considerations for trial protocols. CONCLUSIONS: This project represents the first step towards delineating the clinical development pathway for new Lassa fever therapeutics, following a period of 40 years without advancement. Future planned projects will bolster the work initiated here to continue the advancement of LF clinical research through a regionally-centred, collaborative methodology, with the aim of delineating a clear pathway through which LF clinical trials can progress efficiently and ensure sustainable investments are made in research capacity at a regional level.
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Antivirais/farmacologia , Ensaios Clínicos Fase III como Assunto/métodos , Desenvolvimento de Medicamentos/métodos , Febre Lassa/tratamento farmacológico , Descoberta de Drogas/métodos , Humanos , Vírus Lassa/efeitos dos fármacos , Projetos de Pesquisa , Inquéritos e QuestionáriosRESUMO
COVID-19 mortality rate has not been formally assessed in Nigeria. Thus, we aimed to address this gap and identify associated mortality risk factors during the first and second waves in Nigeria. This was a retrospective analysis of national surveillance data from all 37 States in Nigeria between February 27, 2020, and April 3, 2021. The outcome variable was mortality amongst persons who tested positive for SARS-CoV-2 by Reverse-Transcriptase Polymerase Chain Reaction. Incidence rates of COVID-19 mortality was calculated by dividing the number of deaths by total person-time (in days) contributed by the entire study population and presented per 100,000 person-days with 95% Confidence Intervals (95% CI). Adjusted negative binomial regression was used to identify factors associated with COVID-19 mortality. Findings are presented as adjusted Incidence Rate Ratios (aIRR) with 95% CI. The first wave included 65,790 COVID-19 patients, of whom 994 (1â51%) died; the second wave included 91,089 patients, of whom 513 (0â56%) died. The incidence rate of COVID-19 mortality was higher in the first wave [54â25 (95% CI: 50â98-57â73)] than in the second wave [19â19 (17â60-20â93)]. Factors independently associated with increased risk of COVID-19 mortality in both waves were: age ≥45 years, male gender [first wave aIRR 1â65 (1â35-2â02) and second wave 1â52 (1â11-2â06)], being symptomatic [aIRR 3â17 (2â59-3â89) and 3â04 (2â20-4â21)], and being hospitalised [aIRR 4â19 (3â26-5â39) and 7â84 (4â90-12â54)]. Relative to South-West, residency in the South-South and North-West was associated with an increased risk of COVID-19 mortality in both waves. In conclusion, the rate of COVID-19 mortality in Nigeria was higher in the first wave than in the second wave, suggesting an improvement in public health response and clinical care in the second wave. However, this needs to be interpreted with caution given the inherent limitations of the country's surveillance system during the study.
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The relationship between APOE polymorphisms and Parkinson's disease (PD) in black Africans has not been previously investigated. We evaluated the association between APOE polymorphic variability and self-declared cognition in 1100 Nigerians with PD and 1097 age-matched healthy controls. Cognition in PD was assessed using the single item cognition question (item 1.1) of the MDS-UPDRS. APOE genotype and allele frequencies did not differ between PD and controls (p > 0.05). No allelic or genotypic association was observed between APOE and age at onset of PD. In PD, APOE ε4/ε4 conferred a two-fold risk of cognitive impairment compared to one or no ε4 (HR: 2.09 (95% CI: 1.13-3.89; p = 0.02)), while APOE ε2 was associated with modest protection against cognitive impairment (HR: 0.41 (95% CI 0.19-0.99, p = 0.02)). Of 773 PD with motor phenotype and APOE characterized, tremor-dominant (TD) phenotype predominated significantly in ε2 carriers (87/135, 64.4%) compared to 22.2% in persons with postural instability/gait difficulty (PIGD) (30/135) and 13.3% in indeterminate (ID) (18/135, 13.3%) (p = 0.037). Although the frequency of the TD phenotype was highest in homozygous ε2 carriers (85.7%), the distribution of motor phenotypes across the six genotypes did not differ significantly (p = 0.18). Altogether, our findings support previous studies in other ethnicities, implying a role for APOE ε4 and ε2 as risk and protective factors, respectively, for cognitive impairment in PD.
