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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

OBJECTIVES: To compare the 2003 community-acquired pneumonia (CAP) guideline and the 2005 healthcare-associated pneumonia (HCAP) guideline on time to clinical stability, length of hospital stay, and mortality in nursing home patients hospitalized for pneumonia. DESIGN: Retrospective study. SETTING: Three tertiary-care hospitals. PARTICIPANTS: Three hundred thirty-four nursing home patients. MEASUREMENTS: Patients were classified according to the antibiotic regimens they received based on the 2003 CAP guideline or the 2005 HCAP guideline. Time to clinical stability, time to switch therapy, and mortality were evaluated in an intention-to-treat analysis. A multivariate survival model using propensity analysis was used to adjust for heterogeneity between the two groups. RESULTS: Of the 334 patients, 258 (77%) were treated according to the 2003 HCAP guideline. Time to clinical stability did not differ between those treated according to the 2003 CAP or the 2005 HCAP guidelines. Only the Pneumonia Severity Index (P=.006) and multilobar involvement (P=.005) were significantly associated with delay in achieving clinical stability. Adjusted in-hospital and 30-day mortality were comparable in both cohorts (odds ratio (OR)=0.87, 95% confidence interval (CI)=0.49-1.34, and OR=0.79, 95% CI=0.42-1.31, respectively), although time to switch therapy and length of stay were longer for those treated according to the 2005 HCAP guideline. CONCLUSION: In hospitalized nursing home patients with pneumonia, treatment with an antibiotic regimen according to the 2003 CAP guideline achieved comparable time to clinical stability and in-hospital and 30-day mortality with a regimen based on the 2005 HCAP guideline. [ABSTRACT FROM AUTHOR]

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]

OBJECTIVES: To evaluate the effect on 28-day mortality of implementation of a sepsis 'bundle' protocol for the treatment of older adults with septic shock. DESIGN: Observational prospective study with a historical control group. SETTING: Tertiary care center. PARTICIPANTS: Eighty-seven consecutive patients recruited between May 2004 and February 2007 matched to a historic group identified between March 2001 and April 2004. INTERVENTIONS: Implementation of a sepsis protocol for the management of septic shock. RESULTS: Subjects who were treated according to the sepsis 'bundle' had an absolute risk reduction in 28-day mortality of 16% (95% confidence interval (CI)=-31% to -2%). The treatment group received a larger volume of fluid in the first 6 hours of presentation (3,960 +/- 1,990 vs 2,490 +/- 1,020 mL; P<.001) and lower doses of vasopressors (maximum dosage of norepinephrine 0.51 microg/kg per min (range 0.12-1.7) vs 0.98 microg/kg per min (range 0.15-3.1) P=.009). A high prevalence of adrenal insufficiency (86%) was identified in the study population. There were no significant differences between the treatment and control groups in the surviving patients with respect to duration of mechanical ventilation (median 8.5 vs 12.0, respectively; P=.07) or intensive care unit length of stay (median 12 days vs 15 days; P=.08). According to Cox regression analysis, implementation of the sepsis bundle protocol was independently associated with better 28-day survival (hazard ratio=0.54, 95% CI=0.33-0.86; P=.01). CONCLUSION: Older patients with septic shock had a better 28-day survival rate when treated with a comprehensive sepsis 'bundle' protocol. [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]

OBJECTIVE: To determine pathogen-specific kinetic changes in the alveolar procoagulant (PC) activity, tissue factor (TF), and tissue factor pathway inhibitor (TFPI) expression during the course of ventilator-associated pneumonia (VAP) and to assess the relationship between clinical resolution, intra-alveolar bacterial eradication, and restoration of hemostatic balance. DESIGN: Prospective, multiple-center study in a cohort of VAP patients. SETTING: Two university-affiliated intensive care units. PATIENTS: Thirty-five patients with microbiologically documented VAP who received adequate antimicrobial coverage and 13 controls. INTERVENTIONS: Nonbronchoscopic bronchoalveolar lavage was performed at the onset of VAP and on days 4 and 8 after initiation of antibiotic therapy. Samples were assayed for PC, TF, TFPI, and thrombin-antithrombin complex (TATc). The corresponding Clinical Pulmonary Infection Score (CPIS) was collected simultaneously. MEASUREMENTS AND MAIN RESULTS: Isolated pathogens included Pseudomonas aeruginosa (n=13), methicillin-resistant Staphylococcus aureus (MRSA) (n=8), methicillin-sensitive S. aureus (MSSA) (n=7), and Escherichia coli (n=7). Although PC activity and TF were increased among the various pathogens at the onset of VAP, the levels of those with P. aeruginosa remained elevated at the end of treatment compared with controls and other etiological agents. TFPI levels were elevated for the duration of the study for all pathogens. A universal increase in TATc was noted at the onset of VAP, but the difference among the group of pathogens was significant at days 4 and 8 posttherapy. Despite the persisting hemostatic imbalance and incomplete intra-alveolar eradication of P. aeruginosa at end of therapy, the CPIS fell comparably at each time point irrespective of the etiological agents. CONCLUSIONS: Alveolar activation of the TF-dependent pathway may be species-specific in VAP and may not be adequately balanced by TFPI. The disparity between clinical response and eradication of P. aeruginosa from the intra-alveolar space suggests the need for biological markers to guide response to therapy. [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]

