Sex and gender-based analysis and diversity metric reporting in acute care trials published in high-impact journals: a systematic review.

OBJECTIVE: To characterise sex and gender-based analysis (SGBA) and diversity metric reporting, representation of female/women participants in acute care trials and temporal changes in reporting before and after publication of the 2016 Sex and Gender Equity in Research guideline. DESIGN: Systematic review. DATA SOURCES: We searched MEDLINE for trials published in five leading medical journals in 2014, 2018 and 2020. STUDY SELECTION: Trials that enrolled acutely ill adults, compared two or more interventions and reported at least one clinical outcome. DATA ABSTRACTION AND SYNTHESIS: 4 reviewers screened citations and 22 reviewers abstracted data, in duplicate. We compared reporting differences between intensive care unit (ICU) and cardiology trials. RESULTS: We included 88 trials (75 (85.2%) ICU and 13 (14.8%) cardiology) (n=111 428; 38 140 (34.2%) females/women). Of 23 (26.1%) trials that reported an SGBA, most used a forest plot (22 (95.7%)), were prespecified (21 (91.3%)) and reported a sex-by-intervention interaction with a significance test (19 (82.6%)). Discordant sex and gender terminology were found between headings and subheadings within baseline characteristics tables (17/32 (53.1%)) and between baseline characteristics tables and SGBA (4/23 (17.4%)). Only 25 acute care trials (28.4%) reported race or ethnicity. Participants were predominantly white (78.8%) and male/men (65.8%). No trial reported gendered-social factors. SGBA reporting and female/women representation did not improve temporally. Compared with ICU trials, cardiology trials reported significantly more SGBA (15/75 (20%) vs 8/13 (61.5%) p=0.005). CONCLUSIONS: Acute care trials in leading medical journals infrequently included SGBA, female/women and non-white trial participants, reported race or ethnicity and never reported gender-related factors. Substantial opportunity exists to improve SGBA and diversity metric reporting and recruitment of female/women participants in acute care trials. PROSPERO REGISTRATION NUMBER: CRD42022282565.

Efficacy and safety of corticosteroids in cardiac arrest: a systematic review, meta-analysis and trial sequential analysis of randomized control trials.

BACKGROUND: Post-cardiac arrest, outcomes for most patients are poor, regardless of setting. Many patients who do achieve spontaneous return of circulation require vasopressor therapy to maintain organ perfusion. There is some evidence to support the use of corticosteroids in cardiac arrest. RESEARCH QUESTION: Assess the efficacy and safety of corticosteroids in patients following in- and out-of-hospital cardiac arrest. STUDY DESIGN AND METHODS: We searched databases CINAHL, EMBASE, LILACS, MEDLINE, Web of Science, CENTRAL, ClinicalTrails.gov, and ICTRP. We included randomized controlled trials (RCTs) that examined the efficacy and safety of corticosteroids, as compared to placebo or usual care in patients post-cardiac arrest. We pooled estimates of effect size using random effects meta-analysis and report relative risk (RR) with 95% confidence intervals (CIs). We assessed risk of bias (ROB) for the included trials using the modified Cochrane ROB tool and rated the certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation methodology. RESULTS: We included 8 RCTs (n = 2213 patients). Corticosteroids administered post-cardiac arrest had an uncertain effect on mortality measured at the longest point of follow-up (RR 0.96, 95% CI 0.90-1.02, very low certainty, required information size not met using trial sequential analysis). Corticosteroids probably increase return of spontaneous circulation (ROSC) (RR 1.32, 95% CI 1.18-1.47, moderate certainty) and may increase the likelihood of survival with good functional outcome (RR 1.49, 95% CI 0.87-2.54, low certainty). Corticosteroids may decrease the risk of ventilator associated pneumonia (RR 0.76, 95% CI 0.46-1.09, low certainty), may increase renal failure (RR 1.29, 95% CI 0.84-1.99, low certainty), and have an uncertain effect on bleeding (RR 2.04, 95% CI 0.53-7.84, very low certainty) and peritonitis (RR 10.54, 95% CI 2.99-37.19, very low certainty). CONCLUSIONS: In patients during or after cardiac arrest, corticosteroids have an uncertain effect on mortality but probably increase ROSC and may increase the likelihood of survival with good functional outcome at hospital discharge. Corticosteroids may decrease ventilator associated pneumonia, may increase renal failure, and have an uncertain effect on bleeding and peritonitis. However, the pooled evidence examining these outcomes was sparse and imprecision contributed to low or very low certainty of evidence.

Adherence of Clinical Practice Guidelines for Pharmacologic Treatments of Hospitalized Patients With COVID-19 to Trustworthy Standards: A Systematic Review.

