Potentially effective drugs for the treatment of COVID-19 or MIS-C in children: a systematic review

AbstractIntroductionThe purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C.MethodsWe searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C.ResultsA total of six cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that, after the treatment, 37.1% (95%CI, 0.0% to 74.5%) experienced adverse events, 5.9% (95%CI, 1.5% to 10.2%) died, 37.2% (95%CI, 0% to 76.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, the two included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone.ConclusionsOverall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines.

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Potentially Effective Drugs for the Treatment of COVID-19 or MIS-C in Children: A Systematic Review

10.21203/rs.3.rs-851844/v1 ◽

2021 ◽

Author(s):

Zijun Wang ◽

Siya Zhao ◽

Yuyi Tang ◽

Zhili Wang ◽

Qianling Shi ◽

...

Keyword(s):

Systematic Review ◽

Mechanical Ventilation ◽

Cohort Studies ◽

Children And Adolescents ◽

Meta Analysis ◽

Invasive Mechanical Ventilation ◽

Case Series ◽

Current Evidence ◽

Control Group ◽

Case Series Study

Abstract Introduction: The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. Methods: We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. Results: A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that, after the treatment, 54.7% (95%CI, 10.3% to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2% to 10.1%) died, 27.0% (95%CI, 0% to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone.Conclusions: Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines.

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Clinical, laboratory, and radiologic findings associated with mortality in COVID-19: A systematic review and meta-analysis

10.21203/rs.3.rs-39877/v1 ◽

2020 ◽

Author(s):

Hoo Jung Rhim ◽

Jin Hyun Park ◽

Yuna Lee ◽

Seung Chan Kwon ◽

Min Gyu Yu ◽

...

Keyword(s):

Systematic Review ◽

Troponin I ◽

Clinical Laboratory ◽

Meta Analysis ◽

Invasive Mechanical Ventilation ◽

Case Series ◽

Case Control ◽

Outcome Analysis ◽

Cross Sectional ◽

Case Series Study

Abstract Although there has been a surge in reports on coronavirus disease 2019 (COVID-19), the clinical signs and findings associated with fatal outcomes have rarely been studied. This systematic review and meta-analysis aimed to investigate the clinical, laboratory, and radiologic features associated with mortality in COVID-19. A comprehensive search was performed using PubMed, Embase, Web of Science, and other databases including government sources, for articles and reports published until May 1, 2020. We extracted the number of events (mortality and non-mortality) from case series and case-control and cross-sectional studies. Hazard ratios (HR) of each finding were extracted from studies with time-to-outcome analysis. In total, 23 studies met the inclusion criteria. Of them, 18 studies were case-control, cross-sectional, and case series study. Whereas, only 5 studies included time-to-outcome analysis. Male sex, age over 80 years, dyspnea, cardiovascular disease, chronic kidney disease, increased troponin I level, acute respiratory distress syndrome, acute kidney injury, and need of invasive mechanical ventilation were significantly associated with mortality. The identification of patients at higher risk of mortality has an utmost importance to achieve better treatment outcomes. The findings from our study may aid the prioritization in times of severe shortages of medical resources. Further studies analyzing diverse demographic and geographic populations are needed to generalize the findings from this study.

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Mortality and Clinical Interventions in Critically ill Patient With Coronavirus Disease 2019: A Systematic Review and Meta-Analysis

Frontiers in Medicine ◽

10.3389/fmed.2021.635560 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zhicheng Qian ◽

Shuya Lu ◽

Xufei Luo ◽

Yaolong Chen ◽

Ling Liu

Keyword(s):

