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To improve the delivery of patient care, governments and health-care institutions adopted quality improvement methods that had been developed decades earlier in manufacturing industries. Many health-care practitioners are either unaware or are inexperienced about what these practices entail and whether they are successful in health care. This article reviews Lean, an improvement philosophy made famous by the Toyota Motor Company. Lean uses a set of instruments and incorporates a long-term vision aiming for continuous improvement. It focuses on eliminating waste as perceived by the patient, thereby maximizing quality and safety for the patient. However, the effort required for the attainment of Lean's goals is often not appreciated. Indeed, successful and sustainable implementation requires immense institutional culture change combined with innovative leadership and motivated frontline health-care professionals.

Mechanisms underlying the association between asthma and obesity remain poorly understood. Obesity appears to be a risk factor for asthma, and obese asthmatics fare poorly compared to lean asthmatics.To explore the possibility that reduced regulatory T cell (Treg) number and function contribute to the obesity-asthma association. We concentrated on obese females with childhood-onset asthma, since Treg may be involved in this phenotype.We recruited 64 women (ages 18-50) into four groups: lean (BMI 18-25 kg/mObese asthmatics had worse lung function, asthma control, and quality of life compared to lean asthmatics. Compared to lean or obese control groups, the number of Treg cells in the obese asthmatics was approximately 1.58- or 1.73-fold higher. The ability of Treg cells from obese-asthmatics to suppress Tresp cell proliferation was reduced.Obese, atopic women with childhood diagnosed asthma demonstrate increased Treg cell number and mildly decreased Treg cell function. Our data do not support the view that reduced Treg cell number contributes to this obese-asthma phenotype.

To reduce transfer time of critically ill patients from the emergency department (ED) to the medical intensive care unit (MICU).A prospective, observational study assessing preimplementation and postimplementation of quality improvement interventions in a tertiary academic medical center.A team of frontline health care professional including ED, MICU, and supporting services using the clinical microsystems approach mapped out existing practice patterns, determined causes for delays, and used the Plan-Do-Study-Act to test changes. Measurements and Main Results The team identified multiple issues that contributed to delays. These included poor coordination between transport services, respiratory therapy, and nursing in transferring patients from the ED as well delays in identification and transfer of stable MICU patients. These interventions reduced transfer time from 4.2 (3.4-5.7) hours to 2.2 (1.4-3.1) hours (median [interquartile range]; P.001). Hospital length of stay decreased from 9.9±9 to 8.3±7 days (P.03).A team made up of frontline health care professionals using a structured quality improvement process and implementing multifaceted, multistage interventions, reduced transfer delays, and length of stay. Added benefits included engagement among members of the 2 microsystems and a more cohesive approach to patient care.

Janice Wang,1 Stella S Hahn,1 Myriam Kline,2 Rubin I Cohen1 1Division of Pulmonary, Critical Care and Sleep Medicine, Hofstra Northwell School of Medicine, New Hyde Park, 2Biostatistics Unit, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, USA Background: Prior studies concentrated on unplanned intensive care unit (ICU) transfer to gauge deterioration occurring shortly following hospital admission. However, examining only ICU transfers is not ideal since patients could stabilize with treatment, refuse ICU admission, or not require ICU evaluation. To further explore etiologies of early clinical deterioration, we used rapid response team (RRT) activation within 48 hours of admission as an index of early clinical worsening. Methods: A retrospective analysis of prospectively gathered admissions from the emergency department in an academic medical center was done. Data were reviewed independently by two physicians. We assessed severity of illness, functional status, comorbidity, the frequency of ICU and palliative care consultations, and changes in advance health care directives.Results: Of 655 rapid responses (RRs) within the study period, 24.6% occurred within 48 hours of admission. Disease trajectory was the most frequent perceived reason for RRs (55.6% and 58.9%, reviewer 1 and 2, respectively) followed by medical error (15.6% and 15.2%). Acute physiology and chronic health evaluation II (APACHE-II) and modified early warning scores (MEWS) were higher at the time of RR compared to admission (p

BACKGROUND:Point-of-care ultrasonography performed by frontline intensivists offers the possibility of reducing the use of traditional imaging in the medical ICU (MICU). We compared the use of traditional radiographic studies between two MICUs: one where point-of-care ultrasonography is used as a primary imaging modality, the other where it is used only for procedure guidance. METHODS:This study was a retrospective 3-month chart review comparing the use of chest radiographs, CT scans (chest and abdomen/pelvis), transthoracic echocardiography performed by the cardiology service, and DVT ultrasonography studies performed by the radiology service between two MICUs of similar size and acuity and staffing levels. RESULTS:Total number of admissions, patient demographics, and disease acuity were similar between MICUs. Comparing the non-point-of-care ultrasonography MICU with the point-of-care ultrasonography MICU, there were 3.75 ± 4.6 vs 0.82 ± 1.85 (P< .0001) chest radiographs per patient, 0.10 ± 0.31 vs 0.04 ± 0.20 (P= .0007) chest CT scans per patient, 0.17 ± 0.44 vs 0.05 ± 0.24 (P< .0001) abdomen/pelvis CT scans per patient, 0.20 ± 0.47 vs 0.02 ± 0.14 (P< .0001) radiology service-performed DVT studies per patient, and 0.18 ± 0.40 vs 0.07 ± 0.26 (P< .0001) cardiology service-performed transthoracic echocardiography studies per patient, respectively. CONCLUSIONS:The use of point-of-care ultrasonography in an MICU is associated with a significant reduction in the number of imaging studies performed by the radiology and cardiology services.

