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Critical Care Medicine Jan 2022To determine the associations of demographic, clinical, laboratory, organ dysfunction, and illness severity variable values with: 1) sepsis, severe sepsis, or septic... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the associations of demographic, clinical, laboratory, organ dysfunction, and illness severity variable values with: 1) sepsis, severe sepsis, or septic shock in children with infection and 2) multiple organ dysfunction or death in children with sepsis, severe sepsis, or septic shock.
DATA SOURCES
MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from January 1, 2004, and November 16, 2020.
STUDY SELECTION
Case-control studies, cohort studies, and randomized controlled trials in children greater than or equal to 37-week-old postconception to 18 years with suspected or confirmed infection, which included the terms "sepsis," "septicemia," or "septic shock" in the title or abstract.
DATA EXTRACTION
Study characteristics, patient demographics, clinical signs or interventions, laboratory values, organ dysfunction measures, and illness severity scores were extracted from eligible articles. Random-effects meta-analysis was performed.
DATA SYNTHESIS
One hundred and six studies met eligibility criteria of which 81 were included in the meta-analysis. Sixteen studies (9,629 patients) provided data for the sepsis, severe sepsis, or septic shock outcome and 71 studies (154,674 patients) for the mortality outcome. In children with infection, decreased level of consciousness and higher Pediatric Risk of Mortality scores were associated with sepsis/severe sepsis. In children with sepsis/severe sepsis/septic shock, chronic conditions, oncologic diagnosis, use of vasoactive/inotropic agents, mechanical ventilation, serum lactate, platelet count, fibrinogen, procalcitonin, multi-organ dysfunction syndrome, Pediatric Logistic Organ Dysfunction score, Pediatric Index of Mortality-3, and Pediatric Risk of Mortality score each demonstrated significant and consistent associations with mortality. Pooled mortality rates varied among high-, upper middle-, and lower middle-income countries for patients with sepsis, severe sepsis, and septic shock (p < 0.0001).
CONCLUSIONS
Strong associations of several markers of organ dysfunction with the outcomes of interest among infected and septic children support their inclusion in the data validation phase of the Pediatric Sepsis Definition Taskforce.
Topics: Adolescent; Child; Child, Preschool; Clinical Laboratory Techniques; Consciousness; Female; Global Health; Humans; Infant; Infant, Newborn; Male; Organ Dysfunction Scores; Patient Acuity; Respiration, Artificial; Sepsis; Shock, Septic; Sociodemographic Factors
PubMed: 34612847
DOI: 10.1097/CCM.0000000000005294 -
Neuropathology and Applied Neurobiology Apr 2022The pathological processes leading to synapse loss, neuronal loss, brain atrophy and gliosis in Alzheimer's disease (AD) and their relation to vascular disease and... (Review)
Review
The pathological processes leading to synapse loss, neuronal loss, brain atrophy and gliosis in Alzheimer's disease (AD) and their relation to vascular disease and immunological changes are yet to be fully explored. Amyloid-β (Aβ) aggregation, vascular damage and altered immune response interact at the blood-brain barrier (BBB), affecting the brain endothelium and fuelling neurodegeneration. The aim of the present systematic literature review was to critically appraise and to summarise the published evidence on the clinical correlations and pathophysiological concepts of BBB damage in AD, focusing on human data. The PubMed, Cochrane, Medline and Embase databases were searched for original research articles, systematic reviews and meta-analyses, published in English language from 01/2000 to 07/2021, using the keywords Alzheimer*, amyloid-β or β-amyloid or abeta and BBB. This review shows that specific changes of intercellular structures, reduced expression of transendothelial carriers, induction of vasoactive mediators and activation of both astroglia and monocytes/macrophages characterise BBB damage in human AD and AD models. BBB dysfunction on magnetic resonance imaging takes place early in the disease course in AD-specific brain regions. The toxic effects of Aβ and apolipoprotein E (ApoE) are likely to induce a non-cerebral-amyloid-angiopathy-related degeneration of endothelial cells, independently of cerebrovascular disease; however, some of the observed structural changes may just arise with age. Small vessel disease, ApoE, loss of pericytes, proinflammatory signalling and cerebral amyloid angiopathy enhance BBB damage. Novel therapeutic approaches for AD, including magnetic resonance-guided focused ultrasound, aim to open the BBB, potentially leading to an improved drainage of Aβ along perivascular channels and increased elimination from the brain. In vitro treatments with ApoE-modifying agents yielded promising effects on modulating BBB function. Reducing cardiovascular risk factors represents one of the most promising interventions for dementia prevention at present. However, further research is needed to elucidate the connection of BBB damage and tau pathology, the role of proinflammatory mediators in draining macromolecules and cells from the cerebral parenchyma, including their contribution to cerebral amyloid angiopathy. Improved insight into these pathomechanisms may allow to shed light on the role of Aβ deposition as a primary versus a secondary event in the complex pathogenesis of AD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Blood-Brain Barrier; Brain; Cerebral Amyloid Angiopathy; Endothelial Cells; Humans
PubMed: 34823269
DOI: 10.1111/nan.12782 -
Journal of Gastrointestinal and Liver... Mar 2021Vasoactive agents with endoscopic therapy are used to treat acute variceal bleeding (AVB). There are two main groups of vasoactive agents: terlipressin and vasopressin... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Vasoactive agents with endoscopic therapy are used to treat acute variceal bleeding (AVB). There are two main groups of vasoactive agents: terlipressin and vasopressin (T-V), and octreotide and somatostatin (O-S). However, the benefit/harm balance is unclear. Our aim was to assess the efficacy and safety of T-V versus O-S for the management of AVB.