STUDY OBJECTIVES: Poor dental hygiene has been linked to respiratory pathogen colonization in residents of long-term care facilities. We sought to investigate the association between dental plaque (DP) colonization and lower respiratory tract infection in hospitalized institutionalized elders using molecular genotyping. METHODS: We assessed the dental status of 49 critically ill residents of long-term care facilities requiring intensive care treatment. Plaque index scores and quantitative cultures of DPs were obtained on ICU admission. Protected BAL (PBAL) was performed on 14 patients who developed hospital-acquired pneumonia (HAP). Respiratory pathogens recovered from the PBAL fluid were compared genetically to those isolated from DPs by pulsed-field gel electrophoresis. MEASUREMENTS AND RESULTS: Twenty-eight subjects (57%) had colonization of their DPs with aerobic pathogens. Staphylococcus aureus (45%) accounted for the majority of the isolates, followed by enteric Gram-negative bacilli (42%) and Pseudomonas aeruginosa (13%). The etiology of HAP was documented in 10 patients. Of the 13 isolates recovered from PBAL fluid, nine respiratory pathogens matched genetically those recovered from the corresponding DPs of eight patients. CONCLUSIONS: These findings suggest that aerobic respiratory pathogens colonizing DPs may be an important reservoir for HAP in institutionalized elders. Future studies are needed to delineate whether daily oral hygiene in hospitalized elderly would reduce the risk of nosocomial pneumonia in this frail population. [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: Traditionally, obstructive sleep apnea (OSA) management has focused on continuous positive airway pressure therapy, oral appliances, and in some cases, surgical interventions. However, these treatments do not directly address the underlying metabolic issues contributing to OSA. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for type 2 diabetes management, have demonstrated substantial efficacy in promoting weight., Areas Covered: This review aims to summarize the potential impact of liraglutide, semaglutide, and tirzepatide in managing obese patients with OSA., Expert Opinion: The introduction of GLP-1 RAs has gained attention not only for their ability to produce significant and sustained weight loss but also for their potential to improve OSA symptoms by reducing fat deposition around the upper airway and decreasing systemic inflammation. Emerging clinical trials suggest that GLP-1 RAs may enhance traditional OSA treatments, offering an integrated approach targeting the root cause of obesity in OSA. Additionally, GLP-1 RAs may provide benefits for other obesity-related comorbidities, including hypertension and cardiovascular disease, which are commonly associated with OSA. The future integration of GLP-1 RAs into OSA treatment protocols could mark a paradigm shift toward more comprehensive management strategies, ultimately improving patient outcomes in this complex patient population.

Aspiration pneumonia refers to the process of alveolar inflammation induced by the inhalation of oropharyngeal secretions into the lower respiratory tract. Predisposing factors comprise swallowing dysfunction, impaired cough reflex, and degenerative neurological diseases. Accumulating evidence projects a fading contribution of anaerobic bacteria in aspiration pneumonia at the expense of Gram-negative bacilli, with Escherichia coli , Klebsiella pneumoniae , and Pseudomonas aeruginosa , becoming the predominant organisms recovered from respiratory specimens. Aspiration of oropharyngeal secretions colonized with respiratory pathogens induces a profound disequilibrium of the lung microbiota resulting in a state of dysbiosis. Understanding this complex temporal variability between microbiome-host associations was only made possible with the introduction of metagenomic sequencing. In this narrative review, we summarize existing knowledge and elaborate on the evolving microbiology of aspiration pneumonia including the link between oral microbiome and pulmonary aspiration. We also highlight the progress and challenges in instituting microbiome-targeted strategies for preventing and treating the sequelae of aspiration pneumonia., Competing Interests: None declared., (Thieme. All rights reserved.)

Existing evidence linking insomnia to all-cause mortality in older individuals remains inconclusive. We conducted a retrospective study of a large cohort of veterans aged 65-80 years old identified from the Corporate Data Warehouse, a large data repository derived from the Veterans Health Administration integrated medical records. Veterans' enrollees with and without International Classification of Diseases, Ninth and Tenth Revision, codes corresponding to insomnia diagnosis between 1 January 2010 and 30 March 2019 were assessed for eligibility. The primary outcome was all-cause mortality. A total of 36,269 veterans, 9584 with insomnia and 26,685 without insomnia, were included in the analysis. Baseline mean (SD) age was 72.6 (4.2) years. During a mean follow-up of 6.0 (2.9) years of the propensity score matched sample, the mortality rate was 34.8 [95% confidence interval: 33.2-36.6] deaths per 1000 person-years among patients with insomnia compared with 27.8 [95% confidence interval: 26.6-29.1] among patients without insomnia. In a Cox proportional hazards model, insomnia was significantly associated with higher mortality (hazard ratio: 1.39; [95% confidence interval: 1.27-1.52]). Patients with insomnia also had a higher risk of non-fatal cardiovascular events (hazard ratio: 1.21; [95% confidence interval: 1.06-1.37]). Secondary stratified analyses by sex, race, ethnicity and hypertension showed no evidence of effect modification. A higher risk of mortality (hazard ratio: 1.51; [95% confidence interval: 1.33-1.71]) was observed when depression was present compared with absent (hazard ratio: 1.26; [95% confidence interval: 1.12-1.44]; p = 0.02). In this cohort study, insomnia was associated with increased risk-adjusted mortality and non-fatal cardiovascular events in older individuals., (© 2024 European Sleep Research Society.)

