scholarly journals No evidence of clinical efficacy of hydroxychloroquine in patients hospitalised for COVID-19 infection and requiring oxygen: results of a study using routinely collected data to emulate a target trial

2020 ◽  
Author(s):  
Matthieu Mahévas ◽  
Viet-Thi Tran ◽  
Mathilde Roumier ◽  
Amélie Chabrol ◽  
Romain Paule ◽  
...  
Keyword(s):  
Distress Syndrome ◽  
Routine Care ◽  
Target Trial ◽  
Inverse Probability ◽  
Weighted Analysis ◽  
Routinely Collected Data ◽  
Initial Severity ◽  
Group 3 ◽  
Positive Results ◽  
Composite Primary Endpoint

AbstractBackgroundTreatments are urgently needed to prevent respiratory failure and deaths from coronavirus disease 2019 (COVID-19). Hydroxychloroquine (HCQ) has received worldwide attention because of positive results from small studies.MethodsWe used data collected from routine care of all adults in 4 French hospitals with documented SARS-CoV-2 pneumonia and requiring oxygen ≥ 2 L/min to emulate a target trial aimed at assessing the effectiveness of HCQ at 600 mg/day. The composite primary endpoint was transfer to intensive care unit (ICU) within 7 days from inclusion and/or death from any cause. Analyses were adjusted for confounding factors by inverse probability of treatment weighting.ResultsThis study included 181 patients with SARS-CoV-2 pneumonia; 84 received HCQ within 48 hours of admission (HCQ group) and 97 did not (no-HCQ group). Initial severity was well balanced between the groups. In the weighted analysis, 20.2% patients in the HCQ group were transferred to the ICU or died within 7 days vs 22.1% in the no-HCQ group (16 vs 21 events, relative risk [RR] 0.91, 95% CI 0.47–1.80). In the HCQ group, 2.8% of the patients died within 7 days vs 4.6% in the no-HCQ group (3 vs 4 events, RR 0.61, 95% CI 0.13–2.89), and 27.4% and 24.1%, respectively, developed acute respiratory distress syndrome within 7 days (24 vs 23 events, RR 1.14, 95% CI 0.65–2.00). Eight patients receiving HCQ (9.5%) experienced electrocardiogram modifications requiring HCQ discontinuation.InterpretationThese results do not support the use of HCQ in patients hospitalised for documented SARS-CoV-2-positive hypoxic pneumonia.

scholarly journals Alveolar compartmentalization of inflammatory and immune cell biomarkers in pneumonia-related ARDS

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Inès Bendib ◽  
Asma Beldi-Ferchiou ◽  
Frédéric Schlemmer ◽  
Mathieu Surenaud ◽  
Bernard Maitre ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Hospital Mortality ◽  
Distress Syndrome ◽  
Immune Cell ◽  
Routine Care ◽  
Clinical Endpoint ◽  
Blood Samples ◽  
Hla Dr ◽  
Serum Ratio ◽  
Immunocompetent Patients

Abstract Background Biomarkers of disease severity might help individualizing the management of patients with the acute respiratory distress syndrome (ARDS). Whether the alveolar compartmentalization of biomarkers has a clinical significance in patients with pneumonia-related ARDS is unknown. This study aimed at assessing the interrelation of ARDS/sepsis biomarkers in the alveolar and blood compartments and explored their association with clinical outcomes. Methods Immunocompetent patients with pneumonia-related ARDS admitted between 2014 and 2018 were included in a prospective monocentric study. Bronchoalveolar lavage (BAL) fluid and blood samples were obtained within 48 h of admission. Twenty-two biomarkers were quantified in BAL fluid and serum. HLA-DR+ monocytes and CD8+ PD-1+ lymphocytes were quantified using flow cytometry. The primary clinical endpoint of the study was hospital mortality. Patients undergoing a bronchoscopy as part of routine care were included as controls. Results Seventy ARDS patients were included. Hospital mortality was 21.4%. The BAL fluid-to-serum ratio of IL-8 was 20 times higher in ARDS patients than in controls (p < 0.0001). ARDS patients with shock had lower BAL fluid-to-serum ratio of IL-1Ra (p = 0.026), IL-6 (p = 0.002), IP-10/CXCL10 (p = 0.024) and IL-10 (p = 0.023) than others. The BAL fluid-to-serum ratio of IL-1Ra was more elevated in hospital survivors than decedents (p = 0.006), even after adjusting for SOFA and driving pressure (p = 0.036). There was no significant association between alveolar or alveolar/blood monocytic HLA-DR or CD8+ lymphocytes PD-1 expression and hospital mortality. Conclusions IL-8 was the most compartmentalized cytokine and lower BAL fluid-to-serum concentration ratios of IL-1Ra were associated with hospital mortality in patients with pneumonia-associated ARDS.

scholarly journals Statin Treatment and Clinical Outcomes of Heart Failure Among Africans: An Inverse Probability Treatment Weighted Analysis

