May Measurement Month 2021: an analysis of blood pressure screening results from Nigeria.

There is a need to constantly assess the awareness, treatment, and control of hypertension in Nigeria. This study determined the frequency of undiagnosed hypertension across the six geopolitical zones of Nigeria. We conducted an opportunistic screening of adults aged at least 18 years in the month of May 2021. Participants were recruited by trained volunteers using the May Measurement Month protocol. Blood pressure (BP) was measured using validated digital sphygmomanometers. We defined hypertension as systolic BP ≥ 140 and/or diastolic BP ≥ 90 mmHg and/or the use of BP-lowering medications. A total of 9361 participants (51.5% females) with a mean age of 40.7 ± 15.5 years were screened. Hypertension was present in 3192 (34.1%) of the participants. About half (1491, 46.7%) of the hypertensives were unaware of the diagnosis. Among the 3192 participants with hypertension, less than half (1540, 48.2%) were on antihypertensive medications, while only 36.4% of those on antihypertensive medications had their BP controlled (<140/90 mmHg). About one-third of Nigerians in this opportunistic screening had hypertension, with about half of them being unaware of their diagnosis while only about two out of every five on antihypertensive medications had controlled BP. Urgent health actions are needed in Nigeria to reduce the burden of hypertension and its complications.

Risk Factor Characterization of Ischemic Stroke Subtypes Among West Africans.

BACKGROUND AND PURPOSE: To identify the qualitative and quantitative contributions of conventional risk factors for occurrence of ischemic stroke and its key pathophysiologic subtypes among West Africans. METHODS: The SIREN (Stroke Investigative Research and Educational Network) is a multicenter, case-control study involving 15 sites in Ghana and Nigeria. Cases include adults aged ≥18 years with ischemic stroke who were etiologically subtyped using the A-S-C-O-D classification into atherosclerosis, small-vessel occlusion, cardiac pathology, other causes, and dissection. Controls were age- and gender-matched stroke-free adults. Detailed evaluations for vascular, lifestyle, and psychosocial factors were performed. We used conditional logistic regression to estimate adjusted odds ratios with 95% CI. RESULTS: There were 2431 ischemic stroke case and stroke-free control pairs with respective mean ages of 62.2±14.0 versus 60.9±13.7 years. There were 1024 (42.1%) small vessel occlusions, 427 (17.6%) large-artery atherosclerosis, 258 (10.6%) cardio-embolic, 3 (0.1%) carotid dissections, and 719 (29.6%) undetermined/other causes. The adjusted odds ratio (95% CI) for the 8 dominant risk factors for ischemic stroke were hypertension, 10.34 (6.91-15.45); dyslipidemia, 5.16 (3.78-7.03); diabetes, 3.44 (2.60-4.56); low green vegetable consumption, 1.89 (1.45-2.46); red meat consumption, 1.89 (1.45-2.46); cardiac disease, 1.88 (1.22-2.90); monthly income $100 or more, 1.72 (1.24-2.39); and psychosocial stress, 1.62 (1.18-2.21). Hypertension, dyslipidemia, diabetes were confluent factors shared by small-vessel, large-vessel and cardio-embolic subtypes. Stroke cases and stroke-free controls had a mean of 5.3±1.5 versus 3.2±1.0 adverse cardio-metabolic risk factors respectively (P<0.0001). CONCLUSIONS: Traditional vascular risk factors demonstrate important differential effect sizes with pathophysiologic, clinical and preventative implications on the occurrence of ischemic stroke among indigenous West Africans.

The Nigeria Parkinson Disease Registry: Process, Profile, and Prospects of a Collaborative Project.

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.

Dysphagia following acute stroke and its effect on short-term outcome.

BACKGROUND: Dysphagia is assciated with numerous medical conditions including stroke, and there are wide variations in reported frequency of dysphagia in stroke survivors in the literature. Dysphagia has been shown to be an important risk factor for aspiration pneumonia and has profound impact on survivors. AIMS: This study aims to determine the frequency of dysphagia in stroke survivors and its effects on short-term outcome. METHODS: Consecutive patients hospitalised for first-ever acute stroke at Ahmadu Bello University Teaching Hospital Zaria, Nigeria, were prospectively enrolled from April 2015 to January 2017. Stroke severity was assessed using the National Institute of Health Stroke Scale (NIHSS). Water swallowing test was used to screen patients for the presence of dysphagia. This was followed by swallowing provocative test which was aimed at evaluating swallowing reflexes. All the patients were then followed up till day 30. Outcome measures applied were 30-day mortality and functional impairment on the Modified Rankin Scale. RESULTS: Ninety-four patients (53 males and 41 females) with acute stroke were studied. Mean age of patients was 55.51 ± 15.7 years and 32 (34.4%) patients had dysphagia at presentation. Mean NIHSS score of patients with dysphagia was significantly higher than those without dysphagia. Aspiration pneumonia occurred more significantly in those with dysphagia. In multivariate logistic regression, only aspiration pneumonia was independently associated with 30-day mortality. CONCLUSION: The prevalence of dysphagia in this cohort of stroke patients was 34.4%, and the major independent determinant of 30-day mortality was development of aspiration pneumonia.

