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Sleep Science (Sao Paulo, Brazil) 2022Continuous positive airway pressure (CPAP) is the standard treatment for obstructive sleep apnea (OSA), but its outcomes for the pregnant are still undefined. This study... (Review)
Review
Continuous positive airway pressure (CPAP) is the standard treatment for obstructive sleep apnea (OSA), but its outcomes for the pregnant are still undefined. This study aims to review current CPAP intervention during pregnancy, discuss published trials, and propose relevant issues that have yet to be addressed satisfactorily about the cardiovascular, metabolic, fetal, and neonatal effects of CPAP treatment during gestation. Two authors independently conducted a systematic review until March 28th, 2021 on PubMed, BVS, and Cochrane Library, using PRISMA guidelines, and risk of bias. Discrepancies were reconciled by a third reviewer. Of 59 identified citations, eight original trials have submitted a total of 90 pregnant women to polysomnography and CPAP therapy. Four studies performed in samples with hypertension or preeclampsia presented blood pressure decrease or maintained the antihypertensive drug dose in the CPAP group. After CPAP utilization, one trial registered cardiac output and stroke volume increase with heart rate and peripheral vascular resistance decrease, which were correlated with birth weight increment. Others documented a higher Apgar in the CPAP group and more fetal movements during CPAP use. There was a reduction in serum uric acid and tumor necrosis factor-alpha in the CPAP groups whose blood pressure decreased. However, two weeks of CPAP use in women with gestational diabetes and OSA did not improve glucose levels but raised the insulin secretion in those adherents to CPAP. Despite these positive results without adverse effects, randomized controlled trials with standardized follow-up in larger populations are required to determine CPAP therapy recommendations in pregnancy.
PubMed: 35273777
DOI: 10.5935/1984-0063.20210024 -
Respiratory Care Feb 2022Artificial airway suctioning is a key component of airway management and a core skill for clinicians charged with assuring airway patency. Suctioning of the artificial...
Artificial airway suctioning is a key component of airway management and a core skill for clinicians charged with assuring airway patency. Suctioning of the artificial airway is a common procedure performed worldwide on a daily basis. As such, it is imperative that clinicians are familiar with the most-effective and efficient methods to perform the procedure. We conducted a systematic review to assist in the development of evidence-based recommendations that pertain to the care of patients with artificial airways. From our systematic review, we developed guidelines and recommendations that addressed questions related to the indications, complications, timing, duration, and methods of artificial airway suctioning. By using a modified version of the RAND/UCLA Appropriateness Method, the following recommendations for suctioning were developed for neonatal, pediatric, and adult patients with an artificial airway: (1) breath sounds, visual secretions in the artificial airway, and a sawtooth pattern on the ventilator waveform are indicators for suctioning pediatric and adult patients, and an acute increase in airway resistance may be an indicator for suctioning in neonates; (2) as-needed only, rather than scheduled, suctioning is sufficient for neonatal and pediatric patients; (3) both closed and open suction systems may be used to safely and effectively remove secretions from the artificial airway of adult patients; (4) preoxygenation should be performed before suctioning in pediatric and adult patients; (5) the use of normal saline solution should generally be avoided during suctioning; (6) during open suctioning, sterile technique should be used; (7) suction catheters should occlude < 70% of the endotracheal tube lumen in neonates and < 50% in pediatric and adult patients, and suction pressure should be kept below -120 mm Hg in neonatal and pediatric patients and -200 mm Hg in adult patients; (8) suction should be applied for a maximum of 15 s per suctioning procedure; (9) deep suctioning should only be used when shallow suctioning is ineffective; (10) routine bronchoscopy for secretion removal is not recommended; and (11) devices used to clear endotracheal tubes may be used when airway resistance is increased due to secretion accumulation.
Topics: Adult; Airway Management; Child; Humans; Infant, Newborn; Intubation, Intratracheal; Respiration, Artificial; Suction; Ventilators, Mechanical
PubMed: 35078900
DOI: 10.4187/respcare.09548 -
Sports Medicine - Open Dec 2021Protection against airborne infection is currently, due to the COVID-19-associated restrictions, ubiquitously applied during public transport use, work and leisure time....
