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.

A cardiovascular polypill for secondary stroke prevention in a tertiary centre in Ghana (SMAART): a phase 2 randomised clinical trial.

BACKGROUND: A cardiovascular polypill containing generic drugs might facilitate sustained implementation of and adherence to evidence-based treatments, especially in resource-limited settings. However, the impact of a cardiovascular polypill in mitigating atherosclerotic risk among stroke survivors has not been assessed. We aimed to compare a polypill regimen with usual care on carotid intima-media thickness (CIMT) regression after ischaemic stroke. METHODS: In SMAART, a phase 2 parallel, open-label, assessor-masked, randomised clinical trial, we randomly allocated individuals (aged ≥18 years) who had an ischaemic stroke within the previous 2 months, using a computer-generated randomisation sequence (1:1), to either a polypill or usual care group at a tertiary centre in Ghana. The polypill regimen was a fixed-dose pill containing 5 mg ramipril, 50 mg atenolol, 12·5 mg hydrochlorothiazide, 20 mg simvastatin, and 100 mg aspirin administered as two capsules once per day for 12 months. Usual care was tailored guideline-recommended secondary prevention medications. The primary outcome was the change in CIMT over 12 months with adjustment for baseline values, compared using ANCOVA in all participants with complete data at month 12. Safety was analysed in all randomly assigned participants. This trial is registered at ClinicalTrials.gov, NCT03329599, and is completed. FINDINGS: Between Feb 12, 2019, and Dec 4, 2020, we randomly assigned 148 participants (74 to the usual care group and 74 to the polypill group), 74 (50%) of whom were male and 74 (50%) female. CIMT was assessed in 62 (84%) of 74 participants in the usual care group and 59 (80%) of 74 participants in the polypill group; the main reason for loss to follow-up was participants not completing the study. The mean CIMT change at month 12 was -0·092 mm (95% CI -0·130 to -0·051) in the usual care group versus -0·017 mm (-0·067 to 0·034) in the polypill group, with an adjusted mean difference of 0·049 (-0·008 to 0·109; p=0·11). Serious adverse events occurred among two (3%) participants in the usual care group, and eight (11%) participants in the polypill group (p=0·049). INTERPRETATION: The polypill regimen resulted in similar regression in subclinical atherosclerosis and many secondary and tertiary outcome measures as the tailored drug regimen, but with more serious adverse events. Larger, longer-term, event-based studies, including patients with stroke in primary care settings, are warranted. FUNDING: US National Institutes of Health. TRANSLATION: For the Akan (Twi) translation of the abstract see Supplementary Materials section.

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.

Estimated glomerular filtration rate predicts incident stroke among Ghanaians with diabetes and hypertension.

BACKGROUND: Sub-Saharan Africa is currently experiencing a high burden of both chronic kidney disease (CKD) and stroke as a result of a rapid rise in shared common vascular risk factors such as hypertension and diabetes mellitus. However, no previous study has prospectively explored independent associations between CKD and incident stroke occurrence among indigenous Africans. This study sought to fill this knowledge gap. METHODS: A prospective cohort study involving Ghanaians adults with hypertension or type II diabetes mellitus from 5 public hospitals. Patients were followed every 2 months in clinic for 18 months and assessed clinically for first ever stroke by physicians. Serum creatinine derived estimated glomerular filtration rates (eGFR) were determined at baseline for 2631 (81.7%) out of 3296 participants. We assessed associations between eGFR and incident stroke using a multivariate Cox Proportional Hazards regression model. RESULTS: Stroke incidence rates (95% CI) increased with decreasing eGFR categories of 89, 60-88, 30-59 and <29 ml/min corresponding to incidence rates of 7.58 (3.58-13.51), 14.45 (9.07-21.92), 29.43 (15.95-50.04) and 66.23 (16.85-180.20)/1000 person-years respectively. Adjusted hazard ratios (95%CI) for stroke occurrence according to eGFR were 1.42 (0.63-3.21) for eGFR of 60-89 ml/min, 1.88 (1.17-3.02) for 30-59 ml/min and 1.52 (0.93-2.43) for <30 ml/min compared with eGFR of >89 ml/min. Adjusted HR for stroke occurrence among patients with hypertension with eGFR<60 ml/min was 3.69 (1.49-9.13), p = .0047 and among those with diabetes was 1.50 (0.56-3.98), p = .42. CONCLUSION: CKD is dose-dependently associated with occurrence of incident strokes among Ghanaians with hypertension and diabetes mellitus. Further studies are warranted to explore interventions that could attenuate the risk of stroke attributable to renal disease among patients with hypertension in SSA.

Administration of a pictorial questionnaire to screen for stroke among patients with hypertension or diabetes in rural Ghana.

BACKGROUND: Stroke prevention is an important public health goal in low-and-middle income countries (LMIC) due to its high mortality and morbidity in these settings. Epidemiological data from high-income countries have demonstrated a potent predictive association between self-reported stroke symptoms and risks of future strokes, incident cognitive impairment and all-cause mortality. OBJECTIVE: To utilize a pictographic version of the 8-item Questionnaire for Verifying Stroke Free Status (QVSFS) to screen for stroke symptoms and determine its predictors among hypertensive and diabetic patients in a rural hospital within a LMIC. METHODS: Between July and October 2016, 500 consecutive patients with hypertension and/or diabetes mellitus encountered in clinic at the Agogo Presbyterian Hospital, a district level health institution in Ghana were enrolled. A validated pictographic version of the QVSFS was administered by trained research assistants to all study participants and demographic and clinical information on hypertension and diabetes control were collected. The neurologist/specialist physician examined all patients neurologically using a structured questionnaire and reviewed medical charts for objective documentary evidence of stroke. Predictors of stroke symptoms were assessed using a multivariate logistic regression model. RESULTS: Among the cohort, median (IQR) age was 58 (51-66) years, 399 (79.8%) were women, 388 (77.6%) had hypertension, 92 (18.4%) had diabetes and hypertension, and 20 (4.0%) had just diabetes. 30 (6.0%) patients had confirmed stroke/TIA after physician evaluation, 151 (30.6%) had at least one symptom of stroke (SS) without prior diagnosis of stroke/TIA and 319 (63.8%) reported no stroke symptoms. Independent predictors of reporting stroke symptoms were increasing age - aOR: 1.38 (1.16-1.64) for each 10years older and HBA1C-OR: 1.74 (1.16-2.61) for each 2% increase. Subjects with previous stroke/TIA diagnosis had significantly higher mean±SD systolic blood pressure (148.0±21.2mmHg vs. 136.0±17.3mmHg vs. 138.3±19.7mmHg, p=0.009) and median (IQR) HBA1C (8.8% (6.7-10.2) vs. 8.2 (6.4-10.6) vs. 7.2 (6.3-8.0), p=0.05) compared with SS and asymptomatic groups. CONCLUSION: One in three patients with hypertension and/diabetes in rural Ghana report stroke-like symptoms. Routine use of the pictographic version of the QVSFS could assist in identifying patients with or at high risk for stroke who may benefit from appropriate prevention treatments.