Prevalence and predictors of long-term progression of chronic kidney disease in people with HIV in Ghana from 2003-2018.

BACKGROUND: HIV is associated with an increased risk of progression to chronic kidney disease (CKD), and this risk is higher in people of West African descent than many other ethnicities. Our study assessed the rates of eGFR change and predictors of rapid eGFR progression in patients receiving antiretroviral therapy (ART), including tenofovir disoproxil fumarate (TDF), in central Ghana between 2003 and 2018. METHODS: This single-centre retrospective study enrolled people with HIV (PWH) initiating ART in Ghana between 2003-2018. Demographics, hepatitis B (HBsAg) status, ART regimens and estimated glomerular filtration rate (eGFR) measurements were recorded, and analyses including multi-level model linear regression were performed to determine predictors of greater levels of eGFR decline and risk of rapid eGFR decline. RESULTS: Six hundred and fifty-nine adult participants were included in the study with a median follow-up time of 6 years (IQR 3.6-8.9). 149 participants (22.6%) also had confirmed HBV co-infection. eGFR mean values were lowest at the point of diagnosis and highest on the second measurement taken; mean eGFR slowly decreased over subsequent measures thereafter. TDF use was associated with the highest mean rate of eGFR decline of all nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) with a statistically significant greater annual decline of -1.08 mL/min/1.73m2/year (CI: -1.92, -0.24) compared with zidovudine. Nevirapine (-0.78mL /min/173m2/year; CI: -1.39, -0.17) and protease inhibitors (-1.55mL/mil/173m2/year; CI: -2.68, -0.41) were associated with greater eGFR declines compared with efavirenz. Negative HBsAg status was associated with greater eGFR decline compared with positive HBsAg status (-1.25mL/mil/173m2/year; CI 0.29. -2.20). CONCLUSIONS: Increased rates of eGFR decline amongst PWH in Ghana were associated with TDF, nevirapine, and protease inhibitor use as well as negative HBsAg status. Additional research using mortality outcome data is needed to closely assess long-term predictors of eGFR decline in African populations.

Epigenetics as a target to mitigate excess stroke risk in people of African ancestry: A scoping review.

BACKGROUND: Globally, individuals of African ancestry have a relatively greater stroke preponderance compared to other racial/ethnic groups. The higher prevalence of traditional stroke risk factors in this population, however, only partially explains this longstanding disparity. Epigenetic signatures are transgenerational and could be a plausible therapeutic target to further bend the stroke disparities curve for people of African ancestry. There is, however, limited data on epigenetics and stroke risk in this population. PURPOSE: To examine existing evidence and knowledge gaps on the potential contribution of epigenetics to excess stroke risk in people of African ancestry and avenues for mitigation. MATERIALS AND METHODS: We conducted a scoping review of studies published between January 2003 and July 2023, on epigenetics and stroke risk. We then summarized our findings, highlighting the results for people of African ancestry. RESULTS: Of 104 studies, there were only 6 studies that specifically looked at epigenetic mechanisms and stroke risk in people of African ancestry. Results of these studies show how patterns of DNA methylation and non-coding RNA interact with lifestyle choices, xenobiotics, and FVIII levels to raise stroke risk in people of African ancestry. However, no studies evaluated epigenetic patterns as actionable targets for the influence of psychosocial stressors or social context and excess stroke risk in this population (versus others). Also, no studies interrogated the role of established or novel therapeutic agents with the potential to reprogram DNA by adding or removing epigenetic markers in people of African ancestry. CONCLUSION: Epigenetics potentially offers a promising target for modifying the effects of lifestyle, environmental exposures, and other factors that differentially affect people of African ancestry and place them at relatively greater stroke risk compared to other populations. Studies that precisely assess the pathways by which epigenetic mechanisms modulate population-specific disparities in the risk of stroke are needed.

Polypill Programs to Prevent Stroke and Cut Costs in Low Income Countries: Moving From Clinical Efficacy to Pragmatic Implementation.

Current projections are that the already overwhelming burden of strokes and atherosclerotic cardiovascular diseases in low- and middle-income countries (LMICs) will continue to rise over the coming decades as the prevalence of traditional vascular risk factors burgeon in these countries. Cardiovascular polypills containing combinations of antihypertensive(s), a statin, with or without aspirin or folic acid in the form of a single pill, represent a viable strategy for both primary and secondary prevention of atherosclerotic cardiovascular diseases in LMICs. Large multicenter trials in LMIC and high-income country (HIC) settings have now clearly demonstrated the beneficial effects of the cardiovascular polypill versus placebo (or usual care) in reducing primary stroke risk by 50%. For survivors of a recent myocardial infarction residing in HICs, the polypill reduced risk of major cardiovascular events by 25% due to improved treatment adherence. Data on the clinical efficacy of the polypill for secondary stroke prevention are scanty both in HICs and LMICs. Cost-effectiveness analyses data from LMICs suggest cost savings with the polypill for primary and secondary prevention of stroke and atherosclerotic cardiovascular diseases. However, major contextual barriers in LMICs need to be surmounted through mixed methods research and hybrid clinical trials to assess its real-world effectiveness, before the adoption of the polypill for primary and secondary atherosclerotic cardiovascular disease prevention in routine clinical practice.

