Trajectories of depressive symptoms 10 years after stroke and associated risk factors: a prospective cohort study.

BACKGROUND: Previous studies have investigated the risk factors for post-stroke depression at only one timepoint, neglecting its dynamic nature. We aimed to identify trajectories of post-stroke depression from multiple assessments and explore their risk factors. METHODS: We did a population-based cohort study with the South London Stroke Register (1995-2019). All stroke patients with three or more measurements of the Hospital Anxiety and Depression Scale were included. We identified trajectories of post-stroke depression over a 10-year follow-up using group-based trajectory modelling. We determined the optimal number and shape of trajectories based on the lowest Bayesian information criterion, average posterior probability of assignment of each group over 0·70, and inclusion of at least 5% of participants within each group. We used multinomial logistic regression adjusted for age, sex, ethnicity, comorbidity, physical disability, stroke severity, history of depression and cognitive impairment to explore associations with different trajectories. FINDINGS: The analysis comprised 1968 participants (mean age 64·9 years [SD 13·8], 56·6% male and 43·4% female, 65·1% white ethnicity, 30·7% severe disability and 32·7% severe stroke). We identified four patterns of symptoms: no depressive symptoms (14·1%, n=277), low symptoms (41·7%, n=820), moderate symptoms and symptoms worsening early and then improving (34·6%, n=681), and high and increasing symptoms (9·7%, n=190). Compared with no depressive symptom trajectory, patients with severe disability, severe stroke, pre-stroke depression, and cognitive impairment were more likely to be in the moderate and high symptom groups (adjusted odds ratios [ORs] 2·26 [95% CI 1·56-3·28], 1·75 [1·19-2·57], 2·20 [1·02-4·74], and 2·04 [1·25-3·32], respectively). Female sex was associated with high depression (OR 1·65 [1·13-2·41]), while older age (≥65 years) was associated with moderate depression (OR 1·82 [1·36-2·45]). In men, the ORs for patients with severe disability, severe stroke, pre-stroke depression, and cognitive impairment being in the high depression group were 1·91 (1·01-3·60), 2·41 (1·26-4·60), 2·57 (0·84-7·88), and 2·68 (1·28-5·60), respectively. In women, the ORs were 1·08 (0·52-2·23), 1·30 (0·60-2·79), 19·2 (2·35-156·05), and 3·80 (1·44-10·01), respectively. INTERPRETATION: Female sex and older age were associated with distinct courses of depressive symptoms. In men, high depressive symptom trajectory was associated with severe stroke and severe disability, which was not the case in women. These findings were limited to patients with three or more assessments, who tended to have less severe disabilities than excluded patients and might not generalise to all stroke survivors. FUNDING: National Institute for Health and Care Research (NIHR).

The feasibility, repeatability, validity and responsiveness of the EQ-5D-3L in Krio for patients with stroke in Sierra Leone.

OBJECTIVES: To assess the feasibility, repeatability, validity and responsiveness of the EQ-5D-3L in Krio for patients with stroke in Sierra Leone, the first psychometric assessment of the EQ-5D-3L to be conducted in patients with stroke in Sub Saharan Africa. METHODS: A prospective stroke register at two tertiary government hospitals recruited all patients with the WHO definition of stroke and followed patients up at seven days, 90 days and one year post stroke. The newly translated EQ-5D-3L, Barthel Index (BI), modified Rankin Scale (mRS) and National Institute of Health Stroke Scale (NIHSS), a measure of stroke severity, were collected by trained researchers, face to face during admission and via phone at follow up. Feasibility was assessed by completion rate and proportion of floor/ceiling effects. Internal consistency was assessed by inter item correlations (IIC) and Cronbach's alpha. Repeatability of the EQ-5D-3L was examined using test-retest, EQ-5D-3L utility scores at 90 days were compared to EQ-5D-3L utility scores at one year in the same individuals, whose Barthel Index had remained within the minimally clinical important difference. Known group validity was assessed by stroke severity. Convergent validity was assessed against the BI, using Spearman's rho. Responsiveness was assessed in patients whose BI improved or deteriorated from seven to 90 days. Sensitivity analyses were conducted using the UK and Zimbabwe value sets, to evaluate the effect of value set, in a subgroup of patients with no formal education to evaluate the influence of patient educational attainment, and using the mRS instead of the BI to evaluate the influence of utilising an alternative functional scale. RESULTS: The EQ-5D-3L was completed in 373/460 (81.1%), 360/367 (98.1%) and 299/308 (97.1%) eligible patients at seven days, 90 days and one year post stroke. Missing item data was low overall, but was highest in the anxiety/depression dimension 1.3% (5/373). Alpha was 0.81, 0.88 and 0.86 at seven days, 90 days and one year post stroke and IIC were within pre-specified ranges. Repeatability of the EQ-5D-3L was moderate to poor, weighted Kappa 0.23-0.49. EQ-5D-3L utility was significantly associated with stroke severity at all timepoints. Convergent validity with BI was strong overall and for shared subscales. EQ-5D-3L was moderately responsive to both improvement Cohen's D 0.55 (95% CI:0.15-0.94) and deterioration 0.92 (95% CI:0.29-1.55). Completion rates were similar in patients with no formal education 148/185 (80.0%) vs those with any formal education 225/275 (81.8%), and known group validity for stroke severity in patients with no formal education was strong. Using the Zimbabwe value set instead of the UK value set, and using the mRS instead of the BI did not change the direction or significance of results. CONCLUSIONS: The EQ-5D-3L for stroke in Sierra Leone was feasible, and responsive including in patients with no formal education. However, repeatability was moderate to poor, which may be due to the study design, but should add a degree of caution in the analysis of repeated measures of EQ-5D-3L over time in this population. Known group validity and convergent validity with BI and mRS were strong. Further research should assess the EQ-5D in the general population, examine test-retest reliability over a shorter time period and assess the acceptability and validity of the anxiety/depression dimension against other validated mental health instruments. Development of an EQ-5D value set for West Africa should be a research priority.

