The non-vitamin K antagonist oral anticoagulants (NOACs), rivaroxaban, apixaban, and dabigatran, have been shown in phase 3 trials to be effective for thromboprophylaxis in patients undergoing elective hip or knee arthroplasty. Results from prior studies suggested that the safety of anticoagulants in such patients was improved if the first postoperative dose was delayed for at least 6 h after surgery. The timing of the first postoperative dose of the NOACs tested in phase 2 studies differed among the three NOACs: dabigatran was started 1 to 4 h postoperatively, whereas rivaroxaban and apixaban were started at least 6 and 12 h, postoperatively, respectively. Our review of the timing of initiation of thromboprophylaxis in randomized trials provides three related lessons. First, clinical trials performed before the NOACs were evaluated demonstrated that delaying the first dose of prophylactic anticoagulation until after major surgery is effective and safe. Second, the optimal timing of the first dose of prophylactic anticoagulation after surgery depends on the dose that is selected. Third, the results of the phase 3 trials with NOACs for thromboprophylaxis support the concept that acceptable efficacy and safety can be achieved when the appropriate first postoperative dose of anticoagulant is delayed for at least 6 h after surgery.

OSA is a common condition that has been associated with atrial fibrillation (AF), but there is a paucity of data from large longitudinal cohorts to establish whether OSA is a risk factor for AF independent of obesity and other established risk factors.

Mechanical ventilation is a cornerstone in the management of acute respiratory failure. Both volume-targeted and pressure-targeted ventilations are used, the latter modes being increasingly used. We provide a narrative review of the physiologic principles of these two types of breath delivery, performed a literature search, and analyzed published comparisons between modes.

The purpose of this study was to systematically review the research on volume and outcome relationships in critical care.

During pregnancy, upper airway resistance is increased, predisposing vulnerable women to pregnancy-related OSA. Elevation of the upper body increases upper airway cross-sectional area (CSA) and improves severity of OSA in a subgroup of nonpregnant patients (positional-dependent sleep apnea). We tested the hypothesis that elevated position of the upper body improves OSA early after delivery.

The long-term prognosis of nonasthmatic eosinophilic bronchitis (NAEB) is still unclear. The aim of this study was to observe the frequency of relapse among patients with NAEB and the likelihood of NAEB developing into chronic airflow obstruction over time.

Although patients may find it difficult to describe their breathing discomfort, most are able to select statements among a list to describe their experience. The primary objective of this study was to examine sensitivity and specificity of descriptors of breathing discomfort prospectively in patients with common respiratory conditions as well as those patients who had refractory dyspnea.

There is a bidirectional association between OSA and systemic hypertension. The strengths of this relationship appear to be modulated by factors such as age, sex, and somnolence. The 24-h BP circadian pattern also appears to be influenced by OSA. Patients with this syndrome exhibit a high prevalence of nondipping or riser circadian patterns, which are related to clinical and subclinical organ damage in the heart and brain. However, the influence of OSA on nocturnal hypertension development has not yet been clarified. A special area of interest is the recognized relationship between OSA and resistant hypertension. The majority of patients with resistant hypertension suffer OSA. CPAP treatment significantly reduces BP in such patients and could play a clinical role in the management of BP in these patients. Several meta-analyses have demonstrated a concordant mild effect of CPAP on systemic hypertension. This effect is related to CPAP compliance, somnolence status, and baseline BP. The effects of oral appliances on BP in patients with OSA must be evaluated in randomized controlled trials. In the absence of additional data reported by clinical studies on other antihypertensive drug treatments, diuretics, particularly antialdosteronic diuretic agents, should be considered the first-line antihypertensive drug treatment in patients with OSA. By reducing parapharyngeal edema and secondary upper airway obstruction, these drugs appear to improve OSA severity and also to reduce BP.

Consensus on how best to express bronchodilator reversibility (BDR) is lacking. We tested different BDR criteria against the null hypotheses that BDR should show no sex or size bias. To determine the best criterion for defining BDR, we hypothesized that clinically important BDR should be associated with better survival in respiratory patients compared with that of patients without BDR.

We conducted a systematic review on the management of psychogenic cough, habit cough, and tic cough to update the recommendations and suggestions of the 2006 guideline on this topic.

The overwhelming majority of surgical procedures performed in the United States are done on an outpatient basis. Patients with complicated medical problems are routinely scheduled for ambulatory procedures that have become progressively more complex. Appropriate patient selection is paramount to ensuring optimal perioperative outcomes, and the patient with known or suspected OSA presents unique challenges to the anesthesia care team regarding airway management, pain control, and postoperative monitoring requirements. Currently, a relative paucity of high-quality evidence exists on which to base guidelines or recommendations for the anesthetic care of these patients. It is generally agreed that early identification of those at risk for OSA allows for planning and implementation of strategies to help to reduce the risk of adverse perioperative events. Although various national societies have published consensus statements aimed at guiding the perioperative management of the patient at risk for OSA, more studies are needed to define the optimal approach to the perioperative care of this population.

