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No abstract available. Article truncated after 150 words. A shortage of critical care physicians in the United States has been widely recognized and reported (1). Most intensive care units (ICUs) do no not have a formally-trained intensivist in their staff despite compelling evidence that high-intensity intensivist staffing leads to better patient outcomes (1,2). Critical care telemedicine is one potential solution that has expanded rapidly since its inception in 2000 (3). In its simplest form, telemedicine leverages audiovisual technology and the electronic medical record to provide remote two-way communication between a physician and a patient. Current telemedicine models differ by the type of hardware facilitating remote audiovisual interaction, the location of the provider, and the type of patient-care service provided. We collectively have experience with several of these models and feel that future telemedicine programs will likely integrate the most advantageous aspects of each with an increasing role for telemedicine robotics. The dominant current model for providing Critical Care …

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Streptococcus pneumoniae remains a primary pathogen in hospitalized patients with community-acquired pneumonia (CAP). The objective of this study was to define the epidemiology of pneumococcal pneumonia in Louisville, Kentucky, and to estimate the burden of pneumococcal pneumonia in the United States (US). This study was nested in a prospective population-based cohort study of all adult residents in Louisville, Kentucky, who were hospitalized with CAP from 1 June 2014 to 31 May 2016. In hospitalized patients with CAP, urinary antigen detection of 24 S. pneumoniae serotypes (UAD-24) was performed. The annual population-based pneumococcal pneumonia incidence was calculated. The distribution of S. pneumoniae serotypes was characterized. Ecological associations between pneumococcal pneumonia and income level, race, and age were defined. Mortality was evaluated during hospitalization and at 30 days, 6 months, and 1 year after hospitalization. Among the 5402 CAP patients with a UAD-24 test performed, 708 (13%) patients had pneumococcal pneumonia. The annual cumulative incidence was 93 pneumococcal pneumonia hospitalizations per 100,000 adults (95% CI = 91-95), corresponding to an estimated 226,696 annual pneumococcal pneumonia hospitalizations in the US. The most frequent serotypes were 19A (12%), 3 (11%), and 22F (11%). Clusters of cases were found in areas with low incomes and a higher proportion of Black or African American population. Pneumococcal pneumonia mortality was 3.7% during hospitalization, 8.2% at 30 days, 17.6% at 6 months, and 25.4% at 1 year after hospitalization. The burden of pneumococcal pneumonia in the US remains significant, with an estimate of more than 225,000 adults hospitalized annually, and approximately 1 out of 4 hospitalized adult patients dies within 1 year after hospitalization.

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.

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., Competing Interests: Conflict of interest: R. Cavallazzi has nothing to disclose. Conflict of interest: J.A. Ramirez reports grants or contracts from Pfizer (institutional payment for research); consulting fees from Dompe (personal payment); and participation on a Data Safety Monitoring Board or Advisory Board for Paratek (personal payment), all outside the submitted work., (Copyright ©The authors 2022.)

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

SARS coronavirus 2 (SARS-CoV-2) is a novel viral pathogen that causes a clinical disease called coronavirus disease 2019 (COVID-19). Although most COVID-19 cases are asymptomatic or involve mild upper respiratory tract symptoms, a significant number of patients develop severe or critical disease. Patients with severe COVID-19 commonly present with viral pneumonia that may progress to life-threatening acute respiratory distress syndrome (ARDS). Patients with COVID-19 are also predisposed to venous and arterial thromboses that are associated with a poorer prognosis. The present study identified the emergence of a low-density inflammatory neutrophil (LDN) population expressing intermediate levels of CD16 (CD16Int) in patients with COVID-19. These cells demonstrated proinflammatory gene signatures, activated platelets, spontaneously formed neutrophil extracellular traps, and enhanced phagocytic capacity and cytokine production. Strikingly, CD16Int neutrophils were also the major immune cells within the bronchoalveolar lavage fluid, exhibiting increased CXCR3 but loss of CD44 and CD38 expression. The percentage of circulating CD16Int LDNs was associated with D-dimer, ferritin, and systemic IL-6 and TNF-α levels and changed over time with altered disease status. Our data suggest that the CD16Int LDN subset contributes to COVID-19-associated coagulopathy, systemic inflammation, and ARDS. The frequency of that LDN subset in the circulation could serve as an adjunct clinical marker to monitor disease status and progression.

