Structural Predictors of Lung Function Decline in Young Smokers with Normal Spirometry.

Rationale: Chronic obstructive pulmonary disease (COPD) due to tobacco smoking commonly presents when extensive lung damage has occurred. Objectives: We hypothesized that structural change would be detected early in the natural history of COPD and would relate to loss of lung function with time. Methods: We recruited 431 current smokers (median age, 39 yr; 16 pack-years smoked) and recorded symptoms using the COPD Assessment Test (CAT), spirometry, and quantitative thoracic computed tomography (QCT) scans at study entry. These scan results were compared with those from 67 never-smoking control subjects. Three hundred sixty-eight participants were followed every six months with measurement of postbronchodilator spirometry for a median of 32 months. The rate of FEV1 decline, adjusted for current smoking status, age, and sex, was related to the initial QCT appearances and symptoms, measured using the CAT. Measurements and Main Results: There were no material differences in demography or subjective CT appearances between the young smokers and control subjects, but 55.7% of the former had CAT scores greater than 10, and 24.2% reported chronic bronchitis. QCT assessments of disease probability-defined functional small airway disease, ground-glass opacification, bronchovascular prominence, and ratio of small blood vessel volume to total pulmonary vessel volume were increased compared with control subjects and were all associated with a faster FEV1 decline, as was a higher CAT score. Conclusions: Radiological abnormalities on CT are already established in young smokers with normal lung function and are associated with FEV1 loss independently of the impact of symptoms. Structural abnormalities are present early in the natural history of COPD and are markers of disease progression. Clinical trial registered with www.clinicaltrials.gov (NCT03480347).

Use of CAPTURE to Identify Individuals Who May or May Not Require Treatment for Chronic Obstructive Pulmonary Disease.

Rationale: The CAPTURE tool (Chronic Obstructive Pulmonary Disease [COPD] Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk) was developed to identify patients with undiagnosed COPD with an FEV1 <60% predicted or risk of exacerbation as treatment criteria. Objectives: To test the ability of CAPTURE to identify patients requiring treatment because of symptoms or risk of exacerbation or hospitalization. Methods: Data were from COMPASS (Clinical, Radiological and Biological Factors Associated with Disease Progression, Phenotypes and Endotypes of COPD in China), a prospective study of COPD, chronic bronchitis without airflow limitation (postbronchodilator FEV1/FVC ratio ≥0.70), and healthy never-smokers. CAPTURE was tested as questions alone and with peak expiratory flow measurement. Sensitivity, specificity, and positive and negative predicted values (PPV and NPV) were calculated for COPD Assessment Test (CAT) scores ⩾10 versus <10, modified Medical Research Council (mMRC) scores ⩾2 versus <2, and at least one moderate exacerbation or hospitalization in the previous year versus none. Measurements and Main Results: Patients with COPD (n = 1,696) had a mean age of 65 ± 7.5 years, and 90% were male, with a postbronchodilator FEV1 of 66.5 ± 20.1% predicted. Control participants (n = 307) had a mean age of 60.2 ± 7.0 years, and 65% were male, with an FEV1/FVC ratio of 0.78 ± 0.04. CAPTURE using peak expiratory flow showed the best combination of sensitivity and specificity. Sensitivity and specificity were 68.5% and 64.0%, respectively, to detect a CAT score ⩾10; 85.6% and 61.0% to detect an mMRC score ⩾2; 63.5% and 55.6% to detect at least one moderate exacerbation; and 70.2% and 59.4% to detect at least one hospitalization. PPVs ranged from 15.6% (moderate exacerbations) to 47.8% (CAT score). NPVs ranged from 80.8% (CAT score) to 95.6% (mMRC score). Conclusions: CAPTURE has good sensitivity to identify patients with COPD who may require treatment because of increased symptoms or risk of exacerbations or hospitalization, including those with an FEV1 >60% predicted. High NPV values show that CAPTURE can also exclude those who may not require treatment. Clinical trial registered with www.clinicaltrials.gov (NCT04853225).

A survey on perceived medication guide reading and comprehension ease among US adults.