Systematic Review ◽

Cohort Studies ◽

Critically Ill ◽

Critically Ill Patients ◽

Meta Analysis ◽

Invasive Mechanical Ventilation ◽

Case Series ◽

Cochrane Library ◽

Apache Ii Score ◽

Clinical Interventions

Objective: The aims of this systematic review and meta-analysis were to summarize the current existing evidence on the outcome of critically ill patients with COVID-19 as well as to evaluate the effectiveness of clinical interventions.Data Sources: We searched MEDLINE, the Cochrane library, Web of Science, the China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang Data from their inception to May 15, 2021. The search strings consisted of various search terms related to the concepts of mortality of critically ill patients and clinical interventions.Study Selection: After eliminating duplicates, two reviewers independently screened all titles and abstracts first, and then the full texts of potentially relevant articles were reviewed to identify cohort studies and case series that focus on the mortality of critically ill patients and clinical interventions.Main Outcomes and Measures: The primary outcome was the mortality of critically ill patients with COVID-19. The secondary outcomes included all sorts of supportive care.Results: There were 27 cohort studies and six case series involving 42,219 participants that met our inclusion criteria. All-cause mortality in the intensive care unit (ICU) was 35% and mortality in hospital was 32% in critically ill patients with COVID-19 for the year 2020, with very high between-study heterogeneity (I2 = 97%; p < 0.01). In a subgroup analysis, the mortality during ICU hospitalization in China was 39%, in Asia—except for China—it was 48%, in Europe it was 34%, in America it was 15%, and in the Middle East it was 39%. Non-surviving patients who had an older age [−8.10, 95% CI (−9.31 to −6.90)], a higher APACHE II score [−4.90, 95% CI (−6.54 to −3.27)], a higher SOFA score [−2.27, 95% CI (−2.95 to −1.59)], and a lower PaO2/FiO2 ratio [34.77, 95% CI (14.68 to 54.85)] than those who survived. Among clinical interventions, invasive mechanical ventilation [risk ratio (RR) 0.49, 95% CI (0.39–0.61)], kidney replacement therapy [RR 0.34, 95% CI (0.26–0.43)], and vasopressor [RR 0.54, 95% CI (0.34–0.88)] were used more in surviving patients.Conclusions: Mortality was high in critically ill patients with COVID-19 based on low-quality evidence and regional difference that existed. The early identification of critical characteristics and the use of support care help to indicate the outcome of critically ill patients.

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Sofosbuvir with daclatasvir and the outcomes of patients with COVID-19: a systematic review and meta-analysis with GRADE assessment

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2021-140287 ◽

2021 ◽

pp. postgradmedj-2021-140287

Author(s):

Ahmad Fariz Malvi Zamzam Zein ◽

Catur Setiya Sulistiyana ◽

Wilson Matthew Raffaello ◽

Arief Wibowo ◽

Raymond Pranata

Keyword(s):

Systematic Review ◽

Absolute Risk ◽

Controlled Trial ◽

Meta Analysis ◽

Invasive Mechanical Ventilation ◽

Intervention Group ◽

Control Group ◽

Reduce Mortality Rate ◽

Icu Admission ◽

Clinical Recovery

PurposeThis systematic review and meta-analysis aimed to evaluate the effect of sofosbuvir/daclatasvir (SOF/DCV) on mortality, the need for intensive care unit (ICU) admission or invasive mechanical ventilation (IMV) and clinical recovery in patients with COVID-19.MethodsWe performed a systematic literature search through the PubMed, Scopus and Embase from the inception of databases until 6 April 2021. The intervention group was SOF/DCV, and the control group was standard of care. The primary outcome was mortality, defined as clinically validated death. The secondary outcomes were (1) the need for ICU admission or IMV and (2) clinical recovery. The pooled effect estimates were reported as risk ratios (RRs).ResultsThere were four studies with a total of 231 patients in this meta-analysis. Three studies were randomised controlled trial, and one study was non-randomised. SOF/DCV was associated with lower mortality (RR: 0.31 (0.12, 0.78); p=0.013; I2: 0%) and reduced need for ICU admission or IMV (RR: 0.35 (0.18, 0.69); p=0.002; I2: 0%). Clinical recovery was achieved more frequently in the SOF/DCV (RR: 1.20 (1.04, 1.37); p=0.011; I2: 21.1%). There was a moderate certainty of evidence for mortality and need for ICU/IMV outcome, and a low certainty of evidence for clinical recovery. The absolute risk reductions were 140 fewer per 1000 for mortality and 186 fewer per 1000 for the need for ICU/IMV. The increase in clinical recovery was 146 more per 1000.ConclusionSOF/DCV may reduce mortality rate and need for ICU/IMV in patients with COVID-19 while increasing the chance for clinical recovery.Protocol registrationPROSPERO: CRD42021247510.

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Are Clinical Outcomes Associated With Medication Regimen Complexity? A Systematic Review and Meta-analysis

Annals of Pharmacotherapy ◽

10.1177/1060028019886846 ◽

2019 ◽

Vol 54 (4) ◽

pp. 301-313 ◽

Cited By ~ 4

Author(s):

Vanessa Alves-Conceição ◽

Kérilin Stancine Santos Rocha ◽

Fernanda Vilanova Nascimento Silva ◽

Rafaella de Oliveira Santos Silva ◽

Sabrina Cerqueira-Santos ◽

...

