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Cephalalgia : An International Journal... Feb 2015The objective of this article is to review the literature relating migraine, cardiovascular disease, and stroke during pregnancy in order to better define the... (Review)
Review
OBJECTIVE
The objective of this article is to review the literature relating migraine, cardiovascular disease, and stroke during pregnancy in order to better define the relationship between migraines and vascular disease.
METHODS
We conducted a systematic review of the literature using Medline and Cochrane Review with the following search terms: migraine AND pregnancy and vascular disease OR myocardial infarction OR heart disease OR stroke OR cerebrovascular disease OR hypertension in pregnancy. We also reviewed the bibliographies of papers identified in this search to obtain additional relevant studies.
RESULTS
Of the 219 papers obtained with the primary search, we found 17 that were topically relevant. Altogether, there is an increased risk both of gestational hypertension (OR range from 1.23 to 1.68) and preeclampsia (OR range 1.08 to 3.5) in migraineurs compared to nonmigraineurs. In addition, there is an association between an increased risk of ischemic stroke in pregnancy (OR range 7.9 to 30.7), particularly with active migraine. There is also an association between migraine and increased risk of acute myocardial infarction and heart disease (OR 4.9; 95% CI 1.7, 14.2), and thromboembolic events during pregnancy (deep venous thrombosis OR 2.4; 95% CI 1.3, 4.2 and pulmonary embolus OR 3.1; 95% CI 1.7, 5.6).
CONCLUSION
In this review, we summarized the association between migraine and risk of vascular disease during pregnancy, based on the available literature. Given the limited amount of data, more research on these associations is needed to determine which women with migraine may be at risk while pregnant.
Topics: Cardiovascular Diseases; Female; Humans; Migraine Disorders; Pregnancy; Pregnancy Complications, Cardiovascular; Stroke
PubMed: 25304764
DOI: 10.1177/0333102414554113 -
Metabolites Sep 2022The coronavirus 2019 pandemic has affected many healthcare systems worldwide. While acute respiratory distress syndrome (ARDS) has been well-documented in COVID-19,... (Review)
Review
The coronavirus 2019 pandemic has affected many healthcare systems worldwide. While acute respiratory distress syndrome (ARDS) has been well-documented in COVID-19, there are several cardiovascular complications, such as myocardial infarction, ischaemic stroke, and pulmonary embolism, leading to disability and death. The link between COVID-19 and increasing thrombogenicity potentially occurs due to numerous different metabolic mechanisms, ranging from endothelial damage for direct virus infection, associated excessive formation of neutrophil extracellular traps (NETs), pathogenic activation of the renin-angiotensin-aldosterone system (RAAS), direct myocardial injury, and ischemia induced by respiratory failure, all of which have measurable biomarkers. A search was performed by interrogating three databases (MEDLINE; MEDLINE In-Process and Other Non-Indexed Citations, and EMBASE). Evidence from randomized controlled trials (RCT), prospective series, meta-analyses, and unmatched observational studies were evaluated for the processing of the algorithm and treatment of thromboembolic disease and cardiac thrombotic complications related to COVID-19 during SARS-CoV-2 infection. Studies out with the SARS-Cov-2 infection period and case reports were excluded. A total of 58 studies were included in this analysis. The role of the acute inflammatory response in the propagation of the systemic inflammatory sequelae of the disease plays a major part in determining thromboembolic disease and cardiac thrombotic complication in COVID-19. Some of the mechanisms of activation of these pathways, alongside the involved biomarkers noted in previous studies, are highlighted. Inflammatory response led to thromboembolic disease and cardiac thrombotic complications in COVID-19. NETs play a pivotal role in the pathogenesis of the inflammatory response. Despite moving into the endemic phase of the disease in most countries, thromboembolic complications in COVID-19 remain an entity that substantially impacts the health care system, with long-term effects that remain uncertain. Continuous monitoring and research are required.
