Anxiety and stress among healthcare professionals during COVID-19 in Ethiopia: systematic review and meta-analysis

Objective
This study intended to assess the impact of COVID-19 pandemic on anxiety and stress among healthcare professionals in Ethiopia.

Design
This study applied a design of systematic review and meta-analysis of observational studies.

Data sources

Eligibility criteria and outcomes
Observational studies examining anxiety and stress among healthcare professionals in Ethiopia following COVID-19 pandemic were considered. The primary outcomes were the prevalence of anxiety and stress and the secondary outcomes were factors associated to the prevalence of anxiety and stress.

Data extraction and synthesis
Two authors extracted the data and performed quality assessment independently. The Newcastle-Ottawa Scale was used to evaluate the quality of eligible studies. Random-effect model with the inverse variance method was used to estimate the pooled effect size of the outcome variables with its 95% CI. Publication bias was checked by DOI plot and Luis Furuya Kanamori index. Stata V.14.0 (StataCorp) software was used for statistical analysis.

Results
Thirteen studies were included. From eight studies the pooled prevalence of anxiety was 46% (95% CI 0.30% to 0.61%, 2=0.0497, I2=99.07%, p

Leggi
Febbraio 2023

Abstract TMP119: Increased Stroke Severity In A Model Of Preeclampsia Is Associated With Poor Collateral Flow, Oxidative Stress, And Elevated Thrombin

Stroke, Volume 54, Issue Suppl_1, Page ATMP119-ATMP119, February 1, 2023. Background:Pregnancy is associated with an increased risk of stroke largely driven by the comorbidity of preeclampsia (PE), a hypertensive disorder that complicates 4-8% of all pregnancies. Although stroke treatment has improved in recent years, pregnant women have been excluded from stroke clinical trials and thus little is known about treatment and stroke outcome in this population. We investigated stroke outcome (infarct and hemorrhagic transformation, HT) in normal pregnancy (Preg; n=13) and in a model of preeclampsia (PE; n=6) induced by feeding pregnant Sprague Dawley rats a high cholesterol diet on gestational days 7-21. Nonpregnant (NP; n=7) rats were a control for pregnancy.Methods:Middle cerebral artery occlusion (MCAO) was used to induce focal ischemia for 3 hours with 1 hour of reperfusion. Perfusion deficit in the core MCA and collateral territories were measured using multi-site laser Doppler. Infarction and oxidative stress were determined by cresyl violet and 3-nitrotyrosine staining of fixed brain tissue, respectively. Endothelial oxidative stress and hemostatic factors were measured by ELISA for 8-isoprostane and thrombin.Results:Perfusion deficit in core MCA was similar between groups; however, collateral flow was significantly impaired in ePE vs. NP and LP: -51±8% vs. -21±15% and -25±13% (p

Leggi
Febbraio 2023

Abstract TP237: Cofilin Inhibitor Protects Against Hydrogen Peroxide-induced Neuronal Cytotoxicity Via The Inhibition Of Oxidative Stress And Microglial Cell Activation

Stroke, Volume 54, Issue Suppl_1, Page ATP237-ATP237, February 1, 2023. Microglial activation & the failure of the antioxidant defense mechanisms are major hallmarks in different central nervous system injuries, mainly ischemic & hemorrhagic strokes. Cofilin is a cytoskeleton-associated protein involved in actin binding & severing. In our previous studies, we identified the potential role of cofilin in mediating microglial activation & neuronal apoptosis in ischemic & hemorrhagic conditions. Others have highlighted the involvement of cofilin in ROS production & the resultant neuronal death; however, more studies are needed to delineate the role of cofilin in oxidative stress conditions. Hence, the present study is aimed to investigate the role of cofilin in hydrogen peroxide (H2O2)-induced microglial activation & oxidative neuronal injury & its protection using a first-in-class small-molecule inhibitor of cofilin (SZ-3). An in vitro H2O2-induced cell death model was used in two different types of cells, human neuroblastoma (SH-SY5Y) & microglial (HMC3) cell lines. Cell viability was assessed by the Cell Counting Kit-8 assay. Western blotting was used to measure the expression levels of several proteins. Our results show that treatment with H2O2increases the expression of cofilin & slingshot-1 (SSH-1), an upstream regulator of cofilin, in microglial cells, which was significantly reduced in the SZ3 treated group. Cofilin inhibition significantly attenuated H2O2-induced microglial activation by reducing the release of proinflammatory mediators (HMGB1, TNF-α). Furthermore, we demonstrate that SZ3 protects against H2O2-induced cytotoxicity in SH-SY5Y cells & activates the AKT signaling pathway by increasing its phosphorylation levels. SZ3 treatment also induces the expression of Nrf2, a major transcription factor that regulates the oxidative stress response, & its related antioxidant enzymes (HO-1, SOD2, NQO1) in the SY-SY5Y cell. Together, these results suggest that cofilin inhibition plays an essential role in protecting neuronal cells under H2O2-induced oxidative stress, possibly by activating the antioxidant defense mechanisms & reducing microglial activation.

