The Association Between Alpha-1 Adrenergic Receptor Antagonists and In-Hospital Mortality From COVID-19.
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ABSTRACT:
SUBMITTER: Rose L
PROVIDER: S-EPMC8048524 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Effective therapies for coronavirus disease 2019 (COVID-19) are urgently needed, and preclinical data suggest alpha-1 adrenergic receptor antagonists (α1-AR antagonists) may be effective in reducing mortality related to hyperinflammation independent of etiology. Using a retrospective cohort design with patients in the Department of Veterans Affairs healthcare system, we use doubly robust regression and matching to estimate the association between baseline use of α1-AR antagonists and likelihood of death due to COVID-19 during hospitalization. Having an active prescription for any α1-AR antagonist (tamsulosin, silodosin, prazosin, terazosin, doxazosin, or alfuzosin) at the time of admission had a significant negative association with in-hospital mortality (relative risk reduction 18%; odds ratio 0.73; 95% CI 0.63 to 0.85; p ≤ 0.001) and death within 28 days of admission (relative risk reduction 17%; odds ratio 0.74; 95% CI 0.65 to 0.84; p ≤ 0.001). In a subset of patients on doxazosin specifically, an inhibitor of all three alpha-1 adrenergic receptors, we observed a relative risk reduction for death of 74% (odds ratio 0.23; 95% CI 0.03 to 0.94; p = 0.028) compared to matched controls not on any α1-AR antagonist at the time of admission. These findings suggest that use of α1-AR antagonists may reduce mortality in COVID-19, supporting the need for randomized, placebo-controlled clinical trials in patients with early symptomatic infection.
| S-EPMC7781337 | biostudies-literature
Project description:There is a need for treatments to reduce coronavirus disease 2019 (COVID-19) mortality. Alpha-2 adrenergic receptor (α2 AR) agonists can dampen immune cell and inflammatory responses as well as improve oxygenation through physiologic respiratory parameters. Therefore, α2 AR agonists may be effective in reducing mortality related to hyperinflammation and acute respiratory failure in COVID-19. Dexmedetomidine (DEX) is an α2 AR agonist used for sedation. We performed a retrospective analysis of adults at Rush University System for Health hospitals between March 1, 2020 and July 30, 2020 with COVID-19 requiring invasive mechanical ventilation and sedation (n = 214). We evaluated the association of DEX use and 28-day mortality from time of intubation. Overall, 28-day mortality in the cohort receiving DEX was 27.0% as compared to 64.5% in the cohort that did not receive DEX (relative risk reduction 58.2%; 95% CI 42.4-69.6). Use of DEX was associated with reduced 28-day mortality on multivariable Cox regression analysis (aHR 0.19; 95% CI 0.10-0.33; p < 0.001). Adjusting for time-varying exposure to DEX also demonstrated that DEX was associated with reduced 28-day mortality (aHR 0.51; 95% CI 0.28-0.95; p = 0.03). Earlier DEX use, initiated <3.4 days from intubation, was associated with reduced 28-day mortality (aHR 0.25; 95% CI 0.13-0.50; p < 0.001) while later DEX use was not (aHR 0.64; 95% CI 0.27-1.50; p = 0.30). These results suggest an α2 AR agonist might reduce mortality in patients with COVID-19. Randomized controlled trials are needed to confirm this observation.
| S-EPMC8764306 | biostudies-literature
Project description:Famotidine has been considered to be a potential treatment for COVID-19 but the current data is conflicting. This retrospective study was conducted by utilizing data of 9565 COVID-19 hospitalized patients. Patients treated with and without famotidine were matched by propensity score using a 1:1 matching scheme. A total of 1593 patients (16.7%) received famotidine. In-hospital mortality was similar in patients treated with and without famotidine in the propensity-matched cohorts (28.3% vs. 28.2%, p = 0.97), which remains similar irrespective of severity or concomitant treatment by steroids. Famotidine treatment was not associated with a lower risk of in-hospital mortality of COVID-19 patients.
| S-EPMC8662098 | biostudies-literature
Project description:BackgroundThe impact of obesity on outcomes in acute respiratory distress syndrome (ARDS) is not well understood and remains controversial. Recent studies suggest that obesity might be associated with higher morbidity and mortality in respiratory disease caused by SARS-CoV-2 (COVID-19 disease). Our objective was to evaluate the association between obesity and hospital mortality in critical COVID-19 patients.MethodsWe conducted a retrospective cohort study in a tertiary academic center located in Montréal between March and August 2020. We included all consecutive adult patients admitted to the ICU for COVID-19-confirmed respiratory disease. Our main outcome was hospital mortality. We estimated the association between obesity, using the body mass index as a continuous variable, and hospital survival by fitting a multivariable Cox proportional hazards model.ResultsWe included 94 patients. Median [q1, q3] body mass index (BMI) was 29 [26-32] kg/m2 and 37% of patients were obese (defined as BMI > 30 kg/m2). Hospital mortality for the entire cohort was 33%. BMI was significantly associated with hospital mortality (hazard ratio [HR] = 2.49 per 10 units BMI; 95% CI, from 1.69 to 3.70; p < 0.001) even after adjustment for sex, age and obesity-related comorbidities (adjusted HR = 3.50; 95% CI from 2.03 to 6.02; p < 0.001).ConclusionsObesity was prevalent in hospitalized patients with critical illness secondary to COVID-19 disease and a higher BMI was associated with higher hospital mortality. Further studies are needed to validate this association and to better understand its underlying mechanisms.