PubMed: 36295791
DOI: 10.3390/metabo12100889 -
Cardiology Research Apr 2018The mortality rate of post-infarction cardiogenic shock (CS) was 80.0-90.0%. Recent studies show a significant reduction of hospital mortality to approximately 50.0%. CS... (Review)
Review
The mortality rate of post-infarction cardiogenic shock (CS) was 80.0-90.0%. Recent studies show a significant reduction of hospital mortality to approximately 50.0%. CS is defined as systemic tissue hypoperfusion resulting from systolic and/or diastolic heart dysfunction, the main cause of which is acute myocardial infarction (AMI). The main predictors are biological markers such as troponin, CKMB and lactate. A systematic literature review and meta-analysis is performed in order to present and correlate the main literary findings on CS and its evolution with possible changes in biomarkers such as troponin, lactate and CKMB. After criteria of literary search with the use of the mesh terms: cardiogenic shock; acute myocardial infarction; biomarkers; troponin; CKMB; lactate; clinical trials and use of the bouleanos "and" between the mesh terms and "or" among the historical findings. In the main databases such as Pubmed, Medline, Bireme, EBSCO, Scielo, etc., a total of 96 papers that were submitted to the eligibility analysis were collated and, after that, 41 studies were selected, following the rules of systematic review - PRISMA (Transparent reporting of systematic reviews and meta-analyzes-http://www.prisma-statement.org/). Some risk factors for its development in AMI are advanced age, female gender, anterior wall infarction, diabetes mellitus, systemic arterial hypertension, previous history of infarction and angina. The CS associated with AMI depends on its extent and its complications, being the main ones: mitral regurgitation, rupture of the interventricular septum and rupture of the free wall of the left ventricule. The diagnosis is based on the clinical manifestations, such as mental confusion, oliguria, hypotension, tachycardia, fine pulse, sweating, and cold extremities; in hemodynamic aspects: systolic blood pressure was < 90.0 mm Hg or 30 mm Hg below baseline, pulmonary capillary pressure was > 18.0 mm Hg and cardiac index was < 2.2 L/min/m. Laboratory and imaging exams should be requested to evaluate the possible etiology of CS, its systemic repercussions and comorbidities. The treatment aims at the rapid reestablishment of the blood flow in the affected artery, to improve the patient's prognosis. The biomarkers dosage in the daily clinical practice of the different cardiological centers can facilitate the diagnosis and the conduction of the dubious cases and the best evaluation of the degree of myocardial suffering after CS.
PubMed: 29755623
DOI: 10.14740/cr715w -
The Cochrane Database of Systematic... Mar 2022The primary manifestation of coronavirus disease 2019 (COVID-19) is respiratory insufficiency that can also be related to diffuse pulmonary microthrombosis and... (Review)
Review
BACKGROUND
The primary manifestation of coronavirus disease 2019 (COVID-19) is respiratory insufficiency that can also be related to diffuse pulmonary microthrombosis and thromboembolic events, such as pulmonary embolism, deep vein thrombosis, or arterial thrombosis. People with COVID-19 who develop thromboembolism have a worse prognosis. Anticoagulants such as heparinoids (heparins or pentasaccharides), vitamin K antagonists and direct anticoagulants are used for the prevention and treatment of venous or arterial thromboembolism. Besides their anticoagulant properties, heparinoids have an additional anti-inflammatory potential. However, the benefit of anticoagulants for people with COVID-19 is still under debate.
OBJECTIVES
To assess the benefits and harms of anticoagulants versus active comparator, placebo or no intervention in people hospitalised with COVID-19.
SEARCH METHODS
We searched the CENTRAL, MEDLINE, Embase, LILACS and IBECS databases, the Cochrane COVID-19 Study Register and medRxiv preprint database from their inception to 14 April 2021. We also checked the reference lists of any relevant systematic reviews identified, and contacted specialists in the field for additional references to trials.