The obesity paradox postulates that increased body mass index (BMI) is protective in certain patient populations. We aimed to investigate the association of BMI and different weight classes with outcomes in hospitalised patients with community-acquired pneumonia (CAP). This cohort study is a secondary data analysis of the University of Louisville Pneumonia Study database, a prospective study of hospitalised adult patients with CAP from June, 2014, to May, 2016, in Louisville, KY, USA. BMI as a predictor was assessed both as a continuous and categorical variable. Patients were categorised as weight classes based on World Health Organization definitions: BMI of <18.5 kg·m -2 (underweight), BMI of 18.5 to <25 kg·m -2 (normal weight), BMI of 25.0 to <30 kg·m -2 (overweight), BMI of 30 to <35 kg·m -2 (obesity class I), BMI of 35 to <40 kg·m -2 (obesity class II), and BMI of ≥40 kg·m -2 (obesity class III). Study outcomes, including time to clinical stability, length of stay, clinical failure and mortality, were assessed in hospital, at 30 days, at 6 months and at 1 year. Clinical failure was defined as the need for noninvasive ventilation, invasive ventilation or vasopressors within 1 week of admission. Patient characteristics and crude outcomes were stratified by BMI categories, and generalised additive binomial regression models were performed to analyse the impact of BMI as a continuous variable on study outcomes adjusting for possible confounding variables. 7449 patients were included in the study. Median time to clinical stability was 2 days for every BMI group. There was no association between BMI as a continuous predictor and length of stay <5 days (chi-squared=1.83, estimated degrees of freedom (EDF)=2.74, p=0.608). Clinical failure was highest in the class III obesity group, and higher BMI as a continuous predictor was associated with higher odds of clinical failure. BMI as a continuous predictor was significantly associated with 30-day (chi-squared=39.97, EDF=3.07, p<0.001), 6-month (chi-squared=89.42, EDF=3.44, p<0.001) and 1-year (chi-squared=83.97, EDF=2.89, p<0.001) mortalities. BMI ≤24.14 kg·m -2 was a risk factor whereas BMI ≥26.97 kg·m -2 was protective for mortality at 1-year. The incremental benefit of increasing BMI plateaued at 35 kg·m -2 . We found a protective benefit of obesity on mortality in CAP patients. However, we uniquely demonstrate that the association between BMI and mortality is not linear, and no incremental benefit of increasing BMI levels is observed in those with obesity classes II and III., Competing Interests: Conflict of interest: R.Y. Kim has nothing to disclose. Conflict of interest: C. Connor has nothing to disclose. Conflict of interest: S. Furmanek has nothing to disclose. Conflict of interest: J.A. Ramirez has nothing to disclose. Conflict of interest: R. Cavallazzi has nothing to disclose., (Copyright ©ERS 2021.)

