scholarly journals Hydroxyzine Use and Mortality in Patients Hospitalized for COVID-19: A Multicenter Observational Study

2021 ◽  
Vol 10 (24) ◽  
pp. 5891
Author(s):  
Marina Sánchez-Rico ◽  
Frédéric Limosin ◽  
Raphaël Vernet ◽  
Nathanaël Beeker ◽  
Antoine Neuraz ◽  
...  
Keyword(s):  
Observational Study ◽  
Randomized Clinical Trials ◽  
Acid Sphingomyelinase ◽  
Potential Usefulness ◽  
Sensitivity Analyses ◽  
Post Exposure Prophylaxis ◽  
Multivariable Logistic Regression Model ◽  
Double Blind ◽  
Multicenter Observational Study ◽  
Exposure Prophylaxis

(1) Background: Based on its antiviral activity, anti-inflammatory properties, and functional inhibition effects on the acid sphingomyelinase/ceramide system (FIASMA), we sought to examine the potential usefulness of the H1 antihistamine hydroxyzine in patients hospitalized for COVID-19. (2) Methods: In a multicenter observational study, we included 15,103 adults hospitalized for COVID-19, of which 164 (1.1%) received hydroxyzine within the first 48 h of hospitalization, administered orally at a median daily dose of 25.0 mg (SD = 29.5). We compared mortality rates between patients who received hydroxyzine at hospital admission and those who did not, using a multivariable logistic regression model adjusting for patients’ characteristics, medical conditions, and use of other medications. (3) Results: This analysis showed a significant association between hydroxyzine use and reduced mortality (AOR, 0.51; 95%CI, 0.29–0.88, p = 0.016). This association was similar in multiple sensitivity analyses. (4) Conclusions: In this retrospective observational multicenter study, the use of the FIASMA hydroxyzine was associated with reduced mortality in patients hospitalized for COVID-19. Double-blind placebo-controlled randomized clinical trials of hydroxyzine for COVID-19 are needed to confirm these results, as are studies to examine the potential usefulness of this medication for outpatients and as post-exposure prophylaxis for individuals at high risk for severe COVID-19.

scholarly journals Safety of Hydroxychloroquine among Outpatient Clinical Trial Participants for COVID-19

2020 ◽  
Author(s):  
SARAH M LOFGREN ◽  
Melanie R Nicol ◽  
Ananta S Bangdiwala ◽  
Katelyn A Pastick ◽  
Elizabeth C Okafor ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Side Effect ◽  
Randomized Clinical Trials ◽  
Safety Data ◽  
Post Exposure Prophylaxis ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Gastrointestinal Side Effects ◽  
Exposure Prophylaxis

Introduction: Use of hydroxychloroquine in hospitalized patients with COVID-19, especially in combination with azithromycin, has raised safety concerns. Here, we report safety data from three outpatient randomized clinical trials. Methods: We conducted three randomized, double-blind, placebo-controlled trials investigating hydroxychloroquine as pre-exposure prophylaxis, post-exposure prophylaxis and early treatment for COVID-19. We excluded individuals with contraindications to hydroxychloroquine. We collected side effects and serious adverse events. We report descriptive analyses of our findings. Results: We enrolled 2,795 participants. The median age of research participants was 40 (IQR 34-49) years, and 59% (1633/2767) reported no chronic medical conditions. Overall 2,324 (84%) participants reported side effect data, and 638 (27%) reported at least one medication side effect. Side effects were reported in 29% with daily, 36% with twice weekly, 31% with once weekly hydroxychloroquine compared to 19% with placebo. The most common side effects were upset stomach or nausea (25% with daily, 18% with twice weekly, 16% with weekly, vs. 10% for placebo), followed by diarrhea, vomiting, or abdominal pain (23% for daily, 16% twice weekly, 12% weekly, vs. 6% for placebo). Two individuals were hospitalized for atrial arrhythmias, one on placebo and one on twice weekly hydroxychloroquine. No sudden deaths occurred. Conclusion: Data from three outpatient COVID-19 trials demonstrated that gastrointestinal side effects were common but mild with the use of hydroxychloroquine, while serious side effects were rare. No deaths occurred related to hydroxychloroquine. Randomized clinical trials can safely investigate whether hydroxychloroquine is efficacious 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.