Keyword(s):

Systematic Review ◽

Cohort Studies ◽

Clinical Outcomes ◽

Meta Analysis ◽

Case Control ◽

Current Evidence ◽

Medication Regimen ◽

Medication Regimen Complexity ◽

Complexity Index ◽

Regimen Complexity

Background: Current evidence of the influence of the medication regimen complexity (MRC) on the patients’ clinical outcomes are not conclusive. Objective: To systematically and analytically assess the association between MRC measured by the Medication Regimen Complexity Index (MRCI) and clinical outcomes. Methods: A search was carried out in the databases Cochrane Library, LILACS, PubMed, Scopus, EMBASE, Open Thesis, and Web of Science to identify studies evaluating the association between MRC and clinical outcomes that were published from January 1, 2004, to April 2, 2018. The search terms included outcome assessment, drug therapy, and medication regimen complexity index and their synonyms in different combinations for case-control and cohort studies that used the MRCI to measure MRC and related the MRCI with clinical outcomes. Odds ratios (ORs), hazard ratios (HRs), and mean differences (WMDs) were calculated, and heterogeneity was assessed using the I2 test. Results: A total of 12 studies met the eligibility criteria. The meta-analysis showed that MRC is associated with the following clinical outcomes: hospitalization (HR = 1.20; 95% CI = 1.14 to 1.27; I2 = 0%) in cohort studies, hospital readmissions (WMD = 7.72; 95% CI = 1.19 to 14.25; I2 = 84%) in case-control studies, and medication nonadherence (adjusted OR = 1.05; 95% CI = 1.02 to 1.07; I2 = 0%) in cohort studies. Conclusion and Relevance: This systematic review and meta-analysis gathered relevant scientific evidence and quantified the combined estimates to show the association of MRC with clinical outcomes: hospitalization, hospital readmission, and medication adherence.

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Platelet Concentrate Treatments for Temporomandibular Disorders: A Systematic Review and Meta-analysis

JDR Clinical & Translational Research ◽

10.1177/2380084420927326 ◽

2020 ◽

pp. 238008442092732

Author(s):

F.S. Al-Hamed ◽

A. Hijazi ◽

Q. Gao ◽

Z. Badran ◽

F. Tamimi

Keyword(s):

Systematic Review ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Mouth Opening ◽

Case Series ◽

Platelet Concentrate ◽

Current Evidence ◽

Disc Displacement ◽

Temporomandibular Joint Osteoarthritis ◽

Vas Scores

Objectives: This systematic review compared platelet concentrates (PCs) versus hyaluronic acid (HA) or saline/Ringer’s solution injections as treatments of temporomandibular osteoarthritis and disc displacement in terms of pain and maximum mouth opening (MMO). Methods: PubMed, Cochrane, and Scopus were searched up to March 6, 2020. Inclusion criteria were randomized clinical trials (RCTs). Exclusion criteria were case series, observational studies, animal studies, and reviews. The Effective Public Health Practice Project (EPHPP) quality assessment tool was used to assess the risk of bias in the included studies. The weighted mean difference was used to compare the results. Results: Nine RCTs were included with a total of 407 patients. The numbers of joints treated were 262, 112, and 112 in the PC, HA, and saline groups, respectively. The quality of studies was rated as strong in 4 studies, moderate in 4 studies, and weak in 1 study. The meta-analysis revealed that PCs decreased pain visual analogue scale (VAS) scores compared to HA by an average of −1.11 (CI, −1.62 to −0.60; P < 0.0001) and −0.57 (CI, −1.55 to 0.41; P = 0.26) at 3 and 12 mo follow-up respectively. Also, the average decrease in pain scores with PC compared to saline was −1.33 (CI, −2.61 to −0.06; P = 0.04), −2.07 (CI, −3.46 to −0.69; P = 0.003), and −2.71 (CI, −4.69 to −0.72; P = 0.008) at 3, 6, and 12 mo, respectively. Regarding MMO measurements, PC was comparable to HA, but it was significantly better than saline after 3 and 6 mo [2.9 mm (CI,1.47 to 4.3; P < 0.0001), and 1.69 mm (CI, 0.13 to 3.25; P = 0.03) respectively]. Conclusion: PC reduces pain VAS scores compared to HA during the first 3 m after treatment, and when compared to saline, it reduces pain and increases MMO for longer durations. However, due to differences between groups regarding PC preparation protocols and study heterogeneity, further standardized RCTs are required. Knowledge Transfer Statement: This study provides researchers and clinicians with quantitative and qualitative analyses of the current evidence regarding the clinical outcomes of platelet concentrate injections in the treatment of temporomandibular joint osteoarthritis and disc displacement in terms of pain control and maximum mouth opening.