A systematic review of the incidence and outcomes of ICD-11 defined stroke.

BACKGROUND: The World Health Organisation has expanded the definition of stroke to include people with symptoms less than 24 h if they have evidence of stroke on neuroimaging. The impact is that people previously diagnosed as having a transient ischaemic attack (TIA) would now be considered to have had a stroke. This change will impact incidence and outcomes of stroke and increase eligibility for secondary prevention. We aimed to evaluate the new ICD-11 criteria retrospectively to previous TIA studies to understand the change in incidence and outcomes of this type of stroke. METHODS: We conducted a systematic review of observational studies of the incidence and outcomes of clinically defined TIA. We searched PubMed, EMBASE, and Google Scholar from inception to 23rd May 2023. Study quality was assessed using a risk of bias tool for prevalence studies. FINDINGS: Our review included 25 studies. The rate of scan positivity for stroke among those with clinically defined TIA was 24 %, (95 % CI, 16-33 %) but with high heterogeneity (I2 = 100 %, p <0.001). Sensitivity analyses provided evidence that heterogeneity could be explained by methodology and recruitment method. The scan positive rate when examining only studies at low risk of bias was substantially lower, at 13 % (95 % CI, 11-15 %, I2 = 0, p = 0.77). We estimate from population-based incidence studies that ICD-11 would result in an increase stroke incidence between 4.8 and 10.5 per 100,000 persons/year. Of those with DWI-MRI evidence of stroke, 6 % (95 % CI, 3-11 %) developed a recurrent stroke in the subsequent 90 days, but with substantial heterogeneity (I2 = 67 %, p = 0.02). CONCLUSION: The impact of the ICD-11 change in stroke definition on incidence and outcomes may have been overestimated by individual studies. Community-based stroke services with access to DWI MRI are likely to accurately diagnose greater numbers of people with mild ICD-11 stroke, increasing access to effective prevention.

Prevalence and natural history of depression after stroke: A systematic review and meta-analysis of observational studies.

BACKGROUND: Depression is the most frequent psychiatric condition after stroke and is associated with negative health outcomes. We aim to undertake a systematic review and meta-analysis of the prevalence and natural history of depression after stroke. METHODS AND FINDINGS: Studies published up to 4 November 2022 on Medline, Embase, PsycINFO, and Web of Science Core Collection were searched. We included studies of adults with stroke, where depression was assessed at a prespecified time point. Studies excluding people with aphasia and history of depression are excluded. Critical Appraisal Skills Programme(CASP) cohort study tool was used to assess risk of bias. A total of 77 studies were included in the pooled estimates of the prevalence of poststroke depression (PSD). The overall prevalence of depression was 27% (95% CI 25 to 30). Prevalence of depression was 24% (95% CI 21 to 28) by clinical interview and 29% (95% CI 25 to 32) by rating scales. Twenty-four studies with more than one assessment time point reported the natural history of PSD. Among people who were depressed within 3 months of stroke, 53% (95% CI 47 to 59) experienced persistent depression, while 44% (95% CI 38 to 50) recovered. The incidence of later depression (3 to 12 months after stroke) was 9% (95% CI 7 to 12). The cumulative incidence during 1 year after stroke was 38% (95% CI 33 to 43), and the majority (71% (95% CI 65 to 76)) of depression had onset within 3 months after stroke. The main limitation of the present study is that excluding people in source studies with severe impairments may produce imprecise estimates of the prevalence of PSD. CONCLUSIONS: In this study, we observed that stroke survivors with early-onset depression (within 3 months after stroke) are at high risks for remaining depressed and make up two-thirds of the incident cases during 1 year after stroke. This highlights the need for ongoing clinical monitoring of patients depressed shortly after stroke. TRIAL REGISTRATION: PROSPERO CRD42022314146.

Accuracy and Efficiency of Machine Learning-Assisted Risk-of-Bias Assessments in "Real-World" Systematic Reviews : A Noninferiority Randomized Controlled Trial.

