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PURPOSE OF THE REVIEW: Community-acquired pneumonia (CAP) is increasingly recognized as a complex, multisystemic disease with the potential to cause both acute and long-term sequelae, significantly impacting patient mortality rates. In this manuscript, the authors review the current methodologies for assessing mortality risk among CAP patients. RECENT FINDINGS: The most common prediction scores for ICU care and short-term mortality include Pneumonia Severity Index (PSI), CURB-65, SMART COP, SCAP, and ATS/IDSA criteria. These models have clinical utility in the prediction of short-term mortality, but they have significant limitations in addressing long-term mortality. For patients who are discharged alive from the hospital, we do not have scores to predict long term mortality. SUMMARY: The development of an optimal prognostic tool for postacute sequelae of CAP is imperative. Such a tool should identify specific populations at increased risk. Moreover, accurately identifying at-risk populations is essential for their inclusion in clinical trials that evaluate potential therapies designed to improve short and long-term clinical outcomes in patients with CAP.
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Introduction: This study aims to explore the predictive roles of echocardiographic parameters and biomarkers in determining outcomes among hospitalized COVID-19 patients experiencing cardiovascular events. Methods: A retrospective cohort study was conducted involving 49 COVID-19 patients who encountered cardiovascular events during hospitalization and underwent echocardiography. Our findings revealed notable associations between echocardiographic parameters and survival time. Results: A decrease in left ventricular ejection fraction (LVEF) of 10% was linked to a 20% reduction in survival time (TR: 0.80, 95% CI: 0.67 - 0.96, p = .017). Similarly, an increase in left ventricular (LV) volume by 10 mL was associated with a 9% decrease in survival time (TR: 0.91, 95% CI: 0.84 - 0.98, p = .011). Moreover, an increase in left atrial (LA) volume by 10 mL corresponded to an 8% decrease in survival time (TR: 0.92, 95% CI: 0.86 - 0.99, p = .026). Additionally, each 1 cm increase in right ventricular (RV) diameter was linked to a 22% reduction in survival time (TR: 0.78, 95% CI: 0.61 - 0.99, p = .043). Furthermore, a 10 mL increase in right atrial (RA) volume was associated with a 12% decrease in survival time (TR: 0.88, 95% CI: 0.78 - 0.98, p = .017). Notably, a tenfold rise in troponin levels was linked to a 33% decrease in survival time (TR: 0.67, 95% CI: 0.48 - 0.93, p = .014). Conclusions: Our study emphasizes the significant associations between various echocardiographic parameters and troponin levels with reduced survival time among COVID-19 patients experiencing cardiovascular events. These findings highlight the potential utility of echocardiography and troponin assessment in predicting outcomes and guiding management strategies in this patient population.
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The clinical presentation of community-acquired pneumonia (CAP) can vary widely among patients. While many individuals with mild symptoms can be managed as outpatients with excellent outcomes, there is a distinct subgroup of patients who present with severe CAP. In these cases, the mortality rate can reach approximately 25% within 30 days and even up to 50% within a year. It is crucial to focus attention on these patients who are at higher risk. Among the various definitions of severe CAP found in the literature, one commonly used criterion is the requirement for admission to intensive care unit. Notable epidemiological characteristics of these patients include the impact of acute cardiovascular diseases on clinical outcomes and the enduring, independent effect of pneumonia on long-term outcomes. Factors such as pathogen virulence, the presence of comorbidities, and the host response are important contributors to the pathogenesis of severe CAP. In these patients, the host response may be dysregulated and compartmentalized. Gaining a better understanding of the epidemiology and pathogenesis of severe CAP will provide a foundation for the development of new therapies for this condition. This manuscript aims to review the definition, epidemiology, and pathogenesis of severe CAP, shedding light on important aspects that can aid in the improvement of patient care and outcomes.