Infective endocarditis is associated with a variety of clinical signs, but its association with multisystem vasculitis is rarely reported. A high index of suspicion is necessary to differentiate a primary autoimmune vasculitis from an infectious cause as the wrong treatment can lead to significant morbidity and mortality. We present a 71-year-old female patient with negative blood cultures, on antibiotics for recent bacteraemia, who presented with cutaneous and renal leucocytoclastic vasculitis. Workup revealed a vegetation adjacent to her right atrial pacemaker lead consistent with infective endocarditis and her vasculitis completely resolved with appropriate antibiotics., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Sepsis is associated with high morbidity and mortality and high healthcare costs. We hypothesized that a multifaceted quality improvement project would lead to an improvement in compliance with the sepsis "bundles.", Design: Patients presenting to the emergency department that met criteria for sepsis at triage triggered notification of an emergency department physician and the sepsis response team in order to facilitate timely completion of the 3-hour bundles. The primary outcome was compliance with the seven sepsis bundle components. Secondary outcomes included all-cause inhospital mortality, hospital length of stay, and time in the emergency department., Setting: The study was conducted at a 404-bed tertiary academic medical center over a 2-year period., Patients or Subjects: The study included patients that presented to the emergency department that met criteria for sepsis., Measurements or Main Results: The study included 163 patients. Overall compliance with the sepsis bundle was 79% (95% CI, 72-84%). There was significant improvement in comparison with the hospital's historical compliance of 37% ( p < 0.001). Compliance with the individual bundle components ranged from 80% to 100%. Sixteen patients died (10%) in the hospital. There was no statistically significant difference between the compliant and noncompliant groups regarding the secondary outcomes of length of stay or inhospital mortality., Conclusions: This study found that implementation of a sepsis response team can improve compliance with completion of sepsis bundles. This indicates that it is feasible to implement a multidisciplinary quality initiative to improve timely treatment of patients with sepsis at an academic center using a resident-driven sepsis response team., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Multiple criteria have been proposed to define community-acquired pneumonia (CAP) severity and predict ICU admission. Validity studies have found differing results. We tested four models to assess severe CAP built upon the criteria included in the 2007 IDSA/ATS guidelines, hypothesizing that a model providing different weights for each individual criterion may be of better predictability., Methods: Retrospective analysis of a prospective cohort study of adult hospitalizations for CAP at nine hospitals in Louisville, KY from June 2014 to May 2016. Four models were tested. Model 1: original 2007 IDSA/ATS criteria. Model 2: modified IDSA/ATS criteria by removing multilobar infiltrates and changing BUN threshold to ≥30 mg/dL; adding lactate level >2 mmol/L and requirement of non-invasive mechanical ventilation (NIMV). CAP was severe with 1 major criterion or 3 minor criteria. Model 3: same criteria as model 2, CAP was severe with 1 major criterion or 4 minor criteria. Model 4: multiple regression analysis including the modified criteria as described in models 2 and 3 with a score assigned to each variable according to the magnitude of association between variable and need for ICU., Results: 8284 CAP hospitalizations were included. 1458 (18%) required ICU. Model 4 showed highest prediction of need for ICU with an area under the curve of 0.91, highest accuracy, specificity, positive predictive value, and agreement among models., Conclusion: Assigning differential weights to clinical predictive variables generated a score with accuracy that outperformed the original 2007 IDSA/ATS criteria for severe CAP and ICU admission., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The diagnosis of asthma is not always straightforward and can be even more challenging in older adults. Asthma is ideally confirmed by demonstration of variable expiratory airflow limitation. However, many patients with asthma do not demonstrate airflow obstruction nor show bronchodilator reversibility. We aimed to investigate predictors for a positive bronchial challenge test with methacholine in older adults being evaluated for asthma., Methods: This is a diagnostic accuracy study with a cross-sectional design. Participants ≥60 years with suspected asthma and a negative postbronchodilator response on spirometry were included. All participants underwent a methacholine challenge test (MCT). We assessed the value of standard asthma screening questions and additional clinical questions to predict the MCT results. A multivariable logistic regression model was developed to assess the variables independently impacting the odds of a positive MCT result., Results: Our study included 71 participants. The majority were female (n = 52, 73.2%) and the average age was 67.0 years. Those with a positive MCT (n = 55, 77.5%) were more likely to have wheezing or coughing due to allergens (n = 51, 92.7% vs. n = 12, 75.0%; P = 0.004) and difficulty walking several blocks (n = 14, 25.5% vs. n = 1, 6.3%, P = 0.009). After adjustment, having wheezing or coughing due to allergens (OR = 4.2, 95% CI 1.7-7.8, P = 0.012) remained the only significant independent predictor of a positive MCT., Conclusions: In older adults with suspected asthma, questioning about wheezing or coughing due to allergens provides a modest independent value to predict a MCT result in those who previously had a negative postbronchodilator response on spirometry., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality. Guideline-discordant care of COPD is not uncommon. Further, there is a push to incorporate quality improvement (QI) training into internal medicine (IM) residency curricula. This study compared quality of care of COPD patients in an IM residents' clinic and a pulmonary fellows' clinic and, subsequently, the results of a quality improvement program in the residents' clinic. Pre-intervention rates of quality measure adherence were compared between the IM teaching clinic ( n = 451) and pulmonary fellows' clinic ( n = 177). Patient encounters in the residents' teaching clinic after quality improvement intervention ( n = 119) were reviewed and compared with pre-intervention data. Prior to intervention, fellows were significantly more likely to offer smoking cessation counseling ( p = 0.024) and document spirometry showing airway obstruction ( p < 0.001). Smoking cessation counseling, pneumococcal vaccination, and diagnosis of COPD by spirometry were targets for QI. A single-cycle, resident-led QI project was initiated. After, residents numerically improved in the utilization of spirometry (66.5% vs. 74.8%) and smoking cessation counseling (81.8% vs. 86.6%), and significantly improved rates of pneumococcal vaccination ( p = 0.024). One cycle of resident-led QI significantly improved the rates of pneumococcal vaccination, with numerical improvement in other areas of COPD care.

