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Animal Models and Experimental Medicine Feb 2022Circular RNAs (circRNAs) are endogenous RNAs with a covalently closed single-stranded transcript. They are a novel class of genomic regulators that are linked to many... (Review)
Review
Circular RNAs (circRNAs) are endogenous RNAs with a covalently closed single-stranded transcript. They are a novel class of genomic regulators that are linked to many important development and disease processes and are being pursued as clinical and therapeutic targets. Using the most powerful RNA sequencing and bioinformatics techniques, a large number of circRNAs have been identified and further functional studies have been performed. It is known that circRNAs act as potential biomarkers, sponges for microRNAs (miRNAs) and RNA-binding proteins (RBPs), and regulators of mRNA transcription. They also participate in the translation of peptides or proteins. Many types of circRNAs are dysregulated in plasma or lung tissues, and they may be involved in regulating the proliferation and apoptosis of pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs), leading to pulmonary vascular remodeling in pulmonary hypertension (PH). One possible mechanism is that circRNAs can regulate the function of PAECs and PASMCs by acting as miRNA sponge. However, other potential mechanisms of action of circRNAs are still being actively explored in PH. This paper presents a systematic review of the biogenesis, biological characterization, relevant underlying functions, and future perspectives for studies of circRNAs in the pathogenesis of PH.
Topics: Computational Biology; Endothelial Cells; Humans; Hypertension, Pulmonary; MicroRNAs; RNA, Circular
PubMed: 35229989
DOI: 10.1002/ame2.12208 -
Annals of Medicine and Surgery (2012) Feb 2022The current guidelines recommend targeted temperature management (TTM) as part of the post-resuscitation care for comatose patients following out-of-hospital cardiac... (Review)
Review
BACKGROUND
The current guidelines recommend targeted temperature management (TTM) as part of the post-resuscitation care for comatose patients following out-of-hospital cardiac arrest. These recommendations are based on the weak evidence of benefit seen in the early clinical trials. Recent large multicentered trials have failed to show a meaningful clinical benefit of hypothermia, unlike the earlier studies. Thus, to fully appraise the available data, we sought to perform this systematic review and meta-analysis of randomized controlled trials.
METHODS
We searched four databases for randomized controlled trials comparing therapeutic hypothermia (32-34 °C) with normothermia (≥36 °C with control of fever) in adult patients resuscitated after out-of-hospital cardiac arrest. Independent reviewers did the title and abstract screening, full-text screening, and extraction. The primary outcome was mortality six months after cardiac arrest, and secondary outcomes were neurological outcomes and adverse effects.
RELEVANCE FOR PATIENTS
Six randomized controlled trials were included in this review. There was no significant difference between the hypothermia and normothermia groups in mortality till 6 months follow up after out-of-hospital cardiac arrest (OR 0.88, 95% CI 0.67-1.16; n = 3243; I = 51%), or favorable neurological outcome (OR 1.31, 95% CI 0.93-1.84; n = 3091; I = 68%). Rates of arrhythmias were notably higher in the hypothermia group than the normothermia group (OR 1.43, 95% CI 1.20-1.71; n = 3029; I = 4%). However, odds for development of pneumonia showed no significant differences across two groups (OR 1.13, 95% CI 0.98-1.31; n = 3056; I = 22%). Therefore, targeted hypothermia with a target temperature of 32-34 °C does not provide mortality benefit or better neurological outcome in patients resuscitated after the out-of-hospital cardiac arrest when compared with normothermia.
PubMed: 35145684
DOI: 10.1016/j.amsu.2022.103327 -
Pathogens (Basel, Switzerland) Dec 2021With the current climate change crisis and its influence on infectious disease transmission there is an increased desire to understand its impact on infectious diseases... (Review)
Review
BACKGROUND
With the current climate change crisis and its influence on infectious disease transmission there is an increased desire to understand its impact on infectious diseases globally. Hantaviruses are found worldwide, causing infectious diseases such as haemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS)/hantavirus pulmonary syndrome (HPS) in tropical regions such as Latin America and the Caribbean (LAC). These regions are inherently vulnerable to climate change impacts, infectious disease outbreaks and natural disasters. Hantaviruses are zoonotic viruses present in multiple rodent hosts resident in Neotropical ecosystems within LAC and are involved in hantavirus transmission.