Subject(s)
Community-Acquired Infections , Pneumonia , Humans , Community-Acquired Infections/drug therapy , Comorbidity , Hospitalization , Intensive Care Units , Pneumonia/drug therapyABSTRACT
Influenza and other respiratory viruses are commonly identified in patients with community-acquired pneumonia, hospital-acquired pneumonia, and in immunocompromised patients with pneumonia. Clinically, it is difficult to differentiate viral from bacterial pneumonia. Similarly, the radiological findings of viral infection are in general nonspecific. The advent of polymerase chain reaction testing has enormously facilitated the identification of respiratory viruses, which has important implications for infection control measures and treatment. Currently, treatment options for patients with viral infection are limited but there is ongoing research on the development and clinical testing of new treatment regimens and strategies.
Subject(s)
Community-Acquired Infections , Influenza, Human , Pneumonia, Bacterial , Pneumonia, Viral , Virus Diseases , Viruses , Humans , Influenza, Human/diagnosis , Influenza, Human/drug therapy , Influenza, Human/epidemiology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Pneumonia, Bacterial/microbiology , Community-Acquired Infections/diagnosis , Community-Acquired Infections/drug therapy , Community-Acquired Infections/epidemiologyABSTRACT
Background: The epidemiology and outcomes of community-acquired pneumonia (CAP) in immunocompromised hosts (ICHs) are not well defined. The objective of this study was to define the epidemiology and outcomes of CAP in ICHs as compared with non-ICHs. Methods: This ancillary study included a prospective cohort of hospitalized adult Louisville residents with CAP from 1 June 2014 to 31 May 2016. An ICH was defined per the criteria of the Centers for Disease Control and Prevention. Geospatial epidemiology explored associations between ICHs hospitalized with CAP and income level, race, and age. Mortality for ICHs and non-ICHs was evaluated during hospitalization and 30 days, 6 months, and 1 year after hospitalization. Results: A total of 761 (10%) ICHs were identified among 7449 patients hospitalized with CAP. The most common immunocompromising medical conditions or treatments were advanced-stage cancer (53%), cancer chemotherapy (23%), and corticosteroid use (20%). Clusters of ICHs hospitalized with CAP were found in areas associated with low-income and Black or African American populations. Mortality by time point for ICHs vs non-ICHs was as follows: hospitalization, 9% vs 5%; 30 days, 24% vs 11%; 6 months, 44% vs 21%; and 1 year, 53% vs 27%, respectively. Conclusions: Approximately 1 in 10 hospitalized patients with CAP is immunocompromised, with advanced-stage cancer being the most frequent immunocompromising condition, as seen in half of all patients who are immunocompromised. Risk for hospitalization may be influenced by socioeconomic disparities and/or race. ICHs have a 2-fold increase in mortality as compared with non-ICHs.
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The Federal Highway Administration (FHWA) mandates biannual bridge inspections to assess the condition of all bridges in the United States. These inspections are recorded in the National Bridge Inventory (NBI) and the respective state's databases to manage, study, and analyze the data. As FHWA specifications become more complex, inspections require more training and field time. Recently, element-level inspections were added, assigning a condition state to each minor element in the bridge. To address this new requirement, a machine-aided bridge inspection method was developed using artificial intelligence (AI) to assist inspectors. The proposed method focuses on the condition state assessment of cracking in reinforced concrete bridge deck elements. The deep learning-based workflow integrated with image classification and semantic segmentation methods is utilized to extract information from images and evaluate the condition state of cracks according to FHWA specifications. The new workflow uses a deep neural network to extract information required by the bridge inspection manual, enabling the determination of the condition state of cracks in the deck. The results of experimentation demonstrate the effectiveness of this workflow for this application. The method also balances the costs and risks associated with increasing levels of AI involvement, enabling inspectors to better manage their resources. This AI-based method can be implemented by asset owners, such as Departments of Transportation, to better serve communities.