Importance: The COVID-19 pandemic created the need for rapid and urgent guidance for clinicians to manage COVID-19 among patients and prevent transmission. Objective: To appraise the quality of clinical practice guidelines (CPGs) using the National Academy of Medicine (NAM) criteria. Evidence Review: A search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials to December 14, 2020, and a search of related articles to February 28, 2021, that included CPGs developed by societies or by government or nongovernment organizations that reported pharmacologic treatments of hospitalized patients with COVID-19. Teams of 2 reviewers independently abstracted data and assessed CPG quality using the 15-item National Guideline Clearinghouse Extent of Adherence to Trustworthy Standards (NEATS) instrument. Findings: Thirty-two CPGs were included in the review. Of these, 25 (78.1%) were developed by professional societies and emanated from a single World Health Organization (WHO) region. Overall, the CPGs were of low quality. Only 7 CPGs (21.9%) reported funding sources, and 12 (37.5%) reported conflicts of interest. Only 5 CPGs (15.6%) included a methodologist, described a search strategy or study selection process, or synthesized the evidence. Although 14 CPGs (43.8%) made recommendations or suggestions for or against treatments, they infrequently rated confidence in the quality of the evidence (6 of 32 [18.8%]), described potential benefits and harms (6 of 32 [18.8%]), or graded the strength of the recommendations (5 of 32 [15.6%]). External review, patient or public perspectives, or a process for updating were rare. High-quality CPGs included a methodologist and multidisciplinary collaborations involving investigators from 2 or more WHO regions. Conclusions and Relevance: In this review, few COVID-19 CPGs met NAM standards for trustworthy guidelines. Approaches that prioritize engagement of a methodologist and multidisciplinary collaborators from at least 2 WHO regions may lead to the production of fewer, high-quality CPGs that are poised for updates as new evidence emerges. Trial Registration: PROSPERO Identifier: CRD42021245239.

Risk of dispersion or aerosol generation and infection transmission with nasopharyngeal and oropharyngeal swabs for detection of COVID-19: a systematic review.

OBJECTIVES: SARS-CoV-2-related disease, referred to as COVID-19, has emerged as a global pandemic since December 2019. While there is growing recognition regarding possible airborne transmission, particularly in the setting of aerosol-generating procedures and treatments, whether nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 generate aerosols remains unclear. DESIGN: Systematic review. DATA SOURCES: We searched Ovid MEDLINE and EMBASE up to 3 November 2020. We also searched the China National Knowledge Infrastructure, Chinese Medical Journal Network, medRxiv and ClinicalTrials.gov up to 29 March 2020. ELIGIBILITY CRITERIA: All comparative and non-comparative studies that evaluated dispersion or aerosolisation of viable airborne organisms, or transmission of infection associated with nasopharyngeal or oropharyngeal swab testing. RESULTS: Of 7702 citations, only one study was deemed eligible. Using a dedicated sampling room with negative pressure isolation room, personal protective equipment including N95 or higher masks, strict sterilisation protocols, structured training with standardised collection methods and a structured collection and delivery system, a tertiary care hospital proved a 0% healthcare worker infection rate among eight nurses conducting over 11 000 nasopharyngeal swabs. No studies examining transmissibility with other safety protocols, nor any studies quantifying the risk of aerosol generation with nasopharyngeal or oropharyngeal swabs for detection of SARS-CoV-2, were identified. CONCLUSIONS: There is limited to no published data regarding aerosol generation and risk of transmission with nasopharyngeal and oropharyngeal swabs for the detection of SARS-CoV-2. Field experiments to quantify this risk are warranted. Vigilance in adhering to current standards for infection control is suggested.

The role for high flow nasal cannula as a respiratory support strategy in adults: a clinical practice guideline.

PURPOSE: High flow nasal cannula (HFNC) is a relatively recent respiratory support technique which delivers high flow, heated and humidified controlled concentration of oxygen via the nasal route. Recently, its use has increased for a variety of clinical indications. To guide clinical practice, we developed evidence-based recommendations regarding use of HFNC in various clinical settings. METHODS: We formed a guideline panel composed of clinicians, methodologists and experts in respiratory medicine. Using GRADE, the panel developed recommendations for four actionable questions. RESULTS: The guideline panel made a strong recommendation for HFNC in hypoxemic respiratory failure compared to conventional oxygen therapy (COT) (moderate certainty), a conditional recommendation for HFNC following extubation (moderate certainty), no recommendation regarding HFNC in the peri-intubation period (moderate certainty), and a conditional recommendation for postoperative HFNC in high risk and/or obese patients following cardiac or thoracic surgery (moderate certainty). CONCLUSIONS: This clinical practice guideline synthesizes current best-evidence into four recommendations for HFNC use in patients with hypoxemic respiratory failure, following extubation, in the peri-intubation period, and postoperatively for bedside clinicians.