Linking health-care quality improvement to payment appears straightforward. Improve the care that one provides to one's patients, and one is rewarded financially. Should one fail to improve care, then one is financially penalized. However, this strategy assumes that health-care workers and administrators possess the necessary tools and knowledge to improve care and that the metrics being measured have been rigorously tested. Although health-care workers and hospitals are publically committed to reducing inappropriate care, improving patient safety, achieving better health outcomes, and holding down costs, many are unsure how to do this effectively. We present the case that it is not usually the people who create the problems in our health system; rather, it is the processes of the care-delivery system that require change. Incentivizing performance improvement using simple metrics is unlikely to work before using compensation strategies to incentivize behavior change in clinical systems. But prior to even doing this, leaders and physicians must first create accurate performance measures and understand improvement science.

Common neurological emergencies include overdose or withdrawal from illegal substance abuse, adverse effects of prescription medications, seizures, metabolic encephalopathy, infections and cerebrovascular accidents. Following a thorough clinical and radiologic assessment, a small group of patients escape definitive diagnosis and autoimmune encephalitides should be considered. Of these, limbic encephalitis (LE) is the most common and may result from paraneoplastic or nonparaneoplastic sources. Common to both is the production of antibodies targeting epitopes in the brain parenchyma thought to be responsible for the clinical manifestations. Paraneoplastic Anti-N-methyl D-aspartate receptor (NMDAR) encephalitis is a common cause of LE and has gained awareness in neurological and psychiatric literature. Paraneoplastic and nonparaneoplastic anti NMDAR encephalitis typically presents in young, previously healthy females with subacute onset of psychiatric symptoms, respiratory insufficiency, orofacial dyskinesias, autonomic instability and seizures. Paraneoplastic LE is induced by antibody production against NMDAR with occult ovarian teratoma being the most common inciting tumor. LE has also been described in association with other tumors and also without tumors. The latter are known as nonparaneoplastic or primary autoimmune disease. Diagnosis requires both clinical suspicion along with prompt serum and cerebrospinal fluid analysis for antibody detection. Immunotherapy to remove and suppress these antibodies along with resection of an identified tumor is the therapy of choice. This article will review the clinical presentation and management of LE in patients who present to the medical intensive care unit.

Background: The mechanisms of fat mass (FM) loss in cystic fibrosis (CF) are poorly understood but could represent complex pathways involving dysregulation of appetite-modulating peptides and an amplified inflammatory response. Nesfatin-1 is a newly described peptide that decreases food intake and FM but has not been studied in CF. Objectives: We hypothesized that changes in the appetite-suppressing hormone nesfatin-1 would be physiological, and levels would be lower in advanced CF patients with lower FM compared to those with milder disease and healthy controls. We determined the levels of the cytokines TNF-α, IL-1β, and IL-6 as they have been associated with weight loss in disease states. Methods: Fifty-four adult CF subjects, i.e. 17 with severe, 22 with moderate, and 15 with mild disease, as well as 18 controls were recruited. PFT and body composition analysis (via bioelectrical impedance) were performed. Nesfatin-1 and cytokine levels were determined by ELISA. Results: Contrary to our proposed hypothesis, nesfatin-1 levels were highest in CF patients with severe disease and the lowest FM. A significant negative correlation between nesfatin-1 levels and FM was found only in the severe CF group (r = -0.7, p = 0.003). In forward stepwise regression analysis, only FM was significantly associated with nesfatin-1 levels. Levels of TNF-α and IL-6 were elevated in the severe CF group, but there was no association with either FM or nesfatin-1. Conclusion: In advanced CF and low FM, nesfatin-1 plasma levels are significantly increased and inversely correlated with the FM. Our results further suggest that nesfatin-1 exerts its effects independently of TNF-α or IL-6.

Increased intracranial pressure (ICP) is a serious complication of a variety of neurologic injuries and is a major challenge in intensive care units. The most common causes of increased ICP are: traumatic brain injury (TBI), stroke, neoplasms, hydrocephalus, hepatic encephalopathy, CNS venous return impairment, encephalitis, and abscesses. Prompt diagnosis and intensive monitoring and therapy of this condition are essential for successful management of this potentially devastating condition. Recent technical innovations in neuromonitoring may allow for improvement in morbidity and mortality rates attributable to elevated ICP. Normal ICP ranges from 3-15 mmHg. In routine intensive care unit (ICU) practice, the goal of ICP management is to maintain levels below 20 mmHg. Noninvasive and metabolic monitoring of ICP including imaging-clinical examination has been studied and suggested to be as efficient as the care based on invasive ICP monitoring; however its application in clinical practice is to be established. Raised intracranial pressure correlates with decreased survival and is often the only remediable element of brain pathology. While elimination of the cause of elevated ICP remains the definitive approach, there are maneuvers that should be used to decrease ICP urgently. Surgical decompression of mass effect may rapidly improve ICP elevation. Osmolar therapy, maintenance of euvolemia, cerebral metabolic suppression, and temperature control are part of the advanced management of elevated ICP.

The aim is to review pathophysiological mechanisms and treatment of nocturnal asthma.Physiologic changes accompanying sleep, as well as the nocturnal phase of circadian rhythms, may have an adverse effect on asthma control. Chronotherapeutic principles, which consider circadian variation in relevant biologic rhythms, may improve asthma outcomes. Administration of long-acting bronchodilators and inhaled corticosteroids which achieve maximum efficacy at night may improve nocturnal asthma. Comorbid conditions that may contribute to nocturnal asthma should be considered. The prevalence of obstructive sleep apnea is greater in a cohort of patients with severe asthma than in moderate asthma and in BMI and age matched nonasthmatic controls, suggesting a link between these diseases. A large trial concluded that esomeprazole did not improve asthma control even with comorbid acid reflux, questioning the importance of acid reflux in asthma. The role of polymorphisms of the β2-adrenergic receptor and their relationship with nocturnal asthma remain controversial.Sleep is a time of vulnerability to respiratory compromise, especially in asthma patients experiencing nocturnal exacerbations. This asthma phenotype is associated with poorer control, reduced sleep quality, daytime somnolence and increased morbidity and mortality. Nocturnal asthma is a common but under-recognized problem.