BACKGROUND: Automation is a proposed solution for the increasing difficulty of maintaining up-to-date, high-quality health evidence. Evidence assessing the effectiveness of semiautomated data synthesis, such as risk-of-bias (RoB) assessments, is lacking. OBJECTIVE: To determine whether RobotReviewer-assisted RoB assessments are noninferior in accuracy and efficiency to assessments conducted with human effort only. DESIGN: Two-group, parallel, noninferiority, randomized trial. (Monash Research Office Project 11256). SETTING: Health-focused systematic reviews using Covidence. PARTICIPANTS: Systematic reviewers, who had not previously used RobotReviewer, completing Cochrane RoB assessments between February 2018 and May 2020. INTERVENTION: In the intervention group, reviewers received an RoB form prepopulated by RobotReviewer; in the comparison group, reviewers received a blank form. Studies were assigned in a 1:1 ratio via simple randomization to receive RobotReviewer assistance for either Reviewer 1 or Reviewer 2. Participants were blinded to study allocation before starting work on each RoB form. MEASUREMENTS: Co-primary outcomes were the accuracy of individual reviewer RoB assessments and the person-time required to complete individual assessments. Domain-level RoB accuracy was a secondary outcome. RESULTS: Of the 15 recruited review teams, 7 completed the trial (145 included studies). Integration of RobotReviewer resulted in noninferior overall RoB assessment accuracy (risk difference, -0.014 [95% CI, -0.093 to 0.065]; intervention group: 88.8% accurate assessments; control group: 90.2% accurate assessments). Data were inconclusive for the person-time outcome (RobotReviewer saved 1.40 minutes [CI, -5.20 to 2.41 minutes]). LIMITATION: Variability in user behavior and a limited number of assessable reviews led to an imprecise estimate of the time outcome. CONCLUSION: In health-related systematic reviews, RoB assessments conducted with RobotReviewer assistance are noninferior in accuracy to those conducted without RobotReviewer assistance. PRIMARY FUNDING SOURCE: University College London and Monash University.

Cohort profile: The South London Stroke Register - a population-based register measuring the incidence and outcomes of stroke.

PURPOSE: The South London Stroke Register (SLSR) is a population-based cohort study, which was established in 1995 to study the causes, incidence, and outcomes of stroke. The SLSR aims to estimate incidence, and acute and long term needs in a multi-ethnic inner-city population, with follow-up durations for some participants exceeding 20 years. PARTICIPANTS: The SLSR aims to recruit residents of a defined area within Lambeth and Southwark who experience a first stroke. More than 7700 people have been registered since inception, and >2750 people continue to be followed up. At the 2011 census, the source population was 357,308. FINDINGS TO DATE: The SLSR was instrumental in highlighting the inequalities in risk and outcomes in the UK, and demonstrating the dramatic improvements in care quality and outcomes in recent decades. Data from the SLSR informed the UK National Audit Office in its 2005 report criticising the poor state of stroke care in England. For people living in the SLSR area the likelihood of being treated in a stroke unit increased from 19% in 1995-7 to 75% in 2007-9. The SLSR has investigated health inequalities in stroke incidence and outcome. SLSR analyses have demonstrated that lower socioeconomic status was associated with poorer outcome, and that Black people and younger people have not experienced the same improvements in stroke incidence as other groups. FUTURE PLANS: As part of an NIHR Programme Grant for Applied Research, from April 2022 the SLSR has expanded to recruit ICD-11 defined stroke (including those with <24 h symptoms where there are neuroimaging findings), and have expanded the follow up interviews to collect more detailed information on quality of life, cognition, and care needs. Additional data items will be added over the Programme based on feedback from patients and other stakeholders.

Statin Therapy for Preventing Recurrent Stroke in Patients with Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Observational Cohort Studies.

INTRODUCTION: Statins are effective in preventing vascular disease and are widely recommended and used for the secondary prevention of ischemic stroke. However, there is concern from trials that statins might increase the risk of hemorrhagic stroke, partially reducing their benefit. We sought to systematically review the latest evidence on this question. METHODS: Four electronic databases were searched to identify published randomized controlled trials (RCTs) and observational cohort studies (search date December 2020). Two independent reviewers carried out the eligibility assessment based on predefined inclusion criteria. We examined the outcomes of recurrent stroke (after ischemic stroke) of any type, and separately recurrent ischemic stroke and recurrent hemorrhagic stroke. RCTs and observational cohort studies were meta-analyzed separately. Odds ratios (ORs) were used to assess the effect of statin therapy. Meta-analysis was conducted using RevMan 5.4 software. RESULTS: We retrieved 559 papers in searches, of which 11 RCTs and 12 observational cohort studies were included. Both RCTs and observational studies found that statins reduced the odds of stroke of any type in those with an initial ischemic stroke (11 RCTs: OR = 0.87, 95% CI [0.77,0.97]; p = 0.02; 12 cohort studies: OR = 0.80, 95% CI [0.66, 0.96]; p = 0.02). Both RCTs and observational studies found that recurrence of ischemic stroke was reduced by statins (6 RCTs: OR = 0.81, 95% CI [0.70, 0.93]; p = 0.002; 3 observational studies: OR = 0.67, 95% CI [0.61, 0.75]; p < 0.00001). Data from 7 RCTs and 8 cohort studies did not find a significant difference in hemorrhagic stroke but could not rule out a substantial increase or reduction (7 RCTs: OR = 1.15, 95% CI [0.62, 2.13]; p = 0.66; 8 cohort studies: OR = 0.93, 95% CI [0.71, 1.21]; p = 0.59). CONCLUSIONS: In people who have experienced an ischemic stroke, statins reduce the risk of recurrent stroke of any type medicated through a reduction of ischemic stroke. We found no increase in the risk of hemorrhagic stroke.

Survival and outcomes for stroke survivors living in care homes: a prospective cohort study.