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Although Clostridioides difficile infection (CDI) incidence is high in the United States, standard-of-care (SOC) stool collection and testing practices might result in incidence overestimation or underestimation. We conducted diarrhea surveillance among inpatients >50 years of age in Louisville, Kentucky, USA, during October 14, 2019-October 13, 2020; concurrent SOC stool collection and CDI testing occurred independently. A study CDI case was nucleic acid amplification testâ/cytotoxicity neutralization assayâpositive or nucleic acid amplification testâpositive stool in a patient with pseudomembranous colitis. Study incidence was adjusted for hospitalization share and specimen collection rate and, in a sensitivity analysis, for diarrhea cases without study testing. SOC hospitalized CDI incidence was 121/100,000 population/year; study incidence was 154/100,000 population/year and, in sensitivity analysis, 202/100,000 population/year. Of 75 SOC CDI cases, 12 (16.0%) were not study diagnosed; of 109 study CDI cases, 44 (40.4%) were not SOC diagnosed. CDI incidence estimates based on SOC CDI testing are probably underestimated.
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Clostridioides difficile , Clostridium Infections , Humans , Adult , United States , Clostridioides difficile/genetics , Kentucky/epidemiology , Clostridium Infections/diagnosis , Clostridium Infections/epidemiology , Diagnostic Errors , Diarrhea/diagnosis , Diarrhea/epidemiology , Specimen HandlingABSTRACT
SARS-CoV-2 and influenza are primary causes of viral community-acquired pneumonia (CAP). Both pathogens have exhibited high transmissibility and are recognized causes of pandemics. Controversy still exists regarding the clinical outcomes between patients hospitalized with CAP due to these viruses. This secondary analysis identified patients with either influenza or SARS-CoV-2 infections from three cohorts of patients hospitalized for CAP. Clinical outcomes between patients with CAP due to influenza or due to SARS-CoV-2 were evaluated. Primary outcomes included length of stay and in-hospital mortality. To account for population differences between cohorts, each case of influenza CAP was matched to two controls with SARS-CoV-2 CAP. Matching criteria included sex, age, and nursing home residency. Stratified cox-proportional hazards regression or conditional logistic regression were used where appropriate. A total of 259 patients with influenza CAP were matched to two controls with SARS-CoV-2 CAP, totaling to 518 controls. Patients with SARS-CoV-2 CAP were 2.23 times more likely to remain hospitalized at any point in time (95% confidence interval: 1.77-2.80), and had 3.84 times higher odds of dying in-hospital (95% confidence interval: 1.91-7.76) when compared to patients with influenza CAP. After matching and adjusting for confounding variables, patients admitted with SARS-CoV-2 CAP had consistently worse outcomes in comparison to their influenza CAP counterparts. This information can help clinicians decide on the level of care needed for patients with confirmed infections due to these pathogens. Additionally, estimates of disease burden can inform individuals at-risk for poor clinical outcomes, and further highlight the importance of effective preventative strategies.
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The spectrum of disease severity and the insidiousness of clinical presentation make it difficult to recognize patients with coronavirus disease 2019 (COVID-19) at higher risk of worse outcomes or death when they are seen in the early phases of the disease. There are now well-established risk factors for worse outcomes in patients with COVID-19. These should be factored in when assessing the prognosis of these patients. However, a more precise prognostic assessment in an individual patient may warrant the use of predictive tools. In this manuscript, we conduct a literature review on the severity of illness scores and biomarkers for the prognosis of patients with COVID-19. Several COVID-19-specific scores have been developed since the onset of the pandemic. Some of them are promising and can be integrated into the assessment of these patients. We also found that the well-known pneumonia severity index (PSI) and CURB-65 (confusion, uremia, respiratory rate, BP, age ≥ 65 years) are good predictors of mortality in hospitalized patients with COVID-19. While neither the PSI nor the CURB-65 should be used for the triage of outpatient versus inpatient treatment, they can be integrated by a clinician into the assessment of disease severity and can be used in epidemiological studies to determine the severity of illness in patient populations. Biomarkers also provide valuable prognostic information and, importantly, may depict the main physiological derangements in severe disease. We, however, do not advocate the isolated use of severity of illness scores or biomarkers for decision-making in an individual patient. Instead, we suggest the use of these tools on a case-by-case basis with the goal of enhancing clinician judgment.