Obesity is a risk factor for asthma. Studies in mice suggest that the adipokines leptin and adiponectin affect asthmatic responses. The purpose of this study was to determine if adipokines associated with obesity are (1) altered in obese women with asthma compared to controls and (2) associated with increased cytokines and chemokines involved in allergic inflammation.We performed a cross-sectional study of asthmatic and non-asthmatic obese premenopausal women. Participants answered questionnaires and performed lung function tests. Serum and peripheral blood mononuclear cells (PBMCs) were collected for analysis of cytokines and adipokines.A total of 22 asthmatic (mean body mass index 40.0 ± 5.1 kg/m(2)) and 20 non-asthmatic women (mean body mass index 41.3 ± 5.6 kg/m(2)) participated. We found no difference in serum adipokine concentrations between asthmatics and non-asthmatics. Serum adiponectin correlated positively with PBMC eotaxin (r(s) = 0.55, p = .0003) and RANTES (regulated upon activation, normal T-cell expressed, and secreted) (r(s) = 0.36, p = .03), whereas serum leptin correlated negatively with PBMC eotaxin (r(s) = -0.34, p = .04). There was a negative correlation between serum adiponectin and PBMC interferon-γ (r(s) = -0.41, p = .01).Perturbations of adipokines that occur in obesity were correlated with decreased cytokine production typically associated with allergic responses in PBMC of obese premenopausal women. This study suggests that although obese asthmatics may have elements of Th2-mediated inflammation, adipokine derangements in obesity are associated with Th1 rather than Th2 bias. Obesity has complex effects on allergic inflammation and is likely to be important modifier of the pathogenesis of airway disease in asthma.

Obesity is a risk factor for asthma. Obese asthmatics often have poor asthma control and respond poorly to therapy. It has been suggested that co-morbidities associated with obesity, such as reflux and obstructive sleep apnea, could be important factors contributing to poor asthma control in obese patients.The purpose of this study was to determine if (1) reflux and/or (2) symptoms of sleep apnea contribute to poor asthma control in obesity.We studied asthmatic subjects participating in a trial of reflux treatment. Participants underwent baseline evaluation of asthma symptoms and lung function. Overall 304 participants underwent esophageal pH probe testing; 246 participants were evaluated for obstructive sleep apnea symptoms.Of 402 participants in this trial, 51% were obese. Role of reflux in asthma control. Those with higher body mass index (BMI) reported a higher prevalence of reflux symptoms, but the prevalence of pH probe acid reflux was similar in all groups. Reflux was not associated with measures of asthma control in obese patients. Role of obstructive sleep apnea in asthma control. Symptoms and self-report of obstructive sleep apnea were more common with increasing BMI and associated with worse asthma control as measured by the Juniper Asthma Control questionnaire and Asthma Symptom Utility Index.Our data suggest that obstructive sleep apnea, but not gastroesophageal reflux disease, may contribute significantly to poor asthma control in obese patients.

Cystic fibrosis (CF) is an autosomal recessive disorder that affects approximately 1 in 3000 Caucasian births, or 30,000 individuals in the US and 70,000 worldwide. The discovery of the CF gene, isolation of the CFTR protein and understanding of molecular mechanisms behind the clinical expression of CF are being translated into newer treatments. Treatments for CF and its manifestations are discussed in this article including inhaled antibiotics, hydrator therapies, anti-inflammatory agents and protein modifiers. New and experimental treatments that are in development are also discussed. Outcomes for these treatments are forced expiratory volume in one second (FEV1) improvement, CF-related quality of life, use of intravenous antibiotics and frequency of exacerbations and hospitalizations.

Background: To explore mechanisms of weight loss in cystic fibrosis (CF), we studied ghrelin receptor expression on isolated lymphocytes from CF subjects with different body mass indices (BMIs). Eating behavior is influenced by hormone peptides such as ghrelin, a potent appetite stimulator. However, studies on ghrelin plasma levels in CF showed it to be increased in cachectic subjects, the expected physiological response. Objectives: (1) To compare ghrelin receptor expression between clinically stable CF subjects with normal BMI, CF subjects with cachexia and healthy controls. (2) To investigate ghrelin receptor expression in the same CF subjects before and after treatment for an acute exacerbation. Methods: Lymphocytes were isolated from CF patients with normal BMI and low BMI and from controls. Ghrelin receptor quantification was determined via flow cytometry. Body composition was determined by bioelectrical impedance, and plasma levels of ghrelin, TNF-α, IL-1 and IL-6 were determined. Results: CF subjects with low BMI had increased inflammation evidenced by increased plasma cytokines and showed decreased lymphocytic ghrelin receptor expression. Ghrelin receptor expression in the CF group with normal BMI was similar to controls; it decreased during an acute exacerbation associated with weight loss and returned to baseline following treatment and recovery of the weight loss. Conclusions: Differences exist in ghrelin receptor expression in lymphocytes isolated from stable CF patients with different BMIs. These changes may be due to a disordered pathological response to weight loss.