BACKGROUND: Stroke survivors living in care homes require high levels of support with everyday living. The aims of this study were to describe the survival, health status and care received by stroke survivors living in care homes at 1-year post-stroke, compared with those in their own homes. METHODS: A total of 3,548 stroke survivors with a first ever stroke between 1998 and 2017 in the South London Stroke Register were identified for survival analysis. A total of 2,272 were included in the 1-year follow-up analysis. Cox regression and Kaplan-Meier plots were used to describe survival, stratified into four 5-year cohorts. Health status, medications and rehabilitation received at 1-year post-stroke were compared using descriptive statistics. RESULTS: Over the 20-year period, survival improved for stroke survivors discharged to their own home (P < 0.001) but not for those discharged to care homes (P = 0.75). Care home residents were highly disabled (median Barthel index: 6/20, interquartile range: 2-10). Rates of secondary stroke prevention medications at 1-year follow-up increased over time for care home residents, including antiplatelets from 12.3 to 38.1%, although still lower than for those in their own homes (56.3%). Speech and language problems were common in the care home population (40.0%), but only 16% had received speech and language therapy. CONCLUSIONS: Rates of secondary stroke prevention prescribing increased over 20 years but remained lower in care home residents. The lower levels of rehabilitation received by stroke survivors in care homes, despite their higher levels of disability, suggest a gap in care and urgent need for restorative and/or preventative rehabilitation.

Long-Term Trends in Stroke Survivors Discharged to Care Homes: The South London Stroke Register.

Background and Purpose- Care homes provide care to many stroke survivors, yet little is known about changes in care home use over time. We aim to determine trends in discharge to care homes, to explore the characteristics of stroke survivors over time (1995-2018), and to identify the associations between these characteristics and discharge to care homes poststroke. Methods- Using data from the South London Stroke Register between 1995 and 2018, we estimated the proportions discharged to care homes and their characteristics over time, assessed by tests for trends. Multivariable logistic regression models were built to assess the associations between their characteristics and discharge destination. Results- Of 4172 stroke survivors, 484 (12%) were discharged to care homes. This proportion has decreased from 24% in 1995 to 2000 to 5% in 2013 to 2018. The mean age of those discharged to care homes has increased over time, from 73 to 75 (P<0.001). Among stroke survivors discharged to a care home, the proportion with a prestroke Barthel Index <15 has also increased over time from 7% to 21% (P=0.027), while the proportion with a 7-day poststroke Barthel Index <15 remains largely unchanged over time (93% in 1995-2000, 90% in 2013-2018). The characteristics most strongly associated with discharge to care homes were (odds ratio [95% CI]) age (1.05 [1.04-1.07] per year), stroke subtype (hemorrhagic; 0.64 [0.43-0.95]), stroke severity (Glasgow Coma Scale score, <13; 1.67 [1.19-2.35]), failed swallow test at admission (1.65 [1.20-2.25]), 7-day poststroke Barthel Index <15 (3.58 [2.20-6.03]), and a longer hospital stay (1.02 [1.02-1.03] per day). Conclusions- Over >20 years, there has been an 80% reduction in the proportion of stroke survivors discharged to care homes, influenced by changes in the demographics, disability, and stroke care in the underlying stroke population. In those moving to care homes, the level of poststroke disability remains high, requiring continued attention and investment.

Blood eosinophil count, a marker of inhaled corticosteroid effectiveness in preventing COPD exacerbations in post-hoc RCT and observational studies: systematic review and meta-analysis.

BACKGROUND: Blood eosinophil count has been proposed as a predictor of response to inhaled corticosteroid (ICS) in the prevention of acute exacerbations of COPD. An optimal threshold of blood eosinophil count for prescribing ICS has not been agreed. Doubt has been cast on the role by observational studies. The role of inhaled corticosteroids in this relationship, independent of long-acting bronchodilators, has not been examined. METHODS: We conducted a systematic review of post-hoc analyses of randomised controlled trials (RCTs) and observational studies examining three blood eosinophil thresholds and the independent role of ICS. Included studies were categorised by the form (relative or absolute count) and cut point of eosinophil threshold used. Thresholds assessed were relative eosinophil count of 2%, and absolute counts of 150 cells/µL and 300 cells/µL. Three meta-analyses of the effect of ICS use in post-hoc analyses of RCTs based on these counts were carried out. Initial analysis included all studies of ICS vs. any non-ICS regimen. Further analysis examined the effect of ICS, independent of the effect of long-acting bronchodilators. RESULTS: Sixteen studies examined the association between blood eosinophil count and response of exacerbation risk to ICS, in COPD patients. Eleven studies (25,881 patients) were post-hoc analyses of RCTs. Five studies (109,704 patients) were retrospective observational studies. The independent effect of ICS on the reduction of exacerbation risk was 20% at ≥2% blood eosinophil threshold (RR, 0.80; 95% CI, 0.74-0.85), 35% at ≥150 cells/µL blood eosinophil threshold (RR, 0.65; 0.52-0.79), and 39% at ≥300 cells/µL blood eosinophil threshold (RR, 0.61; 0.44-0.78). No association was found in four out of five observational studies. CONCLUSION: This is the first systematic review to assess, in post-hoc analyses of RCTs, the independent effect of ICS in reducing the risk of COPD exacerbation across a range of blood eosinophil thresholds. Association between ICS prescription and reduced exacerbation risk at these thresholds was confirmed. The lack of association found in the observational studies questions the relevance of these observations to a "real world" COPD population. To clarify the clinical utility of this biomarker, the association should be tested in prospective effectiveness studies.

