Clinical Outcomes of Patients with Combined Idiopathic Pulmonary Fibrosis and Emphysema in the IPF-PRO Registry.

PURPOSE: To assess the impact of concomitant emphysema on outcomes in patients with idiopathic pulmonary fibrosis (IPF). METHODS: The IPF-PRO Registry is a US registry of patients with IPF. The presence of combined pulmonary fibrosis and emphysema (CPFE) at enrollment was determined by investigators' review of an HRCT scan. Associations between emphysema and clinical outcomes were analyzed using Cox proportional hazards models. RESULTS: Of 934 patients, 119 (12.7%) had CPFE. Compared with patients with IPF alone, patients with CPFE were older (median 72 vs 70 years); higher proportions were current/former smokers (88.2% vs 63.7%), used oxygen with activity (49.6% vs 31.9%) or at rest (30.8% vs 18.4%), had congestive heart failure (13.6% vs 4.8%) and had prior respiratory hospitalization (25.0% vs 16.7%); they had higher FVC (median 71.8 vs 69.4% predicted) and lower DLco (median 35.3 vs 43.6% predicted). In patients with CPFE and IPF alone, respectively, at 1 year, rates of death or lung transplant were 17.5% (95% CI: 11.7, 25.8) and 11.2% (9.2, 13.6) and rates of hospitalization were 21.6% (14.6, 29.6) and 20.6% (17.9, 23.5). There were no significant associations between emphysema and any outcome after adjustment for baseline variables. No baseline variable predicted outcomes better in IPF alone than in CPFE. CONCLUSION: Approximately 13% of patients in the IPF-PRO Registry had CPFE. Physiologic characteristics and comorbidities of patients with CPFE differed from those of patients with IPF alone, but the presence of emphysema did not drive outcomes after adjustment for baseline covariates. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01915511; registered August 5, 2013.

Clinical and vital sign changes associated with late-onset sepsis in very low birth weight infants at 3 NICUs.

BACKGROUND: In premature infants, clinical changes frequently occur due to sepsis or non-infectious conditions, and distinguishing between these is challenging. Baseline risk factors, vital signs, and clinical signs guide decisions to culture and start antibiotics. We sought to compare heart rate (HR) and oxygenation (SpO2) patterns as well as baseline variables and clinical signs prompting sepsis work-ups ultimately determined to be late-onset sepsis (LOS) and sepsis ruled out (SRO). METHODS: At three NICUs, we reviewed records of very low birth weight (VLBW) infants around their first sepsis work-up diagnosed as LOS or SRO. Clinical signs prompting the evaluation were determined from clinician documentation. HR-SpO2 data, when available, were analyzed for mean, standard deviation, skewness, kurtosis, and cross-correlation. We used LASSO and logistic regression to assess variable importance and associations with LOS compared to SRO. RESULTS: We analyzed sepsis work-ups in 408 infants (173 LOS, 235 SRO). Compared to infants with SRO, those with LOS were of lower GA and BW, and more likely to have a central catheter and mechanical ventilation. Clinical signs cited more often in LOS included hypotension, acidosis, abdominal distension, lethargy, oliguria, and abnormal CBC or CRP(p < 0.05). HR-SpO2 data were available in 266 events. Cross-correlation HR-SpO2 before the event was associated with LOS after adjusting for GA, BW, and postnatal age. A model combining baseline, clinical and HR-SpO2 variables had AUC 0.821. CONCLUSION: In VLBW infants at 3-NICUs, we describe the baseline, clinical, and HR-SpO2 variables associated with LOS versus SRO.

Blood pressure ranges via non-invasive and invasive monitoring techniques in premature neonates using high resolution physiologic data.

