Building global capacity for brain and nervous system disorders research.

The global burden of neurological, neuropsychiatric, substance-use and neurodevelopmental disorders in low- and middle-income countries is worsened, not only by the lack of targeted research funding, but also by the lack of relevant in-country research capacity. Such capacity, from the individual to the national level, is necessary to address the problems within a local context. As for many health issues in these countries, the ability to address this burden requires development of research infrastructure and a trained cadre of clinicians and scientists who can ask the right questions, and conduct, manage, apply and disseminate research for practice and policy. This Review describes some of the evolving issues, knowledge and programmes focused on building research capacity in low- and middle-income countries in general and for brain and nervous system disorders in particular.

Multiple versus fewer antiplatelet agents for preventing early recurrence after ischaemic stroke or transient ischaemic attack.

BACKGROUND: Stroke is a leading cause of morbidity and mortality worldwide. Antiplatelet agents are considered to be the cornerstone for secondary prevention of stroke, but the role of using multiple antiplatelet agents early after stroke or transient ischaemic attack (TIA) to improve outcomes has not been established. OBJECTIVES: To determine the effectiveness and safety of initiating, within 72 hours after an ischaemic stroke or TIA, multiple antiplatelet agents versus fewer antiplatelet agents to prevent stroke recurrence. The analysis explores the evidence for different drug combinations. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched 6 July 2020), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 7 of 12, 2020) (last searched 6 July 2020), MEDLINE Ovid (from 1946 to 6 July 2020), Embase (1980 to 6 July 2020), ClinicalTrials.gov, and the WHO ICTRP. We also searched the reference lists of identified studies and reviews and used the Science Citation Index Cited Reference search for forward tracking of included studies. SELECTION CRITERIA: We selected all randomised controlled trials (RCTs) that compared the use of multiple versus fewer antiplatelet agents initiated within 72 hours after stroke or TIA. DATA COLLECTION AND ANALYSIS: We extracted data from eligible studies for the primary outcomes of stroke recurrence and vascular death, and secondary outcomes of myocardial infarction; composite outcome of stroke, myocardial infarction, and vascular death; intracranial haemorrhage; extracranial haemorrhage; ischaemic stroke; death from all causes; and haemorrhagic stroke. We computed an estimate of treatment effect and performed a test for heterogeneity between trials. We analysed data on an intention-to-treat basis and assessed bias for all studies. We rated the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 15 RCTs with a total of 17,091 participants. Compared with fewer antiplatelet agents, multiple antiplatelet agents were associated with a significantly lower risk of stroke recurrence (5.78% versus 7.84%, risk ratio (RR) 0.73, 95% confidence interval (CI) 0.66 to 0.82; P < 0.001; moderate-certainty evidence) with no significant difference in vascular death (0.60% versus 0.66%, RR 0.98, 95% CI 0.66 to 1.45; P = 0.94; moderate-certainty evidence). There was a higher risk of intracranial haemorrhage (0.42% versus 0.21%, RR 1.92, 95% CI 1.05 to 3.50; P = 0.03; low-certainty evidence) and extracranial haemorrhage (6.38% versus 2.81%, RR 2.25, 95% CI 1.88 to 2.70; P < 0.001; high-certainty evidence) with multiple antiplatelet agents. On secondary analysis of dual versus single antiplatelet agent therapy, benefit for stroke recurrence (5.73% versus 8.06%, RR 0.71, 95% CI 0.62 to 0.80; P < 0.001; moderate-certainty evidence) was maintained as well as risk of extracranial haemorrhage (1.24% versus 0.40%, RR 3.08, 95% CI 1.74 to 5.46; P < 0.001; high-certainty evidence). The composite outcome of stroke, myocardial infarction, and vascular death (6.37% versus 8.77%, RR 0.72, 95% CI 0.64 to 0.82; P < 0.001; moderate-certainty evidence) and ischaemic stroke (6.30% versus 8.94%, RR 0.70, 95% CI 0.61 to 0.81; P < 0.001; high-certainty evidence) were significantly in favour of dual antiplatelet therapy, whilst the risk of intracranial haemorrhage became less significant (0.34% versus 0.21%, RR 1.53, 95% CI 0.76 to 3.06; P = 0.23; low-certainty evidence). AUTHORS' CONCLUSIONS: Multiple antiplatelet agents are more effective in reducing stroke recurrence but increase the risk of haemorrhage compared to one antiplatelet agent. The benefit in reduction of stroke recurrence seems to outweigh the harm for dual antiplatelet agents initiated in the acute setting and continued for one month. There is lack of evidence regarding multiple versus multiple antiplatelet agents. Further studies are required in different populations to establish comprehensive safety profiles and long-term outcomes to establish duration of therapy.