Machine learning to help researchers evaluate biases in clinical trials: a prospective, randomized user study.

OBJECTIVE: Assessing risks of bias in randomized controlled trials (RCTs) is an important but laborious task when conducting systematic reviews. RobotReviewer (RR), an open-source machine learning (ML) system, semi-automates bias assessments. We conducted a user study of RobotReviewer, evaluating time saved and usability of the tool. MATERIALS AND METHODS: Systematic reviewers applied the Cochrane Risk of Bias tool to four randomly selected RCT articles. Reviewers judged: whether an RCT was at low, or high/unclear risk of bias for each bias domain in the Cochrane tool (Version 1); and highlighted article text justifying their decision. For a random two of the four articles, the process was semi-automated: users were provided with ML-suggested bias judgments and text highlights. Participants could amend the suggestions if necessary. We measured time taken for the task, ML suggestions, usability via the System Usability Scale (SUS) and collected qualitative feedback. RESULTS: For 41 volunteers, semi-automation was quicker than manual assessment (mean 755 vs. 824 s; relative time 0.75, 95% CI 0.62-0.92). Reviewers accepted 301/328 (91%) of the ML Risk of Bias (RoB) judgments, and 202/328 (62%) of text highlights without change. Overall, ML suggested text highlights had a recall of 0.90 (SD 0.14) and precision of 0.87 (SD 0.21) with respect to the users' final versions. Reviewers assigned the system a mean 77.7 SUS score, corresponding to a rating between "good" and "excellent". CONCLUSIONS: Semi-automation (where humans validate machine learning suggestions) can improve the efficiency of evidence synthesis. Our system was rated highly usable, and expedited bias assessment of RCTs.

A Scoping Review of stroke registers in Sub Saharan Africa.

BACKGROUND: Stroke registers are recommended as a key priority by the Lancet Neurology World Stroke Organisation Commission for Stroke, 2023, and the African Stroke Leaders' Summit, 2022. AIMS: This scoping review aims to map where stroke registers have been implemented in SSA. The article then compares and critiques the methods and definitions used and summarizes key results from the registers. SUMMARY: We identified 42 unique stroke registers from 48 individual studies. The registers were located in 20 countries, with 19 from East Africa, 15 West Africa, six Central Africa and two from Southern Africa. Cumulatively, the registers recruited 12,345 participants with stroke, the median number of participants was 183 (IQR:121-312) and the range was 50-1018. Only one study was a population-based register and 41 were hospital-based registers. Of the hospital-based registers, 29 were single site, 10 were conducted at two sites, and two at three sites. 23 (54.7%) of the registers were located in the capital city of their respective country and only one of the hospital-based registers was in a self-described rural area. Length of recruitment ranged from four months to six years, median length of recruitment was 12 months.Methodology and definitions were heteregenous between the registers. Only seven (19.4%) registers referenced the WHO STEPwise approach to implementing stroke registers. 27 (64.3%) registers used the WHO definition of stroke. Mean neuroimaging rate was 84%, and ranged from 0-100%. Stroke severity was measured using the National Institute of Health Stroke Scale (NIHSS) in 22 (52.4%) registers, four registers used Glasgow Coma Scale (GCS), two registers used the miniNIHSS, one used the Scandanavian stroke scale, one mRS and 11 registers did not report a stroke severity measure. 17 (40.5%) registers used the mRS to measure function, six registers used Barthel Index alone and three registers used both mRS and Barthel Index. Only two registers included a quality of life measure, the EQ-5D. 8 registers included a quality of care measure, 26 (61.9%) registers recorded socioeconomic status or a socioeconomic status proxy, most frequently educational attainment. CONCLUSIONS: This scoping review found high heterogeneity of methods and definitions used by stroke registers, with low uptake of the WHO stepwise method of stroke surveillance. A drive to standardize methodology would improve the comparability of stroke data in SSA. The shared use of educational attainment by registers in our review may enable future meta-analyses of inequities in stroke in SSA. Incorporating health-related quality of life measures, such as EQ-5D, into stroke registers should be encouraged, bringing a patient perspective and allow the estimation of quality-adjusted life years lost to stroke. Agreement on a standardized register methodology or further promotion and uptake of the WHO stepwise method is essential to produce comparable data to improve stroke prevention and care.

Quality of life and quality-adjusted life years after stroke in Sierra Leone.

