Screening and prevention of venous thromboembolism in critically ill patients: a decision analysis and economic evaluation.

Am J Respir Crit Care Med. 2011 Dec 1;184(11):1289-98

Authors: Sud S, Mittmann N, Cook DJ, Geerts W, Chan B, Dodek P, Gould MK, Guyatt G, Arabi Y, Fowler RA

Abstract
RATIONALE: Venous thromboembolism is difficult to diagnose in critically ill patients and may increase morbidity and mortality.
OBJECTIVES: To evaluate the cost-effectiveness of strategies to reduce morbidity from venous thromboembolism in critically ill patients.
METHODS: A Markov decision analytic model to compare weekly compression ultrasound screening (screening) plus investigation for clinically suspected deep vein thrombosis (DVT) (case finding) versus case finding alone; and a hypothetical program to increase adherence to DVT prevention. Probabilities were derived from a systematic review of venous thromboembolism in medical-surgical intensive care unit patients. Costs (in 2010 $US) were obtained from hospitals in Canada, Australia, and the United States, and the medical literature. Analyses were conducted from a societal perspective over a lifetime horizon. Outcomes included costs, quality-adjusted life-years (QALY), and incremental cost-effectiveness ratios.
MEASUREMENTS AND MAIN RESULTS: In the base case, the rate of proximal DVT was 85 per 1,000 patients. Screening resulted in three fewer pulmonary emboli than case-finding alone but also two additional bleeding episodes, and cost $223,801 per QALY gained. In sensitivity analyses, screening cost less than $50,000 per QALY only if the probability of proximal DVT increased from a baseline of 8.5-16%. By comparison, increasing adherence to appropriate pharmacologic thromboprophylaxis by 10% resulted in 16 fewer DVTs, one fewer pulmonary emboli, and one additional heparin-induced thrombocytopenia and bleeding event, and cost $27,953 per QALY gained. Programs achieving increased adherence to best-practice venous thromboembolism prevention were cost-effective over a wide range of program costs and were robust in probabilistic sensitivity analyses.
CONCLUSIONS: Appropriate prophylaxis provides better value in terms of costs and health gains than routine screening for DVT. Resources should be targeted at optimizing thromboprophylaxis.

PMID: 21868500 [PubMed - indexed for MEDLINE]

Utility of the COPD Assessment Test™ (CAT) to Evaluate Severity of COPD Exacerbations.

Am J Respir Crit Care Med. 2012 Jan 26;

Authors: Mackay AJ, Donaldson GC, Patel AR, Jones PW, Hurst JR, Wedzicha JA

Abstract
RATIONALE: The COPD Assessment Test™ (CAT) is an 8-item questionnaire designed to assess and quantify the impact of COPD symptoms on health status. COPD exacerbations impair quality of life and are characterized by worsening respiratory symptoms from the stable state. We hypothesized that CAT scores at exacerbation relate to exacerbation severity as measured by exacerbation duration, lung function impairment and systemic inflammation. OBJECTIVES: To evaluate the utility of the CAT to assess exacerbation severity. METHODS: 161 patients enrolled in the London COPD cohort completed the CAT at baseline (stable state), exacerbation and during recovery between April 2010 and June 2011. MEASUREMENTS AND MAIN RESULTS: Frequent exacerbators had significantly higher baseline CAT scores than infrequent exacerbators (19.5±6.6 vs. 16.8±8.0, p=0.025). In 152 exacerbations, CAT scores rose from an average baseline value of 19.4±6.8 to 24.1±7.3 (p<0.001) at exacerbation. Change in CAT score from baseline to exacerbation onset was significantly but weakly related to change in CRP (rho=0.26; p=0.008) but not to change in fibrinogen (rho=0.09, p=0.351) from baseline to exacerbation. At exacerbation, rises in CAT score were significantly associated with falls in FEV1 (rho=-0.20, p=0.032). Median recovery time as judged by symptom diary cards was significantly related to the time taken for the CAT score to return to baseline (rho=0.42; p=0.012). CONCLUSIONS: The CAT provides a reliable score of exacerbation severity. Baseline CAT scores are elevated in frequent exacerbators. CAT scores increase at exacerbation and reflect severity as determined by lung function and exacerbation duration.