The Impact of Ubiquitous Face Masks and Filtering Face Piece Application During Rest, Work and Exercise on Gas Exchange, Pulmonary Function and Physical Performance: A Systematic Review with Meta-analysis.
BACKGROUND
Protection against airborne infection is currently, due to the COVID-19-associated restrictions, ubiquitously applied during public transport use, work and leisure time. Increased carbon dioxide re-inhalation and breathing resistance may result thereof and, in turn, may negatively impact metabolism and performance.
OBJECTIVES
To deduce the impact of the surgical mask and filtering face piece type 2 (FFP2) or N95 respirator application on gas exchange (pulse-derived oxygen saturation (SpO), carbon dioxide partial pressure (PCO), carbon dioxide exhalation (VCO) and oxygen uptake (VO)), pulmonary function (respiratory rate and ventilation) and physical performance (heart rate HR, peak power output W).
METHODS
Systematic review with meta-analysis. Literature available in Medline/Pubmed, the Cochrane Library and the Web of Knowledge with the last search on the 6 of May 2021. Eligibility criteria: Randomised controlled parallel group or crossover trials (RCT), full-text availability, comparison of the acute effects of ≥ 1 intervention (surgical mask or FFP2/N95 application) to a control/comparator condition (i.e. no mask wearing). Participants were required to be healthy humans and > 16 years of age without conditions or illnesses influencing pulmonary function or metabolism. Risk of bias was rated using the crossover extension of the Cochrane risk of bias assessment tool II. Standardised mean differences (SMD, Hedges' g) with 95% confidence intervals (CI) were calculated, overall and for subgroups based on mask and exercise type, as pooled effect size estimators in our random-effects meta-analysis.
RESULTS
Of the 1499 records retrieved, 14 RCTs (all crossover trials, high risk of bias) with 25 independent intervention arms (effect sizes per outcome) on 246 participants were included. Masks led to a decrease in SpO during vigorous intensity exercise (6 effect sizes; SMD = - 0.40 [95% CI: - 0.70, - 0.09], mostly attributed to FFP2/N95) and to a SpO-increase during rest (5 effect sizes; SMD = 0.34 [95% CI: 0.04, 0.64]); no general effect of mask wearing on SpO occurred (21 effect sizes, SMD = 0.34 [95% CI: 0.04, 0.64]). Wearing a mask led to a general oxygen uptake decrease (5 effect sizes, SMD = - 0.44 [95% CI: - 0.75, - 0.14]), to slower respiratory rates (15 effect sizes, SMD = - 0.25 [95% CI: - 0.44, - 0.06]) and to a decreased ventilation (11 effect sizes, SMD = - 0.43 [95% CI: - 0.74, - 0.12]). Heart rate (25 effect sizes; SMD = 0.05 [95% CI: - 0.09, 0.19]), W (9 effect sizes; SMD = - 0.12 [95% CI: - 0.39, 0.15]), PCO (11 effect sizes; SMD = 0.07 [95% CI: - 0.14, 0.29]) and VCO (4 effect sizes, SMD = - 0.30 [95% CI: - 0.71, 0.10]) were not different to the control, either in total or dependent on mask type or physical activity status.
CONCLUSION
The number of crossover-RCT studies was low and the designs displayed a high risk of bias. The within-mask- and -intensity-homogeneous effects on gas exchange kinetics indicated larger detrimental effects during exhausting physical activities. Pulse-derived oxygen saturation was increased during rest when a mask was applied, whereas wearing a mask during exhausting exercise led to decreased oxygen saturation. Breathing frequency and ventilation adaptations were not related to exercise intensity. FFP2/N95 and, to a lesser extent, surgical mask application negatively impacted the capacity for gas exchange and pulmonary function but not the peak physical performance. Registration: Prospero registration number: CRD42021244634.
PubMed: 34897560
DOI: 10.1186/s40798-021-00388-6 -
Medicine Oct 2021Chronic obstructive pulmonary disease (COPD) is a common, preventable disease of airflow limitation that accounts for the third leading deaths of any disease process in... (Meta-Analysis)
Meta-Analysis
BACKGROUNDS
Chronic obstructive pulmonary disease (COPD) is a common, preventable disease of airflow limitation that accounts for the third leading deaths of any disease process in the worldwide. Health benefits of liuzijue qigong (LQG) on patients with stable COPD has been assessed. This study was designed to perform a systemic review and meta-analysis of the effect of Liuzijue breathing exercise on patients with stable COPD.