BACKGROUND: Stroke is a leading cause of mortality and negatively affects health-related quality of life (HRQoL). HRQoL after stroke is understudied in Africa and there are no reports of quality-adjusted life years after stroke (QALYs) in African countries. We determined the impact of stroke on HRQoL after stroke in Sierra Leone. We calculated QALYs at 1 year post-stroke and determined sociodemographic and clinical variables associated with HRQoL and QALYs in this population. METHODS: A prospective stroke register was established at the two-principal adult tertiary government hospitals in Freetown, Sierra Leone. Participants were followed up at 7, 90 days, and 1 year post-stroke to capture all-cause mortality and EQ-5D-3L data. QALYs were calculated at the patient level using EQ-5D-3L utility values and survival data from the register, following the area under the curve method. Utilities were based on the UK and Zimbabwe (as a sensitivity analysis) EQ-5D value sets, as there is no Sierra Leonean or West African value set. Explanatory models were developed based on previous literature to assess variables associated with HRQoL and QALYs at 1 year after stroke. To address missing values, Multiple Imputation by Chained Equations (MICE), with linear and logistic regression models for continuous and binary variables, respectively, were used. RESULTS: EQ-5D-3L data were available for 373/460 (81.1%), 360/367 (98.1%), and 299/308 (97.1%) participants at 7, 90 days, and 1 year after stroke. For stroke survivors, median EQ-5D-3L utility increased from 0.20 (95% CI: -0.16 to 0.59) at 7 days post-stroke to 0.76 (0.47 to 1.0) at 90 days and remained stable at 1 year 0.76 (0.49 to 1.0). Mean QALYs at 1 year after stroke were 0.28 (SD: 0.35) and closely associated with stroke severity. Older age, lower educational attainment, patients with subarachnoid hemorrhage and undetermined stroke types all had lower QALYs and lower HRQoL, while being the primary breadwinner was associated with higher HRQoL. Sensitivity analysis with the Zimbabwe value set did not significantly change regression results but did influence the absolute values with Zimbabwe utility values being higher, with fewer utility values less than 0. CONCLUSION: We generated QALYs after stroke for the first time in an African country. QALYs were significantly lower than studies from outside Africa, partially explained by the high mortality rate in our cohort. Further research is needed to develop appropriate value sets for West African countries and to examine QALYs lost due to stroke over longer time periods. DATA AVAILABILITY: The Stroke in Sierra Leone anonymized dataset is available on request to researchers, see data access section.

Burden of intracerebral haemorrhage in Europe: forecasting incidence and mortality between 2019 and 2050.

Background: Anticipating the burden of intracerebral haemorrhage is crucial for proactive management and building resilience against future health challenges. Prior forecasts are based on population demography and to a lesser extent epidemiological trends. This study aims to utilise selected modifiable risk factors and socio-demographic indicators to forecast the incidence and mortality of intracerebral haemorrhage in Europe between 2019 and 2050. Methods: Three intracerebral haemorrhage risk factors identified in the Global Burden of Diseases, Injuries, and Risk Factors study (GBD 2019)-high systolic blood pressure, high fasting plasma glucose, and high body mass index-were utilised to predict the risk-attributable fractions between 2019 and 2050. Disease burden not attributable to these risk factors was then forecasted using time series models (autoregressive integrated moving average [ARIMA]), incorporating the Socio-demographic Index (SDI) as an external predictor. The optimal parameters of ARIMA models were selected for each age-sex-country group based on the Akaike Information Criterion (AIC). Different health scenarios were constructed by extending the past 85th and 15th percentiles of annualised rates of change in risk factors and SDI across all location-years, stratified by age and sex groups. A decomposition analysis was performed to assess the relative contributions of population size, age composition, and intracerebral haemorrhage risk on the projected changes. Findings: Compared with observed figures in 2019, our analysis predicts an increase in the burden of intracerebral haemorrhage in Europe in 2050, with a marginal rise of 0.6% (95% uncertainty interval [UI], -7.4% to 9.6%) in incident cases and an 8.9% (-2.8% to 23.6%) increase in mortality, reaching 141.2 (120.6-166.5) thousand and 144.2 (122.9-172.2) thousand respectively. These projections may fluctuate depending on trajectories of the risk factors and SDI; worsened trends could result in increases of 16.7% (8.7%-25.3%) in incidence and 31.2% (17.7%-48%) in mortality, while better trajectories may lead to a 10% (16.4%-2.3%) decrease in intracerebral haemorrhage cases with stabilised mortality. Individuals aged ≥80 years are expected to contribute significantly to the burden, comprising 62.7% of the cases in 2050, up from 40% in 2019, and 72.5% of deaths, up from 50.5%. Country-wide variations were noted in the projected changes, with decreases in the standardised rates across all nations but varying crude rates. The largest relative reductions in counts for both incidence and mortality are expected in Latvia, Bulgaria, and Hungary-ranging from -38.2% to -32.4% and -37.3% to -30.2% respectively. In contrast, the greatest increases for both measures were forecasted in Ireland (45.7% and 74.4%), Luxembourg (45% and 70.7%), and Cyprus (44.5% and 74.2%). The modelled increase in the burden of intracerebral haemorrhage could largely be attributed to population ageing. Interpretation: This study provides a comprehensive forecast of intracerebral haemorrhage in Europe until 2050, presenting different trajectories. The potential increase in the number of people experiencing and dying from intracerebral haemorrhage could have profound implications for both caregiving responsibilities and associated costs. However, forecasts were divergent between different scenarios and among EU countries, signalling the pivotal role of public health initiatives in steering the trajectories. Funding: The European Union's Horizon 2020 Research and Innovation Programme under grant agreement No. 754517. The National Institute for Health and Care Research (NIHR) under its Programme Grants for Applied Research (NIHR202339).

Question answering systems for health professionals at the point of care-a systematic review.

