Predictors of 30-day mortality among patients with stroke admitted at a tertiary teaching hospital in Northwestern Tanzania: A prospective cohort study

BackgroundStroke is the second leading cause of death worldwide, with the highest mortality rates in low- to middle-income countries, particularly in sub-Saharan Africa. We aimed to investigate the predictors of 30-day mortality among patients with stroke admitted at a tertiary teaching hospital in Northwestern Tanzania.MethodsThis cohort study recruited patients with the World Health Organization's clinical definition of stroke. Data were collected on baseline characteristics, the degree of neurological impairment at admission (measured using the National Institutes of Health Stroke Scale), imaging and electrocardiogram (ECG) findings, and post-stroke complications. The modified Rankin scale (mRS) was used to assess stroke outcomes. Kaplan–Meier analysis was used to describe survival, and the Cox proportional hazards model was used to examine predictors of mortality.ResultsA total of 135 patients were enrolled, with a mean age of 64.5 years. Hypertension was observed in 76%, and 20% were on regular anti-hypertensive medications. The overall 30-day mortality rate was 37%. Comparing patients with hemorrhagic and ischemic stroke, 25% had died by day 5 [25th percentile survival time (in days): 5 (95% CI: 2–14)] versus day 23 [25th percentile survival time (in days): 23 (95% CI: 11–30) (log-rank p < 0.001)], respectively. Aspiration pneumonia was the most common medical complication, occurring in 41.3% of patients. ECG abnormalities were observed in 54.6 and 46.9% of patients with hemorrhagic and ischemic stroke, respectively. The most common patterns were as follows: ST changes 29.6 vs. 30.9%, T-wave inversion 34.1 vs. 38.3%, and U-waves 18.2 vs. 1.2% in hemorrhagic and ischemic stroke, respectively. Independent predictors for case mortality were as follows: mRS score at presentation (4–5) [aHR 5.50 (95% CI: 2.02–15.04)], aspiration pneumonia [aHR 3.69 (95% CI: 1.71–13.69)], ECG abnormalities [aHR 2.28 (95% CI: 1.86–5.86)], and baseline stroke severity [aHR 1.09 (95% CI: 1.02–1.17)].ConclusionStroke is associated with a high 30-day mortality rate in Northwestern Tanzania. Concerted efforts are warranted in managing patients with stroke, with particular attention to individuals with severe strokes, ECG abnormalities, and swallowing difficulties to reduce early morbidity and mortality

Tranexamic acid for intracerebral haemorrhage within 2 hours of onset : protocol of a phase II randomised placebo-controlled double-blind multicentre trial

Rationale Haematoma growth is common early after intracerebral haemorrhage (ICH), and is a key determinant of outcome. Tranexamic acid, a widely available antifibrinolytic agent with an excellent safety profile, may reduce haematoma growth. Methods and design Stopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units (STOP-MSU) is a phase II double-blind, randomised, placebo-controlled, multicentre, international investigator-led clinical trial, conducted within the estimand statistical framework. Hypothesis In patients with spontaneous ICH, treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo. Sample size estimates A sample size of 180 patients (90 in each arm) would be required to detect an absolute difference in the primary outcome of 20% (placebo 39% vs treatment 19%) under a two-tailed significance level of 0.05. An adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients. Intervention Participants will receive 1 g intravenous tranexamic acid over 10 min, followed by 1 g intravenous tranexamic acid over 8 hours; or matching placebo. Primary efficacy measure The primary efficacy measure is the proportion of patients with haematoma growth by 24 +/- 6 hours, defined as either >= 33% relative increase or >= 6 mL absolute increase in haematoma volume between baseline and follow-up CT scan. Discussion We describe the rationale and protocol of STOP-MSU, a phase II trial of tranexamic acid in patients with ICH within 2 hours from onset, based in participating mobile stroke units and emergency departments.Peer reviewe

Cognitive Impairment Before Intracerebral Hemorrhage Is Associated With Cerebral Amyloid Angiopathy

Background and Purpose—Although the association between cerebral amyloid angiopathy (CAA) and cognitive impairment is increasingly recognized, it is not clear whether this is because of the impact of recurrent intracerebral hemorrhage (ICH) events, disruptions caused by cerebral small vessel damage, or both. We investigated this by considering whether cognitive impairment before ICH was associated with neuroimaging features of CAA on magnetic resonance imaging. Methods—We studied 166 patients with neuroimaging-confirmed ICH recruited to a prospective multicentre observational study. Preexisting cognitive impairment was determined using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Magnetic resonance imaging markers of cerebral small vessel disease, including CAA, were rated by trained observers according to consensus guidelines. Results—The prevalence of cognitive impairment before ICH was 24.7% (n=41) and, in adjusted analyses, was associated with fulfilling the modified Boston criteria for probable CAA at presentation (odds ratio, 4.01; 95% confidence interval, 1.53–10.51; P=0.005) and a higher composite CAA score (for each point increase, odds ratio, 1.42; 95% confidence interval, 1.03–1.97; P=0.033). We also found independent associations between pre-ICH cognitive decline and the presence of cortical superficial siderosis, strictly lobar microbleeds, and lobar ICH location, but not with other neuroimaging markers, or a composite small vessel disease score. Conclusions—CAA (defined using magnetic resonance imaging markers) is associated with cognitive decline before symptomatic ICH. This provides evidence that small vessel disruption in CAA makes an independent contribution to cognitive impairment, in addition to effects due to brain injury caused directly by ICH