Medication guides (MGs) provide patients with important information about certain prescription drugs to help them take these drugs safely. We surveyed US residents about their perceptions of MG readability and understandability. We randomly sampled 5204 US residents (age 18+) from Ipsos's KnowledgePanel to complete a two-part survey. Only respondents who reported receiving an MG with their prescription drugs (n = 3852) completed part 2, which included two key items: How easy to [(1)read/(2)understand] are the MGs that you have received from a pharmacy along with your prescription medicines? (1 = Very easy, 5 = Very difficult; reverse-coded). Health literacy (HL) and demographic data were also collected. After weighting our data, we found that 85% of respondents who reported receiving an MG perceived this information as 'very easy' (27.3%), 'somewhat easy' (28.3%) or 'about average' (29.3%) to read. Eighty-seven percent of respondents who reported receiving an MG perceived it as 'very easy' (27.6%), 'somewhat easy' (30.2%) or 'about average' (29.5%) to understand. ANOVAs revealed higher average perceived MG reading and comprehension ease scores among respondents presumed to have adequate versus inadequate HL (ps ≤ 0.0006). Younger or less-educated respondents and non-Hispanic Blacks perceived MGs as easier to read and understand, on average, than their counterparts (ps ≤ 0.0001). Many of these relationships remained intact in models predicting perceived MG reading and comprehension ease (ps ≤ 0.001). Adjusted R2 values across models were small, however (≤0.06). Our findings suggest most US residents (18+) who received MGs perceived them to be 'about average' to 'very easy' to read and understand.

Determination of change of direction deficit thresholds across a spectrum of angles in basketball players.

Change of direction deficit (CODD) offers valuable insights into a player's balance between linear and multidirectional speed. However, there are still no established reference values for CODD. The objectives of this study were to determine CODD thresholds for various change of direction angles in basketball players according to gender and analyse the relationships between CODD and execution time in speed tests. One hundred and thirty basketball players (46% female; age: 23.7 ± 5.29 years; height: 189.1 ± 11.1 cm; body mass: 84.3 ± 15.7 kg) undertook 10-m linear and change of direction speed test at 45º, 90º and 180º. A k-means cluster analysis was conducted to standardise CODD thresholds and a one-way analysis of variance to identify the differences between clusters. The results revealed angulation-specific CODD thresholds, ranging from 3% to 8%, 17% to 25% and 43% to 51% for 45º, 90º and 180º cutting angles, respectively for the pooled sample. Furthermore, differences inter-clusters (p < 0.05) were observed for execution time at all cutting angles for both genders. Therefore, strength and conditioning coaches are encouraged to assess CODD as a highly valid variable for evaluating change of direction performance and to use current CODD thresholds to tailor training programmes according to each athlete's needs.

Understanding the Gaps in the Reporting of COPD Exacerbations by Patients: A Review.

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with loss of lung function, poor quality of life, loss of exercise capacity, risk of serious cardiovascular events, hospitalization, and death. However, patients underreport exacerbations, and evidence suggests that unreported exacerbations have similar negative health implications for patients as those that are reported. Whilst there is guidance for physicians to identify patients who are at risk of exacerbations, they do not help patients recognise and report them. Newly developed tools, such as the COPD Exacerbation Recognition Tool (CERT) have been designed to achieve this objective. This review focuses on the underreporting of COPD exacerbations by patients, the factors associated with this, the consequences of underreporting, and potential solutions.

Chronic Airways Assessment Test: psychometric properties in patients with asthma and/or COPD.