| S-EPMC8385700 | biostudies-literature
Project description:ObjectiveThis study aims to investigate the relationship between RNs and hospital-based medical specialties staffing levels with inpatient COVID-19 mortality rates.MethodsWe relied on data from AHA Annual Survey Database, Area Health Resource File, and UnitedHealth Group Clinical Discovery Database. In phase 1 of the analysis, we estimated the risk-standardized event rates (RSERs) based on 95,915 patients in the UnitedHealth Group Database 1,398 hospitals. We then used beta regression to analyze the association between hospital- and county- level factors with risk-standardized inpatient COVID-19 mortality rates from March 1, 2020, through December 31, 2020.ResultsHigher staffing levels of RNs and emergency medicine physicians were associated with lower COVID-19 mortality rates. Moreover, larger teaching hospitals located in urban settings had higher COVID-19 mortality rates. Finally, counties with greater social vulnerability, specifically in terms of housing type and transportation, and those with high infection rates had the worst patient mortality rates.ConclusionHigher staffing levels are associated with lower inpatient mortality rates for COVID-19 patients. More research is needed to determine appropriate staffing levels and how staffing levels interact with other factors such as teams, leadership, and culture to impact patient care during pandemics.
| S-EPMC9581383 | biostudies-literature
Project description:ImportanceClinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm.ObjectiveTo estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes.Data sourcesTrials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts.Study selectionEligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria.Data extraction and synthesisIn this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance-weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality.Main outcomes and measuresThe primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days.ResultsA total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P < .001) for tocilizumab and 1.08 (95% CI, 0.86-1.36; P = .52) for sarilumab. The summary ORs for the association with mortality compared with usual care or placebo in those receiving corticosteroids were 0.77 (95% CI, 0.68-0.87) for tocilizumab and 0.92 (95% CI, 0.61-1.38) for sarilumab. The ORs for the association with progression to invasive mechanical ventilation or death, compared with usual care or placebo, were 0.77 (95% CI, 0.70-0.85) for all IL-6 antagonists, 0.74 (95% CI, 0.66-0.82) for tocilizumab, and 1.00 (95% CI, 0.74-1.34) for sarilumab. Secondary infections by 28 days occurred in 21.9% of patients treated with IL-6 antagonists vs 17.6% of patients treated with usual care or placebo (OR accounting for trial sample sizes, 0.99; 95% CI, 0.85-1.16).Conclusions and relevanceIn this prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.Trial registrationPROSPERO Identifier: CRD42021230155.
| S-EPMC8261689 | biostudies-literature
Project description:In severe viral pneumonia, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by hyperinflammation, which can lead to acute respiratory distress syndrome, multi-organ failure, and death. We previously demonstrated that alpha-1 adrenergic receptor (⍺1-AR) antagonists can prevent hyperinflammation and death in mice. Here, we conducted retrospective analyses in two cohorts of patients with acute respiratory distress (ARD, n = 18,547) and three cohorts with pneumonia (n = 400,907). Federated across two ARD cohorts, we find that patients exposed to ⍺1-AR antagonists, as compared to unexposed patients, had a 34% relative risk reduction for mechanical ventilation and death (OR = 0.70, p = 0.021). We replicated these methods on three pneumonia cohorts, all with similar effects on both outcomes. All results were robust to sensitivity analyses. These results highlight the urgent need for prospective trials testing whether prophylactic use of ⍺1-AR antagonists ameliorates lower respiratory tract infection-associated hyperinflammation and death, as observed in COVID-19.
