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Ali A El-Solh,1– 3 Yolanda Lawson,1 Gregory E Wilding4 1Research Department, VA Western New York Healthcare System, Buffalo, NY, USA; 2Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine; Jacobs School of Medicine, Buffalo, NY, USA; 3Department of Epidemiology and Environmental Health, School of Public Health and Health Professions; University at Buffalo, Buffalo, NY, USA; 4Department of Biostatistics, School of Public Health and Health Professions; University at Buffalo, Buffalo, NY, USACorrespondence: Ali A El-Solh, Research Department, VA Western New York Healthcare System, 3495 Bailey Avenue, Buffalo, NY, 14215, USA, Tel +1 (716) 862-7392, Fax +1 (716) 862-6526, Email solh@buffalo.eduPurpose: Hypnotics are commonly prescribed in patients with COPD to manage insomnia. Given the considerable risks associated with these drugs, the aim of the study was to evaluate the risk of all-cause mortality associated with hypnotics in a cohort of veterans with COPD presenting with insomnia.Methods: We conducted a retrospective cohort study that used Veterans Health Administration Corporate Data Warehouse with data supplemented by linkage to Medicare, Medicaid, and National Death Index data from 2010 through 2019. The primary outcome was all-cause mortality. Analyses were conducted using propensity score 1:1 matching to balance baseline characteristics.Results: Of the 5759 veterans with COPD (mean [SD] age, 71.7 [11.2]; 92% men), 3585 newly initiated hypnotic agents during the study period. During a mean follow-up of 7.4 (SD, 2.7) years, a total of 2301 deaths occurred, with 65.2 and 48.7 total deaths per 1000 person-years among hypnotic users and nonusers, respectively. After propensity matching, hypnotic use was associated with a 22% increased risk of mortality compared with hypnotic nonusers (hazard ratio [HR] 1.22; 95% confidence interval [CI],1.11– 1.35). The benzodiazepine receptor agonists (BZRAs) group experienced a higher incidence rate of all-cause mortality compared to hypnotic nonusers (Incidence rate ratio [IRR] 1.27; 95% CI, 1.14– 1.43). Conversely, the mortality rate of non-BZRA hypnotics decreased after the first 2 years and was not significantly different for hypnotic nonusers (IRR 1.04; 95% CI, 0.82– 1.11).Conclusion: Among patients with COPD and insomnia, treatment with hypnotics was associated with a higher risk of all-cause mortality. The association was observed in patients prescribed BZRAs. The risk of mortality for non-BZRAs moderated after the first 2 years, indicating a class effect.Keywords: insomnia, chronic obstructive pulmonary disease, mortality, benzodiazepine receptor agonists

Ali A El-Solh1–4 1Research Department, VA Western New York Healthcare System, Buffalo, NY, USA; 2Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, Buffalo, NY, USA; 3Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University of Buffalo, Buffalo, NY, USA; 4Department of Community and Health Behavior, School of Public Health and Health Professions, University of Buffalo, Buffalo, NY, USA Abstract: Nightmares are considered the hallmark of posttraumatic stress disorder (PTSD). Although the characteristics of these distressing dreams may vary with the type of traumatic event, the pathophysiology exposes central dysfunction of brain structures at the level of the hippocampus, amygdala, and locus coeruleus, modulated by neurochemical imbalance in noradrenergic, dopaminergic, and serotonin pathways. Underlying comorbid conditions, including other sleep disorders, may contribute to worsening symptoms. Addressing sleep disruption can alleviate the severity of these nocturnal events and augment the effectiveness of other PTSD treatments. The expansion of behavioral treatment modalities for PTSD-related nightmares has been encouraging, but the core of these interventions is heavily structured around memory manipulation and imagery rescripting. A lack of a standardized delivery and a high dropout rate continue to pose significant challenges in achieving successful outcomes. The efficacy of existing pharmacological studies, such as α-adrenergic blocking agents, antidepressants, and atypical antipsychotics, has been undermined by methodological limitations and absence of large randomized controlled trials. This review is aimed at reviewing the available treatment strategies for alleviating nightmares in subjects with PTSD. Given the intricate relationship between PTSD and nightmares, future clinical trials have to adopt a more pragmatic approach focused not only on efficacy of novel interventions but also on adjunctive iteration of existing therapies tailored to individual socio-cultural background. Keywords: nightmares, posttraumatic stress disorder, cognitive-behavioral therapy, pharmacotherapy, image rehearsal therapy, prazosin, cannabis

Usama Assaad,2 Ibrahim El-Masri,2 Jahan Porhomayon,1,3 Ali A El-Solh1–41The Veterans Affairs Western New York Healthcare System, Buffalo, NY, USA; 2Division of Pulmonary, Critical Care, and Sleep Medicine, 3Department of Anesthesia, 4Department of Social and Preventive Medicine, State University of New York at Buffalo School of Medicine and Biomedical Sciences and School of Public Health and Health Professions, Buffalo, NY, USAAbstract: Vaccination remains the primary preventive strategy in the elderly against Streptococcus pneumoniae and influenza infections. The effectiveness of this strategy in preventing pneumonia has been in doubt despite the increase in vaccination coverage among older adults. Randomized controlled trials (RCTs) and observational studies aimed at determining clinical outcomes and immune response following pneumococcal vaccination have yielded conflicting results. The protective efficacy of pneumococcal vaccination against pneumonia in older adults has not been firmly established due to a lack of RCTs specifically examining patients ≥ 65 years of age. Similarly, the reported benefits of influenza vaccination have been derived from observational data. The assessment of clinical benefit from influenza vaccination in the elderly population is complicated by varying cohorts, virulence of the influenza strain, and matching of vaccine and circulating viral strains. The presence of selection bias and use of nonspecific end points in these studies make the current evidence inconclusive in terms of overall benefit. The development of more immunogenic vaccines through new formulations or addition of adjuvants holds the promise of revolutionizing delivery and improving efficacy. Dismantling existing barriers through education, providing technology assistance predominantly to developing countries, and establishing clear regulatory guidance on pathways for approval are necessary to ensure timely production and equitable distribution.Keywords: pneumococcal vaccine, influenza vaccine, vaccine effectiveness, pneumonia, older adults