BACKGROUND: No short patient-reported outcome (PRO) instruments assess overall health status across different obstructive lung diseases. Thus, the wording of the introduction to the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) was modified to permit use in asthma and/or COPD. This tool is called the Chronic Airways Assessment Test (CAAT). METHODS: The psychometric properties of the CAAT were evaluated using baseline data from the NOVELTY study (NCT02760329) in patients with physician-assigned asthma, asthma + COPD or COPD. Analyses included exploratory/confirmatory factor analyses, differential item functioning and analysis of construct validity. Responses to the CAAT and CAT were compared in patients with asthma + COPD and those with COPD. RESULTS: CAAT items were internally consistent (Cronbach's alpha: > 0.7) within each diagnostic group (n = 510). Models for structural and measurement invariance were strong. Tests of differential item functioning showed small differences between asthma and COPD in individual items, but these were not consistent in direction and had minimal overall impact on the total score. The CAAT and CAT were highly consistent when assessed in all NOVELTY patients who completed both (N = 277, Pearson's correlation coefficient: 0.90). Like the CAT itself, CAAT scores correlated moderately (0.4-0.7) to strongly (> 0.7) with other PRO measures and weakly (< 0.4) with spirometry measures. CONCLUSIONS: CAAT scores appear to reflect the same health impairment across asthma and COPD, making the CAAT an appropriate PRO instrument for patients with asthma and/or COPD. Its brevity makes it suitable for use in clinical studies and routine clinical practice. TRIAL REGISTRATION: NCT02760329.

Initial heart rate score predicts new-onset atrial tachyarrhythmias in pacemaker patients.

AIMS: Heart rate score (HRSc), the per cent of atrial paced and sensed event in the largest 10 b.p.m. rate histogram bin of a pacemaker, predicts survival in patients with cardiac devices. No correlation between HRSc and development of atrial fibrillation (AF) has been reported. In this study, we evaluated the relationship between pacemaker post-implantation HRSc and the incidence of newly developed atrial tachyarrhythmias (ATAs). METHODS AND RESULTS: Patients with dual-chamber pacemakers, implanted 2013-17, with the LATITUDE remote monitoring data with ≥600 000 beats of histogram data collected at baseline were included (N = 34 543). Heart rate score was determined from the initial 3-month post-implantation histogram data. Patients were excluded if they had ATAs, defined as atrial high-rate episodes >5 min or >1% of right atrial beats >170 b.p.m. during the initial 3 months post-implantation. New ATAs, after the baseline period, were defined by each of the following: >1, >10, or >25% of atrial beats >170 b.p.m. or atrial tachycardia response (ATR) events >24 h. Patients were followed a median of 2.8 (1.0-4.0) years. The incidence of ATAs increased in proportion to HRSc (log-rank P-value <0.001), and the initial HRSc ≥70% was associated with increased ATAs by all definitions. Patients with initial HRSc ≥70% were older, had a higher percentage of right atrium pacing (%RA pacing), had a lower percentage of right ventricular pacing (%RV pacing), and were more likely programmed with rate-response vs. subjects with HRSc <70%. Initial HRSc (hazard ratio: 1.07, 95% confidence interval: 1.05-1.09; P < 0.0001) independently predicted ATAs after adjusting for age, gender, %RV pacing, and rate-response programming. The %RA pacing and initial HRSc were correlated. CONCLUSION: Heart rate score independently predicts any subsequent duration of ATAs in pacemaker patients.

Identification of Mid-Polar and Polar AhR Agonists in Cetaceans from Korean Coastal Waters: Application of Effect-Directed Analysis with Full-Scan Screening.

Major aryl hydrocarbon receptor (AhR) agonists were identified in extracts of blubber, liver, and muscle from six long-beaked common dolphins (Delphinus capensis) and one fin whale (Balaenoptera physalus) collected from Korean coastal waters using effect-directed analysis. Results of the H4IIE-luc bioassay indicated that the polar fractions of blubber and liver extracts from the fin whale exhibited relatively high AhR-mediated potencies. Based on full-scan screening with high-resolution mass spectrometry, 37 AhR agonist candidates, spanning four use categories: pharmaceuticals, pesticides, cosmetics, and natural products, were selected. Among these, five polar AhR agonists were newly identified through toxicological confirmation. Concentrations of polar AhR agonists in cetaceans were tissue-specific, with extracts of blubber and liver containing greater concentrations than muscle extracts. Polar AhR agonists with great log KOA values (>5) were found to biomagnify in the marine food chain potentially. Polar AhR agonists contributed 8.9% of the observed AhR-mediated potencies in blubber and 49% in liver. Rutaecarpine and alantolactone contributed significantly to the total AhR-mediated potencies of blubber, whereas hydrocortisone was a major AhR contributor in the liver of the fin whale. This study is the first to identify the tissue-specific accumulation of polar AhR agonists in blubber and liver extracts of cetaceans.