Effect of an Educational Intervention for Primary Stroke Risk Reduction in Ghana and Nigeria: Pilot Randomized Controlled Trial.

BACKGROUND: Using tailored mobile health interventions to improve global vascular risk awareness and control is yet to be investigated for primary stroke prevention in Africa. METHODS: This 2-arm pilot randomized controlled trial involved 100 stroke-free adults with at least 2 vascular risk factors for stroke. Eligible participants were assigned randomly to a control arm offering 1-time counseling (n=50) or a 2-month educational intervention arm (n=50) comprising a stroke video and riskometer app aimed at improving stroke risk factor awareness and health-seeking behavioral modification to control total vascular risk. Reduction in total stroke risk score was the primary outcome while feasibility and process measures were secondary outcomes. RESULTS: All enrolled participants completed the 2-month follow-up (retention rate=100%). The mean (SD) age of participants was 59.5 (±12.5) years, 38% were males. The mean change in stroke risk score at 2 months was -11.9% (±14.2) in the intervention arm versus -1.2% (±9.1) in the control arm, P=0.0001. Stroke risk awareness improved by 16.1% (±24.7) in the intervention arm versus 8.9% (±24.7) in the control arm, P=0.08. The intervention arm had 11.1 mm Hg reduction in systolic blood pressure compared with 4.8 mm Hg reduction in the control arm. CONCLUSIONS: The intervention demonstrated a positive signal of effect over a 2-month period. A definitive clinical trial with a longer duration of follow-up is warranted on the premise of these promising findings from this pilot randomized clinical trial. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05619406.

Prevalence and predictors of low folate levels among stroke survivors in a country without mandatory folate food fortification: Analysis of a Ghanaian sample.

BACKGROUND: While additional folic acid (FA) treatment has a neutral effect on lowering overall vascular risk in countries that mandate FA fortification of food, meta-analytic data suggest that folate supplementation reduces stroke risk in certain patient subgroups, and among people living in countries without mandatory folate food fortification. However, the burden of folate deficiency among adults with stroke in the world's poorest continent is unknown. PURPOSE: To assess the prevalence and predictors of folate deficiency among recent ischemic stroke survivors. METHODS: We analyzed data among consecutively encountered ischemic stroke patients aged ≥18 years at a tertiary medical center in Kumasi, Ghana between 10/2020 - 08/2021. We identified a modest sample of stroke free adults to serve as a comparator group. Fasting serum folate was measured using a radioimmunoassay and a cut-off of 4ng/mL used to define folate deficiency. Factors associated with serum folate concentration were assessed using a multilinear regression model. RESULTS: Comparing stroke cases (n = 116) with stroke-free comparators (n = 20), mean folate concentration was lower among stroke cases (7 ng/ml vs. 10.2 ng/ml, p = 0.004). Frequency of folate deficiency was higher among stroke cases vs. stroke-free controls (31% vs 5%, p = 0.02). Male sex (beta coefficient of -2.6 (95% CI: -4.2, -0.9) and LDL (ß: -0.76; -1.4, -0.07) were significantly associated with serum folate concentration. CONCLUSION: Almost one in three ischemic stroke survivors have folate deficiency potentially accentuating their risk for further adverse atherosclerotic events in a setting without folate fortification. A clinical trial of folate supplementation among stroke survivors is warranted.

Knowledge and perspectives of community members on risk assessment for stroke prevention using mobile health approaches in Nigeria.