Background: The best predictors of short- and medium-term mortality of cirrhotic patients receiving intensive care support are unknown., Methods: We conducted meta-analyses from 13 studies (2523 cirrhotics) after selection of original articles and response to a standardized questionnaire by the corresponding authors. End-points were in-ICU, in-hospital, and 6-month mortality in ICU survivors. A total of 301 pooled analyses, including 95 analyses restricted to 6-month mortality among ICU survivors, were conducted considering 249 variables (including reason for admission, organ replacement therapy, and composite prognostic scores)., Results: In-ICU, in-hospital, and 6-month mortality was 42.7, 54.1, and 75.1%, respectively. Forty-eight patients (3.8%) underwent liver transplantation during follow-up. In-ICU mortality was lower in patients admitted for variceal bleeding (OR 0.46; 95% CI 0.36-0.59; p < 0.001) and higher in patients with SOFA > 19 at baseline (OR 8.54; 95% CI 2.09-34.91; p < 0.001; PPV = 0.93). High SOFA no longer predicted mortality at 6 months in ICU survivors. Twelve variables related to infection were predictors of in-ICU mortality, including SIRS (OR 2.44; 95% CI 1.64-3.65; p < 0.001; PPV = 0.57), pneumonia (OR 2.18; 95% CI 1.47-3.22; p < 0.001; PPV = 0.69), sepsis-associated refractory oliguria (OR 10.61; 95% CI 4.07-27.63; p < 0.001; PPV = 0.76), and fungal infection (OR 4.38; 95% CI 1.11-17.24; p < 0.001; PPV = 0.85). Among therapeutics, only dopamine (OR 5.57; 95% CI 3.02-10.27; p < 0.001; PPV = 0.68), dobutamine (OR 8.92; 95% CI 3.32-23.96; p < 0.001; PPV = 0.86), epinephrine (OR 5.03; 95% CI 2.68-9.42; p < 0.001; PPV = 0.77), and MARS (OR 2.07; 95% CI 1.22-3.53; p = 0.007; PPV = 0.58) were associated with in-ICU mortality without heterogeneity. In ICU survivors, eight markers of liver and renal failure predicted 6-month mortality, including Child-Pugh stage C (OR 2.43; 95% CI 1.44-4.10; p < 0.001; PPV = 0.57), baseline MELD > 26 (OR 3.97; 95% CI 1.92-8.22; p < 0.0001; PPV = 0.75), and hepatorenal syndrome (OR 4.67; 95% CI 1.24-17.64; p = 0.022; PPV = 0.88)., Conclusions: Prognosis of cirrhotic patients admitted to ICU is poor since only a minority undergo liver transplant. The prognostic performance of general ICU scores decreases over time, unlike the Child-Pugh and MELD scores, even recorded in the context of organ failure. Infection-related parameters had a short-term impact, whereas liver and renal failure had a sustained impact on mortality.

Introduction: Patients with severe community-acquired pneumonia (CAP) are believed to have an exaggerated inflammatory response to bacterial infection. Therapies aiming to modulate the inflammatory response have been largely unsuccessful, perhaps reflecting that CAP is a heterogeneous disorder that cannot be modulated by a single anti-inflammatory approach. We hypothesize that the host inflammatory response to pneumonia may be characterized by distinct cytokine patterns, which can be harnessed for personalized therapies., Methods: Here, we use hierarchical cluster analysis of cytokines to examine if patterns of inflammatory response in 13 hospitalized patients with CAP can be defined. This was a secondary data analysis of the Community-Acquired Pneumonia Inflammatory Study Group (CAPISG) database. The following cytokines were measured in plasma and sputum on the day of admission: interleukin (IL)-1β, IL-1 receptor antagonist (IL-1ra), IL-6, CXCL8 (IL-8), IL-10, IL-12p40, IL-17, interferon (IFN) γ , tumor necrosis factor (TNF)α, and CXCL10 (IP-10). Hierarchical agglomerative clustering algorithms were used to evaluate clusters of patients within plasma and sputum cytokine determinations., Results: A total of thirteen patients were included in this pilot study. Cluster analysis identified distinct inflammatory response patterns of cytokines in the plasma, sputum, and the ratio of plasma to sputum., Conclusions: Inflammatory response patterns in plasma and sputum can be identified in hospitalized patients with CAP. Characterization of the local and systemic inflammatory response may help to better discriminate patients for enrollment into clinical trials of immunomodulatory therapies.

The advent of PCR has improved the identification of viruses in patients with community-acquired pneumonia (CAP). Several studies have used PCR to establish the importance of viruses in the aetiology of CAP.We performed a systematic review and meta-analysis of the studies that reported the proportion of viral infection detected via PCR in patients with CAP. We excluded studies with paediatric populations. The primary outcome was the proportion of patients with viral infection. The secondary outcome was short-term mortality.Our review included 31 studies. Most obtained PCR via nasopharyngeal or oropharyngeal swab. The pooled proportion of patients with viral infection was 24.5% (95% CI 21.5-27.5%). In studies that obtained lower respiratory samples in >50% of patients, the proportion was 44.2% (95% CI 35.1-53.3%). The odds of death were higher in patients with dual bacterial and viral infection (OR 2.1, 95% CI 1.32-3.31).Viral infection is present in a high proportion of patients with CAP. The true proportion of viral infection is probably underestimated because of negative test results from nasopharyngeal or oropharyngeal swab PCR. There is increased mortality in patients with dual bacterial and viral infection., (Copyright ©ERS 2016.)

