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CHEST publishes select peer-reviewed, accepted manuscripts Online First each week. The media embargo is lifted on the date of Online First publication. Final, edited versions will appear in a numbered issue of CHEST and may contain substantive changes. We encourage readers to check back for the final article. Online First papers are indexed in PubMed and by search engines, but the information, including the final title and author list, may be updated on final publication.

original research 
Robyn T. Cohen, Robert C. Strunk, Joshua J. Field, Carol L. Rosen, Fenella J. Kirkham, Susan Redline, Janet Stocks, Mark J. Rodeghier, Michael R. DeBaun
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Abstract 

Background:  The contribution of environmental tobacco smoke exposure (ETS) to pulmonary morbidity in children with sickle cell anemia (SCA) is poorly understood. We tested the hypothesis that children with SCA and ETS would have an increased prevalence of obstructive lung disease and respiratory symptoms compared to children with SCA but without ETS.

Methods:  Parent-report of ETS and respiratory symptom frequency were obtained for 245 children with SCA as part of a multi-center prospective cohort study. 196 children completed pulmonary function testing. Multivariable regression models evaluated the associations between ETS exposures at different time points [prenatal, infant (birth-2 years), preschool (2 years -first grade) and current], and lung function and respiratory symptoms.

Results:  Among 245 participants, a high prevalence of prior (44%) and current (29%) ETS was reported. Of the 196 children who completed pulmonary function testing, those with parent-reported infant and current ETS were more likely to have airway obstruction (defined as Forced Expiratory Volume in 1 second /Forced Vital Capacity ratio (FEV1/FVC) below the lower limit normal) compared to unexposed children (22.0% vs. 3.1%, p<0.001). Those with ETS also had a lower FEF25-75/FVC ratio (0.82 vs. 0.97, p=0.001) and were more likely to have evidence of bronchodilator responsiveness(23% vs. 11%, p=0.03). Current and prior ETS and in utero exposure were associated with increased frequency of respiratory symptoms.

Conclusions:  ETS exposure is associated with evidence of lower airway obstruction and increased respiratory symptoms in SCA.

original research 
Niyada Naksuk, Ken M. Kunisaki, David G. Benditt, Venkatakrishna Tholakanahalli, Selcuk Adabag
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Abstract 

Background:  Chronic obstructive pulmonary disease (COPD) is a common comorbidity in heart failure. The efficacy of implantable cardioverter-defibrillator (ICD) therapy has not been determined in heart failure patients with COPD.

Methods:  We examined the incidence of ICD shocks and mortality in 628 consecutive patients who underwent defibrillator implantation at the Minneapolis Veterans Affairs Medical Center from 2006 to 2010.

Results:  Mean age of the patients was 67±10 years and 99% were male. Patients with COPD (n=246, 39%) were functionally more limited (p<0.0001) and more likely to have ICD for primary prevention of sudden death (p=0.04) than those without COPD. Over a median 4.1 years [IQR25,75 2.2, 5.7] of follow-up, COPD patients had a higher incidence of appropriate shocks (29% vs.17%; p<0.0001) compared to those without COPD, whereas the incidence of inappropriate shocks was similar (9% vs. 10%, respectively; p=0.61). In multivariable analysis, COPD was associated with a 2-fold increase in the odds of appropriate ICD shock (95% confidence interval 1.3-2.9; p=0.001). Incidence of ICD shocks did not vary with severity of COPD. Although all-cause mortality was higher in COPD patients than those without COPD (29% vs. 21% respectively; p=0.029), one-year mortality (5.3% vs. 2.6%, respectively; p=0.08) and the average time from first appropriate ICD shock to death was comparable (median 2.3 years [IQR25,75 1.2, 4.4] vs. 2.8 years [IQR25,75 1.4, 5.3], respectively, p=0.29).

Conclusions:  Patients with COPD have a higher incidence of ICD shocks than those without COPD and appear to benefit from ICD therapy.

original research 
Lauren S. Mott, Karla G. Graniel, Judy Park, Nicholas H. de Klerk, Peter D. Sly, Conor P. Murray, Harm AWM Tiddens, Stephen M. Stick On behalf of AREST CF
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Abstract 

Aim:  This study aimed to determine whether radiologic assessment of early bronchiectasis in young children with cystic fibrosis (CF) is dependent on lung volume.