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Systemic lupus erythematosus and syringomyelia are two distinct conditions with different pathogenetic pathways as well as diverse genetic and clinical characteristics. The coexistence of these two conditions has not been previously documented in the literature. We describe a 38-year-old male who presented with progressive bilateral weakness and pain in the lower limbs and loss of sphincteric functions three years following a diagnosis of lupus nephritis. Relevant autoantibody testing, hypocomplementemia, and biopsy-proven membranous lupus nephritis confirmed the diagnosis of systemic lupus erythematosus and magnetic resonance imaging of the spine confirmed the presence of syringomyelia. Therapy for lupus nephritis was instituted accordingly, while the patient was referred for neurosurgical intervention. The mechanism underlying syrinx formation in this patient is uncertain and, thus, further research is critical in this area.
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BACKGROUND: Fibromyalgia is a chronic pain syndrome of unknown etiology characterized by chronic widespread musculoskeletal pain and tenderness. It affects the quality of life of patients and has been associated with the human immunodeficiency virus (HIV). The study aimed to determine the prevalence of fibromyalgia in HIV-positive patients and assess the effect of fibromyalgia on their functional status. METHODOLOGY: This was a cross-sectional study comprising 160 treatment-naive HIV-positive patients and 160 age- and sex-matched HIV-negative controls. The diagnosis of fibromyalgia was based on the 2011 modification of the 2010 American College of Rheumatology diagnostic criteria by assessing the widespread pain index and symptom severity score. The severity of fibromyalgia was assessed with the revised fibromyalgia impact questionnaire. RESULTS: The prevalence of fibromyalgia in HIV-positive individuals was found to be 10.6%, which was significantly higher compared with controls (3.1%; P = .008). There was no significant association between fibromyalgia and age, gender, or occupation. There was a significant relationship between CD4 count levels (P < .001), WHO clinical stage (P < .001), and fibromyalgia. A statistically significant higher score on the Revised FM Impact Questionnaire was found in HIV-positive individuals with fibromyalgia (P < .001). CONCLUSION: The study found that HIV-positive patients had a significantly higher incidence of fibromyalgia than controls and this was related to active indices of HIV disease. Fibromyalgia had a greater clinical impact on HIV patients than in controls. As a result, fibromyalgia should be identified and treated in people living with HIV.
Assuntos
Fibromialgia/epidemiologia , Infecções por HIV/epidemiologia , Adolescente , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Fibromialgia/diagnóstico , Estado Funcional , Infecções por HIV/diagnóstico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Medição da Dor , Prevalência , Estudos Prospectivos , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Data on non-motor symptoms (NMS) in black Africans with Parkinson's disease (PD) are sparse. OBJECTIVE: To describe the profile of NMS in the Nigeria PD Registry (NPDR) cohort and explore the relationship between NMS and PD motor phenotype. METHODS: We conducted a cross-sectional study of the frequency and burden of NMS, based on the non-motor symptoms scale (NMSS) and the Chaudhuri method respectively in our cohort. Baseline demographics, disease characteristics (Hoehn and Yahr stage, MDS-UPDRS total score and Part III motor score), motor phenotype (based on Stebbin et al's algorithm), and levodopa equivalent daily dose (LEDD) were documented. RESULTS: Data are presented for 825 PD whose mean age at study was 63.7 ± 10.1 years, female sex-221 [26.8%] while median PD duration was 36 months. PD phenotypes included tremor-dominant 466 (56.5%), postural instability and gait disorder (PIGD) 259 (31.4%), and indeterminate 100 (12.1%). 82.6% were on treatment (median LEDD of 500 mg/24 hours). 804 (97.5%) endorsed at least 1 NMS. The median NMSS score was 26.0 while subscores for urinary and sexual function domains were significantly higher in males (P < 0.05). PIGD-PD had more frequent NMS and higher frequency of severe/very severe NMSS burden (P = 0.000 for both). Nocturia and fatigue were the most prevalent NMS overall and across motor subtypes. PIGD phenotype and total UPDRS scores were the independent determinants of NMSS scores (P = 0.000). CONCLUSION: The profile and burden of NMS, and association with motor subtype in our black African cohort is largely similar to descriptions from other populations.