scholarly journals Association between Psychotropic Medications Functionally Inhibiting Acid Sphingomyelinase and reduced risk of Intubation or Death among Individuals with Mental Disorder and Severe COVID-19: an Observational Study

2021 ◽  
Author(s):  
Nicolas Hoertel ◽  
Marina Sánchez-Rico ◽  
Erich Gulbins ◽  
Johannes Kornhuber ◽  
Alexander Carpinteiro ◽  
...  
Keyword(s):  
Mental Disorder ◽  
Psychotropic Medication ◽  
Randomized Clinical Trials ◽  
Cox Regression ◽  
Medication Use ◽  
Psychotropic Medications ◽  
Acid Sphingomyelinase ◽  
Sensitivity Analyses ◽  
Double Blind ◽  
Reduced Risk

ABSTRACTPrior preclinical and clinical evidence suggests that the acid sphingomyelinase (ASM)/ceramide system may provide a useful framework for better understanding SARS-CoV-2 infection and the repurposing of psychotropic medications with functional inhibition of acid sphingomyelinase, called FIASMA psychotropic medications, against COVID-19. We examined the potential usefulness of FIASMA psychotropic medication use among patients with mental disorder hospitalized for severe COVID-19, in an observational multicenter retrospective study conducted at AP-HP Greater Paris University hospitals. Of 545 adult patients with mental disorder hospitalized for severe COVID-19, 164 (30.1%) received a psychotropic FIASMA medication at study baseline, which was defined as the date of hospital admission for COVID-19. The primary endpoint was a composite of intubation or death. We compared this endpoint between patients who received a psychotropic FIASMA medication at baseline and those who did not in time-to-event analyses adjusted for sociodemographic characteristics, psychiatric and other medical comorbidity, and psychotropic and other medications. The primary analysis was a Cox regression model with inverse probability weighting (IPW). There was a significant association between FIASMA psychotropic medication use at baseline and reduced risk of intubation or death both in the crude analysis (HR=0.42; 95%CI=0.31-0.57; p<0.01) and in the primary IPW analysis (HR=0.50; 95%CI=0.37-0.67; p<0.01). This association remained significant in multiple sensitivity analyses. Exploratory analyses suggested that this association was not specific to one FIASMA psychotropic class or medication. These results suggest the usefulness of the ASM/ceramide system framework in COVID-19. Double-blind controlled randomized clinical trials of these medications for COVID-19 are needed.

scholarly journals Daily Lactobacillus Probiotic versus Placebo in COVID-19-Exposed Household Contacts (PROTECT-EHC): A Randomized Clinical Trial

2022 ◽  
Author(s):  
Paul E Wischmeyer ◽  
Helen Tang ◽  
Yi Ren ◽  
Lauren Bohannon ◽  
Zeni E Ramirez ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Lactobacillus Rhamnosus ◽  
The United States ◽  
Post Exposure Prophylaxis ◽  
Event Analysis ◽  
Double Blind ◽  
Intention To Treat ◽  
Tract Infections ◽  
Exposure Prophylaxis ◽  
Vaccine Availability

Background: The COVID-19 pandemic continues to pose unprecedented challenges to worldwide health. While vaccines are effective, supplemental strategies to mitigate the spread and severity of COVID-19 are urgently needed. Emerging evidence suggests susceptibility to infections, including respiratory tract infections, may be reduced by probiotic interventions. Therefore, probiotics may be a low-risk, widely implementable modality to mitigate risk of COVID-19 disease, particularly in areas with low vaccine availability and/or uptake. Methods: We conducted a randomized, double-blind, placebo-controlled trial across the United States testing the probiotic Lactobacillus rhamnosus GG (LGG) as post-COVID-19-exposure prophylaxis. We enrolled individuals > 1 year of age with a household contact with a recent (≤ 7 days) diagnosis of COVID-19. Participants were randomized to receive daily LGG or placebo for 28 days. Stool was collected to evaluate the microbiome. The primary outcome was development of symptoms of illness compatible with COVID-19 within 28 days. Findings: We enrolled 182 COVID-19-exposed participants. Intention-to-treat analysis showed that participants randomized to LGG were less likely to develop symptoms versus those randomized to placebo (26.4% vs. 42.9%, p=0.02). Further, LGG was associated with a statistically significant reduction in COVID-19 diagnosis (log rank p=0.049) via time-to-event analysis. Overall incidence of COVID-19 diagnosis was not significantly different between LGG (8.8%) and placebo (15.4%) (p=0.17). LGG was well-tolerated with no increased side effects versus placebo. Interpretation: These findings suggest that LGG probiotic may protect against the development of COVID-19 infection and symptoms when used as post-exposure prophylaxis within 7 days after exposure. Funding: This work was supported by a grant from the Duke Microbiome Center to A.D.S. and P.E.W. and private philanthropic donations to A.D.S. DSM/iHealth donated the LGG and placebo for the trial but had no role in its design, conduct, analysis, or writing. Trial registration: NCT04399252