SELECTION CRITERIA
Eligible studies were randomised controlled trials (RCTs), quasi-RCTs, cluster-RCTs and cohort studies that compared prophylactic anticoagulants versus active comparator, placebo or no intervention for the management of people hospitalised with COVID-19. We excluded studies without a comparator group and with a retrospective design (all previously included studies) as we were able to include better study designs. Primary outcomes were all-cause mortality and necessity for additional respiratory support. Secondary outcomes were mortality related to COVID-19, deep vein thrombosis, pulmonary embolism, major bleeding, adverse events, length of hospital stay and quality of life.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures. We used Cochrane RoB 1 to assess the risk of bias for RCTs, ROBINS-I to assess risk of bias for non-randomised studies (NRS) and GRADE to assess the certainty of evidence. We meta-analysed data when appropriate.
MAIN RESULTS
We included seven studies (16,185 participants) with participants hospitalised with COVID-19, in either intensive care units, hospital wards or emergency departments. Studies were from Brazil (2), Iran (1), Italy (1), and the USA (1), and two involved more than country. The mean age of participants was 55 to 68 years and the follow-up period ranged from 15 to 90 days. The studies assessed the effects of heparinoids, direct anticoagulants or vitamin K antagonists, and reported sparse data or did not report some of our outcomes of interest: necessity for additional respiratory support, mortality related to COVID-19, and quality of life. Higher-dose versus lower-dose anticoagulants (4 RCTs, 4647 participants) Higher-dose anticoagulants result in little or no difference in all-cause mortality (risk ratio (RR) 1.03, 95% CI 0.92 to 1.16, 4489 participants; 4 RCTs) and increase minor bleeding (RR 3.28, 95% CI 1.75 to 6.14, 1196 participants; 3 RCTs) compared to lower-dose anticoagulants up to 30 days (high-certainty evidence). Higher-dose anticoagulants probably reduce pulmonary embolism (RR 0.46, 95% CI 0.31 to 0.70, 4360 participants; 4 RCTs), and slightly increase major bleeding (RR 1.78, 95% CI 1.13 to 2.80, 4400 participants; 4 RCTs) compared to lower-dose anticoagulants up to 30 days (moderate-certainty evidence). Higher-dose anticoagulants may result in little or no difference in deep vein thrombosis (RR 1.08, 95% CI 0.57 to 2.03, 3422 participants; 4 RCTs), stroke (RR 0.91, 95% CI 0.40 to 2.03, 4349 participants; 3 RCTs), major adverse limb events (RR 0.33, 95% CI 0.01 to 7.99, 1176 participants; 2 RCTs), myocardial infarction (RR 0.86, 95% CI 0.48 to 1.55, 4349 participants; 3 RCTs), atrial fibrillation (RR 0.35, 95% CI 0.07 to 1.70, 562 participants; 1 study), or thrombocytopenia (RR 0.94, 95% CI 0.71 to 1.24, 2789 participants; 2 RCTs) compared to lower-dose anticoagulants up to 30 days (low-certainty evidence). It is unclear whether higher-dose anticoagulants have any effect on necessity for additional respiratory support, mortality related to COVID-19, and quality of life (very low-certainty evidence or no data). Anticoagulants versus no treatment (3 prospective NRS, 11,538 participants) Anticoagulants may reduce all-cause mortality but the evidence is very uncertain due to two study results being at critical and serious risk of bias (RR 0.64, 95% CI 0.55 to 0.74, 8395 participants; 3 NRS; very low-certainty evidence). It is uncertain if anticoagulants have any effect on necessity for additional respiratory support, mortality related to COVID-19, deep vein thrombosis, pulmonary embolism, major bleeding, stroke, myocardial infarction and quality of life (very low-certainty evidence or no data). Ongoing studies We found 62 ongoing studies in hospital settings (60 RCTs, 35,470 participants; 2 prospective NRS, 120 participants) in 20 different countries. Thirty-five ongoing studies plan to report mortality and 26 plan to report necessity for additional respiratory support. We expect 58 studies to be completed in December 2021, and four in July 2022. From 60 RCTs, 28 are comparing different doses of anticoagulants, 24 are comparing anticoagulants versus no anticoagulants, seven are comparing different types of anticoagulants, and one did not report detail of the comparator group.