Methods:  This study, approved by the hospital ethics committee, included 40 young children with CF from a newborn screened population, contributing paired volume-controlled inspiratory and expiratory volumetric chest CT scans, acquired under general anaesthesia while clinically stable. Bronchiectasis was assessed using a semi-quantitative CT score in inspiration and expiration and the sensitivity of the expiratory CT to detect bronchiectasis was compared to the inspiratory CT using sensitivity, intraclass correlation coefficient and Bland-Altman plots. Matched inspiratory and expiratory airway vessel measurements were then obtained in a subset of 10 children and a linear regression model with generalised estimating equations to examine the relationship between lung volume and airway:vessel ratio after adjusting for age and vessel size. The number of visible airways in inspiration and expiration was compared in 20 children using the Wilcoxon signed rank test.

Results:  The expiratory scan had poor sensitivity to detect bronchiectasis (sensitivity 0.46), and underestimated disease extent (p<0.001). Further, the airway:vessel ratio was consistently higher in inspiration, independent of age and vessel size (p<0.001), with significantly more airways were visible in inspiration, independent of age (median visible airways: 60 vs 31, p<0.001).

Conclusion:  Radiologic assessment of early bronchiectasis using chest CT is dependent on lung volume in young children with cystic fibrosis. Lung volume during image acquisition should be standardised to evaluate airway dimensions in young children using chest CT.

original research 
Daniel Yaffe, David Shitrit, Maya Gottfried, Gavriel Bartal, Jacob Sosna
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Abstract 

Background:  To evaluate the efficacy of “Ipsilateral Opposite Side Aspiration”, a new method to overcome resistant pneumothorax after failure of a simple aspiration. The patient position is reversed (from prone to supine or vice versa) and the aspiration repeated.

Methods:  Between January 1, 2010 and April 3, 2012, 129 consecutive CT-guided percutaneous needle biopsies of lung nodules were performed in 127 patients (75 men, 52 women; mean age 67.8 years; range 26–88 years). Two patients underwent repeat biopsies. The mean lesion diameter was 38 mm (range 8–110 mm). Core biopsy and FNA were performed in 126 procedures; in 3 cases, only FNA was performed. In the cases with symptomatic minimal pneumothorax and in all patients with pneumothorax >10 mm, immediate, simple manual aspiration was performed. Ipsilateral opposite side aspiration was performed when simple aspiration failed.

Results:  Among 129 CT-guided biopsies, pneumothorax was detected by CT in 54 (42%); 51 (39%) during the biopsy. Delayed pneumothorax occurred in 2 patients (1.55%). Manual aspiration to treat pneumothorax was performed in 27 (21%) of 129 procedures. Simple aspiration was successful in 20 (74%) of these 27 cases. Ipsilateral opposite side aspiration was accomplished in the remaining 7 (26%) and was successful in 6 (86%). Two (1.55%) of 129 procedures required chest tube placement.

Conclusions:  Immediate, simple, percutaneous aspiration of iatrogenic pneumothorax was successful in 74% of patients needing treatment. Our proposed new method of ipsilateral opposite side aspiration offers a solution for patients who remain with resistant pneumothorax after simple aspiration.

original research 
Lior Fuchs, Joon Lee, Victor Novack, Yael Baumfeld, Daniel Scott, Leo Celi, Tal Mandelbaum, Michael Howell, Daniel Talmor
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Abstract 

Background:  The association between levels of acute kidney injury (AKI) during ICU admission and long term mortality are not well defined.

Methods:  We examined medical records of adult patients admitted to a large tertiary medical center with no history of end stage renal disease (ESRD), who survived 60 days from ICU admission between the years 2001-2007. The extracted data included demographic, clinical information, physiological data as well as dates of death.

Results:  Among 15,048 patients, 12,399 (82.4%) survived 60 days from ICU admission and consisted the study population. 5663 (45.7%) did not develop AKI during their ICU admission, while 4589(37.0%), 1613 (13.0%) and 534 (4.3%) developed progressively severe levels of AKI as defined by the Acute Kidney Injury Network criteria (AKIN 1, AKIN 2 and AKIN 3 respectively). Only 42.5% of Patients who developed AKIN 3 survived two years from ICU admission. AKIN 3 patients had a 61% higher mortality risk two years from ICU discharge compared to patients who did not develop AKI. Patients who developed AKIN 1 and AKIN 2 had similar increased mortality risk two years from ICU admission (HR 1.26 and 1.28 respectively). Level of estimated glomerular filtration rate (eGFR) on ICU discharge and chronic kidney disease (CKD) were found to be associated with long term mortality.

Conclusions:  Patients who develop AKI in the ICU have significantly increased risks of death that extend beyond their high ICU mortality rates. These increased risks of death continue for at least two years after the index ICU admission.

original research 
Damien Urban, Aparna Rao, Mathias Bressel, Dina Neiger, Benjamin Solomon, Linda Mileshkin
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Abstract 

Background:  Suicide rates among lung cancer patients are higher than the general population. This study aims to identify patient and disease characteristics associated with suicide in lung cancer patients.