Leggi
Febbraio 2023

Abstract TMP32: Genetic Knockout Of CD38 Is Associated With Improved Cognitive Performance And Protection Against Oxidative Stress In Aged Mice

Stroke, Volume 54, Issue Suppl_1, Page ATMP32-ATMP32, February 1, 2023. Introduction:CD38 enzymatic activity is the main determinant of the age-dependent decline in nicotinamide adenine dinucleotide (NAD+) levels and the loss of CD38 function has been associated with increased longevity in rodents. Therefore, we hypothesize that the loss of CD38 and its enzymatic function will improve cognitive performance in advanced age through the preservation of NAD+levels and the protection against oxidative stress.Methods:CD38 Knockout (CD38KO) and C57BL/6J (wild type WT) male mice were aged for at least 24 months. The cognitive performance was compared through Barnes maze, Fear conditioning and Y-maze tests. Dihydroethidium (DHE), Diaminofluorescein-2 diacetate (DAF) and nicotinamide adenine dinucleotide phosphate NAD(P)H staining were used to assess the levels of superoxide, nitric oxide (NO) and NAD(P)H in the brain, respectively.Results:5 WT and 5 CD38KO mice aged (24-30) months were included. While there were no significant differences in fear conditioning and Y-maze tests, CD38KO mice showed better memory performance in Barnes maze test including shorter distance travelled (CD38KO: 2±0.06 vs WT: 3.7±1.1 m, p=0.008), longer time in proximity of the holes (CD38KO: 51.2±11.1 vs WT: 34.6±8.4 s, p=0.027), and shorter distance from the hole (CD38KO: 0.17±0.025 vs WT: 0.23±0.04 m, p=0.038) and less errors (CD38KO: 3.5±2.3 vs WKY: 6±0.7, p=0.04). Brain tissue analysis showed 58% lower superoxide (p

Leggi
Febbraio 2023

Abstract TMP66: Correlation Of Cerebrovascular Reserve Assessed By Acetazolamide-stress Spect With Collaterals On Arterial Spin-labeling MRI In Patients With Carotid Occlusive Disease

Stroke, Volume 54, Issue Suppl_1, Page ATMP66-ATMP66, February 1, 2023. Introduction:We investigated the relationship between the level of cerebral collateral circulation on arterial spin-labeling (ASL) magnetic resonance imaging (MRI) and cerebrovascular reserve (CVR) on acetazolamide (ACZ)-stress single photon emission computed tomography (SPECT) brain scans in internal carotid artery (ICA) stenosis.Methods:This study enrolled 129 patients with severe ICA stenosis ( >70%). Collateral circulation was assessed in pulsed ASL images based on the presence of arterial transit artifact (ATA) that late-arriving flow appears as serpiginous high ASL signal within cortical vessels. CVR based on rest-SPECT and ACZ-stress SPECT with Tc-99m-ECD was calculated. The ASL CBF maps were independently assessed by two neuroradiologists blinded to clinical information. The two neuroradiologists graded on two slices of ASL images corresponding to Alberta Stroke Program Early Computed Tomography Score (ASPECTS) location using a 4-point scale for ASL intensity.Results:With ACZ-stress SPECT, the 88/129 (68%) patients showed normal CVR and 41/129 (32%) patients showed decreased CVR. In 73/88 (82%) of the normal CVR group patients, ASL showed ATA in ipsilateral to the stenosis. In 19/41 (46%) of the decreased CVR group patients, ASL showed no evidence of ATA in ipsilateral to the stenosis. Significant positive relationship was observed between the normal CVR group and the ATA showing group in ICA stenosis patients (p = 0.001, chi-square test). The ASL-based ASPECTS scores of brain in the ipsilateral side was lower than the scores in the contralateral side to the ICA stenosis (p < 0.0001, Wilcoxon signed rank test). The ASL-based ASPECTS scores of brain ipsilateral side to the ICA stenosis was lower in the reduced CVR group than normal CVR group (p = 0.005).Conclusion:This study demonstrated the statistically significant positive correlation between good collaterals on ASL MRI and intact CVR in patients with ICA stenosis.