Using Mobile Health (mHealth) Technology in the Management of Diabetes Mellitus, Physical Inactivity, and Smoking.

PURPOSE OF REVIEW: Cardiovascular mortality remains high due to insufficient progress made in managing cardiovascular risk factors such as diabetes mellitus, physical inactivity, and smoking. Healthy lifestyle choices play an important role in the management of these modifiable risk factors. Mobile health or mHealth is defined as the use of mobile computing and communication technologies (i.e., mobile phones, wearable sensors) for the delivery of health services and health-related information. In this review, we examine some recent studies that utilized mHealth tools to improve management of these risk factors, with examples from developing countries where available. RECENT FINDINGS: The mHealth intervention used depends on the availability of resources. While developing countries are often restricted to text messages, more resourceful settings are shifting towards mobile phone applications and wearable technology. Diabetes mellitus has been extensively studied in different settings, and results have been encouraging. Tools utilized to increase physical activity are expensive, and studies have been limited to resource-abundant areas and have shown mixed results. Smoking cessation has had promising initial results with the use of technology, but mHealth's ability to recruit participants beyond those actively seeking to quit has not been established. mHealth interventions appear to be a potential tool in improving control of cardiovascular risk factors that rely on individuals making healthy lifestyle choices. Data related to clinical impact, if any, of commercially available tools is lacking. More studies are needed to assess interventions that target multiple cardiovascular risk factors and their impact on hard cardiovascular outcomes.

Mobile Health (mHealth) Technology for the Management of Hypertension and Hyperlipidemia: Slow Start but Loads of Potential.

PURPOSE OF REVIEW: Hypertension and hyperlipidemia represent two major risk factors for atherosclerotic cardiovascular disease. Mobile health or mHealth is defined as the use of mobile phone and wireless technologies to support the achievement of health objectives. Management of hypertension, and to some extent hyperlipidemia, has often employed mHealth interventions given lower cost and greater patient engagement compared to traditional methods. These interventions include the use of text messaging, wireless devices, and mobile phone applications. This review considers recent studies evaluating the effectiveness of mHealth interventions in the management of hypertension and hyperlipidemia. RECENT FINDINGS: Numerous studies have evaluated the role of mHealth interventions in the management of hypertension, while very few have evaluated their role in hyperlipidemia. Text messaging has been used most frequently. However, the trend is shifting towards the use of mobile phone applications and wireless devices. Interventions in developing countries have been modified for greater applicability to local settings. mHealth interventions were found to be frequently effective. However, studies comparing the relative efficacy of various mHealth strategies are scarce. Long-term cardiovascular outcomes data and analyses relating to cost effectiveness are also lacking. mHealth interventions may be effective in improving hypertension management. More studies are needed to evaluate the role of mHealth strategies in hyperlipidemia management, particularly in identifying high-risk individuals and improving medication adherence. Studies assessing the long-term impact of these interventions, comparing different interventions and analyzing their relative cost effectiveness, are also needed. Following recently published guidelines on reporting results of mHealth interventions will provide a more meaningful context for interpreting these promising early studies.

Adaptation of the Recent Life Changes Questionnaire (RLCQ) to measure stressful life events in adults residing in an urban megapolis in Pakistan.