MAPT allele and haplotype frequencies in Nigerian Africans: Population distribution and association with Parkinson's disease risk and age at onset.

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.

MAPT allele and haplotype frequencies in Nigerian Africans: population distribution and association with Parkinson's disease risk and age at onset.

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.

Urinary proteomics combined with home blood pressure telemonitoring for health care reform trial-First progress report.

High blood pressure (BP) and type-2 diabetes (T2DM) are forerunners of chronic kidney disease and left ventricular dysfunction. Home BP telemonitoring (HTM) and urinary peptidomic profiling (UPP) are technologies enabling risk stratification and personalized prevention. UPRIGHT-HTM (NCT04299529) is an investigator-initiated, multicenter, open-label, randomized trial with blinded endpoint evaluation designed to assess the efficacy of HTM plus UPP (experimental group) over HTM alone (control group) in guiding treatment in asymptomatic patients, aged 55-75 years, with ≥5 cardiovascular risk factors. From screening onwards, HTM data can be freely accessed by all patients and their caregivers; UPP results are communicated early during follow-up to patients and caregivers in the intervention group, but at trial closure in the control group. From May 2021 until January 2023, 235 patients were screened, of whom 53 were still progressing through the run-in period and 144 were randomized. Both groups had similar characteristics, including average age (62.0 years) and the proportions of African Blacks (81.9%), White Europeans (16.7%), women 56.2%, home (31.2%), and office (50.0%) hypertension, T2DM (36.4%), micro-albuminuria (29.4%), and ECG (9.7%) and echocardiographic (11.5%) left ventricular hypertrophy. Home and office BP were 128.8/79.2 mm Hg and 137.1/82.7 mm Hg, respectively, resulting in a prevalence of white-coat, masked and sustained hypertension of 40.3%, 11.1%, and 25.7%. HTM persisted after randomization (48 681 readings up to 15 January 2023). In conclusion, results predominantly from low-resource sub-Saharan centers proved the feasibility of this multi-ethnic trial. The COVID-19 pandemic caused delays and differential recruitment rates across centers.

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

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

Identification of genetic risk loci and causal insights associated with Parkinson's disease in African and African admixed populations: a genome-wide association study.

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 197 918 individuals (1488 cases and 196 430 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=2·397 × 10-14) 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.

Genome-wide Association Identifies Novel Etiological Insights Associated with Parkinson's Disease in African and African Admixed Populations.

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.

APOE E4 is associated with impaired self-declared cognition but not disease risk or age of onset in Nigerians with Parkinson's disease.

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.

Impact of climatic variables on childhood severe malaria in a tertiary health facility in northern Nigeria.

Introduction: Despite the recent progress in the malaria burden, climatic factors are important if the world will achieve the set target of its eradication. Hence, this study determined the impact of climatic conditions on childhood severe malaria in a tertiary health facility in northern Nigeria. Methodology: This was a retrospective descriptive study that involved children with severe malaria managed between July 2016 and August 2017. The diagnosis of severe malaria was according to the World Health Organization 2015 guidelines. We extracted relevant data from case records and obtained the weather information from the Nigerian Meteorological Agency and www.worldweatheronline.com. Data were entered in Microsoft Excel 2013 and analyzed with Statistical Package for the Social Sciences version 20. Results: A total of 483 cases of children with severe malaria were managed. The median age was 4.0 (2.5-8.0) years. Males were 261 (54.0%). In the wet season, 375 (77.6%) cases were recorded, while 108 (22.4%) cases occurred during the dry season. The odds of malaria occurring during the wet season were 2.057 (95% CI, 1.613-2.622). Temperature patterns were not related to malaria cases. Malaria cases showed significant moderate positive cross-correlation at 2- and 3-months lag for the rainfall pattern (best cross-correlation occurred at 3 months lag with a coefficient of 0.598, p = 0.045). Conclusion: This study demonstrated marked seasonality of childhood severe malaria infection with 77% of cases during the wet season. Malaria was associated with only rainfall at a 2 to 3 months lag amongst the climatic variables. We recommend the urgent implementation of seasonal malaria chemoprophylaxis.

Prognostic significance of BIRC7/Livin, Bcl-2, p53, Annexin V, PD-L1, DARC, MSH2 and PMS2 in colorectal cancer treated with FOLFOX chemotherapy with or without aspirin.