Leggi
Febbraio 2023

Abstract WP50: Stress Hyperglycemia And Early Neurological Deterioration In Patients With Acute LVO And Low NIHSS

Stroke, Volume 54, Issue Suppl_1, Page AWP50-AWP50, February 1, 2023. Introduction:Stress hyperglycemia is an essential survival response. However, it is associated with poor prognosis after ischemic stroke, and its contribution to collateral failure is not well defined. We investigated whether stress hyperglycemia would be associated with early neurological deterioration (END) in acute large vessel occlusion (LVO) patients who present with mild neurological deficit.Methods:From a multicenter stroke registry, ischemic stroke patients with acute anterior circulation LVO and mild symptoms (NIHSS

Leggi
Febbraio 2023

Abstract WP61: Impact Of Post-stroke Post Traumatic Stress Disorder On Quality Of Life

Stroke, Volume 54, Issue Suppl_1, Page AWP61-AWP61, February 1, 2023. Introduction:After an ischemic stroke or transient ischemic attack (TIA), patients may have post-event anxiety and re-experience transient neurological symptoms. However, some stroke patients develop persistent and disabling symptoms of post-traumatic stress disorder (PTSD). Data on post-stroke post-traumatic stress disorder (PS-PTSD) is sparse.Methods:We conducted a single-center observational pilot study of 20 adult patients diagnosed with stroke or TIA in the previous 31 days to 1 year. Patients completed the PTSD Check List-5 (PCL-5), Patient Health Questionnaire-9 (PHQ-9), stroke specific Quality of Life Scale-12 (SS-QOL-12), modified Rankin Scale of disability, and the National Institutes of Health Stroke Scale. The PCL-5 is a 20 item self-report score assessing symptoms of re-experiencing (Criterion B), avoidance (Criterion C), negative alterations in cognition or mood (Criterion D), and hyperarousal (Criterion E). Subjects were classified as having PS-PTSD with PCL-5 score ≥33 or endorsement of moderate symptoms in at least one B item, one C item, two D items, and two E items.Results:Twenty patients completed the PCL-5 and 19 completed the follow up scales. Seven patients (35%) were found to have PS-PTSD. Higher PCL-5 scores were significantly correlated with lower SS-QOL12 scores indicating worsened quality of life (r= -0.709, P=.001) and higher PHQ9 scores representing more depressive symptoms (r= 0.727, P

Leggi
Febbraio 2023

Abstract 38: Admission Hyperglycemia In Stroke Patients Increases Oxidative Stress In Red Blood Cells

Stroke, Volume 54, Issue Suppl_1, Page A38-A38, February 1, 2023. Background:Our recent study has shown that admission hyperglycemia in stroke patients is associated with red blood cell (RBC) dysregulation, however, the underlying mechanism is still unclear. In addition to transporting oxygen via hemoglobin, RBCs also carry a robust antioxidant system to remove the reactive oxygen species (ROS) continuously produced from hemoglobin autoxidation (Fig A). It has been reported that in vitro hyperglycemia can increase oxidative stress in RBCs. We thus hypothesize that acute hyperglycemia in stroke patients may also affect the antioxidant system in RBCs.Method:Stroke patients with hyperglycemia and normoglycemia (n=12/group) were prospectively recruited in accordance with IRB protocol. Blood was collected at 2 hr, 24 hr, 72 hr and 3 mon post stroke. RBCs were precipitated from whole blood, and leucocytes were removed with depletion filter. The expression and glycosylation of RBC antioxidants, such as catalase (CAT), superoxide dismutase type 1 (SOD1), glutathione peroxidase 1 (GPX1) and peroxiredoxin 2 (PRX2), were quantified using mass spectrometry-based selected reaction monitoring (SRM) method.Result:CAT, SOD1 and GPX1 showed gradually decreased expression in hyperglycemic stroke patients, which may impair the antioxidant capacity of RBCs (Fig B). The glycosylation level of PRX2 was increased in stroke-related hyperglycemia (Fig C), and increased glycosylation was associated with decreased PRX2 activity (Fig D). Consistent with the expression and glycosylation changes in antioxidants, total RBC antioxidant capacity was reduced in hyperglycemic patients, and ROS was significantly accumulated in RBCs (Fig E).Conclusion:Acute hyperglycemia in stroke patients intensifies RBC oxidative stress by affecting the expression and post-translational modification of RBC antioxidants. Larger studies are underway to verify these findings, and explore how hyperglycemia and RBC oxidative stress influence stroke outcome.