PMID: 22281834 [PubMed - as supplied by publisher]

24 Hour Intensivist Presence: A Pilot Study of Effects on ICU Patients, Families, Doctors and Nurses.

Am J Respir Crit Care Med. 2012 Jan 12;

Authors: Garland A, Roberts D, Graff L

Abstract
RATIONALE: Around-the-clock intensivist presence in ICUs has been promoted as necessary to optimize outcomes. Little data has addressed how it affects the multiple stakeholders in such care.OBJECTIVE: Assess effects of around-the-clock intensivist presence on intensivists, patients, families, housestaff and nurses. METHODS: This 32 week, crossover pilot trial of two intensivist staffing models, performed in two Canadian ICUs, alternated eight-week blocks of two staffing models: (i) standard: one intensivist worked for seven days, taking night call from home; (ii) shiftwork: one intensivist worked seven dayshifts, while other intensivists remained in the ICU at night. MEASUREMENTS: Surveys scaled from 0-100 points assessed outcomes for 24 intensivists (primary outcome: burnout), 119 families (satisfaction), 74 nurses (satisfaction with collaboration and communications, role conflict), and 34 housestaff (autonomy, supervision, learning opportunities). Outcomes for 501 patients included mortality, length of stay (LOS), and resource use. RESULTS: Intensivists doing shiftwork experienced less burnout (-6.9 points, p=0.04). Adjusted hospital mortality (odds ratio 1.22, p=0.44), ICU LOS (-6 hours, p=0.46) and family satisfaction (0.9 points, p=0.79) did not differ between staffing models. Under shiftwork staffing, nurses reported more role conflict (9 points, p<0.001) while nighttime housestaff reported less autonomy, more supervision, but no difference in learning opportunities.CONCLUSIONS: Shiftwork staffing was better for intensivists and the majority were receptive once they had experienced it. While there were no evident negative outcomes for patients or families, further evaluation is needed to clarify how around-the-clock intensivist staffing influences the various stakeholders in ICU care, given power considerations in this study.

PMID: 22246176 [PubMed - as supplied by publisher]

Matrix elastin: a promising biomarker for chronic obstructive pulmonary disease.

Am J Respir Crit Care Med. 2011 Sep 15;184(6):637-41

Authors: Turino GM, Ma S, Lin YY, Cantor JO, Luisetti M

Abstract
Chronic obstructive pulmonary disease (COPD) is a major health problem worldwide and is now the third leading cause of death in the United States. There is a lack of therapies that can stop progression of the disease and improve survival. New drug discovery can be aided by the development of biomarkers, which can act as indicators of severity in the course of the disease and responses to therapy. This perspective brings together the laboratory and clinical evidence, which suggest that elastin degradation products can fulfill the need for such a biomarker. Elastin is a recognized target for injury in COPD. The amino acids desmosine and isodesmosine exist only in matrix elastin; can be measured specifically and sensitively in plasma, urine, and sputum; and indicate changes in the systemic balance between elastase activity and elastase inhibition brought on by the systemic inflammatory state. The biomarker levels in sputum reflect the state of elastin degradation in the lung specifically. Clinical data accumulated over several decades indicate correlations of desmosine and isodesmosine levels with COPD of varying severity and responses to therapy.

PMID: 21757624 [PubMed - indexed for MEDLINE]

Prompting physicians to address a daily checklist and process of care and clinical outcomes: a single-site study.

Am J Respir Crit Care Med. 2011 Sep 15;184(6):680-6

Authors: Weiss CH, Moazed F, McEvoy CA, Singer BD, Szleifer I, Amaral LA, Kwasny M, Watts CM, Persell SD, Baker DW, Sznajder JI, Wunderink RG

