Project description:Hypothesis/Gap Statement. The impacts of increased biomarker testing on antifungal prescribing have not yet been fully examined in a real-life setting.Objectives. Biomarkers for invasive fungal disease (IFD) have been shown to reduce antifungal prescriptions in neutropaenic haemato-oncology patients. Our study aimed to assess the real-life impacts of introducing a novel biomarker-based pathway, incorporating serum galactomannan and Aspergillus PCR, for pyrexial haemato-oncology admissions.Methods. Patients with neutropaenic fever were identified prospectively after introduction of the new pathway from 2013-2015. A historical group of neutropaenic patients who had blood cultures taken from 2009-2012 was generated for comparison. Clinical details, including demographics, underlying diagnosis, investigations, radiology and antimicrobial treatment were obtained.Results. Prospective data from 308 patients were compared to retrospective data from 302 patients. The proportion of patients prescribed an antifungal medication was unchanged by the pathway (P=0.79), but the pattern was different, with more patients receiving targeted antifungals (P=0.04). A negative serum galactomannan test was not sufficient evidence to withhold therapy, with 17.2% of these episodes felt to have possible or probable IFD using the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. There was no difference in 30-day mortality (P=0.21) or 1-year mortality (P=0.57) following introduction of the pathway.Conclusions. Biomarkers can be used safely as part of a multidisciplinary approach to the diagnosis of IFD in neutropaenic haemato-oncology patients. Whilst they do not necessarily result in antifungal therapy being withheld, they can allow more confident diagnosis of IFD and more specific antifungal therapy in selected cases.
Project description:The outbreak of Coronavirus Disease (COVID-19) in Wuhan have affected more than 250 countries and regions worldwide. However, most of the clinical studies have been focused on Wuhan, and little is known about the disease outside of Wuhan in China. In this retrospective cohort study, we report the early clinical features of 80 patients with COVID-19 admitted to the hospital in Beijing. The results show that 27 (33.8%) patients had severe illness. Six (7.5%) patients were admitted to the ICU, and 3 (3.8%) patients died. Forty-eight percent (39/80) of the patients had a history of living/traveling in Wuhan. Patients with severe- illness were significantly older (average age, 71 years old vs 44 years old) and had a high incidence of expectoration (59.3% vs 34.0%), shortness of breath (92.6% vs 9.4%), anorexia (51.9% vs 18.9%) and confusion(18.5% vs 0%) compared with nonsevere patients. The systolic blood pressure (median, 130 mmHg vs 120 mmHg) was higher and the oxygen saturation (median, 98.3% vs 92.0%) was significantly lower in severe patients than nonsevere patients. In addition, myoglobin (median, 56.0 ng/mL vs 35.0 ng/mL), troponin I (median, 0.02 pg/mL vs 0.01 pg/mL), C-reactive protein (median, 69.7 mg/L vs 12.9 mg/L) and neutrophils (median, 3.3×109/L vs 2.2×109/L) were significantly increased, while lymphocytes (median, 0.8×109/L vs 1.2×109/L), albumin (mean, 32.8 g/L vs 36.8 g/L) and the creatinine clearance rate (median, 91.2 vs 108.2 ml/min/1.73m2) were significantly decreased among severe patients. Our study revealed that older patients with high levels of C-reactive protein, myoglobin, troponin I, and neutrophil and high systolic blood pressure as well as low levels of lymphocytes, and albumin and a low creatinine clearance rate and oxygen saturation were more likely to have severe disease.
Project description:Given the urgent need for coronavirus disease 2019 therapeutics, early in the pandemic the Accelerating Coronavirus Disease 2019 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership rapidly designed a unique therapeutic agent intake and assessment process for candidate treatments of coronavirus disease 2019. These treatments included antivirals, immune modulators, severe acute respiratory syndrome coronavirus 2 neutralizing antibodies, and organ-supportive treatments at both the preclinical and clinical stages of development. The ACTIV Therapeutics-Clinical Working Group Agent Prioritization subgroup established a uniform data collection process required to perform an assessment of any agent type using review criteria that were identified and differentially weighted for each agent class. The ACTIV Therapeutics-Clinical Working Group evaluated over 750 therapeutic agents with potential application for coronavirus disease 2019 and prioritized promising candidates for testing within the master protocols conducted by ACTIV. In addition, promising agents among preclinical candidates were selected by ACTIV to be matched with laboratories that could assist in executing rigorous preclinical studies. Between April 14, 2020, and May 31, 2021, the Agent Prioritization subgroup advanced 20 agents into the Accelerating Coronavirus Disease 2019 Therapeutic Interventions and Vaccines master protocols and matched 25 agents with laboratories to assist with preclinical testing.