OBJECTIVES: Question answering (QA) systems have the potential to improve the quality of clinical care by providing health professionals with the latest and most relevant evidence. However, QA systems have not been widely adopted. This systematic review aims to characterize current medical QA systems, assess their suitability for healthcare, and identify areas of improvement. MATERIALS AND METHODS: We searched PubMed, IEEE Xplore, ACM Digital Library, ACL Anthology, and forward and backward citations on February 7, 2023. We included peer-reviewed journal and conference papers describing the design and evaluation of biomedical QA systems. Two reviewers screened titles, abstracts, and full-text articles. We conducted a narrative synthesis and risk of bias assessment for each study. We assessed the utility of biomedical QA systems. RESULTS: We included 79 studies and identified themes, including question realism, answer reliability, answer utility, clinical specialism, systems, usability, and evaluation methods. Clinicians' questions used to train and evaluate QA systems were restricted to certain sources, types and complexity levels. No system communicated confidence levels in the answers or sources. Many studies suffered from high risks of bias and applicability concerns. Only 8 studies completely satisfied any criterion for clinical utility, and only 7 reported user evaluations. Most systems were built with limited input from clinicians. DISCUSSION: While machine learning methods have led to increased accuracy, most studies imperfectly reflected real-world healthcare information needs. Key research priorities include developing more realistic healthcare QA datasets and considering the reliability of answer sources, rather than merely focusing on accuracy.

Natural history of depression up to 18 years after stroke: a population-based South London Stroke Register study.

Background: Current evidence on the long-term natural history of post-stroke depression (PSD) is limited. We aim to determine the prevalence, incidence, duration and recurrence rates of depression to 18-years after stroke and assess differences by onset-time and depression severity. Methods: Data were from the South London Stroke Register (1995-2019, N = 6641 at registration). Depression was defined using the Hospital Anxiety and Depression scale (scores > 7 = depression) at 3-months, then annually to 18-years after stroke. We compared early- (3-months post-stroke) vs late-onset depression (1-year) and initial mild (HADS scores > 7) vs severe depression (scores > 10). Findings: 3864 patients were assessed for depression at any time-points during the follow-up (male:55.4% (2141), median age: 68.0 (20.4)), with the number ranging from 2293 at 1-year to 145 at 18-years after stroke. Prevalence of PSD ranged from 31.3% (28.9-33.8) to 41.5% (33.6-49.3). The cumulative incidence of depression was 59.4% (95% CI 57.8-60.9), of which 87.9% (86.5-89.2) occurred within 5-years after stroke. Of patients with incident PSD at 3-months after stroke, 46.6% (42.1-51.2) recovered after 1 year. Among those recovered, 66.7% (58.0-74.5) experienced recurrent depression and 94.4% (87.5-98.2) of recurrences occurred within 5-years since recovery. Similar estimates were observed in patients with PSD at 1-year. 34.3% (27.9-41.1) of patients with severe depression had recovered at the next time-point, compared to 56.7% (50.5-62.8) with mild depression. Recurrence rate at 1-year after recovery was higher in patients with severe depression (52.9% (35.1-70.2)) compared to mild depression (23.5% (14.1-35.4)) (difference: 29.4% (7.6-51.2), p = 0.003). Interpretation: Long-term depressive status may be established by 5-years post-onset. Early- and late-onset depression presented similar natural history, while severe depression had a longer duration and quicker recurrence than mild depression. These estimates were limited to alive patients completing the depression assessment, who tended to have less severe stroke than excluded patients, so may be underestimated and not generalizable to all stroke survivors. Funding: National Institute for Health and Care Research (NIHR202339).

Trends in risk factor prevalence and management before first stroke: data from the South London Stroke Register 1995-2011.

BACKGROUND AND PURPOSE: Vascular risk factors are suboptimally managed internationally. This study investigated time trends in risk factors diagnosed before stroke and their treatment, and factors associated with appropriate medication use. METHODS: A total of 4416 patients with a first stroke were registered in the population-based South London Stroke Register from 1995 to 2011. Previously diagnosed risk factors and usual medications were collected from patients' primary care and hospital records. Trends and associations were assessed using multivariate logistic regression. RESULTS: Seventy-two percent of patients were diagnosed previously with 1 or more risk factors; 30% had diagnosed risk factors that were untreated. Hypercholesterolemia increased significantly during the study period; myocardial infarction and transient ischemic attack prevalences decreased. Antiplatelet prescription increased in atrial fibrillation (AF), myocardial infarction, and transient ischemic attack (AF, 37%-51%, P<0.001; myocardial infarction, 48%-69%, P<0.001; transient ischemic attack, 49%-61%, P=0.015). Anticoagulant prescription for AF showed a nonsignificant increase (12%-23%; P=0.059). Fewer older patients with AF were prescribed anticoagulants (age, >85 versus <65 years; adjusted relative risk, 0.19; 95% confidence interval, 0.08-0.41). Black ethnicity (adjusted relative risk, 1.17; 95% confidence interval, 1.10-1.23) and female sex (adjusted relative risk, 1.09; 95% confidence interval, 1.03-1.15) were associated with increased antihypertensive drug prescription; other medications did not vary by ethnicity or sex. CONCLUSIONS: Antiplatelet and cholesterol-lowering treatment prescribing have improved significantly over time; however, only a minority with AF received anticoagulants, and this did not improve significantly. Overall, 30% of strokes occurred in patients with previously diagnosed but untreated risk factors.

Automatically Summarizing Evidence from Clinical Trials: A Prototype Highlighting Current Challenges.