OBJECTIVES: To assess the knowledge of community dwelling adults on stroke risk and their willingness to use mobile health (mHealth) technology in assessing their stroke risk. MATERIALS AND METHODS: A cross-sectional study was conducted among adults (≥18 years old) using survey questionnaires designed by neurologists and health promotion experts and administered by trained study staff. Logistic regression models were used to assess factors associated with receptivity toward knowing individual stroke risk score and willingness to use a mobile application (App) to assess stroke risk. RESULTS: The survey was administered to 486 participants in Nigeria, with a mean age of 47.4 ± 15.5 years, comprising 53.5% females. Up to 84% of participants wanted to know their risk for developing stroke but only 29.6% of respondents had ever previously had their stroke risk assessed. Factors associated with willingness to know stroke risk were age [aOR (95% CI): 0.97 (0.95 - 0.99)], and Hausa tribe [16.68 (2.16 - 128.92)]. Up to 66% of participants wanted to know their immediate risk of stroke, compared with 6.6% and 2.1% who wanted to know their 5-year or 10-year future stroke risks respectively. Regarding locations, participants preferred stroke risk assessment to be performed at a health facility, at home by health professional, on their own using mHealth (stroke risk calculator application), or at communal gatherings (decreasing order). About 70% specifically wished to learn about their stroke risk via an mHealth application. CONCLUSIONS: Community dwelling Nigerians wanted to know their immediate risk of stroke using digital platforms, such as a mobile phone stroke risk calculator application. Clinical trials are needed to assess the effectiveness of such a strategy for primary prevention of stroke in sub-Saharan African communities.

Deciphering the contextual barriers to mainstreaming the implementation of stroke thrombolysis in a Ghanaian hospital: Findings from the activate mixed-methods study.

BACKGROUND: Each year, stroke-related death and disability claim over 143 million years of healthy life globally. Despite accounting for much of the global stroke burden, acute stroke care in Low-and-Middle-Income Countries remains suboptimal. Thrombolysis, an effective treatment option for stroke, is only received by a minority of stroke patients in these settings. AIM: To determine the context-specific barriers and facilitators for the implementation of mainstream stroke thrombolysis in a Ghanaian hospital. METHODS: We employed a mixed-methods approach involving key stakeholders (recipients, providers, and leaders) in the acute stroke care continuum. Surveys were administered to acute stroke patients, and in-depth key informant interviews were conducted with experts in stroke care, including a neurologist, medical director, neurology residents, a stroke nurse, emergency physicians, a radiologist, and a pharmacist. The data collected from these interviews were transcribed and analysed using content analysis with the CFIR (Consolidated Framework for Implementation Research) model as a guiding template. Two independent coders were involved in the analysis process to ensure reliability and accuracy. RESULTS: The stroke thrombolysis rate over a 6-month period was 0.83% (2 out of 242), with an average door-to-needle time among thrombolyzed patients being 2 hours, 37 minutes. Only 12.8% of patients (31 out of 242) presented within 4.5 hours of stroke symptom onset. The most significant obstacle to the implementation of acute stroke thrombolysis was related to the characteristics of the individuals involved, notably delays in presenting to the hospital among stroke patients due to a lack of knowledge about stroke symptoms and cultural beliefs. Additionally, a significant bottleneck that contributed to the discrepancy between the number of patients who presented within the 4.5-6 hour window and the number of patients who actually received thrombolysis was the inability to pay for the cost of thrombolytic agents. This was followed by challenges in the implementation processes. CONCLUSIONS: Addressing challenges related to stroke awareness, and financial constraints via multi-level stakeholder engagement, and enactment of stroke protocols are crucial steps in ensuring a successful implementation of a stroke thrombolysis program in a resource-limited setting.

Inpatient Management of Acute Stroke of Unknown Type in Resource-Limited Settings.

Stroke is the second leading cause of death and disability worldwide, with a disproportionate burden on low- and middle-income countries. Critical elements of guideline-based stroke care developed in high-income countries are not applicable to resource-limited settings, where lack of access to neuroimaging prevents clinicians from distinguishing between ischemic stroke and intracranial hemorrhage, requiring challenging clinical decision-making, particularly in the acute setting. We discuss strategies for acute inpatient management of stroke of unknown type with a focus on blood pressure management and antiplatelet therapy when neuroimaging is unavailable, and review some of the challenges and strategies for successfully implementing stroke unit care in resource-limited health care settings.

Course and characteristics of depression over a 12-month period among Ghanaians living with HIV: the EVERLAST study.

Individuals with HIV are predisposed to depression but there is limited data on its dynamics and correlates. We aimed to assess course and characteristics of depression among Ghanaian HIV patients over a 12-month period. We interrogated a longitudinal study dataset of patients at a tertiary hospital and assessed depression at month 0 and 12 using the Patient Health Questionnaire-9 (PHQ-9). Association between clinical, sociodemographic factors and changes in PHQ-9 scores were evaluated. Among 320 study participants, 171 (53.4%) and 55 (17.2%) had depression at month 0 and 12 respectively. Persistent depression was detected in 41 (24.0%) of the 171 patients with depression at month 0, whilst 135 (42.2%) of them never experienced depression. Patients' CD4 count was associated with depression at month 0 and 12 (p<0.05). Predictors of change in depression scores were urban dwelling [-1.98, 95%CI: -3.86 to -0.06, p=0.039], not knowing one's monthly income [2.10, 95%CI: 0.58 to 3.61, p=0.007], participant being single [-1.62 95%CI: -2.45 to -0.78, p<0.001] and being on antiretroviral therapy at recruitment [-1.5, 95%CI: -2.55 to -0.45, p<0.001]. There was a significant decrease in depression scores over a 12-month period and persistent depression is rife among this cohort of Ghanaians with HIV.