To comprehensively evaluate clinical, economic, and patient-reported outcomes associated with various therapeutic classes of asthma controller medications.This observational study, which used administrative claims data from US commercial health plans, included patients with asthma aged 18 through 64 years who filled a prescription for at least 1 asthma controller medication from September 1, 2003, through August 31, 2005. Outcome metrics included the use of short-acting beta-agonists (SABAs), the use of oral corticosteroids, inpatient (INP)/emergency department (ED) visits, and asthma-related health care costs. A subset of 5000 patients was randomly selected for a survey using the Mini-Asthma Quality of Life Questionnaire, the Work Productivity and Activity Impairment questionnaire, and the Asthma Therapy Assessment Questionnaire.Of 56,168 eligible patients, 823 returned completed questionnaires. Compared with inhaled corticosteroids (ICSs), leukotriene modifiers (LMs) were associated with lower odds of INP/ED visits (odds ratio [OR], 0.80; P.001), lower odds of using 6 or more SABA canisters (OR, 0.81; P.001), and higher annual cost ($193; P.001). In the subgroup analysis of adherent patients, LMs were associated with higher odds of INP/ED visits (OR, 1.74; P=.04), lower odds of using 6 or more SABA canisters (OR, 0.46; P.001), and higher annual cost ($235; P.001). Inhaled corticosteroids and LMs had a comparable impact on all patient-reported outcomes. For combination therapy, ICS plus a long-acting beta-agonist consistently showed at least equivalent or better outcomes in the use of SABAs and oral corticosteroids, the risk of INP/ED visits, cost, asthma control level, quality of life, and impairment in productivity and activity.Inhaled corticosteroids were associated with a lower risk of INP/ED visits, and a lower cost if adherence was achieved. When adherence cannot be achieved, LMs may be a reasonable alternative. Combination therapy with ICS plus a long-acting beta-agonist was associated with better or equivalent clinical, economic, and patient-reported outcomes.

Studies in cystic fibrosis (CF) report late attention to advance care planning (ACP). The purpose of this study was to examine ACP with patients receiving care at US adult CF care programs.Chart abstraction was used to examine ACP with adults with CF dying from respiratory failure between 2011 and 2013.We reviewed 210 deaths among 67 CF care programs. Median age at death was 29 years (range 18-73). Median FEV1 in the year preceding death was 33% predicted (range 13-100%); 68% had severe lung disease with FEV140% predicted. ACP was documented for 129 (61%), often during hospitalization (61%). Those with ACP had earlier documentation of treatment preferences, before the last month of life (73% v. 35%; p=0.01). Advance directives were completed by 93% of those with ACP versus 75% without (p0.01); DNR orders and health care proxy designation occurred more often for those with ACP. Patients awaiting lung transplant had similar rates of ACP as those who were not (67% v. 61%; p=0.55). The frequency of ACP varied significantly among the 29 programs contributing data from four or more deaths.ACP in CF often occurs late in the disease course. Important decisions default to surrogates when opportunities for ACP are missed. Provision of ACP varies significantly among adult CF care programs. Careful evaluation of opportunities to enhance ACP and implementation of recommended approaches may lead to better practices in this important aspect of CF care.

Introduction Little is known about the depth of knowledge and preparedness of CF caregivers in delivering end of life and palliative care to CF patients and families. Method Nationwide survey questionnaires for CF care providers using the CF Foundation Listserv electronic web-based tool. Results The majority of non-physician CF care providers (55%) had more than 15years of experience in their discipline and 84% of physician had greater than 15years of experience. The majority reported that they felt "somewhat" or "very" involved in palliative or end of life care in their current role. Yet, when asked whether they felt adequately prepared to deliver palliative and end of life care, only 18% reported that they were "fully prepared" and 45% felt that they were only "minimally" or "not" prepared. Further, only one third of respondents received more than 10h of education in general palliative or end-of-life care, while only 10% had received more than 10h of education specific to CF end of life care. The majority (73%) of CF healthcare providers preferred more education specific to CF end of life care. Conclusion CF healthcare providers are involved in CF end of life issues but a fair number did not understand their role and felt inadequately prepared in delivering suitable end of life and palliative care. Many desired more education in the provision of such care.

Importance Soy isoflavone supplements are used to treat several chronic diseases, although the data supporting their use are limited. Some data suggest that supplementation with soy isoflavone may be an effective treatment for patients with poor asthma control. Objective To determine whether a soy isoflavone supplement improves asthma control in adolescent and adult patients with poorly controlled disease. Design, Setting, and Participants Multicenter, randomized, double-blind, placebo-controlled trial conducted between May 2010 and August 2012 at 19 adult and pediatric pulmonary and allergy centers in the American Lung Association Asthma Clinical Research Centers network. Three hundred eighty-six adults and children aged 12 years or older with symptomatic asthma while taking a controller medicine and low dietary soy intake were randomized, and 345 (89%) completed spirometry at week 24. Interventions Participants were randomly assigned to receive soy isoflavone supplement containing 100 mg of total isoflavones (n=193) or matching placebo (n=193) in 2 divided doses administered daily for 24 weeks. Main Outcomes and Measures The primary outcome measure was change in forced expiratory volume in the first second (FEV 1 ) at 24 weeks. Secondary outcome measures were symptoms, episodes of poor asthma control, Asthma Control Test score (range, 5-25; higher scores indicate better control), and systemic and airway biomarkers of inflammation. Results Mean changes in prebronchodilator FEV 1 over 24 weeks were 0.03 L (95% CI, −0.01 to 0.08 L) in the placebo group and 0.01 L (95% CI, −0.07 to 0.07 L) in the soy isoflavone group, which were not significantly different ( P = .36). Mean changes in symptom scores on the Asthma Control Test (placebo, 1.98 [95% CI, 1.42-2.54] vs soy isoflavones, 2.20 [95% CI, 1.53-2.87]; positive values indicate a reduction in symptoms), number of episodes of poor asthma control (placebo, 3.3 [95% CI, 2.7-4.1] vs soy isoflavones, 3.0 [95% CI, 2.4-3.7]), and changes in exhaled nitric oxide (placebo, −3.48 ppb [95% CI, −5.99 to −0.97 ppb] vs soy isoflavones, 1.39 ppb [95% CI, −1.73 to 4.51 ppb]) did not significantly improve more with the soy isoflavone supplement than with placebo. Mean plasma genistein level increased from 4.87 ng/mL to 37.67 ng/mL ( P Conclusions and Relevance Among adults and children aged 12 years or older with poorly controlled asthma while taking a controller medication, use of a soy isoflavone supplement, compared with placebo, did not result in improved lung function or clinical outcomes. These findings suggest that this supplement should not be used for patients with poorly controlled asthma. Trial Registration clinicaltrials.gov Identifier:NCT01052116

