Systematic review: Pharmacological interventions for the treatment of post-stroke fatigue.

BACKGROUND: Post-stroke fatigue (PSF) affects around 50% of stroke survivors. Previous systematic reviews of randomized controlled trials found insufficient evidence to guide practice, but most excluded Chinese studies. Furthermore, their searches are now out-of-date. AIMS: To systematically review and perform a meta-analysis of randomized placebo-controlled trials of pharmacological interventions for treating PSF. METHODS: We screened Airitri, CNKI, VIP, CINAHL, ClinicalTrials.gov, CENTRAL, Cochrane Stroke Group Trial Register, EMBASE, EU Clinical Trial Register, ISRCTN, MEDLINE, PsycINFO, Wanfang, and WHO ICTRP up to 11 November 2022. Our primary outcome was fatigue severity. We conducted subgroup analysis by drug type and sensitivity analysis after excluding the trials at high risk of bias. Secondary outcomes included mood and quality of life. RESULTS: We screened 33,297 citations and identified 10 published completed trials, 6 unpublished completed trials, and 6 ongoing trials. Pharmacological treatments were associated with lower fatigue severity at the end of treatment (10 published completed trials, 600 participants, pooled standardized mean difference (SMD) = -0.80, 95% confidence interval (CI): -1.29 to -0.31; I2 = 86%, p < 0.00001), but not at follow-up (265 participants, pooled SMD = -0.14, 95% CI: -0.38 to 0.10; I2 = 0, p = 0.51). However, these trials were small and had considerable risk of bias. Beneficial effects were seen in trials with low risk of bias on randomization, missing outcome data, and reporting bias. There were insufficient data on secondary outcomes for meta-analysis, but six trials reported improved quality of life. CONCLUSION: There is insufficient evidence to support a particular pharmacological treatment for PSF, thus current clinical guidelines do not require amendment.

A systematic review and synthesis of global stroke guidelines on behalf of the World Stroke Organization.

BACKGROUND: There are multiple stroke guidelines globally. To synthesize these and summarize what existing stroke guidelines recommend about the management of people with stroke, the World Stroke Organization (WSO) Guideline committee, under the auspices of the WSO, reviewed available guidelines. AIMS: To systematically review the literature to identify stroke guidelines (excluding primary stroke prevention and subarachnoid hemorrhage) since 1 January 2011, evaluate quality (The international Appraisal of Guidelines, Research and Evaluation (AGREE II)), tabulate strong recommendations, and judge applicability according to stroke care available (minimal, essential, advanced). SUMMARY OF REVIEW: Searches identified 15,400 titles; 911 texts were retrieved, 200 publications scrutinized by the three subgroups (acute, secondary prevention, rehabilitation), and recommendations extracted from most recent version of relevant guidelines. For acute treatment, there were more guidelines about ischemic stroke than intracerebral hemorrhage; recommendations addressed pre-hospital, emergency, and acute hospital care. Strong recommendations were made for reperfusion therapies for acute ischemic stroke. For secondary prevention, strong recommendations included establishing etiological diagnosis; management of hypertension, weight, diabetes, lipids, and lifestyle modification; and for ischemic stroke, management of atrial fibrillation, valvular heart disease, left ventricular and atrial thrombi, patent foramen ovale, atherosclerotic extracranial large vessel disease, intracranial atherosclerotic disease, and antithrombotics in non-cardioembolic stroke. For rehabilitation, there were strong recommendations for organized stroke unit care, multidisciplinary rehabilitation, task-specific training, fitness training, and specific interventions for post-stroke impairments. Most recommendations were from high-income countries, and most did not consider comorbidity, resource implications, and implementation. Patient and public involvement was limited. CONCLUSION: The review identified a number of areas of stroke care where there was strong consensus. However, there was extensive repetition and redundancy in guideline recommendations. Future guideline groups should consider closer collaboration to improve efficiency, include more people with lived experience in the development process, consider comorbidity, and advise on implementation.

Predictors of post-stroke cognitive impairment using acute structural MRI neuroimaging: A systematic review and meta-analysis.