METHODS
Published articles from 1970 to December 2020 were conducted using electronic searches. Two independents reviewers conducted data extraction. The Cochrane risk of bias assessment tool was used to evaluate the quality of the included studies.
RESULTS
A total of 16 eligible trials with 1039 patients with stable COPD were identified. Compared with control group, the pool meta-analysis of LQG showed a significant improvement in forced expiratory volume in one second (FEV1) (MD = -0.16, 95% CI [0.09, 0.23], P < .00001), FEV1% (MD = 9.71, 95% CI [8.44, 10.98], P < .00001), the ratio of forced expiratory volume to forced vital capacity in the first second (FEV1/FVC [%]) (MD = 4.81, 95% CI [2.12, 7.51], P = .0005), 6 minutes walking distance (6MWD) (MD = 21.89, 95% CI [14.67, 29.11], P < .00001), health-related quality of life (SMD = -0.84, 95% CI [-1.12,-0.55], P < .00001) and modified medical research council dyspnea scale (mMRC) (MD = -0.73, 95% CI [-0.96, -0.50], P < .00001). The observed effect was more pronounced for short term and medium-term duration interventions of study. It also showed improvements in the secondary outcome measures by LQG.
CONCLUSIONS
In this systematic review and meta-analysis, LQG can improve lung ventilation function, exercise endurance and health-related quality of life of patients with stable COPD.
ETHIC AND DISSEMINATION
This study is a systematic review and it does not involve harming to the rights of participants. Ethical approval will not be require for this study. The research results may be published in a peer-reviewed journals.
Topics: Airway Resistance; Forced Expiratory Volume; Physical Endurance; Pulmonary Disease, Chronic Obstructive; Qigong; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 34731105
DOI: 10.1097/MD.0000000000027344 -
Sleep & Breathing = Schlaf & Atmung Sep 2022This systematic review was conducted to answer the following 3 questions: 'Does nasal pathology affect CPAP use?', 'What is the effect of CPAP on the nose?' and 'Does... (Review)
Review
PURPOSE
This systematic review was conducted to answer the following 3 questions: 'Does nasal pathology affect CPAP use?', 'What is the effect of CPAP on the nose?' and 'Does treatment of nasal pathology affect CPAP use?'.
METHODS
Pubmed and Scopus databases were searched for articles relevant to the study questions up to October 2020.
RESULTS
Sixty-three articles were selected, of which a majority were observational studies. Most studies identified a correlation between larger nasal cross-sectional area or lower nasal resistance and higher CPAP compliance or lower CPAP pressures; however, nasal symptoms at baseline did not appear to affect CPAP use. The effect of CPAP on the nose remains uncertain: while most studies suggested increased mucosal inflammation with CPAP, those investigating symptoms presented contradictory results, with some reporting an increase and others an improvement in nasal symptoms. Evidence is clearer for nasal surgery leading to an increase in CPAP compliance and a decrease in CPAP pressures, whereas there is little evidence available for the use of topical nasal steroids.
CONCLUSION
There appears to be a link between nasal volumes or nasal resistance and CPAP compliance, an increase in nasal inflammation caused by CPAP and a beneficial effect of nasal surgery on CPAP usage, but no significant effect of CPAP on nasal patency or effect of topical steroids on CPAP compliance. Results are more mitigated with regard to the effect of nasal symptoms on CPAP use and vice versa, and further research in this area would help identify patients who may benefit from additional support or treatment alongside CPAP.