Study Objectives: This study aimed to examine the effect of sleep state (rapid eye movement [REM] versus non-rapid eye movement [NREM]) and position (supine versus non-supine position) on obstructive respiratory events distribution in adolescent population (ages 12 to 18 y)., Methods: This was a retrospective study that included 150 subjects between the ages of 12 to 18 y with an apnea-hypopnea index (AHI) > 1/h. Subjects using REM sleep-suppressant medications and subjects with history of genetic anomalies or craniofacial syndromes were excluded., Results: The median age was 14 y with interquartile range (IQR) of 13 to 16 y, 56% of patients were males and the median body mass index (BMI) z-score was 2.35 (IQR: 1.71-2.59) with 77.3% of patients fulfilling obesity criteria. Respiratory obstructive events were more common in REM sleep. The median REM obstructive AHI (OAHI) was 8.9 events per hour (IQR: 2.74-22.8), whereas the median NREM OAHI was 3.2 events per hour (IQR: 1.44-8.29; p < 0.001). African American adolescents had more REM obstructive events with median REM OAHI of 13.2 events per hour (IQR: 4.88-30.6), which was significantly higher than median REM OAHI of 4.94 (IQR: 2.05-11.36; p = 0.004) in white adolescents. Obstructive events were more common in supine position with higher median supine OAHI of 6.55 (IQR: 4-17.73) when compared to median non-supine OAHI of 2.94 (IQR: 1-6.54; p < 0.001)., Conclusions: This study shows that sleep related obstructive respiratory events in the adolescents (12 to 18 y of age) occur predominantly in REM sleep and in supine position., (© 2016 American Academy of Sleep Medicine.)

The composition of the upper respiratory tract microbiome may play an important role in the development of lower respiratory tract infections. Here, we characterised the microbiome of the nasopharynx and oropharynx of hospitalised patients with community-acquired pneumonia (CAP) with unknown aetiology in an attempt to obtain insight into the aetiology of CAP. A random sample of 10 patients hospitalised with CAP previously enrolled in a separate clinical trial (ClinicalTrials.gov registry, Study ID: NCT01248715) in which a complete microbiological workup was not able to define an aetiology were analysed in this pilot study. This larger trial ( n = 1,221) enrolled patients from 9 adult hospitals in Louisville, Kentucky, USA. Nasopharyngeal and oropharyngeal swabs were obtained for metagenomic analysis. Polymerase chain reaction (PCR) for Streptococcus pneumoniae was performed in all patients. One patient had a distinct nasophararyngeal microbiome consisting largely of Haemophilus influenzae . This was the only patient with a negative PCR for S. pneumoniae in both nasophararyngeal and oropharyngeal specimens. Overall, substantial differences were found between nasophararyngeal and oropharyngeal microbiomes. The upper respiratory tract microbiome of only one patient suggested H. influenzae as a probable aetiology of CAP. Although this was a pilot study of only 10 patients, the presence of S. pneumoniae in the upper respiratory tract of the other 9 patients warrants further investigation., (© The Author(s) 2015.)

