Clinical trial NCT03728153
Conditions: Acute Stroke Stroke, Ischemic
Keywords: Motor recovery
Sponsor: Massachusetts General Hospital
Start date: 2019-11-26; Completion date: 2021-01-06
Enrollment: 34 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a phase II, randomized study of 120 adults age 18 or above who will prescribed 20mg daily Fluoxetine for 90 days following acute, ischemic stroke.

Detailed description:
This is a prospective, phase II study of fluoxetine for motor recovery post-stroke in adults with new-onset ischemic stroke in urban Tanzania. Participants will be enrolled at the Muhimbili National Hospital (MNH) in Dar Es Salaam after confirmation of exclusion and inclusion criteria, including a head CT. Participants will be enrolled within 21 days of acute, ischemic stroke. The study will utilize a novel method for monitoring patient medication adherence: electronic pill bottles that can record medication use events. The primary goals of this study are to assess the safety and tolerability of fluoxetine post-stroke to evaluate the feasibility of conducting a larger, phase III study in the future.

Vital status will be monitored throughout the study's enrollment period. At enrollment, participants will have cognitive tests administered, receive lumbar puncture, and receive an MRI brain. After discharge from the hospital, participants will be seen at 30-, 60-, and 90-days post-enrollment for an in-person study visit. At each time point, investigators will draw 10-15 mL of blood; download medication adherence data from participants' electronic pill bottles; and inquire about adverse events and evaluate patient disability through the modified Rankin Scale. If participants stop taking their daily pill, stroke specific reasons for non-adherence will be inquired including dysphagia, self-administration, and other concerns.

Primary assessments will be for safety and tolerability, as well as measurement of the Fugl-Meyer Motor Scale. Medication use data will also be collected through the electronic pill bottle, which will be returned to study investigators. As secondary assessments, the PHQ-9, and the Asberg Depressive Symptom Questionnaire will be administered. All 90-day assessments will be administered by senior site investigators, who will take a final 10-15mL blood draw to test for serum sodium and liver enzymes, possible adverse events related to long-term fluoxetine use, conduct a second MRI brain, evaluate participant mRS, and inquire about tolerability issues. Completion of the 90-day visit and associated assessments is considered the study endpoint.

Arms: arm 1: Fluoxetine 20 MG Oral Tablet
Interventions: intervention 1: Fluoxetine 20 MG Oral Tablet
Intervention descriptions: intervention 1: Once-daily dosing for 90 days

Protocol documents:
Prot_SAP_001.pdf: 
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Protocol Title: MAMBO: Measuring Post-Stroke Cognitive, Ambulation, Motor, and Behavioral 
Outcomes in Tanzania 
Principal investigator: Farrah J. Mateen, MD, PhD 
Funding: National Institutes of Health (R21) 
Version date: 11/30/2020 
Version 4.3 
 
I. 
Background and Significance:  
There is an under-recognized and growing epidemic of stroke in sub-Sharan Africa. Stroke is 
the leading cause of death and disability globally and accounts for more deaths than 
HIV/AIDS, malaria, and tuberculosis combined.1,2 Sixteen million people suffer a first-ever 
stroke each year worldwide. Of these, 5.7 million die and 5 million survivors remain 
disabled. In the United States, a person suffers a stroke every 40 seconds and dies of stroke 
every 4 minutes. In low- and middle-income countries (LMIC), the incidence of stroke is 
even higher: 85% of all strokes occur in LMIC.3,4,5 There exists research on post-stroke 
cognitive outcomes; however, little research has specifically centered LMIC populations that 
may benefit from the implications of such work. 
Additionally, this study has been funded by the NIH’s Fogarty International Center. The 
funding opportunity is on global brain and nervous system disorders research with a 
requirement to have a foreign site that is a low- or middle-income country.  The funding 
mechanism is meant to build capacity and enhance the understanding of brain disorders in the 
world’s low- and middle-income countries in collaboration with a high-income country. This 
study site is in the United Republic of Tanzania, a low-income country according to the 
World Bank (2016) designation. The Massachusetts General Hospital in the U.S.A. is the 
high-income country which will participate in capacity building and support all research 
endeavors. Ipso factor the study will be in a low-income country and in this case, in Tanzania, 
due to its synergies of need, science, and human resources.   
There are multiple possible benefits to the participants of this study, including accessibility to 
more expertise, increased access to physicians, and expert-provided care. In several cases, 
participants may receive better than usual care while enrolled in the study. Some may go on 
to receive neurosurgical intervention or have a diagnosis that is treatable (e.g. diagnosis of 
liver disease).  
A more thorough appreciation of stroke and its etiologies is likely both to lead to better 
clinical care and to inform new directions for care at MNH. Participants will receive free 
head CT imaging to potentially identify unrecognized and untreated causes of stroke. This 
could lead to improved health knowledge and more selected treatment approaches and care.  
At MNH, training and knowledge of stroke, clinical research, and neuroimaging will occur 
throughout this study. Neurological research and focused expert neurological care post-stroke 
are nearly non-existent in Tanzania. Therefore, initial care provisions for brain disorders will 
provide foundational knowledge of neurological care to health care workers. This is likely to 
lead to better medical care for future patients with stroke who are not involved in the study. 
II. 
Specific Aims:  