Treatment Trials in Young Patients with Chronic Obstructive Pulmonary Disease and Pre-Chronic Obstructive Pulmonary Disease Patients: Time to Move Forward.

Chronic obstructive pulmonary disease (COPD) is the end result of a series of dynamic and cumulative gene-environment interactions over a lifetime. The evolving understanding of COPD biology provides novel opportunities for prevention, early diagnosis, and intervention. To advance these concepts, we propose therapeutic trials in two major groups of subjects: "young" individuals with COPD and those with pre-COPD. Given that lungs grow to about 20 years of age and begin to age at approximately 50 years, we consider "young" patients with COPD those patients in the age range of 20-50 years. Pre-COPD relates to individuals of any age who have respiratory symptoms with or without structural and/or functional abnormalities, in the absence of airflow limitation, and who may develop persistent airflow limitation over time. We exclude from the current discussion infants and adolescents because of their unique physiological context and COPD in older adults given their representation in prior randomized controlled trials (RCTs). We highlight the need of RCTs focused on COPD in young patients or pre-COPD to reduce disease progression, providing innovative approaches to identifying and engaging potential study subjects. We detail approaches to RCT design, including potential outcomes such as lung function, patient-reported outcomes, exacerbations, lung imaging, mortality, and composite endpoints. We critically review study design components such as statistical powering and analysis, duration of study treatment, and formats to trial structure, including platform, basket, and umbrella trials. We provide a call to action for treatment RCTs in 1) young adults with COPD and 2) those with pre-COPD at any age.

Reproductive compatibility among sympatric and allopatric isofemale lines of Trichogramma pretiosum Riley, 1879.

The present study evaluated the reproductive compatibility of Trichogramma pretiosum Riley, 1879, through an integrative approach using biological data and morphometry of three isofemale lines (isolines) collected from two geographical areas. These isolines differed in sequences of mitochondrial DNA and reproductive performance in the laboratory. The wasps used to initiate the isolines were collected in different environments: two lines from a Mediterranean climate in Irvine, California, USA, and one line from a tropical climate in Piracicaba, São Paulo, Brazil. Reproductive compatibility was studied by evaluating the sex ratio and number of adult offspring produced of all mating combinations between adults from these isolines. Morphometry was studied by measuring 26 taxonomically useful characters, followed by a multivariate analysis. For the allopatric matings among Brazilian and North American isolines, a low level of crossing incompatibility was recorded, in only one direction of the crosses; whereas the sympatric North American isolines were incompatible in both directions. Multivariate analysis of the morphometric data indicated no distinct groups, suggesting that despite the genetic and biological differences, the isofemale lines are morphologically similar.

Adaptive leadership during challenging times: Effective strategies for health professions educators: AMEE Guide No. 148.

Leadership and management are becoming increasingly recognised as vital for high-performing organisations and teams in health professions education. It is often difficult for those embarking on leadership activities (as well as more experienced leaders) to find their way through the volume of literature and generic information on the topic. This guide aims to provide a framework for developing educators' understanding of leadership, management, and followership in the context of health professions education. It explains many relevant approaches to leadership and suggests various strategies through which educators can develop their practice to become more effective.

Development of a Communication Tool between Patients and Physicians for Recognizing COPD Exacerbations in Japan.

In Japan, exacerbations are underreported compared with other countries, possibly due in part to a failure to recognize them. This study aimed to create a simple chronic obstructive pulmonary disease (COPD) Exacerbation Recognition Tool (CERT-J) specifically for Japanese patients. Patients ≥40 years with confirmed COPD or asthma-COPD overlap were included. Focus groups were held to identify words and phrases used by patients to describe symptoms associated with an exacerbation, resulting in candidate items being identified. Following cognitive debriefing, the items were refined based on item frequency, level of endorsement and effect of demographic factors. Exploratory factor analysis (EFA) was then performed to inform an expert panel's choice of items to form the new tool. A total of 41 patients were included in the focus groups and nine patients performed the cognitive debrief. Following this, the expert panel identified 26 items for testing in a further 100 patients (mean age 72 years, forced expiratory volume in 1 s 54.8% predicted and 1.8 exacerbations in the preceding 12 months). Eleven items were associated with breathlessness or activity limitation and seven of these were the most frequently endorsed. EFA identified four factors, with one (breathlessness) being dominant. The expert panel recommended that the CERT-J should include six items: breathlessness and activity limitation (3 items), cough (1 item) and phlegm (2 items). The final CERT-J should benefit patients with COPD by providing them with an increased understanding and recognition of exacerbations.Clinical Trial Registration: GSK K.K (jRCT1080224526).