METHODS
We conducted a systematic review to assess the association of climatic factors with human hantavirus infections in the LAC region. Literature searches were conducted on MEDLINE and Web of Science databases for published studies according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) criteria. The inclusion criteria included at least eight human hantavirus cases, at least one climatic factor and study from > 1 LAC geographical location.
RESULTS
In total, 383 papers were identified within the search criteria, but 13 studies met the inclusion criteria ranging from Brazil, Chile, Argentina, Bolivia and Panama in Latin America and a single study from Barbados in the Caribbean. Multiple mathematical models were utilized in the selected studies with varying power to generate robust risk and case estimates of human hantavirus infections linked to climatic factors. Strong evidence of hantavirus disease association with precipitation and habitat type factors were observed, but mixed evidence was observed for temperature and humidity.
CONCLUSIONS
The interaction of climate and hantavirus diseases in LAC is likely complex due to the unknown identity of all vertebrate host reservoirs, circulation of multiple hantavirus strains, agricultural practices, climatic changes and challenged public health systems. There is an increasing need for more detailed systematic research on the influence of climate and other co-related social, abiotic, and biotic factors on infectious diseases in LAC to understand the complexity of vector-borne disease transmission in the Neotropics.
PubMed: 35055965
DOI: 10.3390/pathogens11010015 -
Resuscitation Plus Dec 2021To perform a systematic review of cardiopulmonary resuscitation (CPR) and/or defibrillation in the prone position compared to turning the patient supine prior to... (Review)
Review
AIM
To perform a systematic review of cardiopulmonary resuscitation (CPR) and/or defibrillation in the prone position compared to turning the patient supine prior to starting CPR and/or defibrillation.
METHODS
The search included PubMed, Embase, Web of Science, Cochrane, CINAHL Plus, and medRxiv on December 9, 2020. The population included adults and children in any setting with cardiac arrest while in the prone position. The outcomes included arterial blood pressure and end-tidal capnography during CPR, time to start CPR and defibrillation, return of spontaneous circulation, survival and survival with favorable neurologic outcome to discharge, 30 days or longer. ROBINS-I was performed to assess risk of bias for observational studies.
RESULTS
The systematic review identified 29 case reports (32 individual cases), two prospective observational studies, and two simulation studies. The observational studies enrolled 17 patients who were declared dead in the supine position and reported higher mean systolic blood pressure from CPR in prone position (72 mmHg vs 48 mmHg, < 0.005; 79 ± 20 mmHg vs 55 ± 20 mmHg, = 0.028). One simulation study reported a faster time to defibrillation in the prone position. Return of spontaneous circulation, survival to discharge or 30 days were reported in adult and paediatric case reports. Critical risk of bias limited our ability to perform pooled analyses.
CONCLUSIONS
We identified a limited number of observational studies and case reports comparing prone versus supine CPR and/or defibrillation. Prone CPR may be a reasonable option if immediate supination is difficult or poses unacceptable risks to the patient.
PubMed: 34934996
DOI: 10.1016/j.resplu.2021.100186 -
Artificial Organs May 2022Extracorporeal carbon dioxide removal (ECCO R) provides respiratory support to patients suffering from hypercapnic respiratory failure by utilizing an extracorporeal... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Extracorporeal carbon dioxide removal (ECCO R) provides respiratory support to patients suffering from hypercapnic respiratory failure by utilizing an extracorporeal shunt and gas exchange membrane to remove CO from either the venous (VV-ECCO R) or arterial (AV-ECCO R) system before return into the venous site. AV-ECCO R relies on the patient's native cardiac function to generate pressures needed to deliver blood through the extracorporeal circuit. VV-ECCO R utilizes a mechanical pump and can be used to treat patients with inadequate native cardiac function. We sought to evaluate the existing evidence comparing the subgroups of patients supported on VV and AV-ECCO R devices.