Evasion of apoptosis is associated with treatment resistance and metastasis in colorectal cancer (CRC). Various cellular processes are associated with evasion of apoptosis. These include overexpression of pro-apoptotic proteins (including p53 and PD-L1), anti-apoptotic proteins (BIRC7/Livin and Bcl-2), chemokine receptors (including DARC), and dysregulation of DNA mismatch repair proteins (including MSH2 and PMS2). The aim of this study was to determine the effect of folinic acid, 5-FU and oxaliplatin (FOLFOX) as a single agent and aspirin plus FOLFOX in various combinations on the aforementioned proteins in human CRC, SW480 cell line and rat models of N-Methyl-N-Nitrosourea (NMU)-induced CRC. In addition, effects of the NMU-induced CRC and chemotherapeutic regimens on haematological and biochemical parameters in the rat models were studied. Immunohistochemistry, immunofluorescence and immunoblot techniques were used to study the expression pattern of the related proteins in the human CRC cells pre- and post-treatment. Double contrast barium enema, post-mortem examination and histological analyses were used to confirm tumour growth and the effect of the treatment in vivo in rat models. Notably, we found in human mucinous CRC, a significant increase in expression of the BIRC7/Livin post-FOLFOX treatment compared with pre-treatment (p = 0.0001). This increase provides new insights into the prognostic role of BIRC7/Livin in evasion of apoptosis and facilitation of treatment resistance, local recurrence and metastasis particularly among mucinous CRCs post-FOLFOX chemotherapy. These poor prognostic features in the CRC may be further compounded by the significant suppression of DARC, PD-L1, PMS2 and overexpression of MSH2 and anti-apoptotic Bcl-2 and p53 proteins observed in our study (p < 0.05). Importantly, we found a significant reduction in expression of BIRC7/Livin and reactivation of DARC and PD-L1 with a surge in Annexin V expression in rat models of CRC cells post-treatment with a sequential dose of aspirin plus FOLFOX compared with other treatments in vivo (p <0.05). The mechanistic rational of these effects underscores the importance of expanded concept of possible aspirin combination therapy with FOLFOX sequentially in future CRC management. Validation of our findings through randomized clinical trials of aspirin plus FOLFOX sequentially in patients with CRC is therefore warranted.

Hypokalemic Periodic Paralysis in Pregnancy: A Case Report.

Background: Myopathy is a disorder of skeletal muscles and has a rare occurrence in pregnancy. It may present with numbness/weakness. The occurrence of isolated weakness involving all the limbs is alarming to the patient and the diagnosis can be challenging to the Obstetrician. We present a case of hypokalaemic paralysis in pregnancy. Case report: A 32-year-old grand multipara presented at 31 weeks gestation with numbness in all limbs for nine days and one-day history of weakness in all limbs. She had a similar episode in her last pregnancy with complete resolution by the end of puerperium. On examination, she was conscious with a Glasgow Coma Scale score was 15/15, had no signs of meningeal irritation, and no cranial nerve palsy. She had normal muscle bulk; the power of 4/5 in both upper limbs and 3/5 in both lower limbs. There was no clearly defined sensory level. Planter reflex was flexor symmetrically. A review of other systems was unremarkable. Her PCV was 35% and random blood glucose was 4.2mmol/l. Serum biochemistry showed severe hypokalaemia of 1.8mmol/l with normal levels of sodium and chloride. Urinary potassium level was normal. She had parenteral correction of potassium with complete resolution of weakness, and she was maintained on oral potassium supplements. She had an uneventful delivery at 37 weeks gestation. Conclusion: Measuring the serum level of potassium should be part of the initial workup when evaluating pregnant women presenting with muscle weakness. Multidisciplinary management leads to early diagnosis, prompt management, and a good prognosis.

A Cross-Sectional Comprehensive Assessment of the Profile and Burden of Non-motor Symptoms in Relation to Motor Phenotype in the Nigeria Parkinson Disease Registry Cohort.

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.

A four-year-old Nigerian boy with battered child syndrome: implications for public health.

Battered child syndrome (BCS) is a form of physical abuse that is characterised by multiple injuries and potentially fatal outcome. Despite the high prevalence of physical abuse in developing countries, BCS is rarely reported. Hence, this report highlighted a four-year-old Nigerian boy who suffered multiple injuries (scalp haematoma, bruises, right clavicular fracture, and burns) from the paternal uncle's wife. This case report is discussed along the line of public health approach for curbing the social menace.

Diabetic-ketoacidosis in a nine-year-old child with homozygous sickle cell anaemia: a rare case report.