High-Flow Nasal Cannula Compared With Conventional Oxygen Therapy or Noninvasive Ventilation Immediately Postextubation: A Systematic Review and Meta-Analysis.

OBJECTIVES: Reintubation after failed extubation is associated with increased mortality and longer hospital length of stay. Noninvasive oxygenation modalities may prevent reintubation. We conducted a systematic review and meta-analysis to determine the safety and efficacy of high-flow nasal cannula after extubation in critically ill adults. DATA SOURCES: We searched MEDLINE, EMBASE, and Web of Science. STUDY SELECTION: We included randomized controlled trials comparing high-flow nasal cannula to other noninvasive methods of oxygen delivery after extubation in critically ill adults. DATA EXTRACTION: We included the following outcomes: reintubation, postextubation respiratory failure, mortality, use of noninvasive ventilation, ICU and hospital length of stay, complications, and comfort. DATA SYNTHESIS: We included eight randomized controlled trials (n = 1,594 patients). Compared with conventional oxygen therapy, high-flow nasal cannula decreased reintubation (relative risk, 0.46; 95% CI, 0.30-0.70; moderate certainty) and postextubation respiratory failure (relative risk, 0.52; 95% CI, 0.30-0.91; very low certainty), but had no effect on mortality (relative risk, 0.93; 95% CI, 0.57-1.52; moderate certainty), or ICU length of stay (mean difference, 0.05 d fewer; 95% CI, 0.83 d fewer to 0.73 d more; high certainty). High-flow nasal cannula may decrease use of noninvasive ventilation (relative risk, 0.64; 95% CI, 0.34-1.22; moderate certainty) and hospital length of stay (mean difference, 0.98 d fewer; 95% CI, 2.16 d fewer to 0.21 d more; moderate certainty) compared with conventional oxygen therapy, however, certainty was limited by imprecision. Compared with noninvasive ventilation, high-flow nasal cannula had no effect on reintubation (relative risk, 1.16; 95% CI, 0.86-1.57; low certainty), mortality (relative risk, 1.12; 95% CI, 0.82-1.53; moderate certainty), or postextubation respiratory failure (relative risk, 0.82; 95% CI, 0.48-1.41; very low certainty). High-flow nasal cannula may reduce ICU length of stay (moderate certainty) and hospital length of stay (moderate certainty) compared with noninvasive ventilation. CONCLUSIONS: High-flow nasal cannula reduces reintubation compared with conventional oxygen therapy, but not compared with noninvasive ventilation after extubation.

High-Flow Nasal Cannula in the Immediate Postoperative Period: A Systematic Review and Meta-analysis.

BACKGROUND: Studies have demonstrated that high-flow nasal cannula (HFNC) prevents intubation in acute hypoxic respiratory failure when compared with conventional oxygen therapy (COT). However, the data examining routine HFNC use in the immediate postoperative period are less clear. RESEARCH QUESTION: Is routine HFNC use superior to COT or noninvasive ventilation (NIV) use in preventing intubation in patients postoperatively? STUDY DESIGN AND METHODS: We comprehensively searched databases (PubMed, Embase, Web of Science) to identify randomized controlled trials (RCTs) that compared the effect of HFNC use with that of COT or NIV in the immediate postoperative period on reintubation, escalation of respiratory support, hospital mortality, ICU and hospital length of stay (LOS), postoperative hypoxemia, and treatment complications. We assessed individual study risk of bias (RoB) by using the revised Cochrane RoB 2 tool and rated certainty in outcomes by using the Grading of Recommendations Assessment, Development and Evaluation framework. RESULTS: We included 11 RCTs enrolling 2,201 patients. Ten compared HFNC with COT and one with NIV. Compared with COT use, HFNC use in the postoperative period was associated with a lower reintubation rate (relative risk [RR], 0.32; 95% CI, 0.12-0.88; absolute risk reduction [ARR], 2.9%; moderate certainty) and decreased escalation of respiratory support (RR, 0.54; 95% CI, 0.31-0.94; ARR, 5.8%; very low certainty). Post hoc subgroup analysis suggested that this effect was driven by patients who were obese and/or at high risk (subgroup differences, P = .06). We did not find differences in any of the other stated outcomes between HFNC and COT. HFNC was also no different from NIV in reintubation rate, respiratory therapy failure, or ICU LOS. INTERPRETATION: With evidence of moderate certainty, prophylactic HFNC reduces reintubation and escalation of respiratory support compared with COT in the immediate postoperative period after cardiothoracic surgery. This effect is likely driven by patients who are at high risk and/or obese. These findings support postoperative prophylactic HFNC use in the patients who are at high risk and/or obese undergoing cardiothoracic surgery.