BACKGROUND: Contextually relevant stressful life events are integral to the quantification of stress. None such measures have been adapted for the Pakistani population. METHODS: The RLCQ developed by Richard Rahe measures stress of an individual through recording the experience of life changing events. We used qualitative methodology in order to identify contextually relevant stressors in an open ended format, using serial in-depth interviews until thematic saturation of reported stressful life events was achieved. In our next phase of adaptation, our objective was to scale each item on the questionnaire, so as to weigh each of these identified events, in terms of severity of stress. This scaling exercise was performed on 200 random participants residing in the four communities of Karachi namely Kharadar, Dhorajee, Gulshan and Garden. For analysis of the scaled tool, exploratory factor analysis was used to inform structuring. Finally, to complete the process of adaption, content and face validity exercises were performed. Content validity by subject expert review and face validity was performed by translation and back translation of the adapted RLCQ. This yielded our final adapted tool. RESULTS: Stressful life events emerging from the qualitative phase of the study reflect daily life stressors arising from the unstable socio-political environment. Some such events were public harassment, robbery/theft, missed life opportunities due to nepotism, extortion and threats, being a victim of state sponsored brutality, lack of electricity, water, sanitation, fuel, destruction due to natural disasters and direct or media based exposure to suicide bombing in the city. Personal or societal based relevant stressors included male child preference, having an unmarried middle aged daughter, lack of empowerment and respect reported by females. The finally adapted RLCQ incorporated "Environmental Stress" as a new category. CONCLUSION: The processes of qualitative methodology, in depth interview, community based scaling and face and content validity yielded an adapted RLCQ that represents contextually relevant life stress for adults residing in urban Pakistan. TRIAL REGISTRATION: Clinicaltrials.gov NCT02356263 . Registered January 28, 2015. (Observational Study Only).

Quality of life after stroke in Pakistan.

BACKGROUND: There is very little information about the quality of life (QOL) of stroke survivors in LMIC countries with underdeveloped non communicable health infrastructures, who bear two thirds of the global stroke burden. METHODOLOGY: We used a sequential mix methods approach. First, a quantitative analytical cross-sectional study was conducted on 700 participants, who constituted 350 stroke survivor and their caregiver dyads. QOL of stroke survivor was assessed via Stroke Specific Quality of Life Scale (SSQOLS) whereas QOL of caregivers was assessed through RAND-36. In addition; we assessed complications, psychosocial and functional disability of stroke survivors. Following this quantitative survey, caregivers were qualitatively interviewed to uncover contextually relevant themes that would evade quantitative surveys. Multiple linear regression technique was applied to report adjusted ß-coefficients with 95% C.I. RESULTS: The QOL study was conducted from January 2014 till June 2014, in two large private and public centers. At each center, 175 dyads were interviewed to ensure representativeness. Median age of stroke survivors was 59(17) years, 68% were male, 60% reported depression and 70% suffered post-stroke complications. The mean SSQOLS score was 164.18 ± 32.30. In the final model severe functional disability [adjß -33.77(-52.44, -15.22)], depression [adjß-23.74(-30.61,-16.82)], hospital admissions [adjß-5.51(-9.23,-1.92)] and severe neurologic pain [adjß -12.41(-20.10,-4.77)] negatively impacted QOL of stroke survivors (P < 0.01). For caregivers, mean age was 39.18 ± 13.44 years, 51% were female and 34% reported high stress levels. Complementary qualitative study revealed that primary caregivers were depressed, frustrated, isolated and also disappointed by health services. CONCLUSION: The QOL of Stroke survivors as reported by SSQOLS score was better than compared to those reported from other LMIC settings. However, Qualitative triangulation revealed that younger caregivers felt isolated, depressed, overwhelmed and were providing care at great personal cost. There is a need to develop cost effective holistic home support interventions to improve lives of the survivor dyad as a unit. TRIAL REGISTRATION: NCT02351778 (Registered as Observational Study).

Use of medical abbreviations and acronyms: knowledge among medical students and postgraduates.

INTRODUCTION: Inappropriate use of abbreviations and acronyms in healthcare has become an international patient safety issue. The aim of this study was to assess the knowledge of medical abbreviations and acronyms among residents of the department of medicine at a tertiary-care hospital. METHODS: Internal medicine residents (IMRs), subspecialty residents (SRs) and students were asked to complete a self-administered questionnaire which comprised standard abbreviations used in medicine and its various subspecialties. Scores obtained by the residents were classified into three categories: >70% correct answers; 50-69% correct answers; <50% correct answers. RESULTS: A total of 77 IMRs, SRs and medical students participated. Overall, good responses were achieved by 53 (68.8%), 16 (20.8%) attained satisfactory responses, and eight (10.4%) had unsatisfactory scores. The majority of SRs achieved good responses (19/22 (86%)), followed by IMRs (30/40 (75%)) and students (4/15 (26.7%)). Evaluation of their knowledge taken from the list of 'do not use' abbreviations showed that 89.6% reported using 'Q.D.' instead of 'once a day', and 93% used 'IU' instead of the entire phrase 'international unit'. The top five 'not to use' abbreviations were ZnSO4, µg, MgSO4, IU and SC, with the frequency 100%, 96%, 94.8%, 93% and 90%, respectively. CONCLUSIONS: This study showed that there is a knowledge gap among trainees in medicine regarding the meaning and usage of common medical abbreviations. We therefore recommend proper education of trainees in medicine to ensure they understand the meaning of abbreviations and are aware of the list of 'do not use' abbreviations.