Rationale: Pseudomonas aeruginosa is one of the leading causes of gram-negative ventilator-associated pneumonia (VAP) associated with a mortality rate of 34 to 68%. Recent evidence suggests that P. aeruginosa in patients with VAP may persist in the alveolar space despite adequate antimicrobial therapy. We hypothesized that failure to eradicate P. aeruginosa from the lung is linked to type III secretory system (TTSS) isolates.Objectives: To determine the mechanism by which infection with P. aeruginosa in patients with VAP may evade the host immune response.Methods: Thirty-four patients with P. aeruginosa VAP underwent noninvasive bronchoalveolar lavage (BAL) at the onset of VAP and on Day 8 after initiation of antibiotic therapy. Isolated pathogens were analyzed for secretion of type III cytotoxins. Neutrophil apoptosis in BAL fluid was quantified by assessment of nuclear morphology on Giemsa-stained cytocentrifuge preparations. Neutrophil elastase was assessed by immunoenzymatic assay.Measurements and Main Results: Twenty-five out of the 34 patients with VAP secreted at least one of type III proteins. There was a significant difference in apoptotic rate of neutrophils at VAP onset between those strains that secreted cytotoxins and those that did not. Neutrophil elastase levels were positively correlated with the rate of apoptosis (r = 0.43, P < 0.01). Despite adequate antimicrobial therapy, 13 out of 25 TTSS(+) isolates were recovered at Day 8 post-VAP, whereas eradication was achieved in all patients who had undetectable levels of type III secretion proteins.Conclusions: The increased apoptosis in neutrophils by the TTSS(+) isolates may explain the delay in eradication of Pseudomonas strains in patients with VAP. Short-course antimicrobial therapy may not be adequate in clearing the infection with a TTSS secretory phenotype. [ABSTRACT FROM AUTHOR]

Rationale: Patients with obstructive sleep apnea (OSA) are at increased risk for cardiovascular diseases. Injury of endothelial cells has been advanced as an initial trigger to atherosclerosis. Objectives: To study the association between circulating apoptotic endothelial cells and vasomotor dysfunction as a function of sleep apnea. Methods: Brachial artery flow-mediated dilation was determined in 14 subjects with documented OSA and 10 healthy control subjects at baseline and 8 weeks after continuous positive airway pressure (CPAP) therapy. Quantification of circulating apoptotic endothelial cells (CD146(+) Annexin V(+)) was performed by flow cytometry. Measurements and Main Results: Compared with healthy subjects, patients with OSA had higher numbers of circulating CD146(+) Annexin V(+) cells (39.2 +/- 13.6 cells/mL and17.8 +/- 9.4, respectively; p < 0.001). Increased apoptotic endothelial cells correlated moderately with abnormal vascular function (r = -0.61; p = 0.001). A significant correlation was observed between CD146 Annexin V(+) cells and the apnea-hypopnea index (r = 0.56; p = 0.004). After 8 weeks of treatment with CPAP, the numbers of circulating apoptotic endothelial cells were reduced significantly from 39.2 +/- 13.6 to 22.3 +/- 12.9 apoptotic cells per milliliter (p < 0.001) and correlated with improvement in endothelium-dependent vasodilation (r = 0.49; p = 0.07). Conclusions: In patients with OSA, impairment of endothelial-dependent vasodilation correlated with the degree of endothelial cell apoptosis. CPAP therapy led to significant decline in circulating apoptotic endothelial cells. These findings provide an additional mechanism for the predisposition of patients with OSA to premature vascular disease. [ABSTRACT FROM AUTHOR]

Grading the strength of recommendations and the quality of under-lying evidence enhances the usefulness of clinical practice guide-lines. Professional societies and other organizations, including the American Thoracic Society (ATS), should reach consensus about whether they will use one common grading system and which of the numerous grading systems they would apply across all guide-lines. The profusion of guideline grading systems confuses consumers of guidelines, and undermines the value of the grading exercise in conveying a transparent message. In response to this dilemma, the international GRADE working group has developed an approach that is useful for many guideline contexts, and that several national and international organizations have adopted. The GRADE system classifies recommendations as strong or weak, according to the balance of the benefits and downsides (harms, burden, and cost) after considering the quality of evidence. The quality of evidence reflects the confidence in estimates of the true effects of an intervention, and the system classifies quality of evidence as high, moderate, low, or very low according to factors that include the study methodology, the consistency and precision of the results, and the directness of the evidence. On recommendation of the ATS Documents Development and Implementation Committee, the ATS adopted the GRADE approach for its guidelines in line with many other organizations that have recently chosen the GRADE approach. This article informs ATS guideline developers, investigators, and those interpreting future ATS guidelines that follow the GRADE approach about the methodology and applicability of ATS guidelines and recommendations. [ABSTRACT FROM AUTHOR]