Substance use disorders (SUDs) are associated with profound sleep disturbances, including insomnia, sleep fragmentation, and circadian rhythm dysfunction resulting in serious mental and physical consequences. This minireview presents an overview of the neurocircuitry underlying sleep disturbances in SUDs and elaborates on treatment options with emphasis on alcohol use disorder (AUD) and opioid use disorder (OUD). A PubMed, Embase, CINAHL Plus, Cochrane, and Scopus search were conducted using sleep- and AUD/OUD related keywords from January 1st, 2000, to January 31st, 2023, with preferences for recent publications and randomized-controlled trials. A bidirectional relationship exists between insomnia and addiction with the status of each condition impacting the other in dictating clinical outcome. Existing evidence points to a resurgence of insomnia during detoxification, and unless treated satisfactorily, insomnia may lead to relapse. The discussion summarizes the strengths and limitations of cognitive behavioral therapy and pharmacological treatment for insomnia in SUDs covering evidence from both animal and clinical studies. The assumption of reestablishing normal sleep patterns by attaining and maintaining sobriety is misguided. Comorbid insomnia in patients with SUDs should be approached as an independent condition that requires its own treatment. Future clinical trials are needed with the aim of providing a resource for guiding clinical management of the many patients with insomnia and SUD., Competing Interests: Conflict of interestNone., (© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024.)

Objectives: To examine whether hypnotic use in patients with insomnia reduces major adverse cardiovascular events, including all-cause mortality and nonfatal major adverse cardiovascular events., Methods: Using the Veterans Affairs Corporate Data Warehouse, we conducted a retrospective cohort study of 16,064 patients who were newly diagnosed with insomnia between January 1, 2010, and December 31, 2019. A pair of 3912 hypnotic users and nonusers were selected based on a 1:1 propensity score methodology. The primary outcome was extended major adverse cardiovascular events, a composite of the first occurrence of all-cause mortality or nonfatal major adverse cardiovascular events., Results: During the median follow-up of 4.8 years, a total of 2791 composite events occurred, including 2033 deaths and 762 nonfatal major adverse cardiovascular events. Although the incidence rates of major adverse cardiovascular events were comparable between hypnotic users and nonusers in the propensity-matched cohort, users of benzodiazepines and Z-drugs had a higher risk of all-cause mortality (hazard ratio 1.47 [95% CI, 1.17-1.88] and 1.20 [95% CI, 1.03-1.39], respectively), while serotonin antagonist and reuptake inhibitors users had a survival advantage (hazard ratio 0.79 [95% CI, 0.69-0.91]) compared with nonusers. There were no differences in the risk of nonfatal major adverse cardiovascular events between all classes of hypnotics. Male patients and those aged 60 years or younger who were using benzodiazepines or Z-drugs experienced higher major adverse cardiovascular events than their counterparts., Conclusions: In patients with newly diagnosed insomnia, treatment with hypnotics resulted in higher extended major adverse cardiovascular events but not nonfatal major adverse cardiovascular events with benzodiazepine and Z-drug users compared with nonusers. The use of serotonin antagonist and reuptake inhibitors agents had a protective effect against major adverse cardiovascular events warranting further investigation., Competing Interests: Declaration of Conflict of Interest The authors report no conflicts of interest., (Published by Elsevier Inc.)