How can the findings of the EMAX trial on long-acting bronchodilation in chronic obstructive pulmonary disease be applied in the primary care setting?

This review addresses outstanding questions regarding initial pharmacological management of chronic obstructive pulmonary disease (COPD). Optimizing initial treatment improves clinical outcomes in symptomatic patients, including those with low exacerbation risk. Long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA) dual therapy improves lung function versus LAMA or LABA monotherapy, although other treatment benefits have been less consistently observed. The benefits of dual bronchodilation in symptomatic patients with COPD at low exacerbation risk, and its duration of efficacy and cost effectiveness in this population, are not yet fully established. Questions remain on the impact of baseline symptom severity, prior treatment, degree of reversibility to bronchodilators, and smoking status on responses to dual bronchodilator treatment. Using evidence from EMAX (NCT03034915), a 6-month trial comparing the LAMA/LABA combination umeclidinium/vilanterol with umeclidinium and salmeterol monotherapy in symptomatic patients with COPD at low exacerbation risk who were inhaled corticosteroid-naïve, we describe how these findings can be applied in primary care.

Implementation of a midline catheter service in a regional setting.

Introduction: Midline catheters have been reported to be an effective and safe means of providing patients with intravenous access within the hospital and community setting. With minimal experience in the introduction of a midline service across the local health network, a regional hospital pursued this task. This observational study assesses the provision of a safe clinical framework for midline insertion, and the improvement of patient care and experiences by avoiding treatment interruptions and unnecessary cannulation attempts from failed traditional peripheral vascular access devices. Methods: From the introduction of the midline service in June 2018, outcome measures of all patients who received a midline over the following two-year period were documented including rate of line success, complication rates, dwell time, and the number of insertion attempts. Results: The midline service provided 207 lines over a two-year period with a total dwell time of 1,585 days. Project goals were achieved with 85% (Aim > 85%) of all lines completing treatment prior to removal. First attempt insertion was 86% (Aim > 80%) with a maximum insertion attempt of two. Rates of line-related complications were less than 8%, with five documented cases of phlebitis (2.5%) and one deep vein thrombosis with no infections documented. Conclusion: Despite limited resources, a successful midline service was introduced. Future expansion will see an increase in insertor numbers providing improved access to the service.

Effects of 6 weeks in-season flywheel squat resistance training on strength, vertical jump, change of direction and sprint performance in professional female soccer players.

Flywheel resistance training devices (FRTD) is shown effective in improving strength, sprinting, jumping and changes of direction (COD) performance in male soccer players, however, this is not elucidated in female soccer players. We aimed to assess the effect of FRTD on these physical abilities in females soccer players. 24 professional female soccer players (age: 20.4 ± 2.6 years) were randomly assigned to a flywheel training group (FWTG) that trained twice a week for 6 weeks on a rotary inertia device with an initial volume of 3 sets of 6 repetitions and an inertia of 0,025 kg · m-2, increasing intensity and volume or a control group (CG) that did not performed any additional resistance training program. Concentric peak torque of the knee extensors (CONEXT) and flexors (CONFLEX), eccentric peak torque of the knee extensors (ECCEXT) and flexors (ECCFLEX) at 60° · s-1 on an isokinetic dynamometer, countermovement jump (CMJ) height, COD and 30-metres sprint were assessed. Significant time by group interactions were found in CONEXT (p = 0.002; η²p = 0.425), CONFLEX (p = 0.037; η²p = 0.22), ECCEXT (p = 0.002; η²p = 0.43) and ECCFLEX (p = 0.008; η²p = 0.334). No time by group effect was found in CMJ (p = 0.061; η²p = 0.182), COD (p = 0.067; η²p = 0.184) or sprint (p = 0.926; η²p = 4.979 · e-4). In conclusion, 6 weeks of flywheel squat training improved strength (especially eccentric strength) but not soccer-specific abilities such as jumping, changing of direction or sprinting in professional soccer players.