Methods:  We conducted an analysis of subjects with primary lung cancer diagnosed between 1973 – 2008 recorded in the Surveillance, Epidemiology and End Results (SEER) database.

Results:  Of 871,230 persons diagnosed with lung cancer, 1184 suicides were identified. The rate of suicide did not change considerably over time, with 8.83 compared to 7.17 suicides per 10,000 persons-years in 1973-79 and 2000-09, respectively. The standardized mortality ratio (SMR) of the entire cohort was 4.95, with an SMR of 13.4 within 3 months of a cancer diagnosis. Despite most subgroups having a higher SMR than the general population, a wide variation of suicide risk was seen amongst different subgroups, including histologic type (SMR 1.58 vs 7.28 in bronchoalveolar and small cell carcinoma, respectively). The highest SMR’s were found in: males; older age; higher grade tumour; metastatic disease, and patients who did not receive or refused treatment. Despite the higher SMR among metastatic patients, over 50% of suicides occurred in those with locoregional, and potentially curable disease.

Conclusion(s):  Lung cancer patients have a higher risk of suicide compared with the general US population, especially within 3 months of diagnosis. Despite the higher SMR among poorer prognosis patients, a concerning proportion of suicides occur in potentially curable patients, highlighting the need for effective screening strategies to avoid this preventable cause of death.

original research 
Shigeki Sawada, Natsumi Yamashita, Hiroshi Suehisa, Motohiro Yamashita
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Abstract 

Background:  Patients with lung cancer often present with recurrence, even after resection. The identification of risk factors for recurrence after resection is useful.

Methods:  Among 1338 patients with lung cancer who underwent a complete resection, 277 developed recurrences post-surgery. Data regarding the TNM factors, histological subtype and the presence/absence of vessel invasion were analyzed retrospectively using the survival tree method to identify groups with a high risk of recurrence after resection.

Results:  The results revealed that the T factor, the N factor, and lymphatic (ly) and blood (v) vessel invasion were related to the risk of recurrence and six combinations of these factors were identified using the survival tree method; Group A: v = 0, T <= 1b, ly = 0; Group B: v = 0, T <= 1b, ly >= 1; Group C: v = 0, T >= 2a; Group D: v >= 1, N <= 1,T <= 2b; Group E: v >= 1, N <= 1, T >= 3; and Group F: v >= 1, N >= 2. The six groups were then further classified into three groups: a low-risk group (Group A), a moderate-risk group (Groups B, C and D), and a high-risk group (Groups E and F). The 5-year recurrence-free survival rate was approximately 98% for the low-risk group, 75% for the moderate-risk group, and 30 % for the high-risk group.

Conclusions:  Combining the T, N, v and ly factors allowed the precise identification of a group with a high risk of recurrence after resection.

original research 
Tania Janaudis-Ferreira, Marla K. Beauchamp, Priscila Games Robles, Roger S. Goldstein, Dina Brooks
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Abstract 

Background:  The objectives of this systematic review were to: synthesize the literature on measures of activities of daily living (ADL) that have been used in individuals with chronic obstructive pulmonary disease (COPD); provide an overview of the psychometric properties of the identified measures and describe the relationship of the disease-specific instruments with other relevant outcome measures for individuals with COPD and health-care utilization.

Methods:  Studies that included a measure of ADL in individuals with COPD were identified using electronic and hand searches. Two investigators performed the literature search. One investigator reviewed the study title, abstract and full-text of the articles to determine study eligibility and performed the data extraction and tabulation. In case of uncertainty, a second reviewer was consulted.

Results:  A total of 679 articles were identified. Of those, 116 met the inclusion criteria. Twenty-seven ADL instruments were identified, of which 11 instruments were respiratory disease-specific while 16 were generic. Most instruments combined Instrumental ADL (IADL) with Basic ADL (BADL). The majority of the instruments were self-reported; only 3 instruments were performance-based. Twenty-one studies assessed psychometric properties of 16 ADL instruments in patients with COPD.

Conclusions:  Although several ADL instruments were identified, psychometric properties have only been reported in a few. Selection of the most appropriate measure should focus on the target construct (BADL or IADL or both), type of test (disease-specific vs. generic and self-reported vs. performance-based), depth of information obtained and psychometric properties of the instruments. Given the relevance of ADL to the lives of patients with COPD its assessment should be more frequently incorporated as a clinical outcome in their management.

original research 
Vincent Mysliwiec, Jessica Gill, Hyunhwa Lee, Tristin Baxter, Roslyn Pierce, Taura L. Barr, Barry Krakow, Bernard J. Roth
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Abstract 

Background:  Sleep disturbances are among the most common symptoms of military personnel who return from deployment. The objective of our study was to determine the presence of sleep disorders in U.S. Military Personnel referred for evaluation of sleep disturbances after deployment and examine associations between sleep disorders and service-related diagnoses of depression, mild traumatic brain injury (TBI), pain and post-traumatic stress disorder (PTSD).