Objectives a) To determine whether decreased sarcoplasmic calcium release channel (CRC) activity is a mechanism by which myocardial contractility is reduced in endotoxemia; b) to determine whether nitric oxide modulates CRC activity in endotoxemia; and c) to examine two nitric oxide signaling pathways in relation to CRC function in endotoxemia. Design Randomized, prospective using a rat model of endotoxemia. Setting : Research laboratory. Subjects Sprague-Dawley rats. Interventions Endotoxemia was induced by lipopolysaccharide administration. The effects of nitric oxide were studied using the highly selective inducible nitric oxide synthase inhibitor N-(3-(aminomethyl)benzyl)acetamidine dihydrochloride (1400W) and the specific guanylyl cyclase inhibitor 1-H (1, 2, 4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Measurements and main results We assessed myocardial contractility, myocardial nitric oxide content, and guanosine-3',5' (cyclic) phosphate (cGMP) content. We determined CRC activity by calcium release and ryanodine binding assays. We followed these variables at four time points through the course of endotoxemia. We found that myocardial contractility and CRC activity were decreased in late but not in early endotoxemia. Furthermore, inducible nitric oxide synthase inhibition with 1400W restored contractility and CRC activity in late endotoxemia but paradoxically worsened these variables in early endotoxemia. Through the use of the guanylyl cyclase inhibitor ODQ, we demonstrate that nitric oxide acts through cGMP-mediated mechanisms in early and late endotoxemia. We investigated cGMP-independent pathways by assessing the oxidative status of the CRC. We found that in late endotoxemia, nitric oxide decreased the number of free thiols, demonstrating that nitric oxide also acts through cGMP-independent pathways. Conclusions Nitric oxide has a dual effect on the CRC in endotoxemia. At low concentrations, as measured in early endotoxemia, nitric oxide stabilizes the CRC through cGMP-mediated mechanisms. In late endotoxemia, high nitric oxide concentrations decrease channel activity through both cGMP-dependent and cGMP-independent mechanisms.

Obesity is a risk factor for being diagnosed with asthma, but there is conflicting evidence on whether obesity is a risk factor for lung function abnormalities characteristic of asthma. We studied a cohort of 488 subjects, 47% of whom were obese. Obese and non-obese subjects with asthma had similar airflow limitation and bronchodilator responsiveness, but obese participants had increased sleep disturbance and gastroesophageal reflux disease, higher cytokine levels, and a trend towards increased exacerbations when treated with theophylline. Obese and non-obese asthmatics have similar lung function abnormalities, but comorbidities and altered responses to medications may significantly affect asthma control in obese people.

This article examines the management and outcomes of pregnant women with cystic fibrosis, primary pulmonary hypertension, and sarcoidosis. Pregnancy and the puerperium are associated with important cardiopulmonary changes that can adversely affect the clinical condition. Management of pregnant women with CF should be done with careful attention to complications of altered body weight, diabetes, and liver disease. Primary pulmonary hypertension is characterized by a progressive increase in pulmonary pressure and resistance in the absence of an identified cardiac or pulmonary cause. A multidisciplinary approach to the management of patients with primary pulmonary hypertension is of great importance for a successful maternal and fetal outcome. Good maternal and fetal outcomes are possible in women with restrictive lung disease in general and sarcoidosis in particular. The management of pregnancy, labor, and delivery are not altered by the presence of sarcoidosis.

Study objectives To characterize the metabolic status of weight-stable and clinically stable individuals with advanced emphysema. Patients Seventy-nine patients with severe emphysema (FEV 1 , 29 ± 13% of predicted [mean ± SD]) evaluated for enrollment in the National Emphysema Treatment Trial and 20 age-matched healthy subjects were studied. Setting Pulmonary function laboratory of university-affiliated teaching hospital. Interventions Data collection. Measurements and results We measured lung function, body composition, serum leptin levels, serum tumor necrosis factor receptors (sTNF-Rs), resting oxygen consumption (R V ˙ o 2 ) normalized to weight in kilograms (R V ˙ o 2 /kg), and R V ˙ o 2 normalized to fat-free mass (FFM) [R V ˙ o 2 /FFM]. The patient group and healthy group had similar age, body mass index (BMI), and body composition. R V ˙ o 2 /kg, R V ˙ o 2 /FFM, and sTNF-R levels were higher in patients compared to healthy subjects. There were no differences in serum leptin levels between emphysematous and healthy subjects, and there was no correlation between leptin and sTNF-R and R V ˙ o 2 /kg. Furthermore, both groups had similar gender-related differences in FFM, percentage of body fat, and serum leptin levels. Patients with lower BMI showed the greatest differences from control subjects in R V ˙ o 2 /kg. Conclusion In weight-stable subjects with advanced emphysema, R V ˙ o 2 /kg and R V ˙ o 2 /FFM were higher compared to healthy subjects, especially in those with BMI in the lower end of the normal range. R V ˙ o 2 /kg and R V ˙ o 2 /FFM did not correlate with leptin or sTNF-R levels. These data show that a higher metabolic rate is found in patients with emphysema who are clinically and weight stable. Thus, hypermetabolism is a feature of the disease and not sufficient to lead to weight loss.