scholarly journals Network meta‐analysis of post‐exposure prophylaxis randomized clinical trials

HIV Medicine ◽  
2020 ◽  
Author(s):  
I Fernández ◽  
E. Lazzari ◽  
A. Inciarte ◽  
V. Diaz‐Brito ◽  
A. Milinkovic ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Post Exposure Prophylaxis ◽  
Post Exposure ◽  
Exposure Prophylaxis

scholarly journals Laninamivir octanoate for post-exposure prophylaxis of influenza in household contacts: a randomized double blind placebo controlled trial

2013 ◽  
Vol 19 (4) ◽  
pp. 740-749 ◽  
Author(s):  
Seizaburo Kashiwagi ◽  
Akira Watanabe ◽  
Hideyuki Ikematsu ◽  
Shinichiro Awamura ◽  
Takako Okamoto ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Post Exposure Prophylaxis ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Post Exposure ◽  
Household Contacts ◽  
Exposure Prophylaxis

scholarly journals Association between SSRI Antidepressant Use and Reduced Risk of Intubation or Death in Hospitalized Patients with Coronavirus Disease 2019: a Multicenter Retrospective Observational Study

2020 ◽  
Author(s):  
Nicolas Hoertel ◽  
Marina SANCHEZ RICO ◽  
Raphael VERNET ◽  
Nathanael BEEKER ◽  
Anne-Sophie JANNOT ◽  
...  
Keyword(s):  
Lower Risk ◽  
Randomized Clinical Trials ◽  
Hospitalized Patients ◽  
Sensitivity Analyses ◽  
University Hospitals ◽  
Double Blind ◽  
Cox Models ◽  
Risk Of Death ◽  
Antidepressant Use ◽  
Reduced Risk

Objective: To examine the association between antidepressant use and the risk of intubation or death in hospitalized patients with COVID-19. Design: Multicenter observational retrospective cohort study. Setting: Greater Paris University hospitals, France. Participants: 7,345 adults hospitalized with COVID-19 between 24 January and 1 April 2020, including 460 patients (6.3%) who received an antidepressant during the visit. Data source: Assistance Publique-Hopitaux de Paris Health Data Warehouse. Main outcome measures: The primary endpoint was a composite of intubation or death. We compared this endpoint between patients who received antidepressants and those who did not in time-to-event analyses adjusting for patient characteristics (such as age, sex, and comorbidities), disease severity and other psychotropic medications. The primary analyses were multivariable Cox models with inverse probability weighting. Results: Over a mean follow-up of 18.5 days (SD=27.1), 1,331 patients (18.1%) had a primary end-point event. Unadjusted hazard ratio estimates of the association between antidepressant use and the primary outcome stratified by age (i.e., 18-50, 51-70, 71-80, and 81+) were non-significant (all p>0.072), except in the group of patients aged 71-80 years (HR, 0.66; 95% CI, 0.45 to 0.98; p=0.041). Following adjustments, the primary analyses showed a significant association between use of any antidepressant (HR, 0.64; 95% CI, 0.51 to 0.80; p<0.001), SSRI (HR, 0.56; 95% CI, 0.42 to 0.75; p<0.001), and SNRI (HR, 0.57; 95% CI, 0.34 to 0.96; p=0.034), and reduced risk of intubation or death. Specifically, exposures to escitalopram, fluoxetine, and venlafaxine were significantly associated with lower risk of intubation or death (all p<0.05). These associations remain significant in multiple sensitivity analyses, except for the association between SNRI use and the outcome. Conclusions: SSRI use could be associated with lower risk of death or intubation in hospitalized patients with COVID-19. Double-blind controlled randomized clinical trials of these medications for COVID-19 are needed.