Sickle cell anaemia (SCA) and type 1 diabetes mellitus (type 1 DM) are chronic medical conditions whose co-existence is uncommon in childhood. Furthermore, complications of SCA such as mesenteric crisis typically present with abdominal pain, which is also common in children with diabetic ketoacidosis (DKA) and this may possess diagnostic challenge. Herewith in, we report a rare case of a nine-year-old child with homozygous sickle cell anaemia, who presented with features of mesenteric crisis and diabetic ketoacidosis. The DKA was diagnosed based on the presence of hyperglycaemia (32.2 mmol/L), ketonaemia (4.6 mmol/L) and acidosis (11.6 mmol/L). The fluids deficit was corrected over 24 hours, with improvement in the vaso-occlusive crises (VOC) without precipitating cerebral oedema.

A Nationwide Survey of Parkinson's Disease Medicines Availability and Affordability in Nigeria.

BACKGROUND AND OBJECTIVES: Limited access to medicines can impact negatively on outcomes in people with Parkinson's disease (PD). The study objectives were to determine the availability and assess the affordability of antiparkinsonian medications in pharmacies across Nigeria. METHODS: This was a cross-sectional nationwide study utilizing the World Health Organization/Health Action Initiative methodology. Strategically selected private- and public-sector pharmacies in the six geopolitical zones of Nigeria were surveyed for availability of medicines for management of early and advanced PD. The nine categories were: levodopa/peripheral decarboxylase inhibitors, dopamine receptor agonists, monoamine oxidase type B inhibitors, anticholinergics, catechol-o-methyl transferase inhibitors, atypical antipsychotics, antidepressants, antidementia drugs, and miscellaneous (e.g., drugs for orthostatism, urinary incontinence, and sleep disturbance). Unaffordability was defined as paying more than 1 days' wages (>N600 or > US$1.67) for a standard 30-day supply. RESULTS: One hundred twenty-three pharmacies were surveyed (62 private [50.4%] and 61 public sector [49.6%]; range of 15-25 pharmacies in each geopolitical zone). Private exceeded public-sector availability across all nine categories of PD medicines (P < 0.05). The most available medicines were dopamine receptor agonists (68.3%; predominantly ergot-derived bromocriptine), anticholinergics (56.1%; mainly trihexyphenidyl), and l-dopa formulations (48%; mainly 250/25 l-dopa/carbidopa). Only two medications (trihexyphenidyl tablets and biperiden injection) were affordable. The average number of day's minimum wages for a 30-day supply of PD medicines was 41.3 days (range, 1-371). CONCLUSIONS: PD medicines access is limited in Nigeria. Strategies, including engagement of stakeholders to consider interventions to improve and prioritize PD medicines access, are urgently warranted.

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.

Epidemiologic profile of peripartum cardiomyopathy in a tertiary care hospital.

BACKGROUND: An epidemiologic link between peripartum cardiomyopathy (PPCM) and customary puerperal practices have been described among Nigerians. It is not, however, known if these practices have changed and influenced the epidemiology of PPCM over the years. OBJECTIVES: To describe the current epidemiologic profile of PPCM. METHODS: Cross sectional analysis of prospectively recruited 65 patients with PPCM seen from January 2003 to December 2005 in a tertiary care hospital in Sokoto, northwest Nigeria. RESULTS: Incidence rate was one case per 102 deliveries. Peripartum cardiomyopathy (PPCM) constituted 2.4% of total medical admissions, 32.5% of overall admissions for heart failure, and 60% of admissions for heart failure in females. Patients were predominantly (84.6%) of Hausa and Fulani ethnic groups; and 20 (30.8%) were primiparous and 45 (69.2%) were multiparous women aged 28.2 +/- 8.1 years (range 15-45 years). Literacy rate was 6.2%. Sixty-one (93.8%) patients belonged to the low socioeconomic class. All patients presented during the postpartum period; the interval between delivery and presentation was 6.7 +/- 10.3 weeks (range .25-40 weeks, median 4 weeks). Customary puerperal practices were observed in 53 (81.5%). Hospital admission peaked during the peaks of cold harmattan and rainy seasons. Transient hypertension occurred in 18 (27.7%) patients. Complications included pericardial effusion (13.5%), intracardiac thrombosis (12.3%), and atrial fibrillation (3.1%). Stroke, pulmonary embolism, and acute lower extremity arterial occlusion each occurred in one (1.5%) patient. Mortality rate was 12.3%. Compared to the survivors, the deceased had significantly lower diastolic pressure (67.5 +/- 10.4 mm Hg vs 83.4 +/- 19.4 mm Hg; P = .04) and higher cardiothoracic index (70.2% +/- 14.4% vs 60.9% +/- 5.5%; P = .007). The outcome of PPCM correlated with cardiothoracic index (r = .7; P = .007), ejection fraction (r = .5; P = .03), and diastolic blood pressure (r = .4; P = .04). CONCLUSIONS: The epidemiologic profile of PPCM has not changed among the ethnic Hausa and Fulani groups of northwest Nigeria. Peripartum cardiomyopathy (PPCM) is an important cause of maternal morbidity and mortality in this population.