Improving medication adherence in stroke patients through Short Text Messages (SMS4Stroke)-study protocol for a randomized, controlled trial.

BACKGROUND: Stroke is a major cause of morbidity and mortality, especially in low and middle income countries. Medical management is the mainstay of therapy to prevent recurrence of stroke. Current estimates are that only 1 in 6 patients have perfect adherence to medication schedules. Using SMS (Short Messaging Service) as reminders to take medicines have been used previously for diseases such as diabetes and HIV with moderate success. We aim to explore the effectiveness and acceptability of SMS in increasing adherence to medications in patients with stroke. METHODS: This will be a randomized, controlled, assessor blinded single center superiority trial. Adult participants with access to a cell phone and a history of stroke longer than 1 month on multiple risk modifying medications will be selected from Neurology and Stroke Clinic. They will be randomized into two parallel groups in a 1:1 ratio via block technique with one group receiving the standard of care as per institutional guidelines while the parallel group receiving SMS reminders for each dose of medicine in addition to the standard of care. In addition intervention group will receive messages for lifestyle changes, medication information, risk factors and motivation for medication adherence. These will bemodeled on Social Cognitive Theory and Health Belief Model and will be categorized by Michies Taxonomy of Behavioral Change Communication. Patient compliance to medicines will be measured at baseline and then after 2 months in each group by using the Morisky Medication Adherence Scale. The change in compliance to medication regimen after the intervention and the difference between the two groups will be used to determine the effectiveness of SMS reminders as a tool to increase medication compliance. The acceptability of the SMS will be determined by a tool designed for this study whose attributes are based Rogers Diffusion of innovation theory. A sample size of 86 participants in each arm will be sufficient to detect a difference of 1 point on the MMAS with a power of 90 % and significance level of 5 % between the two groups; using an attrition rate of 15 %, 200 participants in all will be randomized. DISCUSSION: The SMS for Stroke Study will provide evidence for feasibility and effectiveness of SMS in improving post stroke medication adherence in an LMIC setting. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01986023 11 /11/2013.

A randomized controlled behavioral intervention trial to improve medication adherence in adult stroke patients with prescription tailored Short Messaging Service (SMS)-SMS4Stroke study.

BACKGROUND: The effectiveness of mobile technology to improve medication adherence via customized Short Messaging Service (SMS) reminders for stroke has not been tested in resource poor areas. We designed a randomized controlled trial to test the effectiveness of SMS on improving medication adherence in stroke survivors in Pakistan. METHODS: This was a parallel group, assessor-blinded, randomized, controlled, superiority trial. Participants were centrally randomized in fixed block sizes. Adult participants on multiple medications with access to a cell phone and stroke at least 4 weeks from onset (Onset as defined by last seen normal) were eligible. The intervention group, in addition to usual care, received reminder SMS for 2 months that contained a) Personalized, prescription tailored daily medication reminder(s) b) Twice weekly health information SMS. The Health Belief Model and Social Cognitive theory were used to design the language and content of messages. Frontline SMS software was used for SMS delivery. Medication adherence was self-reported and measured on the validated Urdu version of Morisky Medication Adherence Questionnaire. Multiple linear regression was used to model the outcome against intervention and other covariates. Analysis was conducted by intention-to-treat principle. RESULTS: Two hundred participants were enrolled. 38 participants were lost to follow-up. After 2 months, the mean medication score was 7.4 (95 % CI: 7.2-7.6) in the intervention group while 6.7 (95 % CI: 6.4-7.02) in the control group. The adjusted mean difference (Δ) was 0.54 (95 % CI: 0.22-0.85). The mean diastolic blood pressure in the intervention group was 2.6 mmHg (95 % CI; -5.5 to 0.15) lower compared to the usual care group. CONCLUSION: A short intervention of customized SMS can improve medication adherence and effect stroke risk factors like diastolic blood pressure in stroke survivors with complex medication regimens living in resource poor areas. TRIAL REGISTRATION: Clinicaltrials.gov NCT01986023 last accessed at https://clinicaltrials.gov/ct2/show/NCT01986023.