Utilizing Implementation Science to Bridge Cerebrovascular Health Disparities: a Local to Global Perspective.

PURPOSE OF REVIEW: Stroke is a prime example of a medical disorder whose incidence, prevalence, and outcomes are strongly characterized by health disparities across the globe. This scoping literature review seeks to depict how implementation science could be utilized to advance health equity in the prevention, acute treatment, and post-acute management of stroke in the underserved regions of high-income countries as well as in all low-income countries. RECENT FINDINGS: A major reason for the persisting and widening cerebrovascular disease disparities is that evidence-based stroke prevention and treatment interventions have been differentially translated (if at all) to various populations and settings. The field of implementation science is endowed with frameworks, theories, methodological approaches, and outcome measures, including equity indices, which could be harnessed to facilitate the translation of evidence-based interventions into clinical practice for underserved and vulnerable communities. Encouragingly, there are several novel frameworks, which eminently merge implementation science constructs with health equity determinants, thereby opening up key opportunities to bridge burgeoning worldwide gaps in cerebrovascular health equity.

Promise of Physiological Profiling to Prevent Stroke in People of African Ancestry: Prototyping Ghana.

PURPOSE OF REVIEW: Worldwide, compared to other racial/ethnic groups, individuals of African ancestry have an excessively higher burden of hypertension-related morbidities, especially stroke. Identifying modifiable biological targets that contribute to these disparities could improve global stroke outcomes. In this scoping review, we discuss how pathological perturbations in the renin-angiotensin-aldosterone pathways could be harnessed via physiological profiling for the purposes of improving blood pressure control for stroke prevention among people of African ancestry. RECENT FINDINGS: Transcontinental comparative data from the USA and Ghana show that the prevalence of treatment-resistant hypertension among stroke survivors is 42.7% among indigenous Africans, 16.1% among African Americans, and 6.9% among non-Hispanic Whites, p < 0.0001. A multicenter clinical trial of patients without stroke in 3 African countries (Nigeria, Kenya, and South Africa) demonstrated that physiological profiling using plasma renin activity and aldosterone to individualize selection of antihypertensive medications compared with usual care resulted in better blood pressure control with fewer medications over 12 months. Among Ghanaian ischemic stroke survivors treated without renin-aldosterone profiling data, an analysis revealed that those with low renin phenotypes did not achieve any meaningful reduction in blood pressure over 12 months on 3-4 antihypertensive medications despite excellent adherence. For a polygenic condition such as hypertension, individualized therapy based on plasma renin-aldosterone-guided selection of therapy for uncontrolled BP following precision medicine principles may be a viable strategy for primary and secondary stroke prevention with the potential to reduce disparities in the poor outcomes of stroke disproportionately shared by individuals of African ancestry. A dedicated clinical trial to test this hypothesis is warranted.

Long-term determinants of death after stroke in Ghana: Analysis by stroke types & subtypes.

BACKGROUND: Determinants of long-term mortality after stroke by mechanistic type and subtype are unknown in sub-Saharan Africa (SSA). Such data are crucial for targeting specific pathophysiologic pathways to improve stroke outcomes in the region. PURPOSE: To evaluate rates and predictors of mortality up to 8 years after stroke, by type and subtype, in Ghana. METHODS: We prospectively collected data on stroke patients presenting at a tertiary medical facility in Ghana between 2013 and 2018 who were followed up until October 31, 2021. Stroke diagnosis was confirmed using a Computerized Tomography scan; ischemic strokes were mechanistically typed using the TOAST classification while intracerebral hemorrhages were subtyped using the SMASH-U scheme. Demographic and clinical predictors of stroke mortality were evaluated using Cox proportional hazards regression modelling. RESULTS: Of 564 patients encountered during the study period, data on vital status were available for 556 (98.6%) subjects at discharge and 442 (78.4%) on follow-up. Mean age was 61.1 ±15.1 years, and 223 (53.1%) were male. Mortality rates at 1, 3, 12, 36, 60 and 96 months were 37.5%, 43.2%, 49.7%, 57.4%, 62.9%, and 73.7% respectively. Three (3) factors remained significantly associated with risk of death namely age, adjusted hazard ratios (aHR) of 1.12 (95%CI: 1.04-1.20), no formal education 1.36 (95% CI: 1.02-1.81) and modified Rankin score 1.67 (95%CI: 1.42 - 1.98) for each unit rise. For ischemic stroke the four (4) factors associated with long-term mortality were low formal education, low monthly income, having diabetes mellitus and higher functional score on admission. For intracerebral hemorrhage, the two factors were increasing age and high functional score. CONCLUSION: Stroke severity is the key predictor of long-term mortality after an index stroke in Ghana, regardless of the underlying pathophysiologic mechanism. Instituting acute stroke systems of care to facilitate timely reperfusion efforts may greatly improve long term survival outcomes after stroke in SSA.