Manipulation of task constraints is the most effective motor learning method for reducing risk factors for ACL injury during side-step cutting in both male and female athletes.

This study compared the efficacy of linear, non-linear and differential methods on variables related to ACL injury risk of a side-step cutting task in male and female basketball players. Thirty males and thirty females practiced basketball skills in sixty 90-minute sessions across 5 months. Ten players trained in each of the LP, NLP and DL female/male groups separately. Before and after the intervention, each player was tested on a side-step cutting task. A repeated 3 × 2 × 2 factorial ANOVA with repeated measures was performed for each biomechanical variable. Variables (trunk, hip, and knee flexion angle, knee valgus angle, ankle dorsiflexion angle, hip, knee, and ankle ROM, peak VGRF and knee extension/flexion, knee moment and ankle dorsiflexion moment) all revealed significant test by group interactions (P < 0.05) but no significant group by sex interactions (P > 0.05). In both sex, biomechanical changes were better in the NLP, followed by the DL and LP. It is argued that the advantage of the NLP method results from increased exploration of movement solutions induced by the manipulation of task constraints. Therefore, according to the NLP, it is possible to manipulate the constraints without feedback and the model/pattern can keep the athlete away from possible risks.

Associations of lipoprotein particle profile and objectively measured physical activity and sedentary time in schoolchildren: a prospective cohort study.

BACKGROUND: Our understanding of the mechanisms through which physical activity might benefit lipoprotein metabolism is inadequate. Here we characterise the continuous associations between physical activity of different intensities, sedentary time, and a comprehensive lipoprotein particle profile. METHODS: Our cohort included 762 fifth grade (mean [SD] age = 10.0 [0.3] y) Norwegian schoolchildren (49.6% girls) measured on two separate occasions across one school year. We used targeted proton nuclear magnetic resonance (1H NMR) spectroscopy to produce 57 lipoprotein measures from fasted blood serum samples. The children wore accelerometers for seven consecutive days to record time spent in light-, moderate-, and vigorous-intensity physical activity, and sedentary time. We used separate multivariable linear regression models to analyse associations between the device-measured activity variables-modelled both prospectively (baseline value) and as change scores (follow-up minus baseline value)-and each lipoprotein measure at follow-up. RESULTS: Higher baseline levels of moderate-intensity and vigorous-intensity physical activity were associated with a favourable lipoprotein particle profile at follow-up. The strongest associations were with the larger subclasses of triglyceride-rich lipoproteins. Sedentary time was associated with an unfavourable lipoprotein particle profile, the pattern of associations being the inverse of those in the moderate-intensity and vigorous-intensity physical activity analyses. The associations with light-intensity physical activity were more modest; those of the change models were weak. CONCLUSION: We provide evidence of a prospective association between time spent active or sedentary and lipoprotein metabolism in schoolchildren. Change in activity levels across the school year is of limited influence in our young, healthy cohort. TRIAL REGISTRATION: ClinicalTrials.gov , # NCT02132494 . Registered 7th April 2014.

Inflammation of Gill Epithelia in Fish Causes Increased Permeation of Petrogenic Polar Organic Chemicals via Disruption of Tight Junctions.

The epithelial cell layer that lines the gills of fish controls paracellular permeation of chemicals through tight junctions. The integrity of tight junctions can be affected by inflammation, which likely affects the bioavailability of chemicals. Here, the inflammation of the rainbow trout gill cell line RTgill-W1 was induced via exposure to bacterial lipopolysaccharides (LPS). Cells were then coexposed to extracts of oil sands process-affected water (OSPW), which contain complex mixtures of chemicals. After 24 h of exposure, cells exposed to LPS showed a reduction in transepithelial electrical resistance, an indicator of tight junction integrity. Quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis determined that abundances of transcripts of genes coding for tight junction proteins were significantly less in cells exposed to 20, 50, or 100 mg L-1 LPS. Chemical analysis revealed increased permeation of constituents of OSPW across epithelia at all studied LPS concentrations. These in vitro findings were confirmed in vivo in rainbow trout exposed to LPS and OSPW for 48 h, which resulted in greater accumulation of chemicals relative to that for fish exposed to OSPW alone. Our results demonstrated that inflammation and disruption of tight junctions could lead to greater uptake of potentially harmful chemicals from the environment, which has implications for mixture risk assessment.