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 (1) To calculate the cognitive outcomes, as measured by the SIDSA and MoCA for 90 days 
post-stroke in 200 participants. (2) To collect medical history survey data from 200 
participants. (3) To calculate other variables of interest to the study population, including 
motor recovery (FugI Meyer, modified Rankin scale), depression (PHQ-9, Asberg Depression 
Scale), lab variables (serum sodium, ALT), and quality of life (Stroke Impact Scale). 
 
III. 
Subject selection:  
 
Both male and female subjects greater than 18 years old and subjects from any racial and 
ethnic group may be enrolled in the study. Tanzania is an ethnically homogenous country; 
nearly all residents are ethnically Tanzanian. Therefore, in practice we expect little to no 
enrollment of other ethnicities and races beyond Tanzanian Africans. Recruitment of an 
approximately 1:1 male to female ratio is expected. Total recruitment is aimed at 200 
participants with new-onset acute ischemic or hemorrhagic stroke presenting at Muhimbili 
National Hospital (MNH) within 21 days of symptomatic onset.  
 
No children will be enrolled in the study. The mechanisms of stroke in pediatric age groups 
are presumed to be very different (e.g. non- atherosclerotic) and are outside the scope of the 
study question. 
 
Study recruitment will occur exclusively at Muhimbili National Hospital (MNH) in Dar es 
Salaam, Tanzania. Patients presenting to the hospital with symptoms of stroke will be 
administered a head CT paid for through study funds. The head CT will thus be administered 
as part of the screening process, not the study itself. Head CT is, in principle, the standard of 
care at MNH for patients with stroke; however, in reality most patients cannot afford a head 
CT within 21 days of presentation. Many patients do, at some point, receive a head CT, but it 
generally takes time as the patient’s family members must come together to pool financial 
resources to pay for the scan. In the interest of financially equitable subject selection – in 
order not to immediately screen out poor stroke patients who cannot afford head CT – we 
have made the decision to pay for head CTs for all patients who present with the symptoms of 
stroke. The head CT will be read by a local team, which will determine ischemic or 
hemorrhagic stroke. A consulting neuro-radiologist will confirm the local team’s findings.  
 
Sub-classification of ischemic or hemorrhagic stroke will be based on the TOAST (1993) 
categorization. Following confirmation of ischemic or hemorrhagic stroke, study 
investigators will determine patient eligibility for inclusion in the study. The investigators 
will administer questionnaires to collect patient health history and perform blood tests to 
measure physical health characteristics. Questionnaires will follow the Get with the 
Guidelines® survey intake forms of the American Heart Association, as developed in 
preliminary studies. Blood tests will be comprehensive: Testing for HIV will include CD4 
count and viral load (HIV ELISA and Uni-GoldTM) performed at MNH; serum sodium, 
potassium, liver tests, creatinine, and hemoglobin A1c will be tested; women of childbearing 
potential will have a B-HCG test. Participants will be screened for dysphagia. Sub-
classification of ischemic stroke will be based on the TOAST (1993) categorization. 