BACKGROUND: There are limited evidence-based published blood pressure ranges for premature neonates. The aim of the study was to determine blood pressure ranges in a large cohort of premature neonates based on gestational and post-menstrual age. METHODS: Retrospective observational study of premature neonates admitted to the neonatal intensive care unit at our institution between January 2009 and October 2015. We stratified data by gestational and post-menstrual age groups as well as by method of blood pressure measurement (non-invasive vs. invasive). RESULTS: Over two billion blood pressure values in 1708 neonates were analyzed to generate heat maps and establish percentile-based reference ranges. The median gestational age of the cohort was 31 weeks (IQR 28-33 weeks). We found moderate correlation (r = 0.57) between simultaneously obtained non-invasive and invasive blood pressure measurements. CONCLUSIONS: Our results can serve as a reference during the bedside assessment of the critically-ill neonate.

Study protocol for targeted interventions to prevent chronic low back pain in high-risk patients: A multi-site pragmatic cluster randomized controlled trial (TARGET Trial).

BACKGROUND: Low back pain (LBP) is one of the most prevalent and potentially disabling conditions for which people seek health care. Patients, providers, and payers agree that greater effort is needed to prevent acute LBP from transitioning to chronic LBP. METHODS AND STUDY DESIGN: The TARGET (Targeted Interventions to Prevent Chronic Low Back Pain in High-Risk Patients) Trial is a primary care-based, multisite, cluster randomized, pragmatic trial comparing guideline-based care (GBC) to GBC + referral to Psychologically Informed Physical Therapy (PIPT) for patients presenting with acute LBP and identified as high risk for persistent disabling symptoms. Study sites include primary care clinics within each of five geographical regions in the United States, with clinics randomized to either GBC or GBC + PIPT. Acute LBP patients at all clinics are risk stratified (high, medium, low) using the STarT Back Tool. The primary outcomes are the presence of chronic LBP and LBP-related functional disability determined by the Oswestry Disability Index at 6 months. Secondary outcomes are LBP-related processes of health care and utilization of services over 12 months, determined through electronic medical records. Study enrollment began in May 2016 and concluded in June 2018. The trial was powered to include at least 1860 high-risk patients in the randomized controlled trial cohort. A prospective observational cohort of approximately 6900 low and medium-risk acute LBP patients was enrolled concurrently. DISCUSSION: The TARGET pragmatic trial aims to establish the effectiveness of the stratified approach to acute LBP intervention targeting high-risk patients with GBC and PIPT. TRIAL REGISTRATION: ClinicalTrials.govNCT02647658 Registered Jan. 6, 2016.

Waveguide effects and implications for cardiac magnetic resonance elastography: A finite element study.

Magnetic resonance elastography (MRE) is increasingly being applied to thin or small structures in which wave propagation is dominated by waveguide effects, which can substantially bias stiffness results with common processing approaches. The purpose of this work was to investigate the importance of such biases and artifacts on MRE inversion results in: (i) various idealized 2D and 3D geometries with one or more dimensions that are small relative to the shear wavelength; and (ii) a realistic cardiac geometry. Finite element models were created using simple 2D geometries as well as a simplified and a realistic 3D cardiac geometry, and simulated displacements acquired by MRE from harmonic excitations from 60 to 220 Hz across a range of frequencies. The displacement wave fields were inverted with direct inversion of the Helmholtz equation with and without the application of bandpass filtering and/or the curl operator to the displacement field. In all geometries considered, and at all frequencies considered, strong biases and artifacts were present in inversion results when the curl operator was not applied. Bandpass filtering without the curl was not sufficient to yield accurate recovery. In the 3D geometries, strong biases and artifacts were present in 2D inversions even when the curl was applied, while only 3D inversions with application of the curl yielded accurate recovery of the complex shear modulus. These results establish that taking the curl of the wave field and performing a full 3D inversion are both necessary steps for accurate estimation of the shear modulus both in simple thin-walled or small structures and in a realistic cardiac geometry when using simple inversions that neglect the hydrostatic pressure term. In practice, sufficient wave amplitude, signal-to-noise ratio, and resolution will be required to achieve accurate results.