Can trained field community workers identify stroke using a stroke symptom questionnaire as well as neurologists? Adaptation and validation of a community worker administered stroke symptom questionnaire in a peri-urban Pakistani community.

BACKGROUND: Stroke is a leading cause of morbidity and mortality worldwide. There is a paucity of data from South Asia where stroke is highly prevalent. Validated tools administrable by community health workers (CHWs) are required to identify stroke in the community in a resource-strapped region such as this. METHODS: The study was conducted in a transitional slum in Karachi, Pakistan. Questionnaire to Verify Stroke-Free Status (QVSFS) was adapted and translated into Urdu. Two CHWs, trained by a neurologist, selected 322 community-dwelling subjects using purposive sampling. Each CHW collected data independently, which was validated by a vascular neurologist who directly examined each participant. To assess the effect of audit and feedback, data from the final 10% of the subjects were collected after a second training session for the CHWs. Sensitivity, specificity, and Cohen kappa were determined for the CHW-administered questionnaire against neurovascular assessment. RESULTS: Mean age of participants was 56.5 years with 71% of participants being women. The sensitivity and specificity of the questionnaire of detecting stroke was 77.1% (confidence interval [CI], 64.1-86.9) and 85.8% (CI, 83.5-87.5), respectively. The chance-corrected agreement using the Cohen kappa statistic was .51 (CI, .38-.60). Kappa ranged from .37 to .58 for each of the 7 stroke symptoms. Hemianesthesia (72.9%) and hemiplegia (64.6%) were the most sensitive symptoms. The performance and agreement improved from moderate to substantial after audit and feedback. CONCLUSIONS: We found a reasonable sensitivity and specificity and moderate agreement between CHW-administered QVSFS and assessment by a vascular neurologist.

Clinical, lifestyle, socioeconomic determinants and rate of asymptomatic intracranial atherosclerosis in stroke free Pakistanis.

BACKGROUND: Intracranial Atherosclerotic Disease (ICAD) is the most frequent etiology of stroke with high prevalence among Asians. Despite this, early determinants of ICAD have not been described from this region. METHODS: The study is an analytical prospective cross-sectional study of 200 adults from Radiology Departments of two diagnostic centers in Karachi. Eligible participants confirmed the absence of stroke symptoms via the Questionnaire for Verifying Stroke Free Status (QVSFS) and underwent an interview covering medical, socio demographic, lifestyle and anthropometric evaluation using locally validated and standardized definitions. Magnetic Resonance Images (MRI) were centrally reviewed to detect ICAD using the criterion used in the Warfarin-Aspirin Symptomatic Intracranial Disease study. The risk factors associated with asymptomatic ICAD are reported along with prevalence ratios. RESULTS: Of the 200 participants, ICAD was found in 34.5% (n = 69) of the participants. Mean age was 37.1 (S.D 15.1) years with 62% younger than 45 years. Self-reported hypertension was found in 26.5% subjects, diabetes in 9%, dyslipidemia in 5% and depression in 60%. Smokeless tobacco (Adjusted PR 3.27 (1.07-6.05)), Western diet, high socioeconomic status (Adjusted PR 2.26 (1.99-5.62)) and dyslipidemia (Adjusted PR 1.88 (1.25-2.21)) had significant associations with ICAD after multivariable analysis. Age, gender, diabetes, hypertension, depression and physical activity did not have a significant association. CONCLUSION: ICAD was found on MRI in one in three asymptomatic Pakistanis and was associated with modifiable risks. Initiatives targeting primary prevention may be able to decrease the burden of disease caused by stroke due to ICAD. STUDY REGISTRATION NUMBER: NCT02072876 2/25/2014.

