Drug therapy for delirium in terminally ill adult patients.

BACKGROUND: Delirium is a syndrome characterised by a disturbance of consciousness (often fluctuating), cognition and perception. In terminally ill patients it is one of the most common causes of admission to clinical care. Delirium may arise from any number of causes and treatment should be directed at addressing these causes rather than the symptom cluster. In cases where this is not possible, or treatment does not prove successful, the use of drug therapy to manage the symptoms may become necessary. This is an update of the review published on 'Drug therapy for delirium in terminally ill adult patients' in The Cochrane Library 2004, Issue 2 ( Jackson 2004). OBJECTIVES: To evaluate the effectiveness of drug therapies to treat delirium in adult patients in the terminal phase of a disease. SEARCH METHODS: We searched the following sources: CENTRAL (The Cochrane Library 2012, Issue 7), MEDLINE (1966 to 2012), EMBASE (1980 to 2012), CINAHL (1982 to 2012) and PSYCINFO (1990 to 2012). SELECTION CRITERIA: Prospective trials with or without randomisation or blinding involving the use of drug therapies for the treatment of delirium in adult patients in the terminal phase of a disease. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality using standardised methods and extracted trial data. We collected outcomes related to efficacy and adverse effects. MAIN RESULTS: One trial met the criteria for inclusion. In the 2012 update search we retrieved 3066 citations but identified no new trials. The included trial evaluated 30 hospitalised AIDS patients receiving one of three agents: chlorpromazine, haloperidol and lorazepam. The trial under-reported key methodological features. It found overall that patients in the chlorpromazine group and those in the haloperidol group had fewer symptoms of delirium at follow-up (to below the diagnostic threshold using the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) and that both were equally effective (at two days mean difference (MD) 0.37; 95% confidence interval (CI) -4.58 to 5.32; between two and six days MD -0.21; 95% CI -5.35 to 4.93). Chlorpromazine and haloperidol were found to be no different in improving cognitive status in the short term (at 48 hours) but at subsequent follow-up cognitive status was reduced in those taking chlorpromazine. Improvements from baseline to day two for patients randomised to lorazepam were not apparent. All patients on lorazepam (n = 6) developed adverse effects, including oversedation and increased confusion, leading to trial drug discontinuation. AUTHORS' CONCLUSIONS: There remains insufficient evidence to draw conclusions about the role of drug therapy in the treatment of delirium in terminally ill patients. Thus, practitioners should continue to follow current clinical guidelines. Further research is essential

Operational Improvements From Using the In-Trail Procedure in the North Atlantic Organized Track System

This paper explains the computerized batch processing experiment examining the operational impacts of the introduction of Automatic Dependent Surveillance-Broadcast (ADS-B) equipment and the In-Trail Procedure (ITP) to the North Atlantic Organized Track System. This experiment was conducted using the Traffic Manager (TMX), a desktop simulation capable of simulating airspace environments and aircraft operations. ADS-B equipment can enable the use of new ground and airborne procedures, such as the ITP. ITP is among the first of these new procedures, which will make use of improved situation awareness in the local surrounding airspace of ADS-B equipped aircraft to enable more efficient oceanic flight level changes. The collected data were analyzed with respect to multiple operationally relevant parameters including fuel burn, request approval rates, and the distribution of fuel savings. This experiment showed that through the use of ADS-B or ADS-B and the ITP that operational improvements and benefits could be achieved

Single maintenance and reliever therapy (SMART) of asthma: a critical appraisal

The use of a combination inhaler containing budesonide and formoterol as both maintenance and quick relief therapy (SMART) has been recommended as an improved method of using inhaled corticosteroid/long-acting β agonist (ICS/LABA) therapy. Published double-blind trials show that budesonide/formoterol therapy delivered in SMART fashion achieves better asthma outcomes than budesonide monotherapy or lower doses of budesonide/formoterol therapy delivered in constant dosage. Attempts to compare budesonide/formoterol SMART therapy with regular combination ICS/LABA dosing using other compounds have been confounded by a lack of blinding and unspecified dose adjustment strategies. The asthma control outcomes in SMART-treated patients are poor; it has been reported that only 17.1% of SMART-treated patients are controlled. In seven trials of 6–12 months duration, patients using SMART have used quick reliever daily (weighted average 0.92 inhalations/day), have awakened with asthma symptoms once every 7–10 days (weighted average 11.5% of nights), have suffered asthma symptoms more than half of days (weighted average 54.0% of days) and have had a severe exacerbation rate of one in five patients per year (weighted average 0.22 severe exacerbations/patient/year). These poor outcomes may reflect the recruitment of a skewed patient population. Although improvement from baseline has been attributed to these patients receiving additional ICS therapy at pivotal times, electronic monitoring has not been used to test this hypothesis nor the equally plausible hypothesis that patients who are non-compliant with maintenance medication have used budesonide/formoterol as needed for self-treatment of exacerbations. Although the long-term consequences of SMART therapy have not been studied, its use over 1 year has been associated with significant increases in sputum and biopsy eosinophilia. At present, there is no evidence that better asthma treatment outcomes can be obtained by moment-to-moment symptom-driven use of ICS/LABA therapy than conventional physician-monitored and adjusted ICS/LABA therapy

Charge Transfer in Single Chains of a Donor-Acceptor Conjugated Tri-Block Copolymer.