We sought to investigate prospectively the microbial etiology and prognostic indicators of 95 institutionalized elders with severe aspiration pneumonia, and to investigate its relation to oral hygiene in using quantitative bronchial sampling. Data collection included demographic information, Activity of Daily Living, Plaque Index, antimicrobial therapy, and outcome. Out of the 67 pathogens identified, Gram-negative enteric bacilli were the predominant organisms isolated (49%), followed by anaerobic bacteria (16%), and Staphylococcus aureus (12%). The most commonly encountered anaerobes were Prevotella and Fusobacterium species. Aerobic Gram-negative bacilli were recovered in conjunction with 55% of anaerobic isolates. The Plaque Index did not differ significantly between the aerobic (2.2 +/- 0.4) and the anaerobic group (2.3 +/- 0.3). Functional status was the only determinant of the presence of anaerobic bacteria. Although seven cases with anaerobic isolates received initially inadequate antimicrobial therapy, six had effective clinical response. The crude mortality was 33% for the aerobic and 36% for the anaerobic group (p = 0.9). Stepwise multivariate analysis identified hypoalbuminemia (p < 0.001) and the burden of comorbid diseases (p < 0.001) as independent risk factors of poor outcome. In view of the rising resistance to antimicrobial agents, the importance of adding anaerobic coverage for aspiration pneumonia in institutionalized elders needs to be reexamined. [ABSTRACT FROM AUTHOR]

Introduction: Cigarette smoking is associated with development of significant comorbidities. Patients with underlying comorbidities have been found to have worse outcomes associated with Coronavirus Disease 2019 (Covid-19). This study evaluated 30-day mortality in Covid-19 positive patients based on smoking status., Methods: This retrospective study of veterans nationwide examined Covid-19 positive inpatients between March 2020 and January 2021. Bivariate analysis compared patients based on smoking history. Propensity score matching adjusted for age, gender, race, ethnicity, Charlson comorbidity index (0-5 and 6-19) and dexamethasone use was performed. A multivariable logistic regression with backwards elimination and Cox Proportional Hazards Ratio was utilized to determine odds of 30-day mortality., Results: The study cohort consisted of 25,958 unique Covid-19 positive inpatients. There was a total of 2,995 current smokers, 12,169 former smokers, and 8,392 non-smokers. Death was experienced by 13.5% (n = 3503) of the cohort within 30 days. Former smokers (OR 1.15; 95% CI, 1.05-1.27) (HR 1.13; 95% CI, 1.03-1.23) had higher risk of 30-day mortality compared with non-smokers. Former smokers had a higher risk of death compared to current smokers (HR 1.16 95% CI 1.02-1.33). The odds of death for current vs. non-smokers did not significantly differ., Conclusion: Compared to veteran non-smokers with Covid-19, former, but not current smokers with Covid-19 had a significantly higher risk of 30-day mortality., (Published by Elsevier Ltd.)

Objective: Our objective is to compare the predictive accuracy of four recently established outcome models of patients hospitalized with coronavirus disease 2019 (COVID-19) published between January 1st and May 1st 2020., Methods: We used data obtained from the Veterans Affairs Corporate Data Warehouse (CDW) between January 1st, 2020, and May 1st 2020 as an external validation cohort. The outcome measure was hospital mortality. Areas under the ROC (AUC) curves were used to evaluate discrimination of the four predictive models. The Hosmer-Lemeshow (HL) goodness-of-fit test and calibration curves assessed applicability of the models to individual cases., Results: During the study period, 1634 unique patients were identified. The mean age of the study cohort was 68.8±13.4 years. Hypertension, hyperlipidemia, and heart disease were the most common comorbidities. The crude hospital mortality was 29% (95% confidence interval [CI] 0.27-0.31). Evaluation of the predictive models showed an AUC range from 0.63 (95% CI 0.60-0.66) to 0.72 (95% CI 0.69-0.74) indicating fair to poor discrimination across all models. There were no significant differences among the AUC values of the four prognostic systems. All models calibrated poorly by either overestimated or underestimated hospital mortality., Conclusions: All the four prognostic models examined in this study portend high-risk bias. The performance of these scores needs to be interpreted with caution in hospitalized patients with COVID-19., Competing Interests: The authors have declared that no competing interests exist