Abstract
RATIONALE: Checklists may reduce errors of omission for critically ill patients.
OBJECTIVES: To determine whether prompting to use a checklist improves process of care and clinical outcomes.
METHODS: We conducted a cohort study in the medical intensive care unit (MICU) of a tertiary care university hospital. Patients admitted to either of two independent MICU teams were included. Intervention team physicians were prompted to address six parameters from a daily rounding checklist if overlooked during morning work rounds. The second team (control) used the identical checklist without prompting.
MEASUREMENTS AND MAIN RESULTS: One hundred and forty prompted group patients were compared with 125 control and 1,283 preintervention patients. Compared with control, prompting increased median ventilator-free duration, decreased empirical antibiotic and central venous catheter duration, and increased rates of deep vein thrombosis and stress ulcer prophylaxis. Prompted group patients had lower risk-adjusted ICU mortality compared with the control group (odds ratio, 0.36; 95% confidence interval, 0.13-0.96; P = 0.041) and lower hospital mortality compared with the control group (10.0 vs. 20.8%; P = 0.014), which remained significant after risk adjustment (odds ratio, 0.34; 95% confidence interval, 0.15-0.76; P = 0.008). Observed-to-predicted ICU length of stay was lower in the prompted group compared with control (0.59 vs. 0.87; P = 0.02). Checklist availability alone did not improve mortality or length of stay compared with preintervention patients.
CONCLUSIONS: In this single-site, preliminary study, checklist-based prompting improved multiple processes of care, and may have improved mortality and length of stay, compared with a stand-alone checklist. The manner in which checklists are implemented is of great consequence in the care of critically ill patients.

PMID: 21616996 [PubMed - indexed for MEDLINE]

Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers.

Am J Respir Crit Care Med. 2011 Sep 15;184(6):662-71

Authors: Bafadhel M, McKenna S, Terry S, Mistry V, Reid C, Haldar P, McCormick M, Haldar K, Kebadze T, Duvoix A, Lindblad K, Patel H, Rugman P, Dodson P, Jenkins M, Saunders M, Newbold P, Green RH, Venge P, Lomas DA, Barer MR, Johnston SL, Pavord ID, Brightling CE

Abstract
RATIONALE: Exacerbations of chronic obstructive pulmonary disease (COPD) are heterogeneous with respect to inflammation and etiology.
OBJECTIVES: Investigate biomarker expression in COPD exacerbations to identify biologic clusters and determine biomarkers that recognize clinical COPD exacerbation phenotypes, namely those associated with bacteria, viruses, or eosinophilic airway inflammation.
METHODS: Patients with COPD were observed for 1 year at stable and exacerbation visits. Biomarkers were measured in sputum and serum. Viruses and selected bacteria were assessed in sputum by polymerase chain reaction and routine diagnostic bacterial culture. Biologic phenotypes were explored using unbiased cluster analysis and biomarkers that differentiated clinical exacerbation phenotypes were investigated. Measurements and Main Results: A total of 145 patients (101 men and 44 women) entered the study. A total of 182 exacerbations were captured from 86 patients. Four distinct biologic exacerbation clusters were identified. These were bacterial-, viral-, or eosinophilic-predominant, and a fourth associated with limited changes in the inflammatory profile termed “pauciinflammatory.” Of all exacerbations, 55%, 29%, and 28% were associated with bacteria, virus, or a sputum eosinophilia. The biomarkers that best identified these clinical phenotypes were sputum IL-1?, 0.89 (area under receiver operating characteristic curve) (95% confidence interval [CI], 0.83–0.95); serum CXCL10, 0.83 (95% CI, 0.70–0.96); and percentage peripheral eosinophils, 0.85 (95% CI, 0.78–0.93), respectively.
CONCLUSIONS: The heterogeneity of the biologic response of COPD exacerbations can be defined. Sputum IL-1?, serum CXCL10, and peripheral eosinophils are biomarkers of bacteria-, virus-, or eosinophil-associated exacerbations of COPD. Whether phenotype-specific biomarkers can be applied to direct therapy warrants further investigation.

PMID: 21680942 [PubMed - indexed for MEDLINE]

Intensive care unit management of patients with severe pulmonary hypertension and right heart failure.