The African Stroke Organization Conference 2021: Building Capacity, Careers, Collaborations, and Contributions.

The inaugural African Stroke Organization Conference (ASOC) aimed to create a forum to discuss the latest stroke science, highlight opportunities to address the high burden of stroke in Africa, develop a viable pipeline of emerging African stroke researchers, honor leading scientists and policy makers, and provide networking avenues to bolster future collaboration. Using a virtual platform, ASOC was held from Nov 3-4, 2021, and was attended by 236 participants. ASOC 2021 sessions included: (1) Osuntokun Award Lecture delivered by Prof. Richard Walker of Newcastle University; (2) Distinguished Policy Maker Lecture delivered by Dr. Raj Tajudeen of the African Centers for Disease Control and Prevention; (3) Invited presentations by prominent global stroke academicians on acute stroke, vascular malformations, vascular brain injury, Covid-19, nursing/allied care, rehabilitation/recovery, health services, imaging, pediatric stroke, precision medicine, and unusual causes of stroke; (4) six oral scientific abstract presentations; and (5) fifteen moderated oral poster presentations. Other sessions were (i) Vascular Brain Trust where early career African scholars presented manuscripts and grant proposals under development for feedback from seasoned researchers (ii) Moving on Up during which presentations were given to early career scholars about pathways for success in funding and advancement. A capstone event was the Frontiers of Research in Africa session which showcased the work and capabilities of 20 scientists and sites in Africa. All the ASOC sessions were lively and post-conference feedback from attendees showed high levels of satisfaction for the conference platforms and content. The ASOC marks a new dawn in the era of an escalating stroke burden in Africa, and it is anticipated to serve as a catalyst for exponentially building the capacity, careers, collaborations, and contributions of Africans to ameliorating stroke within and beyond the continent.

Life's Simple 7 at Midlife and Risk of Recurrent Cardiovascular Disease and Mortality after Stroke: The ARIC study.

BACKGROUND: Stroke is a leading cause of morbidity and mortality among adults in the U.S. Ideal levels of the Life's Simple 7 (LS7) are associated with lower cardiovascular disease (CVD) and all-cause mortality. However, the association of LS7 with CVD, recurrent stroke, and all-cause mortality after incident stroke is unknown. METHODS: We used data from the ARIC study, a cohort of 13,508 adults from four US communities, 45-64 years old at baseline (1987-1989). Cardiovascular hospitalizations and mortality were ascertained in follow-up through December 31st, 2017. We defined cardiovascular health (CVH) based on AHA definitions for LS7 (range 0-14) and categorized CVH into four levels: LS7 0-3, 4-6, 7-9, and ≥10 (ideal LS7), according to prior studies. Outcomes included incident stroke, CVD, recurrent stroke, all-cause mortality, and a composite outcome including all the above. Adjusted hazard ratios (95% CI) were estimated with Cox proportional hazards regression models. RESULTS: Median (25%-75%) follow-up for incident stroke was 28 (18.6-29.2) years. Participants with incident stroke were 55.7 (SD 5.6) years-old at baseline, 53% were women and 35% Black. Individuals with LS7 score ≥10 had 65% lower risk (HR: 0.35; 95% CI: 0.29-0.41) of incident stroke than those with LS7 4-6 (reference group). Of 1,218 participants with incident stroke, 41.2% (n=502) had composite CVD and 68.3% (n=832) died during a median (25%-75%) follow-up of 4.0 (0.76-9.95) years. Adjusted HR (95% CI) for stroke survivors with LS7≥10 at baseline were 0.74 (0.58-0.94) for the composite outcome, 0.38(0.17-0.85) for myocardial infarction, 0.60 (0.40-0.90) for heart failure, 0.63 (0.48-0.84) for all-cause mortality, and 0.65 (0.39-1.08) for recurrent stroke. CONCLUSIONS: Good and excellent midlife cardiovascular health are associated with lower risks of incident stroke and CVD after stroke. Clinicians should stress the importance of a healthy lifestyle for primary and secondary CVD prevention.

Differential associations between pre-diabetes, diabetes and stroke occurrence among West Africans.

