Clinically important differences in the intensity of chronic refractory breathlessness

Context: Clinically important differences in chronic refractory breathlessness are ill defined but important in clinical practice and trial design. Objectives: To estimate the clinical relevance of differences in breathlessness intensity using distribution and patient anchor methods. Methods: This was a retrospective data analysis from 213 datasets from four clinical trials for refractory breathlessness. Linear regression was used to explore the relationship between study effect size and change in breathlessness score (0-100 mm visual analogue scale) and to estimate the change in score equivalent to small, moderate, and large effect sizes. Pooled individual blinded patient preference data from three randomized controlled trials were analyzed. The difference between the mean change in Day 4 minus baseline scores between preferred and non-preferred arms was calculated. Results: There was a strong relationship between change in score and effect size (P = 0.001; R 2 = 0.98). Values for small, moderate, and large effects were -5.5, -11.3, and -18.2 mm. The participant preference change in score was -9 mm (95% CI, -15.8, -2.1) (P = 0.008). Conclusion: This larger dataset supports a clinically important difference of 10 mm. Studies should be powered to detect this difference

Effects of low dose morphine on perceived sleep quality in patients with refractory breathlessness : a hypothesis generating study

© 2015 Asian Pacific Society of Respirology. Background and objective The management of chronic refractory breathlessness is one of the indications for regular low-dose (≤30 mg/24 h) oral sustained release morphine. Morphine may disrupt sleep in some conditions and improve sleep quality in others. This study aimed to determine any signal of regular, low-dose morphine on perceived sleep disruption due to breathlessness and perceived sleep quality. Methods This is a secondary analysis of data from 38 participants with refractory breathlessness (30 male; 33 with COPD) aged 76 ± 0.9 years who completed a double-blind, randomized, placebo-controlled, cross-over study in which they received 20 mg oral sustained release morphine daily and placebo for 4 days each. Participant ratings of sleep disruption due to breathlessness and perceived sleep quality were obtained daily throughout the 8-day trial. Results Perceived sleep disruption due to breathlessness over the 4-day period ranged between 13% and 32% of participants for placebo and 13% and 26% for morphine, decreasing by each day of the study during the morphine arm. Most participants reported 'very good' or 'quite good' sleep throughout the trial and were less likely to perceive poor sleep quality during the morphine arm (odds ratio = 0.55, 95% confidence interval: 0.34-0.88, P = 0.01). Participants who reported decreased breathlessness during the 4 days on morphine were also likely to report improved sleep quality with morphine (P = 0.039). Conclusion Four days of low-dose morphine improved perceived sleep quality in elderly participants with refractory breathlessness. Regular low-dose morphine targeted to reduce refractory breathlessness may yield associated benefits by reducing sleep disruption and improving sleep quality

Blinded patient preference for morphine compared to placebo in the setting of chronic refractory breathlessness – an exploratory study

Context Patients’ preference for morphine therapy has received little attention in the setting of chronic refractory breathlessness. However, this is one important factor in considering longer term therapy. Objectives The aim of this secondary analysis is to explore blinded patient preference of morphine compared to placebo for this indication and to define any predictors of preference. Methods Data were pooled from three randomized, double-blind, crossover, placebo-controlled studies of morphine (four days each) in chronic refractory breathlessness. Blinded patient preferences were chosen at the end of each study. A multivariable regression model was used to establish patient predictors of preference. Results Sixty-five participants provided sufficient data (60 males; median age 74 years; heart failure 55%, chronic obstructive pulmonary disease 45%; median Eastern Cooperative Oncology Group performance status 2). Forty-three percent of participants preferred morphine (32% placebo and 25% no preference). Morphine preference and younger age were strongly associated: odds ratio = 0.85, 95% confidence interval 0.78, 0.93;

Antigen-Independent Maturation of CD2, CD11a/CD18, CD44, and CD58 Expression on Thymic Emigrants in Fetal and Postnatal Sheep