BACKGROUND: Stroke survivors are at an increased risk of developing post-stroke cognitive impairment and post-stroke dementia; those at risk could be identified by brain imaging routinely performed at stroke onset. AIM: This systematic review aimed to identify features which are associated with post-stroke cognitive impairment (including dementia) on magnetic resonance imaging (MRI) performed at stroke diagnosis. SUMMARY OF REVIEW: We searched the literature from inception to January 2022 and identified 10,284 records. We included studies that performed MRI at the time of stroke (0-30 days after a stroke) and assessed cognitive outcome at least 3 months after stroke. We synthesized findings from 26 papers, comprising 27 stroke-populations (N = 13,114, average age range = 40-80 years, 19-62% female). When data were available, we pooled unadjusted (ORu) and adjusted (ORa) odds ratios.We found associations between cognitive outcomes and presence of cerebral atrophy (three studies, N = 453, ORu = 2.48, 95% CI = 1.15-4.62), presence of microbleeds (two studies, N = 9151, ORa = 1.36, 95% CI = 1.08-1.70), and increasing severity of white matter hyperintensities (three studies, N = 704, ORa = 1.26, 95% CI = 1.06-1.49). Increasing cerebral small vessel disease score was associated with cognitive outcome following unadjusted analysis only (two studies, N = 499, ORu = 1.34, 95%CI = 1.12-1.61; three studies, N = 950, ORa = 1.23, 95% CI = 0.96-1.57). Associations remained after controlling for pre-stroke cognitive impairment. We did not find associations between other stroke features and cognitive outcome, or there were insufficient data. CONCLUSION: Acute stroke MRI features may enable healthcare professionals to identify patients at risk of post-stroke cognitive problems. However, there is still substantial uncertainty about the prognostic utility of acute MRI for this.

Perceptual Disorders After Stroke: A Scoping Review of Interventions.

Perceptual disorders relating to hearing, smell, somatosensation, taste, touch, and vision commonly impair stroke survivors' ability to interpret sensory information, impacting on their ability to interact with the world. We aimed to identify and summarize the existing evidence for perceptual disorder interventions poststroke and identify evidence gaps. We searched 13 electronic databases including MEDLINE and Embase and Grey literature and performed citation tracking. Two authors independently applied a priori-defined selection criteria; studies involving stroke survivors with perceptual impairments and interventions addressing those impairments were included. We extracted data on study design, population, perceptual disorders, interventions, and outcomes. Data were tabulated and synthesized narratively. Stroke survivors, carers, and clinicians were involved in agreeing definitions and organizing and interpreting data. From 91 869 records, 80 studies were identified (888 adults and 5 children); participant numbers were small (median, 3.5; range, 1-80), with a broad range of stroke types and time points. Primarily focused on vision (34/80, 42.5%) and somatosensation (28/80; 35.0%), included studies were often case reports (36/80; 45.0%) or randomized controlled trials (22/80; 27.5%). Rehabilitation approaches (78/93; 83.9%), primarily aimed to restore function, and were delivered by clinicians (30/78; 38.5%) or technology (28/78; 35.9%; including robotic interventions for somatosensory disorders). Pharmacological (6/93; 6.5%) and noninvasive brain stimulation (7/93; 7.5%) approaches were also evident. Intervention delivery was poorly reported, but most were delivered in hospital settings (56/93; 60.2%). Study outcomes failed to assess the transfer of training to daily life. Interventions for stroke-related perceptual disorders are underresearched, particularly for pediatric populations. Evidence gaps include interventions for disorders of hearing, taste, touch, and smell perception. Future studies must involve key stakeholders and report this fully. Optimization of intervention design, evaluation, and reporting is required, to support the development of effective, acceptable, and implementable interventions. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42019160270.

Predicting post-stroke cognitive impairment using acute CT neuroimaging: A systematic review and meta-analysis.