2017 ◽  
Vol 6 (4) ◽  
Author(s):  
Kwadwo Osei Bonsu ◽  
Isaac Kofi Owusu ◽  
Kwame Ohene Buabeng ◽  
Daniel D. Reidpath ◽  
Amudha Kadirvelu
Keyword(s):  
Heart Failure ◽  
Clinical Outcomes ◽  
Statin Treatment ◽  
Inverse Probability ◽  
Weighted Analysis

scholarly journals Surveillance for Hepatocellular Carcinoma Reduces Mortality: an Inverse Probability of Treatment Weighted Analysis

2017 ◽  
Vol 16 (3) ◽  
pp. 421-429 ◽  
Author(s):  
Roongruedee Chaiteerakij ◽  
Piyanat Chattieng ◽  
Jonggi Choi ◽  
Nutcha Pinchareon ◽  
Kessirin Thanapirom ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Inverse Probability ◽  
Weighted Analysis

Twelve Years' Experience With Bronchopulmonary Dysplasia

PEDIATRICS ◽  
1977 ◽  
Vol 59 (6) ◽  
pp. 839-846 ◽  
Author(s):  
David K. Edwards ◽  
Wayne M. Dyer ◽  
William H. Northway
Keyword(s):  
Mechanical Ventilation ◽  
Retrospective Study ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Bronchopulmonary Dysplasia ◽  
Distress Syndrome ◽  
Stage Iv ◽  
Assisted Ventilation ◽  
Severity Of Disease ◽  
Initial Severity

A retrospective study of 299 successive infants who were ventilated for respiratory distress syndrome (RDS) showed that 62 (21%) developed radiographic stage IV bronchopulmonary dysplasia (BPD). The largest, most mature, and least ill infants tended to survive without developing BPD; the smallest, least mature, and most ill infants tended to die without developing BPD. The patients who developed BPD tended to be intermediate in terms of weight, maturity, and severity of disease; they required longer exposures to elevated oxygen and assisted ventilation than patients who did not develop BPD. The data suggest that in addition to varying individual susceptibility (primarily degree of immaturity and initial severity of disease), elevated oxygen is more important than mechanical ventilation in the pathogenesis of BPD.

scholarly journals Clinical outcomes of intravenous immunoglobulin therapy in COVID-19 related acute respiratory distress syndrome: a retrospective cohort study

2021 ◽  
Author(s):  
Husain S Ali ◽  
Moustafa S Elshafei ◽  
Mohamed O Saad ◽  
Hassan A Mitwally ◽  
Mohammad Al Wraidat ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Propensity Score ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Intravenous Immunoglobulin ◽  
Primary Outcome ◽  
Distress Syndrome ◽  
Ivig Therapy ◽  
Routine Care ◽  
Icu Mortality

Abstract Background: Immunomodulatory property of intravenous immunoglobulin (IVIG) has been used to counteract severe systemic inflammation in coronavirus disease 2019 (COVID-19). However, its use in acute respiratory distress syndrome (ARDS) due to COVID-19 pneumonia is not well established.Methods: In this retrospective study, we analyzed electronic health records of COVID-19 patients admitted to intensive care units (ICUs) at Hazm Mebaireek General Hospital, Qatar, between March 7, 2020, and September 9, 2020. Patients receiving invasive mechanical ventilation for moderate-to-severe ARDS were divided into two groups based on whether they received IVIG therapy. The primary outcome was all-cause ICU mortality. Secondary outcomes studied were ventilator-free days and ICU-free days at day-28 and incidence of acute kidney injury (AKI). Propensity score matching was used to adjust for confounders, and the primary outcome was compared using competing-risks survival analysis.Results: Among 590 patients included in the study, 400 received routine care, and 190 received IVIG therapy in addition to routine care. One hundred eighteen pairs were created after propensity score matching with no statistically significant differences between the groups. Overall ICU mortality in the study population was 27.1%, and in the matched cohort, it was 25.8%. Mortality was higher among IVIG-treated patients (36.4% vs. 15.3%; sHR 3.5; 95% CI 1.98- 6.19; P<0.001). Ventilator-free days and ICU-free days at day-28 were lower (P<0.001 for both), and the incidence of AKI was significantly higher (85.6% vs. 67.8%; P=0.001) in the IVIG group.Conclusion: IVIG therapy in mechanically ventilated patients with COVID-19 related moderate-to-severe ARDS was associated with higher ICU mortality. A randomized controlled study is required to confirm this observation further.