We present TrialsSummarizer, a system that aims to automatically summarize evidence presented in the set of randomized controlled trials most relevant to a given query. Building on prior work (Marshall et al., 2020), the system retrieves trial publications matching a query specifying a combination of condition, intervention(s), and outcome(s), and ranks these according to sample size and estimated study quality. The top-k such studies are passed through a neural multi-document summarization system, yielding a synopsis of these trials. We consider two architectures: A standard sequence-to-sequence model based on BART (Lewis et al., 2019), and a multi-headed architecture intended to provide greater transparency to end-users. Both models produce fluent and relevant summaries of evidence retrieved for queries, but their tendency to introduce unsupported statements render them inappropriate for use in this domain at present. The proposed architecture may help users verify outputs allowing users to trace generated tokens back to inputs. The demonstration video is available at: https://vimeo.com/735605060 The prototype, source code, and model weights are available at: https://sanjanaramprasad.github.io/trials-summarizer/.

In a pilot study, automated real-time systematic review updates were feasible, accurate, and work-saving.

OBJECTIVES: The aim of this study is to describe and pilot a novel method for continuously identifying newly published trials relevant to a systematic review, enabled by combining artificial intelligence (AI) with human expertise. STUDY DESIGN AND SETTING: We used RobotReviewer LIVE to keep a review of COVID-19 vaccination trials updated from February to August 2021. We compared the papers identified by the system with those found by the conventional manual process by the review team. RESULTS: The manual update searches (last search date July 2021) retrieved 135 abstracts, of which 31 were included after screening (23% precision, 100% recall). By the same date, the automated system retrieved 56 abstracts, of which 31 were included after manual screening (55% precision, 100% recall). Key limitations of the system include that it is limited to searches of PubMed/MEDLINE, and considers only randomized controlled trial reports. We aim to address these limitations in future. The system is available as open-source software for further piloting and evaluation. CONCLUSION: Our system identified all relevant studies, reduced manual screening work, and enabled rolling updates on publication of new primary research.

Stroke in Sierra Leone: Case fatality rate and functional outcome after stroke in Freetown.

BACKGROUND: There is limited information on long-term outcomes after stroke in sub-Saharan Africa (SSA). Current estimates of case fatality rate (CFR) in SSA are based on small sample sizes with varying study design and report heterogeneous results. AIMS: We report CFR and functional outcomes from a large, prospective, longitudinal cohort of stroke patients in Sierra Leone and describe factors associated with mortality and functional outcome. METHODS: A prospective longitudinal stroke register was established at both adult tertiary government hospitals in Freetown, Sierra Leone. It recruited all patients ⩾ 18 years with stroke, using the World Health Organization definition, from May 2019 until October 2021. To reduce selection bias onto the register, all investigations were paid by the funder and outreach conducted to raise awareness of the study. Sociodemographic data, National Institute of Health Stroke Scale (NIHSS), and Barthel Index (BI) were collected on all patients on admission, at 7 days, 90 days, 1 year, and 2 years post stroke. Cox proportional hazards models were constructed to identify factors associated with all-cause mortality. A binomial logistic regression model reports odds ratio (OR) for functional independence at 1 year. RESULTS: A total of 986 patients with stroke were included, of which 857 (87%) received neuroimaging. Follow-up rate was 82% at 1 year, missing item data were <1% for most variables. Stroke cases were equally split by sex and mean age was 58.9 (SD: 14.0) years. About 625 (63%) were ischemic, 206 (21%) primary intracerebral hemorrhage, 25 (3%) subarachnoid hemorrhage, and 130 (13%) were of undetermined stroke type. Median NIHSS was 16 (9-24). CFR at 30 days, 90 days, 1 year, and 2 years was 37%, 44%, 49%, and 53%, respectively. Factors associated with increased fatality at any timepoint were male sex (hazard ratio (HR): 1.28 (1.05-1.56)), previous stroke (HR: 1.34 (1.04-1.71)), atrial fibrillation (HR: 1.58(1.06-2.34)), subarachnoid hemorrhage (HR: 2.31 (1.40-3.81)), undetermined stroke type (HR: 3.18 (2.44-4.14)), and in-hospital complications (HR: 1.65 (1.36-1.98)). About 93% of patients were completely independent prior to their stroke, declining to 19% at 1 year after stroke. Functional improvement was most likely to occur between 7 and 90 days post stroke with 35% patients improving, and 13% improving between 90 days to 1 year. Increasing age (OR: 0.97 (0.95-0.99)), previous stroke (OR: 0.50 (0.26-0.98)), NIHSS (OR: 0.89 (0.86-0.91)), undetermined stroke type (OR: 0.18 (0.05-0.62)), and ⩾1 in-hospital complication (OR: 0.52 (0.34-0.80)) were associated with lower OR of functional independence at 1 year. Hypertension (OR: 1.98 (1.14-3.44)) and being the primary breadwinner of the household (OR: 1.59 (1.01-2.49)) were associated with functional independence at 1 year. CONCLUSION: Stroke affected younger people and resulted in high rates of fatality and functional impairment relative to global averages. Key clinical priorities for reducing fatality include preventing stroke-related complications through evidence-based stroke care, improved detection and management of atrial fibrillation, and increasing coverage of secondary prevention. Further research into care pathways and interventions to encourage care seeking for less severe strokes should be prioritized, including reducing the cost barrier for stroke investigations and care.