METHODS
We performed a systematic search for randomized controlled trials (RCTs) in PubMed, Scopus, and CENTRAL. Our main outcomes were mortality and adverse events. Secondary outcomes were bleeding control, rebleeding, blood transfusion, hospital stay. We evaluated the certainty of evidence using GRADE methodology.
RESULTS
We included 21 RCTs. The risk of mortality (RR: 1.01; 95%CI: 0.83-1.22), bleeding control (RR: 0.96; 95%CI: 0.91-1.02; I 2 =53%), early rebleeding (RR: 0.91; 95%CI: 0.66-1.24: I 2 =0%), late rebleeding (RR: 0.94; 95 CI: 0.56-1.60; I 2 =0%), blood transfusion (MD: 0.04; 95%CI: -0.31-0.39; I 2 =68%) and hospital stay (MD: -1.06; 95%CI: -2.80-0.69; I 2 =0%) were similar between T-V and O-S groups. Only 15 studies reported adverse events, which were significantly higher in the T-V compared to the O-S group (RR 2.39; 95%CI: 1.58-3.63; I 2 =57%). The certainty of evidence was moderate for the main outcomes, and low or very low for others.
CONCLUSIONS
In cirrhotic patients with AVB, those treated with T-V had similar mortality risk compared to O-S. However, the use of T-V showed an increased risk of adverse events compared to O-S.
Topics: Adult; Aged; Blood Transfusion; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Length of Stay; Liver Cirrhosis; Male; Middle Aged; Octreotide; Recurrence; Somatostatin; Terlipressin; Treatment Outcome; Vasopressins
PubMed: 33723542
DOI: 10.15403/jgld-3191 -
European Review For Medical and... May 2021We aimed to analyze clinical characteristics, treatment patterns, and prognosis of patients with reversible cerebral vasoconstriction syndrome (RCVS).
OBJECTIVE
We aimed to analyze clinical characteristics, treatment patterns, and prognosis of patients with reversible cerebral vasoconstriction syndrome (RCVS).
MATERIALS AND METHODS
Two investigators independently searched PubMed and EMBASE, and 191 cases were included in this study. Information regarding demographics, triggering factors, brain imaging findings, treatment modalities, recurrence, and clinical outcome was collected.
RESULTS
The mean age of the patients was 39.9 years, and 155 (81.2%) were female. The most common triggering factor for RCVS was an exposure to vasoactive substances (41.4%), followed by pregnancy/postpartum (20.9%), and sexual intercourse (10.5%). Multifocal stenosis (84.0%) and beading shape (82.4%) were the leading abnormal findings on angiography, while cerebral ischemic lesions (47.6%) and cerebral hemorrhage (mainly subarachnoid hemorrhage) (35.1%) were the main findings on brain computed tomography (CT)/magnetic resonance imaging (MRI). Calcium channel blockers (nimodipine/verapamil) were the most commonly used medications (44.5%) in the treatment of RCVS. Multivariate analysis identified that RCVS was precipitated by trauma/surgery/procedure (hazard ratio (HR): 3.29, 95% confidence interval (CI) (1.21-8.88), p=0.019), and presence of aphasia/neglect/apraxia during the acute phase of the disease (HR: 3.83, 95% CI (1.33-11.05), p=0.013) were found to be the two independent risk factors for residual neurological deficit after RCVS.
CONCLUSIONS
In our systematic review, vasoactive substances were the most frequent triggers for RCVS, which was most commonly accompanied by angiographic findings of multifocal stenotic lesions. Patients with RCVS precipitated by trauma or surgical procedures and those with focal cortical deficits had a higher risk of residual neurological deficits, and these patients should closely be monitored.