Early Pulse Oximetry Data Improves Prediction of Death and Adverse Outcomes in a Two-Center Cohort of Very Low Birth Weight Infants.

BACKGROUND: We previously showed, in a single-center study, that early heart rate (HR) characteristics predicted later adverse outcomes in very low birth weight (VLBW) infants. We sought to improve predictive models by adding oxygenation data and testing in a second neonatal intensive care unit (NICU). METHODS: HR and oxygen saturation (SpO2) from the first 12 hours and first 7 days after birth were analyzed for 778 VLBW infants at two NICUs. Using multivariate logistic regression, clinical predictive scores were developed for death, severe intraventricular hemorrhage (sIVH), bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity (tROP), late-onset septicemia (LOS), and necrotizing enterocolitis (NEC). Ten HR-SpO2 measures were analyzed, with first 12 hours data used for predicting death or sIVH and first 7 days for the other outcomes. HR-SpO2 models were combined with clinical models to develop a pulse oximetry predictive score (POPS). Net reclassification improvement (NRI) compared performance of POPS with the clinical predictive score. RESULTS: Models using clinical or pulse oximetry variables alone performed well for each outcome. POPS performed better than clinical variables for predicting death, sIVH, and BPD (NRI > 0.5, p < 0.01), but not tROP, LOS, or NEC. CONCLUSION: Analysis of early HR-SpO2 characteristics adds to clinical risk factors to predict later adverse outcomes in VLBW infants.

MR Elastography Analysis of Glioma Stiffness and IDH1-Mutation Status.

BACKGROUND AND PURPOSE: Our aim was to noninvasively evaluate gliomas with MR elastography to characterize the relationship of tumor stiffness with tumor grade and mutations in the isocitrate dehydrogenase 1 (IDH1) gene. MATERIALS AND METHODS: Tumor stiffness properties were prospectively quantified in 18 patients (mean age, 42 years; 6 women) with histologically proved gliomas using MR elastography from 2014 to 2016. Images were acquired on a 3T MR imaging unit with a vibration frequency of 60 Hz. Tumor stiffness was compared with unaffected contralateral white matter, across tumor grade, and by IDH1-mutation status. The performance of the use of tumor stiffness to predict tumor grade and IDH1 mutation was evaluated with the Wilcoxon rank sum, 1-way ANOVA, and Tukey-Kramer tests. RESULTS: Gliomas were softer than healthy brain parenchyma, 2.2 kPa compared with 3.3 kPa (P < .001), with grade IV tumors softer than grade II. Tumors with an IDH1 mutation were significantly stiffer than those with wild type IDH1, 2.5 kPa versus 1.6 kPa, respectively (P = .007). CONCLUSIONS: MR elastography demonstrated that not only were gliomas softer than normal brain but the degree of softening was directly correlated with tumor grade and IDH1-mutation status. Noninvasive determination of tumor grade and IDH1 mutation may result in improved stratification of patients for different treatment options and the evaluation of novel therapeutics. This work reports on the emerging field of "mechanogenomics": the identification of genetic features such as IDH1 mutation using intrinsic biomechanical information.

Author Correction: Demonstration of sub-luminal propagation of single-cycle terahertz pulses for particle acceleration.

The original version of this Article contained an error in the abstract, referring to "multi-megawatt-per-metre" instead of "multi-megavolt-per-metre". This has now been corrected in both the PDF and HTML versions of the Article.

Demonstration of sub-luminal propagation of single-cycle terahertz pulses for particle acceleration.