Study Objectives: Despite the overall improvement in posttraumatic stress disorder (PTSD) symptomatology with continuous positive airway pressure (CPAP) therapy, adherence to CPAP is far worse in veterans with PTSD compared to the general population with obstructive sleep apnea (OSA). The aim of this study was to compare the efficacy, adherence, and preference of CPAP versus mandibular advancement device (MAD) and the effect of these treatments on health outcomes in veterans with PTSD., Methods: Forty-two subjects with PTSD and newly diagnosed OSA by polysomnography were treated in a randomized, crossover trial of 12 weeks with CPAP alternating with MAD separated by a 2-week washout period. The primary outcome was the difference in titration residual apnea-hypopnea index (AHI) between CPAP and MAD. Secondary outcome measures included PTSD Checklist and health-related quality of life (Medical Outcomes Study 36-Item Short Form and Pittsburgh Sleep Quality Index)., Results: Analyses were limited to the 35 subjects (mean age 52.7 ± 11.6 years) who completed the trial, regardless of compliance with their assigned treatment. CPAP was more efficacious in reducing AHI and improving nocturnal oxygenation than MAD ( P < .001 and P = .04, respectively). Both treatments reduced PTSD severity and ameliorated scores of the Medical Outcomes Study Short Form 36 and Pittsburgh Sleep Quality Index, although no differences were detected between the CPAP and MAD arms. The reported adherence to MAD was significantly higher than CPAP ( P < .001), with 58% preferring MAD to CPAP., Conclusions: Although CPAP is more efficacious than MAD at improving sleep apnea, both treatment modalities imparted comparable benefits for veterans with PTSD in relation to PTSD severity and health-related quality of life. MAD offers a viable alternative for veterans with OSA and PTSD who are nonadherent to CPAP., Clinical Trial Registration: Title: A Randomized Cross Over Trial of Two Treatments for Sleep Apnea in Veterans With Post-Traumatic Stress Disorder; URL: https://www.clinicaltrials.gov/ct/show/NCT01569022; Identifier: NCT01569022., (© 2017 American Academy of Sleep Medicine)

Background: The primary objective of this study is to assess whether baseline renal function impacts treatment outcomes of linezolid and vancomycin (with a dose-optimized regimen) for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia., Methods: We conducted a retrospective cohort analysis of data generated from a prospective, randomized, controlled clinical trial (NCT 00084266). The analysis included 405 patients with culture-proven MRSA pneumonia. Baseline renal function was stratified based on creatinine clearance. Clinical and microbiological success rates and presence of nephrotoxicity were assessed at the end of treatment (EOT) and end of study (EOS). Multivariate logistic regression analyses of baseline patient characteristics, including treatment, were performed to identify independent predictors of efficacy. Vancomycin concentrations were analyzed using a nonlinear mixed-effects modeling approach. The relationships between vancomycin exposures, pharmacokinetic-pharmacodynamic index (trough concentration, area under the curve over a 24-h interval [AUC 0-24 ], and AUC 0-24 /MIC) and efficacy/nephrotoxicity were assessed in MRSA pneumonia patients using univariate logistic regression or Cox proportional hazards regression analysis approach., Results: After controlling for use of vasoactive agents, choice of antibiotic therapy and bacteremia, baseline renal function was not correlated with clinical and microbiological successes in MRSA pneumonia at either end of treatment or at end of study for both treatment groups. No positive association was identified between vancomycin exposures and efficacy in these patients. Higher vancomycin exposures were correlated with an increased risk of nephrotoxicity (e.g., hazards ratio [95% confidence interval] for a 5 μg/ml increase in trough concentration: 1.42 [1.10, 1.82])., Conclusions: In non-dialysis patients, baseline renal function did not impact the differences in efficacy or nephrotoxicity with treatment of linezolid versus vancomycin in MRSA pneumonia.

Study Objectives: Sleep fragmentation has been linked to poor pain tolerance and lowered pain threshold. Little evidence exists on whether continuous positive airway pressure (CPAP) adherence in veterans with obstructive sleep apnea (OSA) who are taking opioids for non-malignant pain would ameliorate pain and reduce consumption of opioids., Methods: A retrospective case-control study was performed at a VA sleep center. Pain intensity was assessed using the Numerical Categorical Scale prior to CPAP treatment and 12-mo follow-up. Opioids intake was assessed using the morphine equivalent daily dose (MEDD). Adherence to CPAP was evaluated with the built-in meter., Results: We reviewed 113 patients with OSA (apnea-hypopnea index [AHI] 35.9 ± 29.5) using a MEDD of 61.6 mg (range 5-980 mg) and a control group of 113 veterans with OSA (AHI 33.4 ± 27.3) on no opioids treatment. CPAP adherence was significantly lower at 12 mo in opioid-treated patients compared to controls (37% versus 55%; p = 0.01). Greater pain intensity was the only independent variable associated with CPAP non-adherence at 12-mo follow-up (p = 0.03). Compared to baseline, no significant difference was observed in pain intensity or consumption of opioids in CPAP adherent patients., Conclusions: CPAP treatment did not reduce pain intensity or consumption of opioids in veterans with chronic pain who have coexisting OSA. CPAP adherence was lower in opioid-treated veterans with OSA compared to opioid-free veterans with OSA. Pain intensity was the only determinant of CPAP adherence. Future studies are needed to evaluate pain management program on adherence to CPAP., (© 2016 American Academy of Sleep Medicine.)

Background: The primary objective of this meta-analysis is aimed at determining whether β-lactams prolonged infusion in patients with nosocomial pneumonia (NP) results in higher cure rate and improved mortality compared to intermittent infusion., Materials and Methods: Relevant studies were identified from searches of MEDLINE, EMBASE, and CENTRAL from inception to September 1st, 2015. All published articles which evaluated the outcome of extended/continuous infusion of antimicrobial therapy versus intermittent infusion therapy in the treatment of NP were reviewed., Results: A total of ten studies were included in the analysis involving 1,051 cases of NP. Prolonged infusion of β-lactams was associated with higher clinical cure rate (OR 2.45, 95% CI, 1.12, 5.37) compared to intermittent infusion. However, there was no significant difference in mortality (OR 0.85, 95% CI 0.63-1.15) between the two groups. Subgroup analysis for β-lactam subclasses and for severity of illness showed comparable outcomes., Conclusion: The limited data available suggest that reduced clinical failure rates when using prolonged infusions of β-lactam antibiotics in critically ill patients with NP. More detailed studies are needed to determine the impact of such strategy on mortality in this patient population.

