Clinical Outcomes of Coronavirus Disease 2019 With Evidence-based Supportive Care.

Calls for adherence to evidence-based medicine have emerged during the initial wave of the COVID-19 pandemic but reports of outcomes are lacking. This retrospective study of an institutional cohort including 135 patients with confirmed COVID-19 demonstrates positive outcomes when organizational standards of care consist of evidence-based supportive therapies.

Posttraumatic Stress Disorder Is Associated With a Decrease in Anaerobic Threshold, Oxygen Pulse, and Maximal Oxygen Uptake.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been linked to respiratory symptoms and functional limitations, but the mechanisms leading to this association are poorly defined. RESEARCH QUESTION: What is the relationship between PTSD, lung function, and the cardiopulmonary response to exercise in combat veterans presenting with chronic respiratory symptoms? STUDY DESIGN AND METHODS: This study prospectively enrolled military service members with respiratory symptoms following deployment to southwest Asia. All participants underwent a comprehensive evaluation that included pulmonary function testing and cardiopulmonary exercise testing. Pulmonary function test variables and cardiopulmonary response to exercise were compared in subjects with and without PTSD by using multivariable linear regression to adjust for confounders. RESULTS: A total of 303 participants were included (PTSD, n = 70; non-PTSD, n = 233). Those with PTSD had a greater frequency of current respiratory symptoms. There were no differences in measures for airway disease or lung volumes, but patients with PTSD had a reduction in diffusing capacity that was eliminated following adjustment for differences in hemoglobin levels. Participants with PTSD had a lower anaerobic threshold (23.9 vs 26.4 cc/kg per minute; P = .004), peak oxygen pulse (19.7 vs 18.5 cc/beat; P = .03), and peak oxygen uptake (34.5 vs 38.8 cc/kg per minute; P < .001). No significant difference was observed in gas exchange, respiratory reserve, or effort at peak exercise between participants with and without PTSD. INTERPRETATION: A diagnosis of PTSD was associated with a reduced anaerobic threshold, oxygen pulse, and peak oxygen uptake. This objective reduction in cardiopulmonary work is independent of baseline lung function, was not associated with abnormalities in gas exchange or respiratory reserve, and may be related to deconditioning.

Optimizing routine screening for cardiac sarcoidosis through use of commonly available studies.

BACKGROUND: Sarcoidosis is a multisystem granulomatous disorder with unclear etiology. Morbidity and mortality vary based on organ involvement, with cardiac sarcoidosis (CS) associated with higher mortality; despite this, CS remains underdiagnosed. The Heart Rhythm Society (HRS) expert consensus statement recommends screening sarcoidosis patients for CS utilizing a symptom screen, EKG, and echocardiogram (TTE), while the American Thoracic Society (ATS) guideline recommends only EKG and symptom screening. These recommendations, however, are based on limited data with recommendations for further studies. RESEARCH QUESTION: The purpose is to evaluate the prevalence of abnormal screening tests in patients with sarcoidosis and the correlation of these tests with the subsequent diagnosis of CS. A specific emphasis was placed on evaluating the sensitivity of the recommendations versus the sensitivity of a modified criteria. STUDY DESIGN: and Methods: This study retrospectively evaluated a database of prospectively enrolled patients from a tertiary military academic center. All patients who underwent imaging with cardiac MRI and/or FDG-PET were identified. These results were correlated with screening studies (symptom screen, EKG, TTE, and ambulatory rhythm monitoring (ARM)) and used to calculate sensitivity, specificity, and positive and negative predictive values for each test. Using a clinical diagnosis of CS as the reference standard, the sensitivity and specificity of the HRS criteria were calculated and compared to a modified screening rubric developed a priori, consisting of minor changes to the criteria and the addition of ARM. RESULTS: This study evaluated 114 patients with sarcoidosis with 132 advanced imaging events, leading to a diagnosis of CS in 36 patients. Utilizing HRS screening recommendations, the sensitivity for CS was 63.9%, while the modified criteria increased sensitivity to 94.4%. INTERPRETATION: This study suggests that the HRS guidelines lack sensitivity to effectively screen for CS and that a modified screening model which includes ARM may be more effective.