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Following confirmation of ischemic or hemorrhagic stroke, study investigators will determine 
patient eligibility for inclusion in the study. The investigators will administer questionnaires 
to collect patient health history and perform blood tests to measure physical health 
characteristics. Questionnaires will follow the Get with the Guidelines® survey intake forms 
of the American Heart Association, as developed in preliminary studies. Blood tests will be 
comprehensive: Testing for HIV will include CD4 count and viral load (HIV ELISA and Uni-
GoldTM) performed at MNH; serum sodium, potassium, liver tests, creatinine, and 
hemoglobin A1c will be tested; women of childbearing potential will have a B-HCG test. 
Participants will be screened for dysphagia.  
 
Participants will be screened by study physicians upon presentation for eligibility according 
to the following exclusion criteria: (1) NIH Stroke Scale Score >20 points, (2) unconscious at 
presentation, (3) transient ischemic symptoms <24h, (4) history of recent head trauma, (5) 
baseline motor deficits from other etiologies including prior stroke, and (6) patients who are 
moribund for other reasons and unlikely to survive to 90 days will also be excluded from 
participation. Additionally, (7) contraindication to MRI (e.g. piercings/tattoos, 
electronic/metallic implants, claustrophobia). All assessments of exclusion criteria/safety will 
be conducted by trained, IRB-approved study neurologists who are familiar with the 
procedures.  
 
If a patient is found eligible, he or she will be approached, in person, by Tanzanian study 
coordinators and presented with the opportunity to enroll in the study.   
 
IV. 
Subject Enrollment: 
 
Consent will be obtained after confirmation both of acute ischemic or hemorrhagic stroke and 
patient eligibility criteria. A trained study staff member who is a licensed physician, without 
prior clinical connection to the patient, will be present in person to administer consent forms 
either in Swahili or English. Since there is limited outpatient stroke care prior to a new-onset 
stroke, we do not anticipate familiarity between the neurologist on duty at MNH and the 
newly admitted patients.  
 
Since 50% of strokes occur in the dominant hemisphere and 50% of strokes occur in the non-
dominant hemisphere, we expect that about half of eligible patients will be unable to give 
independent consent for participation. This is because strokes that occur in the dominant 
brain hemisphere can result in aphasia, dysphasia, or motor deficits in the dominant hand. 
There is no ethical or legal prerogative to exclude 50% of stroke patients simply because they 
are unable to speak or move their hand. Thus, in the case that study investigators encounter 
aphasic, dysphasic, or motor-impaired patients, investigators will seek surrogate consent 
through a medical proxy. 
 
Additionally, stroke patients often experience fluctuating states of lucidity, which can result 
in various decisional or cognitive impairments. Surrogate consent will be sought from 
medical proxies in the case of patients with decisional impairments. Such patients should be 
included in research to study interventions that can potentially benefit their condition and 
their recovery. Furthermore, inclusion of patients with decisional impairments is currently 
standard in stroke research.  


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Three classes of medical proxies will be allowed to give surrogate consent in writing. These 
classes are, in preferred order: (1) a court appointed guardian with specific authority to 
consent to participation in research studies or the authority to make health care decisions 
within the class of diagnostic and therapeutic procedures of this study. (2) A proxy with 
durable power of attorney with the specific authority to make health care decisions inclusive 
of this research. And (3) a spouse, adult child, or other close family member who knows the 
potential participant well and has been previously involved in their care or any other class of 
surrogates that the local ethics committee deems appropriate. A surrogate who provides 
consent will be advised that his/her decision should reflect the potential participant’s own 
views when he/she had the capacity to express them. If the potential subject did not 
previously express a view on the matter, the surrogate will be advised to make a decision 
based on the potential subject’s best interest.  
 
If a medical proxy is necessary to provide consent for a subject’s participation, a note will be 
made in the research record. The relation of the proxy to the subject will be recorded as will 
the subject’s ability to provide assent to participation. If the subject provides assent, this will 
be noted. If the subject is unable to provide assent due to his/her medical condition, a note 
documenting this will be made in the research record.  
 
Participants will be enrolled if they meet eligibility criteria (> 18 years of age, confirmed 
ischemic or hemorrhagic stroke), are able to provide written consent or have a medical proxy 
who can provide surrogate consent, are able to be contacted for follow up at 30, 60, and 90 
days, and are willing to be examined and interviewed by study investigators on the outcomes. 
Participants must be geographically reachable and able to either return to MNH or have a 
study investigator complete a home visit at 90 days. Participants >100km away by land or 
residing on islands will be considered geographically unreachable.  
 