Subject(s)
COVID-19 , Pneumonia , Humans , Aged , Severity of Illness Index , Prognosis , Biomarkers , Patient AcuityABSTRACT
BACKGROUND: Hospitalized patients with SARS-CoV-2 community-acquired pneumonia (CAP) and associated comorbidities are at increased risk of cardiovascular complications. The magnitude of effect of cardiovascular complications and the role of prior comorbidities on clinical outcomes are not well defined. RESEARCH QUESTION: What is the impact of cardiovascular complications on mortality in hospitalized patients with SARS-CoV-2 CAP? What is the impact of comorbidities and other risk factors on the risk of developing cardiovascular complications and mortality in these patients? STUDY DESIGN AND METHODS: This cohort study included 1,645 hospitalized patients with SARS-CoV-2 CAP. Cardiovascular complications were evaluated. The clinical course during hospitalization was described by using a multistate model with four states: (1) hospitalized with no cardiovascular complications; (2) hospitalized with cardiovascular complications; (3) discharged alive; (4) and dead. Cox proportional hazards regression was used to analyze the impact of prior comorbid conditions on transitions between these states. Hazard ratios (HRs) and 95% CIs are reported. RESULTS: Cardiovascular complications occurred in 18% of patients hospitalized with SARS-CoV-2 CAP. The mortality rate in this group was 45% vs 13% in patients without cardiovascular complications. Male subjects (HR, 1.32; 95% CI, 1.03-1.68), older adults (HR, 1.34; 95% CI, 1.03-1.75), and patients with congestive heart failure (HR, 1.59; 95% CI, 1.18-2.15), coronary artery disease (HR, 1.34; 95% CI, 1.00-1.79), atrial fibrillation (HR, 1.43; 95% CI, 1.06-1.95), direct admissions to the ICU (HR, 1.77; 95% CI, 1.36-2.32), and Pao2/Fio2 < 200 (HR, 1.46; 95% CI, 1.11-1.92) were more likely to develop cardiovascular complications following hospitalization for SARS-CoV-2 CAP; however, these factors are not associated with increased risk of death following a cardiovascular complication. INTERPRETATION: Prior comorbidities, older age, male sex, severity of illness, and hypoxemia are associated with increased risk of cardiovascular complications. Once patients develop cardiovascular complications, the risk of death is extremely high. Cardiovascular complications are the primary drivers of mortality in hospitalized patients with SARS-CoV-2 CAP.
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COVID-19 , Pneumonia , Humans , Male , Aged , SARS-CoV-2 , COVID-19/complications , Cohort Studies , Pneumonia/epidemiology , Hospitalization , Risk Factors , Retrospective StudiesABSTRACT
Lower respiratory infections include acute bronchitis, influenza, community-acquired pneumonia, acute exacerbation of COPD and acute exacerbation of bronchiectasis. They are a major cause of death worldwide and often affect the most vulnerable: children, elderly and the impoverished. In this paper, we review the clinical presentation, diagnosis, severity assessment and treatment of adult outpatients with lower respiratory infections. The paper is divided into sections on specific lower respiratory infections, but we also dedicate a section to COVID-19 given the importance of the ongoing pandemic. Lower respiratory infections are heterogeneous entities, carry different risks for adverse events, and require different management strategies. For instance, while patients with acute bronchitis are rarely admitted to hospital and generally do not require antimicrobials, approximately 40% of patients seen for community-acquired pneumonia require admission. Clinicians caring for patients with lower respiratory infections face several challenges, including an increasing population of patients with immunosuppression, potential need for diagnostic tests that may not be readily available, antibiotic resistance and social aspects that place these patients at higher risk. Management principles for patients with lower respiratory infections include knowledge of local surveillance data, strategic use of diagnostic tests according to surveillance data, and judicious use of antimicrobials.