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Hyaluronic acid for post sinus surgery care: systematic review and meta-analysis

The Journal of Laryngology & Otology ◽

10.1017/s0022215116009269 ◽

2017 ◽

Vol 131 (S1) ◽

pp. S2-S11 ◽

Cited By ~ 8

Author(s):

E Fong ◽

M Garcia ◽

C M Woods ◽

E Ooi

Keyword(s):

Systematic Review ◽

Hyaluronic Acid ◽

Endoscopic Sinus Surgery ◽

Meta Analysis ◽

Adhesion Formation ◽

Sinus Surgery ◽

Current Evidence ◽

Secondary Outcome ◽

Control Group ◽

Patient Reported

AbstractBackground:Wound healing after endoscopic sinus surgery may result in adhesion formation. Hyaluronic acid may prevent synechiae development. A systematic review was performed to evaluate the current evidence on the clinical efficacy of hyaluronic acid applied to the nasal cavity after sinus surgery.Methods:Studies using hyaluronic acid as an adjunct treatment following endoscopic sinus surgery for chronic rhinosinusitis were identified. The primary outcome was adhesion formation rates. A meta-analysis was performed on adhesion event frequency. Secondary outcome measures included other endoscopic findings and patient-reported outcomes.Results:Thirteen studies (501 patients) met the selection criteria. A meta-analysis of adhesion formation frequency on endoscopy demonstrated a lower risk ratio in the hyaluronic acid intervention group (42 out of 283 cases) compared to the control group (81 out of 282) of 0.52 (95 per cent confidence interval = 0.37–0.72). Hyaluronic acid use was not associated with any significant adverse events.Conclusion:Hyaluronic acid appears to be clinically safe and well tolerated, and may be useful in the early stages after sinus surgery to limit adhesion rate. Further research, including larger randomised controlled trials, is required to evaluate patient- and clinician-reported outcomes of hyaluronic acid post sinus surgery.

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Lumbar Fusion for Degenerative Disease: A Systematic Review and Meta-Analysis

Neurosurgery ◽

10.1093/neuros/nyw162 ◽

2017 ◽

Vol 80 (5) ◽

pp. 701-715 ◽

Cited By ~ 31

Author(s):

Daniel Yavin ◽

Steven Casha ◽

Samuel Wiebe ◽

Thomas E Feasby ◽

Callie Clark ◽

...

Keyword(s):

Systematic Review ◽

Cohort Studies ◽

Spinal Stenosis ◽

Lumbar Fusion ◽

Meta Analysis ◽

Current Evidence ◽

Controlled Trials ◽

Cochrane Central Register ◽

Safety And Efficacy ◽

Relative Safety

Abstract BACKGROUND: Due to uncertain evidence, lumbar fusion for degenerative indications is associated with the greatest measured practice variation of any surgical procedure. OBJECTIVE: To summarize the current evidence on the comparative safety and efficacy of lumbar fusion, decompression-alone, or nonoperative care for degenerative indications. METHODS: A systematic review was conducted using PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (up to June 30, 2016). Comparative studies reporting validated measures of safety or efficacy were included. Treatment effects were calculated through DerSimonian and Laird random effects models. RESULTS: The literature search yielded 65 studies (19 randomized controlled trials, 16 prospective cohort studies, 15 retrospective cohort studies, and 15 registries) enrolling a total of 302 620 patients. Disability, pain, and patient satisfaction following fusion, decompression-alone, or nonoperative care were dependent on surgical indications and study methodology. Relative to decompression-alone, the risk of reoperation following fusion was increased for spinal stenosis (relative risk [RR] 1.17, 95% confidence interval [CI] 1.06-1.28) and decreased for spondylolisthesis (RR 0.75, 95% CI 0.68-0.83). Among patients with spinal stenosis, complications were more frequent following fusion (RR 1.87, 95% CI 1.18-2.96). Mortality was not significantly associated with any treatment modality. CONCLUSION: Positive clinical change was greatest in patients undergoing fusion for spondylolisthesis while complications and the risk of reoperation limited the benefit of fusion for spinal stenosis. The relative safety and efficacy of fusion for chronic low back pain suggests careful patient selection is required (PROSPERO International Prospective Register of Systematic Reviews number, CRD42015020153).

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Oral hormone pregnancy tests and the risks of congenital malformations: a systematic review and meta-analysis

F1000Research ◽

10.12688/f1000research.16758.2 ◽

2019 ◽

Vol 7 ◽

pp. 1725 ◽

Cited By ~ 1

Author(s):

Carl Heneghan ◽

Jeffrey K. Aronson ◽

Elizabeth Spencer ◽

Bennett Holman ◽

Kamal R. Mahtani ◽

...