The sub-luminal phase velocity of electromagnetic waves in free space is generally unobtainable, being closely linked to forbidden faster than light group velocities. The requirement of sub-luminal phase-velocity in laser-driven particle acceleration schemes imposes a limit on the total acceleration achievable in free space, and necessitates the use of dispersive structures or waveguides for extending the field-particle interaction. We demonstrate a travelling source approach that overcomes the sub-luminal propagation limits. The approach exploits ultrafast optical sources with slow group velocity propagation, and a group-to-phase front conversion through nonlinear optical interaction. The concept is demonstrated with two terahertz generation processes, nonlinear optical rectification and current-surge rectification. We report measurements of longitudinally polarised single-cycle electric fields with phase and group velocity between 0.77c and 1.75c. The ability to scale to multi-megavolt-per-metre field strengths is demonstrated. Our approach paves the way towards the realisation of cheap and compact particle accelerators with femtosecond scale control of particles.Controlled generation of terahertz radiation with subluminal phase velocities is a key issue in laser-driven particle acceleration. Here, the authors demonstrate a travelling-source approach utilizing the group-to-phase front conversion to overcome the sub-luminal propagation limit.

Recombinant human pentraxin-2 therapy in patients with idiopathic pulmonary fibrosis: safety, pharmacokinetics and exploratory efficacy.

Abnormal fibrogenic repair response upon alveolar injury is believed to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). PRM-151 (recombinant human pentraxin-2, also known as serum amyloid P), has been shown to reduce fibrosis in preclinical lung fibrosis models, and was well tolerated with a favourable pharmacokinetic profile in an earlier single-dose phase I study.A randomised, double-blind, placebo-controlled, multiple ascending dose trial was performed to assess the tolerability and pharmacokinetic and pharmacodynamic characteristics of multiple doses of PRM-151 in IPF patients. Subjects in three successive cohorts (1, 5, or 10 mg·kg(-1) versus placebo) received intravenous study drug on days 1, 3, 5, 8 and 15, and were followed-up to day 57.PRM-151 was well tolerated at all dose levels, with no serious adverse reactions. Administration of PRM-151 resulted in two- to eight-fold dose-dependent increases in circulating pentraxin-2 levels. Forced vital capacity and 6-min walk test showed trends towards improvement in the combined PRM-151 dose groups. On high-resolution computed tomography scans, stable or improved lung volume unoccupied by interstitial lung abnormality was noted in some PRM-151 subjects compared to placebo subjects on day 57.The efficacy of PRM-151 in IPF remains to be investigated in dedicated future trials.

Corneal collagen crosslinking for keratoconus or corneal ectasia without epithelial debridement.

PURPOSE: Corneal collagen crosslinking (CXL) is a relatively new technique to reduce the progression of keratoconus. The technique can be performed with or without complete debridement of the corneal epithelium. We describe a novel intermediate technique involving mechanical disruption of the epithelium, and evaluate its safety and efficacy. METHODS: The case notes of 128 eyes with progressive keratoconus or iatrogenic corneal ectasia who had undergone CXL using the epithelial disruption technique were retrospectively reviewed. Thin corneas were treated with hypotonic riboflavin. All others were treated with an isotonic solution. Note was made of preoperative and postoperative parameters, including uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), refraction, endothelial cell count, and corneal tomography. Occurrence of procedure-related complications was recorded. Statistical analyses were performed using the paired sample t-test and Wilcoxon signed-rank test, with a level of P<0.05 being accepted as statistically significant. RESULTS: At 12 months, 41.8% of patients treated with isotonic riboflavin had improved UCVA and 29.7% had improved BSCVA. Only 13.4% lost lines of UCVA and 14.9% lost BSCVA. Of the patients treated with hypotonic riboflavin, at 12 months, 75% demonstrated stability of BSCVA and 25% had stable Kmax. In addition, 25% showed improved visual acuity at 12 months, and 58.3% showed regression of their Kmax. Our rate of short-term complications was comparable to studies using complete epithelial removal. CONCLUSIONS: CXL with epithelial disruption is a safe and effective treatment for keratoconus or iatrogenic corneal ectasia, and may be better tolerated by patients than the epithelium-off technique.

Quantitative proteomics of bronchoalveolar lavage fluid in idiopathic pulmonary fibrosis.