Decompressive surgery for malignant cerebral venous sinus thrombosis: a retrospective case series from Pakistan and comparative literature review.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke in the West; however, it is prevalent in Asia and the Middle East. CVST is treated with dose-adjusted heparin or heparinoid followed by warfarin to facilitate recanalization of venous sinuses. For those with progressive malignant cerebral edema, the role of decompressive surgery has been reported from developed countries. We present data on decompressive craniectomy from a tertiary care stroke center in a developing country and compare our results and population with that described in the international literature. METHODS: We retrospectively analyzed data of all patients who underwent a decompressive hemicraniectomy for CVST at the Aga Khan University Hospital, Karachi, Pakistan from 1999 till 2011. A record review of the Aga Khan University Hospital was performed as decompressive hemicraniectomy for malignant CVST is not being performed elsewhere in the country and the hospital is a major referral center. Using the International Classification of Diseases, Ninth Edition codes for CVST, we identified a total of 7 patients. Patients are presented along with descriptions of their presentation, neuroimaging, intraoperative findings, and long-term outcomes. Pearson chi-square test was done to identify features that predicted survival. A comparative literature review was also done through PubMed to identify all other reports of surgery for CVST. RESULTS: During a 12-year review, 134 patients were diagnosed with CVST. Of these, 7 received intervention. The age range of the patients was 15-60 years. Four of the 7 patients had an excellent outcome, 2 of 7 died, and 1 of 7 left against medical advice (in a comatose state) and was lost to follow-up. Patients presented alert but progressively deteriorated preoperatively. All those patients who had preoperative reactive pupils with low Glasgow Coma Scale scores made a complete neurologic recovery, and patients with fixed, dilated, and nonreactive pupils preoperatively died in the first postoperative week (P = .05). CONCLUSIONS: Patients who received decompressive hemicraniectomy in Pakistan for CVST had excellent outcomes in all cases when intervention was performed with intact preoperative pupillary reflexes. Of the data reviewed, most reported (two-third) patients show the same prognosticators; however, one third show that even with nonreactive pupils complete recovery is possible.

Frequency and determinants of intracranial atherosclerotic stroke in urban Pakistan.

BACKGROUND: Intracranial atherosclerosis (ICAD) is a frequent underlying mechanism of ischemic stroke. There is little direct evidence on its frequency and determinants from regions of high prevalence. This study explores the conventional and socioeconomic risk factors of ICAD in a South Asian population. METHODS: The Karachi Intracranial Stenosis Study is a case-control study of 313 cases of ischemic stroke secondary to ICAD and 331 controls enrolled from 4 major hospitals in Karachi, Pakistan. Stroke subtype was verified by a vascular neurologist using the Trial of Org 10172 in Acute Stroke Treatment classification. Relationships of conventional and socioeconomic risk factors with ICAD-related strokes are reported by calculating odds ratios (ORs) and their 95% confidence intervals (CIs). RESULTS: ICAD was the cause of stroke in 81.1% cases with large-artery atherosclerosis and 19.5% of all stroke events. Along with risk factors like history of hypertension (OR, 3.33; CI, 2.31-4.78), history of diabetes (OR, 2.29; CI, 1.56-3.35), use of tobacco (OR, 1.49; CI, 1.03-2.16), waist-to-hip ratio (OR, 1.58; CI, 1.04-2.41), and family history of stroke (OR, 1.89; CI, 1.21-2.95), other significant social determinants of ICAD strokes were monthly income (OR, 1.59; CI, 1.01-2.51), unemployment (OR, 2.15; CI, 1.21-3.83), and chronic stress (OR, 3.67; CI, 2.13-6.34). These social determinants were independent predictors of the risk of ICAD, in addition to those described in other world populations. CONCLUSIONS: ICAD accounted for one fifth of all strokes making it the most common ischemic stroke mechanism. In addition to aggressive risk factor control, data also indicated broader holistic efforts on ameliorating inequity, unemployment, and stress reduction to reduce stroke because of ICAD.

Left atrial volumes and associated stroke subtypes.