Isolated Small Airway Dysfunction and Ventilatory Response to Cardiopulmonary Exercise Testing.

BACKGROUND: The effect of isolated small airway dysfunction (SAD) on exercise remains incompletely characterized. We sought to quantify the relationship between isolated SAD, identified with lung testing, and the respiratory response to exercise. METHODS: We conducted a prospective evaluation of service members with new-onset dyspnea. All subjects underwent plethysmography, diffusing capacity of the lung for carbon monoxide (DLCO), impulse oscillometry, high-resolution computed tomography (HRCT), and cardiopulmonary exercise testing (CPET). In subjects with normal basic spirometry, DLCO, and HRCT, SAD measures were analyzed for associations with ventilatory parameters at submaximal exercise and at maximal exercise during CPET. RESULTS: We enrolled 121 subjects with normal basic spirometry (ie, FEV1, FVC, and FEV1/FVC), DLCO, and HRCT. Mean age and body mass index were 37.4 ± 8.8 y and 28.4 ± 3.8 kg/m2, respectively, and 110 (90.9%) subjects were male. The prevalence of SAD varied from 2.5% to 28.8% depending on whether FEV3/FVC, FEF25-75%, residual volume/total lung capacity, and R5-R20 were used to identify SAD. Agreement on abnormal SAD across tests was poor (kappa = -0.03 to 0.07). R5-R20 abnormalities were related to higher minute ventilation ([Formula: see text]) and higher [Formula: see text]/maximum voluntary ventilation (MVV) during submaximal exercise and to lower [Formula: see text] during maximal exercise. After adjustment for differences at baseline, there remained a trend toward a relationship between R5-R20 and an elevated [Formula: see text]/MVV during submaximal exercise (ß = 0.04, 95% CI -0.01 to 0.09, P = .10), but there was no significant association with [Formula: see text] during submaximal exercise or with [Formula: see text] during maximal exercise. No other SAD measures showed a relationship with ventilatory parameters. CONCLUSIONS: In 121 subjects with normal basic spirometry, DLCO, and HRCT, we found poor agreement across tests used to detect SAD. Among young, healthy service members with postdeployment dyspnea, SAD as identified by lung function testing does not predict changes in the ventilatory response to exercise.

Clinical Evaluation of Deployed Military Personnel With Chronic Respiratory Symptoms: Study of Active Duty Military for Pulmonary Disease Related to Environmental Deployment Exposures (STAMPEDE) III.

BACKGROUND: Chronic respiratory symptoms are frequently reported after Southwest Asia deployment in support of combat operations. The full spectrum of clinical lung diseases related to these deployments is not well characterized. METHODS: Military personnel with chronic symptoms, primarily exertional dyspnea, underwent a standardized cardiopulmonary evaluation at two tertiary medical centers. Pulmonary function testing consisted of spirometry, lung volume, diffusing capacity, impulse oscillometry, and bronchodilator testing. Further testing included methacholine challenge, exercise laryngoscopy, high-resolution CT scan, ECG, and transthoracic echocardiography. RESULTS: A total of 380 participants with a mean age of 38.5 ± 8.4 years completed testing. Asthma was the most common diagnosis in 87 patients (22.9%) based on obstructive spirometry/impulse oscillometry and evidence of airway hyperreactivity, whereas another 57 patients (15.0%) had reactivity with normal spirometry. Airway disorders included 25 (6.6%) with laryngeal disorders and 16 (4.2%) with excessive dynamic airway collapse. Interstitial lung disease was identified in six patients (1.6%), whereas 11 patients (2.9%) had fixed obstructive lung disorders. Forty patients (10.5%) had isolated pulmonary function abnormalities and 16 (4.2%) had miscellaneous disorders. The remaining 122 patients (32.1%) with normal studies were classified as undiagnosed exertional dyspnea. Significant comorbidities identified included elevated BMI > 30 kg/m2 (34.2%), smoking (36.4%), positive allergy testing (43.7%), sleep apnea (38.5%), and esophageal reflux (13.6%). Mental health disorders and posttraumatic stress disorder were likewise common. CONCLUSIONS: Postdeployment pulmonary evaluation should focus on common diseases, such as asthma and airway hyperreactivity, and include testing for upper airway disorders. Diffuse lung diseases were rarely diagnosed, whereas numerous comorbidities were common.