scholarly journals 2279. Study of Prescribing patterns and Effectiveness of Ceftolozane–tazobactam (C/T): Real-world Analysis (SPECTRA): a multi-national, multicenter observational study

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S780-S781
Author(s):  
Alex Soriano ◽  
Laura Puzniak ◽  
David Paterson ◽  
Florian Thalhalmmer ◽  
Stefan Kluge ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Observational Study ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Prescribing Patterns ◽  
National Study ◽  
Multicenter Observational Study ◽  
E Coli ◽  
Source Of Infection ◽  
Hospital Acquired

Abstract Background C/T has demonstrated efficacy in randomized clinical trials to treat cIAI and cUTI and recently completed a study in ventilator-associated bacterial and ventilated hospital-acquired bacterial pneumonia. The purpose of this study was to evaluate the real-world clinical use and outcomes of C/T in a multi-national study. Methods SPECTRA is a multi-national, multicenter, retrospective, inpatient, observational study of patients treated with C/T in Australia, Austria, Germany, Italy, Spain and United Kingdom. Patients admitted with greater than 48 hours of C/T treatment were included. Demographics, clinical characteristics, treatment management patterns, microbiological findings and outcomes were analyzed. Results There were 155 patients from 20 participating hospitals in 6 countries. The average age was 58.0 years (±17.8) and most were male 114 (74%). The majority 130 (84%) had at least one comorbidity, with the most common being renal impairment 87 (56%), immunocompromised 62 (40%), and diabetes 52 (34%). The majority, 94 (61%), had previous hospitalizations ≥ 6 months prior to receiving C/T, of which 29 (31%) had an ICU stay and surgeries 64 (42%). Most patients 126 (82%) received antibacterials within 30 days of receiving C/T, 61 (40%) received carbapenems and 47 (31%) received aminoglycoside. The average duration of C/T was 15 (SD12) days. The source of infection was cUTI for 31 (20%), cIAI for 19 (12%) and respiratory for 43 (28%) of C/T treated patients. Most 107 (70%) had an ID consult with an average of 7 (SD 11.3) consults. The top pathogen was Pseudomonas 124 (81%) followed by E. coli 22 (14%), with 56 (37%) having a polymicrobial infection. Over half of the patients were in the ICU 84 (55%), 58 (38%) underwent at least 1 surgery, with 65 (48%) being related to the infection, 60 (39%) had sepsis and 21 (14%) had septic shock. All-cause in hospital mortality was 16%. 30-day all-cause readmission was 12% and 6% were infection related. Conclusion Despite the complexity of the patients in this real-world analysis, most C/T patients had beneficial outcomes that are similar to results of controlled clinical trials. Disclosures All authors: No reported disclosures.

scholarly journals COVID-19 Convalescent Plasma Is More Than Neutralizing Antibodies: A Narrative Review of Potential Beneficial and Detrimental Co-Factors

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1594
Author(s):  
Daniele Focosi ◽  
Massimo Franchini ◽  
Liise-anne Pirofski ◽  
Thierry Burnouf ◽  
DeLisa Fairweather ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Neutralizing Antibodies ◽  
Randomized Clinical Trials ◽  
Neutralizing Antibody ◽  
Causal Link ◽  
Fresh Frozen Plasma ◽  
Post Exposure Prophylaxis ◽  
Fresh Frozen ◽  
Antibody Effects ◽  
Exposure Prophylaxis

COVID-19 convalescent plasma (CCP) is currently under investigation for both treatment and post-exposure prophylaxis. The active component of CCP mediating improved outcome is commonly reported as specific antibodies, particularly neutralizing antibodies, with clinical efficacy characterized according to the level or antibody affinity. In this review, we highlight the potential role of additional factors in CCP that can be either beneficial (e.g., AT-III, alpha-1 AT, ACE2+ extracellular vesicles) or detrimental (e.g., anti-ADAMTS13, anti-MDA5 or anti-interferon autoantibodies, pro-coagulant extracellular vesicles). Variations in these factors in CCP may contribute to varied outcomes in patients with COVID-19 and undergoing CCP therapy. We advise careful, retrospective investigation of such co-factors in randomized clinical trials that use fresh frozen plasma in control arms. Nevertheless, it might be difficult to establish a causal link between these components and outcome, given that CCP is generally safe and neutralizing antibody effects may predominate.

Sign in / Sign up

Export Citation Format

Share Document