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Scalable Bio Marker Combinations for Early Stroke Diagnosis: A Systematic Review.

ABSTRACT: Background: Acute stroke treatment is a time-critical process in which every minute counts. Laboratory biomarkers are needed to aid clinical decisions in the diagnosis. Although imaging is critical for this process, these biomarkers may provide additional information to distinguish actual stroke from its mimics and monitor patient condition and the effect of potential neuroprotective strategies. For such biomarkers to be effectively scalable to public health in any economic setting, these must be cost-effective and non-invasive. We hypothesized that blood-based combinations (panels) of proteins might be the key to this approach and explored this possibility through a systematic review. Methods: We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines for systematic review. Initially, the broader search for biomarkers for early stroke diagnosis yielded 704 hits, and five were added manually. We then narrowed the search to combinations (panels) of the protein markers obtained from the blood. Results: Twelve articles dealing with blood-based panels of protein biomarkers for stroke were included in the systematic review. We observed that NR2 peptide (antibody against the NR2 fragment) and glial fibrillary acidic protein (GFAP) are brain-specific markers related to stroke. Von Willebrand factor (vWF), matrix metalloproteinase 9 (MMP-9), and S100β have been widely used as biomarkers, whereas others such as the ischemia-modified albumin (IMA) index, antithrombin III (AT-III), and fibrinogen have not been evaluated in combination. We herein propose the following new combination of biomarkers for future validation: panel 1 (NR2 + GFAP + MMP-9 + vWF + S100β), panel 2 (NR2 + GFAP + MMP-9 + vWF + IMA index), and panel 3 (NR2 + GFAP + AT-III + fibrinogen). Conclusions: More research is needed to validate, identify, and introduce these panels of biomarkers into medical practice for stroke recurrence and diagnosis in a scalable manner. The evidence indicates that the most promising approach is to combine different blood-based proteins to provide diagnostic precision for health interventions. Through our systematic review, we suggest three novel biomarker panels based on the results in the literature and an interpretation based on stroke pathophysiology.

SUBMITTER: Baez SC

PROVIDER: S-EPMC8193128 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and purposeAccurate aphasia diagnosis is important in stroke care. A wide range of language tests are available and include informal assessments, tests developed by healthcare institutions and commercially published tests available for purchase in pre-packaged kits. The psychometrics of these tests are often reported online or within the purchased test manuals, not the peer-reviewed literature, therefore the diagnostic capabilities of these measures have not been systematically evaluated. This review aimed to identify both commercial and non-commercial language tests and tests used in stroke care and to examine the diagnostic capabilities of all identified measures in diagnosing aphasia in stroke populations.MethodsLanguage tests were identified through a systematic search of 161 publisher databases, professional and resource websites and language tests reported to be used in stroke care. Two independent reviewers evaluated test manuals or associated resources for cohort or cross-sectional studies reporting the tests' diagnostic capabilities (sensitivity, specificity, likelihood ratios or diagnostic odds ratios) in differentiating aphasic and non-aphasic stroke populations.ResultsFifty-six tests met the study eligibility criteria. Six "non-specialist" brief screening tests reported sensitivity and specificity information, however none of these measures reported to meet the specific diagnostic needs of speech pathologists. The 50 remaining measures either did not report validity data (n = 7); did not compare patient test performance with a comparison group (n = 17); included non-stroke participants within their samples (n = 23) or did not compare stroke patient performance against a language reference standard (n = 3). Diagnostic sensitivity analysis was completed for six speech pathology measures (WAB, PICA, CADL-2, ASHA-FACS, Adult FAVRES and EFA-4), however all studies compared aphasic performance with that of non-stroke healthy controls and were consequently excluded from the review.ConclusionsNo speech pathology test was found which reported diagnostic data for identifying aphasia in stroke populations. A diagnostically validated post-stroke aphasia test is needed.