Tanzanian investigators will be primarily performing screening, consent, and enrollment. 
Participants will be asked for contact information including phone number and address. Three 
additional ways to contact the participant will be inquired including phone numbers of next of 
kin.  
 
Following the consenting process, Tanzanian site investigators will provide participants with 
a study ID number. 
 
V. 
Study Procedures:  
 
After consent has been furnished, study staff will record baseline data for each subject. The 
majority of baseline data will come from the screening process, including serum sodium and 
hepatic enzyme levels. They will receive an MRI brain. Initial motor impairment will be 
evaluated through the Fugl-Meyer Motor Scale, the assessment of which will be digitally 
filmed in order to allow for validation of aberrant scores. Recordings of the Fugl-Meyer 
assessment will be stored on encrypted, password-protected external hard-drives. Participants 
in the videos will be identified only through study ID number and the files will be labeled 
with the study ID number. The video will be used to validate Fugl-Meyer scores; since the 
Fugl-Meyer assessment is complex, if any issues arise in the administration and scoring 


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process, we will be able to show the video to study-staff who are experts in the Fugl-Meyer 
assessment to guarantee that each subject’s baseline Fugl-Meyer score is accurate. 
Participants will have initial cognitive capacity measured through the MoCA scale and IDEA 
scale, administered in English or Kiswahili per patient preference.  
Study participants will be contacted within three days of the 30-, 60-, and 90-day time-points 
to schedule an in-person visit, either at the hospital or at the participant’s home. At each study 
visit, participants will be evaluated for medication and evaluated for adverse side-effects 
through verbal inquiry on the part of the investigator; investigators will draw 10-15mL of 
blood, in order to perform sodium and hepatic enzyme labs; investigators will assess 
participant disability through the modified Rankin Scale (mRS).  
Analysis of serum sodium and hepatic enzyme levels will be conducted at MNH. Blood 
samples will also be shipped to the US for analysis of biomarkers of post-stroke cognitive 
decline.  
If participants are unable to be reached in person during the 30- and 60-day follow-up visits, 
they will be called by Tanzanian site investigators. During these calls, investigators will 
evaluate the mRS of the participant and will inquire about adverse side-effects. The 90-day 
follow-up will occur either at MNH or at participants’ home, whichever location was 
indicated as preferable during the screening and consent process. 
Study Design: This study will be an observational trial to determine cognitive outcomes for 
90 days following acute ischemic/hemorrhagic stroke in Tanzania. 200 patients presenting to 
Muhimbili National Hospital (MNH) with acute stroke will be enrolled. Subjects will be 
followed at 30, 60, and 90 days. The study endpoint will be considered as completion of the 
90-day follow-up. Subjects will be remunerated the Tanzanian Schilling equivalent of 50 
USD.  
 
Objectives: (1) To calculate the cognitive outcomes, as measured by the SIDSA and MoCA 
for 90 days post-stroke in 200 participants. (2) To collect medical history survey data from 
200 participants. (3) To calculate other variables of interest to the study population, including 
motor recovery (FugI Meyer, modified Rankin scale), depression (PHQ-9, Asberg Depression 
Scale), lab variables (serum sodium, ALT), and quality of life (Stroke Impact Scale).  
 
All 90-day assessments will be administered by senior site investigators, who will also take 
the final 10-15mL blood draw, evaluate participant mRS, and inquire about adverse events. 
Participants will receive a second MRI brain at 90-days and will be administered the MoCA 
and IDEA screens. As at baseline, the 90-day Fugl-Meyer assessment will be filmed and 
stored on an encrypted external hard drive. In the case of aberrant scores or difficulty scoring, 
the video will be shown to expert study staff for validation of the correct Fugl-Meyer score.  
It is possible that during the 90-day raft of questionnaires, participants will endorse survey 
questions that indicate suicidality. In such cases, participants will be formally referred to the 
study-site neurologist for psychiatric care and thorough psychological evaluation. Participants 