Purpose: The causes of residual excessive sleepiness (RES) in patients with post-traumatic stress disorder (PTSD) and obstructive sleep apnea (OSA) are multifactorial and modulated by comorbid conditions. The aim of the present study was to elucidate clinical and polysomnographic determinants of RES in continuous positive airway pressure (CPAP)-adherent OSA veterans with PTSD., Methods: The study protocol consisted of a retrospective analysis of consecutive cases of patients with PTSD who presented to the Veterans Affairs sleep clinics with adequately treated OSA between June 1, 2017 and October 15, 2021. Based on the Epworth Sleepiness Scale (ESS), patients were categorized into RES (ESS ≥ 11) and no RES (ESS < 11) groups. Demographic and PSG data were subjected to univariate and multivariate analyses to ascertain predictive factors of RES., Results: Out of 171 veterans with PTSD who were adherent to CPAP, 59 (35%) continued to experience RES. The RES group had a decrease in mean ESS score of 1.2 ± 4.5 after CPAP treatment compared with 4.6 ± 4.9 for the no RES group (< 0.001). A dose-response was observed between CPAP use and RES (p = 0.003). Multivariate regression analysis identified higher baseline ESS (OR 1.30; 95% CI 1.16-1.44), greater percentage of time spent in REM sleep (OR 0.91; 95% CI 0.85-0.96), CPAP use less than 6 h (OR 2.82; 95% CI 1.13-7.01), and a positive screen for depression (OR 1.69; 95% CI 1.03-4.72) as independent predictors of RES in patients with PTSD and OSA., Conclusion: RES is highly prevalent in patients with PTSD and OSA despite adherence to CPAP and is independently associated with percentage time spent in REM, duration of CPAP utilization, and symptoms of depression., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Both post-traumatic stress disorder (PTSD) and insomnia are independently associated with a greater risk of cardiovascular mortality. The objective of this study is to determine whether PTSD plus insomnia is associated with a higher risk of major adverse cardiovascular events (MACEs) than either condition alone in a large cohort of veterans., Methods: We conducted a retrospective analysis of the national Veterans Health Administration (VHA) electronic medical records covering veterans 18 years or older with the diagnosis of PTSD, insomnia, or both from January 1, 2015, to December 31, 2020. MACE was defined as new-onset myocardial infarction (MI), transient ischemic attack (TIA) or stroke, based on ICD-9 and ICD-10 diagnosis codes from inpatient or outpatient encounters., Results: A total of 19,080 veterans, 1840 with PTSD plus insomnia and 17,240 with either PTSD or insomnia, were included in the analysis. Baseline mean (SD) age was 46.3 (11.5) years. During median follow-up of 3.9 (interquartile range, 2.4-5.1) years, 206 (1%) veterans developed incident MACE. Cumulative incidence for MI, TIA and/or stroke was larger in veterans with PTSD plus insomnia compared to PTSD and insomnia alone (p=0.008). In a Cox proportional hazards model, PTSD plus insomnia was significantly associated with greater risk of developing MACEs (hazard ratio [HR], 1.44; 95% CI, 1.38-1.50, p=0.01) than either condition after adjusting for multiple covariates including age, gender, smoking, hypertension, depression, and burden of comorbidities., Conclusions: This cohort study found that PTSD plus insomnia is a risk factor for MACEs of greater magnitude than PTSD- or insomnia-alone., Competing Interests: Declaration of competing interest The contents of this paper do not represent the views of the Department of Veterans Affairs or the United States Government., (Published by Elsevier B.V.)

Rationale: Patient-centered outcomes are increasingly sought to evaluate social interactions and healthcare interventions in patients with sleep disorders. Yet, measures to assess quality of life (QoL) are lacking for those who experience nightmares., Objective: The aim of the study is to describe the development and validation of a new health-related quality of life (HRQoL) instrument for patients with nightmares., Methods: Attributes obtained from a focus group of patients (n = 113) with established nightmares were analyzed using exploratory factor analysis to elicit salient QoL themes for the new instrument. A validation cohort (n = 34) was used to determine the psychometric performance of the 16-item questionnaire including item-scaling, concurrent validity, and test-retest reliability tested four weeks apart., Results: Four factors (sleep health, emotional and psychological well-being, social interaction, and motivation) explained 53.9% of the total variance. The Nightmare Quality of Life (NQoL) showed good internal consistency (Cronbach's alpha 0.85) and test-retest reliability (ICC = 0.89). Concurrent validity was evidenced by a strong correlation with the Nightmare Distress Questionnaire (r = 0.87; p < .001) and more modest associations with the Nightmare Frequency Questionnaire (r = , 0.69; p < .001), SF-36 (r = -0.68; p < .001), and PSQI (r = 0.45; p = .007)., Conclusions: The NQoL has demonstrable construct validity and reliability and represents a promising multi-dimensional instrument to assess outcome measures for quality of life in patients with nightmares.

Background: Given concerns over immune function, the decision whether to continue disease modifying therapy (DMT) in multiple sclerosis (MS) patients during the COVID-19 pandemic has been challenging, complicated by the risk of MS disease progression in the absence of treatment., Methods: This retrospective analysis of patients treated for COVID-19 infection at veteran affairs healthcare systems across the United States, investigated 30-day all-cause mortality after first positive COVID-19 in patients with and without MS. We examined mortality risk impact of disease modifying therapy for MS, accounting for other relevant factors known to be associated with COVID-19 mortality. Patients were propensity score matched in a 1:20 fashion based on MS diagnosis., Results: 49,737 COVID-19 inpatient cases were identified, of which 258 were diagnosed with MS. In the propensity score matched cohort, MS patients taking DMT (excluding those receiving anti-CD20 antibodies) had a lower odds of 30 day mortality (OR: 0.18 [95%CI: 0.00988-0.94] p=0.041). Similarly, in the unmatched cohort, patients on DMT had a lower risk of death (OR: 0.16 [95%CI: 0.01-0.82] p=0.023). There was no statistically significant difference in mortality between those with and without MS. In the propensity matched cohort, age over 65, heart failure, chronic kidney disease (CKD), and diabetes increased the risk of mortality while vaccination reduced the risk of mortality., Conclusion: Veteran patients with MS hospitalized for COVID-19 were less likely to die when taking DMTs (excluding those receiving anti-CD20 antibodies), accounting for other relevant factors. Results suggest that, in relation to the COVID-19 pandemic, not only is it safe to continue most DMTs in people with MS, but it may be beneficial given the decreased risk of COVID-19 mortality and decreased risk of MS disease progression., (Copyright © 2022. Published by Elsevier B.V.)