METHODS
A literature search was performed to identify all relevant studies published between 2000 and 2019. Demographic information, medical indications, perioperative variables, and clinical outcomes were extracted for systematic review and meta-analysis.
RESULTS
Twenty-five studies including 826 patients were reviewed. 60% of patients (497/826) were supported on VV-ECCO R. The most frequent indications were acute respiratory distress syndrome (ARDS) [69%, (95%CI: 53%-82%)] and chronic obstructive pulmonary disease (COPD) [49%, (95%CI: 37%-60%)]. ICU length of stay was significantly shorter in patients supported on VV-ECCO R compared to AV-ECCO R [15 (95%CI: 7-23) vs. 42 (95%CI: 17-67) days, p = 0.05]. In-hospital mortality was not significantly different [27% (95%CI: 18%-38%) vs. 36% (95%CI: 24%-51%), p = 0.26].
CONCLUSION
Both VV and AV-ECCO R provided clinically meaningful CO removal with comparable mortality.
Topics: Carbon Dioxide; Extracorporeal Circulation; Humans; Respiration, Artificial; Respiratory Distress Syndrome; Respiratory Insufficiency
PubMed: 34897748
DOI: 10.1111/aor.14130 -
Thrombosis Research Nov 2021D-dimer is included in the diagnostic algorithm for deep vein thrombosis and pulmonary embolism. However, its role in the diagnosis of splanchnic vein thrombosis (SVT)...
BACKGROUND
D-dimer is included in the diagnostic algorithm for deep vein thrombosis and pulmonary embolism. However, its role in the diagnosis of splanchnic vein thrombosis (SVT) is still controversial. The aim of this study was to evaluate the diagnostic accuracy of D-dimer for SVT.
METHODS
We performed a systematic review of the literature with meta-analysis (PROSPERO protocol registration number: CRD42020184300). The electronic databases MEDLINE, EMBASE, and CENTRAL were searched from inception to March 2021 week 4. Studies which evaluated D-dimer accuracy for SVT in any category of patients were selected. The index test was any D-dimer assay; the reference standard was any radiological imaging. The QUADAS-2 checklist was used for the risk of bias assessment. A bivariate random-effects regression model was used to calculate summary estimates of sensitivity and specificity.
RESULTS
12 studies (with a total of 1298 patients) evaluating the accuracy of D-dimer in patients at high risk of SVT (surgical patients, patients with liver cirrhosis or hepatocellular carcinoma) were included. None of the included studies was at low risk of bias. The weighted mean prevalence of SVT was 33.4% (95% CI, 22.5-45.2%, I = 94.8%). D-dimer accuracy was expressed by sensitivity 96% (95% CI, 72-100%); specificity 25% (95% CI, 5-67%); positive likelihood ratio 1.3 (95% CI, 0.9-1.9); negative likelihood ratio 0.16 (95% CI, 0.03-0.84); area under the ROC curve 0.80 (95% CI, 0.76-0.83).
CONCLUSIONS
D-dimer seems to have high sensitivity in the diagnosis of patients at high-risk for SVT. However, there is a strong need for more robust evidence on this topic.
PubMed: 34600286
DOI: 10.1016/j.thromres.2021.09.016 -
Annals of Palliative Medicine Jul 2021Patients with chronic thromboembolic pulmonary hypertension (CTEPH) still have impaired exercise training and quality of life (QoL) despite pulmonary arterial... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with chronic thromboembolic pulmonary hypertension (CTEPH) still have impaired exercise training and quality of life (QoL) despite pulmonary arterial hypertension (PAH)-targeted drugs. Exercise training is considered to improve exercise capacity and QoL in patients with pulmonary hypertension (PH), but this has not been fully studied in CTEPH patients. We conducted the meta-analysis and systematic review to evaluate the effectiveness and safety of exercise training in patients with CTEPH.