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will be referred to the managing neurologist because the number of psychiatrists in Dar Es 
Salaam is very low.  
It may be necessary to drop certain participants from the study. In such cases, Tanzanian site 
investigators will evaluate the participant’s continued participation in the study according to 
the following drop criteria: (1) participants who develop a serious, non-stroke related disease, 
like cancer, that will alter their life or seriously affect their medicine regimen; (2) participants 
who die; (3) participants who are lost to follow-up, defined as not being available during 
three attempts at contact 3 days apart over the course of 9 days; (4) participants who are 
unconscious or bed-ridden, defined as having an mRS score of 5 or great; and (5) participants 
who become pregnant.  
If a participant meets any drop criteria, Tanzanian site investigators will send a proposal, in 
writing, to U.S.  site investigators to withdraw the participant from the study. U.S. site 
investigators will respond within 24 hours. When approved by U.S. site investigators, the 
participant will be formally withdrawn from the study. In cases where a participant develops 
a serious non-stroke related disease, he or she will be referred to appropriate physicians at 
MNH. In cases of death, loss to follow-up, or unconsciousness, Tanzanian site investigators 
will make a reasonable attempt to discover the circumstances surrounding participant 
withdrawal. Participant withdrawal will be noted in a Withdrawal Log alongside a brief 
explanation. 
Payment will be provided to participants. Payment will be the equivalent of 50 USD, 
approximately 116,000 Tanzanian Shillings. We expect this amount to fully cover the 
costs of transportation to and from the MNH. 
VI. 
Biostatistical Analysis:  
Data will include stroke motor-function recovery, cognition, serum sodium and hepatic 
enzyme laboratories, and quality-of-life/depression data, which will be captured, respectively, 
through changes in the Fugl-Meyer motor assessment between study enrollment and 
completion, through the IDEA and MoCA assessments, and through both the Asberg 
Depressive Symptom and PHQ-9 questionnaires. 
The number of participants has been chosen based on an estimated natural history from our 
pilot observation work.  A post-stroke mortality of approximately 30% at 90 days is assumed. 
Of n=200 enrolled participants, 140 are assumed to be alive at 90 days. 
VII. 
Risks and Discomforts:  
Risks associated with blood draws: During venous blood draws the skin is pierced by a 
needle. Any insult to the skin can result in discomfort, pain, and bruising. There is a slight 
risk of infections associated with blood draws. Risks will be minimized through the use of 
established blood-draw safety protocols, including exclusive use of sterile needles and use of 
alcohol swabs to disinfect the skin area that the needle will pierce. 
Risks associated with MRI: During MRI, patients can experience discomfort due to the loud 
noises and closely enclosed space of the machine. Risks will be minimized by explaining 
MRI procedures to patients. MRI is also known to be safe and used in routine stroke clinical 
care in the US.  


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Potential psychological stress/discomfort: There exists a risk of incurring psychological 
discomfort due to diagnostic questions about mood. Discomfort includes embarrassment, 
anxiety, panic, or depression. In the event of severe psychological distress, subjects will be 
promptly referred to appropriate mental health experts. 
Potential risks due to higher than usual standard of care: Participants in this study will be 
exposed to a better than normal standard of care. This includes access to physical and 
neuroimaging exams that may normally be outside patients’ financial reach. There is a risk of 
identifying a previously unknown serious medical illness or subclinical finding on brain 
imaging. Such a finding could cause a participant to be worried, anxious, or scared; however, 
discovery of an unknown, potentially life-threatening condition will prompt immediate care. 
The care that patients then receive will be at least as good as usual care, if not significantly 
better due to institution of systematized evaluations, documentation, free neuroimaging and 
blood tests, documentation of clinical course, and access to a team of expert physicians 
throughout the course of the study.  
Potential risks related to data safety and security: Participants will be exposed to risk of loss 
of confidentiality and breach of privacy. Such risks are related to the collection and 
maintenance of study data, the collection of video recordings of study procedures, and the 
collection of blood samples. These risks will be protected against via secure software 
purchases, secure data storage, training of study subjects in confidentiality best practices, and 
disclosure to participants of the intent to maintain data security at all times. All files of 
recordings of Fugl-Meyer assessments will be labeled only through participant ID.  
Unanticipated problems involving or giving rise to risks to subjects, including adverse events, 
will be reported to the Partners Healthcare Research Council (PHRC) in accordance with 
PHRC unanticipated problems reporting guidelines.  
VIII. 
Potential Benefits:  
There are multiple benefits to the participants of this study, including accessibility to more 
expertise, efficiencies in the MNH healthcare system, access to physicians, and expert-
provided care. In several cases, participants may be better treated and their underlying 
conditions better addressed. Some may go on to receive neurosurgical intervention or have a 
diagnosis that is treatable (e.g. diagnosis of liver disease).  
A more thorough appreciation of stroke and its etiologies is likely to lead to better than usual 
clinical care and inform new directions for care at MNH. Potential participants will receive 
free head CT and MRI imaging- better than usual care- to identify unrecognized and 
untreated causes of stroke. This could lead to improved health knowledge and more selected 
treatment approaches and care.  
Among the health care Hospitals, training and knowledge of stroke, clinical research, and 
neuroimaging will occur throughout this study. Neurological research and focused expert 
neurological care post-stroke are nearly non-existent in Tanzania. Therefore, initial care 
provisions for brain disorders will provide foundational knowledge of neurological care to 
health care workers. This is likely to lead to better medical care for future patients with stroke 
who are not involved in the study 
IX. 
Monitoring and quality assurance: 