BACKGROUND: There are limited data from Africa on the burden and associations between pre-diabetes (pre-DM), diabetes mellitus (DM) and stroke occurrence in a region experiencing a profound rise in stroke burden. PURPOSE: To characterize the associations between stroke and dysglycemic status among West Africans. METHODS: The Stroke Investigative Research and Educational Network (SIREN) is a multicenter, case-control study involving 15 sites in Ghana and Nigeria. Cases include adults aged ≥18 years with clinical and radiological evidence of an acute stroke. Controls were age-and-gender matched stroke-free adults. Detailed evaluations for vascular factors were performed. Pre-diabetes was defined as HBA1c of 5.7%-6.4% or Fasting blood glucose (FBG) 5.6-7.0 mmol/L and DM as HBA1c >6.5% or FBG>7.0 mmol/L. We used conditional logistic regression to estimate adjusted odds ratios (aOR) with 95% Confidence Interval. RESULTS: Among 2,935 stroke cases the mean age was 60.0 ± 14.2 years with 55.2% being males. By glycemic status, 931 (31.7%) were euglycemic, 633 (21.6%) had Pre-diabetes and 1371 (46.7%) had DM. Of the age- and sex-matched stroke-free controls 69.2% were euglycemic, 13.3% had pre-DM and 17.5% had DM. Pre-DM [aOR (95% CI): 3.68(2.61-5.21)] and DM [4.29 (3.19-5.74)] were independently associated with stroke. The aOR of Pre-DM for ischemic stroke 3.06 (2.01-4.64)] was lower than 4.82 (3.37-6.89) for DM. However, the aOR of Pre-DM for hemorrhagic stroke 6.81 (95% CI: 3.29 - 14.08)] was higher than 3.36 (1.94-5.86) for DM. Furthermore, the aOR of pre-DM for ischemic stroke subtypes were 9.64 (1.30-71.57) for cardio-embolic stroke, 3.64 (1.80-7.34) for small-vessel occlusive disease and 4.63 (0.80-26.65) for large-vessel disease. CONCLUSION: Pre-DM is strongly and independently associated with stroke in Africans. Improving glycemic control through screening, healthy lifestyle and pharmacotherapy at a population level may be strategic in reducing the rising burden of stroke in Africa.

Rifampicin and clarithromycin (extended release) versus rifampicin and streptomycin for limited Buruli ulcer lesions: a randomised, open-label, non-inferiority phase 3 trial.

BACKGROUND: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans infection that damages the skin and subcutis. It is most prevalent in western and central Africa and Australia. Standard antimicrobial treatment with oral rifampicin 10 mg/kg plus intramuscular streptomycin 15 mg/kg once daily for 8 weeks (RS8) is highly effective, but streptomycin injections are painful and potentially harmful. We aimed to compare the efficacy and tolerability of fully oral rifampicin 10 mg/kg plus clarithromycin 15 mg/kg extended release once daily for 8 weeks (RC8) with that of RS8 for treatment of early Buruli ulcer lesions. METHODS: We did an open-label, non-inferiority, randomised (1:1 with blocks of six), multicentre, phase 3 clinical trial comparing fully oral RC8 with RS8 in patients with early, limited Buruli ulcer lesions. There were four trial sites in hospitals in Ghana (Agogo, Tepa, Nkawie, Dunkwa) and one in Benin (Pobè). Participants were included if they were aged 5 years or older and had typical Buruli ulcer with no more than one lesion (caterories I and II) no larger than 10 cm in diameter. The trial was open label, and neither the investigators who took measurements of the lesions nor the attending doctors were masked to treatment assignment. The primary clinical endpoint was lesion healing (ie, full epithelialisation or stable scar) without recurrence at 52 weeks after start of antimicrobial therapy. The primary endpoint and safety were assessed in the intention-to-treat population. A sample size of 332 participants was calculated to detect inferiority of RC8 by a margin of 12%. This study was registered with ClinicalTrials.gov, NCT01659437. FINDINGS: Between Jan 1, 2013, and Dec 31, 2017, participants were recruited to the trial. We stopped recruitment after 310 participants. Median age of participants was 14 years (IQR 10-29) and 153 (52%) were female. 297 patients had PCR-confirmed Buruli ulcer; 151 (51%) were assigned to RS8 treatment, and 146 (49%) received oral RC8 treatment. In the RS8 group, lesions healed in 144 (95%, 95% CI 91 to 98) of 151 patients, whereas lesions healed in 140 (96%, 91 to 99) of 146 patients in the RC8 group. The difference in proportion, -0·5% (-5·2 to 4·2), was not significantly greater than zero (p=0·59), showing that RC8 treatment is non-inferior to RS8 treatment for lesion healing at 52 weeks. Treatment-related adverse events were recorded in 20 (13%) patients receiving RS8 and in nine (7%) patients receiving RC8. Most adverse events were grade 1-2, but one (1%) patient receiving RS8 developed serious ototoxicity and ended treatment after 6 weeks. No patients needed surgical resection. Four patients (two in each study group) had skin grafts. INTERPRETATION: Fully oral RC8 regimen was non-inferior to RS8 for treatment of early, limited Buruli ulcer and was associated with fewer adverse events. Therefore, we propose that fully oral RC8 should be the preferred therapy for early, limited lesions of Buruli ulcer. FUNDING: WHO with additional support from MAP International, American Leprosy Missions, Fondation Raoul Follereau France, Buruli ulcer Groningen Foundation, Sanofi-Pasteur, and BuruliVac.