METHODS
The relevant literature was retrieved for the meta-analysis using the PubMed, EMBASE, and Cochrane Library databases published before December 2020. The primary outcome was a change in six-minute walk distance (6MWD). We also assessed the effect of exercise training on peak oxygen uptake per kilogram (peak VO2/kg), mean pulmonary artery pressure (mPAP) assessed by right heart catheterization (RHC), N-terminal pro-brain-type natriuretic peptide (NT-proBNP), and QoL.
RESULTS
A total of 6 studies with 234 exercise training patients were included. In the pooled analysis, 6MWD significantly improved by 70.14 m (WMD: 58.33 to 81.95, I2=0) after 3-week exercise training. After 12 or 15-week exercise training, 6MWD and peak VO2/kg significantly improved (WMD: 106.22 m, 95% CI: 65.90 to 146.55, I2=87.4%, P<0.0001; 1.84 mL/min/kg, 95% CI: 0.72 to 2.96, P=0.001, respectively). Furthermore, the mPAP decreased by 12.17 mmHg after 12-week exercise training (95% CI: -14.53 to -9.82, P<0.001, I2=99%). The subscales of QoL such as physical function, general health perception, and mental health improved in varying degrees. NT-proBNP did not improve significantly in the pooled analysis. In addition, exercise training was well tolerated without major adverse events occurred during training, and the dropout rate was low.
DISCUSSION
Exercise training may improve exercise capacity, mPAP, and QoL, and was well tolerated among patients with CTEPH. However, more large-scale multicenter studies are needed to confirm the effectiveness and safety of exercise training in patients with CTEPH.
Topics: Chronic Disease; Exercise; Exercise Tolerance; Humans; Hypertension, Pulmonary; Pulmonary Embolism; Quality of Life
PubMed: 34353098
DOI: 10.21037/apm-21-1758 -
Frontiers in Pharmacology 2021This systematic review and meta-analysis is aimed at assessing the risks of cardiovascular adverse events in patients with rheumatoid arthritis (RA) who have been... (Review)
Review
This systematic review and meta-analysis is aimed at assessing the risks of cardiovascular adverse events in patients with rheumatoid arthritis (RA) who have been treated with fostamatinib. The electronic databases of OVID Medline, OVID EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science were searched to identify studies that reported cardiovascular events or hypertension in RA patients treated with fostamatinib. Two reviewers separately and simultaneously screened the retrieved studies based on study selection criteria, collected data and performed methodological quality assessments. The effect size of meta-analysis was estimated by the Peto odds ratio (OR) or relative risk (RR) with 95% confidence intervals (95%CI). Funnel plot was used to estimate publication bias and sensitivity analysis was performed to test the robustness of the results. A total of 12 trials composed of 5,618 participants with low to moderate risk of bias were included. In comparison to the placebo, the use of fostamatinib was found to elevate the risk of hypertension (RR=3.82, 95%CI 2.88-5.05) but was not associated with the risks of all-cause death (Peto OR=0.16, 95%CI 0.02-1.24), major adverse cardiovascular events (Peto OR=1.24, 95%CI 0.26-5.97), pulmonary heart disease and disease of pulmonary circulation (Peto OR=1.23, 95%CI 0.13-11.87), in addition to other forms of heart disease (Peto OR=1.96, 95%CI 0.72-5.38). Furthermore, sensitivity analysis showed no significant change in effective trends and no publication bias was found. Fostamatinib is associated with increased risk of hypertension; however, no increased risks of cardiovascular events were observed. Further well-planned cohort studies with large study populations and longer follow-up times are needed to elucidate the outcomes. : [PROSPERO], identifier [CRD42020198217].
PubMed: 34349639
DOI: 10.3389/fphar.2021.632551 -
International Journal of Rheumatic... Oct 2021Takayasu arteritis (TAK) is a rare large vessel vasculitis, and epidemiological data on TAK are lacking in China. Thus, we designed this study to estimate the TAK...