| S-EPMC8195605 | biostudies-literature
Project description:ObjectivesWe investigated the association between multimorbidity among patients hospitalised with COVID-19 and their subsequent risk of mortality. We also explored the interaction between the presence of multimorbidity and the requirement for an individual to shield due to the presence of specific conditions and its association with mortality.DesignWe created a cohort of patients hospitalised in Scotland due to COVID-19 during the first wave (between 28 February 2020 and 22 September 2020) of the pandemic. We identified the level of multimorbidity for the patient on admission and used logistic regression to analyse the association between multimorbidity and risk of mortality among patients hospitalised with COVID-19.SettingScotland, UK.ParticipantsPatients hospitalised due to COVID-19.Main outcome measuresMortality as recorded on National Records of Scotland death certificate and being coded for COVID-19 on the death certificate or death within 28 days of a positive COVID-19 test.ResultsAlmost 58% of patients admitted to the hospital due to COVID-19 had multimorbidity. Adjusting for confounding factors of age, sex, social class and presence in the shielding group, multimorbidity was significantly associated with mortality (adjusted odds ratio 1.48, 95%CI 1.26-1.75). The presence of multimorbidity and presence in the shielding patients list were independently associated with mortality but there was no multiplicative effect of having both (adjusted odds ratio 0.91, 95%CI 0.64-1.29).ConclusionsMultimorbidity is an independent risk factor of mortality among individuals who were hospitalised due to COVID-19. Individuals with multimorbidity could be prioritised when making preventive policies, for example, by expanding shielding advice to this group and prioritising them for vaccination.
| S-EPMC8811325 | biostudies-literature
Project description:ImportanceThere has been limited research on patients with ST-segment elevation myocardial infarction (STEMI) and COVID-19.ObjectiveTo compare characteristics, treatment, and outcomes of patients with STEMI with vs without COVID-19 infection.Design, setting, and participantsRetrospective cohort study of consecutive adult patients admitted between January 2019 and December 2020 (end of follow-up in January 2021) with out-of-hospital or in-hospital STEMI at 509 US centers in the Vizient Clinical Database (N = 80 449).ExposuresActive COVID-19 infection present during the same encounter.Main outcomes and measuresThe primary outcome was in-hospital mortality. Patients were propensity matched on the likelihood of COVID-19 diagnosis. In the main analysis, patients with COVID-19 were compared with those without COVID-19 during the previous calendar year.ResultsThe out-of-hospital STEMI group included 76 434 patients (551 with COVID-19 vs 2755 without COVID-19 after matching) from 370 centers (64.1% aged 51-74 years; 70.3% men). The in-hospital STEMI group included 4015 patients (252 with COVID-19 vs 756 without COVID-19 after matching) from 353 centers (58.3% aged 51-74 years; 60.7% men). In patients with out-of-hospital STEMI, there was no significant difference in the likelihood of undergoing primary percutaneous coronary intervention by COVID-19 status; patients with in-hospital STEMI and COVID-19 were significantly less likely to undergo invasive diagnostic or therapeutic coronary procedures than those without COVID-19. Among patients with out-of-hospital STEMI and COVID-19 vs out-of-hospital STEMI without COVID-19, the rates of in-hospital mortality were 15.2% vs 11.2% (absolute difference, 4.1% [95% CI, 1.1%-7.0%]; P = .007). Among patients with in-hospital STEMI and COVID-19 vs in-hospital STEMI without COVID-19, the rates of in-hospital mortality were 78.5% vs 46.1% (absolute difference, 32.4% [95% CI, 29.0%-35.9%]; P < .001).Conclusions and relevanceAmong patients with out-of-hospital or in-hospital STEMI, a concomitant diagnosis of COVID-19 was significantly associated with higher rates of in-hospital mortality compared with patients without a diagnosis of COVID-19 from the past year. Further research is required to understand the potential mechanisms underlying this association.
| S-EPMC8596198 | biostudies-literature
Project description:ObjectiveTo identify markers associated with in-hospital death in patients with coronavirus disease 2019 (COVID-19)-associated pneumonia.Patients and methodsA retrospective cohort study was conducted of 140 patients with moderate to critical COVID-19-associated pneumonia requiring oxygen supplementation admitted to the hospital from January 28, 2020, through February 28, 2020, and followed up through March 13, 2020, in Union Hospital, Wuhan, China. Oxygen saturation (SpO2) and other measures were tested as predictors of in-hospital mortality in survival analysis.ResultsOf 140 patients with COVID-19-associated pneumonia, 72 (51.4%) were men, with a median age of 60 years. Patients with SpO2 values of 90% or less were older and were more likely to be men, to have hypertension, and to present with dyspnea than those with SpO2 values greater than 90%. Overall, 36 patients (25.7%) died during hospitalization after median 14-day follow-up. Higher SpO2 levels after oxygen supplementation were associated with reduced mortality independently of age and sex (hazard ratio per 1-U SpO2, 0.93; 95% CI, 0.91 to 0.95; P<.001). The SpO2 cutoff value of 90.5% yielded 84.6% sensitivity and 97.2% specificity for prediction of survival. Dyspnea was also independently associated with death in multivariable analysis (hazard ratio, 2.60; 95% CI, 1.24 to 5.43; P=.01).ConclusionIn this cohort of patients with COVID-19, hypoxemia was independently associated with in-hospital mortality. These results may help guide the clinical management of patients with severe COVID-19, particularly in settings requiring strategic allocation of limited critical care resources.Trial registrationChictr.org.cn Identifier: ChiCTR2000030852.
| S-EPMC7151468 | biostudies-literature