Differences between low-molecular-weight and unfractionated heparin for venous thromboembolism prevention following ischemic stroke: a metaanalysis.

BACKGROUND: Venous thromboembolism (VTE) remains a major cause of morbidity following stroke. The optimal form of pharmacologic prophylaxis following stroke is unknown. METHODS: We identified randomized trials comparing unfractionated heparin (UFH) to low-molecular-weight heparin (LMWH) for VTE prevention in ischemic stroke patients. We focused on the risk for VTE, pulmonary embolism (PE), bleeding, and mortality as a function of the type of agent used for prophylaxis. Findings were pooled with a random-effects model. RESULTS: We identified three trials including 2,028 patients. Two of the studies were blinded, two studies relied on enoxaparin, while one study utilized certoparin. In two studies, UFH was administered three times a day, while it was administered twice daily in the remaining study. The use of LMWH was associated with a significant risk reduction for any VTE (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.41 to 0.70; p < 0.001). Limiting the analysis to proximal VTEs also indicated that LMWHs were superior (OR with LMWH vs UFH, 0.53; 95% CI, 0.37 to 0.75; p < 0.001). LMWH use led to fewer PEs as well (OR, 0.26; 95% CI, 0.07 to 0.95; p = 0.042). There were no differences in rates of overall bleeding, intracranial hemorrhage, or mortality based on the type of agent employed. Restricting the analysis to the reports employing enoxaparin did not alter our findings. CONCLUSIONS: The prophylactic use of LMWH compared to UFH following ischemic stroke is associated with a reduction in both VTE and PE. This benefit is not associated with an increased incidence of bleeding. Broader use of LMWH for VTE prevention after ischemic stroke is warranted.

Inhaled prostacyclin in combination with high-frequency percussive ventilation.

We present a case of severe acute respiratory distress syndrome pursuant to inhalation of a compressed gas computer keyboard cleaner. Despite the use of multimodal therapy to include empiric antibiotics, intravenous paralytics, intravenous concentrated albumin, high-dose corticosteroids as well as sustained high mean airway pressure mechanical ventilation by airway pressure release and high-frequency percussive ventilation (HFPV) modes, the patient demonstrated an unchanging arterial oxygen tension/fraction of inspired oxygen ratio of only 57 mm Hg. A trial of nebulized prostacyclin was initiated during HFPV leading to a significant improvement in arterial oxygen tension/fraction of inspired oxygen to 147 mm Hg. The improved oxygen tension allowed for a reduction in mean airway pressure and oxygen concentration as well the safe aeromedical evacuation of the patient from the combat theater. Further, prospective studies are required to validate the magnitude of response to inhaled prostacyclin during HFPV.

Do clinical features allow for accurate prediction of fungal pathogenesis in bloodstream infections? Potential implications of the increasing prevalence of non-albicans candidemia.

OBJECTIVE: To describe the evolving epidemiology of fungal bloodstream infections in critically ill and noncritically ill patients and to identify predictors of infection with non-albicans yeast species. DESIGN: Retrospective case series. SETTING: Two academic, tertiary care centers. PARTICIPANTS: All persons during a 4-yr period who developed fungemia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We initially compared subjects with Candida albicans vs. alternative yeast. In a sensitivity analysis, we compared persons with potentially fluconazole-resistant organisms (Candida glabrata and Candida krusei) to those with other fungi. We also repeated these analyses in the subgroup of persons in the intensive care unit when they developed fungemia. The study cohort included 245 patients (60% in the intensive care unit), and C. albicans accounted for 52% of infections, whereas C. glabrata represented 20% of cases. The distribution of isolates was similar in both intensive care unit patients and those on the wards. In the entire population, no variable, including both previous fluconazole exposure and severity of illness, correlated with the fungemia due to a non-albicans species. In our sensitivity analysis, no factor was independently associated with a potentially fluconazole-resistant yeast. For the subgroup of subjects whose fungemia was diagnosed while they were in the intensive care unit, no variable differentiated C. albicans from non-albicans isolates. CONCLUSIONS: Non-albicans yeast are common both in the intensive care unit and on the wards. Simple clinical factors do not allow the clinician to effectively identify patients likely infected with non-albicans pathogens or with possible fluconazole-resistant fungi.