AUTHORS' CONCLUSIONS
When compared to a lower-dose regimen, higher-dose anticoagulants result in little to no difference in all-cause mortality and increase minor bleeding in people hospitalised with COVID-19 up to 30 days. Higher-dose anticoagulants possibly reduce pulmonary embolism, slightly increase major bleeding, may result in little to no difference in hospitalisation time, and may result in little to no difference in deep vein thrombosis, stroke, major adverse limb events, myocardial infarction, atrial fibrillation, or thrombocytopenia. Compared with no treatment, anticoagulants may reduce all-cause mortality but the evidence comes from non-randomised studies and is very uncertain. It is unclear whether anticoagulants have any effect on the remaining outcomes compared to no anticoagulants (very low-certainty evidence or no data). Although we are very confident that new RCTs will not change the effects of different doses of anticoagulants on mortality and minor bleeding, high-quality RCTs are still needed, mainly for the other primary outcome (necessity for additional respiratory support), the comparison with no anticoagulation, when comparing the types of anticoagulants and giving anticoagulants for a prolonged period of time.
Topics: Aged; Anticoagulants; COVID-19; Heparin; Humans; Middle Aged; SARS-CoV-2; Thromboembolism
PubMed: 35244208
DOI: 10.1002/14651858.CD013739.pub2 -
BMJ Clinical Evidence Jan 2011About one quarter of people having an acute myocardial infarction (MI) in the USA will die of it, half of them within 1 hour of the onset of symptoms. Cardiogenic shock... (Review)
Review
INTRODUCTION
About one quarter of people having an acute myocardial infarction (MI) in the USA will die of it, half of them within 1 hour of the onset of symptoms. Cardiogenic shock develops in over 5% of people surviving the first hour after an acute MI, with a mortality of 50% to 80% in the first 48 hours.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: Which treatments improve outcomes in acute MI? Which treatments improve outcomes for cardiogenic shock after MI? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 52 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: angiotensin-converting enzyme (ACE) inhibitors, aspirin, beta-blockers, calcium channel blockers, early cardiac surgery, early invasive cardiac revascularisation, glycoprotein IIb/IIIa inhibitors, intra-aortic balloon counterpulsation, nitrates (with or without thrombolysis), positive inotropes, primary percutaneous transluminal coronary angioplasty (PTCA), pulmonary artery catheterisation, thrombolysis (with or without low molecular weight heparin, with or without unfractionated heparin), vasodilators, and ventricular assistance devices and cardiac transplantation.
Topics: Administration, Oral; Angioplasty, Balloon, Coronary; Heparin; Humans; Incidence; Myocardial Infarction; Platelet Glycoprotein GPIIb-IIIa Complex; Shock, Cardiogenic
PubMed: 21477402
DOI: No ID Found -
European Heart Journal Open Mar 2022Takotsubo syndrome (TTS) is a rare cardiovascular condition characterized by reversible ventricular dysfunction and a presentation resembling that of acute myocardial... (Review)
Review
Takotsubo syndrome (TTS) is a rare cardiovascular condition characterized by reversible ventricular dysfunction and a presentation resembling that of acute myocardial infarction. An increasing number of studies has shown the association of respiratory diseases with TTS. Here, we comprehensively reviewed the literature and examined the available evidence for this association. After searching PubMed, EMBASE, and Cochrane Library databases, two investigators independently reviewed 3117 studies published through May 2021. Of these studies, 99 met the inclusion criteria ( = 108 patients). In patients with coexisting respiratory disease and TTS, the most common TTS symptom was dyspnoea (70.48%), followed by chest pain (24.76%) and syncope (2.86%). The most common type of TTS was apical, accounting for 81.13% of cases, followed by the midventricular (8.49%), basal (8.49%), and biventricular (1.89%) types. Among the TTS cases, 39.82% were associated with obstructive lung disease and 38.89% were associated with pneumonia. Coronavirus disease 2019 (COVID-19), which has been increasingly reported in patients with TTS, was identified in 29 of 42 (69.05%) patients with pneumonia. The overall mortality rate for patients admitted for respiratory disease complicated by TTS was 12.50%. Obstructive lung disease and pneumonia are the most frequently identified respiratory triggers of TTS. Medications and invasive procedures utilized in managing respiratory diseases may also contribute to the development of TTS. Furthermore, the diagnosis of TTS triggered by these conditions can be challenging due to its atypical presentation. Future prospective studies are needed to establish appropriate guidelines for managing respiratory disease with concurrent TTS.