The proteomic analysis of bronchoalveolar lavage fluid (BALF) can give insight into pulmonary disease pathology and response to therapy. Here, we describe the first gel-free quantitative analysis of BALF in idiopathic pulmonary fibrosis (IPF), a chronic and fatal scarring lung disease. We utilized two-dimensional reversed-phase liquid chromatography and ion-mobility-assisted data-independent acquisition (HDMSE) for quantitation of >1000 proteins in immunodepleted BALF from the right middle and lower lobes of normal controls and patients with IPF. Among the analytes that were increased in IPF were well-described mediators of pulmonary fibrosis (osteopontin, MMP7, CXCL7, CCL18), eosinophil- and neutrophil-derived proteins, and proteins associated with fibroblast foci. For additional discovery and targeted validation, BALF was also screened by multiple reaction monitoring (MRM), using the JPT Cytokine SpikeMix library of >400 stable isotope-labeled peptides. A refined MRM assay confirmed the robust expression of osteopontin, and demonstrated, for the first time, upregulation of the pro-fibrotic cytokine, CCL24, in BALF in IPF. These results show the utility of BALF proteomics for the molecular profiling of fibrotic lung diseases and the targeted quantitation of soluble markers of IPF. More generally, this study addresses critical quality control measures that should be widely applicable to BALF profiling in pulmonary disease.

Sterile keratitis after combined riboflavin-UVA corneal collagen cross-linking for keratoconus.

PURPOSE: To investigate patient risk factors and to look for potential causes of sterile infiltrates following an unexpected cluster of sterile keratitis after a routine collagen cross-linking (CXL) list. METHODS: The records of all 148 cases of CXL were reviewed retrospectively. The equipment and solutions used and our clinic's standard operating procedure for CXL were reviewed. An in-vitro experiment to explore the variation in ultraviolet A (UVA) irradiance from fluctuations in the working distance of the UVA lamp was conducted. RESULTS: The four patients who developed sterile infiltrates had steeper maximum corneal curvatures (68.0±7.3 D) and thinner pachymetry (389.9±49.0 µm) than the 144 who did not (57.0±8.2 D, P=0.05; 454.6±45.4 µm, P=0.08). A corneal curvature of >60 Dand a pachymetry of <425 µm were significant risk factors. All four affected cases obtained a complete resolution with topical antibiotics and steroids. The unaided VA and the maximum K improved from their pre-operative levels in three out of four patients. A 2-mm reduction in distance of the VEGA C.B.M. X-Linker from a treated surface increased irradiance to 3.5-3.7 mW/cm(2), which is above the threshold for endothelial toxicity. CONCLUSION: Patients with thinner and steeper corneas are at an increased risk of developing sterile keratitis. The visual outcomes despite this complication are good.

Abnormal heart rate characteristics are associated with abnormal neuroimaging and outcomes in extremely low birth weight infants.

OBJECTIVE: Brain injury in preterm infants may lead to an inflammatory response and central nervous system dysfunction reflected by abnormal heart rate characteristics (HRC). We hypothesized that a continuously monitored HRC index reflecting reduced HR variability and decelerations correlates with abnormal neuroimaging and outcomes in extremely low birth weight infants (ELBW). STUDY DESIGN: We analyzed the average HRC index within 28 days after birth (aHRC28) and head ultrasound (HUS) in 384 ELBW infants. In 50 infants with brain magnetic resonance imaging (MRI) and 70 infants with Bayley neurodevelopmental testing at 1 year of age, we analyzed the relationship between aHRC28, MRI abnormalities and low Bayley scores. RESULT: aHRC28 was higher in infants with severe HUS abnormalities (2.65±1.27 for Grade III-IV intraventricular hemorrhage (IVH) or cystic periventricular leukomalacia (cPVL) versus 1.72±0.95 for normal or Grade I-II IVH, P<0.001). Higher aHRC28 was also associated with white matter damage on MRI and death or Bayley motor or mental developmental index <70. Associations persisted after adjusting for gestational age, birth weight and septicemia. For every one point increase in aHRC28, the odds ratio of death or Bayley score <70 was 2.45 (95% CI 1.46, 4.05, P<0.001). CONCLUSION: A continuously monitored HRC index provides an objective, noninvasive measure associated with abnormal brain imaging and adverse neurologic outcomes in ELBW infants.