Background: The practice of low vs. high sedation dosing strategy may impact the cognitive and mental health function in the intensive care unit (ICU). We aim to demonstrate that high sedation strategy will result in change of mental health function in ICU patients., Methods: We performed a systemic search and meta-analysis of medical databases in MEDLINE (from 1966 to March 2013) and EMBASE (from 1980 to March 2013), as well as the Cochrane Library using the MESH terms "Intensive Care Unit," and "Mental Health, for assessing the impact of sedation on posttraumatic stress disorder (PTSD) or anxiety/depression and delirium in the mix ICU setting including cardiac surgery patients. A total of 1216 patients were included in the final analysis., Results: We included 11 studies in the final analysis and concluded that high dose sedation strategy resulted in higher incidence of cognitive dysfunction with P value of 0.009. The result for subgroup of delirium showed P = 0.11 and PTSD/depression or anxiety of P = 0.001, Heterogeneity I2 was 64%. Overall analysis was statistically significant with a P value of 0.002., Conclusion: High sedation dosing strategy will negatively affect cognitive function in critically ill patients. Large randomized trials are needed to address cognitive dysfunction in subgroup of patients with delirium.

Background. The optimal timing of tracheotomy and its impact on weaning from mechanical ventilation in critically ill morbidly obese patients remain controversial. Methods. We conducted a retrospective chart review of morbidly obese subjects (BMI ≥ 40 kg/m(2) or BMI ≥ 35 kg/m(2) and one or more comorbid conditions) who underwent a tracheotomy between July 2008 and June 2013 at a medical intensive care unit (ICU). Clinical characteristics, rates of nosocomial pneumonia (NP), weaning from mechanical ventilation (MV), and mortality rates were analyzed. Results. A total of 102 subjects (42 men and 60 women) were included; their mean age and BMI were 56.3 ± 15.1 years and 53.3 ± 13.6 kg/m(2), respectively. There was no difference in the rate of NP between groups stratified by successful weaning from MV (P = 0.43). Mortality was significantly higher in those who failed to wean (P = 0.02). A cutoff value of 9 days for the time to tracheotomy provided the best balanced sensitivity (72%) and specificity (59.8%) for predicting NP onset. Rates of NP and total duration of MV were significantly higher in those who had tracheostomy ≥ 9 days (P = 0.004 and P = 0.002, resp.). Conclusions. The study suggests that tracheotomy in morbidly obese subjects performed within the first 9 days may reduce MV and decrease NP but may not affect hospital mortality.

Health care-associated infections, including Pseudomonas aeruginosa bloodstream infection, have been linked to delays in appropriate antibiotic therapy and an increased mortality rate. The objective of this study was to evaluate intrinsic virulence, bacterial resistance, and clinical outcomes of health care-associated bloodstream infections (HCABSIs) in comparison with those of community-acquired bloodstream infections (CABSIs) caused by P. aeruginosa. We conducted a retrospective multicenter study of consecutive P. aeruginosa bacteremia patients at two university-affiliated hospitals. Demographic, clinical, and treatment data were collected. Microbiologic analyses included in vitro susceptibility profiles and type III secretory (TTS) phenotypes. Sixty CABSI and 90 HCABSI episodes were analyzed. Patients with HCABSIs had more organ dysfunction at the time of bacteremia (P = 0.05) and were more likely to have been exposed to antimicrobial therapy (P < 0.001) than those with CABSIs. Ninety-two percent of the carbapenem-resistant P. aeruginosa infections were characterized as HCABSIs. The 30-day mortality rate for CABSIs was 26% versus 36% for HCABSIs (P = 0.38). The sequential organ failure assessment score at the time of bacteremia (hazard ratio [HR], 1.2; 95% confidence interval [CI], 1.1 to 1.3) and the TTS phenotype (HR 2.1; 95% CI, 1.1 to 3.9) were found to be independent predictors of the 30-day mortality rate. No mortality rate difference was observed between CABSIs and HCABSIs caused by P. aeruginosa. Severity of illness and expression of TTS proteins were the strongest predictors of the 30-day mortality rate due to P. aeruginosa bacteremia. Future P. aeruginosa bacteremia trials designed to neutralize TTS proteins are warranted.

Study Objectives: The significance of residual excessive daytime sleepiness (EDS) on cardiovascular markers in patients with adequately treated obstructive sleep apnea (OSA) remains unclear. The objective of this study was to investigate flow-mediated dilatation (FMD) and inflammatory markers (C-reactive protein [CRP], tumor necrosis factor [TNF]-alpha, and interleukin [IL]-6) in continuous positive airway pressure (CPAP)-compliant patients with residual EDS compared with CPAP-compliant patients without residual EDS., Methods: FMD of the brachial artery was measured by ultrasound in 12 CPAP-compliant patients with OSA who had residual EDS and 12 age-, sex-, and body mass index-matched CPAP-compliant patients with OSA who did not have residual EDS on week 8 after initiation of CPAP. Twelve otherwise-healthy subjects without sleep disordered breathing were used as control subjects. Serum concentrations of CRP, TNF-alpha, and IL-6 were quantified by enzyme-linked immunosorbent assays., Results: Baseline FMD was comparable among CPAP-compliant patients with residual EDS (7.2 +/- 2.3), CPAP-compliant patients without residual EDS (8.6 +/- 2.1), and control subjects (7.7 +/- 1.4) (p = 0.37). The concentrations of CRP, TNF-alpha, and IL-6 were also not significantly different between subjects with CPAP-compliant residual EDS and those without residual EDS (p = 0.44, p = 0.37, and p = 0.42; respectively)., Conclusions: Residual EDS in patients with adequately treated OSA may not represent a risk factor for cardiovascular diseases.