BACKGROUND: Cardio embolism and cerebrovascular atherosclerosis are two major mechanisms of stroke. Studies investigating associations between advanced echocardiographic parameters and stroke mechanisms are limited. METHODS: This study is a standardized review of 633 patients admitted to the stroke service of a tertiary care hospital following a standardized stroke investigation and management pathway. Stroke subtypes were characterized using the Causative Classification System, using the hospitals online radiologic archival system with CCS certified stroke investigators. Patients with two mechanisms were excluded. RESULTS: Patients with cardioembolic stroke had a higher proportion of atrial fibrillation (p < 0.001), acute myocardial infarction (p < 0.001) and ischemic heart disease (p < 0.001). On electrocardiogram (ECG) and transthoracic Echo (TTE), patients with cardioembolic stroke had a greater atrial fibrillation (p < .00), left ventricular thrombus (p < .00), left ventricular ejection fraction <30% (p < .00) and global hypokinesia (p < .00) Patients with cardioembolic stroke had higher mean left atrial volume indices (LAVi) (p < 0.001), mean left ventricular mass indices (LVMi) (p < 0.05) and mean left atrial diameters (LAD) (p < 0.05). At LAVi of 29-33 ml/m2, the risk of atherothrombotic stroke increased. The risk of cardioembolic stroke increased with LAVi of 34 ml/m2 and above. CONCLUSION: Left atrial volume indices may be linked to specific stroke phenotype. At mild increases in left atrial dimensions, the risks of atherosclerotic stroke are high, and probably reflect hypertension as the unifying mechanism. Further increases in left atrial dimensions shifts the risk towards cardioembolic stroke.

Granulocyte-colony stimulating factor for mobilizing bone marrow stem cells in the sub acute stroke. How safe is the use of granulocyte-colony stimulating factor in sub-acute stroke? Is this stem cell trial of recovery enhancement beneficial?

Efforts are being made to develop neuroprotective agents for recovery and prevention of further deterioration of brain tissues in patient with stroke.Granulocyte-colony stimulating factor (GCSF) is a glycoprotein hormone encoded by a single gene located on chromosome 17q 11-22. It functions in the regulation of granulopoiesis& terminal maturation of neutrophills. It is being used for the treatment of neutropenia for the production of CD34+ haematopoietic stem cell (HSC) for bone marrow transplant patients. Neuroprotective effect of GCSF is being studied in various experimental studies but its mechanism of action is not well understood and appears to be multimodal.

Are myocardial infarction--associated single-nucleotide polymorphisms associated with ischemic stroke?

BACKGROUND AND PURPOSE: Ischemic stroke (IS) shares many common risk factors with coronary artery disease (CAD). We hypothesized that genetic variants associated with myocardial infarction (MI) or CAD may be similarly involved in the etiology of IS. To test this hypothesis, we evaluated whether single-nucleotide polymorphisms (SNPs) at 11 different loci recently associated with MI or CAD through genome-wide association studies were associated with IS. METHODS: Meta-analyses of the associations between the 11 MI-associated SNPs and IS were performed using 6865 cases and 11 395 control subjects recruited from 9 studies. SNPs were either genotyped directly or imputed; in a few cases a surrogate SNP in high linkage disequilibrium was chosen. Logistic regression was performed within each study to obtain study-specific ßs and standard errors. Meta-analysis was conducted using an inverse variance weighted approach assuming a random effect model. RESULTS: Despite having power to detect odds ratio of 1.09-1.14 for overall IS and 1.20-1.32 for major stroke subtypes, none of the SNPs were significantly associated with overall IS and/or stroke subtypes after adjusting for multiple comparisons. CONCLUSIONS: Our results suggest that the major common loci associated with MI risk do not have effects of similar magnitude on overall IS but do not preclude moderate associations restricted to specific IS subtypes. Disparate mechanisms may be critical in the development of acute ischemic coronary and cerebrovascular events.

Cilostazol versus aspirin for secondary prevention of vascular events after stroke of arterial origin.

