There is a strong association between sleep-related problems and neurologic diseases. Neurologic diseases of the CNS can directly cause sleep problems when sleep-wake mechanisms associated with the ascending reticular activating system are involved. The major sleep disorders associated with neurologic problems are outlined in the International Classification of Sleep Disorders, 2nd edition, as hypersomnias of central origin, sleep-related breathing disorders, the insomnias, circadian rhythm sleep disorders, sleep-related movement disorders, parasomnias, and sleep-related epilepsy. In a patient with CNS disease and excessive sleepiness, sleep-related breathing disorders should be a first concern, given the known association between obstructive sleep apnea (OSA) and cerebrovascular disease and the potential confounding effects that OSA might have on an otherwise compromised ischemic CNS penumbra. A basic knowledge of the anatomy and physiology of the sleep-wake mechanisms provides a rationale for pharmacologic intervention. Nonpharmacologic treatments are also important, especially when sleep-related breathing disorders are a concern. In addition, as patients with neurologic diseases are often prone to the adverse effects of many medications, the specific treatment regimen for any given individual should always include good sleep hygiene practices that use cognitive behavioral therapy.

Part 2 of this review of ICU scoring systems examines how scoring system data should be used to assess ICU performance. There often are two different consumers of these data: lCU clinicians and quality leaders who seek to identify opportunities to improve quality of care and operational efficiency, and regulators, payors, and consumers who want to compare performance across facilities. The former need to know how to garner maximal insight into their care practices; this includes understanding how length of stay (LOS) relates to quality, analyzing the behavior of different subpopulations, and following trends over time. Segregating patients into low-, medium-, and high-risk populations is especially helpful, because care issues and outcomes may differ across this severity continuum. Also, LOS behaves paradoxically in high-risk patients (survivors often have longer LOS than nonsurvivors); failure to examine this subgroup separately can penalize ICUs with superior outcomes. Consumers of benchmarking data often focus on a single score, the standardized mortality ratio (SMR). However, simple SMRs are disproportionately affected by outcomes in high-risk patients, and differences in population composition, even when performance is otherwise identical, can result in different SMRs. Future benchmarking must incorporate strategies to adjust for differences in population composition and report performance separately for low-, medium- and high-acuity patients. Moreover, because many ICUs lack the resources to care for high-acuity patients (predicted mortality >50%), decisions about where patients should receive care must consider both ICU performance scores and their capacity to care for different types of patients.

Over the past 50 years, we have seen dramatic changes in cardiovascular science and clinical care, accompanied by marked declines in the morbidity and mortality. Nonetheless, cardiovascular disease remains the leading cause of death and disability in the world, and its nature is changing as Americans become older, fatter, and ethnically more diverse. Instead of young or middle-aged men with ST-segment elevation myocardial infarction, the "typical" cardiac patient now presents with acute coronary syndrome or with complications related to chronic hypertension or ischemic heart disease, including heart failure, sudden death, and atrial fibrillation. Analogously, structural heart disease is now dominated by degenerative valve or congenital disease, far more common than rheumatic disease. The changing clinical scene presents cardiovascular scientists with a number of opportunities and challenges, including taking advantage of high-throughput technologies to elucidate complex disease mechanisms, accelerating development and implementation of evidence-based strategies, assessing evolving technologies of unclear value, addressing a global epidemic of cardiovascular disease, and maintaining high levels of innovation in a time of budgetary constraint and economic turmoil.

The OX40 receptor is preferentially expressed by T cells, and its cognate ligand OX40L is primarily expressed by antigen-presenting cells such as dendritic cells following activation by thymic stromal lymphopoietin (TSLP). TSLP is released by the bronchial epithelium, airway smooth muscle, and some inflammatory cells in response to numerous insults such as allergens, viruses, and physical damage. OX40L is a costimulatory molecule that plays a sentinel role in the adaptive immune response by promoting T helper (Th) 2 polarization of naive T cells within the lymph node. These polarized T cells produce Th2 cytokines such as IL-4, IL-5, and IL-13, which have been implicated particularly in allergic eosinophilic asthma. Animal models have positioned both TSLP and OX40/OX40L as critical in the development of airway inflammation and hyperreactivity. In human disease, there is good evidence that TSLP is upregulated in asthma, but there are limited data to demonstrate overexpression of OX40 or OX40L in disease. Targeting the OX40/OX40L axis or TSLP presents a novel therapeutic strategy that has the potential of modifying the disease process and, therefore, impacting on its natural history. Whether this approach can demonstrate efficacy in established disease rather than at disease onset is unknown. Biologic therapies directed toward OX40/OX40L are in early phases of development, and results from these studies are eagerly awaited.

Postthrombotic syndrome (PTS) is a frequent, chronic complication of DVT. The effectiveness and safety of available treatments are unknown. The objective of this study was to systematically review the literature to assess whether pharmacologic and compression therapies are effective and safe for the treatment of PTS.