Objectives: To determine the time course for myocardial production of nitric oxide, peroxynitrite, and glutathione, to determine the activities of the myocardial antioxidant enzymes glutathione peroxidase, superoxide dismutase, and glutathione reductase throughout endotoxemia and into recovery, and to correlate the levels of these variables to left ventricular contractility in endotoxemia. Design: Rats were treated with lipopolysaccharide. Endotoxemic hearts were examined at baseline, 4, 16, 24, and 48 hrs after lipopolysaccharide. Saline time-control groups were treated identically. Setting: A pulmonary research laboratory of a university teaching hospital. Measurements and Main Results: Lipopolysaccharide administration resulted in decreased contractility at 16 hrs as assessed by the isolated papillary muscle technique. Contractility recovered by 24 hrs. Myocardial glutathione content initially increased, but it was decreased from baseline by 16 hrs, as was glutathione peroxidase activity. Both superoxide dismutase and glutathione reductase activities were increased early (4 hrs) and remained elevated throughout the course of the experiment. Myocardial nitric oxide content (assessed by the chemiluminescence technique) was increased by 4 hrs and was markedly elevated by 16 hrs. Nitric oxide levels remained elevated despite recovery of contractility at 24 hrs. Similarly, peroxynitrite (assessed by measurement of 3-nitrotyrosine by high-pressure liquid chromatography) was elevated at 16 hrs and remained elevated despite normalization of contractility at 24 and 48 hrs. Conclusions: Myocardial dysfunction in endotoxemia correlates mainly with decreased glutathione content and glutathione peroxidase activity rather than nitric oxide or peroxynitrite formation. These data indicate that lipopolysaccharide-induced myocardial dysfunction is not solely caused by elevated myocardial nitric oxide levels but rather caused by the sum of complex interactions between various oxygen- and nitrogen-derived radicals.

Rationale Critical care consults requested shortly after admission could represent a triage error. This consult process has not been adequately assessed, and data are retrospective relying on discharge diagnoses. Objectives The aims of this study were to identify reasons for medical Intensive care unit (MICU) consultations within 48 hours of admission and to detect differences between those accepted and those denied MICU admission. Methods Data were prospectively collected including demographics, reason for consultation, Acute Physiology and Chronic Health Evaluation II score, Elixhauser comorbidity measure, functional status, need for assisted ventilation or vasopressor, presence of do-not-resuscitate (DNR) order, and whether a DNR order was obtained after MICU consultation. Results Ninety-four percent of patients consulted were not initially evaluated in the emergency department, half of whom were accepted. Respiratory failure, sepsis, and alcohol withdrawal were the most frequent reasons for MICU transfers. Factors predicting MICU admission included respiratory illness, better baseline functional status, and less comorbidity, whereas DNR predicted rejection. We did not find differences in hospital mortality; but hospital length of stay was longer. Conclusions Prospective examination of the consult process suggests that disease progression rather than triage error accounted for most unplanned transfers. Functional status and comorbidity predicted MICU admission rather than illness severity. Goals of care were not being discussed adequately. We did not detect differences in mortality although hospital length of stay was increased.

OBJECTIVE To compare the cardiopulmonary and peripheral circulatory effects of the nonselective nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) to the more selective inducible NOS inhibitor S-methylisothiourea (SMT) and to phenylephrine (PE) in endotoxic and normal swine. DESIGN Prospective, randomized, unblinded study. SETTING Research laboratory of academic medical center. SUBJECTS Nonanesthetized, sedated, mechanically ventilated, minimally invasive swine model. INTERVENTIONS Animals received either lipopolysaccharide (LPS, LPS groups) or equivalent volume of saline (normal groups). LPS animals were further randomized into four groups when mean arterial pressure (MAP) had dropped to

OBJECTIVES Scorpion envenomation may be accompanied by metabolic acidosis even in the absence of hypoxia and cardiovascular derangement. We tested the hypothesis that venom causes ischemia of the gastrointestinal tract rather than failure of delivery of oxygen to the periphery. DESIGN Repeated measures, prospective study in experimental animals. SETTING University-affiliated hospital research laboratory. INTERVENTIONS In ten spontaneously breathing, intubated, sedated pigs, purified dried venom (Leiurus quinquestriatus), 0.05 mg/kg, was administered intravenously. Measurements were obtained before (baseline), and 5, 15, 30, 60, 120, 180, and 240 mins after injection. MEASUREMENTS AND MAIN RESULTS Variables measured included: mean arterial pressure (MAP), heart rate (HR), mean pulmonary arterial pressure, pulmonary artery occlusion pressure, cardiac output, stroke volume, right ventricular ejection fraction (rapid thermistor), left ventricular dimensions (echocardiography), arterial gas tensions, lactate and catecholamine concentrations, gastric interstitial mucosal pH (tonometry), as well as systemic and pulmonary vascular resistances. Within 5 mins after venom injection, there was a hyperdynamic state accompanied by significantly increased MAP (97 +/- 18 to 136 +/- 47 mm Hg, p < .0003), HR (70 +/- 12 to 121 +/- 24 beats/min, p < .00006), and cardiac output (1.88 +/- 0.35 to 2.95 +/- 0.53 L/min, p < .0003), with no change in stroke volume, or pulmonary artery occlusion pressure. Right ventricular ejection fraction increased from 38.1 +/- 4.3 to 48.6 +/- 9.0% (p < .0009) by 15 mins. No change in left ventricular function was observed. There were significant decreases in systemic vascular resistance and pulmonary vascular resistance following envenomation. Arterial and gastric mucosal pH significantly decreased from 7.40 +/- 0.04 to 7.25 +/- 0.07 (p < .0001) for arterial pH, and 7.33 +/- 0.08 to 7.17 +/- 0.13 (p < .00001) for gastric mucosal pH by 30 mins after envenomation. The decrease in arterial pH was not sufficient to account for the change in gastric mucosal pH, indicating gastric mucosal ischemia. Arterial lactate increased from 2.6 +/- 1.4 to 7.4 +/- 1.9 (p < .05 x 10(-8)). There were significant increases in serum epinephrine and norepinephrine values by 5 mins. All hemodynamic variables and catecholamine concentrations returned to baseline by 4 hrs. However, there was persistent arterial and gastric mucosal acidosis and increased lactate concentrations even at 4 hrs. Oxygen delivery remained normal or supernormal for 4 hrs following envenomation. However, despite this finding, systemic and gastric mucosal pH changes indicate impaired gastrointestinal oxygen delivery. CONCLUSIONS Despite increased peripheral oxygen delivery, scorpion envenomation was associated with evidence of ischemia of the gastrointestinal tract. This association could be due to shunting of blood from metabolically active areas, possibly associated with massive catecholamine release, or a direct toxic effect of the venom on regional oxygen transport at the cellular level.