Methods:  Cross-sectional study of military personnel with sleep disturbances who returned from combat within 18 months. Sleep disorder rendered by clinical evaluation and polysomnogram with validated instruments to diagnose service-related illnesses.

Results:  Of 110 military personnel included in our analysis, 97.3% were male (mean age 33.6 ± 8.0 years; mean BMI of 30.0 ± 4.3) and 70.9% returned from combat within 12 months. Nearly half, 47.3% met diagnostic criteria for 2 or more service-related diagnoses. Sleep disorders were diagnosed in 88.2% and 11.8% had a normal sleep evaluation and served as controls. Overall, 62.7% met diagnostic criteria for obstructive sleep apnea (OSA) and 63.6% for insomnia. The exclusive diagnoses of insomnia and OSA were present in 25.5% and 24.5% respectively; 38.2% had comorbid insomnia and OSA. Military personnel with comorbid insomnia and OSA were significantly more likely to meet criteria for depression (p <0.01) and PTSD (p<0.01) compared to controls and those with OSA.

Conclusions:  Comorbid insomnia and OSA is a frequent diagnosis in military personnel referred for evaluation of sleep disturbances after deployment. This diagnosis, which is difficult to treat, may explain the refractory nature of many service-related diagnoses.

original research 
Lara N. Roberts, Gayle Porter, Richard D. Barker, Richard Yorke, Lynda Bonner, Raj K. Patel, Roopen Arya
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Abstract 

Background:  Venous thromboembolism (VTE) is a common complication of hospitalisation and is associated with significant morbidity and mortality. The use of appropriate thromboprophylaxis can significantly reduce the risk of VTE but remains underutilised. In England, a comprehensive approach to VTE prevention was launched in 2010. This study aimed to evaluate the impact of the implementation of the national programme in a single centre.

Methods:  A prospective quality improvement programme was established at King’s College Hospital NHS Foundation Trust in 2010. The multidisciplinary thrombosis team launched mandatory documented VTE risk assessment and updated thromboprophylaxis guidance. Root cause analysis of hospital-associated thrombosis (HAT) was implemented to identify system failures, enable outcome measurement and to facilitate learning to improve VTE prevention practice. The key outcomes were the incidence of HAT and the proportion of events preventable with appropriate thromboprophylaxis.

Results:  Documented VTE risk assessment improved from less than 40% to >90% in the first nine months. 425 episodes of HAT were identified over two years. A significant reduction in the incidence of HAT was observed following sustained achievement of 90% risk assessment (RR 0.88, 95% CI 0.74 – 0.98; P=0.014). The proportion of HAT attributable to inadequate thromboprophylaxis fell significantly from 37.5% to 22.4% (P=0.005).

Conclusion:  Mandatory VTE risk assessment can significantly reduce preventable HAT and thereby improve patient safety.

original research 
Edward J. Dill, Ree Dawson, Deborah E. Sellers, Walter M. Robinson, Gregory S. Sawicki
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Abstract 

Background:  Health-related quality of life (HRQOL) measures have been used as patient-reported outcomes in clinical trials in cystic fibrosis (CF), but there is limited data on HRQOL changes over time in adults with CF.

Methods:  The Project on Adult Care in Cystic Fibrosis (PAC-CF), a prospective longitudinal panel study of 333 adults with CF at 10 CF centers in the US, administered a disease-specific HRQOL measure, the Cystic Fibrosis Questionnaire-Revised (CFQ-R), 7 times over 21 months. The CFQ-R assesses both physical and psychosocial domains of health. Growth curve regression models were developed for each CFQ-R domain adjusting for demographic and clinical characteristics.

Results:  Between 205-303 adults (response rate 70%- 93%) completed surveys. Mean age at baseline was 33 years (range 19–64); mean FEV1% predicted was 59.8% (SD 22%). Over the 21 months of follow-up, lung function, frequency of pulmonary exacerbations, and nutritional indices were associated with physical CFQ-R domain scores. There were no significant population trends over time in physical domain scores. However, there were population time trends in 3 psychosocial domains: Treatment Burden (+8.9 points/year), Emotional Functioning (+3.2 points/year), and Social Functioning (-2.4 points/year). Individual variation was seen over 21 months in both physical and psychosocial subscales.