Recognizing and managing the different types of aspiration events remain a challenging task due to the lack of distinguishing clinical or laboratory characteristics. Numerous biomarkers in serum, sputum and bronchoalveolar lavage have been studied, and their role in the recognition of aspiration remains controversial at this time. Recent animal investigations using an array of biomarkers based on distinct pathogenic features of each aspiration event have produced promising results; however, they have not been validated in humans. Newer markers are being introduced as diagnostic and prognostic tools in conditions such as community-acquired pneumonia and sepsis, but they have not been examined in aspiration. The present review summarizes the different biomarkers that have been studied in aspiration and those who might have a potential clinical use in the future.

Background and Objective: Conventional methods to establish pleural infection are time-consuming and sometimes inadequate. Biomarkers may aid in making rapid diagnosis of infection. In an observational study we evaluated and compared the diagnostic value of pleural fluid levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), C-reactive protein and procalcitonin in intensive care patients with pleural effusions., Methods: Thirty-six patients with de novo pleural effusions were included and 20 patients with pleural effusions after cardiothoracic surgery and 20 patients with pleural effusions after esophagus surgery acted as controls. Levels of sTREM-1, C-reactive protein and procalcitonin were measured in pleural effusions., Results: Levels of sTREM-1 were highest in empyemas, followed by infectious exudates. Levels of sTREM-1 were low in transudates and non-infectious exudates. C-reactive protein levels were highest in exudates and empyemas, while procalcitonin levels were highest in exudates. Pleural fluid with positive culture results contained higher sTREM-1 and C-reactive protein levels as compared to samples with negative culture results. A cut-off level of 50pg/mlsTREM-1 yielded a sensitivity of 93% and a specificity of 86%, while these were 87% and 67% respectively for a cut-off value of 7.5microg/ml C-reactive protein, and 60% and 64% respectively for a cut-off value of 0.15 ng/ml procalcitonin., Conclusion: sTREM-1 is superior to C-reactive protein and procalcitonin in detecting infection.

Introduction: Diagnostic strategies based on tracheal aspirates in patients with severe nursing home-acquired pneumonia have not previously been evaluated. The objectives of the study were to investigate, in patients with severe nursing home-acquired pneumonia, the diagnostic value of quantitative endotracheal aspirate (QEA) cultures using increasing interpretative cutoff points, as compared with bronchoalveolar lavage (BAL) and protected specimen brush (PSB) quantitative cultures., Methods: Seventy-five nursing home patients requiring mechanical ventilation for suspected pneumonia were studied. Endotracheal aspirate, PSB, and BAL samples were obtained consecutively. The diagnostic yield of QEA at thresholds raging from 10(3) to 10(7) colony-forming units (cfu)/ml was assessed by calculating sensitivities, specificities, and accuracy rates. A receiver operator characteristic curve for the series of cutoff points was constructed., Results: Forty-nine patients were diagnosed with pneumonia either by BAL (

Introduction: There is little objective comparative information about the postoperative complications of tracheostomy in morbidly obese patients. The aim of this study was to determine the incidence and severity of complications associated with open tracheostomy in critically ill morbidly obese patients during hospitalization., Methods: During a six year period, all consecutive morbidly obese patients (body mass index [BMI] of greater than or equal to 40 kg/m2) who underwent an elective open tracheostomy were compared to a control group (BMI of less than 40 kg/m2) of the same institution. Variables examined included age, gender, BMI, Charlson index, and reasons for tracheostomy. All postoperative tracheotomy-related complications that occurred during hospitalization, including death, were recorded., Results: A tracheostomy was performed in 89 morbidly obese patients out of 427 critically ill patients. A total of 27 complications were recorded in 22 morbidly obese patients (25%) compared to 65 complications in 49 patients (14%) of the control group (p = 0.03). The majority of these complications were minor in origin. Overall, nine serious events were responsible for two deaths in the morbidly obese compared to seven cases and two deaths in the control group (p = 0.001). Life-threatening complications were attributed to tube obstruction and malpositioning of the tracheostomy after being dislodged. In multivariate analysis, morbid obesity (odds ratio 4.4, 95% confidence interval 2.1 to 11.7) was independently associated with increased risk of tracheostomy-related complications., Conclusion: In the present series, morbid obesity is associated with increased frequency and life-threatening complications from conventional tracheostomy. Special techniques and operative policies must be applied to overcome loss of airway control.