This review examines the use of scoring systems to assess ICU performance. APACHE (Acute Physiology and Chronic Health Evaluation), MPM (mortality probability model), and SAPS (simplified acute physiology score) are the three major ICU scoring systems in use today. Central to all three is the use of physiologic data for severity adjustment. Differences in the size, nature, and time horizon of the data set translate into minor differences in accuracy and difficulty of data abstraction. APACHE IV provides ICU and hospital predictions for mortality and length of stay, whereas MPM and SAPS only provide hospital mortality predictions (although new algorithms generated from MPM data elements may predict ICU length of stay adequately). The primary use of scoring systems is for assessing ICU performance, with the ratio of actual-to-predicted outcomes in the study cohort providing performance comparisons to the reference ICUs. The reliability of scoring system predictions depends on the completeness and accuracy of the abstracted data; accordingly, ICUs must implement robust data quality control processes. CIs of the ratios are inversely related to sample size, and care must be taken to avoid overinterpreting changes in outcomes. ICU structural and process issues also can affect scoring system performance measures. Despite good discrimination and calibration, scoring systems are used in only 10% to 15% of US ICUs. Without ICU performance data, there is little hope of improving quality and reducing costs. Current demands for transparency and computerization of documentation are likely to drive future use of ICU scoring systems.

In the > 30 years since the New Jersey Supreme Court's seminal opinion in the case of Karen Ann Quinlan, all 50 states and the District of Columbia have enacted legislation to recognize the legal right of competent adults to write advance directives. The purpose of advance directives is to provide direction for health-care decisions near the end of life, when the ravages of illness, disease, or injury have taken the ability to decide for one's self. This article reviews the defining features of advance directives and the governing law, discusses some common practical concerns regarding the use and effectiveness of advance directives, and identifies several significant ethical-legal challenges for honoring advance directives at the bedside. With a primary focus on the health-care proxy, the anatomy of advance directives is analyzed under four general rubrics: formal requirements, decisional capacity and when the directive takes effect, rights and responsibilities of proxies and health-care providers, and the scope and limitations of decisions to forego life-sustaining treatment. There is much common ground among state laws, but particular legal provisions may vary from state to state. Physicians, nurses, social workers, and other health-care professionals should be familiar with the law of their home state.

There is increasing clinical, radiologic, and pathologic recognition of the coexistence of emphysema and pulmonary fibrosis in the same patient, resulting in a clinical syndrome known as combined pulmonary fibrosis and emphysema (CPFE) that is characterized by dyspnea, upper-lobe emphysema, lower-lobe fibrosis, and abnormalities of gas exchange. This syndrome frequently is complicated by pulmonary hypertension, acute lung injury, and lung cancer. The CPFE syndrome typically occurs in male smokers, and the mortality associated with this condition, especially if pulmonary hypertension is present, is significant. In this review, we explore the current state of the literature and discuss etiologic factors and clinical characteristics of the CPFE syndrome.

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling of the precapillary pulmonary arteries, with excessive proliferation of vascular cells. Although the exact pathophysiology remains unknown, there is increasing evidence to suggest an important role for inflammation. Firstly, pathologic specimens from patients with PAH reveal an accumulation of perivascular inflammatory cells, including macrophages, dendritic cells, T and B lymphocytes, and mast cells. Secondly, circulating levels of certain cytokines and chemokines are elevated, and these may correlate with a worse clinical outcome. Thirdly, certain inflammatory conditions such as connective tissue diseases are associated with an increased incidence of PAH. Finally, treatment of the underlying inflammatory condition may alleviate the associated PAH. Underlying pathologic mechanisms are likely to be "multihit" and complex. For instance, the inflammatory response may be regulated by bone morphogenetic protein receptor type 2 (BMPR II) status, and, in turn, BMPR II expression can be altered by certain cytokines. Although antiinflammatory therapies have been effective in certain connective-tissue-disease-associated PAH, this approach is untested in idiopathic PAH (iPAH). The potential benefit of antiinflammatory therapies in iPAH is of importance and requires further study.

This article describes the conceptual basis for the P value and the CI. We show that both are derived from the same underlying concepts and provide useful, but similar information.

Technology-enhanced patient simulation has emerged as an important new modality for teaching and learning in medicine. In particular, immersive simulation platforms that replicate the clinical environment promise to revolutionize medical education by enabling an enhanced level of safety, standardization, and efficiency across health-care training. Such an experiential approach seems unique in reliably catalyzing a level of emotional engagement that fosters immediate and indelible learning and allows for increasingly reliable levels of performance evaluation-all in a completely risk-free environment. As such, medical simulation is poised to emerge as a critical component of training and certification throughout health care, promising to fundamentally enhance quality and safety across disciplines. To encourage routine simulation-based practice as part of its core quality and safety mission, Massachusetts General Hospital now incorporates simulation resources within its historic medical library (est. 1847), located at the center of the campus. In this new model, learners go to the library not only to read about a patient's illness, but also to take care of their "patient." Such an approach redefines and advances the central role of the library on the campus and ensures that simulation-based practice is centrally available as part of everyday hospital operations. This article describes the reasons for identifying simulation as an institutional priority leading up to the Massachusetts General Hospital Bicentennial Celebration (1811-2011) and for creating a simulation-based learning laboratory within a hospital library.

