Online First

Abstract 

Background:  Heparin-induced thrombocytopenia (HIT) is diagnosed using clinical criteria and detection of platelet-activating anti-platelet factor 4/heparin (PF4/H) antibodies, usually through a surrogate enzyme-linked immunosorbent assay (ELISA). The high false positive rate (FPR) of this ELISA prompted us to re-examine its interpretation.

Methods:  We analyzed anti-PF4/H ELISA results from a previously published dataset of 1958 patients, using clinical suspicion and serotonin-release assay (SRA) to diagnose HIT. We performed receiver operating characteristic (ROC) analysis using stratum-specific likelihood ratios (SSLRs) and used Bayes’ theorem to construct a clinical decision-support algorithm.

Results:  The most discriminant single cutoff by anti-PF4/H ELISA for the diagnosis of HIT was found to be 0.8 optical density (OD) units, not 0.4 OD (currently accepted practice). This change reduced the FPR from 31% to 6% (95%CI: 5%-8%). ELISA results were grouped into five strata, which yielded SSLRs ranging from 0.02 (strongly ruling HIT out) to 104.4 (strongly ruling HIT in). Comparison of ROC curves demonstrated that this five-strata approach is statistically more accurate than current accepted practice at discriminating whether patients have HIT or not (AUROC 0.97 (95%CI0.93-1.00) vs. 0.83, (95%CI:0.80-0.89)). Our decision-support algorithm incorporated clinical assessment into this stratified model, and clarified HIT diagnosis with a high degree of certainty and without the need for SRA testing in ∼90% of patients.

Conclusions:  Diagnostic accuracy of the anti-PF4/heparin ELISA can be optimized by using a higher cutoff, and a stratified interpretation of the results. Our algorithm should significantly reduce over-diagnosis of HIT and the need for SRA testing.

Abstract 

Background:  Evidence-based guidelines recommend mediastinal sampling as the first invasive test in patients with suspected lung cancer and mediastinal adenopathy. The goal of this study was to assess practice patterns and outcomes of diagnostic strategies in this patient population.

Methods:  We conducted a retrospective analysis of all patients in 2009 that had mediastinal adenopathy without distant metastatic disease to determine whether or not guideline consistent care was delivered. Guideline consistent care was defined as mediastinal lymph node sampling being performed as part of the first invasive procedure.

Results:  137 patients were included. Guideline consistent care was provided in 30 (22%) cases. Patients receiving guideline consistent care had fewer invasive tests than patients with guideline inconsistent care (1.3 ± 0.5 vs. 2.3 ± 0.5 tests/patient respectively, p<0.0001) and fewer complications (0 of 30, 0% vs. 18 of 108, 17%; p=0.01). Most of the complications (16 of 18) were related to CT guided needle biopsy. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was sufficient to guide treatment decisions without any other invasive tests in 88 (64%) patients. While not all of the complications and costs due to CT guided biopsies could have been avoided, roughly two thirds could have been eliminated by just changing the testing sequence.

Conclusion:  Quality gaps in lung cancer staging in patients with mediastinal adenopathy are common and lead to unnecessary testing and increased complications. In patients with suspected lung cancer without distant metastatic disease with mediastinal adenopathy, EBUS-TBNA should be the first test.

Abstract 

Background:  The executive committee of the American College of Chest Physicians 9th edition of the Antithrombotic guidelines (AT9) developed a strategy to limit the impact of conflict of interest (COI) on recommendations. This policy excluded conflicted panelists from voting on recommendations with which they had conflicts. The objective of the study is to explore the compliance of the attendees of the AT9 final conference.

Methods:  We conducted a survey and reviewed public declarations of COI of all the final AT9 conference attendees. For each of the controversies on which voting occurred (9 of 628 total recommendations), we estimated the compliance with COI policy as the proportion of attendees who recused themselves from voting on controversies for which they were conflicted. In order to evaluate the potential effect of non-compliance, we assumed that every vote cast by an ineligible conference attendee was cast in direction of the majority vote.