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All adverse events, both those considered serious and those considered non-serious, will be 
recorded in an adverse events log; however, serious adverse events (SAE) will prompt swift 
action to preserve patient safety. Serious adverse events are defined as: death, a life-
threatening event, inpatient hospitalization or prolongation of an existing hospitalization, 
persistent or significant physical disability/incapacity, and/or congenital anomalies or birth 
defects. Non-serious adverse events include stomach discomfort and gastrointestinal distress.  
All serious adverse events/experiences as defined will be reported to the project manager at 
MNH and then to MGH within 24 hours of the Tanzanian site’s awareness, regardless of 
whether the Tanzanian investigator feels that the experience is related to the study or was 
expected. Within that 24-hour period, the site investigator in Tanzania will also complete a 
MedWatch FDA form 3500 (or modified version of this for the Tanzanian authorities) and 
email it the MGH site. For AE or significant abnormal results that are identified during a 
visit, telephone call, or other study activity, the site staff will ensure that the information is 
available to the participant and his/her primary physician (should one exist). The number of 
patients with primary physicians in Tanzania is very low. As appropriate and permitted by the 
participant, the primary care physician will be notified by the research staff via written 
correspondence to ensure follow up. If the finding affects the participant’s immediate safety 
(e.g. laboratory value far out of range), appropriate and immediate action will be taken by the 
site investigator to ensure the participant’s wellbeing. 
The site study staff will assess AEs at every point of contact with subjects by recording all 
voluntary complaints by the participant and by assessment of clinical features. All AEs will 
be recorded in a study Adverse Events log. The log will include the event term, onset date, 
resolution date, AE, and participation in the study. If a participant is withdrawn from the 
study, it will be recorded. Causality definitions will include the following: unrelated (no 
possible causation), unlikely (not reasonably related although a causal relationship cannot be 
ruled out), possibly (causal relationship uncertain), probably (high degree of certainty for a 
causal relationship), and definite (causal relationship certain). 
Additionally, participants will be advised in the written consent form that they have the right 
to permanently discontinue the study medication and/or withdraw from the study at any time 
without prejudice and may be withdrawn from the study at the discretion of the Tanzanian 
site investigator or MGH principal investigator. Administrative reasons for participant 
withdrawal include: participant withdrawal of consent, request of investigator or PI, request 
of primary care physician, nonadherence to study procedures, protocol deviation, and 
premature termination of the study.  
Patient safety will further be ensured through the appointment of an independent data safety 
monitoring board (DSMB). The responsibilities of the DSMB will span review of the 
research protocol and ongoing study activities, review of the adequacy of participant 
recruitment and retention, data quality and completeness, and fidelity to the research study 
protocol. On a regular basis, the DSMB will review medical data connected to the trial; it will 
track SAEs, medical discontinuations, and premature withdrawals in real time. The frequency 
and format of DSMB meetings and reports will be established prior to study participant 
enrollment. Its scope and operations are specified by the “NINDS Guidelines for Data and 
Safety Monitoring in Clinical Trials” at 
http://www/ninds/nih/gov/research/clinical_research/policiies/data_safety_monitoring.htm. If 