Baseline factors associated with early and late death in intracerebral haemorrhage survivors

Background and purpose: The aim of this study was to determine whether early and late death are associated with different baseline factors in intracerebral haemorrhage (ICH) survivors. Methods: This was a secondary analysis of the multicentre prospective observational CROMIS‐2 ICH study. Death was defined as ‘early’ if occurring within 6 months of study entry and ‘late’ if occurring after this time point. Results: In our cohort (n = 1094), there were 306 deaths (per 100 patient‐years: absolute event rate, 11.7; 95% confidence intervals, 10.5–13.1); 156 were ‘early’ and 150 ‘late’. In multivariable analyses, early death was independently associated with age [per year increase; hazard ratio (HR), 1.05, P = 0.003], history of hypertension (HR, 1.89, P = 0.038), pre‐event modified Rankin scale score (per point increase; HR, 1.41, P < 0.0001), admission National Institutes of Health Stroke Scale score (per point increase; HR, 1.11, P < 0.0001) and haemorrhage volume >60 mL (HR, 4.08, P < 0.0001). Late death showed independent associations with age (per year increase; HR, 1.04, P = 0.003), pre‐event modified Rankin scale score (per point increase; HR, 1.42, P = 0.001), prior anticoagulant use (HR, 2.13, P = 0.028) and the presence of intraventricular extension (HR, 1.73, P = 0.033) in multivariable analyses. In further analyses where time was treated as continuous (rather than dichotomized), the HR of previous cerebral ischaemic events increased with time, whereas HRs for Glasgow Coma Scale score, National Institutes of Health Stroke Scale score and ICH volume decreased over time. Conclusions: We provide new evidence that not all baseline factors associated with early mortality after ICH are associated with mortality after 6 months and that the effects of baseline variables change over time. Our findings could help design better prognostic scores for later death after ICH

Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2):a multicentre observational cohort study

Background: Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack. Methods: Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316. Findings: Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0–20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1–5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27–10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29–0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53–0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60–0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07–0·43, p=0·0065; and 0·33, 0·14–0·51, p=0·00059, respectively). Interpretation: In patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation. Funding: The Stroke Association and the British Heart Foundation

Incidence, aetiology, and sequelae of viral meningitis in UK adults: a multicentre prospective observational cohort study

© 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Viral meningitis is increasingly recognised, but little is known about the frequency with which it occurs, or the causes and outcomes in the UK. We aimed to determine the incidence, causes, and sequelae in UK adults to improve the management of patients and assist in health service planning. Methods: We did a multicentre prospective observational cohort study of adults with suspected meningitis at 42 hospitals across England. Nested within this study, in the National Health Service (NHS) northwest region (now part of NHS England North), was an epidemiological study. Patients were eligible if they were aged 16 years or older, had clinically suspected meningitis, and either underwent a lumbar puncture or, if lumbar puncture was contraindicated, had clinically suspected meningitis and an appropriate pathogen identified either in blood culture or on blood PCR. Individuals with ventricular devices were excluded. We calculated the incidence of viral meningitis using data from patients from the northwest region only and used these data to estimate the population-standardised number of cases in the UK. Patients self-reported quality-of-life and neuropsychological outcomes, using the EuroQol EQ-5D-3L, the 36-Item Short Form Health Survey (SF-36), and the Aldenkamp and Baker neuropsychological assessment schedule, for 1 year after admission. Findings: 1126 patients were enrolled between Sept 30, 2011, and Sept 30, 2014. 638 (57%) patients had meningitis: 231 (36%) cases were viral, 99 (16%) were bacterial, and 267 (42%) had an unknown cause. 41 (6%) cases had other causes. The estimated annual incidence of viral meningitis was 2·73 per 100 000 and that of bacterial meningitis was 1·24 per 100 000. The median length of hospital stay for patients with viral meningitis was 4 days (IQR 3–7), increasing to 9 days (6–12) in those treated with antivirals. Earlier lumbar puncture resulted in more patients having a specific cause identified than did those who had a delayed lumbar puncture. Compared with the age-matched UK population, patients with viral meningitis had a mean loss of 0·2 quality-adjusted life-years (SD 0·04) in that first year. Interpretation: Viruses are the most commonly identified cause of meningitis in UK adults, and lead to substantial long-term morbidity. Delays in getting a lumbar puncture and unnecessary treatment with antivirals were associated with longer hospital stays. Rapid diagnostics and rationalising treatments might reduce the burden of meningitis on health services. Funding: Meningitis Research Foundation and UK National Institute for Health Research

Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study

Summary Background: Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack. Methods: Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316. Findings: Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0–20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1–5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27–10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29–0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53–0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60–0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07–0·43, p=0·0065; and 0·33, 0·14–0·51, p=0·00059, respectively). Interpretation In patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation. Funding The Stroke Association and the British Heart Foundation

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke