scholarly journals Observational Study of Haloperidol in Hospitalized Patients with Covid-19

2020 ◽  
Author(s):  
Nicolas HOERTEL ◽  
Marina SANCHEZ RICO ◽  
Raphael VERNET ◽  
Anne-Sophie JANNOT ◽  
Antoine NEURAZ ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Observational Study ◽  
Primary Endpoint ◽  
Cox Regression ◽  
Adult Patients ◽  
Secondary Endpoint ◽  
Sensitivity Analyses ◽  
University Hospitals ◽  
Discharge Home

Background: Haloperidol, a widely used antipsychotic, has been suggested as potential effective treatment for Covid-19 on the grounds of its in-vitro antiviral effects against SARS-CoV-2. Methods: We examined the association between haloperidol use and respiratory failure at AP-HP Greater Paris University hospitals. Data were obtained regarding all adult patients hospitalized with Covid-19 since the beginning of the epidemic. Study baseline was defined as the date of hospital admission. The primary endpoint was a composite of intubation or death and the secondary endpoint was discharge home among survivors in time-to-event analyses. We compared outcomes between patients who were exposed to haloperidol and those who were not, using a multivariable Cox regression model with inverse probability weighting according to the propensity score. Results: Of the 13,279 hospitalized adult patients with positive Covid-19 RT-PCR test, 667 patients (5.0%) were excluded because of missing data. Of the remaining 12,612 patients, 104 (0.8%) were exposed to haloperidol. Over a mean follow-up of 20.8 days, the primary endpoint of respiratory failure respectively occurred in 27 patients (26.0%) exposed to haloperidol and 1,700 patients (13.6%) who were not. Among survivors, the secondary endpoint of discharge home occurred in 26 patients (32.1%) who received haloperidol and 6,110 patients (55.3%) who did not. In the main analysis, there were no significant associations between haloperidol use and the primary (HR, 1.09; 95% CI, 0.60 to 1.97, p=0.772) and secondary (HR, 0.88; 95% CI, 0.50 to 1.53, p=0.643) endpoints. Results were similar in multiple sensitivity analyses. Conclusion: In this observational study involving patients with Covid-19 who had been admitted to the hospital, haloperidol use was not associated with risk of intubation or death, or with time to hospital discharge home. These results suggest that haloperidol is unlikely to have a clinical efficacy for Covid-19.

scholarly journals Observational study of haloperidol in hospitalized patients with COVID-19

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247122 ◽  
Author(s):  
Nicolas Hoertel ◽  
Marina Sánchez-Rico ◽  
Raphaël Vernet ◽  
Anne-Sophie Jannot ◽  
Antoine Neuraz ◽  
...  
Keyword(s):  
Observational Study ◽  
Primary Endpoint ◽  
Regression Models ◽  
Cox Regression ◽  
Adult Patients ◽  
Secondary Endpoint ◽  
Sensitivity Analyses ◽  
University Hospitals ◽  
Discharge Home

Background Haloperidol, a widely used antipsychotic, has been suggested as potentially useful for patients with COVID-19 on the grounds of its in-vitro antiviral effects against SARS-CoV-2, possibly through sigma-1 receptor antagonist effect. Methods We examined the associations of haloperidol use with intubation or death and time to discharge home among adult patients hospitalized for COVID-19 at Assistance Publique-Hôpitaux de Paris (AP-HP) Greater Paris University hospitals. Study baseline was defined as the date of hospital admission. The primary endpoint was a composite of intubation or death and the secondary endpoint was discharge home among survivors in time-to-event analyses. In the primary analyses, we compared these two outcomes between patients receiving and not receiving haloperidol using univariate Cox regression models in matched analytic samples based on patient characteristics and other psychotropic medications. Sensitivity analyses included propensity score analyses with inverse probability weighting and multivariable Cox regression models. Results Of 15,121 adult inpatients with a positive COVID-19 PT-PCR test, 39 patients (0.03%) received haloperidol within the first 48 hours of admission. Over a mean follow-up of 13.8 days (SD = 17.9), 2,024 patients (13.4%) had a primary end-point event and 10,179 patients (77.6%) were discharged home at the time of study end on May 1st. The primary endpoint occurred in 9 patients (23.1%) who received haloperidol and 2,015 patients (13.4%) who did not. The secondary endpoint of discharge home occurred in 16 patients (61.5%) who received haloperidol and 9,907 patients (85.8%) who did not. There were no significant associations between haloperidol use and the primary (HR, 0.80; 95% CI, 0.39 to 1.62, p = 0.531) and secondary (HR, 1.30; 95% CI, 0.74 to 2.28, p = 0.355) endpoints. Results were similar in multiple sensitivity analyses. Conclusion Findings from this multicenter observational study suggest that haloperidol use prescribed at a mean dose of 4.5 mg per day (SD = 5.2) for a mean duration of 8.4 days (SD = 7.2) may not be associated with risk of intubation or death, or with time to discharge home, among adult patients hospitalized for COVID-19.