PubMed: 35919117
DOI: 10.1093/ehjopen/oeac009 -
Lung Oct 2021There is limited evidence on the role of the type of lobectomy after primary lung cancer with postoperative cerebral infarction (CI). The purpose of this review was to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is limited evidence on the role of the type of lobectomy after primary lung cancer with postoperative cerebral infarction (CI). The purpose of this review was to evaluate the role of left upper lobectomy (LUL) in pulmonary vein thrombosis (PVT) and eventual CI.
METHODS
A search was performed on MEDLINE, Embase, and Web of Science from inception to January 2021. Prospective and retrospective cohort studies investigating the association between types of lobectomies for primary lung cancer with PVT and/or CI were included. Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias. A random-effect model meta-analysis was utilized if significant heterogeneity was observed.
RESULTS
Twelve studies, including 5266 patients were included. The majority of studies were having a low risk of bias. LUL was associated with higher likelihood of CI (OR 6.27, 95% Confidence Interval (CI) 3.12-12.56; p < 0.00001) and PVT (OR 13.46, 95% CI 5.97-30.33; p < 0.00001) as compared to other lobectomies. Sensitivity analysis showed an independent role of LUL without underlying PVT in CI (OR 2.44, 95% CI 1.25-4.74; p = 0.009). Male and diabetic patients were at a higher risk, while Video-Assisted Thoracoscopic Surgery (VATS) was protective from CI.
CONCLUSION
The results of this review indicate that LUL after lung cancer is an independent risk factor for developing CI without underlying PVT. In addition, the risk of CI increases significantly when PVT develops after LUL. LUL is also a risk factor for PVT. A more frequent follow-up may be beneficial in lung cancer patients after LUL, especially in those with diabetes or undergoing adjuvant systemic therapy.
Topics: Cerebral Infarction; Humans; Lung Neoplasms; Male; Pneumonectomy; Prospective Studies; Retrospective Studies; Risk Factors; Thoracic Surgery, Video-Assisted
PubMed: 34570282
DOI: 10.1007/s00408-021-00480-4 -
Journal of Clinical Medicine Mar 2021Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a pro-apoptotic protein showing broad biological functions. Data from animal studies indicate that... (Review)
Review
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a pro-apoptotic protein showing broad biological functions. Data from animal studies indicate that TRAIL may possibly contribute to the pathophysiology of cardiomyopathy, atherosclerosis, ischemic stroke and abdominal aortic aneurysm. It has been also suggested that TRAIL might be useful in cardiovascular risk stratification. This systematic review aimed to evaluate whether TRAIL is a risk factor or risk marker in cardiovascular diseases (CVDs) focusing on major adverse cardiovascular events. Two databases (PubMed and Cochrane Library) were searched until December 2020 without a year limit in accordance to the PRISMA guidelines. A total of 63 eligible original studies were identified and included in our systematic review. Studies suggest an important role of TRAIL in disorders such as heart failure, myocardial infarction, atrial fibrillation, ischemic stroke, peripheral artery disease, and pulmonary and gestational hypertension. Most evidence associates reduced TRAIL levels and increased TRAIL-R2 concentration with all-cause mortality in patients with CVDs. It is, however, unclear whether low TRAIL levels should be considered as a risk factor rather than a risk marker of CVDs. Further studies are needed to better define the association of TRAIL with cardiovascular diseases.
PubMed: 33803523
DOI: 10.3390/jcm10061252 -
The Korean Journal of Internal Medicine Jan 2024There may be many predictors of anticoagulation-related gastrointestinal bleeding (GIB), but until now, systematic reviews and assessments of the certainty of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
There may be many predictors of anticoagulation-related gastrointestinal bleeding (GIB), but until now, systematic reviews and assessments of the certainty of the evidence have not been published. We conducted a systematic review to identify all risk factors for anticoagulant-associated GIB to inform risk prediction in the management of anticoagulation- related GIB.