Conclusion:  In a longitudinal multi-center population of adults with CF, clinical variables such as FEV1, exacerbation frequency, and weight were correlated with related CFQ-R subscales. For the population as a whole, physical domains of CFQ-R such as Respiratory Symptoms were stable. In contrast, population changes in several psychosocial domains of CFQ-R suggest that differentiating the physical and psychosocial trajectories in health among adults with CF is critical in evaluating patient-reported outcomes.

original research 
Benjamin Sztrymf, Sven Günther, Elise Artaud-Macari, Laurent Savale, Xavier Jaïs, Olivier Sitbon, Gérald Simonneau, Marc Humbert, Denis Chemla
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Background:  Novel non-invasive tools may improve the management of patients with pulmonary arterial hypertension (PAH) experiencing heart failure. Major right ventricle overload leads to decreased stroke volume, which shortens left ventricular ejection time (LVET). Our arterial tonometry study tested the hypothesis that LVET carries prognostic value in PAH patients with heart failure.

Methods:  Clinical, biological and radial artery tonometry variables were prospectively obtained at admission and at day 3-5 in 53 consecutive PAH patients admitted in our ICU for clinical deterioration. LVET was measured from the reconstructed aortic pressure curve.

Results:  Overall ICU mortality (median stay 5 days) was 17% and 28%. At admission, the LVET was shorter in patients with unfavourable outcome (median 228 ms (212-278) vs 257 ms (237-277), p=0.032), while other tonometric indices were similar. The LVET at entry (237 ms) had 73% sensitivity and 89% specificity for identifying death in the ICU. Other prognostic factors at admission were higher serum levels of brain natriuretic peptide (BNP) and creatinine, and lower natremia. Dobutamine requirement, higher furosemide dose and higher oxygen flow were associated with unfavourable outcome. At the second evaluation, higher serum level of creatinine and BNP, higher furosemide dose and oxygen flow, and dobutamine or norepinephrine requirement were associated with poor outcome. The change in LVET between admission and follow-up measurement was not associated with outcome. The 90-day mortality was 28%.

Conclusions:  Shortened LVET at ICU admission was a prognostic factor in PAH with heart failure. Previously documented prognostic factors were also confirmed in this cohort.

original research 
Victor F. Tapson, Zhi-Cheng Jing, Kai-Feng Xu, Lei Pan, Jeremy Feldman, David G. Kiely, Eugene Kotlyar, C. Shane McSwain, Kevin Laliberte, Carl Arneson, Lewis J. Rubin On Behalf of the FREEDOM-C2 Study Team
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Background:  Treprostinil is a stable prostacyclin analogue approved for the treatment of pulmonary arterial hypertension (PAH) as parenteral or inhaled therapy. Treprostinil diolamine is a sustained-release oral formulation of treprostinil that was studied to determine if it could provide a more convenient prostacyclin treatment option for PAH patients with less severe disease.

Objective:  To evaluate the efficacy and safety of oral treprostinil in PAH patients receiving stable background endothelin receptor antagonist (ERA) and/or phosphodiesterase type 5 inhibitor (PDE-5I) therapy.

Methods:  A 16-week, multicenter, double-blind, placebo-controlled study in 310 PAH patients comparing the twice daily administration of oral treprostinil (n=157) to placebo (n=153). The primary endpoint was change in 6-minute walk distance (6MWD) at week 16. Secondary efficacy endpoints included: World Health Organization functional class, Borg dyspnea score, dyspnea-fatigue index, signs and symptoms of PAH, and clinical worsening.

Results:  One hundred thirty-two (84%) oral treprostinil and 138 (90%) placebo patients completed the study. The mean dose (±standard deviation) of oral treprostinil for completers at week 16 was 3.1 ± 1.9 mg BID. The Hodges-Lehmann placebo-corrected median difference in 6MWD at week 16 was 10.0 m (95% confidence interval: -2 to 22; P=0.089). There were no significant changes in secondary endpoints. The most common adverse events associated with oral treprostinil included headache (71%), diarrhea (55%), nausea (46%), flushing (35%), and jaw pain (25%).

Conclusions:  The addition of oral treprostinil to background ERA and/or PDE-5I therapy did not result in a statistically significant improvement in exercise capacity. Side effects were common but were tolerated by most subjects.