Endoscopic ultrasonography-guided portal injection chemotherapy for hepatic metastases.

INTRODUCTION: We hypothesized that endoscopic ultrasonography-guided portal injection chemotherapy (EPIC) using irinotecan-loaded microbeads may achieve increased intrahepatic concentrations, while decreasing systemic exposure. This may achieve enhanced efficacy for the treatment of diffuse liver metastases, while decreasing systemic toxicities. MATERIALS AND METHODS: In eight anesthetized 35 kg pigs, EPIC was performed transgastrically using the linear-array echoendoscope and a 22 g fine-needle aspiration. In four animals, irinotecan (100 mg) loaded onto 75-150 micron liquid chromatography (LC) beads was injected. In four animals, saline was injected into the portal vein and unloaded irinotecan (100 mg) was injected into the jugular vein. Plasma (every 15 min), and at 1 h bone marrow, liver and skeletal muscle samples were obtained. Irinotecan and SN-38 (active metabolite) concentrations were assayed by LC/mass spectrometry. RESULTS: The procedure was performed safely in all eight animals. Compared with systemic administration, EPIC resulted in almost twice the hepatic concentration of irinotecan (6242 vs. 3692 ng/g) and half the systemic concentrations in plasma (1092 vs. 2762 ng/mL), bone marrow (815 vs. 1703 ng/mL) and skeletal muscle (521 vs. 1058 ng/g). SN-38 levels were lower with EPIC (liver: 166 vs. 681 ng/g; plasma: 1.8 vs. 2.4 ng/mL; bone marrow: 0.9 vs. 1.4 ng/mL; muscle 4.6 vs. 9.2 ng/g). Liver histology showed the beads within small portal venules. CONCLUSIONS: EPIC using irinotecan-loaded microbeads can enhance hepatic exposure to irinotecan, while decreasing systemic concentrations. SN-38 levels were lower with EPIC indicating that a substantial portion of the irinotecan was still loaded onto beads. The microbeads may act as a reservoir resulting in prolonged hepatic drug exposure.

Application of dynamical analyses of heart rate to rhythm classification and prognosis.

We have developed numerical approaches to dynamical analysis of heart rates, measured as interbeat or RR, intervals, based on entropy and fluctuation analyses in a large data base of consecutive Holter monitor recordings. In Part I, we present a RR interval-based classifier that distinguishes normal sinus rhythm (NSR), atrial fibrillation (AF) and sinus rhythm with ectopy with an accuracy of 99%, 81% and 77%respectively, using 10-minute segments. In Part II, we present 2-year mortality estimation based on the entropy calculations. The major finding is that normal dynamics identify a very low risk group. Taken together, these results point to automated analysis of heart rate time series with important clinical applications.

Abnormal heart rate characteristics before clinical diagnosis of necrotizing enterocolitis.

OBJECTIVE: Earlier diagnosis and treatment of necrotizing enterocolitis (NEC) in preterm infants, before clinical deterioration, might improve outcomes. A monitor that measures abnormal heart rate characteristics (HRC) of decreased variability and transient decelerations was developed as an early warning system for sepsis. As NEC shares pathophysiologic features with sepsis, we tested the hypothesis that abnormal HRC occur before clinical diagnosis of NEC. STUDY DESIGN: Retrospective review of Bells stage II to III NEC cases among infants <34 weeks gestation enrolled in a prospective randomized clinical trial of HRC monitoring at three neonatal intensive care units. RESULT: Of 97 infants with NEC and HRC data, 33 underwent surgical intervention within 1 week of diagnosis. The baseline HRC index from 1 to 3 days before diagnosis was higher in patients who developed surgical vs medical NEC (2.06±1.98 vs 1.22±1.10, P=0.009). The HRC index increased significantly 16 h before the clinical diagnosis of surgical NEC and 6 h before medical NEC. At the time of clinical diagnosis, the HRC index was higher in patients with surgical vs medical NEC (3.3±2.2 vs 1.9±1.7, P<0.001). CONCLUSION: Abnormal HRC occur before clinical diagnosis of NEC, suggesting that continuous HRC monitoring may facilitate earlier detection and treatment.

Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterized by formation and proliferation of fibroblast foci. Endothelin-1 induces lung fibroblast proliferation and contractile activity via the endothelin A (ETA) receptor. OBJECTIVE: To determine whether ambrisentan, an ETA receptor-selective antagonist, reduces the rate of IPF progression. DESIGN: Randomized, double-blind, placebo-controlled, event-driven trial. (ClinicalTrials.gov: NCT00768300). SETTING: Academic and private hospitals. PARTICIPANTS: Patients with IPF aged 40 to 80 years with minimal or no honeycombing on high-resolution computed tomography scans. INTERVENTION: Ambrisentan, 10 mg/d, or placebo. MEASUREMENTS: Time to disease progression, defined as death, respiratory hospitalization, or a categorical decrease in lung function. RESULTS: The study was terminated after enrollment of 492 patients (75% of intended enrollment; mean duration of exposure to study medication, 34.7 weeks) because an interim analysis indicated a low likelihood of showing efficacy for the end point by the scheduled end of the study. Ambrisentan-treated patients were more likely to meet the prespecified criteria for disease progression (90 [27.4%] vs. 28 [17.2%] patients; P = 0.010; hazard ratio, 1.74 [95% CI, 1.14 to 2.66]). Lung function decline was seen in 55 (16.7%) ambrisentan-treated patients and 19 (11.7%) placebo-treated patients (P = 0.109). Respiratory hospitalizations were seen in 44 (13.4%) and 9 (5.5%) patients in the ambrisentan and placebo groups, respectively (P = 0.007). Twenty-six (7.9%) patients who received ambrisentan and 6 (3.7%) who received placebo died (P = 0.100). Thirty-two (10%) ambrisentan-treated patients and 16 (10%) placebo-treated patients had pulmonary hypertension at baseline, and analysis stratified by the presence of pulmonary hypertension revealed similar results for the primary end point. LIMITATION: The study was terminated early. CONCLUSION: Ambrisentan was not effective in treating IPF and may be associated with an increased risk for disease progression and respiratory hospitalizations. PRIMARY FUNDING SOURCE: Gilead Sciences.

Using a venous thromboembolism checklist significantly improves VTE prevention: a junior doctor led intervention.

AIMS: Given that venous thromboembolic disease is a significant cause of morbidity and mortality, the aim of this study was to increase the rate of VTE risk assessment performed by junior doctors in the acute setting. We also wanted to increase the rates of prescription of thromboembolic preventative measures in those patients whom the assessment identified as being high risk. METHODS: A survey of all patients admitted to three medical wards over a 3-week period was performed to determine whether VTE risk assessment had been performed, and whether prescription of prophylactic measures had been carried out where appropriate. A prompt sheet was subsequently attached to the drug card, and the survey repeated to assess impact on risk assessment and prescription rates. RESULTS: Use of the prompt sheet significantly increased the percentage of patients being appropriately prescribed VTE prophylaxis. CONCLUSIONS/MESSAGE FOR THE CLINIC: Most physicans are aware of the risk of VTE to inpatients, but because of human factors throughout the daily ward activities, VTE assessment can be missed. A simple intervention such as a VTE assessment prompt sheet on the front of the drug card can significantly improve VTE assessment and therefore patient safety.