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there is a significantly greater than expected occurrence in the incidence of SAEs, the DSMB 
will make recommendations to the study PI concerning trial continuation, modification, or 
termination.   
X. 
References:  
1 
GBD 2015 Neurological Disorders Collaborator Group. Global, regional, and national 
burden of neurological disorders during 1990-2015: a systematic analysis for the Global 
Burden of Disease Study 2015. Lancet Neurol 2017;16:877-97. 
2 
Walker RW, Viney R, Green L, et al. Trends in stroke admissions to a Tanzanian  
hospital over four decades: a retrospective audit. Trop Med Int Health 2015;20:1290-6. 
3 
Stenumgård PS, Rakotondranaivo MJ, Sletvold O, et al. Stroke in a resource-constrained 
hospital in Madagascar. BMC Res Notes 2017;10:307. 
4 
Walker RW, Viney R, Green L, et al. Trends in stroke admissions to a Tanzanian hospital 
over four decades: a retrospective audit. Trop Med Int Health 2015;20:1290-6. 
5 
Seremwe F, Kaseke F, Chikwanha TM, Chikwasha V. Factors associated with hospital 
arrival time after the onset of stroke symptoms: A cross-sectional study at two teaching 
hospitals in Harare, Zimbabwe. Malawi Med J 2017;29: 171-6. 
6 
GBD 2015 Neurological Disorders Collaborator Group. Global, regional, and national
 
burden of neurological disorders during 1990-2015: a systematic analysis for the Global
 
Burden of Disease Study 2015. Lancet Neurol 2017;16:877-97. 
7 
Baatiema L, Chan CKY, Sav A, Somerset S. Interventions for acute stroke management
 
in Africa: a systematic review of the evidence. Syst Rev 2017;6:213. 
8 
Stenumgård PS, Rakotondranaivo MJ, Sletvold O, et al. Stroke in a resource-
 
constrained hospital in Madagascar. BMC Res Notes 2017;10:307. 
9  Okeng'o K, Chillo P, Gray WK, et al. 3Early mortality and associated factors among 
 
patients with stroke admitted to a large teaching hospital in Tanzania. J Stroke 
 
Cerebrovasc Dis 2017;26:871-8. 
10 Walker RW, Viney R, Green L, et al. Trends in stroke admissions to a Tanzanian 
 
hospital over four decades: a retrospective audit. Trop Med Int Health 2015;20:1290-6. 
11 Ezejimofor MC, Uthman OA, Maduka O, et al. Stroke survivors in Nigeria: A door-to-
 
door prevalence survey from the Niger Delta region. J Neurol Sci 2017;372:262-9. 
12  Mead G, Hackett ML, Lundstrom E, et. al. The FOCUS, AFFINITY, and EFFECTS   
trials studying the effect(s) of fluoxetine in patients with a recent stroke: a study protocol 
for three multicenter randomized controlled trials. Trials 16:369 (2015) 
13 Fugl-Meyer AR, Jääskö L, Leyman I, Olsson S, Steglind S. The post-stroke hemiplegic 
patient. 1. a method for evaluation of physical performance. Scandinavian journal of 
rehabilitation medicine. 1975;7(1):13-31.. 
14 Inc, P. Pillsy | 24x7 Digital Medication Coach, with smart pill bottle and app. Available 
at: https://www.pillsy.com. (Accessed: 3rd October 2018) 
15 Kroenke, K., Spitzer, R. L. & Williams, J. B. W. The PHQ-9. J Gen Intern Med 16, 606–
613 (2001). 


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16  Montgomery, S. A. & Asberg, M. A new depression scale designed to be sensitive to 
change. Br J Psychiatry 134, 382–389 (1979). 
17   Mead G, Hackett ML, Lundstrom E, et. al. The FOCUS, AFFINITY, and EFFECTS 
trials studying the effect(s) of fluoxetine in patients with a recent stroke: a study protocol 
for three multicenter randomized controlled trials. Trials 16:369 (2015) 
18 Health, C. for D. and R. Medical X-ray Imaging - What are the Radiation Risks from CT? 
Available at: https://www.fda.gov/radiation-
emittingproducts/radiationemittingproductsandprocedures/medicalimaging/medicalx-
rays/ucm115329.htm. (Accessed: 3rd October 2018)