Topics: Continuous Positive Airway Pressure; Humans; Inflammation; Patient Compliance; Sleep Apnea, Obstructive
PubMed: 34476729
DOI: 10.1007/s11325-021-02478-x -
The Cochrane Database of Systematic... Aug 2021Croup is an acute viral respiratory infection with upper airway mucosal inflammation that may cause respiratory distress. Most cases are mild. Moderate to severe croup... (Review)
Review
BACKGROUND
Croup is an acute viral respiratory infection with upper airway mucosal inflammation that may cause respiratory distress. Most cases are mild. Moderate to severe croup may require treatment with corticosteroids (the benefits of which are often delayed) and nebulised epinephrine (adrenaline) (the benefits of which may be short-lived and which can cause dose-related adverse effects including tachycardia, arrhythmias, and hypertension). Rarely, croup results in respiratory failure necessitating emergency intubation and ventilation. A mixture of helium and oxygen (heliox) may prevent morbidity and mortality in ventilated neonates by reducing the viscosity of the inhaled air. It is currently used during emergency transport of children with severe croup. Anecdotal evidence suggests that it relieves respiratory distress. This review updates versions published in 2010, 2013, and 2018.
OBJECTIVES
To examine the effect of heliox compared to oxygen or other active interventions, placebo, or no treatment on relieving signs and symptoms in children with croup as determined by a croup score and rates of admission and intubation.
SEARCH METHODS
We searched CENTRAL, which includes the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE, Embase, CINAHL, Web of Science, and LILACS, on 15 April 2021. We also searched the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch/) and ClinicalTrials.gov (clinicaltrials.gov) on 15 April 2021. We contacted the British Oxygen Company, a leading supplier of heliox.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs comparing the effect of heliox in comparison with placebo, no treatment, or any active intervention(s) in children with croup.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Data that could not be pooled for statistical analysis were reported descriptively.
MAIN RESULTS
We included 3 RCTs involving a total of 91 children aged between 6 months and 4 years. Study duration was from 7 to 16 months, and all studies were conducted in emergency departments. Two studies were conducted in the USA and one in Spain. Heliox was administered as a mixture of 70% heliox and 30% oxygen. Risk of bias was low in two studies and high in one study because of its open-label design. We did not identify any new trials for this 2021 update. One study of 15 children with mild croup compared heliox with 30% humidified oxygen administered for 20 minutes. There may be no difference in croup score changes between groups at 20 minutes (mean difference (MD) -0.83, 95% confidence interval (CI) -2.36 to 0.70) (Westley croup score, scale range 0 to 16). The mean croup score at 20 minutes postintervention may not differ between groups (MD -0.57, 95% CI -1.46 to 0.32). There may be no difference between groups in mean respiratory rate (MD 6.40, 95% CI -1.38 to 14.18) and mean heart rate (MD 14.50, 95% CI -8.49 to 37.49) at 20 minutes. The evidence for all outcomes in this comparison was of low certainty, downgraded for serious imprecision. All children were discharged, but information on hospitalisation, intubation, or re-presenting to emergency departments was not reported. In another study, 47 children with moderate croup received one dose of oral dexamethasone (0.3 mg/kg) with either heliox for 60 minutes or no treatment. Heliox may slightly improve Taussig croup scores (scale range 0 to 15) at 60 minutes postintervention (MD -1.10, 95% CI -1.96 to -0.24), but there may be no difference between groups at 120 minutes (MD -0.70, 95% CI -1.56 to 0.16). Children treated with heliox may have lower mean Taussig croup scores at 60 minutes (MD -1.11, 95% CI -2.05 to -0.17) but not at 120 minutes (MD -0.71, 95% CI -1.72 to 0.30). Children treated with heliox may have lower mean respiratory rates at 60 minutes (MD -4.94, 95% CI -9.66 to -0.22), but there may be no difference at 120 minutes (MD -3.17, 95% CI -7.83 to 1.49). There may be a difference in hospitalisation rates between groups (odds ratio 0.46, 95% CI 0.04 to 5.41). We assessed the evidence for all outcomes in this comparison as of low certainty, downgraded due to imprecision and high risk of bias related to an open-label design. Information on heart rate and intubation was not reported. In the third study, 29 children with moderate to severe croup all received continuous cool mist and intramuscular dexamethasone (0.6 mg/kg). They were then randomised to receive either heliox (given as a mixture of 70% helium and 30% oxygen) plus one to two doses of nebulised saline or 100% oxygen plus nebulised epinephrine (adrenaline), with gas therapy administered continuously for three hours. Heliox may slightly improve croup scores at 90 minutes postintervention, but may result in little or no difference overall using repeated-measures analysis. We assessed the evidence for all outcomes in this comparison as of low certainty, downgraded due to high risk of bias related to inadequate reporting. Information on hospitalisation or re-presenting to the emergency department was not reported. The included studies did not report on adverse events, intensive care admissions, or parental anxiety. We could not pool the available data because each comparison included data from only one study.