The photophysics of a conjugated triblock copolymer comprising poly(9,9-dioctylfluorene-co-bis-N,N'-(4-methylphenyl)-bis-N,N'-phenyl-1,4-phenylenediamine) (PFM) electron donor and poly(4-(9,9-dioctyl-9H-fluoren-2-yl)benzo[c][1,2,5]-thiadiazole) (F8BT) electron acceptor blocks has been studied in solution, in films, and as single chains. While an additional long-wavelength emission apparent in neat films of the copolymer is attributed to interchain exciplex formation, no such long-wavelength emission is apparent in solution or from single molecules. However, in these cases, time-resolved fluorescence measurements indicate the presence of a delayed fluorescence. The kinetics of the delayed emission can be interpreted in terms of an equilibrium between a locally excited and a charge-transfer state at the interface of the copolymer block components. Rate constants and thermodynamic quantities associated with these processes have been evaluated. The single-molecule results allow the assignment of an intramolecular charge-transfer state in an isolated conjugated block copolymer chain.We thank the Australian Research Council (ARC) for financial support of this research through grants DP0986166, LE100100131 and LE110100161. ENH acknowledges an Australian Postgraduate Award. We acknowledge Sam Ashworth for technical assistance with data collection. NCG is grateful to the School of Chemistry, The University of Melbourne for a Wilsmore Fellowship, and to Queen’s College, Melbourne for a Sugden Fellowship.This is the accepted manuscript. The final version is available from ACS at http://pubs.acs.org/doi/abs/10.1021/jp510769p

Operational Improvements From the In-Trail Procedure in the North Atlantic Organized Track System

This paper explains the computerized batch processing experiment examining the operational impacts of the introduction of Automatic Dependent Surveillance-Broadcast (ADS-B) equipment and the In-Trail Procedure (ITP) to the North Atlantic Organized Track System (NATOTS). This experiment was conducted using the Traffic Manager (TMX), a desktop simulation capable of simulating airspace environments and aircraft operations. ADS-B equipment can enable the use of new ground and airborne procedures, such as the ITP. The ITP is among the first of these new procedures, which will make use of improved situation awareness in the local surrounding airspace of ADS-B equipped aircraft to enable more efficient oceanic flight level changes. The data collected were analyzed with respect to multiple operationally relevant parameters including fuel burn, request approval rates, and the distribution of fuel savings. This experiment showed that through the use of ADS-B or ADS-B and the ITP that operational improvements and benefits could be achieved

Pairwise Trajectory Management (PTM): Concept Description and Documentation

Pairwise Trajectory Management (PTM) is an Interval Management (IM) concept that utilizes airborne and ground-based capabilities to enable the implementation of airborne pairwise spacing capabilities in oceanic regions. The goal of PTM is to use airborne surveillance and tools to manage an "at or greater than" inter-aircraft spacing. Due to the accuracy of Automatic Dependent Surveillance-Broadcast (ADS-B) information and the use of airborne spacing guidance, the minimum PTM spacing distance will be less than distances a controller can support with current automation systems that support oceanic operations. Ground tools assist the controller in evaluating the traffic picture and determining appropriate PTM clearances to be issued. Avionics systems provide guidance information that allows the flight crew to conform to the PTM clearance issued by the controller. The combination of a reduced minimum distance and airborne spacing management will increase the capacity and efficiency of aircraft operations at a given altitude or volume of airspace. This document provides an overview of the proposed application, a description of several key scenarios, a high level discussion of expected air and ground equipment and procedure changes, a description of a NASA human-machine interface (HMI) prototype for the flight crew that would support PTM operations, and initial benefits analysis results. Additionally, included as appendices, are the following documents: the PTM Operational Services and Environment Definition (OSED) document and a companion "Future Considerations for the Pairwise Trajectory Management (PTM) Concept: Potential Future Updates for the PTM OSED" paper, a detailed description of the PTM algorithm and PTM Limit Mach rules, initial PTM safety requirements and safety assessment documents, a detailed description of the design, development, and initial evaluations of the proposed flight crew HMI, an overview of the methodology and results of PTM pilot training requirements focus group and human-in-the-loop testing activities, and the PTM Pilot Guide

Pairwise Trajectory Management (PTM): Concept Overview

Pairwise Trajectory Management (PTM) is an Interval Management (IM) concept that utilizes airborne and ground-based capabilities to enable the implementation of airborne pairwise spacing capabilities in oceanic regions. The goal of PTM is to use airborne surveillance and tools to manage an "at or greater than" inter-aircraft spacing. Due to the precision of Automatic Dependent Surveillance-Broadcast (ADS-B) information and the use of airborne spacing guidance, the PTM minimum spacing distance will be less than distances a controller can support with current automation systems that support oceanic operations. Ground tools assist the controller in evaluating the traffic picture and determining appropriate PTM clearances to be issued. Avionics systems provide guidance information that allows the flight crew to conform to the PTM clearance issued by the controller. The combination of a reduced minimum distance and airborne spacing management will increase the capacity and efficiency of aircraft operations at a given altitude or volume of airspace. This paper provides an overview of the proposed application, description of a few key scenarios, high level discussion of expected air and ground equipment and procedure changes, overview of a potential flight crew human-machine interface that would support PTM operations and some initial PTM benefits results

Rapid Saline Permafrost Thaw Below a Shallow Thermokarst Lake in Arctic Alaska

Permafrost warming and degradation is well documented across the Arctic. However, observation- and model-based studies typically consider thaw to occur at 0°C, neglecting the widespread occurrence of saline permafrost in coastal plain regions. In this study, we document rapid saline permafrost thaw below a shallow arctic lake. Over the 15-year period, the lakebed subsided by 0.6 m as ice-rich, saline permafrost thawed. Repeat transient electromagnetic measurements show that near-surface bulk sediment electrical conductivity increased by 198% between 2016 and 2022. Analysis of wintertime Synthetic Aperture Radar satellite imagery indicates a transition from a bedfast to a floating ice lake with brackish water due to saline permafrost thaw. The regime shift likely contributed to the 65% increase in thermokarst lake lateral expansion rates. Our results indicate that thawing saline permafrost may be contributing to an increase in landscape change rates in the Arctic faster than anticipated