Clinical trial information:  A 16-Week, International, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy and Safety of Oral UT-15C Sustained Release Tablets in Subjects With Pulmonary Arterial Hypertension (FREEDOM-C2); NCT00887978

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Abstract 

Background  When oral anticoagulation (OAC) with adjusted dose Vitamin K antagonist (VKA,) is used, the quality of anticoagulation control (as reflected by time in therapeutic range (TTR) of the International Normalised Ratio, INR) is an important determinant of thromboembolism and bleeding. Our objective was to derive a validated scheme using patient-related clinical parameters for assessing the likelihood of poor INR control amongst atrial fibrillation (AF) patients on VKA therapy.

Methods  The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial population was randomly divided into derivation and internal validation cohorts using an 1:1 ratio. We used linear regression analysis to detect clinical factors associated with TTR and binary logistic regression to evaluate the predictive performance of a model incorporating these factors for different cut-off values of TTR. The derived model was externally validated in a cohort of anticoagulated patients prospectively recruited.

Results  In the linear regression model, 9 variables emerged as independent predictors of TTR: female gender (p<0.0001), age <50 years p<0.0001), age 50-60 years (p=0.02), ethnic minority status (p<0.0001) smoking (p=0.03), more than 2 comorbidities (p<0.0001) and being treated with a beta blocker (p=0.02), verapamil (p=0.02) or inversely, with amiodarone use (p=0.05).We incorporated these factors in a simple clinical prediction scheme with the acronym SAMe-TT2R2. The score demonstrated good discrimination performance in both the internal and external validation cohorts (c index 0.72 95%CI 0.64-0.795 and 0.7 95%CI 0.57-0.82 respectively).

Conclusion  Common clinical and demographic factors can influence quality of oral anticoagulation. We incorporated these factors in a simple score (SAMe-TT2R2) that can predict poor INR control and aid decision making by identifying those AF patients that would do well on VKA (SAMe-TT2R2 score=0-1), or conversely, those (ie. SAMe-TT2R2 score ≥2) who require additional interventions to achieve acceptable anticoagulation control.

original research 
Catia Cillóniz, Eva Polverino, Santiago Ewig, Stefano Aliberti, Albert Gabarrús, Rosario Menéndez, Josep Mensa, Francesco Blasi, Antoni Torres
Topics: , , ,
Abstract 

Background:  Prolonged life expectancy has currently increased the proportion of the very elderly among patients with community-acquired pneumonia (CAP). The aim of this study was to determine the influence of age and comorbidity on microbial patterns in CAP patients over 65 years of age.

Methods:  Prospective observational study of adult CAP patients (excluding nursing home) over a 12-year period. We compared patients aged 65-74 years, 75-84 years and >85 years for potential differences in clinical presentation, comorbidities, severity on admission, microbial investigations, etiologies, antimicrobial treatment, and outcomes.

Results:  We studied a total of 2149 patients: 759 (35.3%) patients aged 65-74 years, 941 (43.7%) aged 75-84 years, and 449 (20.8%) patients aged >85 years. At least one comorbidity was present in 1710 (79.6%) patients. Streptococcus pneumoniae was the most frequent pathogen in all age groups, regardless of comorbidity. Staphylococcus aureus, Enterobacteriaceae, and Pseudomonas aeruginosa accounted for 9.1% of isolates and Haemophilus influenzae, 6.4%. All these pathogens were isolated only in patients with ≥1 comorbidity. Mortality increased with age (65-74 y, 6.9%; 75-84 y, 8.9%; >85 y, 17.1%; p<0.001) and was associated with increased comorbidities (neurological, OR: 2.1, 95% CI: 1.5-2.1), PSI IV-V (OR: 3.2, 95% CI: 1.8-6.0), bacteremia (OR: 1.7, 95% CI: 1.1-2.7), the presence of a potential MDR pathogen (S. aureus, P. aeruginosa, Enterobacteriaceae; OR: 2.4, 95% CI: 1.3-4.3) and ICU admission (OR: 4.2, 95% CI: 2.9-6.1) on multivariate analysis.

Conclusions:  Age does not influence microbial etiology itself, while comorbidities are associated with specific etiologies such as H. influenzae and potential MDR pathogens. Mortality in the elderly is mainly driven by the presence of comorbidities and potential MDR.

original research 
Stein Silva, Caroline Biendel, Jean Ruiz, Michel Olivier, Benoit Bataille, Thomas Geeraerts, Arnaud Mari, Beatrice Riu, Olivier Fourcade, Michele Genestal
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Background:  This study investigates the clinical relevance of early general chest ultrasonography (i.e. associating heart and lung ultrasound recording) in patients with acute respiratory failure (ARF) admitted to the intensive care unit (ICU).