Leggi
Febbraio 2023

Abstract WMP31: Lifetime Stress, Acute Stress, And Long-term Outcomes After Stroke: A Longitudinal Study

Stroke, Volume 54, Issue Suppl_1, Page AWMP31-AWMP31, February 1, 2023. Background:Stroke is a sudden-onset, unexpected life event over which individuals have little control. These features can make the experience of having a stroke extremely stressful, which may potentiate its debilitating effects. We previously identified short-term associations among lifetime stress/trauma exposure (LSE), post-stroke acute stress (AS), Modified Rankin Scale (mRS) and Fugl-Meyer at 90 days post-stroke. However, their association with long-term stroke-related disability remains unknown.Hypothesis:Higher lifetime trauma and AS symptoms will be associated with poorer long-term disability 1-year post stroke.Method:Multi-site national study of patients admitted for a new stroke. Assessments included Acute Stress Disorder Interview 2-10 days post-stroke, LSE 90 days post-stroke, and Stroke Impact Scale (SIS), modified Rankin Scale (mRS), & Telephone Montreal Cognitive Assessment (tMOCA) at 1-year post-stroke. Structural Equation Modeling examined relationships among LSE, AS, and outcomes, controlling for admission NIHSS score and demographics.Results:Among key predictors and covariates (demographics, acute NIHSS), AS immediately post-stroke was the strongest direct correlate of poorer mRS scores and SIS scores at 1-year (ps < .001), and the second strongest direct correlate of tMOCA scores at 1-year; higher d90 LSE was directly associated with poorer SIS (p< .001), and indirectly associated with poorer mRS, SIS, & tMOCA scores at 1-year (allps < .001) through its association with high AS (p< .001) at admission.Conclusion:Lifetime stress and stress symptoms in the acute stroke setting are both associated with disability and cognitive impairment 12 months post-stroke; their assessment may be useful to facilitate early identification of high-risk patients and development of interventions that help improve functional and cognitive outcomes after stroke.

Leggi
Febbraio 2023

Abstract WP13: Value Of Stress Hyperglycemia Ratio In Predicting The Prognosis Of Patients With Acute Ischemic Stroke:a Subgroup Analysis Of The Rescue Bt Clinical Trial

Stroke, Volume 54, Issue Suppl_1, Page AWP13-AWP13, February 1, 2023. Objective:This study aimed to evaluate the correlation between the stress hyperglycemia and clinical outcomes after large vessel occlusion stroke (LVO) at 90 days.Methods:The RESCUE BT trial was a multicenter, randomized, double-blind, placebo-controlled clinical trial, consisting of 948 patients from 55 centers in China. In this subgroup study, 542 consecutive stroke patients with glucose or glycated hemoglobin values were included. Stress hyperglycemia was evaluated both as a tri-categorical variable (≤1.07 vs 1.08-1.29 vs ≥1.30) and a continuous variable. The primary outcome was favorable functional outcome (modified Rankin Scale [mRS] ≤ 2) at 90 days. The secondary outcome contained excellent functional outcome (modified Rankin Scale [mRS] ≤ 1) and safety outcomes such as 90-day mortality and intracranial hemorrhage.Results:542 patients were included. Compared to patients with the lowest tertiles of stress hyperglycemia, calculated as glucose/GA ratio, the highest tertiles of stress hyperglycemia was obviously associated with a higher rate of poor functional outcome at 90-day (modified Rankin Scale [mRS] score 3-6) after adjusted for potential covariates (adjusted hazard ratio, 0.44; 95% confidence interval, 0.28-0.69, P < 0.001). This result was also consistent in the excellent clinical outcome of 90-day mRS score 2-6 (adjusted hazard ratio, 0.48; 95% confidence interval, 0.29-0.79, P =0.004).Conclusion:In patients with acute ischemic stroke, lower stress hyperglycemia, as measured by glucose/GA ratio, was more likely to have favorable outcome at 90-day.Trial registrationChinese Clinical Trial Registry Identifier: ChiCTR-IOR-17014167, December 27, 2017.