Project description:Objective: To study the potential effect of COVID-19 on the endometrium of affected symptomatic women. Design: Preliminary study of the endometrial transcriptomes in women with COVID-19 through RNA sequencing. Setting: Hospital and university laboratories. Subjects: Women with COVID-19 lacking SARS-CoV-2 infection in endometrial tissue. Intervention/Exposure: Endometrial biopsy collection. Main outcomes measures: Endometrial gene expression and functional analysis of patients with COVID-19 versus uninfected individuals. Results: COVID-19 systemic disease alters endometrial gene expression in 75% of women, with patients exhibiting a preponderance of 163 up-regulated (e.g., UTS2, IFI6, IFIH1, BNIP3) and 72 down-regulated genes (e.g., CPZ, CDH3, IRF4) (FDR<0.05). A total of 161 dysregulated functions (36 up-regulated and 125 down-regulated) were typically enriched in COVID-19 endometria, including upregulation in pathways involved in response to virus and cytokine inflammation, highlighting upregulation of a COVID-19 response pathway. Conclusion: COVID-19 affects endometrial gene expression despite the absence of SARS-CoV-2 particles in endometrial tissues.
Project description:Effective treatments for the critically ill patient with novel coronavirus disease 2019 are desperately needed. Given the role of cytokine release syndrome in the pathogenesis of coronavirus disease 2019-associated respiratory distress, therapies aimed at mitigating cytokine release, such as the interleukin-6 receptor-inhibiting monoclonal antibody tocilizumab, represent potential treatment strategies. Therefore, we examined the outcomes of critically ill coronavirus disease 2019 patients treated with tocilizumab and factors associated with clinical improvement. Design:A retrospective cohort analysis of 21-day outcomes for consecutive mechanically ventilated patients treated with tocilizumab from March 24, 2020, to May 4, 2020. Setting:Nine ICUs at six hospitals within a hospital system in Houston, Texas, United States. Patients:The first 62 coronavirus disease 2019 patients on invasive mechanical ventilation who were treated with tocilizumab, which was considered for all patients with severe disease. Interventions:Tocilizumab was administered either at a weight-based dose of 4-8?mg/kg or at a flat dose of 400?mg, with repeat administration in some patients at the physician's discretion. Measurements and Main Results:The primary outcomes were mortality and clinical improvement, defined as extubation. By day 21 post-tocilizumab, clinical improvement occurred in 36 patients (58%) and 13 patients (21%) died. In both univariable and multivariable analyses, age less than 60 years was associated with clinical improvement. Transient transaminitis was the most common adverse reaction, occurring in 25 patients (40%). Conclusions:Based on clinical outcomes and mortality rates seen in previous reports of mechanically ventilated patients, tocilizumab, as part of the management strategy for severe coronavirus disease 2019, represents a promising option. These findings support the need for evaluation of tocilizumab in a randomized controlled trial.
Project description:OBJECTIVE:To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died. DESIGN:Retrospective case series. SETTING:Tongji Hospital in Wuhan, China. PARTICIPANTS:Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020. MAIN OUTCOME MEASURES:Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms. RESULTS:The median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients. CONCLUSION:Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.
Project description:BackgroundThe objective of this study was to characterize hospitalized coronavirus disease 2019 (COVID-19) patients and describe their real-world treatment patterns and outcomes over time.MethodsAdult patients hospitalized on May 1, 2020-December 31, 2020 with a discharge diagnosis of COVID-19 were identified from the Premier Healthcare Database. Patient and hospital characteristics, treatments, baseline severity based on oxygen support, length of stay (LOS), intensive care unit (ICU) utilization, and mortality were examined.ResultsThe study included 295657 patients (847 hospitals), with median age of 66 (interquartile range, 54-77) years. Among each set of demographic comparators, the majority were male, white, and over 65. Approximately 85% had no supplemental oxygen charges (NSOc) or low-flow oxygen (LFO) at baseline, whereas 75% received no more than NSOc or LFO as maximal oxygen support at any time during hospitalization. Remdesivir (RDV) and corticosteroid treatment utilization increased over time. By December, 50% were receiving RDV and 80% were receiving corticosteroids. A higher proportion initiated COVID-19 treatments within 2 days of hospitalization in December versus May (RDV, 87% vs 40%; corticosteroids, 93% vs 62%; convalescent plasma, 68% vs 26%). There was a shift toward initiating RDV in patients on NSOc or LFO (68.0% [May] vs 83.1% [December]). Median LOS decreased over time. Overall mortality was 13.5% and it was highest for severe patients (invasive mechanical ventilation/extracorporeal membrane oxygenation [IMV/ECMO], 53.7%; high-flow oxygen/noninvasive ventilation [HFO/NIV], 32.2%; LFO, 11.7%; NSOc, 7.3%). The ICU use decreased, whereas mortality decreased for NSOc and LFO.ConclusionsClinical management of COVID-19 is rapidly evolving. This large observational study found that use of evidence-based treatments increased from May to December 2020, whereas improvement in outcomes occurred over this time-period.