scholarly journals Association between Functional Inhibitors of Acid Sphingomyelinase and Reduced Risk of Intubation or Death in Individuals Hospitalized for Severe COVID-19: results from an observational multicenter study

2021 ◽  
Author(s):  
Nicolas Hoertel ◽  
Marina Sánchez-Rico ◽  
Erich Gulbins ◽  
Johannes Kornhuber ◽  
Alexander Carpinteiro ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Randomized Clinical Trials ◽  
Cox Regression ◽  
Acid Sphingomyelinase ◽  
Sensitivity Analyses ◽  
University Hospitals ◽  
Primary Analysis ◽  
Double Blind ◽  
Treatment Target

ABSTRACTSeveral medications commonly used for a number of medical conditions share a property of functional inhibition of acid sphingomyelinase (ASM), or FIASMA. Preclinical and clinical evidence suggest that the (ASM)/ceramide system may be central to SARS-CoV-2 infection. We examined the potential usefulness of FIASMA use among patients hospitalized for severe COVID-19 in an observational multicenter retrospective study conducted at Greater Paris University hospitals. Of 2,846 adult patients hospitalized for severe COVID-19, 277 (9.7%) were taking a FIASMA medication at the time of their hospital admission. The primary endpoint was a composite of intubation and/or death. We compared this endpoint between patients taking vs. not taking a FIASMA medication in time-to-event analyses adjusted for sociodemographic characteristics and medical comorbidities. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Over a mean follow-up of 9.2 days (SD=12.5), the primary endpoint occurred in 104 patients (37.5%) who were taking a FIASMA medication, and 1,060 patients (41.4%) who were not. Taking a FIASMA medication was associated with reduced likelihood of intubation or death in both crude (HR=0.71; 95%CI=0.58-0.87; p<0.001) and the primary IPW (HR=0.58; 95%CI=0.46-0.72; p<0.001) analyses. This association remained significant in multiple sensitivity analyses and was not specific to one FIASMA class or medication. These results show the potential importance of the ASM/ceramide system as a treatment target in COVID-19. Double-blind controlled randomized clinical trials of these medications for COVID-19 are needed.

Abstract 3095: Prognostic Significance Of Post-revascularisation Irreversible Myocardial Injury Detected By Cardiovascular Magnetic Resonance Imaging

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Joseph B Selvanayagam ◽  
Kazem Rahimi ◽  
Adrian Banning ◽  
Adrian S Cheng ◽  
Tammy J Pegg ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Myocardial Injury ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Total Mortality ◽  
Secondary Endpoint ◽  
Consecutive Series ◽  
Post Intervention ◽  
Cox Regression Analysis

Background The prognostic significance of revascularization procedure related myocardial injury is uncertain. Delayed enhancement CMR (DE-CMR) has been shown to reliably identify areas of irreversible myocardial injury. We evaluated the prognostic significance of procedure related myocardial injury in a consecutive series of patients undergoing high risk PCI or CABG. Methods/Results 152 patients underwent DE-CMR pre and 1– 6 days post elective PCI or CABG. Primary endpoint was defined as total mortality, non-fatal MI, ventricular arrhythmia terminated by ICD (VA), and unstable angina or heart failure requiring hospitalization. Secondary endpoint was the composite of total mortality, non-fatal MI and VA. During a median follow-up of 2.9 years, 27 patients (18%) reached the primary endpoint and 12 patients (8%) the secondary endpoint. 49 patients (32%) had evidence of new myocardial hyperenhancement (HE) with a median mass of 5.0g (IQR 4.8 –7.1). In a univariate analysis, age, LV EF post intervention, and presence of new HE were predictive of the primary outcome. Elevated troponin (at 24 h) showed a trend towards poorer outcome. In a multivariate Cox regression analysis only age and presence of new HE (HR 2.7, 95% CI 1.1, 5.8) remained independently correlated with occurrence of the primary endpoint. New myocardial HE was the single independent predictor of the composite secondary endpoint (HR 4.2 95% CI 1.2, 16.1). Conclusion Even small amounts of procedure-related myocardial injury are associated with poorer medium term clinical outcomes. CMR identified myocardial injury may be a stronger prognostic marker than cardiac troponin in the setting of coronary revascularisation.