Results:  Sixty-three panelists voted in at least one controversy at the final conference; the percentage of conflicted panelists varied from 6% to 39% for eight controversies. The compliance with the COI policy was 14/14 (100%) for one controversy, and varied from 1/19 (5%) to 1/3 (33%) in the remaining seven. In two of the eight controversies (“Compression Device plus Aspirin versus LMWH in tromboprophylaxis in orthopedic surgery” and “LMWH versus vitamin K antagonists for treatment”) the low compliance may have affected the final recommendations

Conclusions:  The low compliance raises concerns about implementation of COI restrictions in the context of anonymous voting.

Abstract 

Background:  Minimally symptomatic obstructive sleep apnea (OSA) is a highly prevalent disorder and the effects of continuous positive airway pressure (CPAP) on vascular function in these patients are unknown. This trial aimed to investigate whether CPAP improves vascular function in minimally symptomatic OSA.

Methods:  In two centres taking part in the MOSAIC trial 253 patients with minimally symptomatic OSA were randomized to 6 months of CPAP or standard care. 208 patients attended their follow-up visit within the predefined time window and had complete measurements of arterial stiffness (augmentation index, AIx) and 64 patients had endothelial function measurements by brachial artery flow-mediated dilatation (FMD). Multivariable analyses adjusting for baseline measurements and minimisation factors were performed to assess the effect of CPAP treatment on FMD (%dilatation) and AIx (%augmentation) compared to standard care.

Results:  The mean±SD baseline oxygen desaturation index and Epworth sleepiness score (ESS) of the 208 patients (age 58±7.3 years, 31 females) were 13.7±12.8 events/hour and 8.3±4.2, respectively. There was no CPAP treatment effect on arterial stiffness (AI_x, -1.4%, 95% CI -3.6 to +0.9%, p=0.23), but CPAP improved endothelial function (FMD, +2.1%, 95% CI +1.0 to +3.2%, p<0.0001). CPAP reduced daytime sleepiness (ESS, -2.2, 95% CI -3.0 to -1.5, p<0.0001) compared to standard care. There was a larger improvement in FMD in patients using CPAP for more than 4 hours/night than those who used it less (p=0.013).

Conclusions:  CPAP improves endothelial function, but not arterial stiffness in minimally symptomatic OSA. Thus minimally symptomatic OSA may be a cardiovascular risk factor.

Clinical Trial registration:  ISRCTN 34164388 (http://isrctn.org)

Background:  Lung cytotoxic mechanisms trigger the release of Perforin and Granzymes, causing oxidative DNA damage that ultimately leads to apoptosis. These effects, although demonstrated in chronic obstructive pulmonary disease (COPD), have not been investigated in patients with asthma and in particular in smoking asthmatics. Our aim was to measure Perforin, Granzyme A, Granzyme B and 8-OHdG expression in sputum from smoking and non-smoking asthmatics, compared to smoking and non-smoking controls.

Methods:  Perforin, Granzyme A, Granzyme B and 8-OHdG expression levels were detected by ELISA assays, in induced sputum specimens.

Results:  Perforin expression was increased in 40% of smokers and 45% of smoking asthmatics, while only in 7% of asthma patients (p=0.004), compared to controls’ values. In contrast, Granzymes A and B levels were increased in more that 40% of patients in all three groups versus controls. Finally, 8-OHdG levels were elevated in 35% of smoking asthmatics, in 20% of smokers and only in 10% of asthma patients. Statistical analysis revealed a positive correlation between Granzyme A (p<0.001) and Granzyme B (p=0.006) expression levels and the number of pack-years in smoking asthmatic patients.

Conclusions:  Asthma cytotoxic immune response is mainly represented by Granzymes A and B, while in smoking asthmatics Perforin and 8-OHdG are additionally involved, resembling the immune response in COPD.

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 FEF_25-75/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.

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 [IQR_25,75 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 [IQR_25,75 1.2, 4.4] vs. 2.8 years [IQR_25,75 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.