Project description:Background and aimsOver 404 million people worldwide have been infected with coronavirus disease-2019 (COVID-19), 145 million in the United States (77 million) and Europe (151 million) alone (as of February 10, 2022). This paper aims to analyze data from studies reporting gastrointestinal bleeding (GIB) and/or endoscopic findings in COVID-19 patients in Western countries.MethodsWe conducted a systematic review of articles on confirmed COVID-19 cases with GIB in Western countries published in PubMed and Google Scholar databases from June 20, 2020, to July 10, 2021.ResultsA total of 12 studies reporting GIB and/or endoscopic findings in 808 COVID-19 patients in Western countries were collected and analyzed. Outcomes and comorbidities were compared with 18,179 non-GIB COVID-19 patients from Italy and the United States. As per our study findings, the overall incidence of GIB in COVID-19 patients was found to be 0.06%. When compared to the non-GIB cohort, the death rate was significantly high in COVID-19 patients with GIB (16.4% vs 25.4%, P < .001, respectively). Endoscopic treatment was rarely necessary, and blood transfusion was the most common GIB treatment. The most common presentation in GIB patients is melena (n = 117, 47.5%). Peptic, esophageal, and rectal ulcers were the most common endoscopic findings in upper (48.4%) and lower (36.4%) endoscopies. The GIB cohort had worse outcomes and higher incidence of hypertension (61.1%), liver disease (11.2%), and cancer (13.6%) than the non-GIB cohort. Death was strongly associated with hypertension (P < .001, r = 0.814), hematochezia (P < .001, r = 0.646), and esophagogastroduodenoscopy (P < .001, r = 0.591) in COVID-19 patients with GIB.ConclusionsOverall, the incidence of GIB in COVID-19 patients is similar to that estimated in the overall population, with melena being the most common presentation. The common endoscopic findings in GIB COVID-19 patients were ulcers, esophagitis, gastritis, and colitis. Patients with GIB were more prone to death than non-GIB COVID-19 patients.
Project description:BackgroundThe clinical significance of Coronavirus disease 2019 (COVID-19) as an associate of myocardial injury is controversial.HypothesisType 2 MI/Myocardial Injury are associated with worse outcomes if complicated by COVID-19.MethodsThis longitudinal cohort study involved consecutive patients admitted to a large urban hospital. Myocardial injury was determined using laboratory records as ≥1 hs-TnI result >99th percentile (male: >34 ng/L; female: >16 ng/L). Endotypes were defined according to the Fourth Universal Definition of Myocardial Infarction (MI) and COVID-19 determined using PCR. Outcomes of patients with myocardial injury with and without COVID-19 were assessed.ResultsOf 346 hospitalized patients with elevated hs-TnI, 35 (10.1%) had laboratory-confirmed COVID-19 (median age [IQR]; 65 [59-74]; 64.8% male vs. COVID-19 negative: 74 [63-83] years; 43.7% male). Cardiac endotypes by COVID-19 status (yes vs. no) were: Type 1 MI (0 [0%] vs. 115 [100%]; p < .0005), Type 2 MI (13 [16.5%] vs. 66 [83.5%]; p = .045), and non-ischemic myocardial injury (cardiac: 4 [5.8%] vs. 65 [94.2%]; p = .191, non-cardiac:19 [22.9%] vs. 64 [77.%]; p < .0005). COVID-19 patients had less comorbidity (median [IQR] Charlson Comorbidity Index: 3.0 [3.0] vs. 5.0 [4.0]; p = .001), similar hs-TnI concentrations (median [IQR] initial: 46 [113] vs. 62 [138]; p = .199, peak: 122 [474] vs. 79 [220] ng/L; p = .564), longer admission (days) (median [IQR]: 14[19] vs. 6[12]; p = .001) and higher in-hospital mortality (63.9% vs. 11.3%; OR = 13.2; 95%CI: 5.90, 29.7).ConclusionsCardiac sequelae of COVID-19 typically manifest as Non-cardiac myocardial injury/Type 2MI in younger patients with less co-morbidity. Paradoxically, the admission duration and in-hospital mortality are increased.