Darbepoetin Alfa (DA) - Pattern of Use and Outcomes in Adult Patients with Non-Myeloid Malignancies and Chemotherapy-Induced Anemia: A French Observational Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3347-3347
Author(s):  
Arnaud P.M. Pigneux ◽  
Isabelle L. Ray-Coquard ◽  
Philippe J.M. Dalivoust ◽  
Gaelle Chenuc Biostat ◽  
Anne M. Bastie
Keyword(s):  
Observational Study ◽  
Daily Practice ◽  
Public Hospitals ◽  
Adult Patients ◽  
University Hospitals ◽  
Private Hospitals ◽  
Myeloid Malignancies ◽  
Nccn Guidelines ◽  
Tumor Types

Abstract INTRODUCTION: DA is widely used to treat anemia in patients undergoing chemotherapy (CT) for non-myeloid malignancies. Three years after the commercialization of DA in France, a study of the pattern of DA use in daily practice was conducted in this population. METHODS: A nationwide, retrospective observational study of DA use and patient outcomes was conducted in 239 centers between September 2004 and May 2005. Adult patients with non-myeloid malignancies, who had received DA for CT-induced anemia for at least three 3- or 4-weekly or at least five 2-weekly CT cycles (min. 9–12 weeks) were studied. Response was defined as hemoglobin (Hb) ≥ 12g/dL or a Hb increase of at least 2 g/dL from baseline to week 6/8. In addition, the proportion of patients achieving a Hb level of ≥ 11 g/dL as suggested by NCCN guidelines was assessed. Hb levels were evaluated at baseline, week 3 and week 6 (CT cycles of 21 days) or week 4 and week 8 (CT cycles of 15 or 28 days). RESULTS: Of 2017 patients recruited, 1865 (92.5%) were evaluable at week 6 or 8. Analyses were conducted on the evaluable patient population. A total of 51% were female and the mean age was 62.5 years [range: 18–96 years]. The most common tumor types were non-myeloid hematological malignancies (25%), lung cancer (21%), breast cancer (16%) and gastrointestinal tumors (14%). A total of 37% of centers were University hospitals, 30% public hospitals, 21% private hospitals and 11% specialized cancer centers. Baseline mean Hb level was 10g/dL [range 5–16.6 g/dL]. A total of 843 patients at week 0 (45.4%) had a Hb <10g/dL. The first DA dose was administered to 40% of patients at the first CT cycle and to 60% of patients at subsequent cycles. At week 6/8, 707 patients (38%) had a Hb ≥ 12 g/dL and 1096 patients (58.8%) had a Hb ≥ 11 g/dL. During the study period, between week 0 and week 6/8, 272 pts (15.9%) received RBC transfusions. CONCLUSIONS: Despite the very short follow-up of 6/8 weeks, almost 40% of the patients achieved a Hb ≥ 12 g/dL. More importantly, the proportion of patients reaching a Hb level within the range recommended by NCCN guidelines (≥ 11 g/dL) at this short follow-up was around 60%, which is comparable to results published in other trials of DA.

scholarly journals Observational Study of Chlorpromazine in Hospitalized Patients with Covid-19

2020 ◽  
Author(s):  
Nicolas Hoertel ◽  
Marina Sanchez Rico ◽  
Raphael Vernet ◽  
Anne-Sophie Jannot ◽  
Antoine Neuraz ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Cox Regression ◽  
Cox Model ◽  
Event Analysis ◽  
Time To Event ◽  
Rt Pcr ◽  
University Hospitals ◽  
Inverse Probability ◽  
Antiviral Effects

On the grounds of its anti-inflammatory and potential antiviral effects, chlorpromazine has been suggested to be effective treatment for Covid-19. We examined the association between chlorpromazine use and respiratory failure among all hospitalized adults with Covid-19 at the 39 Greater Paris University hospitals since the beginning of the epidemic. Study baseline was defined as the date of hospital admission. The primary endpoint was a composite of intubation or death in a time-to-event analysis adjusting for numerous potential confounders. We used a multivariable Cox model with inverse probability weighting according to the propensity score. Of the 12,217 adult inpatients with a positive Covid-19 RT-PCR test included in the analyses, 57 (0.47%) received chlorpromazine. Over a mean follow-up of 20.8 days, the primary endpoint occurred in 29 patients (50.9%) exposed to chlorpromazine and 1,899 patients (15.6%) who were not. In the main analysis, there was a positive significant association between chlorpromazine use and the outcome (HR, 1.67; 95% CI, 1.09 to 2.56, p=0.019), while a Cox regression in a matched analytic sample yielded non-significant association (1.38; 95% CI, 0.91 to 2.09, p=0.123). These findings suggest that chlorpromazine is unlikely to have a clinical efficacy for Covid-19.