High-flow nasal cannula for acute hypoxemic respiratory failure in patients with COVID-19: systematic reviews of effectiveness and its risks of aerosolization, dispersion, and infection transmission.

PURPOSE: We conducted two World Health Organization-commissioned reviews to inform use of high-flow nasal cannula (HFNC) in patients with coronavirus disease (COVID-19). We synthesized the evidence regarding efficacy and safety (review 1), as well as risks of droplet dispersion, aerosol generation, and associated transmission (review 2) of viral products. SOURCE: Literature searches were performed in Ovid MEDLINE, Embase, Web of Science, Chinese databases, and medRxiv. Review 1: we synthesized results from randomized-controlled trials (RCTs) comparing HFNC to conventional oxygen therapy (COT) in critically ill patients with acute hypoxemic respiratory failure. Review 2: we narratively summarized findings from studies evaluating droplet dispersion, aerosol generation, or infection transmission associated with HFNC. For both reviews, paired reviewers independently conducted screening, data extraction, and risk of bias assessment. We evaluated certainty of evidence using GRADE methodology. PRINCIPAL FINDINGS: No eligible studies included COVID-19 patients. Review 1: 12 RCTs (n = 1,989 patients) provided low-certainty evidence that HFNC may reduce invasive ventilation (relative risk [RR], 0.85; 95% confidence interval [CI], 0.74 to 0.99) and escalation of oxygen therapy (RR, 0.71; 95% CI, 0.51 to 0.98) in patients with respiratory failure. Results provided no support for differences in mortality (moderate certainty), or in-hospital or intensive care length of stay (moderate and low certainty, respectively). Review 2: four studies evaluating droplet dispersion and three evaluating aerosol generation and dispersion provided very low certainty evidence. Two simulation studies and a crossover study showed mixed findings regarding the effect of HFNC on droplet dispersion. Although two simulation studies reported no associated increase in aerosol dispersion, one reported that higher flow rates were associated with increased regions of aerosol density. CONCLUSIONS: High-flow nasal cannula may reduce the need for invasive ventilation and escalation of therapy compared with COT in COVID-19 patients with acute hypoxemic respiratory failure. This benefit must be balanced against the unknown risk of airborne transmission.

RéSUMé: OBJECTIF: Nous avons réalisé deux comptes rendus sur commande de l'Organisation mondiale de la santé pour guider l'utilisation de canules nasales à haut débit (CNHD) chez les patients ayant contracté le coronavirus (COVID-19). Nous avons synthétisé les données probantes concernant leur efficacité et leur innocuité (compte rendu 1), ainsi que les risques de dispersion des gouttelettes, de génération d'aérosols, et de transmission associée d'éléments viraux (compte rendu 2). SOURCE: Des recherches de littérature ont été réalisées dans les bases de données Ovid MEDLINE, Embase, Web of Science, ainsi que dans les bases de données chinoises et medRxiv. Compte rendu 1 : nous avons synthétisé les résultats d'études randomisées contrôlées (ERC) comparant les CNHD à une oxygénothérapie conventionnelle chez des patients en état critique atteints d'insuffisance respiratoire hypoxémique aiguë. Compte rendu 2 : nous avons résumé sous forme narrative les constatations d'études évaluant la dispersion de gouttelettes, la génération d'aérosols ou la transmission infectieuse associées aux CNHD. Pour les deux comptes rendus, des réviseurs appariés ont réalisé la sélection des études, l'extraction des données et l'évaluation du risque de biais de manière indépendante. Nous avons évalué la certitude des données probantes en nous fondant sur la méthodologie GRADE. CONSTATATIONS PRINCIPALES: Aucune étude éligible n'incluait de patients atteints de COVID-19. Compte rendu 1 : 12 ERC (n = 1989 patients) ont fourni des données probantes de certitude faible selon lesquelles les CNHD réduiraient la ventilation invasive (risque relatif [RR], 0,85; intervalle de confiance [IC] 95 %, 0,74 à 0,99) et l'intensification de l'oxygénothérapie (RR, 0,71; IC 95 %, 0,51 à 0,98) chez les patients atteints d'insuffisance respiratoire. Les résultats n'ont pas démontré de différences en matière de mortalité (certitude modérée), ni de durée du séjour hospitalier ou à l'unité des soins intensifs (certitude modérée et faible, respectivement). Compte rendu 2 : quatre études évaluant la dispersion de gouttelettes et trois évaluant la génération et la dispersion d'aérosols ont fourni des données probantes de très faible certitude. Deux études de simulation et une étude croisée ont donné des résultats mitigés quant à l'effet des CNHD sur la dispersion des gouttelettes. Bien que deux études de simulation n'aient rapporté aucune augmentation associée concernant la dispersion d'aérosols, l'une a rapporté que des taux de débit plus élevés étaient associés à des régions à densité d'aérosols élevée plus grandes. CONCLUSION: Les canules nasales à haut débit pourraient réduire la nécessité de recourir à la ventilation invasive et l'escalade des traitements par rapport à l'oxygénothérapie conventionnelle chez les patients atteints de COVID-19 souffrant d'insuffisance respiratoire hypoxémique aiguë. Cet avantage doit être soupesé contre le risque inconnu de transmission atmosphérique.