AUTHORS' CONCLUSIONS
Given the very limited available evidence, uncertainty remains regarding the effectiveness and safety of heliox. Heliox may not be more effective than 30% humidified oxygen for children with mild croup, but may be beneficial in the short term for children with moderate croup treated with dexamethasone. The effect of heliox may be similar to 100% oxygen given with one or two doses of adrenaline. Adverse events were not reported, and it is unclear if these were monitored in the included studies. Adequately powered RCTs comparing heliox with standard treatments are needed to further assess the role of heliox in the treatment of children with moderate to severe croup.
Topics: Airway Obstruction; Airway Resistance; Child; Child, Preschool; Croup; Helium; Humans; Infant; Oxygen; Oxygen Inhalation Therapy; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34397099
DOI: 10.1002/14651858.CD006822.pub6 -
International Journal of Molecular... Jul 2021Airway inflammation represents an important characteristic in asthma, modulating airflow limitation and symptom control, and triggering the risk of asthma exacerbation....
Airway inflammation represents an important characteristic in asthma, modulating airflow limitation and symptom control, and triggering the risk of asthma exacerbation. Thus, although corticosteroids represent the cornerstone for the treatment of asthma, severe patients may be dependent on oral corticosteroids (OCSs). Fortunately, the current humanised monoclonal antibodies (mAbs) benralizumab, dupilumab, mepolizumab, omalizumab, and reslizumab have been proven to induce an OCS-sparing effect in randomized controlled trials (RCTs), thus overcoming the problem of OCS dependence in severe asthma. Nevertheless, a large discrepancy has been recognized between selected patients enrolled in RCTs and non-selected asthmatic populations in real-world settings. It is not possible to exclude that the OCS-sparing effect of mAbs resulting from the RCTs could be different than the real effect resulting in clinical practice. Therefore, we performed a systematic review and correlation analysis to assess whether mAbs are effective in eliciting an OCS-sparing effect and overcoming the OCS dependence in severe asthmatic patients in real-world settings. Overall, real-world studies support the evidence that OCS dependence is a real condition that, however, can be found only in a small number of really severe asthmatic patients. In most patients, the dependence on OCS can be related to modifying factors that, when adequately modulated, may lead to a significant reduction or suspension of OCS maintenance. Conversely, in severe asthmatics in whom OCS resistance is proved by a high daily dose intake, mAbs allow reversion of the OCS dependence, leading to the suspension of OCS therapy in most patients or >50% reduction in the daily OCS dose.
Topics: Administration, Oral; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Antibodies, Monoclonal; Asthma; Humans; Randomized Controlled Trials as Topic; Substance-Related Disorders
PubMed: 34281184
DOI: 10.3390/ijms22137132 -
Journal of Oral Rehabilitation Aug 2021Chin tuck against resistance (CTAR) exercise has been recently reported to be a new therapeutic exercise method that can help improve swallowing function in patients... (Review)
Review
BACKGROUND
Chin tuck against resistance (CTAR) exercise has been recently reported to be a new therapeutic exercise method that can help improve swallowing function in patients with dysphagia. However, due to the differences in exercise protocols, methods and the tools used across studies of CTAR exercise, an overall systematic review of these studies is necessary.
OBJECTIVE
The present study investigated the exercise protocols, methods and tools used in various studies of CTAR exercise and summarised their findings.
METHODS
We searched for studies related to CTAR exercise using electronic databases and selected nine articles for review. The articles were categorised on the basis of four criteria: study design and quality, training protocol, outcome measures and clinical effect.
RESULTS
Four articles reported that CTAR exercise not only helped activate the suprahyoid muscle in healthy adults, but also activated the sternocleidomastoid muscle less than Shaker exercise. In addition, five articles reported that CTAR exercise was effective in improving swallowing function and oral diet stage in the pharyngeal phase, including reduction of airway aspiration in patients with dysphagia after stroke.