Topics: Cerebrovascular Disorders; Headache Disorders, Primary; Humans; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Vasoconstriction
PubMed: 34002826
DOI: 10.26355/eurrev_202105_25834 -
BMC Nephrology Jul 2020Due to the high incidence and mortality of sepsis-associated acute kidney injury, a significant number of studies have explored the causes of sepsis-associated acute... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Due to the high incidence and mortality of sepsis-associated acute kidney injury, a significant number of studies have explored the causes of sepsis-associated acute kidney injury (AKI). However, the opinions on relevant predictive risk factors remain inconclusive. This study aimed to provide a systematic review and meta-analysis to determine the predisposing factors for sepsis-associated AKI.
METHOD
A systematic literature search was performed in the Medline, Embase, Cochrane Library, PubMed, and Web of Science, databases, with an end-date of 25th May 2019. Valid data were retrieved in compliance with specific inclusion and exclusion criteria.
RESULT
Forty-seven observational studies were included for analysis, achieving a cumulative patient number of 55,911. The highest incidence of AKI was caused by septic shock. Thirty-one potential risk factors were included in the meta-analysis. Analysis showed that 20 factors were statistically significant. The odds ratio (OR) and 95% confidence interval (CI), as well as the prevalence of the most frequently-seen predisposing factors for sepsis-associated AKI, were as follows: septic shock [2.88 (2.36-3.52), 60.47%], hypertension [1.43 (1.20-1.70), 38.39%], diabetes mellitus [1.59 (1.47-1.71), 27.57%], abdominal infection [1.44 (1.32-1.58), 30.87%], the administration of vasopressors [2.95 (1.67-5.22), 64.61%], the administration of vasoactive drugs [3.85 (1.89-7.87), 63.22%], mechanical ventilation [1.64 (1.24-2.16), 68.00%], positive results from blood culture [1.60 (1.35-1.89), 41.19%], and a history of smoking [1.60 (1.09-2.36), 43.09%]. Other risk factors included cardiovascular diseases, coronary artery diseases, liver diseases, unknown infections, the administration of diuretics and ACEI/ARB, the infection caused by gram-negative bacteria, and organ transplantation.
CONCLUSION
Risk factors of S-AKI arise from a wide range of sources, making it difficult to predict and prevent this condition. Comorbidities, and certain drugs, are the main risk factors for S-AKI. Our review can provide guidance on the application of interventions to reduce the risks associated with sepsis-associated acute kidney injury and can also be used to tailor patient-specific treatment plans and management strategies in clinical practice.
Topics: Acute Kidney Injury; Bacteremia; Blood Culture; Diabetes Mellitus; Humans; Hypertension; Intraabdominal Infections; Respiration, Artificial; Risk Factors; Sepsis; Shock, Septic; Smoking; Vasoconstrictor Agents
PubMed: 32736541
DOI: 10.1186/s12882-020-01974-8 -
Critical Care Medicine Oct 2022Hepatorenal syndrome (HRS) is associated with high rates of morbidity and mortality. Evidence examining commonly used drug treatments remains uncertain. We assessed the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Hepatorenal syndrome (HRS) is associated with high rates of morbidity and mortality. Evidence examining commonly used drug treatments remains uncertain. We assessed the comparative effectiveness of inpatient treatments for HRS by performing a network meta-analysis of randomized clinical trials (RCTs).
DATA SOURCES
We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Medline In-Process & Other Non-Indexed Citations, Scopus, and Web of Science from inception.
STUDY SELECTION AND DATA EXTRACTION
Pairs of reviewers independently identified eligible RCTs that enrolled patients with type 1 or 2 HRS. Pairs of reviewers independently extracted data.
DATA SYNTHESIS
We assessed risk of bias using the Cochrane tool for RCTs and certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations approach. Our main outcomes are all-cause mortality, HRS reversal, and serious adverse events. Of 3,079 citations, we included 26 RCTs examining 1,736 patients. Based on pooled analysis, terlipressin increases HRS reversal compared with placebo (142 reversals per 1,000 [95% CI, >87.7 to >210.9]; high certainty). Norepinephrine (112.7 reversals per 1,000 [95% CI, 52.6 to >192.3]) may increase HRS reversal compared with placebo (low certainty). The effect of midodrine+octreotide (67.8 reversals per 1,000 [95% CI, <2.8 to >177.4]; very low) on HRS reversal is uncertain. Terlipressin may reduce mortality compared with placebo (93.7 fewer deaths [95% CI, 168.7 to <12.5]; low certainty). Terlipressin probably increases the risk of serious adverse events compared with placebo (20.4 more events per 1,000 [95% CI, <5.1 to >51]; moderate certainty).