Subject(s)
Anti-Infective Agents , Bronchitis , COVID-19 , Community-Acquired Infections , Pneumonia , Respiratory Tract Infections , Adult , Child , Humans , Aged , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/epidemiology , Community-Acquired Infections/diagnosis , Community-Acquired Infections/drug therapy , Community-Acquired Infections/epidemiology , Bronchitis/diagnosis , Bronchitis/drug therapy , Pneumonia/diagnosis , Acute Disease , Anti-Infective Agents/therapeutic use , Hospitals , Anti-Bacterial Agents/adverse effectsSubject(s)
COVID-19 , Cardiovascular Diseases , Humans , Troponin , Natriuretic Peptide, Brain , Echocardiography , BiomarkersABSTRACT
BACKGROUND: Newly arriving Syrian refugees can present with specific health characteristics and medical conditions when entering the United States. Given the lack of epidemiological data available for the refugee populations, our study examined the demographic features of Syrian refugees resettled in the state of Kentucky. Specifically, we examined mental and physical health clinical data in both pre-departure health screenings and domestic Refugee Health Assessments (RHA; Kentucky Office for Refugees, n.d.) performed after resettlement. METHOD: The current study adopted a cross-sectional research design. We analyzed outcome data collected from participants from 2013 and 2015. Specifically, a comparative cross-sectional analysis was performed using clinical data from Syrian refugees who underwent an RHA as part of the resettlement process between January 2015 and August 2016. Those data were compared to data derived from refugees from other countries who resettled in Kentucky between 2013 and 2015. RESULTS: Mental health screenings using the Refugee Health Screener (RHS-15; Hollifield et al., 2013) found that 19.5% (n = 34) of adult Syrian refugees reported signs and symptoms from posttraumatic stress, depressive symptoms, and/or anxiety, and nearly 40% (n = 69) reported personal experiences of imprisonment or violence, and/or having witnessed someone experiencing torture or violence. Intestinal parasites and lack of immunity to varicella were the most prevalent communicable diseases among Syrian refugees. Dental abnormalities and decreased visual acuity account for the first and second most prevalent non-communicable conditions. When comparing these results to all refugees arriving during the same years, significant differences arose in demographic variables, social history, communicable diseases, and non-communicable diseases. CONCLUSION: This study provides an initial health profile of Syrian refugees resettling in Kentucky, which reflects mental health as a major healthcare concern. Posttraumatic stress and related symptoms are severe mental health conditions among Syrian refugees above and beyond other severe physical problems.
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Refugees , Adult , Anxiety , Cross-Sectional Studies , Humans , Mental Health , Refugees/psychology , SyriaABSTRACT
This study analyzed the levels at admission of biomarkers for their association with and ability to predict risk of severe outcomes, including admission to the ICU, need for invasive mechanical ventilation (IMV), need for vasopressor use (VU), and in-hospital mortality (IHM) in 700 patients hospitalized with COVID-19. Biomarker data split by outcomes was compared using Mann-Whitney U tests; frequencies of biomarker values were compared using Chi-square tests and multivariable logistic regression analysis was performed to look at the impact of biomarkers by outcome. Patients that suffered IHM were more likely to have reduced platelet numbers and high blood urea nitrogen (BUN) levels among patients admitted to the ICU. Risk factors for mortality were related to hyper-coagulability (low platelet count and increased D-dimer) and decreased respiratory (PaO2/FiO2 ratio) and kidney function (BUN). Association with risks of other severe outcomes were as follows: ICU with hyper-inflammation (IL-6) and decreased respiratory function; IMV with low platelet count, abnormal neutrophil-lymphocyte ratio with reduced respiratory function, VU with inflammatory markers (IL-6), and low platelet count with respiratory function. Our studies confirmed the association of biomarkers of hematological, inflammatory, coagulation, pulmonary and kidney functions with disease severity. Whether these biomarkers have any mechanistic or causal role in the disease progress requires further investigation.