Project description:BackgroundPrevious studies have shown the beneficial effects of aerobic exercise in chronic stroke. Most motor and functional recovery occurs in the first months after stroke. Improving cardiovascular capacity may have potential to precipitate recovery during early stroke rehabilitation. Currently, little is known about the effects of early cardiovascular exercise in stroke survivors. The aim of this systematic review was to evaluate the effectiveness of cardiovascular exercise early after stroke.MethodsA systematic literature search was performed. For this review, randomized and non-randomized prospective controlled cohort studies using a cardiovascular, cardiopulmonary or aerobic training intervention starting within 6 months post stroke were considered. The PEDro scale was used to detect risk of bias in individual studies. Inter-rater agreement was calculated (kappa). Meta-analysis was performed using a random-effects model.ResultsA total of 11 trials were identified for inclusion. Inter-rater agreement was considered to be "very good" (Kappa: 0.81, Standard Error: 0.06, CI95%: 0.70-0.92), and the methodological quality was "good" (7 studies) to "fair" (4 studies). Peak oxygen uptake data were available for 155 participants. Pooled analysis yielded homogenous effects favouring the intervention group (standardised mean difference (SMD) = 0.83, CI95% = 0.50-1.16, Z = 4.93, P < 0.01). Walking endurance assessed with the 6 Minute Walk Test comprised 278 participants. Pooled analysis revealed homogenous effects favouring the cardiovascular training intervention group (SMD = 0.69, CI95% = 0.45-0.94, Z = 5.58, P < 0.01). Gait speed, measured in 243 participants, did not show significant results (SMD = 0.51, CI95% = -0.25-1.26, Z = 1.31, P = 0.19) in favour of early cardiovascular exercise.ConclusionThis meta-analysis shows that stroke survivors may benefit from cardiovascular exercise during sub-acute stages to improve peak oxygen uptake and walking distance. Thus, cardiovascular exercise should be considered in sub-acute stroke rehabilitation. However, concepts to influence and evaluate aerobic capacity in severely affected individuals with sub-acute stroke, as well as in the very early period after stroke, are lacking.Further research is needed to develop appropriate methods for cardiovascular rehabilitation early after stroke and to evaluate long-term effects of cardiovascular exercise on aerobic capacity, physical functioning, and quality-of-life.

Project description:A recent review highlighted important relationships between combinations of movement behaviours (i.e., sleep, sedentary behaviour, and physical activity) and health indicators among school-aged children and youth (aged 5-17 years). It is unclear whether similar relationships exist in younger children. Therefore, this review sought to examine the relationships between combinations of movement behaviours and health indicators in the early years (1.00 month to 4.99 years).Medline, EMBASE, PsycINFO, and SportDiscus were searched for relevant studies up to November 2016, with no date or study design limits. Included studies met the a priori-determined population (apparently healthy children aged 1.00 month to 4.99 years), intervention (combination of ?2 movement behaviours [i.e., sleep and sedentary behaviour; sleep and physical activity; sedentary behaviour and physical activity; and sleep, sedentary behaviour, and physical activity]), comparator (various levels and combinations of movement behaviours), and health outcome/indicator (Critical: adiposity, motor development, psychosocial health/emotional regulation, cognitive development, fitness, and growth; Important: bone and skeletal health, cardiometabolic health, and risks). For each health indicator, quality of evidence was assessed by study design using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.Ten articles (n = 7436 participants; n = 5 countries) were included. Across observational and experimental study designs, the most ideal combinations of sedentary behaviour and physical activity were: favourably associated with motor development and fitness among preschool-aged children (3.00 to 4.99 years); both favourably and not associated with adiposity among toddlers (1.10 to 2.99 years) and preschool-aged children; and not associated with growth among toddlers and preschool-aged children. The most ideal combinations of sleep and sedentary behaviour were favourably associated with adiposity among infants (1.00 month to 1.00 years) and toddlers. Quality of evidence ranged from "very low" to "moderate".The most ideal combinations of movement behaviours (e.g., high sleep, low sedentary behaviour, high physical activity) may be important for optimal health in the early years. Findings can help inform movement behaviour guidelines for the early years. Given the limited evidence, future research is needed to determine the ideal distribution of daily movement behaviours for optimal health throughout the early years.

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Scalable Bio Marker Combinations for Early Stroke Diagnosis: A Systematic Review.

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