Statins have been advocated as a potential treatment for coronavirus disease-2019 (COVID-19) due to its pleotropic properties. The aim of the study was to elucidate the association between antecedent statin exposure and 30-day all-cause mortality, intensive care unit (ICU) admission and hypoxic respiratory failure requiring mechanical ventilation in patients diagnosed with COVID-19. Observational cohort study derived from the VA Corporate Data Warehouse of all veterans tested positive for COVID-19 between January 1st and May 31st, 2020. Antecedent use of statins was defined as a redeemed drug prescription in the 6 months prior to COVID-19 diagnosis. Propensity-matched mixed-effects logistic regression was performed, stratified by statin use. The study population comprised 14,268 patients with COVID-19 (median age 66 years (25th-75th percentile, 53-74), 90.7% men), of whom 7,168 were receiving a prescription for statins. Patients with statin exposure had a greater prevalence of comorbidities and a higher risk of mortality (Odd ratio [OR] 1.52; 95% confidence interval [CI] 1.37-1.68). After adjusting for covariates, statin exposure was not associated with a decreased mortality in the overall cohort by either Cox proportional hazards stratified model (HR 0.99; 95% CI 0.88-1.12) or propensity matching (HR .86; 95% CI 0.74-1.01). Similarly, there was no demonstrated advantage of statins in reducing the risk of ICU admission (HR 0.92; 95% CI 0.74-1.31) or hypoxic respiratory failure requiring mechanical ventilation (HR 1.02; 95% CI 0.81-1.29). Antecedent statin exposure in patients with COVID-19 was not associated with a decreased risk of 30-day all-cause mortality or need for mechanical ventilation., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Introduction: Patients with persistent sleepiness after adequate treatment of obstructive sleep apnea (OSA) with nasal continuous positive airway pressure (nCPAP) experience impaired cognition, reduced productivity, and worse quality of life. Although the mechanisms responsible for this phenomenon are not completely understood, neuroimaging studies have identified reduced gray matter in the frontal cortex and alterations in white matter integrity suggestive of axonal and myelin damage. The intermittent hypoxia with resulting oxidative injury is considered a prime culprit behind the loss of wake-promoting catecholaminergic neurons., Areas Covered: This narrative review gives an overview of the pathophysiology and approaches to managing patients with residual sleepiness. The authors explore different targeted strategies aimed at improving selection of appropriate pharmacotherapy., Expert Opinion: Wake-stimulant medications (modafinil and armodafinil) have demonstrated efficacy in reducing sleepiness in adequately treated OSA. The recent FDA approval of pitolisant and solriamfetol complements the use of modafinil by substituting for direct sympathomimetic agents. The distinctive pharmacologic profile and mode of action of each of these agents offer the opportunity of a personalized approach to the management of this disorder. Further studies should be conducted on the long-term effect of these agents alone or in combination on brain structural and functional changes.

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.)

Purpose: We sought to determine the prevalence of low arousal threshold (LAT) in veterans with post-traumatic stress disorder (PTSD) and whether or not LAT is associated with decreased use of continuous positive airway pressure (CPAP)., Methods: We conducted a retrospective study of all veterans with documented PTSD who had an apnea hypopnea index > 5/h over a 27-month period. Demographic, clinical characteristics, and CPAP usage were extracted from the medical records. A multivariate analysis was conducted to assess predictors of CPAP use at 3 months in patients with LAT after adjusting for severity of PTSD., Results: LAT was identified in 55% of 119 patients with PTSD and newly diagnosed OSA. LAT was associated with younger age (odds ratio [OR] 0.91; 95% confidence interval [CI] 0.86-0.95), lower BMI (OR 0.82; 95% CI 0.73-0.91), presence of insomnia (OR 1.34; 95% CI 1.19-1.81), and use of antidepressant (OR 1.14; 95% CI 1.09-2.01). PTSD severity, REM rebound, and the presence of baseline comorbid insomnia were each associated with CPAP use at 3 months. Neither daytime sleepiness, body mass index (BMI), nor LAT endotype was correlated with CPAP utilization. Insomnia was the only factor associated with decreased CPAP use in patients with PTSD and LAT (P = 0.04)., Conclusion: The LAT endotype is common among veterans with PTSD. An improved understanding of how insomnia in this population affects CPAP utilization would be instrumental in designing targeted therapy to improve sleep quality.

Background: Mortality attributable to coronavirus disease-19 (COVID-19) 2 infection occurs mainly through the development of viral pneumonia-induced acute respiratory distress syndrome (ARDS)., Research Question: The objective of the study is to delineate the clinical profile, predictors of disease progression, and 30-day mortality from ARDS using the Veterans Affairs Corporate Data Warehouse., Study Design and Methods: Analysis of a historical cohort of 7,816 hospitalized patients with confirmed COVID-19 infection between January 1, 2020, and August 1, 2020. Main outcomes were progression to ARDS and 30-day mortality from ARDS, respectively., Results: The cohort was comprised predominantly of men (94.5%) with a median age of 69 years (interquartile range [IQR] 60-74 years). 2,184 (28%) were admitted to the intensive care unit and 643 (29.4%) were diagnosed with ARDS. The median Charlson Index was 3 (IQR 1-5). Independent predictors of progression to ARDS were body mass index (BMI) ≥40 kg/m 2 , diabetes, lymphocyte counts <700 × 109/L, LDH >450 U/L, ferritin >862 ng/ml, C-reactive protein >11 mg/dL, and D-dimer >1.5 ug/ml. In contrast, the use of an anticoagulant lowered the risk of developing ARDS (OR 0.66 [95% CI 0.49-0.89]. Crude 30-day mortality rate from ARDS was 41% (95% CI 38%-45%). Risk of death from ARDS was significantly higher in those who developed acute renal failure and septic shock. Use of an anticoagulant was associated with 2-fold reduction in mortality. Survival benefit was observed in patients who received corticosteroids and/or remdesivir but there was no advantage of combination therapy over either agent alone., Conclusions: Among those hospitalized for COVID-19, nearly 1 in 10 progressed to ARDS. Septic shock, and acute renal failure are the leading causes of death in these patients. Treatment with either remdesivir and corticosteroids reduced the risk of mortality from ARDS. All hospitalized patients with COVID-19 should be placed at a minimum on prophylactic doses of anticoagulation.