BACKGROUND: Aspirin is widely used for secondary prevention after stroke. Cilostazol has shown promise as an alternative to aspirin in Asian people with stroke. OBJECTIVES: To determine the relative effectiveness and safety of cilostazol compared directly with aspirin in the prevention of stroke and other serious vascular events in patients at high vascular risk for subsequent stroke, those with previous transient ischaemic attack (TIA) or ischaemic stroke of arterial origin. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched September 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 4), MEDLINE (1950 to May 2010) and EMBASE (1980 to May 2010). In an effort to identify further published, ongoing and unpublished studies we searched journals, conference proceedings and ongoing trial registers, scanned reference lists from relevant studies and contacted trialists and Otsuka Pharmaceutical Co Ltd. SELECTION CRITERIA: We selected all randomised controlled trials (RCTs) comparing cilostazol with aspirin where participants were treated for at least one month and followed systematically for development of vascular events. DATA COLLECTION AND ANALYSIS: Data extracted from eligible studies included: (1) a composite outcome of vascular events (stroke, myocardial infarction or vascular death) during follow up (primary outcome); (2) separate outcomes of stroke (ischaemic or haemorrhagic, fatal or non-fatal), myocardial infarction (MI) (fatal or non-fatal), vascular death and death from all causes; and (3) main outcomes of safety including any intracranial, extracranial or gastrointestinal (GI) haemorrhage and other outcomes during treatment follow up (secondary outcomes). We computed an estimate of treatment effect and performed a test for heterogeneity between trials. We analysed data on an intention-to-treat basis and assessed bias for all included studies. MAIN RESULTS: We included two RCTs with 3477 Asian participants. Compared with aspirin, cilostazol was associated with a significantly lower risk of composite outcome of vascular events (6.77% versus 9.39%, risk ratio (RR) 0.72, 95% confidence interval (CI) 0.57 to 0.91), and lower risk of haemorrhagic stroke (0.53% versus 2.01%, RR 0.26, 95% CI 0.13 to 0.55). In terms of outcome of safety compared with aspirin, cilostazol was significantly associated with minor adverse effects (8.22% versus 4.95%, RR 1.66, 95% CI 1.51 to 1.83). AUTHORS' CONCLUSIONS: Cilostazol is more effective than aspirin in the prevention of vascular events secondary to stroke. Cilostazol has more minor adverse effects, although there is evidence of fewer bleeds.

Risk factors of stroke in Pakistan: a dedicated stroke clinic experience.

BACKGROUND: Secondary prevention of cerebrovascular disease through dedicated stroke clinics has been shown to decrease recurrent vascular events in patients. However, there is limited literature describing such stroke clinic experiences from low and middle income countries. This study describes patient characteristics and observations made at the first systematized stroke clinic in Pakistan. METHODS: A retrospective audit of medical records of all patients presenting between September 2006 and August 2008 with a cerebrovascular event was conducted. Information about clinical presentation, modifiable risk factors and laboratory and radiological investigations was collected. Burden of disability was assessed using Modified Rankin score. Data was entered and analyzed using SPSS 14.0. RESULTS: 159 patients with a mean age of 57.0 +/- 13.9 years were included in this study and 34.6% of all patients were women. 108 patients were diagnosed with ischemic stroke (67.9%) while 34 patients presented with hemorrhagic stroke (21.4%) and 17 patients presented with transient ischemic attacks (10.7%). Hypertension was the most common modifiable risk factor seen in 78.0%, followed by diabetes in 40.3% and dyslipidemia in 31.5%. At presentation to clinic, only 26.0% patients with dyslipidemia and 64.5% patients with hypertension were on appropriate medications. CONCLUSION: A high prevalence of modifiable risk factors such as hypertension in stroke patients was observed and it presents an opportunity for conventional interventions in Pakistan. Systematized clinics for stroke and an algorithmic approach in primary care towards stroke may improve the implementation of evidence based secondary prevention strategies in developing countries.

Utilization and outcome of thrombolytic therapy for acute stroke in Pakistan.

Our objective was to identify the outcome of patients treated with tissue plasminogen activator (r-tPa) in Pakistan and compare these data to available regional and international data. The charts of all patients treated with r-tPa for acute stroke at two centers in Pakistan (Aga Khan University, Karachi and Liaquat National hospital, Karachi) were retrospectively reviewed. We identified 21 patients. The utilization of tPa at Aga Khan Hospital was 18/1,185 patients (1.5%) from 2005 to 2007 while at Liaquat National Hospital was 3/575 patients (0.52%) over 1 year (2007). Mean time interval between stroke onset and start of r-tPa infusion was 169 min. Three patients (14%) developed fatal hemorrhage and two (10%) developed non-fatal hemorrhage. Four patients (19%) died. We identified protocol violations in seven patients (33%). In conclusion, the utilization of thrombolytic therapy is low and complication rate is high. Interventions for training physicians are needed.