Prevalence and incidence of pre-diabetes and diabetes mellitus among people living with HIV in Ghana: Evidence from the EVERLAST Study.

BACKGROUND: Available data from high-income countries suggest that people living with HIV (PLWH) have a four-fold higher risk of diabetes compared with HIV-negative people. In sub-Saharan Africa, with 80% of the global burden of HIV, there is a relative paucity of data on the burden and determinants of prevalent and incident dysglycaemia. OBJECTIVES: To assess the prevalence and incidence of pre-diabetes (pre-DM) and overt diabetes mellitus (DM) among PLWH in a Ghanaian tertiary medical centre. METHODS: We first performed a cross-sectional comparative analytical study involving PLWH on combination antiretroviral therapy (cART) (n = 258), PLWH not on cART (n = 244) and HIV-negative individuals (n = 242). Diabetes, pre-DM and normoglycaemia were defined as haemoglobin A1C (HBA1c) > 6.5%, in the range 5.7-6.4% and < 5.7% respectively. We then prospectively followed up the PLWH for 12 months to assess rates of new-onset DM, and composite of new-onset DM and pre-DM. Multivariate logistic regression models were fitted to identify factors associated with dysglycaemia among PLWH. RESULTS: The frequencies of DM among PLWH on cART, PLWH not on cART and HIV-negative individuals were 7.4%, 6.6% and 7.4% (P = 0.91), respectively, while pre-DM prevalence rates were 13.2%, 27.9% and 27.3%, respectively (P < 0.0001). Prevalent DM was independently associated with increasing age [adjusted odds ratio (95% confidence interval) (aOR, 95% CI) = 1.82 (1.20-2.77) for each 10-year rise], male sex [aOR = 2.64 (1.20-5.80)] and log(triglyceride/HDL cholesterol) [aOR = 8.54 (2.53-28.83)]. Prevalent pre-DM was independently associated with being on cART [aOR (95% CI) = 0.35 (0.18-0.69)]. There were a total of 12 cases of incident DM over 359.25 person-years, giving 33.4/1000 person-years of follow-up (PYFU) (95% CI: 18.1-56.8/1000), and an rate of incident pre-DM of 212.7/1000 PYFU (95 CI: 164.5-270.9/1000). The two independent factors associated with new-onset DM were having pre-DM at enrolment [aOR = 6.27 (1.89-20.81)] and being established on cART at enrolment [aOR = 12.02 (1.48-97.70)]. CONCLUSIONS: Incidence rates of pre-DM and overt DM among Ghanaian PLWH on cART ranks among the highest in the literature. There is an urgent need for routine screening and a multidisciplinary approach to cardiovascular disease risk reduction among PLWH to reduce morbidity and mortality from the detrimental effects of dysglycaemia.

Natural history of motor symptoms in Parkinson's disease and the long-duration response to levodopa.