BACKGROUND
Takayasu arteritis (TAK) is a rare large vessel vasculitis, and epidemiological data on TAK are lacking in China. Thus, we designed this study to estimate the TAK prevalence and incidence in residential Shanghai, China.
METHODS
Data on diagnosed TAK cases aged over 16 years were retrieved from 22 tertiary hospitals in Shanghai through hospital electronic medical record systems between January 1, 2015 and December 31, 2017 to estimate the prevalence and incidence. A systematic literature review based on searches in PubMed, Ovid-Medline, Excerpta Medica Database (EMBASE), Web of Science, and China National Knowledge Infrastructure (CNKI) was performed to summarize TAK distribution across the world.
RESULTS
In total 102 TAK patients, with 64% female, were identified. The point prevalence (2015-2017) was 7.01 (95% CI 5.65-8.37) cases per million, and the mean annual incidence was 2.33 (1.97-3.21) cases per million. The average age of TAK patients was 44 ± 16 years, with the highest prevalence (11.59 [9.23-19.50] cases per million) and incidence (3.55 [0.72 3.74] cases per million) in the 16 to 34 years population. Seventeen reports were included in the system review, showing that the epidemiology of TAK varied greatly across the world. The incidence and prevalence were both relatively higher in Asian countries, with the prevalence ranging 3.3-40 cases per million and annual incidence ranging 0.34-2.4 cases per million.
CONCLUSIONS
The prevalence and incidence of TAK in Shanghai was at moderate to high levels among the previous reports. The disease burden varied globally among racial populations.
Topics: Adolescent; Adult; Age Distribution; China; Female; Hospitals; Humans; Incidence; Male; Middle Aged; Prevalence; Race Factors; Sex Distribution; Takayasu Arteritis; Time Factors; Young Adult
PubMed: 34314100
DOI: 10.1111/1756-185X.14183 -
The Cochrane Database of Systematic... Jul 2021Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterised by shortness of breath, cough and recurrent exacerbations. People with COPD... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterised by shortness of breath, cough and recurrent exacerbations. People with COPD often live with one or more co-existing long-term health conditions (comorbidities). People with more severe COPD often have a higher number of comorbidities, putting them at greater risk of morbidity and mortality.
OBJECTIVES
To assess the effectiveness of any single intervention for COPD adapted or tailored to their comorbidity(s) compared to any other intervention for people with COPD and one or more common comorbidities (quantitative data, RCTs) in terms of the following outcomes: Quality of life, exacerbations, functional status, all-cause and respiratory-related hospital admissions, mortality, pain, and depression and anxiety. To assess the effectiveness of an adapted or tailored single COPD intervention (simple or complex) that is aimed at changing the management of people with COPD and one or more common comorbidities (quantitative data, RCTs) compared to usual care in terms of the following outcomes: Quality of life, exacerbations, functional status, all-cause and respiratory-related hospital admissions, mortality, pain, and depression and anxiety. To identify emerging themes that describe the views and experiences of patients, carers and healthcare professionals when receiving or providing care to manage multimorbidities (qualitative data).
SEARCH METHODS
We searched multiple databases including the Cochrane Airways Trials Register, CENTRAL, MEDLINE, Embase, and CINAHL, to identify relevant randomised and qualitative studies. We also searched trial registries and conducted citation searches. The latest search was conducted in January 2021.
SELECTION CRITERIA
Eligible randomised controlled trials (RCTs) compared a) any single intervention for COPD adapted or tailored to their comorbidity(s) compared to any other intervention, or b) any adapted or tailored single COPD intervention (simple or complex) that is aimed at changing the management of people with COPD and one or more comorbidities, compared to usual care. We included qualitative studies or mixed-methods studies to identify themes.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods for analysis of the RCTs. We used Cochrane's risk of bias tool for the RCTs and the CASP checklist for the qualitative studies. We planned to use the Mixed Methods Appraisal tool (MMAT) to assess the risk of bias in mixed-methods studies, but we found none. We used GRADE and CERQual to assess the quality of the quantitative and qualitative evidence respectively. The primary outcome measures for this review were quality of life and exacerbations.