Background: Patients who have had an unprovoked deep venous thrombosis (DVT) or pulmonary embolus (PE) are at a high risk for recurrent venous thromboembolism (VTE). Extended "life-long" anticoagulation has been recommended in these patients. However, the risk benefit ratio of this approach is controversial and the role of the direct oral anticoagulants (DOACs) and aspirin is unclear. Furthermore, in some patients with a "weak provoking factor" there is clinical equipoise regarding continuation or cessation of anticoagulant therapy after treatment of the acute VTE event., Objective: A systematic review and meta-analysis to determine the risks (major bleeding) and benefits (recurrent VTE and mortality) of extended anticoagulation with vitamin k antagonists (VKA), DOACs and aspirin in patients with an unprovoked VTE and in those patients with clinical equipoise regarding continuation or cessation of anticoagulant therapy. In addition, we sought to determine the risk of recurrent VTE events once extended anti-thrombotic therapy was discontinued., Data Sources: MEDLINE, Cochrane Register of Controlled Trials, citation review of relevant primary and review articles., Study Selection: Randomized placebo-controlled trials (RCTs) that compared the risk of recurrent VTE in patients with an unprovoked DVT or PE who had been treated for at least 3 months with a VKA or a DOAC and were then randomized to receive an oral anti-thrombotic agent or placebo for at least 6 additional months. We included studies that included patients in whom clinical equipoise existed regarding the continuation or cessation of anticoagulant therapy., Data Extraction: Independent extraction of articles by both authors using predefined data fields, including study quality indicators. Data were abstracted on study size, study setting, initial event (DVT or PE), percentage of patients where the initial VTE event was unprovoked, the number of recurrent VTE events, major bleeds and mortality during the period of extended anticoagulation in the active treatment and placebo arms. In addition, we recorded the event rate once extended treatment was stopped. Meta-analytic techniques were used to summarize the data. Studies were grouped according to the type of anti-thrombotic agent., Data Synthesis: Seven studies which enrolled 6778 patients met our inclusion criteria; two studies evaluated the extended use of Coumadin, three studies evaluated a DOAC and two studies evaluated the use of aspirin. The duration of followup varied from 6 to 37 months. In the Coumadin and aspirin studies 100% of the randomized patients had an unprovoked VTE, while in the DOAC studies between 73.5% and 93.2% of the VTE events were unprovoked. In the control group recurrent VTE occurred in 9.7% of patients compared to 2.8% in the active treatment group (OR 0.21; 95% CI 0.11-0.42, p<0.0001). VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with VKA and DOACs being significantly more effective than aspirin. Major bleeding events occurred in 12 patients in the control group (0.4%) and 25 of 3815 (0.6%) patients in the active treatment group (OR 1.64; 95% CI 0.69-3.90, NS). There were 39 (1.3%) deaths in control patients and 33 (0.9%) deaths in the anti-thrombotic group during the treatment period (OR 0.73; 95% CI 0.40-1.33, NS). Patients whose initial VTE event was a PE were more likely to have a recurrent PE than a DVT. The annualized event rate after discontinuation of extended antithrombotic therapy was 4.4% in the control group and 6.5% in the active treatment arm., Conclusions: VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with DOACs and VKA being more effective than aspirin. The decision regarding life-long anticoagulation following an unprovoked DVT or PE should depend on the patients' risk for recurrent PE as well as the patients' values and preferences.

Introduction: Severe community-acquired pneumonia (CAP) portends a serious prognosis. The temporal trend in outcome of severe CAP is not well established. We evaluated the temporal trends in the outcomes of severe CAP., Methods: This is a secondary analysis of 800 patients with severe CAP enrolled in the Community-Acquired Pneumonia Organization International Cohort. Severe CAP was defined as CAP requiring admission to the intensive care unit. Only patients admitted to the ICU upon hospital admission were included in this study. We assessed the trend in outcomes of these patients during three time periods: Period I (June 2001 to April 2004), Period II (May 2004 to January 31 2008), and Period III (February 2008 to February 2013)., Results: After adjustment for other variables, mortality was higher for patients admitted during Period II compared with Period I (RR: 1.46; 95% CI: 1.002 to 2.14; P value = 0.049), and for Period III compared with Period I (RR: 1.70; 95% CI: 1.15 to 2.50; P value = 0.008). No significant difference in length of stay or time to clinical stability was found among the three periods., Conclusion: The mortality of patients with severe CAP increased over time in our study population. This finding has important health policy implications if confirmed by other studies., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: The initial prognostic assessment of patients with community-acquired pneumonia( CAP) has important clinical implications. We hypothesized that midregional proadrenomedullin(MR-proADM) is a valuable test for the prediction of outcomes in patients with CAP.Methods: We performed a systemic review of the literature and a meta-analysis to evaluate the prognostic value of MR-proADM for short and long-term mortality in patients with CAP.Results: Twelve studies were included in the systematic review. Elevated MR-proADM was associated with an increase in short-term mortality (OR Z 6.8; 95% CI: 4.65-10.13; P value < 0.001) and complications (OR = 5.0; 95% CI: 3.86-6.49; P value < 0.001). The pooled analysis of 4 studies showed an improvement in the discriminant ability by 8% (95% CI: 2%e14%)when MR-proADM was added to CURB-65/CRB-65. Studies that reported long-term prognosis indicated an increased risk of death in patients with elevated MR-proADM.Conclusion: Elevated level of MR-proADM is significantly associated with both short-term mortality and complications in patients with CAP. Studies also indicate that MR-proADM has prognostic value for prediction of long-term mortality in these patients. The addition of MR-proADM improves the discriminant ability of CURB-65/CRB-65.

