Measurements of absolute, single charge-exchange cross sections of H+, He+ and He2+ with H2O and CO2

Absolute measurements have been made of single-electron charge-exchange cross sections of H+, He+, and He2+ in H2O and CO2 in the energy range 0.3-7.5 keV amu(-1). Collisions of this type occur in the interaction of solar wind ions with cometary gases and have been observed by the Giotto spacecraft using the Ion Mass Spectrometer/High Energy Range Spectrometer (IMS/HERS) during a close encounter with comet Halley in 1986. Increases in the He+ ion density, and in the He2+ to H+ density ratio were reported by Shelley et al, and Fuselier et al. and were explained by charge exchange. However, the lack of reliable cross sections for this process made interpretation of the data difficult. New cross sections are presented and discussed in relation to the Giotto observations.

Extravascular lung water indexed to predicted body weight is a novel predictor of intensive care unit mortality in patients with acute lung injury

Objectives: Acute lung injury and the acute respiratory distress syndrome are characterized by noncardiogenic pulmonary edema, which can be assessed by measurement of extravascular lung water. Traditionally, extravascular lung water has been indexed to actual body weight (mL/kg). Because lung size is dependent on height rather than weight, we hypothesized indexing to predicted body weight may be a better predictor of mortality in acute lung injury/acute respiratory distress syndrome.

ABSOLUTE DOUBLY DIFFERENTIAL CROSS-SECTIONS FOR ELECTRON-EMISSION IN COLLISIONS OF 3.5-MEV/U FE(17+) AND FE(22+) IONS WITH HE AND AR GAS TARGETS

Absolute doubly differential cross sections have been measured as a function of electron energy and angle of observation for electron emission in collisions of 3.5-MeV/u Fe17+ and Fe22+ ions with He and Ar gas targets under single-collision conditions. The measured electron emission cross sections are compared to theoretical and scaled cross sections based on the Born approximation. The results using intermediate-mass ions are discussed with reference to previously reported cross sections from collisions with highly charged lighter- and heavier-ion species at MeV/u projectile energies. The continuum-distorted-wave-eikonal-initial-state approximation shows good agreement with experiments except in the

Low-pressure solubilities and thermodynamics of solvation of eight gases in 1-butyl-3-methylimidazolium hexafluorophosphate

Experimental values for the solubility of carbon dioxide, ethane, methane, oxygen, nitrogen, hydrogen, argon and carbon monoxide in 1-butyl-3-methylimidazolium hexafluorophosphate, [bmim][PF6] - a room temperature ionic liquid - are reported as a function of temperature between 283 and 343 K and at pressures close to atmospheric. Carbon dioxide is the most soluble and hydrogen is the least soluble of the gases studied with mole fraction solubilities of the order of 10-2 and 10-4, respectively. All the mole fraction solubilities decrease with temperature except for hydrogen for which a maximum is observed at temperatures close to 310 K. From the variation of solubility, expressed as Henry's law constants, with temperature, the partial molar thermodynamic functions of solvation such as the standard Gibbs energy, the enthalpy, and the entropy are calculated. The precision of the experimental data, considered as the average absolute deviation of the Henry's law constants from appropriate smoothing equations, is better than ±1%. © 2005 Elsevier B.V. All rights reserved.

Lack of effect of glutamine administration to boost the innate immune system response in trauma patients in the intensive care unit

The use of glutamine as a dietary supplement is associated with a reduced risk of infection. We hypothesized that the underlying mechanism could be an increase in the expression and/or functionality of Toll-like receptors (TLR), key receptors sensing infections. The objective of this study was to evaluate whether glutamine supplementation alters the expression and functionality of TLR2 and TLR4 in circulating monocytes of trauma patients admitted to the intensive care unit (ICU).

Impaired lung function and Health Status in Adult Survivors of Bronchopulmonary Dysplasia

More infants with bronchopulmonary dysplasia (BPD) now survive to adulthood but little is known regarding persisting respiratory impairment. We report respiratory symptoms, lung function and health-related quality of life (HRQoL) in adult BPD survivors compared with preterm (non-BPD) and full term (FT) controls.

Respiratory symptoms (European Community Respiratory Health Survey) and HRQoL [EuroQol 5D (EQ-5D)] were measured in 72 adult BPD survivors [mean(SD) study age 24.1(4.0)y; mean(SD) gestational age (GA)=27.1(2.1)wk; mean(SD) birth weight (BW)=955(256)g] cared for in the Regional Neonatal Intensive Care Unit, Belfast (between 1978 and 1993) were compared with 57 non-BPD controls [mean(SD) study age 25.3(4.0)y; mean(SD) GA 31.0(2.5)wk; mean(SD) BW 1238(222)g] and 78 FT controls [mean(SD) study age 25.7(3.8)y; mean(SD) GA=39.7(1.4)wk; mean(SD) BW=3514(456)g] cared for at the same hospital. Spirometry was performed on 56 BPD, 40 non-BPD and 55 FT participants.