MAIN RESULTS
Quantitative studies We included seven studies (1197 participants) in the quantitative analyses, with interventions including telemonitoring, pulmonary rehabilitation, treatment optimisation, water-based exercise training and case management. Interventions were either compared with usual care or with an active comparator (such as land-based exercise training). Duration of trials ranged from 4 to 52 weeks. Mean age of participants ranged from 64 to 72 years and COPD severity ranged from mild to very severe. Trials included either people with COPD and a specific comorbidity (including cardiovascular disease, metabolic syndrome, lung cancer, head or neck cancer, and musculoskeletal conditions), or with one or more comorbidities of any type. Overall, we judged the evidence presented to be of moderate to very low certainty (GRADE), mainly due to the methodological quality of included trials and imprecision of effect estimates. Intervention versus usual care Quality of life as measured by the St George's Respiratory Questionnaire (SGRQ) total score may improve with tailored pulmonary rehabilitation compared to usual care at 52 weeks (mean difference (MD) -10.85, 95% confidence interval (CI) -12.66 to -9.04; 1 study, 70 participants; low-certainty evidence). Tailored pulmonary rehabilitation is likely to improve COPD assessment test (CAT) scores compared with usual care at 52 weeks (MD -8.02, 95% CI -9.44 to -6.60; 1 study, 70 participants, moderate-certainty evidence) and with a multicomponent telehealth intervention at 52 weeks (MD -6.90, 95% CI -9.56 to -4.24; moderate-certainty evidence). Evidence is uncertain about effects of pharmacotherapy optimisation or telemonitoring interventions on CAT improvement compared with usual care. There may be little to no difference in the number of people experiencing exacerbations, or mean exacerbations with case management compared with usual care (OR 1.09, 95% CI 0.75 to 1.57; 1 study, 470 participants; very low-certainty evidence). For secondary outcomes, six-minute walk distance (6MWD) may improve with pulmonary rehabilitation, water-based exercise or multicomponent interventions at 38 to 52 weeks (low-certainty evidence). A multicomponent intervention may result in fewer people being admitted to hospital at 17 weeks, although there may be little to no difference in a telemonitoring intervention. There may be little to no difference between intervention and usual care for mortality. Intervention versus active comparator We included one study comparing water-based and land-based exercise (30 participants). We found no evidence for quality of life or exacerbations. There may be little to no difference between water- and land-based exercise for 6MWD (MD 5 metres, 95% CI -22 to 32; 38 participants; very low-certainty evidence). Qualitative studies One nested qualitative study (21 participants) explored perceptions and experiences of people with COPD and long-term conditions, and of researchers and health professionals who were involved in an RCT of telemonitoring equipment. Several themes were identified, including health status, beliefs and concerns, reliability of equipment, self-efficacy, perceived ease of use, factors affecting usefulness and perceived usefulness, attitudes and intention, self-management and changes in healthcare use. We judged the qualitative evidence presented as of very low certainty overall.
AUTHORS' CONCLUSIONS
Owing to a paucity of eligible trials, as well as diversity in the intervention type, comorbidities and the outcome measures reported, we were unable to provide a robust synthesis of data. Pulmonary rehabilitation or multicomponent interventions may improve quality of life and functional status (6MWD), but the evidence is too limited to draw a robust conclusion. The key take-home message from this review is the lack of data from RCTs on treatments for people living with COPD and comorbidities. Given the variation in number and type of comorbidity(s) an individual may have, and severity of COPD, larger studies reporting individual patient data are required to determine these effects.
Topics: Aged; Bias; Case Management; Cause of Death; Comorbidity; Confidence Intervals; Disease Progression; Evaluation Studies as Topic; Exercise; Humans; Middle Aged; Odds Ratio; Pulmonary Disease, Chronic Obstructive; Quality of Life; Randomized Controlled Trials as Topic; Severity of Illness Index; Telemedicine; Time Factors; Walk Test
PubMed: 34309831
DOI: 10.1002/14651858.CD013384.pub2