Leggi
Febbraio 2023

Abstract 104: Cytochrome B5 Reductase 3 Regulates The Erythropoietin Response To Ischemic Stroke In A Mouse Model Of Chronic Anemia And Oxidative Stress

Stroke, Volume 54, Issue Suppl_1, Page A104-A104, February 1, 2023. Introduction:Cytochrome b5 reductase 3 (Cyb5R3) is a heme iron reductase that reverses oxidized soluble guanylate cyclase (sGC) heme iron (Fe3+Fe2+) to preserve nitric oxide signaling. Under oxidative stress, such as occurs with sickle cell disease (SCD) and ischemic stroke, Cyb5R3 redox signaling provides resilience against tissue damage. A loss-of-function (roughly 50%) Cyb5R3 missense variant (T117S) occurs with high frequency (0.23 minor allele) in persons of African ancestry, who also suffer a greater burden of sickle cell anemia and ischemic stroke than other races. We hypothesized that Cyb5R3 regulates the erythropoietin response to ischemic stroke in a mouse model of SCD.Methods:Age-matched male SCD mice with wild-type Cyb5R3 (SSWT) or T117S Cyb5R3 (SST117S) underwent middle cerebral artery occlusion (55 min) and reperfusion (48 hr). Blood was sampled at baseline and 48h reperfusion for hematology measurements. Brains were stained with 2,3,5-triphenyltetrazolium chloride to quantify infarct volume. Erythropoietin (EPO), heme oxygenase 1 (HMOX1) and sGC were assayed by Western blot.Results:We found brain infarct volume to be greater in SST117Svs SSWT(63 vs 27 cm3, respectively; P=0.003). Red cells, hematocrit and hemoglobin decreased in SST117Spost-stroke, which was opposite to SSWT(red cells: -13% vs 13%, P=0.01; hematocrit: -20% vs 0%, P=0.03; hemoglobin: -18% vs 3%, P=0.02, respectively). In the absence of stroke (age-matched controls), SSWThad elevated HMOX1 protein compared to SST117S, which normalized in post-stroke SSWTbut was unchanged in post-stroke SST117S. Kidney and plasma EPO levels significantly increased in SSWTpost-stroke, but not in SST117S. In vitro studies using HEK293 cells showed EPO and HMOX1 decrease with Cyb5R3 knockdown by siRNA.Conclusion:Our findings suggest a modifying role for Cyb5R3 in brain-kidney crosstalk during ischemic stroke, wherein loss of T117S Cyb5R3 activity negatively impacts renal and plasma EPO levels and resilience against infarct of ischemic brain tissue. The Cyb5R3 axis on which the brain-kidney-blood response to stroke in SCD turns represents a novel target for precision medicine approaches to managing stroke risk and pathology in SCD carriers of the T117S variant.

Leggi
Febbraio 2023

Abstract TMP13: Thin Wall Regions Of Intracranial Aneurysms Are Associated With High Wall Shear Stress

Stroke, Volume 54, Issue Suppl_1, Page ATMP13-ATMP13, February 1, 2023. Background:Intra-saccular hemodynamics play a key role in the pathobiological remodeling of the intracranial aneurysm (IA) wall. Evaluating the relationship between hemodynamic forces at the aneurysm wall and wall presentation can help us understand the complex processes of dysregulated vascular remodeling that occurs during IA natural history.Hypothesis:We hypothesized that greater hemodynamic insult, i.e., high wall shear stress (WSS) and high wall shear stress divergence (WSSD), results in endothelial damage and loss of internal elastic lamina, which presents as thin, translucent regions on interoperative imaging.Methods:From digital subtraction angiography images of 15 patients with IAs, aneurysm and surrounding vessels were segmented. Computational fluid dynamics (CFD) simulations were performed using generic boundary conditions for all the patients. Aneurysm walls were identified from 2D intraoperative images of IAs taken during clipping, and wall regions were classified as thick regions (white), normal (purple-crimson), and thin/translucent (red), using a semi-supervised machine learning algorithm. 2D wall classifications were mapped onto the 3D geometries for statistical analysis of differences between average hemodynamic properties across wall regions.Results:On an average, more than 30% of IA sac was visible on the 2D intra-operative image. Of then=15 IAs,n=8,n=5 andn=2 showed pre-dominantly thick, thin, and normal wall types respectively. Average WSS and WSSD were significantly higher at thin regions of IAs as compared to both normal and thick regions. Thin wall regions also tended to co-locate with significantly lower RRT as compared to the thick and normal regions.Conclusion:Thin wall regions observed on intra-operative images of IAs are associated with greater hemodynamic insult (higher WSS and WSSD) and higher flow velocity (lower RRT).

Leggi
Febbraio 2023