CONCLUSIONS
Terlipressin increases HRS reversal compared with placebo. Terlipressin may reduce mortality. Until access to terlipressin improves, initial norepinephrine administration may be more appropriate than initial trial with midodrine+octreotide. Our review has the potential to inform future guideline and practice in the treatment of HRS.
Topics: Hepatorenal Syndrome; Humans; Midodrine; Network Meta-Analysis; Norepinephrine; Octreotide; Terlipressin; Treatment Outcome; Vasoconstrictor Agents
PubMed: 35777925
DOI: 10.1097/CCM.0000000000005595 -
Shock (Augusta, Ga.) Dec 2023Background: Septic shock is a distributive shock with decreased systemic vascular resistance and MAP. Septic shock contributes to the most common causes of death in the... (Meta-Analysis)
Meta-Analysis
Background: Septic shock is a distributive shock with decreased systemic vascular resistance and MAP. Septic shock contributes to the most common causes of death in the intensive care unit (ICU). Current guidelines recommend the use of norepinephrine as the first-line vasopressor, whereas adrenergic agonists and vasopressin analogs are also commonly used by physicians. To date, very few studies have synthetically compared the effects of multiple types of vasoactive medications. The aim of this study was to systemically evaluate the efficacy of vasoactive agents both individually and in combination to treat septic shock. Methods: The PubMed, MEDLINE, Embase, Web of Science, and Cochrane Central Register for Controlled Trials (CENTRAL) were searched up to May 12, 2022, to identify relevant randomized controlled trials. A network meta-analysis was performed to evaluate the effect of different types of vasopressors. The primary outcome was 28-day all-cause mortality. The secondary outcome was the ICU length of stay. Adverse events are defined as any undesirable outcomes, including myocardial infarction, cardiac arrhythmia, peripheral ischemia, or stroke and cerebrovascular events. Findings: Thirty-three randomized controlled trials comprising 4,966 patients and assessing 8 types of vasoactive treatments were included in the network meta-analysis. The surface under the cumulative ranking curve provided a ranking of vasoactive medications in terms of 28-day all-cause mortality from most effective to least effective: norepinephrine plus dobutamine, epinephrine, vasopressin, terlipressin, norepinephrine, norepinephrine plus vasopressin, dopamine, and dobutamine. Dopamine was associated with a significantly shorter ICU stay than norepinephrine, terlipressin, and vasopressin, whereas other vasoactive medications showed no definite difference in ICU length of stay. Regarding adverse events, norepinephrine was associated with the highest incidences of myocardial infarction and peripheral ischemia. Dopamine was associated with the highest incidence of cardiac arrhythmia. Epinephrine and terlipressin were associated with the highest incidences of myocardial infarction and peripheral ischemia. Interpretation: The results of this network meta-analysis suggest that norepinephrine plus dobutamine is associated with a lower risk of 28-day mortality in septic shock patients than other vasoactive medications, and the use of dopamine is associated with a higher risk of 28-day mortality due to septic shock than norepinephrine, terlipressin, and vasopressin.
Topics: Humans; Shock, Septic; Dopamine; Terlipressin; Dobutamine; Network Meta-Analysis; Vasoconstrictor Agents; Epinephrine; Norepinephrine; Vasopressins; Arrhythmias, Cardiac; Ischemia; Myocardial Infarction
PubMed: 37548686
DOI: 10.1097/SHK.0000000000002193 -
The American Journal of Emergency... Nov 2020Vasopressors are mainstay treatment for patients in shock and are usually infused through central venous catheters (CVCs). However, CVCs are associated with risk of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vasopressors are mainstay treatment for patients in shock and are usually infused through central venous catheters (CVCs). However, CVCs are associated with risk of infection or delay from the needs of confirmation of placement. Infusing vasopressor through peripheral venous catheter (PIVs) could be an alternative in the Emergency Departments (ED) but data regarding complications is inconclusive. We performed a random-effects meta-analysis to assess literature involving prevalence of complications from infusing vasopressors via PIVs.
METHODS
We searched PubMed, EMBASE and Scopus databases from beginnings to 02/02/2020 to identify relevant randomized control trials, cohort, case-control studies. We excluded case reports. Authors assessed studies' quality with Newcastle-Ottawa Scale and Cochrane Risk of Bias tool. Kappa score was used to assess interrater agreement. Outcome was complications as direct results from infusing vasopressors through PIVs.