Am J Respir Crit Care Med. 2011 Nov 15;184(10):1114-24

Authors: Hoeper MM, Granton J

Abstract
Despite advances in medical therapies, pulmonary arterial hypertension (PAH) continues to cause significant morbidity and mortality. Although the right ventricle (RV) can adapt to an increase in afterload, progression of the pulmonary vasculopathy that characterizes PAH causes many patients to develop progressive right ventricular failure. Furthermore, acute right ventricular decompensation may develop from disorders that lead to either an acute increase in cardiac demand, such as sepsis, or to an increase in ventricular afterload, including interruptions in medical therapy, arrhythmia, or pulmonary embolism. The poor reserve of the right ventricle, RV ischemia, and adverse right ventricular influence on left ventricular filling may lead to a global reduction in oxygen delivery and multiorgan failure. There is a paucity of data to guide clinicians caring for acute right heart failure in PAH. Treatment recommendations are frequently based on animal models of acute right heart failure or case series in humans with other causes of pulmonary hypertension. Successful treatment often requires that invasive hemodynamics be used to monitor the effect of strategies that are based primarily on biological plausibility. Herein we have developed an approach based on the current understanding of RV failure in PAH and have attempted to develop a treatment paradigm based on physiological principles and available evidence.

PMID: 21700906 [PubMed - indexed for MEDLINE]

Unstable Angina and Non-ST Elevation Myocardial Infarction.

Am J Respir Crit Care Med. 2011 Dec 28;

Authors: Braunwald E

Abstract
Non ST elevation acute coronary syndromes (NSTE-ACS) are responsible for approximately 1 million admissions to U.S. hospitals and twice as many to European hospitals each year. Thus, it is one of the most common serious illnesses in adults, and it is associated with an in-hospital mortality of approximately 5%. The most common cause is rupture of an atherosclerotic coronary plaque, resulting in subtotal coronary occlusion. Diagnosis is based on the clinical picture of retrosternal chest pain, aided by electrocardiographic findings of ST segment deviations and biomarker abnormalities (elevation of troponin and natriuretic peptides) and cardiac imaging (myocardial scans showing perfusion defects). Treatment involves anti-ischemic agents (nitrates and beta blockers), antiplatelet drugs (aspirin, P2Y12 and GP IIb/IIIa receptor blockers) and anticoagulants (unfractionated and low molecular heparins). Patients should undergo risk stratification and those with high risk factors should undergo coronary arteriography promptly with the intent to carry out coronary revascularization. Those at low risk should continue to receive intensive anti-ischemic and anti-thrombotic therapy. At discharge, patients should receive intensive lipid lowering therapy with high doses of a statin, as tolerated.

PMID: 22205565 [PubMed - as supplied by publisher]

The Use of Non-Physician Providers in Adult Intensive Care Units.

Am J Respir Crit Care Med. 2011 Dec 1;

Authors: Gershengorn HB, Johnson MP, Factor P

Abstract
In the United States there are not currently enough critical care trained practitioners to provide care to all critically ill patients. With calls for "high intensity" staffing and 24-hour coverage of our ICUs, the board-certified intensivists we do have are being stretched ever more thin. Non-physician providers (physician assistants (PAs) and nurse practitioners (NPs)) are being used with increasing frequency in critical care settings to provide care to critically ill patients. In this review, we explore the impact of introducing non-physician providers into the adult ICU.

PMID: 22135345 [PubMed - as supplied by publisher]

Use of central venous oxygen saturation to guide therapy.

Am J Respir Crit Care Med. 2011 Sep 1;184(5):514-20

Authors: Walley KR

Abstract
The use of pulmonary artery catheters has diminished, so that other technologies are emerging. Central venous oxygen saturation measurement (ScvO?) as a surrogate for mixed venous oxygen saturation measurement (SvO?) is simple and clinically accessible. To maximize the clinical utility of ScvO? (or SvO?) measurement, it is useful to review what the measurement means in a physiologic context,how the measurement is made, important limitations, and how this measurement may be helpful in common clinical scenarios. Compared with cardiac output measurement, SvO? is more directly related to tissue oxygenation. Furthermore,when tissue oxygenation is a clinical concern, SvO? is less prone to error compared with cardiac output, where small measurement errors may lead to larger errors in interpreting adequacy of oxygen delivery. ScvO? should be measured from the tip of a central venous catheter placed close to, or within, the right atrium to reduce measurement error. Correct clinical interpretation of SvO?, or its properly measured ScvO? surrogate, can be used to (1) estimate cardiac output using the Fick equation, (2) better understand whether a patient's oxygen delivery is adequate to meet their oxygen demands, (3) help guide clinical practice, particularly when resuscitating patients using validated early goal directed therapy treatment protocols, (4) understand and treat arterial hypoxemia, and (5) rapidly estimate shunt fraction (venous admixture).