Clostridium difficile infection (CDI) management has become more daunting over the past decade because of alarming increases in CDI incidence and severity both in the hospital and in the community. This increase has concomitantly caused significant escalation of the health-care economic burden caused by CDI, and it will likely be translated to increased ICU admission and attributable mortality. Some possible causes for difficulty in management of CDI are as follows: (1) inability to predict and prevent development of severe/complicated or relapsing CDI in patients who initially present with mild symptoms; (2) lack of a method to determine who would have benefited a priori from initiating vancomycin treatment first instead of treatment with metronidazole; (3) lack of sensitive and specific CDI diagnostics; (4) changing epidemiology of CDI, including the emergence of a hypervirulent, epidemic C difficile strain associated with increased morbidity and mortality; (5) association of certain high-usage nonantimicrobial medications with CDI; and (6) lack of treatment regimens that leave the normal intestinal flora undisturbed while treating the primary infection. The objective of this article is to present current management and prevention guidelines for CDI based on recommendations by the Society for Healthcare Epidemiology of America and Infectious Diseases Society of America and potential new clinical management strategies on the horizon.

Rationing is the allocation of scarce resources, which in health care necessarily entails withholding potentially beneficial treatments from some individuals. Rationing is unavoidable because need is limitless and resources are not. How rationing occurs is important because it not only affects individual lives but also expresses society's most important values. This article discusses the following topics: (1) the inevitability of rationing of social goods, including medical care; (2) types of rationing; (3) ethical principles and procedures for fair allocation; and (4) whether rationing ICU care to those near the end of life would result in substantial cost savings.

Every country has finite resources that are expended to provide citizens with social "goods," including education, protection, infrastructure, and health care. Rationing-of any resource-refers to distribution of an allotted amount and may involve withholding some goods that would benefit some citizens. Health-care rationing is controversial because good health complements so many human endeavors. We explored (perceptions regarding) critical care rationing in seven industrialized countries. Academic physicians from England, Spain, Italy, France, Argentina, Canada, and the United States wrote essays that addressed specific questions including: (1) What historical, cultural, and medical institutional features inform my country's approach to rationing of health care? (2) What is known about formal rationing, especially in critical care, in my country? (3) How does rationing occur in my ICU? Responses suggest that critical care is rationed, by varying mechanisms, in all seven countries. We speculate that while no single "best" method of rationing is likely to be acceptable or optimal for all countries, professional societies could serve international health by developing evidence-based guidelines for just and effective rationing of critical care.

As ICU survival continues to improve, clinicians are faced with short- and long-term consequences of critical illness. Deconditioning and weakness have become common problems in survivors of critical illness requiring mechanical ventilation. Recent literature, mostly from a medical population of patients in the ICU, has challenged the patient care model of prolonged bed rest. Instead, the feasibility, safety, and benefits of early mobilization of mechanically ventilated ICU patients have been reported in recent publications. The benefits of early mobilization include reductions in length of stay in the ICU and hospital as well as improvements in strength and functional status. Such benefits can be accomplished with a remarkably acceptable patient safety profile. The importance of interactions between mind and body are highlighted by these studies, with improvements in patient awareness and reductions in ICU delirium being noted. Future research to address the benefits of early mobilization in other patient populations is needed. In addition, the potential for early mobilization to impact long-term outcomes in ICU survivors requires further study.

The purpose of this systematic literature review was to examine current empirical research on general and respiratory health outcomes in adult survivors of bronchopulmonary dysplasia (BPD).

This is the third article of a three-part series that reviews the care of poisoned patients in the ICU. This article focuses on natural toxins, such as heavy metals and those produced by plants, mushrooms, arthropods, and snakes. The first article discussed the general approach to the patient, including laboratory testing; the second article focused on specific toxic agents, grouped into categories.

Optimal performance of bronchoscopy requires patient's comfort, physician's ease of execution, and minimal risk. There is currently a wide variation in the use of topical anesthesia, analgesia, and sedation during bronchoscopy.

Thoracic ultrasonography is a noninvasive and readily available imaging modality that has important applications in pulmonary medicine outside of the ICU. It allows the clinician to diagnose a variety of thoracic disorders at the point of care. Ultrasonography is useful in imaging lung consolidation, pleural-based masses and effusions, pneumothorax, and diaphragmatic dysfunction. It can identify complex or loculated effusions and be useful in planning treatment. Identifying intrathoracic mass lesions can guide sampling by aspiration and biopsy. This article summarizes thoracic ultrasonography applications for the pulmonary specialist, related procedural codes, and reimbursement. The major concepts are illustrated with cases. These case summaries are enhanced with online supplemental videos and chest radiograph, chest CT scan, and ultrasound correlation.

Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare pulmonary disease caused by functional deficiency of granulocyte-macrophage colony-stimulating factor (GM-CSF). Administration of GM-CSF represents a potential therapeutic strategy in management of aPAP. Herein, we systematically review the efficacy of GM-CSF therapy in aPAP.