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Biomarkers/metabolism , COVID-19/metabolism , COVID-19/pathology , Aged , Female , Hospital Mortality , Hospitalization , Humans , Inflammation/metabolism , Inflammation/pathology , Intensive Care Units , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/pathogenicity , Severity of Illness IndexABSTRACT
BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have poor outcomes in the setting of community-acquired pneumonia (CAP) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The primary objective is to compare outcomes of SARS-CoV-2 CAP and non-SARS-CoV-2 CAP in patients with COPD. The secondary objective is to compare outcomes of SARS-CoV-2 CAP with and without COPD. METHODS: In this analysis of two observational studies, three cohorts were analyzed: (1) patients with COPD and SARS-CoV-2 CAP; (2) patients with COPD and non-SARS-CoV-2 CAP; and (3) patients with SARS-CoV-2 CAP without COPD. Outcomes included length of stay, ICU admission, cardiac events, and in-hospital mortality. RESULTS: Ninety-six patients with COPD and SARS-CoV-2 CAP were compared to 1129 patients with COPD and non-SARS-CoV-2 CAP. 536 patients without COPD and SARS-CoV-2 CAP were analyzed for the secondary objective. Patients with COPD and SARS-CoV-2 CAP had longer hospital stay (15 vs 5 days, p < 0.001), 4.98 higher odds of cardiac events (95% CI: 3.74-6.69), and 7.31 higher odds of death (95% CI: 5.36-10.12) in comparison to patients with COPD and non-SARS-CoV-2 CAP. In patients with SARS-CoV-2 CAP, presence of COPD was associated with 1.74 (95% CI: 1.39-2.19) higher odds of ICU admission and 1.47 (95% CI: 1.05-2.05) higher odds of death. CONCLUSION: In patients with COPD and CAP, presence of SARS-CoV-2 as an etiologic agent is associated with more cardiovascular events, longer hospital stay, and seven-fold increase in mortality. In patients with SARS-CoV-2 CAP, presence of COPD is associated with 1.5-fold increase in mortality.
Subject(s)
COVID-19/physiopathology , Cardiovascular Diseases/epidemiology , Community-Acquired Infections/physiopathology , Hospital Mortality , Intensive Care Units/statistics & numerical data , Length of Stay/statistics & numerical data , Pneumonia/physiopathology , Pulmonary Disease, Chronic Obstructive/physiopathology , Aged , Arrhythmias, Cardiac/epidemiology , COVID-19/epidemiology , COVID-19/therapy , Case-Control Studies , Community-Acquired Infections/epidemiology , Community-Acquired Infections/therapy , Comorbidity , Edema, Cardiac/epidemiology , Female , Heart Failure/epidemiology , Hospitalization , Humans , Male , Middle Aged , Myocardial Infarction/epidemiology , Pneumonia/epidemiology , Pneumonia/therapy , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/therapy , Pulmonary Edema/epidemiology , Pulmonary Embolism/epidemiology , Stroke/epidemiologyABSTRACT
BACKGROUND: The Confusion, Urea > 7 mM, Respiratory Rate ≥ 30 breaths/min, BP < 90 mm Hg (Systolic) or < 60 mm Hg (Diastolic), Age ≥ 65 Years (CURB-65) score and the Pneumonia Severity Index (PSI) are well-established clinical prediction rules for predicting mortality in patients hospitalized with community-acquired pneumonia (CAP). SARS-CoV-2 has emerged as a new etiologic agent for CAP, but the role of CURB-65 score and PSI have not been established. RESEARCH QUESTION: How effective are CURB-65 score and PSI at predicting in-hospital mortality resulting from SARS-CoV-2 CAP compared with non-SARS-CoV-2 CAP? Can these clinical prediction rules be optimized to predict mortality in SARS-CoV-2 CAP by addition of procalcitonin and D-dimer? STUDY DESIGN AND METHODS: Secondary analysis of two prospective cohorts of patients with SARS-CoV-2 CAP or non-SARS-CoV-2 CAP from eight adult hospitals in Louisville, Kentucky. RESULTS: The in-hospital mortality rate was 19% for patients with SARS-CoV-2 