Abstract 11446: Systemic Administration of Mitochondria Alleviates 100% Oxygen-Induced Acute Respiratory Distress Syndrome in Rats

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Hon Kan Yip ◽  
Tzu -Hsien Tsai ◽  
Steve Leu ◽  
Sarah Chua
Keyword(s):  
Oxidative Stress ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Distress Syndrome ◽  
Ki 67 ◽  
Opposite Pattern ◽  
Protein Expressions ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background: We tested the hypothesis that mitochondria-replacement therapy ameliorated 100% oxygen-induced rat acute respiratory distress syndrome (ARDS). Methods and Results: Adult-Male SD rats (n=24) were equally categorized into group 1 (controls, room air inhalation), group 2 (ARDS: induced by inhalation of 100% oxygen for 48 hrs), and group 3 [ARDS + mitochondrial transfusion (1400 μg/each rat) from intra-venous administration 6 h after ARDS induction]. By 72 h after ARDS induction, the oxygen saturation (O 2 -Sat) was significantly lower in group 3 and more significantly lower in group 2 than in group 1, whereas pulmonary artery systolic-blood pressure showed a reversed pattern of O 2 -Sat among three groups (all p<0.001). H&E stain for lung crowded score showed an identical pattern of O 2 -Sat and number of alveolar sacs and lung weight exhibited an opposite pattern of O 2 -Sat among the three groups. The protein expressions of apoptotic (mitochondrial Bax, cleaved caspase 3 & PARP), fibrotic (Smad5, TGF-β), ROS (NOX-1, NOX-2, NOX-4), oxidative stress (oxidized protein), DNA- & mitochondrial-damaged (γ-H2AX, Ki-67; cytosolic cytochrome-c) and inflammatory (TNF-α, MMP-9, NF-κB) biomarkers, and IHC/IF microscopic findings of inflammatory (CD14+, CD68+), DNA-damaged (γ-H2AX+, Ki-67+) cells exhibited an opposite pattern, whereas the protein expressions of anti-apoptotic (Smad1/3, BMP-2) markers exhibited an identical pattern of O 2 -Sat among three groups (all p<0.001). The anti-oxidant (HO-2, NQO-1), mitochondrial-preserved (mitochondrial cytochrome-c) biomarkers, and cellular levels of anti-oxidants (HO-1, NQO-1, GR, GPx) were significantly higher in group 2 and more significantly higher in group 3 than in group 1 (all p<0.0001). Conclusions: Mitochondria therapy protects against 100% oxygen-induced ARDS. Key words: mitochondrial replacement, acute lung injury, inflammation, oxidative stress, DNA and mitochondrial damage

scholarly journals The Choice of Analytical Strategies in Inverse-Probability-of-Treatment–Weighted Analysis: A Simulation Study

2015 ◽  
Vol 182 (6) ◽  
pp. 520-527
Author(s):  
Shibing Yang ◽  
Juan Lu ◽  
Charles B. Eaton ◽  
Spencer Harpe ◽  
Kate L. Lapane
Keyword(s):  
Simulation Study ◽  
Inverse Probability ◽  
Weighted Analysis ◽  
Analytical Strategies

scholarly journals Assessing the external validity of the VALIDATE-SWEDEHEART trial

2021 ◽  
pp. 174077452110124
Author(s):  
Rebecca T Rylance ◽  
Philippe Wagner ◽  
Elmir Omerovic ◽  
Claes Held ◽  
Stefan James ◽  
...  
Keyword(s):  
Propensity Score ◽  
Confidence Interval ◽  
Cox Regression ◽  
Hazard Ratio ◽  
Inclusion Criteria ◽  
Cox Regression Analysis ◽  
Inverse Probability ◽  
Weighted Analysis ◽  
Score Difference ◽  
Inverse Probability Weighted

Aims: The VALIDATE-SWEDEHEART trial was a registry-based randomized trial comparing bivalirudin and heparin in patients with acute myocardial infarction undergoing percutaneous coronary intervention. It showed no differences in mortality at 30 or 180 days. This study examines how well the trial population results may generalize to the population of all screened patients with fulfilled inclusion criteria in regard to mortality at 30 and 180 days. Methods: The standardized difference in the mean propensity score for trial inclusion between trial population and the screened not-enrolled with fulfilled inclusion criteria was calculated as a metric of similarity. Propensity scores were then used in an inverse-probability weighted Cox regression analysis using the trial population only to estimate the difference in mortality as it would have been had the trial included all screened patients with fulfilled inclusion criteria. Patients who were very likely to be included were weighted down and those who had a very low probability of being in the trial were weighted up. Results: The propensity score difference was 0.61. There were no significant differences in mortality between bivalirudin and heparin in the inverse-probability weighted analysis (hazard ratio 1.11, 95% confidence interval (0.73, 1.68)) at 30 days or 180 days (hazard ratio 0.98, 95% confidence interval (0.70, 1.36)). Conclusion: The propensity score difference demonstrated that the screened not-enrolled with fulfilled inclusion criteria and trial population were not similar. The inverse-probability weighted analysis showed no significant differences in mortality. From this, we conclude that the VALIDATE results may be generalized to the screened not-enrolled with fulfilled inclusion criteria.

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