Critical care nurses are an integral part of rapid response (RR) teams. The length of time they spend away from an intensive care unit (ICU) to attend RRs and how ICU nurses perceive the time away from the ICU has not been previously evaluated.To determine: (1) the time an ICU nurse spends at RRs; (2) ICU nurses' view of nursing absence; and (3) RR characteristics associated with longer nursing time.A prospective analysis of RRs in one 500-bed adult academic medical center over 1 year. Nurses' perception was assessed through surveys and semistructured interviews.There were 536 RRs. An ICU nurse was present for 20 minutes or less in 54% of the RRs, 21-40 minutes in 26%, 41-60 minutes in 11%, and more than 60 minutes in 9% of RRs. Compared with nursing time required in RRs for neurologic instability (median [Q1 first quartile {25th percentile}, Q3 third quartile {75th percentile}] = 15.0 [10.0, 27.0] min), nursing time was longer in RRs for hemodynamic instability (30.0 [15.0, 45.0] min) and respiratory failure (25.0 [12.0, 45.0] min; P0.0001). Of the 85 nurses surveyed, 47% considered 41-60 minutes as a substantial amount of time at RRs; 99% perceived ICU workload as busier when a nurse attended RRs, and 87% believed ICU care was compromised, defined as reduction in the quality of care.In this study of one midsized academic medical center, about half of critical care nurse involvement in RRs takes them away from their ICU patients for less than 20 minutes. Nevertheless, nurses felt that ICU care was compromised when an ICU nurse responded to an RR.

Patients with cystic fibrosis (CF) hospitalized for pulmonary exacerbations complained of delayed and missed treatments. We analyzed the complaints and implemented two microsystem-based quality initiatives to improve care.A prospective, observational study using quantitative and qualitative data collection strategies was conducted. Two interventions were implemented: a CF order set followed 9 months later by a self-administration program.Thirty-six of 40 patients with CF received initial respiratory therapy within 2 hours of admission compared with 1 of 17 before intervention. Initial antibiotic administration time was reduced from a mean of 18 hours to within 4 hours in the majority of admissions after implementation of quality initiatives. The interventions led to improved medication delivery and increased satisfaction. Hospital length of stay for patients with CF decreased from a mean of 9.5 to 7.8 days.Application of a microsystem-based strategy that engaged patients and families as well as caregivers brought about substantial changes in CF care delivery, increased satisfaction among staff and patients, and decreased hospital length of stay.

Linking health-care quality improvement to payment appears straightforward. Improve the care that one provides to one's patients, and one is rewarded financially. Should one fail to improve care, then one is financially penalized. However, this strategy assumes that health-care workers and administrators possess the necessary tools and knowledge to improve care and that the metrics being measured have been rigorously tested. Although health-care workers and hospitals are publically committed to reducing inappropriate care, improving patient safety, achieving better health outcomes, and holding down costs, many are unsure how to do this effectively. We present the case that it is not usually the people who create the problems in our health system; rather, it is the processes of the care-delivery system that require change. Incentivizing performance improvement using simple metrics is unlikely to work before using compensation strategies to incentivize behavior change in clinical systems. But prior to even doing this, leaders and physicians must first create accurate performance measures and understand improvement science.

Objectives: People with CF are increasingly surviving into adulthood, yet there is little research on the employment consequences of having CF. We investigated, for the first time in a UK-wide cohort, longitudinal employment status, and its association with deprivation, disease severity, and time in hospital. Methods: Longitudinal registry study of adults with CF in the UK aged 20 to 40 (3458 people with 15,572 observations between 1996 and 2010). Mixed effects models were used to assess the association between small area deprivation and employment status, adjusting for clinically important covariates. Results: Around 50% of adults were in employment. People in the most deprived quintile were less likely to be in full time employment (log-odds −2.66 95%CI −3.1 to −2.26, compared to the least). Poor lung function is approximately twice as harmful to employment chances in people living in the most deprived areas, compared to the least. Men with higher %FEV1 and BMI were more likely to be in employment, whereas time in hospital was associated with decreased employment chances. Genotype and use of home IV therapy were not associated with employment status. Conclusion: Deprivation is a more important predictor of employment chances than disease severity and time in hospital. Furthermore, deprivation amplifies the harmful effects of disease severity on employment: the employment chances of people with poor lung function from disadvantaged areas are damaged to a greater extent than for their counterparts living in the least disadvantaged circumstances. We acknowledge the support of the MRC and the UK Cystic Fibrosis Trust. WS11.6 Unmet needs in end of life care for the adult cystic fibrosis patient: A review of expectations, challenges, and current practice B.J. Quinn1, L.-C. Wann1, P. Maniscalco1, R.I. Cohen1. 1North Shore-LIJ School of Medicine at Hofstra University, New Hyde Park, United States