BACKGROUND: Identifying whether acute stroke patients are at risk of cognitive decline could improve prognostic discussions and management. Structural computed tomography neuroimaging is routine in acute stroke, and may identify those at risk of post-stroke dementia or post-stroke cognitive impairment (PSCI). AIM: To systematically review the literature to identify which stroke or pre-stroke features on brain computed tomography scans, performed at the time of stroke, are associated with post-stroke dementia or PSCI. SUMMARY OF REVIEW: We searched electronic databases to December 2020. We included studies reporting acute stroke brain computed tomography, and later diagnosis of a cognitive syndrome. We created summary estimates of size of unadjusted association between computed tomography features and cognition. Of 9536 citations, 28 studies (41 papers) were eligible (N = 7078, mean age 59.8-78.6 years). Cognitive outcomes were post-stroke dementia (10 studies), PSCI (17 studies), and one study analyzed both. Fifteen studies (N = 2952) reported data suitable for meta-analyses. White matter lesions (WML) (six studies, N = 1054, OR = 2.46, 95% CI = 1.25-4.84), cerebral atrophy (four studies, N = 558, OR = 2.80, 95% CI = 1.21-6.51), and pre-existing stroke lesions (three studies, N = 352, OR = 2.38, 95% CI = 1.06-5.32) were associated with post-stroke dementia. WML (four studies, N = 473, OR = 3.46, 95% CI = 2.17-5.52) were associated with PSCI. Other computed tomography features were either not associated with cognitive outcome, or there were insufficient data. CONCLUSIONS: Cognitive impairment following stroke is of great concern to patients and carers. Features seen on visual assessment of acute stroke computed tomography brain scans are strongly associated with cognitive outcomes. Clinicians should consider when and how this information should be discussed with stroke survivors.

Palliative care after stroke: A review.

BACKGROUND: Palliative care is an integral aspect of stroke unit care. In 2016, the American Stroke Association published a policy statement on palliative care and stroke. Since then there has been an expansion in the literature on palliative care and stroke. AIM: Our aim was to narratively review research on palliative care and stroke, published since 2015. RESULTS: The literature fell into three broad categories: (a) scope and scale of palliative care needs, (b) organization of palliative care for stroke, and (c) shared decision making. Most literature was observational. There was a lack of evidence about interventions that address specific palliative symptoms or improve shared decision making. Racial disparities exist in access to palliative care after stroke. There was a dearth of literature from low- and middle-income countries. CONCLUSION: We recommend further research, especially in low- and middle-income countries, including research to explore why racial disparities in access to palliative care exist. Randomized trials are needed to address specific palliative care needs after stroke and to understand how best to facilitate shared decision making.

Interventions to support the resilience and mental health of frontline health and social care professionals during and after a disease outbreak, epidemic or pandemic: a mixed methods systematic review.