The 22 risk factors suggested by the Centers for Disease Control and Prevention (CDC) to predict patients at risk for Mycobacterium tuberculosis have not been evaluated in hospitalised patients with community-acquired pneumonia (CAP). We evaluated which of the CDC risk factors best predict M. tuberculosis in these patients. To our knowledge, this is the first time a score has been developed assessing these risk factors. This was a secondary analysis of 6976 patients hospitalised with CAP enrolled in the Community-Acquired Pneumonia Organization International Cohort Study. Using Poisson regression, we selected the subset of risk factors that best predicted the presence of CAP due to M. tuberculosis. This subset was compared to the CDC risk factors using receiver operating characteristic (ROC) curve analysis. Five risk factors were found to best predict CAP due to M. tuberculosis: night sweats, haemoptysis, weight loss, M. tuberculosis exposure and upper lobe infiltrate. The area under the ROC curve for all CDC risk factors was 71% and 89% for the subset of five risk factors. The CDC-suggested risk factors are poor at predicting the presence of M. tuberculosis in hospitalised patients with CAP. With a subset of five risk factors identified in this study, we developed a new score, which will improve our capacity to isolate patients at risk of CAP due to M. tuberculosis at the time of hospitalisation.

Delirium is characterized by a disturbance of consciousness with accompanying change in cognition. Delirium typically manifests as a constellation of symptoms with an acute onset and a fluctuating course. Delirium is extremely common in the intensive care unit (ICU) especially amongst mechanically ventilated patients. Three subtypes have been recognized: hyperactive, hypoactive, and mixed. Delirium is frequently undiagnosed unless specific diagnostic instruments are used. The CAM-ICU is the most widely studied and validated diagnostic instrument. However, the accuracy of this tool may be less than ideal without adequate training of the providers applying it. The presence of delirium has important prognostic implications; in mechanically ventilated patients it is associated with a 2.5-fold increase in short-term mortality and a 3.2-fold increase in 6-month mortality. Nonpharmacological approaches, such as physical and occupational therapy, decrease the duration of delirium and should be encouraged. Pharmacological treatment for delirium traditionally includes haloperidol; however, more data for haloperidol are needed given the paucity of placebo-controlled trials testing its efficacy to treat delirium in the ICU. Second-generation antipsychotics have emerged as an alternative for the treatment of delirium, and they may have a better safety profile. Dexmedetomidine may prove to be a valuable adjunctive agent for patients with delirium in the ICU.

Background: Central venous access (CVA) is widely used. However, its thrombotic, stenotic and infectious complications can be life-threatening and involve high-cost therapy. Research revealed that the risk of catheter-related complications varied according to the site of CVA. It would be helpful to find the preferred site of insertion to minimize the risk of catheter-related complications. This review was originally published in 2007 and was updated in 2011., Objectives: 1. Our primary objective was to establish whether the jugular, subclavian or femoral CVA routes resulted in a lower incidence of venous thrombosis, venous stenosis or infections related to CVA devices in adult patients.2. Our secondary objective was to assess whether the jugular, subclavian or femoral CVA routes influenced the incidence of catheter-related mechanical complications in adult patients; and the reasons why patients left the studies early., Search Methods: We searched CENTRAL (The Cochrane Library 2011, Issue 9), MEDLINE, CINAHL, EMBASE (from inception to September 2011), four Chinese databases (CBM, WANFANG DATA, CAJD, VIP Database) (from inception to November 2011), Google Scholar and bibliographies of published reviews. The original search was performed in December 2006. We also contacted researchers in the field. There were no language restrictions., Selection Criteria: We included randomized controlled trials comparing central venous catheter insertion routes., Data Collection and Analysis: Three authors assessed potentially relevant studies independently. We resolved disagreements by discussion. Dichotomous data on catheter-related complications were analysed. We calculated relative risks (RR) and their 95% confidence intervals (CI) based on a random-effects model., Main Results: We identified 5854 citations from the initial search strategy; 28 references were then identified as potentially relevant. Of these, we Included four studies with data from 1513 participants. We undertook a priori subgroup analysis according to the duration of catheterization, short-term (< one month) and long-term (> one month) defined according to the Food and Drug Administration (FDA).No randomized controlled trial (RCT) was found comparing all three CVA routes and reporting the complications of venous stenosis.Regarding internal jugular versus subclavian CVA routes, the evidence was moderate and applicable for long-term catheterization in cancer patients. Subclavian and internal jugular CVA routes had similar risks for catheter-related complications. Regarding femoral versus subclavian CVA routes, the evidence was high and applicable for short-term catheterization in critically ill patients. Subclavian CVA routes were preferable to femoral CVA routes in short-term catheterization because femoral CVA routes were associated with higher risks of catheter colonization (14.18% or 19/134 versus 2.21% or 3/136) (n = 270, one RCT, RR 6.43, 95% CI 1.95 to 21.21) and thrombotic complications (21.55% or 25/116 versus 1.87% or 2/107) (n = 223, one RCT, RR 11.53, 95% CI 2.80 to 47.52) than with subclavian CVA routes. Regarding femoral versus internal jugular routes, the evidence was moderate and applicable for short-term haemodialysis catheterization in critically ill patients. No significant differences were found between femoral and internal jugular CVA routes in catheter colonization, catheter-related bloodstream infection (CRBSI) and thrombotic complications, but fewer mechanical complications occurred in femoral CVA routes (4.86% or 18/370 versus 9.56% or 35/366) (n = 736, one RCT, RR 0.51, 95% CI 0.29 to 0.88)., Authors' Conclusions: Subclavian and internal jugular CVA routes have similar risks for catheter-related complications in long-term catheterization in cancer patients. Subclavian CVA is preferable to femoral CVA in short-term catheterization because of lower risks of catheter colonization and thrombotic complications. In short-term haemodialysis catheterization, femoral and internal jugular CVA routes have similar risks for catheter-related complications except internal jugular CVA routes are associated with higher risks of mechanical complications.