Purpose: Nitric oxide (NO) synthase inhibition has been reported to cause elevation in mean arterial pressure (MAP) and a decrease in cardiac index (Cl), the cause of which is not completely understood. It has been shown that increased concentrations of NO synthase inhibitors cause a further drop in cardiac output without a corresponding increase in arterial pressure, prompting the conclusion that NO inhibition results in direct myocardial depression. However, myocardial ischemia was not completely ruled out as a cause for myocardial dysfunction in these studies. The purpose of this study was to examine the effects of 30 mg/kg of the NO synthase inhibitor NG-nitro-l-arginine-methyl ester (L-NAME) to those of 300 mg/kg and assess the effects on coronary ischemia and myocardial function. Materials and Methods: Eight anesthetized dogs underwent median sternotomy and pericardiectomy. L-NAME 30 mg/kg was administered and the effects were recorded at 5, 15, and 30 minutes. Thereafter, 300 mg/kg was administered and the effects were observed for 5, 15, and 30 minutes. We measured MAP, heart rate (HR), Cl, left ventricle (LV) end systolic and diastolic pressures, the first derivative of LV pressure (dP/dt), left anterior descending artery blood flow, regional LV contraction, gas tensions, and lactates. A coronary sinus catheter allowed for measurements of coronary sinus pressure, lactate, and gas tensions. Stroke volume, percent myocardial shortening (dL/dt) myocardial oxygen consumption, and net lactate myocardial production were calculated. Results: Whereas 30 mg/kg had minimal effects on coronary blood flow and LV function, 300 mg/kg resulted in profound hypotension, drop in Cl, and acidocis. Conclusions: L-NAME at 30 mg/kg caused a rise in MAP and systemic vascular resistance; however, it had no effect on ventricular function. High dose NO synthase inhibition causes myocardial depression not related to increased afterload, coronary vasoconstriction, or myocardial ischemia.

A 77-year-old man presented with slowly progressive fatigue, muscle weakness, daytime somnolence, hoarseness, and wheezing. He noted also a chronic cough especially with the ingestion of food and liquid. These symptoms had accelerated over the last several years. Poliomyelitis was diagnosed at 11 years of age, but he never had required ventilatory support. The patient maintained an active business career up until the time of his most recent hospital admission. He was a current one-half pack per day cigarette smoker with a total of 50 pack-years.

Little is known about how drug presentation influences medication adherence.To examine the effect of an educational program aimed at increasing expectations of treatment benefit on medication adherence.Data are analyzed from 99 participants who underwent electronic drug monitoring during the Trial of Asthma Patient Education, a randomized, placebo-controlled, multicenter trial. Participants with suboptimally controlled asthma were randomized to placebo or montelukast in conjunction with a presentation mode that was either neutral or designed to increase outcome expectancy. Adherence was monitored electronically over 4 weeks and was defined as ≥ 80% use of prescribed doses. Outcome expectancy, peak expiratory flow, prebronchodilator FEV₁, asthma control (Juniper asthma control questionnaire), and asthma-related quality of life were assessed at baseline and at the 4-week follow-up.Average electronic medication adherence was 69.9%. There was a significant interaction between presentation mode and drug assignment, with participants in the enhanced/montelukast group having a higher change in outcome expectancy (Δ 2.1 points; P.001) and better medication adherence (odds ratio, 4.0; 95% CI, 1.1-14.3) compared with those in the neutral/placebo group. There was no difference in asthma symptoms, quality of life, or clinical outcomes on the basis of presentation mode. Rather, increased outcome expectancy was associated with modest improvements in asthma symptoms after adjusting for presentation mode, drug assignment, and medication adherence.The use of an enhanced presentation aimed at increasing outcome expectancy may lead to improved medication adherence.

Background: Sinusitis and rhinitis are associated with uncontrolled asthma. There are no simple, validated tools to screen for these diseases. The objective of this study was to assess instruments to assist in the diagnosis of chronic sinonasal disease. Methods: Participants without acute sinonasal symptoms underwent an extensive evaluation. The results were submitted to an expert panel that used the Delphi method to achieve consensus. Using the consensus diagnosis of the panel, we determined the sensitivity and specificity of test procedures to diagnose chronic sinonasal disease. We determined the reproducibility of the most sensitive and specific instrument in a separate cohort. Results: Fifty-nine participants were evaluated, and the expert panel reached consensus for all (42 participants with chronic sinonasal disease, 17 participants without chronic sinonasal disease). A six-item questionnaire based on the frequency of nasal symptoms was the most sensitive tool used to diagnose sinonasal disease (minimum specificity, 0.90). Reproducibility testing in a separate cohort of 63 participants (41 chronic sinonasal disease with asthma, 22 chronic sinonasal disease without asthma) showed a concordance correlation coefficient of 0.91 (95% CI, 0.85 to 0.94) when this questionnaire was limited to five items (ie, excluding a question on smell). This five-item questionnaire had a sensitivity of 0.90 (95% CI, 0.77 to 0.97), a specificity of 0.94 (95% CI, 0.71 to 1.00), and an area under the receiver operating characteristic curve of 0.97 (95% CI, 0.93 to 1.0). Sinus CT scans and nasal endoscopy lacked sensitivity for use in the diagnosis of chronic sinonasal disease. Conclusions: We have developed a sensitive, specific, and reproducible instrument to screen for chronic sinonasal disease. Validation studies of this five-item questionnaire are needed, including in patients with asthma. (CHEST 2009; 136:1324–1332) Abbreviations: AUC area under the curve; ROC receiver operating characteristic; SNQ sinonasal questionnaire