scholarly journals Association between benzodiazepine receptor agonist use and increased mortality among patients hospitalized for COVID-19: results from an observational study

2021 ◽  
Author(s):  
N. Hoertel ◽  
M. Sánchez-Rico ◽  
E. Gulbins ◽  
J. Kornhuber ◽  
R. Vernet ◽  
...  
Keyword(s):  
Hospital Admission ◽  
Primary Endpoint ◽  
Receptor Agonist ◽  
Cox Regression ◽  
Benzodiazepine Receptor ◽  
Sensitivity Analyses ◽  
Primary Analysis ◽  
Dependent Relationship ◽  
Benzodiazepine Receptor Agonist ◽  
Dose Dependent

ABSTRACTObjectiveTo examine the association between benzodiazepine receptor agonist (BZRA) use and mortality in patients hospitalized for COVID-19.MethodsWe conducted an observational multicenter retrospective cohort study at AP-HP Greater Paris University hospitals. The sample involved 14,381 adult patients hospitalized for COVID-19. 686 (4.8%) inpatients received a BZRA within at the time of hospital admission at a mean daily diazepam-equivalent dose of 19.7 mg (SD=25.4). The study baseline was the date of hospital admission and the primary endpoint was death. We compared this endpoint between patients who received BZRAs and those who did not in time-to-event analyses adjusted for patient characteristics (such as age, sex, obesity and comorbidity) and other medications. The primary analysis was a Cox regression model with inverse probability weighting (IPW).ResultsOver a mean follow-up of 14.5 days (SD=18.1), the primary endpoint occurred in 186 patients (27.1%) who received a BZRA and in 1,134 patients (8.3%) who did not. There was a significant association between BZRA use and increased mortality both in the crude analysis (HR=3.20; 95% CI=2.74-3.74; p<0.01) and in the primary IPW analysis (HR=1.61; 95% CI=1.31-1.98, p<0.01), with a significant dose-dependent relationship (HR=1.55; 95% CI=1.08-2.22; p=0.02). This association remained significant in multiple sensitivity analyses.ConclusionsBZRA use was associated with increased mortality among patients hospitalized for COVID-19 with a dose-dependent relationship, suggesting a potential benefit of decreasing dose or tapering off these medications when possible in these patients.

scholarly journals Thrombomodulin is Associated with Increased Mortality and Organ Failure in Mechanically Ventilated Children with Acute Respiratory Failure: A Prospective Observational Study.

2021 ◽  
Author(s):  
Ana C Monteiro ◽  
Heidi Flori ◽  
Mary K Dahmer ◽  
Myung Shin Sim ◽  
Michael W. Quasney ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Observational Study ◽  
Vascular Injury ◽  
Prospective Observational Study ◽  
Cox Regression ◽  
Multiorgan Failure ◽  
Invasive Mechanical Ventilation ◽  
Oxygenation Index ◽  
Mixed Effect ◽  
Soluble Thrombomodulin

Abstract BACKGROUNDAcute respiratory failure (ARF) can progress to acute respiratory distress syndrome (ARDS) and death. Biomarkers such as soluble thrombomodulin (sTM), implicated in pulmonary vascular injury, may allow for risk stratification and prognostic enrichment in ARF.METHODSThis was a prospective observational study of 432 patients aged 2 weeks - 17 years requiring invasive mechanical ventilation. It was ancillary to the multicenter clinical trial, Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE). After consent, patients had up to 3 plasma samples collected at 24-hour intervals within 5 days after intubation. sTM was assayed by ELISA. Hazard ratio (HR) for 90-day mortality was determined by cox regression. Mixed effect models (MEM) were used to test for association with extrapulmonary multiorgan failure (MOF) and oxygenation index (OI). Age, race, sex and PRISM-III scores were used as confounding variables for multivariable analyses.RESULTSsTM values ranged from 16.6 to 670.9 ng/ml within 5 days after intubation. Higher sTM was associated with increased 90-day mortality (n=432, adjusted HR= 1.003, p=0.02) and worse OI in the first 5 days after intubation (n=252, Estimate = 0.02, p<0.01). Both initial and slope of sTM were associated with increased extrapulmonary MOF in unadjusted and adjusted analyses (Intercept, Estimate=0.003, p<0.0001; and slope, Estimate=0.01, p=0.0009, n= 386). CONCLUSIONSPlasma sTM are associated with mortality, severity of ARDS extrapulmonary MOF in children with ARF. This suggests a role of vascular injury in pathogenesis of ARF and provide potential application for targeted therapies. TRIAL REGISTRATIONNCT00814099