Background: Observational studies have suggested an association between HIV infection and emphysema., Aims: The primary aim of this study was to estimate the prevalence of obstructive lung disease in HIV-infected patients seen in an outpatient infectious disease clinic. The secondary aim was to estimate the prevalence of Obstructive Lung Disease (OLD) in smokers and non smokers in this population., Methods: This was a prospective cross-sectional study. Consecutive patients who were seen for routine HIV care underwent spirometry and answered the St. George's Respiratory Questionnaire (SGRQ). Further, we collected information from the charts on demographics, co-morbidities, CD4 cell count, and HIV viral load (current, baseline, etc)., Results: This study included 98 HIV-infected patients with mean age of 45 years, (SD: 11) and 84% male. They were seen from November 2008 to May 2009 at Thomas Jefferson University in Philadelphia. According to established criteria, spirometry results were classified as normal in 69% and obstructive in 16.3%. Among those who never smoked, the prevalence of obstructive lung disease on spirometry was 13.6%. The prevalence of obstruction in HIV patients with a history of smoking was 18.5%. Current and ever smokers comprised 21.4% and 55% of the patients respectively. The mean SGRQ total score was 7. The mean SGRQ score in active smokers was 17 and 15 in those subjects with a prior history of smoking. The mean SGRQ score among patients with obstruction in spiromerty was 27.7 in patients with obstruction on spirometry., Conclusion: This urban population of HIV-infected persons has a relatively high prevalence of obstructive lung disease as assessed by spirometry. Furthermore, the high prevalence of obstructive lung disease in never smokers may suggest a possible association between HIV infection and emphysema. In addition the SGRQ total score was comparatively higher in patients with obstruction on spirometry. Our data suggests that potentially all patients with HIV should be screened a for OLD., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Adult-onset asthma and periocular xanthogranuloma is an uncommon and recently described disease. Little is known about the condition because only a few case reports and series are available., Objective/methods: To describe the clinical manifestations, lung physiology, and response to systemic treatment of three patients with adult-onset asthma and periocular xanthogranuloma, followed by a review of the literature., Results: Three men, with an age at diagnosis ranging from 48 to 51 years, presented with right periorbital swelling, asthma and chronic rhinosinusitis. The patients' lung physiology was consistent with airway obstruction. Diagnosis was established by periorbital biopsy. All patients received oral corticosteroids for their periorbital swelling, without significant clinical response. Two patients received oral methotrexate, with nearly complete resolution of periorbital swelling. A third patient received oral azathioprine, without clinical response. The three patients had improvement of their asthma with inhaled steroids/long-acting bronchodilator, and immunosuppressive medication., Conclusion: A triad consisting of periorbital swelling, asthma and chronic rhinosinusitis should raise the suspicion of adult-onset asthma and periocular xanthogranuloma. Oral methotrexate should be considered as an alternative to corticosteroids in the treatment of this disorder.

Objective: To analyze the available evidence regarding the effect that corticosteroids have on the prevention of fat embolism syndrome after long bone fracture of the lower limbs or pelvic fracture., Methods: In March of 2007, we performed a search of various electronic databases, including Medline, the Excerpta Medica database, the Cochrane Library, the Latin American and Caribbean Health Sciences Literature database and the Scientific Electronic Library Online. We selected randomized controlled trials that compared the effect of corticosteroids with that of placebo (or standard care) on the prevention of fat embolism syndrome after long bone fracture of the lower limbs or pelvic fracture. References from the studies included were also reviewed., Results: Six studies were included. The pooled relative risk for developing fat embolism syndrome was 0.16 (95% CI: 0.08-0.35) in the corticosteroid group as compared with the control group. The pooled relative risk for developing hypoxemia was 0.34 (95% CI: 0.19-0.59) in the corticosteroid group as compared with the control group., Conclusion: The analysis of evidence showed that corticosteroids decrease the risk of developing fat embolism syndrome and hypoxemia after long bone fracture of the lower limbs.