Current recommendations for management of obese patients post-extubation are based on clinical experience and expert opinions. It was hypothesised that the application of noninvasive ventilation (NIV) during the first 48 h after extubation in severely obese patients would reduce post-extubation failure and avert the need for reintubation. Following protocol-driven weaning trials, 62 consecutive severely obese patients (body mass index > or =35 kg x m(-2)) were assigned to NIV via nasal mask immediately post-extubation and compared with 62 historically matched controls who were treated with conventional therapy. The primary end-point was the incidence of respiratory failure in the first 48 h post-extubation. Compared with conventional therapy, the institution of NIV resulted in 16% (95% confidence interval 2.9-29.3%) absolute risk reduction in the rate of respiratory failure. There was a significant difference in the intensive care unit and lengths of hospital stay between the two groups. Subgroup analysis of hypercapnic patients showed reduced hospital mortality in the NIV group compared with the control group. In conclusion, noninvasive ventilation may be effective in averting respiratory failure in severely obese patients when applied during the first 48 h post-extubation. In selected patients with chronic hypercarbia, early application of noninvasive ventilation may confer a survival benefit.

Increased oxidative stress in obstructive sleep apnoea is thought to contribute to endothelial dysfunction. The objective of this study was to test the hypothesis that inhibition of xanthine oxidase by allopurinol can improve endothelial function in patients with obstructive sleep apnoea. A randomised double-blind placebo-controlled crossover study was performed on 12 patients with moderate-to-severe obstructive sleep apnoea, comparing 300 mg allopurinol daily for 2 weeks with placebo. Endothelial function was assessed using hyperaemia-induced flow-mediated vasodilation (FMD) at baseline and following treatment. Plasma malondialdehyde levels were compared in order to assess significant changes in oxidative stress. Baseline FMD correlated significantly with the severity of sleep apnoea and the time spent with an arterial oxygen saturation of <90%. Allopurinol caused a significant increase in FMD compared to placebo (10.4+/-3.2 versus 7.4+/-2.8%, respectively). Plasma malondialdehyde levels were significantly reduced with allopurinol treatment (1.5+/-0.3 versus 1.2+/-0.3 micromol.L(-1)), consistent with reduced oxidative stress. Allopurinol improves endothelial dysfunction in patients with moderate-to-severe obstructive sleep apnoea. These observations suggest that xanthine oxidase contributes significantly to vasodilatory impairment.

Objective: To identify modifiable risk factors of nosocomial pneumonia (NP) in elderly patients post-cardiac surgery., Design: A case-control study., Setting: Post-operative intensive care unit of a tertiary-level university affiliated hospital., Subjects: Seventy three case-control pairs. Case patients referred to elderly patients who developed pneumonia post-cardiac surgery. Controls subjects were matched for age, gender, type of surgery, forced expiratory volume in 1s (FEV(1)), and ejection fraction., Measurements: Baseline sociodemograpahic information, Charlson Comorbidity Index score, intra- and post-operative data were collected. When suspected, the presence of NP was confirmed by quantitative culture of protected bronchoalveolar lavage fluid 10(3) colony forming unit/ml or positive blood/pleural fluid culture identical to that recovered from respiratory samples., Results: The incidence of NP in elderly post-heart surgery was 8.3%. The mean duration after heart surgery to the occurrence of pneumonia was 7.2+/-4.9 days. Four variables were found to be significantly related to the development of NP by multivariate analysis: Charlson Index >2 (adjusted odds ratio [AOR] 4.7; 95% confidence interval [CI], 1.9-11.4; P<0.001), reintubation (AOR 6.2; 95% CI, 1.1-36.1; P=0.04), transfusion 4 units of PRBC (AOR 2.8; 95% CI, 1.2-6.3; P=0.01), and the mean equivalent daily dose of morphine (AOR 4.6; 95% CI, 1.4-14.6; P=0.01)., Conclusions: Although there are limited effective measures to lessen the burden of comorbidities, avoiding reintubation, finding a substitute to allogenic blood transfusion, and improved assessment of pain management could reduce the rate of NP in the post-operative period of cardiac surgery in the elderly population.

Introduction: Nosocomial pneumonia is a significant cause of in-hospital morbidity and mortality. Oral care interventions have great potential to reduce the occurrence of nosocomial pneumonia. Studies using topical antiseptic agents yielded mixed results. We hypothesized that the use of chlorhexidine for oral decontamination would reduce the incidence of nosocomial pneumonia in patients requiring mechanical ventilation., Methods: This study is a meta-analysis of randomized controlled trials assessing the effect of chlorhexidine on the incidence of nosocomial pneumonia. Data sources were Medline, EMBASE, Cochrane library, citation review of relevant primary and review articles, and contact with expert informants. Out of 1,251 articles screened, 4 randomized, controlled trials were identified that included a total of 1,202 patients. Descriptive and outcome data were extracted by two reviewers independently. Main outcome measures were the incidence of nosocomial pneumonia, and mortality. A random effects model was used., Results: The incidence of nosocomial pneumonia in the control group was 7% (41 out of 615) compared to 4% (24 out of 587) in the treatment group. Gram-negative bacteria accounted for 78% of the total isolates, with Pseudomonas aeruginosa being the most frequently isolated pathogen irrespective of the intervention provided. Duration of mechanical ventilation and intensive care unit length of stay were comparable between the two groups. Overall, the use of oral decontamination with chlorhexidine did not affect the incidence of nosocomial pneumonia (odds ratio of 0.42; 95% confidence interval 0.16-1.06) or the mortality rate (odds ratio 0.77, 95% confidence interval 0.28-2.11)., Conclusion: The use of oral decontamination with chlorhexidine did not result in significant reduction in the incidence of nosocomial pneumonia in patients who received mechanical ventilation, nor altered the mortality rate. The lack of benefit may reflect the few studies conducted in this area. Future trials should focus on a combination strategy of mechanical and pharmacological interventions.