Methods:  We prospectively compared this diagnostic approach (‘Ultrasound’) to a routine evaluation established from clinical, radiological and biological data (‘Standard’). Patients were consecutively admitted to the ICU of a University Teaching Hospital during 1-yr period. Inclusion criteria were age at least 18 years and the presence of criteria of severe ARF justifying ICU admission. We compared the diagnostic approaches and the final diagnosis determined by the panel of experts.

Results:  Seventy-eight patients were included (age 70 +/- 18 yr; sex ratio 1). Three patients with two or more simultaneous diagnoses were subsequently excluded. The ‘Ultrasound’ approach was more accurate than the ‘Standard’ (83 % vs 63 % respectively, p < 0.02). ROC curve analysis showed greater diagnosis performance of ‘Ultrasound’ in cases of pneumonia (standard: 0.74 +/- 0.12; ultrasound 0.87 +/- 0.14; p < 0.02), acute hemodynamic pulmonary oedema (standard 0.79 +/- 0.11; ultrasound 0.93 +/- 0.08; p < 0.007), decompensated chronic obstructive pulmonary disease (standard 0.8 +/- 0.09; ultrasound 0.92 +/- 0.15; p < 0.05), and pulmonary embolism (standard 0.65 +/- 0.12; ultrasound 0.81 +/- 0.17; p < 0.04). Furthermore, we showed that the use of ultrasound data, could have significantly improved the initial treatment.

Conclusions:  The use of cardiothoracic ultrasound appears to be an attractive complementary diagnostic tool and seems able to contribute to an early therapeutic decision based on reproducible physiopathological data.

original research  OPEN ACCESS
Earl S. Ford, Janet B. Croft, David M. Mannino, Anne G. Wheaton, Xingyou Zhang, Wayne H. Giles
Topics: ,

Background:  This report updates surveillance results for chronic obstructive pulmonary disease (COPD) in the United States.

Methods:  For 1999 to 2011, data from national data systems for adults aged ≥25 years were analyzed.

Results:  In 2011, 6.5% of adults (13.7 million) reported having been diagnosed with COPD. From 1999 to 2011, the overall age-adjusted prevalence of having been diagnosed with COPD declined (p=0.019). In 2010, there were 10.3 million (494.8 per 10,000) physician office visits, 1.5 million (72.0 per 10,000) emergency room visits, and 699,000 (32.2 per 10,000) hospital discharges for COPD. From 1999-2010, no significant overall trends were noted for physician office visits and emergency room visits; however, the age-adjusted hospital discharge rate for COPD declined significantly (p=0.001). In 2010 there were 312,654 (11.2 per 1000) Medicare hospital discharge claims submitted for COPD. Medicare claims (1999-2010) declined overall (p=0.045), among men (p=0.022), and among enrollees aged 65-74 years (p=0.033). There were 133,575 deaths (63.1 per 100,000) from COPD in 2010. The overall age-adjusted death rate for COPD did not change during 1999-2010 (p=0.163). Death rates (1999-2010) increased among adults aged 45-54 years (p<0.001) and among American Indian/Alaska Natives (p=0.008) but declined among those aged 55-64 years (p=0.002) and 65-74 years (p<0.001), Hispanics (p=0.038), Asian/Pacific Islanders (p<0.001), and men (p=0.001). Geographic clustering of prevalence, Medicare hospitalizations, and deaths was observed.

Conclusion:  Declines in the age-adjusted prevalence, death rate in men, and hospitalizations for COPD since 1999 suggest progress in the prevention of COPD in the United States.

original research 
Stefania Crotti, Giorgio A. Iotti, Alfredo Lissoni, Mirko Belliato, Marinella Zanierato, Monica Chierichetti, Guendalina Di Meo, Federica Meloni, Marilena Pappalettera, Mario Nosotti, Luigi Santambrogio, Mario Viganò, Antonio Braschi, Luciano Gattinoni
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Background:  The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation (LTX) is still debated.

Methods:  We performed a retrospective two-center analysis on the relationship between ECMO bridging duration and survival in twenty-five patients. Further survival analysis was obtained by dividing the patients according to waiting time on ECMO: up to 14 days (Early) or longer (Late). We also analyzed the impact of the ventilation strategy during ECMO bridging, i.e. spontaneous breathing and non-invasive ventilation (NIV) or intubation and invasive mechanical ventilation (IMV).