CAP and 6.5% for patients with non-SARS-CoV-2 CAP. For the PSI score, receiver operating characteristic (ROC) curve analysis resulted in an area under the ROC curve (AUC) of 0.82 (95% CI, 0.78-0.86) and 0.79 (95% CI, 0.77-0.80) for patients with SARS-CoV-2 CAP and non-SARS-CoV-2 CAP, respectively. For the CURB-65 score, ROC analysis resulted in an AUC of 0.79 (95% CI, 0.75-0.84) and 0.75 (95% CI, 0.73-0.77) for patients with SARS-CoV-2 CAP and non-SARS-CoV-2 CAP, respectively. In SARS-CoV-2 CAP, the addition of D-dimer (optimal cutoff, 1,813 µg/mL) and procalcitonin (optimal cutoff, 0.19 ng/mL) to PSI and CURB-65 score provided negligible improvement in prognostic performance. INTERPRETATION: PSI and CURB-65 score can predict in-hospital mortality for patients with SARS-CoV-2 CAP and non-SARS-CoV-2 CAP comparatively. In patients with SARS-CoV-2 CAP, the inclusion of either D-dimer or procalcitonin to PSI or CURB-65 score did not improve the prognostic performance of either score. In patients with CAP, regardless of cause, PSI and CURB-65 score remain adequate for predicting mortality in clinical practice.
Subject(s)
COVID-19 , Community-Acquired Infections , Pneumonia , Adult , Aged , Hospital Mortality , Humans , Pneumonia/diagnosis , Procalcitonin , Prognosis , Prospective Studies , ROC Curve , Retrospective Studies , SARS-CoV-2 , Severity of Illness IndexABSTRACT
BACKGROUND: Influenza is associated with excess morbidity and mortality of individuals each year. Few therapies exist for treatment of influenza infection, and each require initiation as early as possible in the course of infection, making efficacy difficult to estimate in the hospitalized patient with lower respiratory tract infection. Using causal machine learning methods, we re-analyze data from a randomized trial of oseltamivir versus standard of care aimed at reducing clinical failure in hospitalized patients with lower respiratory tract infection during the influenza season. METHODS: This was a secondary analysis of the Rapid Empiric Treatment with Oseltamivir Study (RETOS). Conditional average treatment effects (CATE) and 95% confidence intervals were computed from causal forest including 85 clinical and demographic variables. RETOS was a multicenter, randomized, unblinded, trial of adult patients hospitalized with lower respiratory tract infections in Kentucky from 2009 through 2012. Adult hospitalized patients with lower respiratory tract infection were randomized to standard of care or standard of care plus oseltamivir as early as possible after hospital admission but within 24 h of enrollment. After randomization, oseltamivir was initiated in the treatment arm per package insert. The primary outcome was clinical failure, a composite measure including failure to reach clinical improvement within 7 days, transfer to intensive care 24 h after admission, or rehospitalization or death within 30 days. RESULTS: A total of 691 hospitalized patients with lower respiratory tract infections were included in the study. The only subgroup of patients with a statistically significant CATE was those with laboratory-confirmed influenza infection with a 26% lower risk of clinical failure when treated with oseltamivir (95% CI 3.2-48.0%). CONCLUSIONS: This study suggests that addition of oseltamivir to standard of care may decrease clinical failure in hospitalized patients with influenza-associated lower respiratory tract infection versus standard of care alone. These results are supportive of current recommendations to initiate antiviral treatment in hospitalized patients with confirmed or suspected influenza as soon as possible after admission. Trial registration Original trial: Clinical Trials.Gov; Rapid Empiric Treatment With Oseltamivir Study (RETOS) (RETOS); ClinicalTrials.gov Identifier: NCT01248715 https://clinicaltrials.gov/ct2/show/NCT01248715.