Thermal and Catalytic Decomposition of 2-Hydroxyethylhydrazine and 2-Hydroxyethylhydrazinium Nitrate Ionic Liquid.

To develop chemical kinetics models for the combustion of ionic liquid-based monopropellants, identification of the elementary steps in the thermal and catalytic decomposition of components such as 2-hydroxyethylhydrazinium nitrate (HEHN) is needed but is currently not well understood. The first decomposition step in protic ionic liquids such as HEHN is typically the proton transfer from the cation to the anion, resulting in the formation of 2-hydroxyethylhydrazine (HEH) and HNO3. In the first part of this investigation, the high-temperature thermal decomposition of HEH is probed with flash pyrolysis (<1400 K) and vacuum ultraviolet (10.45 eV) photoionization time-of-flight mass spectrometry (VUV-PI-TOFMS). Next, the investigation into the thermal and catalytic decomposition of HEHN includes two mass spectrometric techniques: (1) tunable VUV-PI-TOFMS (7.4-15 eV) and (2) ambient ionization mass spectrometry utilizing both plasma and laser ionization techniques whereby HEHN is introduced onto a heated inert or iridium catalytic surface and the products are probed. The products can be identified by their masses, their ionization energies, and their collision-induced fragmentation patterns. Formation of product species indicates that catalytic surface recombination is an important reaction process in the decomposition mechanism of HEHN. The products and their possible elementary reaction mechanisms are discussed.

Direct healthcare costs associated with management of asthma: comparison of two treatment regimens in Indonesia, Thailand and Vietnam.

OBJECTIVE: Daily inhaled corticosteroid (ICS) and long-acting beta-2-agonist (LABA) combinations comprising either regular maintenance therapy with ICS/LABA plus as-needed short-acting beta-2-agonist (SABA) or ICS-formoterol combinations used as maintenance and reliever therapy (MART) are recommended for moderate asthma. This analysis compares the direct costs of twice-daily fluticasone propionate/salmeterol (FP/salm) and budesonide/formoterol MART in three Southeast Asian countries. METHODS: A literature review identified three randomized trials in patients with asthma (≥ 12 years) comparing regular twice-daily FP/salm with as-needed SABA versus MART in moderate asthma: AHEAD (NCT00242775/17 countries/2309 patients), COMPASS (AstraZeneca study SD-039-0735/16 countries/3335 patients), and COSMOS (AstraZeneca study SD-039-0691/16 countries/2143 patients). Economic analyses, conducted from a healthcare sector perspective (medication costs + healthcare utilization costs), applied unit costs from countries where healthcare costs are publicly available: Indonesia, Thailand and Vietnam. Results are expressed in British pound sterling (GBP/patient/year). RESULTS: Annual exacerbation rates were low and differences between treatment strategies were small (range, FP/salm: 0.31-0.38, MART: 0.24-0.25) although statistically significant in favor of MART. Total average (minimum-maximum) direct costs (in GBP/patient/year) across the three studies were £187 (£137-£284), £158 (£125-£190), and £151 (£141-£164) for those who used FP/salm, and £242 (£217-£267), £284 (£237-£340) and £266 (£224-£315) for MART in Indonesia, Thailand and Vietnam, respectively. On average, total direct costs/patient/year with FP/salm were 22.8%, 44.6% and 43.0% lower than with MART for Indonesia, Thailand and Vietnam, respectively. CONCLUSIONS: In the three countries evaluated, total treatment costs with regular twice-daily FP/salm were consistently lower than with budesonide/formoterol MART due to lower direct healthcare costs.