scholarly journals Continuous Aerosol Medication Therapy in an in vitro High-Flow System Using Wire Mesh Technology

2020 ◽  
Author(s):  
Jhaymie Cappiello ◽  
Carla Bremenour ◽  
Jason Boyle ◽  
Jessica Lumbard ◽  
Kamrouz Ghadimi
Keyword(s):  
Success Rate ◽  
Primary Endpoint ◽  
Flow System ◽  
Wire Mesh ◽  
Secondary Endpoint ◽  
Residual Volume ◽  
Fluid Level ◽  
Medication Therapy ◽  
Jet Nebulizers

AbstractBACKGROUNDJet nebulizers are commonly used to provide continuous aerosolized medication therapy (CAMT). We observed the function of our CAMT system that utilizes the Aeroneb Solo nebulizer system (Aerogen Ltd, Galway, Ireland). METHODS: An observational study was performed on 2 CAMT systems with 15 Aeroneb nebulizers for each system. CAMT was simulated for 1, 2 and 3 hours. Continuous nebulization was monitored and residual volumes were recorded at the end of each simulation. Our primary endpoint was established as intermittent nebulization observed by nebulizer filling of > 1 ml during CAMT simulation. Secondary endpoint was a residual volume of < 0.1 ml.RESULTSOut of 30 simulations in two arms, a fluid level was observed to accumulate intermittently in three nebulizers with a residual volume of 0.7 mls in one of these three. This produced a total success rate of 90%, Arm-A 80%, Arm B-100%, for our primary endpoint. Our secondary endpoint was achieved in 29 of the 30 nebulizers for an overall 97% success rate, Arm A-93%, Arm B-100%. CONCLUSION: Our Aerogen Solo CAMT system successfully emitted the set dose with 90% accuracy.

FRAGILE: FRench Attitude reGistry in case of ICD LEad replacement

EP Europace ◽  
2020 ◽  
Author(s):  
Christine Alonso ◽  
Christelle Marquie ◽  
Pascal Defaye ◽  
Nicolas Clementy ◽  
Pierre Mondoly ◽  
...  
Keyword(s):  
Observational Study ◽  
Implantable Cardioverter Defibrillator ◽  
Primary Endpoint ◽  
Statistical Difference ◽  
Prospective Observational Study ◽  
Secondary Endpoint ◽  
Dwelling Time ◽  
Cardioverter Defibrillator ◽  
The Mean ◽  
Set Up

Abstract Aims FRench Attitude reGistry in case of ICD LEad replacement (FRAGILE) registry was set-up to describe the attitude in different French institutions in case of implantable cardioverter-defibrillator (ICD) lead replacement, extraction, or abandonment and to compare outcomes in both groups. Methods and results Prospective observational study comparing two attitudes in case of ICD lead replacement, extraction, or abandonment. Primary endpoint describes the attitude in different French centres, collect parameters that may influence the decision. Secondary endpoint compares early and mid-term (2 years) complications in both groups. Between April 2013 and April 2017, 552 patients were included in 32 centres. 434 (78.6%) were male, mean patient’s age was 60.3 ± 14.4 years. In 56.9% of the cases, the decision was to explant the lead. Patients in the extraction group were younger than in the abandonment group (56.7 ± 14.5 vs. 65 ± 12.7 P &lt; 0.0001) and less likely to have comorbidities (46.5% vs. 58.3% of the patients P = 0.022). The mean lead dwelling time was significantly longer in the abandonment group as compared with the extraction group (7.6 ± 3.9 vs. 5.2 ± 3.1 years, P &lt; 0.0001). There was no statistical difference between both groups concerning early and 2 years complications. Conclusion In this registry, the strategy in case of non-infected ICD lead replacement was mainly influenced by patient’s age and comorbidities and lead dwelling time. No difference was observed in outcomes in both strategies.

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