BPD subjects were twice as likely to report wheeze and three times more likely to use asthma medication than controls. BPD adults had significantly lower FEV1 and FEF25–75 than both the preterm non-BPD and FT controls (all p<0.01). Mean EQ-5D was 6 points lower in BPD adults compared to FT controls (p<0.05).

BPD survivors have significant respiratory and quality of life impairment persisting into adulthood.

Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial: study protocol for a randomized controlled trial

Background: Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI.

Methods/Design: Patients fulfilling the American-European Consensus Conference Definition of ALI will be randomized in a 1: 1 ratio to receive enteral simvastatin 80 mg or placebo once daily for a maximum of 28 days. Allocation to randomized groups will be stratified with respect to hospital of recruitment and vasopressor requirement. Data will be recorded by participating ICUs until hospital discharge, and surviving patients will be followed up by post at 3, 6 and 12 months post randomization. The primary outcome is number of ventilator-free days to day 28. Secondary outcomes are: change in oxygenation index and sequential organ failure assessment score up to day 28, number of non pulmonary organ failure free days to day 28, critical care unit mortality; hospital mortality; 28 day post randomization mortality and 12 month post randomization mortality; health related quality of life at discharge, 3, 6 and 12 months post randomization; length of critical care unit and hospital stay; health service use up to 12 months post-randomization; and safety. A total of 540 patients will be recruited from approximately 35 ICUs in the UK and Ireland. An economic evaluation will be conducted alongside the trial. Plasma and urine samples will be taken up to day 28 to investigate potential mechanisms by which simvastatin might act to improve clinical outcomes.

Simvastatin decreases the level of heparin-binding protein in patients with acute lung injury

Heparin-binding protein is released by neutrophils during inflammation and disrupts the integrity of the alveolar and capillary endothelial barrier implicated in the development of acute lung injury and systemic organ failure. We sought to investigate whether oral administration of simvastatin to patients with acute lung injury reduces plasma heparin-binding protein levels and improves intensive care unit outcome.

Prospective clinical audit of chloral hydrate administration practices in a neonatal unit

Aim: Chloral hydrate is generally considered a safe and effective single dosing procedural sedative for neonates in the clinical setting. However, its safety profile as a repetitive dosing maintenance sedative is largely unknown. This study aimed to document current administration practices of chloral hydrate in the Neonatal Unit, Royal Children's Hospital, Melbourne, Australia, over a 6-month period.

Methods: Patients who had been prescribed chloral hydrate during the specified audit period were recruited into the study and prospectively followed for a period of 28 days, or until they were discharged from the unit. Demographic data were collected on recruitment, and daily documentation of chloral hydrate administration was recorded.

Results: A total of 238 doses of chloral hydrate were administered to a cohort of 32 patients during the study period. The majority of the audited doses (84%) were ordered as repeating doses. Doses were more likely to be given at night than during the day, and the median dosage for repetitive dosing was found to be above the study site's recommended dosing range. Pre-dose and/or post-dose assessment of distress/agitation accompanied dosage approximately half of the time. The audit did not reveal any recognisable pattern of sedation maintenance or weaning process for patients who received multiple doses.

Conclusions: Health-care professionals caring for hospitalised infants should be made aware of the potential risks of chloral hydrate as a repetitive dosing sedative, and of the importance of systematically evaluating the appropriateness and effectiveness of utilising such pharmacological intervention for managing and treating distress.

Metastatic non-small cell lung cancer: a benchmark for quality end-of-life cancer care?

Objectives: To investigate the quality of end-of-life care for patients with metastatic non-small cell lung cancer (NSCLC). Design and participants: Retrospective cohort study of patients from first hospitalisation for metastatic disease until death, using hospital, emergency department and death registration data from Victoria, Australia, between 1 July 2003 and 30 June 2010. Main outcome measures: Emergency department and hospital use; aggressiveness of care including intensive care and chemotherapy in last 30 days; palliative and supportive care provision; and place of death. Results: Metastatic NSCLC patients underwent limited aggressive treatment such as intensive care (5%) and chemotherapy (< 1%) at the end of life; however, high numbers died in acute hospitals (42%) and 61% had a length of stay of greater than 14 days in the last month of life. Although 62% were referred to palliative care services, this occurred late in the illness. In a logistic regression model adjusted for year of metastasis, age, sex, metastatic site and survival, the odds ratio (OR) of dying in an acute hospital bed compared with death at home or in a hospice unit decreased with receipt of palliative care (OR, 0.25; 95% CI, 0.21–0.30) and multimodality supportive care (OR, 0.65; 95% CI, 0.56–0.75). Conclusion: Because early palliative care for patients with metastatic NSCLC is recommended, we propose that this group be considered a benchmark of quality end-of-life care. Future work is required to determine appropriate quality-of-care targets in this and other cancer patient cohorts, with particular focus on the timeliness of palliative care engagement.