Increasingly compelling data link chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) to cardiovascular complications independent of known comorbidities. It remains unclear whether the association is amplified in the presence of both conditions. The aims of this study are to assess the prevalence of atrial fibrillation (AF) in overlap syndrome (OS) and to identify risk factors predisposing to this atrial arrhythmia. We conducted a retrospective cohort study of 268 adults without past or current AF who were referred for an initial diagnostic polysomnogram from 2012 to 2019. A logistic regression analysis was performed to identify risk factors for incident AF. Incident AF occurred in 64 subjects [cumulative probability 24%, 95% confidence interval (CI) 19-29]. Independent predictors of incident AF were age-adjusted Charlson index [Odds ratio (OR) 1.62; 95% confidence interval (CI) 1.3-2.0], percentage of time spent with O 2 saturation below 90% (CT90) (OR 3.72, 95% CI 1.18-11.71), and CPAP adherence (OR 0.32, 95% CI 0.13-0.71). OS patients with AF experienced higher hospitalization rates (OR 1.25, 95% CI 1.03-2.37) and worse mortality rates (OR 1.92, 95% CI 1.04-3.54). In multivariate Cox proportional regression, age-adjusted Charlson Index, severity of airflow obstruction, and CPAP adherence were independent predictors of mortality. The burden of hypoxemia and severity of comorbidities are independent factors for incident AF in individuals with OS. CPAP adherence may mitigate the risk of AF and reduce the rate of mortality in this population.

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

Introduction: Chronic insomnia, whether it is primary or in combination with another medical or psychiatric disorder, is a prevalent condition associated with significant morbidity, reduced productivity, increased risk of accidents, and poor quality of life. Pharmacologic and behavioral treatments have equivalent efficacy with each having its own advantages and limitations., Areas Covered: The purpose of this perspective is to delineate the limitations encountered in implementing cognitive behavioral therapy (CBT) and to review the pharmacological treatments designed to target the different phenotypes of insomnia. The discussions address how to choose the optimal medication or combination thereof based on patients' characteristics, available medications, and the presence of comorbid conditions. Selective nonbenzodiazepine sedative 'Z-drug' hypnotics, melatonin receptor agonist-ramelteon, and low-dose doxepin are the agents of choice for treatment of primary and comorbid insomnia., Expert Opinion: A pharmacological intervention should be offered if cognitive behavioral therapy for insomnia is not available or has failed to achieve its goals. Increasing evidence of the significant adverse consequences of long-term benzodiazepines should limit the prescription of these agents to specific conditions. Testing novel dosing regimens with a combination of hypnotic classes augmented with CBT deserve further investigation.

Introduction: Patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA)-overlap syndrome-have a substantially greater risk of morbidity and mortality, compared to those with either COPD or OSA alone., Objectives: The aim of this retrospective study was to identify clinical modifiable factors associated with COPD exacerbations and all-cause mortality in patients with overlap syndrome., Methods: The electronic records of patients with simultaneous COPD and OSA who had a documented acute exacerbation of COPD during a 42-month period were evaluated for reviewed. A control group of overlap syndrome patients without exacerbations was matched 1:1 for age and body mass index. Vital status and cause of death were assessed through the population death registry., Results: Out of 225 eligible cases, 92 patients had at least one episode of COPD exacerbation. There was no significant association between severity of airflow limitation and apnoea hypopnea index (P = .31). After adjusting for confounding variables, patients who had at least one COPD exacerbation were more likely to be active smokers (P = .01), have poorer lung function (P = .001) and less likely to adhere to continuous positive airway pressure (CPAP) use (P = .03). All-cause mortality was also correlated with low forced expiratory volume in 1 second (P = .006), CPAP use (P = .007), and burden of comorbidities (P < .001)., Conclusion: Lung function and CPAP use were independent predictors of COPD exacerbations and all-cause mortality in a cohort of patients with overlap syndrome. These factors should be taken into account when considering the management and prognosis of these patients., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Insomnia is a well-recognized co-morbid condition in veterans with post-traumatic stress disorder (PTSD) with negative personal and social consequences. Cognitive behavioral therapy (CBT) is considered an efficacious treatment, yet little attention has been devoted to treatment response in this population. The aim of this study was to identify factors that may predict clinical response to CBT for insomnia (CBT-I) in veterans with PTSD., Methods: A retrospective chart review of 136 veterans with PTSD-related insomnia was conducted. Epworth Sleepiness Score (ESS), PTSD Checklist (PCL), and Insomnia Severity Index (ISI) were assessed at baseline. We converted prescribed antidepressant and hypnotic dosages before and after CBT-I to dose equivalent of fluoxetine diazepam, respectively. A 6-point reduction or greater in ISI scores at 6-month follow-up visit was defined as CBT-I responsiveness., Results: CBT-I responsiveness was observed in 47% of veterans with PTSD. Seventy-seven percent completed treatment. Lack of perceived benefit was the most given reason for failure to return for follow-up. In contrast to hypnotics, antidepressants usage decreased in those who had experienced benefit from CBT-I (p = 0.001). Younger age, non-white race, and use of hypnotics prior to behavioral therapy were independently associated with lack of response to CBT-I., Conclusions: While CBT-I ameliorates insomnia in veterans with PTSD, the use of hypnotics prior to instituting behavioral therapy may negatively affect the response rate to CBT-I. Future studies should examine whether racial and cultural influences on the generation of insomnia in veterans with PTSD affects the response to CBT-I.