CONCLUSIONS
CTAR exercise more selectively activates the suprahyoid muscle and is an effective therapeutic exercise for improving swallowing function in patients with dysphagia. Because it is less strenuous than Shaker exercise, it requires less physical burden and effort, allowing greater compliance.
Topics: Adult; Chin; Deglutition; Deglutition Disorders; Exercise Therapy; Humans; Resistance Training
PubMed: 33973284
DOI: 10.1111/joor.13181 -
Minerva Medica Oct 2021Asthma is a complex disorder characterized by expiratory airflow limitation, wheeze, shortness of breath, chest tightness and cough, which can vary over time and in...
INTRODUCTION
Asthma is a complex disorder characterized by expiratory airflow limitation, wheeze, shortness of breath, chest tightness and cough, which can vary over time and in intensity. Being highly heterogeneous, asthma was characterized and classified in several asthma phenotypes and endotypes from 1947 until today. The present systematic review aims to summarize and describe evidence that was published in the last ten years in the field of asthma phenotyping and endotyping.
EVIDENCE ACQUISITION
The systematic review resumed high-quality evidence (clinical trials and randomized control trials) retrieved on MEDLINE and EMBASE databanks and involving adult asthmatic populations. Analyses of literature were conducted according to PRISMA and CASP guidelines.
EVIDENCE SYNTHESIS
Querying MEDLINE and EMBASE databanks, 5019 and 12261 entries were retrieved, respectively. Applying limitations for year of publication, age of participants, and type of publication, the search results were reduced to 98 and 132 articles, respectively. After data abstraction and resolution of duplications, only 50 articles were further evaluated. The research products were then classified first in macro-areas of interest (phenotypes or endotypes) and then in detailed micro-areas.
CONCLUSIONS
This systematic review overviews the principal findings available from high-quality literature in the last decade concerning asthma phenotypes and endotypes. Asthma has been described from different points of view, characterizing symptoms, microbiota composition, comorbidities, viral infections, and airway and/or systemic inflammatory status. The comprehension of precise mechanisms underlying asthma pathogenesis is thereby the basis for the development of novel therapeutic strategies, likely essential to the development of precision medicine.
Topics: Adult; Age Factors; Asthma; Biological Products; Clinical Trials as Topic; Comorbidity; Cough; Disease Progression; Drug Resistance; Humans; Microbiota; Obesity; Phenotype; Randomized Controlled Trials as Topic; Respiratory Sounds; Sputum; Steroids; Treatment Outcome
PubMed: 33969960
DOI: 10.23736/S0026-4806.21.07498-X -
Phytotherapy Research : PTR Sep 2021Viral infections of the lower respiratory tract are considered a public health problem. They affect millions of people worldwide, causing thousands of deaths, and are... (Meta-Analysis)
Meta-Analysis Review
Effectiveness of supplementation with quercetin-type flavonols for treatment of viral lower respiratory tract infections: Systematic review and meta-analysis of preclinical studies.
Viral infections of the lower respiratory tract are considered a public health problem. They affect millions of people worldwide, causing thousands of deaths, and are treated with expensive medicines, such as antivirals or palliative measures. In this study, we conducted a systematic review to describe the use of quercetin-type flavonols against lower respiratory tract viruses and discussed the preclinical impact of this approach on different signs and clinical mechanisms of infection. The systematic review was performed in PubMed/MEDLINE, Scopus, Scielo, and Biblioteca Virtual de Saúde (BVS). After the database search, 11 relevant studies were identified as eligible. The analysis of these studies showed evidence of antiviral activity of quercetin-type flavonols with significantly reduced mortality rate (M-H = 0.19, 95% CI: 0.05 to 0.65, p-value = 0.008) of infected animals and a reduction in the average viral load (IV = -1.93, 95% CI: -3.54 to -0.31, p-value = 0.02). Additionally, quercetin and its derivatives reduced the amount of proinflammatory cytokines, chemokines, reactive oxygen species, mucus production, and airway resistance in animals infected with a respiratory virus. Overall, supplementation with quercetin-type flavonols is a promising strategy for treating viral-induced lower respiratory tract infections.
Topics: Animals; Dietary Supplements; Flavonols; Humans; Quercetin; Respiratory Tract Infections; Virus Diseases
PubMed: 33864310
DOI: 10.1002/ptr.7122