BACKGROUND: Evidence from disease epidemics shows that healthcare workers are at risk of developing short- and long-term mental health problems. The World Health Organization (WHO) has warned about the potential negative impact of the COVID-19 crisis on the mental well-being of health and social care professionals. Symptoms of mental health problems commonly include depression, anxiety, stress, and additional cognitive and social problems; these can impact on function in the workplace. The mental health and resilience (ability to cope with the negative effects of stress) of frontline health and social care professionals ('frontline workers' in this review) could be supported during disease epidemics by workplace interventions, interventions to support basic daily needs, psychological support interventions, pharmacological interventions, or a combination of any or all of these. OBJECTIVES: Objective 1: to assess the effects of interventions aimed at supporting the resilience and mental health of frontline health and social care professionals during and after a disease outbreak, epidemic or pandemic. Objective 2: to identify barriers and facilitators that may impact on the implementation of interventions aimed at supporting the resilience and mental health of frontline health and social care professionals during and after a disease outbreak, epidemic or pandemic. SEARCH METHODS: On 28 May 2020 we searched the Cochrane Database of Systematic Reviews, CENTRAL, MEDLINE, Embase, Web of Science, PsycINFO, CINAHL, Global Index Medicus databases and WHO Institutional Repository for Information Sharing. We also searched ongoing trials registers and Google Scholar. We ran all searches from the year 2002 onwards, with no language restrictions. SELECTION CRITERIA: We included studies in which participants were health and social care professionals working at the front line during infectious disease outbreaks, categorised as epidemics or pandemics by WHO, from 2002 onwards. For objective 1 we included quantitative evidence from randomised trials, non-randomised trials, controlled before-after studies and interrupted time series studies, which investigated the effect of any intervention to support mental health or resilience, compared to no intervention, standard care, placebo or attention control intervention, or other active interventions. For objective 2 we included qualitative evidence from studies that described barriers and facilitators to the implementation of interventions. Outcomes critical to this review were general mental health and resilience. Additional outcomes included psychological symptoms of anxiety, depression or stress; burnout; other mental health disorders; workplace staffing; and adverse events arising from interventions. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently applied selection criteria to abstracts and full papers, with disagreements resolved through discussion. One review author systematically extracted data, cross-checked by a second review author. For objective 1, we assessed risk of bias of studies of effectiveness using the Cochrane 'Risk of bias' tool. For objective 2, we assessed methodological limitations using either the CASP (Critical Appraisal Skills Programme) qualitative study tool, for qualitative studies, or WEIRD (Ways of Evaluating Important and Relevant Data) tool, for descriptive studies. We planned meta-analyses of pairwise comparisons for outcomes if direct evidence were available. Two review authors extracted evidence relating to barriers and facilitators to implementation, organised these around the domains of the Consolidated Framework of Implementation Research, and used the GRADE-CERQual approach to assess confidence in each finding. We planned to produce an overarching synthesis, bringing quantitative and qualitative findings together. MAIN RESULTS: We included 16 studies that reported implementation of an intervention aimed at supporting the resilience or mental health of frontline workers during disease outbreaks (severe acute respiratory syndrome (SARS): 2; Ebola: 9; Middle East respiratory syndrome (MERS): 1; COVID-19: 4). Interventions studied included workplace interventions, such as training, structure and communication (6 studies); psychological support interventions, such as counselling and psychology services (8 studies); and multifaceted interventions (2 studies). Objective 1: a mixed-methods study that incorporated a cluster-randomised trial, investigating the effect of a work-based intervention, provided very low-certainty evidence about the effect of training frontline healthcare workers to deliver psychological first aid on a measure of burnout. Objective 2: we included all 16 studies in our qualitative evidence synthesis; we classified seven as qualitative and nine as descriptive studies. We identified 17 key findings from multiple barriers and facilitators reported in studies. We did not have high confidence in any of the findings; we had moderate confidence in six findings and low to very low confidence in 11 findings. We are moderately confident that the following two factors were barriers to intervention implementation: frontline workers, or the organisations in which they worked, not being fully aware of what they needed to support their mental well-being; and a lack of equipment, staff time or skills needed for an intervention. We are moderately confident that the following three factors were facilitators of intervention implementation: interventions that could be adapted for local needs; having effective communication, both formally and socially; and having positive, safe and supportive learning environments for frontline workers. We are moderately confident that the knowledge or beliefs, or both, that people have about an intervention can act as either barriers or facilitators to implementation of the intervention. AUTHORS' CONCLUSIONS: There is a lack of both quantitative and qualitative evidence from studies carried out during or after disease epidemics and pandemics that can inform the selection of interventions that are beneficial to the resilience and mental health of frontline workers. Alternative sources of evidence (e.g. from other healthcare crises, and general evidence about interventions that support mental well-being) could therefore be used to inform decision making. When selecting interventions aimed at supporting frontline workers' mental health, organisational, social, personal, and psychological factors may all be important. Research to determine the effectiveness of interventions is a high priority. The COVID-19 pandemic provides unique opportunities for robust evaluation of interventions. Future studies must be developed with appropriately rigorous planning, including development, peer review and transparent reporting of research protocols, following guidance and standards for best practice, and with appropriate length of follow-up. Factors that may act as barriers and facilitators to implementation of interventions should be considered during the planning of future research and when selecting interventions to deliver within local settings.