Introduction: Insomnia is among the most reported sleep disturbances in patients with post-traumatic stress disorder (PTSD). The pervasiveness of this disorder among trauma-inflicted civilians and military personnel has been associated with reduced quality of life, impaired psychosocial functioning including cognitive impairments, negative mood swings, cardiovascular complications, and increased utilization of medical services., Areas Covered: This review describes the current state of science with respect to the impact of the most dispensed pharmacological interventions for posttraumatic insomnia. At the present, there are no established treatment algorithms for PTSD-related insomnia. Pharmacotherapy offers an alternative treatment modality for patients with PTSD who fail or decline cognitive behavioral therapy (CBT). Selection of a hypnotic/sedative agent should be based on the patient's history, precipitating and perpetuating factors of insomnia, side effect profile, and potential medication-related interactions. Antipsychotics and benzodiazepines appear ineffective or are associated with significant harm in treating PTSD-related insomnia., Expert Opinion: In the absence of randomized controlled trials, prescription patterns have been guided by anecdotal reports and expert opinion. Due to the complexity and multifactorial etiology of insomnia in PTSD, clinical investigations should examine available pharmacologic agents in comparative trials or in combination with CBT or complementary therapies to assess both short-term and long-term sleep outcomes in this population.

Background: Patients commonly present to primary care services with upper and lower respiratory tract infections, and guidelines to help physicians investigate and treat acute cough due to suspected pneumonia and influenza are needed., Methods: A systematic search was carried out with eight patient, intervention, comparison, outcome questions related to acute cough due to suspected pneumonia or influenza., Results: There was a lack of randomized controlled trials in the setting of outpatients presenting with acute cough due to suspected pneumonia or influenza who were not hospitalized. Both clinical suggestions and research recommendations were made on the evidence available and CHEST Expert Cough Panel advice., Conclusions: For outpatient adults with acute cough due to suspected pneumonia, we suggest the following clinical symptoms and signs are suggestive of pneumonia: cough; dyspnea; pleural pain; sweating, fevers, or shivers; aches and pains; temperature ≥ 38°C; tachypnea; and new and localizing chest examination signs. Those suspected of having pneumonia should undergo chest radiography to improve diagnostic accuracy. Although the measurement of C-reactive protein levels strengthens both the diagnosis and exclusion of pneumonia, there was no added benefit of measuring procalcitonin levels in this setting. We suggest that there is no need for routine microbiological testing. We suggest the use of empiric antibiotics according to local and national guidelines when pneumonia is suspected in settings in which imaging cannot be performed. Where there is no clinical or radiographic evidence of pneumonia, we do not suggest the routine use of antibiotics. There is insufficient evidence to make recommendations for or against specific nonantibiotic, symptomatic therapies. Finally, for outpatient adults with acute cough and suspected influenza, we suggest that initiating antiviral treatment (according to Centers for Disease Control and Prevention advice) within 48 hours of symptoms could be associated with decreased antibiotic use and hospitalization and improved outcomes., (Copyright © 2018 American College of Chest Physicians. All rights reserved.)

A growing body of evidence supports a bidirectional relationship between posttraumatic stress disorder (PTSD) and sleep disturbances. Fragmented sleep induced by sleep-related breathing disorders, insomnia, and nightmares impacts recovery and treatment outcomes and worsens PTSD symptoms. Despite recent attention, management of these disorders has been unrewarding in the setting of PTSD. This review summarizes the evidence for empirically supported treatments of these sleep ailments, including psychotherapeutic and pharmacologic interventions, as it relates to PTSD. Recent advances in positive airway pressure technology have made treatment of OSA more acceptable; however, adherence to CPAP therapy presents a substantial challenge. Concomitant insomnia, which engenders psychiatric and medical conditions, including depression, suicide, and alcohol and substance abuse, can be managed with cognitive behavioral therapy. Hypnotic agents are considered an alternative therapy, but concerns about adverse events and lack of high-level evidence supporting their efficacy in PTSD treatment have limited their use to resistant cases or as adjuncts to behavioral therapy when the response is less than desirable. Intrusion of nightmares can complicate PTSD treatment and exert serious strain on social, occupational, and marital relations. Imagery rehearsal therapy has shown significant reduction in nightmare intensity and frequency. The success of noradrenergic blocking agents has not been consistent among studies, with one-half reporting treatment failure. An integrated stepped care approach that includes components of both behavioral and pharmacologic interventions customized to patients' sleep-maladaptive behaviors may offer a solution to delivering accessible, effective, and efficient services for individuals with PTSD., (Published by Elsevier Inc.)