PMID: 21177882 [PubMed - indexed for MEDLINE]

Randomized, placebo-controlled clinical trial of an aerosolized ??-agonist for treatment of acute lung injury.

Am J Respir Crit Care Med. 2011 Sep 1;184(5):561-8

Authors: , Matthay MA, Brower RG, Carson S, Douglas IS, Eisner M, Hite D, Holets S, Kallet RH, Liu KD, MacIntyre N, Moss M, Schoenfeld D, Steingrub J, Thompson BT

Abstract
RATIONALE: ??-Adrenergic receptor agonists accelerate resolution of pulmonary edema in experimental and clinical studies.
OBJECTIVES: This clinical trial was designed to test the hypothesis that an aerosolized ??-agonist, albuterol, would improve clinical outcomes in patients with acute lung injury (ALI).
METHODS: We conducted a multicenter, randomized, placebo-controlled clinical trial in which 282 patients with ALI receiving mechanical ventilation were randomized to receive aerosolized albuterol (5 mg) or saline placebo every 4 hours for up to 10 days. The primary outcome variable for the trial was ventilator-free days.
MEASUREMENTS AND MAIN RESULTS: Ventilator-free days were not significantly different between the albuterol and placebo groups (means of 14.4 and 16.6 d, respectively; 95% confidence interval for the difference, -4.7 to 0.3 d; P = 0.087). Rates of death before hospital discharge were not significantly different between the albuterol and placebo groups (23.0 and 17.7%, respectively; 95%confidence interval for the difference,-4.0 to 14.7%;P = 0.30). In the subset of patients with shock before randomization, the number of ventilator-free days was lower with albuterol, although mortality was not different. Overall, heart rates were significantly higher in the albuterol group by approximately 4 beats/minute in the first 2 days after randomization, but rates of new atrial fibrillation (10% in both groups) and other cardiac dysrhythmias were not significantly different.
CONCLUSIONS: These results suggest that aerosolized albuterol does not improve clinical outcomes in patients with ALI. Routine use of ??-agonist therapy in mechanically ventilated patients with ALI cannot be recommended. Clinical trial registered with www.clinicaltrials.gov (NCT 00434993).

PMID: 21562125 [PubMed - indexed for MEDLINE]

Current controversies and future perspectives in chronic obstructive pulmonary disease.

Am J Respir Crit Care Med. 2011 Sep 1;184(5):507-13

Authors: Agustí A, Vestbo J

Abstract
Over the past decade there has been much research and interest in COPD. As a result, the understanding and management of the disease has improved significantly. Yet, there are many uncertainties and controversies that require further work. This review discusses these controversies and anticipates some of the changes that may occur in the near future in the field of COPD.

PMID: 21680951 [PubMed - indexed for MEDLINE]

Peripheral Blood Proteins Predict Mortality in Idiopathic Pulmonary Fibrosis.

Am J Respir Crit Care Med. 2011 Oct 20;

Authors: Richards TJ, Kaminski N, Baribaud F, Flavin S, Brodmerkel C, Horowitz D, Li K, Choi J, Vuga LJ, Lindell KO, Klesen M, Zhang Y, Gibson KF