Moderate Certainty Evidence Suggests the Use of High-Flow Nasal Cannula Does Not Decrease Hypoxia When Compared With Conventional Oxygen Therapy in the Peri-Intubation Period: Results of a Systematic Review and Meta-Analysis.

OBJECTIVE: The role of high-flow nasal cannula during and before intubation is unclear despite a number of randomized clinical trials. Our objective was to conduct a systematic review and meta-analysis examining the benefits of high-flow nasal cannula in the peri-intubation period. DATA SOURCES: We performed a comprehensive search of relevant databases (MEDLINE, EMBASE, and Web of Science). STUDY SELECTION: We included randomized clinical trials that compared high-flow nasal cannula to other noninvasive oxygen delivery systems in the peri-intubation period. DATA EXTRACTION: Our primary outcome was severe desaturation (defined as peripheral oxygen saturation reading < 80% during intubation). Secondary outcomes included peri-intubation complications, apneic time, PaO2 before and after intubation, PaCO2 after intubation, ICU length of stay, and short-term mortality. DATA SYNTHESIS: We included 10 randomized clinical trials (n = 1,017 patients). High-flow nasal cannula had no effect on the occurrence rate of peri-intubation hypoxemia (relative risk, 0.98; 95% CI, 0.68-1.42; 0.3% absolute risk reduction, moderate certainty), serious complications (relative risk, 0.87; 95% CI, 0.71-1.06), apneic time (mean difference, 10.3 s higher with high-flow nasal cannula; 95% CI, 11.0 s lower to 31.7 s higher), PaO2 measured after preoxygenation (mean difference, 3.6 mm Hg higher; 95% CI, 3.5 mm Hg lower to 10.7 mm Hg higher), or PaO2 measured after intubation (mean difference, 27.0 mm Hg higher; 95% CI, 13.2 mm Hg lower to 67.2 mm Hg higher), when compared with conventional oxygen therapy. There was also no effect on postintubation PaCO2, ICU length of stay, or 28-day mortality. CONCLUSIONS: We found moderate-to-low certainty evidence that the use of high-flow nasal cannula likely has no effect on severe desaturation, serious complications, apneic time, oxygenation, ICU length of stay, or overall survival when used in the peri-intubation period when compared with conventional oxygen therapy.

Pulmonary Arterial Wedge Pressure at Rest and During Exercise in Healthy Adults: A Systematic Review and Meta-analysis.

BACKGROUND: The pulmonary arterial wedge pressure (PAWP) response to exercise may unmask latent heart failure with preserved ejection fraction. There remains a lack of consensus over threshold values for PAWP during exercise. A systematic review of studies examining PAWP by means of right heart catheterization at rest and during exercise in healthy individuals was performed. METHODS AND RESULTS: Relevant data derived from healthy volunteers were stratified by age (older than 40 years vs 40 years or younger) and sex. Three exercise intensities were predefined: light, moderate, and strenuous. Weighted means and weighted 95% confidence intervals (CIs) for the aggregate data were calculated. A total of 424 individuals from 32 unique studies were included, of which 19% (n = 82) were female. PAWP reached weighted mean and 95% CI values of 19 (17-21) and 17 (16-18) mm Hg at light and moderate exercise, respectively. The PAWP response to exercise was similar between men and women >40 years of age. However, exercise intensities were lower in women. CONCLUSIONS: PAWP increases during exercise, reaching up to 20 mm Hg in adults >40 years of age. Older women achieve PAWP values similar to those of older men, but at lower intensities. Findings support a threshold of at least 25 mm Hg as an absolute cutoff value for "normal" PAWP response to exercise in individuals >40 years old.