Ataluren for the treatment of nonsense-mutation cystic fibrosis: a randomised, double-blind, placebo-controlled phase 3 trial

Background: Ataluren was developed to restore functional protein production in genetic disorders caused by nonsense mutations, which are the cause of cystic fibrosis in 10% of patients. This trial was designed to assess the efficacy and safety of ataluren in patients with nonsense-mutation cystic fibrosis. 

Methods: This randomised, double-blind, placebo-controlled, phase 3 study enrolled patients from 36 sites in 11 countries in North America and Europe. Eligible patients with nonsense-mutation cystic fibrosis (aged ≥6 years; abnormal nasal potential difference; sweat chloride >40 mmol/L; forced expiratory volume in 1 s [FEV₁] ≥40% and ≤90%) were randomly assigned by interactive response technology to receive oral ataluren (10 mg/kg in morning, 10 mg/kg midday, and 20 mg/kg in evening) or matching placebo for 48 weeks. Randomisation used a block size of four, stratified by age, chronic inhaled antibiotic use, and percent-predicted FEV₁. The primary endpoint was relative change in percent-predicted FEV₁ from baseline to week 48, analysed in all patients with a post-baseline spirometry measurement. This study is registered with ClinicalTrials.gov, number NCT00803205. 

Findings: Between Sept 8, 2009, and Nov 30, 2010, 238 patients were randomly assigned, of whom 116 in each treatment group had a valid post-baseline spirometry measurement. Relative change from baseline in percent-predicted FEV₁ did not differ significantly between ataluren and placebo at week 48 (-2·5% vs -5·5%; difference 3·0% [95% CI -0·8 to 6·3]; p=0·12). The number of pulmonary exacerbations did not differ significantly between treatment groups (rate ratio 0·77 [95% CI 0·57-1·05]; p=0·0992). However, post-hoc analysis of the subgroup of patients not using chronic inhaled tobramycin showed a 5·7% difference (95% CI 1·5-10·1) in relative change from baseline in percent-predicted FEV₁ between the ataluren and placebo groups at week 48 (-0·7% [-4·0 to 2·1] vs -6·4% [-9·8 to -3·7]; nominal p=0·0082), and fewer pulmonary exacerbations in the ataluern group (1·42 events [0·9-1·9] vs 2·18 events [1·6-2·7]; rate ratio 0·60 [0·42-0·86]; nominal p=0·0061). Safety profiles were generally similar for ataluren and placebo, except for the occurrence of increased creatinine concentrations (ie, acute kidney injury), which occurred in 18 (15%) of 118 patients in the ataluren group compared with one (<1%) of 120 patients in the placebo group. No life-threatening adverse events or deaths were reported in either group. I

nterpretation: Although ataluren did not improve lung function in the overall population of nonsense-mutation cystic fibrosis patients who received this treatment, it might be beneficial for patients not taking chronic inhaled tobramycin. 

Funding: PTC Therapeutics, Cystic Fibrosis Foundation, US Food and Drug Administration's Office of Orphan Products Development, and the National Institutes of Health. 

Non-invasive Ventilation of Patients with ARDS: Insights from the LUNG SAFE Study

Background: Non-invasive ventilation (NIV) is increasingly used in patients with Acute Respiratory Distress Syndrome (ARDS). Whether, during NIV, the categorization of ARDS severity based on the PaO2/FiO2 Berlin criteria is useful is unknown. The evidence supporting NIV use in patients with ARDS remains relatively sparse.

Methods: The Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study described the management of patients with ARDS. This sub-study examines the current practice of NIV use in ARDS, the utility of the PaO2/FiO2 ratio in classifying patients receiving NIV and the impact of NIV on outcome.

Results: Of 2,813 patients with ARDS, 436 (15.5%) were managed with NIV on days 1 and 2 following fulfillment of diagnostic criteria. Classification of ARDS severity based on PaO2/FiO2 ratio was associated with an increase in intensity of ventilatory support, NIV failure, and Intensive Care Unit (ICU) mortality. NIV failure occurred in 22.2% of mild, 42.3% of moderate and 47.1% of patients with severe ARDS. Hospital mortality in patients with NIV success and failure was 16.1 % and 45.4%, respectively. NIV use was independently associated with increased ICU (HR 1.446; [1.159-1.805]), but not hospital mortality. In a propensity matched analysis, ICU mortality was higher in NIV than invasively ventilated patients with a PaO2/FiO2 lower than 150 mmHg.

Conclusions: NIV was used in 15% of patients with ARDS, irrespective of severity category. NIV appears to be associated with higher ICU mortality in patients with a PaO2/FiO2 lower than 150 mmHg.

Trial Registration: ClinicalTrials.gov NCT02010073