The natural pattern of progression of Parkinson's disease is largely unknown because patients are conventionally followed on treatment. As Parkinson's disease progresses, the true magnitude of the long-duration response to levodopa remains unknown, because it can only be estimated indirectly in treated patients. We aimed to describe the natural course of motor symptoms by assessing the natural OFF in consecutive Parkinson's disease patients never exposed to treatment (drug-naïve), and to investigate the effects of daily levodopa on the progression of motor disability in the OFF medication state over a 2-year period. In this prospective naturalistic study in sub-Saharan Africa, 30 Parkinson's disease patients (age at onset 58 ± 14 years, disease duration 7 ± 4 years) began levodopa monotherapy and were prospectively assessed using the Unified Parkinson's disease Rating Scale (UPDRS). Data were collected at baseline, at 1-year and 2-years follow-up. First-ever levodopa intake induced a significant improvement in motor symptoms (natural OFF versus ON state UPDRS-III 41.9 ± 15.9 versus 26.8 ± 15.1, respectively; P < 0.001). At 1-year follow-up, OFF state UPDRS-III score after overnight withdrawal of levodopa was considerably lower than natural OFF (26.5 ± 14.9; P < 0 .001). This effect was not modified by disease duration. At the 2-year follow-up, motor signs after overnight OFF (30.2 ± 14.2) were still 30% milder than natural OFF (P = 0.001). The ON state UPDRS-III at the first-ever levodopa challenge was similar to the overnight OFF score at 1-year follow-up and the two conditions were correlated (r = 0.72, P < 0.001). Compared to the natural progression of motor disability, levodopa treatment resulted in a 31% lower annual decline in UPDRS-III scores in the OFF state (3.33 versus 2.30 points/year) with a lower model's variance explained by disease duration (67% versus 36%). Using the equation regressed on pretreatment data, we predicted the natural OFF at 1-year and 2-year follow-up visits and estimated that the magnitude of the long-duration response to levodopa ranged between 60% and 65% of total motor benefit provided by levodopa, independently of disease duration (P = 0.13). Although levodopa therapy was associated with motor fluctuations, overnight OFF disability during levodopa was invariably less severe than the natural course of the disease, independently of disease duration. The same applies to the yearly decline in UPDRS-III scores in the OFF state. Further research is needed to clarify the mechanisms underlying the long-duration response to levodopa in Parkinson's disease. Understanding the natural course of Parkinson's disease and the long-duration response to levodopa may help to develop therapeutic strategies increasing its magnitude to improve patient quality of life and to better interpret the outcome of randomized clinical trials on disease-modifying therapies that still rely on the overnight OFF to define Parkinson's disease progression.

Prevalence and Predictors of Multivitamin Supplement Use After Stroke in Ghana.

BACKGROUND: Multivitamins are commonly used supplements in high income countries, but their net benefit-risk, remains inconclusive. Little is known about the prevalence and predictors of multivitamin supplementation among individual with chronic illnesses in sub-Saharan Africa, especially stroke. PURPOSE: To assess the frequency and factors associated with of use of multivitamin supplement among stroke survivors in Ghana. METHODS: We analyzed prospectively collected data on consecutively encountered stroke survivors seen at an out-patient clinic in Ghana between January 2018 and March 2020. We collected baseline demographic and clinical details, and use of multivitamins among other secondary prevention medications prescribed. We assessed factors associated with multivitamin supplementation using a multivariable logistic regression analysis. RESULTS: Among 1,101 stroke survivors, 324 (29.4%) were on multivitamin supplements. Factors independently associated with multivitamin use were being divorced (OR 2.88; 95% CI: 1.52-5.47), time since diagnosis of index per each month increase (OR 0.99; 95% CI: 0.99-1.00), and number of prescribed classes of antihypertensive medications (OR 0.81; 95% CI: 0.72-0.92). CONCLUSION: Nearly a third of stroke survivors in this Ghanaian sample were on multivitamin supplementation, with select socio-clinical factors being linked to this practice. Future studies should examine how/if this practice is interfering with optimal stroke outcomes.

Factors Linked to Chronic Kidney Disease Among Stroke Survivors in Ghana.

BACKGROUND: Chronic kidney disease (CKD) is associated with poor outcomes among stroke survivors. In Africa, where both stroke and CKD incidence rates are escalating, little, if anything, is known about the burden of CKD among stroke survivors. OBJECTIVE: To assess the frequency and factors associated with CKD among stroke survivors by primary stroke types. METHODS: Stroke registry data were prospectively collected on consecutively encountered stroke survivors seen at an out-patient clinic in Ghana between January 2018 and March 2020. We calculated estimated glomerular filtration rate (eGFR) using the CKD-EPI formula and defined CKD as eGFR <60ml/min. Factors associated with CKD were assessed using multiple logistic regression modelling. RESULTS: Among 759 stroke survivors, 159 had CKD giving a prevalence of 21.0% (95%CI: 18.1% - 23.8%). The mean age of those with CKD was 61.6 ± 14.2 years compared with 57.5 ± 13.6 years, p=0.0007 among those without CKD. Five factors remained significantly associated with CKD with the following adjusted odds ratio (aOR and 95% CI). Age per decile rise 1.30 (1.13-1.50), male sex 1.99 (1.36-2.93), rural dwelling residence 1.95 (1.06-3.59), prior use of antihypertensive meds before index stroke onset 1.63 (1.08-2.47), and number of antihypertensive medication classes 1.25 (1.06-1.45). CONCLUSION: 1 in 5 stroke survivors have evidence of chronic kidney disease in this Ghanaian study. Targeted interventions focusing on optimizing blood pressure control and rural dwellers may mitigate their risk for adverse outcomes.