Keyword(s):

Systematic Review ◽

Cohort Studies ◽

Congenital Malformations ◽

Meta Analysis ◽

Case Control ◽

Control Group ◽

Case Control Studies ◽

Renal Anomalies ◽

Congenital Heart Malformations ◽

Increased Risk

Background: Oral hormone pregnancy tests (HPTs), such as Primodos, containing ethinylestradiol and high doses of norethisterone, were given to over a million women from 1958 to 1978, when Primodos was withdrawn from the market because of concerns about possible teratogenicity. We aimed to study the association between maternal exposure to oral HPTs and congenital malformations. Methods: We have performed a systematic review and meta-analysis of case-control and cohort studies that included data from pregnant women and were exposed to oral HPTs within the estimated first three months of pregnancy, if compared with a relevant control group. We used random-effects meta-analysis and assessed the quality of each study using the Newcastle–Ottawa Scale for non-randomized studies. Results: We found 16 case control studies and 10 prospective cohort studies, together including 71 330 women, of whom 4,209 were exposed to HPTs. Exposure to oral HPTs was associated with a 40% increased risk of all congenital malformations: pooled odds ratio (OR) = 1.40 (95% CI 1.18 to 1.66; P<0.0001; I2 = 0%). Exposure to HPTs was associated with an increased risk of congenital heart malformations: pooled OR = 1.89 (95% CI 1.32 to 2.72; P = 0.0006; I2=0%); nervous system malformations OR = 2.98 (95% CI 1.32 to 6.76; P = 0.0109 I2 = 78%); gastrointestinal malformations, OR = 4.50 (95% CI 0.63 to 32.20; P = 0.13; I2 = 54%); musculoskeletal malformations, OR = 2.24 (95% CI 1.23 to 4.08; P= 0.009; I2 = 0%); the VACTERL syndrome (Vertebral defects, Anal atresia, Cardiovascular anomalies, Tracheoesophageal fistula, Esophageal atresia, Renal anomalies, and Limb defects), OR = 7.47 (95% CI 2.92 to 19.07; P < 0.0001; I2 = 0%). Conclusions: This systematic review and meta-analysis shows that use of oral HPTs in pregnancy is associated with increased risks of congenital malformations.

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Steroid therapy for COVID-19: A systematic review and meta-analysis of randomized controlled trials

Monaldi Archives for Chest Disease ◽

10.4081/monaldi.2021.1716 ◽

2021 ◽

Author(s):

Tarun Krishna Boppana ◽

Saurabh Mittal ◽

Karan Madan ◽

Anant Mohan ◽

Vijay Hadda ◽

...

Keyword(s):

Systematic Review ◽

Mechanical Ventilation ◽

Randomized Controlled Trials ◽

Steroid Therapy ◽

Meta Analysis ◽

Risk Of Bias ◽

Treatment Modalities ◽

Control Group ◽

Controlled Trials ◽

Randomized Controlled

There is an urgent need for effective treatment modalities for coronavirus disease 2019 (COVID-19). Data for the use of steroids in COVID-19 is emerging. We conducted this systematic review and meta-analysis to estimate the effectiveness of steroid administration in mortality reduction due to COVID-19 compared to the control group. A systematic search of the Pubmed and Embase databases was performed to extract randomized controlled trials (RCTs) regarding the use of steroid therapy for COVID-19. An overall and subgroup (based upon the type of steroid) pooled mortality analysis was performed, and odds ratios were reported. Cochrane risk of bias assessment tool was used to assess the risk of bias. Heterogeneity was assessed using the I2 statistic. Six RCTs, including 7707 patients, were selected for review. Three trials reported 28-day mortality, and two trials reported 21-day mortality, and one trial reported in-hospital mortality. There were 730 deaths among 2837 participants in the steroid group while 1342 deaths among 4870 patients randomized to the control group (Odds ratio 0.76, 95% confidence interval 0.58-1.00, p=0.05). The effect was significant in patients on oxygen or mechanical ventilation. There was no difference in the various preparations and doses of the steroids. There was heterogeneity among the trials as the I2 value was 53%, with a p-value of 0.06. There was no indication of increased serious adverse events. This meta-analysis of RCTs demonstrated that the use of systemic corticosteroids is associated with a reduction in all-cause mortality in patients with COVID-19 on oxygen or mechanical ventilation.

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