METHODS
A systematic review and meta-analysis were conducted to search PubMed, EMBASE, Web of Science, and Cochrane Library databases (from inception through January 21, 2022) using the following search terms: anticoagulants, heparin, warfarin, dabigatran, rivaroxaban, apixaban, DOACs, gastrointestinal hemorrhage, risk factors. According to inclusion and exclusion criteria, studies of risk factors for anticoagulation-related GIB were identified. Risk factors for anticoagulant-associated GIB were used as the outcome index of this review.
RESULTS
We included 34 studies in our analysis. For anticoagulant-associated GIB, moderate-certainty evidence showed a probable association with older age, kidney disease, concomitant use of aspirin, concomitant use of the antiplatelet agent, heart failure, myocardial infarction, hematochezia, renal failure, coronary artery disease, helicobacter pylori infection, social risk factors, alcohol use, smoking, anemia, history of sleep apnea, chronic obstructive pulmonary disease, international normalized ratio (INR), obesity et al. Some of these factors are not included in current GIB risk prediction models. such as anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction, etc.
CONCLUSION
The study found that anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction et al. were associated with anticoagulation-related GIB, and these factors were not in the existing prediction models. This study informs risk prediction for anticoagulant-associated GIB, it also informs guidelines for GIB prevention and future research.
Topics: Humans; Anemia; Anticoagulants; Diltiazem; Gastrointestinal Hemorrhage; Gemfibrozil; Heart Failure; Helicobacter Infections; Helicobacter pylori; Myocardial Infarction; Risk Factors; Verapamil
PubMed: 38062723
DOI: 10.3904/kjim.2023.098 -
Respiratory Care Apr 2023Daily application of mechanical insufflation-exsufflation (MI-E) is used increasingly in patients with neuromuscular diseases (NMDs) to prevent pulmonary congestion and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Daily application of mechanical insufflation-exsufflation (MI-E) is used increasingly in patients with neuromuscular diseases (NMDs) to prevent pulmonary congestion and thereby respiratory tract infections, although its beneficial effect remains uncertain. We, therefore, conducted a systematic review, registered in PROSPERO (CRD42020158278), to compile available evidence for daily MI-E use in subjects with NMDs and stable respiratory condition.
METHODS
We performed a systematic comprehensive search of MEDLINE, Embase, CINAHL, and Web of Science up to December 23, 2021. We excluded articles studying the effect of MI-E in case of acute respiratory failure or infections and studies comparing different MI-E devices and settings. Studied outcomes were prevalence and severity of respiratory infections, lung function, respiratory characteristics, and patient satisfaction. We performed a meta-analysis using DerSimonian-Laird random effects model and assessed methodological quality by using the Alberta Heritage Foundation for Medical Research tool.
RESULTS
A total of 3,374 records were screened, of which 25 were included, studying 608 subjects. One randomized controlled trial (RCT) found a trend toward reduced duration of respiratory infections compared to air stacking (AS) that was not statistically significant. Long-term effects on pulmonary function tests (PFT) results were reported in one RCT and one retrospective study, with mixed results regarding vital capacity. Most studies compared PFT results before and immediately after MI-E use. Meta-analysis showed an overall beneficial effect of MI-E on cough peak flow (CPF) compared to unassisted CPF (mean difference 91.6 L/min [95% CI 28.3-155.0], < .001). Subject satisfaction was high, though possibly influenced by major bias.
CONCLUSIONS
There is limited evidence available to support beneficial effects of daily use of MI-E in clinically stable subjects with NMDs, with the possible exception of increased CPF immediately after MI-E application. Lack of longitudinal studies preclude conclusions regarding long-term effects. The very limited data comparing MI-E to AS preclude comparisons.
Topics: Humans; Insufflation; Respiration, Artificial; Neuromuscular Diseases; Cough; Respiratory Tract Infections; Myocardial Infarction; Randomized Controlled Trials as Topic
PubMed: 36963967
DOI: 10.4187/respcare.09664