Invasive approaches to the diagnosis of ventilator-associated pneumonia: a meta-analysis.

OBJECTIVE: Ventilator-associated pneumonia remains a major challenge in the intensive care unit. The role for invasive diagnostic methods (e.g., bronchoscopy) remains unclear. We hypothesized that invasive testing would alter antibiotic management in patients with ventilator-associated pneumonia but would not necessarily alter mortality. DESIGN: Meta-analysis of randomized, controlled trials of invasive diagnostic strategies in suspected ventilator-associated pneumonia and a separate pooled analysis of prospective, observational studies of the effect of invasive cultures on antibiotic utilization in ventilator-associated pneumonia. SETTING: NA. PATIENTS: Subjects enrolled in the various clinical trials identified. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified four randomized, controlled trials that included 628 patients. The overall quality of these studies was moderate (median Jadad score of 5) and there was both clinical and statistical heterogeneity among these trials. Ventilator-associated pneumonia was confirmed bronchoscopically in 44-69% of participants, with Pseudomonas aeruginosa and Staphylococcus aureus being the most frequently isolated pathogens. Most subjects (90.3%) received adequate antibiotics; however, in one trial there was a significant difference between the invasive and noninvasive arms with respect to this factor. Overall, an invasive approach did not alter mortality (odds ratio 0.89, 95% confidence interval 0.56-1.41). Invasive testing, though, affected antibiotic utilization (odds ratio for change in antibiotic management after invasive sampling, 2.85, 95% confidence interval 1.45-5.59). Five prospective observational studies examined invasive testing and included 635 subjects. These reports confirm that invasive sampling leads to modifications in the antibiotic regimen in more than half of patients (pooled estimate for rate of alteration in antibiotic prescription, 50.3%, 95% confidence interval 35.9-64.6%). CONCLUSIONS: Few trials have systematically examined the impact of diagnostic techniques on outcomes for patients suspected of suffering from ventilator-associated pneumonia. Invasive strategies do not alter mortality. Invasive approaches to ventilator-associated pneumonia affect antibiotic use and prescribing.

Effect of standardized orders and provider education on head-of-bed positioning in mechanically ventilated patients.

OBJECTIVE: Semirecumbent head-of-bed positioning in mechanically ventilated patients decreases the risk of developing ventilator-associated pneumonia (VAP). The purpose of this study was to determine whether the addition of a standardized order followed by the initiation of a provider education program would increase the frequency with which our patients were maintained in the semirecumbent position. DESIGN: Prospective, pre-, and postintervention observational study. SETTING: A tertiary care, U.S. Army teaching hospital. PATIENTS: Mechanically ventilated medical and surgical intensive care unit patients. INTERVENTIONS: The first intervention involved the addition of an order for semirecumbent head-of-bed positioning to our intensive care unit order sets. This was followed 2 months later with a second intervention, which was a nurse and physician education program emphasizing semirecumbent positioning. MEASUREMENTS AND MAIN RESULTS: Data regarding head-of-bed positioning were collected on 100 patient observations at baseline and at 1 and 2 months after each of our interventions. The mean angle of head of bed increased from 24 +/- 9 degrees at baseline to 35 +/- 9 degrees (p <.05) 2 months after the addition of the standard order. The percentage of observations with head of bed >45 degrees increased from 3% to 16% 2 months after the standardized order (p <.05). Two months after our provider education program, the mean angle of the head of bed was 34 +/- 11 degrees and the percentage of patients with head of bed >45 degrees was 29% (p = NS compared with values after the first intervention). Data collected 6 months after completion of our education programs showed that these improvements were maintained. CONCLUSIONS: Standardizing the process of care via the addition of an order specifying head-of-bed position significantly increased the number of patients who were placed in the semirecumbent position. In an era of cost-conscious medicine, interventions that utilize protocols and education programs should be emphasized.