Despite massive investments in the development of novel treatments for heterogeneous diseases such as COPD, the resources spent have only benefited a fraction of the population treated. Personalized health care to guide selection of a suitable patient population already in the clinical development of new compounds could offer a solution. This review discusses past successes and failures in drug development and biomarker research in COPD, describes research in COPD phenotypes and the required characteristics of a suitable biomarker for identifying patients at higher risk of progression, and examines the role of extracellular matrix proteins found to be upregulated in COPD. Novel biomarkers of connective tissue remodeling that may provide added value for a personalized approach by detecting subgroups of patients with active disease suitable for pharmacologic intervention are discussed.

Mortality caused by acute cardiopulmonary disease is decreasing, and in many countries the population is aging rapidly. Yet, the life-years gained are often spent with multiple chronic and slowly progressive conditions, and this particularly applies to patients with cardiopulmonary disease. Affected individuals often have multiple diagnoses related to the cardiopulmonary-metabolic axis with accelerated aging and gradually progressive failure of organs that provide the body with oxygen and nutrients. This more or less reflects an "engine running out of fuel." This, for instance, is the case with the concurrent presence of COPD and heart failure in one patient that is often combined with other comorbidities such as atrial fibrillation, renal failure, or diabetes. This asks for a paradigm shift: away from single-disease-oriented patient management and toward patient-tailored multimorbidity medicine. Daily clinical practice is already recognizing this on a daily basis, yet clinical research and guidelines are still lagging behind. Thus, novel research approaches are needed to better guide evidence-based clinical practice. These approaches include the construction of diagnostic models to predict the presence of multiple diseases simultaneously, individual patient data meta-analysis as a method to examine variation in the effects of treatments or diagnostic tests depending on comorbidity, and the construction of therapeutic prediction models that predict the therapeutic effect of drugs based on the presence (or absence) of relevant comorbidity. We argue that multimorbidity should be regarded as a "friend" and not as a "foe" in clinical research addressing the current clinical problems in daily practice.

Systemic thrombolysis for acute pulmonary embolism (PE) carries up to a 20% risk of major bleeding, including a 2% to 5% risk of hemorrhagic stroke. We evaluated the safety and effectiveness of catheter-directed therapy (CDT) as an alternative treatment of acute PE.

FVC outcomes in clinical trials on idiopathic pulmonary fibrosis (IPF) can be substantially influenced by the analytic methodology and the handling of missing data. We conducted a series of sensitivity analyses to assess the robustness of the statistical finding and the stability of the estimate of the magnitude of treatment effect on the primary end point of FVC change in a phase 3 trial evaluating pirfenidone in adults with IPF.

Caring for patients affected with Ebola virus disease (EVD) while simultaneously preventing EVD transmission represents a central ethical challenge of the EVD epidemic. To address this challenge, we propose a model policy for resuscitation and emergent procedure policy of patients with EVD and set forth ethical principles that lend support to this policy. The policy and principles we propose bear relevance beyond the EVD epidemic, offering guidance for the care of patients with other highly contagious, virulent, and lethal diseases. The policy establishes (1) a limited code status for patients with confirmed or suspected EVD. Limited code status means that a code blue will not be called for patients with confirmed or suspected EVD at any stage of the disease; however, properly protected providers (those already in full protective equipment) may initiate resuscitative efforts if, in their clinical assessment, these efforts are likely to benefit the patient. The policy also requires that (2) resuscitation not be attempted for patients with advanced EVD, as resuscitation would be medically futile; (3) providers caring for or having contact with patients with confirmed or suspected EVD be properly protected and trained; (4) the treating team identify and treat in advance likely causes of cardiac and respiratory arrest to minimize the need for emergency response; (5) patients with EVD and their proxies be involved in care discussions; and (6) care team and provider discretion guide the care of patients with EVD. We discuss ethical issues involving medical futility and the duty to avoid harm and propose a utilitarian-based principle of triage to address resource scarcity in the emergency setting.

Surfactant has been shown to be dysfunctional in ARDS, and exogenous surfactant has proven effective in many forms of neonatal and pediatric acute lung injury (ALI). In view of the positive results of our studies in children along with evidence that surfactant-associated protein B containing pharmaceutical surfactants might be more effective, we designed a multiinstitutional, randomized, controlled, and masked trial of calfactant, a calf lung surfactant, in adults and children with ALI/ARDS due to direct lung injury.