RESULTS
We identified 325 articles and included 9 studies after reviewing 16 full text articles. Our analysis included 1835 patients whose mean age was 63 (Standard Deviation 12) years and 48% was female. There were 122 (7%) complications, of which 117 (96%) were minor. The meta-analysis with random effects showed the pooled prevalence of complications as 0.086 (95%CI 0.031-0.21). Studies reporting infusion safety guidelines had significantly lower prevalence of complications (0.029, 95%CI 0.018-0.045), compared to those not reporting a safety guideline (0.12, 95%CI 0.038-0.30, p = 0.024).
CONCLUSION
There was low prevalence of complications as a direct result from infusing vasopressors through PIVs. Studies with safety guidelines were associated with significantly lower prevalence of complications. Further studies are needed to confirm our observations.
Topics: Catheterization, Central Venous; Catheterization, Peripheral; Central Venous Catheters; Emergency Service, Hospital; Erythema; Extravasation of Diagnostic and Therapeutic Materials; Humans; Infusions, Intravenous; Intensive Care Units; Practice Guidelines as Topic; Shock; Time-to-Treatment; Vasoconstrictor Agents; Venous Thrombosis
PubMed: 33039229
DOI: 10.1016/j.ajem.2020.09.047 -
Clinical Anatomy (New York, N.Y.) Jul 2021Myocardial bridges are anatomical entities characterized by myocardium covering segments of coronary arteries. In some patients, the presence of a myocardial bridge is... (Meta-Analysis)
Meta-Analysis
Myocardial bridges are anatomical entities characterized by myocardium covering segments of coronary arteries. In some patients, the presence of a myocardial bridge is benign and is only incidentally found on autopsy. In other patients, however, myocardial bridges can lead to compression of the coronary artery during systolic contraction and delayed diastolic relaxation, resulting in myocardial ischemia. This ischemia in turn can lead to myocardial infarction, ventricular arrhythmias and sudden cardiac death. Myocardial bridges have also been linked to an increased incidence of atherosclerosis, which has been attributed to increased shear stress and the presence of vasoactive factors. Other studies however, demonstrated the protective roles of myocardial bridges. In this study, using systematic review and a meta-analytical approach we investigate the prevalence and morphology of myocardial bridges in both clinical imaging and cadaveric dissections. We also discuss the pathophysiology, clinical significance, and management of these anatomical entities.
Topics: Animals; Cadaver; Humans; Myocardial Bridging; Prevalence
PubMed: 33078444
DOI: 10.1002/ca.23697 -
Environmental Science and Pollution... Mar 2023Vascular endothelial dysfunction is an early stage to cardiovascular diseases (CVDs), but whether air pollution exposure has an effect on it remains unknown. We... (Meta-Analysis)
Meta-Analysis Review
Vascular endothelial dysfunction is an early stage to cardiovascular diseases (CVDs), but whether air pollution exposure has an effect on it remains unknown. We conducted a systematic review and meta-analysis to summarize epidemiological evidence between air pollution and endothelial dysfunction. We searched the database of PubMed, EMBASE, the Cochrane Library, and Web of Science up to November 10, 2022. Fixed and random effect models were used to pool the effect change or percent change (% change) and 95% confidence interval (95% CI) of vascular function associated with particulate matter (PM) and gaseous pollutants. I statistics, funnel plot, and Egger's test were used to evaluate heterogeneity and publication bias. There were 34 articles included in systematic review, and 25 studies included in meta-analysis. For each 10 µg/m increment in short-term PM exposure, augmentation index (AIx) and pulse wave velocity (PWV) increased by 2.73% (95% CI: 1.89%, 3.57%) and 0.56% (95% CI: 0.22%, 0.89%), and flow-mediated dilation (FMD) decreased by 0.17% (95% CI: - 0.33%, - 0.00%). For each 10 µg/m increment in long-term PM exposure, FMD decreased by 0.99% (95% CI: - 1.41%, - 0.57%). The associations between remaining pollutants and outcomes were not statistically significant. The effect of short-term PM exposure on FMD change was stronger in population with younger age, lower female proportion, higher mean body mass index and higher PM exposure. Cardiac or vasoactive medication might attenuate this effect. Our study provides evidence that PM exposure had adverse impact on vascular endothelial function, indicating the importance of air quality improvement for early CVD prevention.
Topics: Female; Humans; Air Pollutants; Pulse Wave Analysis; Environmental Exposure; Air Pollution; Particulate Matter; Cardiovascular Diseases; Environmental Pollutants
PubMed: 36702984
DOI: 10.1007/s11356-023-25156-9