Purpose: The purpose of this study was to determine the impact of insomnia in Veterans with post-traumatic stress disorder (PTSD) and obstructive sleep apnea (OSA) on health-related outcomes before and after 12 weeks of continuous positive airway pressure (CPAP) treatment., Methods: We conducted a prospective cohort study of Veterans with PTSD and documented apnea hypopnea index (AHI) ≥ 5 with and without clinically significant insomnia as determined by the Insomnia Severity Index (ISI). Health-related outcomes including PTSD checklist (PCL-M), SF-36, and Pittsburgh Sleep Quality Index (PSQI) were assessed at baseline and 12 weeks after initiation of OSA treatment. CPAP adherence was retrieved at each visit., Results: Seventy-two Veterans including 36 with comorbid insomnia and OSA (COMISA) and 36 OSA-only were enrolled. Veterans with COMISA were younger (p = 0.03), had lower BMI (p < 0.001), and were more likely to report depression than those with OSA-only (p = 0.004). Although AHI was higher in the COMISA (p = 0.01), both groups expressed comparable daytime sleepiness (p = 0.16). The COMISA group had no significant change in SF-36 and PSQI after 12 weeks of treatment and used CPAP much less frequently than OSA-only group (p = 0.001)., Conclusions: COMISA in Veterans with PTSD is associated with worse quality of life than those with OSA-only. Insomnia should be assessed in Veterans with PTSD who are not adherent to CPAP treatment.

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.

Objectives: Previous retrospective studies have shown that continuous positive airway pressure (CPAP) exerts salutary effect on post-traumatic stress disorder (PTSD) symptoms and nightmare distress. The relative magnitude of therapeutic benefits from CPAP and the strength of associations between duration of CPAP use and PTSD symptomatology are unknown., Methods: A prospective cohort design involving 47 combat veterans with PTSD and documented obstructive sleep apnea (OSA) by overnight polysomnography. Epworth Sleepiness Scale (ESS) score, PTSD checklist-Military (PCL-M), Nightmare Distress Questionnaire (NDQ), and Nightmare Frequency Questionnaire (NFQ) were administered at baseline and 3 months after CPAP therapy. Objective adherence was assessed at the 3-month follow-up., Results: Twenty-two veterans with mild-to-moderate PTSD (PCL-M score 17-59) and 18 with severe-to-very-severe PTSD (PCL-M score 60-85) completed the study. There was a dose-dependent response of PCL-M to duration of CPAP usage (r = 0.45; p = 0.003). Veterans with severe-to-very-severe PTSD had a larger improvement in PTSD symptoms (d = 0.65; p = 0.004) compared with those with mild-to-moderate PTSD (d = 0.47; p = 0.04). CPAP usage was the only significant predictor of overall subjective improvement in PTSD symptoms (OR 10.5; p = 0.01). Significant changes in NDQ and NFQ scores following 3 months of treatment were observed in veterans adherent to CPAP, but the correlations with duration of CPAP use were not statistically significant (r = 0.24; p = 0.13 and r = 0.13; p = 0.4, respectively)., Conclusions: Improvement of PTSD symptoms in veterans with OSA was more pronounced with prolonged use of CPAP. Adherence to treatment was linked to abatement in nightmare distress and frequency. Future investigation of multimodal treatment, including behavioral intervention combined with CPAP, is warranted., (Published by Elsevier B.V.)

The use of nasal high-flow oxygen therapy (NHFOT) has become increasingly common in hospitals across Europe, Asia, and North America. These high utility devices provide an efficient and comfortable access points for providing supplemental oxygen to patients with variety of respiratory disorders. They are relatively easy to set up, and clinicians and patients alike give very positive feedback about their ease of use and comfort for patients in the hospital setting. However, it remains uncertain whether NHFOT improves patient survival or even reduces respiratory complications. Outcome data in adult populations are few and frequently underpowered to guide physicians for their widespread use in hospital setting. In this article, we present a review of the current technology and available studies pertinent to NHFOT.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

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.

The practice of sedation dosing strategy in mechanically ventilated patient has a profound effect on cognitive function. We conducted a comprehensive review of outcome of sedation on mental health function in critically ill patients on mechanical ventilation in the intensive care unit (ICU). We specifically evaluated current sedative dosing strategy and the development of delirium, post-traumatic stress disorders (PTSDs) and agitation. Based on this review, heavy dosing sedation strategy with benzodiazepines contributes to cognitive dysfunction. However, outcome for mental health dysfunction is mixed in regard to newer sedatives agents such as dexmedetomidine and propofol. Moreover, studies that examine the impact of sedatives for persistence of PTSD/delirium and its long-term cognitive and functional outcomes for post-ICU patients are frequently underpowered. Most studies suffer from low sample sizes and methodological variations. Therefore, larger randomized controlled trials are needed to properly assess the impact of sedation dosing strategy on cognitive function.