Background: Knowledge of the determinant factors responsible for the presence of antimicrobial-resistant pathogens in severe nursing home-acquired pneumonia (NHAP) is deemed essential for antibiotic selection., Methods: Data for institutionalized patients with cases of severe pneumonia confirmed by culture of protected bronchoalveolar lavage fluid samples (> or =10(3) cfu/mL) during a 36-month period were analyzed. A classification tree with a sensitivity of 100% was developed using binary recursive partitioning to predict which patients are unlikely to have drug-resistant pathogen (DRP)-related pneumonia., Results: Of the 88 patients who satisfied the inclusion criteria, 17 had at least 1 DRP recovered from the lower respiratory tract. The predictor variables were the Activity of Daily Living score and previous use of antibiotics. Prospective application of the model in 47 patients over a 24-month period yielded a sensitivity of 100% (95% confidence interval [CI], 71.3%-100%) and a specificity of 69.4% (95% CI, 51.9%-83.6%)., Conclusions: The use of the tree may provide a more rational basis for selecting initial therapy for severe NHAP after it is validated in a large prospective study.

To determine the causes, risk factors and complications of planned extubation failure of critically ill elderly patients, we conducted a prospective study of 175 consecutive patients (> or = 70 years old) admitted with respiratory failure. Thirty-six (21%) failed extubation within 72 h after planned extubation. Compared to a younger age group (< 70 years old) matched for severity of illness, inability to handle secretions (20%) was the most common reason of airway causes leading to extubation failure in the elderly while upper airway obstruction (22%) was the predominant cause in the control group. As for nonairway causes, COPD related hypercapnic respiratory failure accounted for the majority of cases in both groups. After adjusting for severity of illness, elderly patients who required reintubation had a higher risk of developing nosocomial pneumonia. The presence of underlying pulmonary disease (odds ratio (OR), 2.9; 95% confidence interval (CI) 1.2-6.9), length of intubation > 4 days (OR, 4.3; 95% CI 1.8-10.2), and albumin levels < 2.5 g/dl (OR, 2.7; 95% CI 1.2-6.7) were independently associated with extubation failure in the old. Objective measurements of cough strength and secretion volume are needed to reduce the morbidity of elderly patients at risk for extubation failure.

The aim of the study was to investigate the etiology and the impact of invasive quantitative sampling on the management of severe pneumonia in institutionalized older people with antimicrobial treatment failure. Fifty-two institutionalized patients aged 70 years and older hospitalized with a presumptive diagnosis of severe pneumonia and failure to respond to treatment after 72 hours of initiation of outpatient antimicrobial therapy were enrolled. Microbial investigation included blood culture, serology, pleural fluid, and bronchoalveolar samples. A definite etiology could be established in 24 of 52 (46%) patients. Methicillin-resistant Staphylococcus aureus (33%), enteric Gram-negative bacilli (24%), and Pseudomonas aeruginosa (14%) accounted for most isolates. Atypical infections (2%) were uncommon. Invasive bronchial sampling directed a change of microbial therapy in 8 (40%) and discontinuation of antibiotics in 2 of 20 cases (10%) of definite pneumonia. Overall hospital mortality was 42%. There was no difference in mortality among definite or unverified cases or those who had invasive bronchial sampling-guided change in therapy. We conclude that antimicrobial therapy should be targeted toward "nosocomial" pathogens in those institutionalized patients who received prior antibiotic treatment. When combined with microbial investigation, direct visualization of the tracheobronchial tree might be useful in determining the presence of bacterial pneumonia.

The etiology of severe pneumonia requiring mechanical ventilation in the very elderly has been imprecise because of lack of comprehensive studies and low yield of diagnostic approach. Overall, 104 patients 75 yr of age and older with severe pneumonia were studied prospectively at two university-affiliated hospitals. Microbial investigation included blood culture, serology, pleural fluid, and bronchoalveolar secretions. Streptococcus pneumoniae (14%), gram-negative enteric bacilli (14%), Legionella sp. (9%), Hemophilus influenzae (7%), and Staphylococcus aureus (7%) were the predominant pathogens in community-acquired pneumonia (CAP). Staphylococcus aureus (29%), gram-negative enteric bacilli (15%), Streptococcus pneumoniae (9%), and Pseudomonas aeruginosa (4%) accounted for most isolates of nursing home-acquired pneumonia (NHAP). The case fatality rate was 55% (53% for CAP and 57% for NHAP; p > 0.5). Activity of Daily Living (ADL) Index, pulmonary, endocrine and central nervous system (CNS) comorbidities were associated with distinct microbial etiology. By multivariate analysis, hospital mortality was associated independently with 24-h urine output (odds ratio [OR], 5.6; 95% confidence interval [CI], 2.5 to 7.9; p < 0.001), septic shock (OR, 4.3; 95% CI, 1.9 to 8.9; p = 0.0059), radiographic multilobar involvement (OR, 3.7; 95% CI, 1.8 to 15.6; p = 0.02), and inadequate antimicrobial therapy (OR, 2.6; 95% CI, 1.4 to 23.9; p = 0.034). Further studies should focus on identifying effective antimicrobial regimens in randomized trials.