Abstract
Introduction/ BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of unknown etiology with a variable and unpredictable course. The aim of this study was to identify and validate plasma proteins that are predictive of outcome in IPF. METHODS: Plasma samples were available for 241 IPF patients (140 - derivation and 101 validation). In derivation cohort, concentrations of 92 proteins were analyzed using a multiplex bead-based immunoassay and concentrations of MMP7, MMP1, and SPD were assessed by ELISA. In the validation cohort concentrations of ICAM1, IL8, VCAM1 were assessed by bead-based multiplex assay, and S100A12 and MMP7 by ELISA. Associations of biomarkers with mortality, transplant free survival, and disease progression were tested in derivation and validation cohorts using nonparametric methods of survival analysis and the Cox proportional hazards model, and an integrated risk prediction score was derived and tested. RESULTS: High concentrations of MMP7, ICAM1, IL8, VCAM1, and S100A12 predicted poor overall survival, poor transplant free survival and poor progression free survival in the derivation cohort. In the independent validation cohort high concentrations of all five were predictive of poor transplant free survival, MMP7, ICAM1, and IL8 of overall survival and ICAM1 of poor progression free survival. The personal clinical and molecular mortality prediction index (PCMI) derived in the derivation cohort was highly predictive of mortality in the validation cohort. CONCLUSIONS: Our results suggest that plasma proteins should be evaluated as a tool for prognosis determination in prioritization of patients for lung transplantation and stratification in drug studies.

PMID: 22016448 [PubMed - as supplied by publisher]

Outcomes of Non-invasive Ventilation for Acute Exacerbations of COPD in the United States, 1998-2008.

Am J Respir Crit Care Med. 2011 Oct 20;

Authors: Chandra D, Stamm JA, Taylor B, Ramos RM, Satterwhite L, Krishnan JA, Mannino D, Sciurba FC, Holguin F

Abstract
RATIONALE: The patterns and outcomes of non-invasive positive-pressure ventilation (NIPPV) use in patients hospitalized for acute exacerbations of COPD nationwide are unknown. METHODS: We used data from the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample, to assess the pattern and outcomes of NIPPV use for acute exacerbations of COPD during 1998-2008. RESULTS: An estimated 7,511,267 admissions for acute exacerbations occurred from 1998-2008. There was a 462% increase in NIPPV use (from 1.0% to 4.5% of all admissions), and a 42% decline in invasive mechanical ventilation (IMV) use (from 6.0% to 3.5% of all admissions) during these years. This was accompanied by an increase in the size of a small cohort of patients requiring transition from NIPPV to IMV. In-hospital mortality in this group appeared to be worsening over time. By 2008, these patients had a high mortality rate (29.3%) which represented 61% higher odds of death compared to patients directly placed on IMV (95% CI 24-109%), and 677% greater odds of death compared to patients treated with NIPPV alone (95% CI 475-948%). With the exception of patients transitioned from NIPPV to IMV, in-hospital outcomes were favorable and improved steadily year by year. CONCLUSIONS: The use of NIPPV has increased significantly over time among patients hospitalized for acute exacerbations of COPD, while the need for intubation and in-hospital mortality has declined. However, the rising mortality rate in a small but expanding group of patients requiring invasive mechanical ventilation after treatment with non-invasive ventilation needs further investigation.

PMID: 22016446 [PubMed - as supplied by publisher]

Decision Making in the Patient with Pulmonary Nodules.

Am J Respir Crit Care Med. 2011 Oct 6;

Authors: Ost DE, Gould MK

Abstract
Integrating current evidence with fundamental concepts from decision analysis suggests that management of patients with pulmonary nodules should begin with estimating the pretest probability of cancer from the patient's clinical risk factors and computed tomography characteristics. Then, the consequences of treatment should be considered, by comparing the benefits of surgery if the patient has lung cancer with the potential harm if the patient does not have cancer. This analysis determines the "treatment threshold", which is the point around which the decision centers. This varies widely among patients depending on their cardiopulmonary reserve, comorbidities, and individual preferences. For patients with a very low probability of cancer, careful observation with serial computed tomography is warranted. For those with a high probability of cancer, surgical diagnosis is warranted. For patients in the intermediate range of probabilities, either computed tomography-guided fine-needle aspiration biopsy or positron emission tomography, possibly followed by computed tomography-guided fine-needle aspiration biopsy, is best. Patient preferences should be considered because the absolute difference in outcome between strategies may be small. The optimal approach to the management of patients with pulmonary nodules is evolving as technologies develop. Areas of uncertainty include quantifying the hazard of delayed diagnosis; determining the optimal duration of follow-up for ground-glass and semisolid opacities; establishing the roles of volumetric imaging, advanced bronchoscopic technologies, and limited surgical resections; and calculating the cost-effectiveness of different strategies.

PMID: 21980032 [PubMed - as supplied by publisher]