Results:  17 out of 25 patients were transplanted (with 76% 1-year survival) while 8 patients died on bridge. In the 17 transplanted patients, mortality was positively related to waiting days until LTX (HR 1.12 per day, 95%CI 1.02–1.23, p=0.02) and the group Early showed better Kaplan-Meier curves (p=0.02), higher 1-year survival rates (100% versus 50% p=0.03) and lower morbidity (days on IMV, length of stay in ICU and hospital). During bridge to transplantation, mortality steadily increased with time. Considering the overall outcome of the bridging program (25 patients), bridge duration adversely affected survival (HR 1.06 per day, 95%CI 1.01-1.11, p=0.015) and 1-year survival (Early group 82 % versus Late 29%, p=0.015). Morbidity indices were lower in patients treated with NIV during bridge.

Conclusions:  The duration of bridge on ECMO is a relevant co-factor for mortality and morbidity of critically ill patients awaiting organ allocation. The NIV strategy was associated with a less complicated clinical course after LTX.

original research 
Rodrigo P. Pedrosa, Luciano F. Drager, Lílian K. G de Paula, Aline C. S. Amaro, Luiz A. Bortolotto, Geraldo Lorenzi-Filho
Topics: , ,

Abstract 

Background:  Obstructive sleep apnea is extremely common among patients with resistant hypertension. However, the impact of the treatment of obstructive sleep apnea with continuous positive airway pressure on blood pressure in patients with resistant hypertension is not well established.

Methods:  In the present study, 40 patients with confirmed resistant hypertension and moderate to severe obstructive sleep apnea confirmed by full polysomnography were randomized to medical therapy or medical treatment plus continuous positive airway pressure for 6 months. Patients were evaluated at study baseline and after 6 months by 24-hr ambulatory blood pressure monitoring.

Results:  Thirty-five patients (77% males, age: 56±1years, body mass index: 32 (28-39) kg/m2, apnea-hypopnea index: 29 (24-48) events/hr, Epworth Sleepiness Scale: 10±1, systolic/diastolic office BP: 162±4/97±2mmHg, on 4 (4-5) antihypertensive drugs completed the study. Continuous positive airway pressure was used for 6:01±0:20 (range, 3:42 to 7:44) hours/night. Compared to the control group, awake systolic/diastolic ambulatory blood pressure monitoring decreased significantly in the continuous positive airway pressure group (Delta: +3.1±3.3 /+2.1±2.7 vs. -6.5±3.3/-4.5±1.9mmHg, respectively, p<0.05). Interestingly, the blood pressure changes were only observed while patients were awake, but not during nocturnal ambulatory blood pressure monitoring (Delta: +2.8±4.5/+1.8±3.5 vs. +1.6±3.5/+0.8±2.9mmHg, p=NS).

Conclusions:  The treatment of obstructive sleep apnea with continuous positive airway pressure significantly reduces daytime blood pressure in patients with resistant hypertension. Therefore, our study reinforces the importance of recognizing and treating obstructive sleep apnea in patients with resistant hypertension.Clinical trial registered with www.clinicaltrials.gov (NCT00812695).

original research 
Malcolm M. Bersohn, Michelle P. Turner, Glenna L. Traiger, Adaani E. Frost, Shelley Shapiro

Abstract 

Background:  Heart rate (HR) and systolic blood pressure (SBP) are significant multivariate predictors of survival in patients with pulmonary arterial hypertension (PAH) as part of a 19-element formula. To what extent HR and BP alone predict survival and future hospitalization in patients with PAH are unknown.

Methods:  We analyzed data from the REVEAL (Registry to EValuate Early And Long-term PAH Disease Management) Registry, a prospective, observational study of patients with PAH. Patients were analyzed by quintile (Q) according to values of HR, SBP, and SBP/HR. Kaplan-Meier curves were calculated by quintile for survival and freedom from hospitalization.

Results:  One-year survival after enrollment of patients in the worst quintile for SBP was 85%±2%, 86%±2% for HR, and 84%±2% for SBP/HR versus 91%±1% for the middle 3 quintiles (P<.001). Hospitalization occurred more frequently than mortality but with a similar pattern among quintiles. One-year survival after first follow-up of patients in the worst quintile for change (∆) in SBP since enrollment was 85%±2% (P=.006), 86%±2% for ∆HR (P=.091), and 84%±2% for ∆SBP/HR (P=.011) versus the middle 3 quintiles (∆SBP:91%±1%; ∆HR:90%±1%; ∆SBP/HR:90%±1%).

Conclusions:  Changes in vital signs from enrollment to first follow-up were less predictive of mortality than the values of vital sign parameters at either enrollment or first follow-up. HR, SBP, and SBP/HR at enrollment identified high-risk groups with survival differences of 5%–7% and freedom from hospitalization differences of 9%–11% versus lower-risk groups. SBP/HR defines the highest-risk group, including most of the high-risk patients defined by HR and SBP separately.ClinicalTrials.gov Registration Number: NCT00370214

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  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543