We have compared the expression of CD2, CD11a/CD18, CD44, and CD58 on αβ and γδ T cells emigrating from the fetal and postnatal thymus. We report that both γδ and the CD4+ CD8- and CD4-CD8+ subsets of αβ T cells express mature levels of the adhesion molecules CD11a/CD18, CD44, and CD58 upon emigration from the thymus. Whereas CD44 is up-regulated on γδ+ thymocytes prior to export, down-regulation of both CD11a/CD18 and CD58 occurs prior to emigration from the thymus, suggesting that down-regulation of these molecules may be a final maturational step taken by developing γδ T cells before their export from the thymus. In contrast, there is continued up-regulation of CD2 on αβ and γδ T cells upon emigration from the thymus and as they move into the mature peripheral T-cell pool. There was also a marked reduction in the number of CD2+ γδ T cells exported during fetal development that was associated with a marked reduction in the percentage of CD22+ γδ thymocytes exported. The postthymic maturation of CD2 and the other changes in adhesion-molecule expression appear to be independent of extrinsic antigen, as the same changes were observed in the antigen-free environment of the fetus as in the postnatal lamb, which has been exposed to extrinsic antigen. It thus appears that these changes in adhesion-molecule expression are as a result of the normal maturation pathway from a developing thymocyte to a mature peripheral T cell

Practical dyspnea assessment: relationship between the 0–10 numerical rating scale and the four-level categorical verbal descriptor scale of dyspnea intensity

Context—Measurement of dyspnea is important for clinical care and research. Objectives—To characterize the relationship between the 0–10 Numerical Rating Scale (NRS) and four-level categorical Verbal Descriptor Scale (VDS) for dyspnea assessment. Methods—This was a substudy of a double-blind randomized controlled trial comparing palliative oxygen to room air for relief of refractory breathlessness in patients with life-limiting illness. Dyspnea was assessed with both a 0–10 NRS and a four-level categorical VDS over the one-week trial. NRS and VDS responses were analyzed in cross section and longitudinally. Relationships between NRS and VDS responses were portrayed using descriptive statistics and visual representations. Results—Two hundred twenty-six participants contributed responses. At baseline, mild and moderate levels of breathlessness were reported by 41.9% and 44.6% of participants, respectively. NRS scores demonstrated increasing mean and median levels for increasing VDS intensity, from a mean (SD) of 0.6 (±1.04) for VDS none category to 8.2 (1.4) for VDS severe category. The Spearman correlation coefficient was strong at 0.78 (P < 0.0001). Based on the distribution of NRS scores within VDS categories, we calculated test characteristics of two different cutpoint models. Both models yielded 75% correct translations from NRS to VDS; however, Model A was more sensitive for moderate or greater dyspnea, with fewer misses downcoded. Conclusion—There is strong correlation between VDS and NRS measures for dyspnea. Proposed practical cutpoints for the relationship between the dyspnea VDS and NRS are 0 for none, 1–4 for mild, 5–8 for moderate, and 9–10 for severe

Hydrogen reduction of ilmenite: Towards an in situ resource utilization demonstration on the surface of the Moon

Water is one of the most vital resources required for future space exploration. By obtaining water from lunar regolith, humans are one step closer to being independent of Earth's resources enabling longer term exploration missions. Hydrogen reduction of ilmenite is often proposed as a technique for producing water on the Moon. ProSPA, a miniature analytical laboratory, will perform reduction of lunar soils as an In-Situ Resource Utilization (ISRU) demonstration on the lunar surface. The technique used by ProSPA will be useful for prospecting payloads with limited mass and power resources. This work considers the development and optimization of an ilmenite (FeTiO3) reduction procedure for use with the ProSPA instrument. It is shown that the reaction can be performed in a static (non-flowing) system, by utilizing a cold finger to collect the water produced from the reaction. Among the investigated parameters an initial H2:FeTiO3 ratio of 1, in this case equating to a hydrogen pressure of 418 mbar, proved to be best for providing maximum yields over 4 h when operating at 1000 °C. Results indicate that a maximum yield of 3.40 ± 0.17 wt % O2 can be obtained at 1000 °C (with a maximum possible yield of 10.5 wt % O2). When operating at higher temperatures of 1100 °C the ilmenite grains undergo a subsolidus reaction resulting in the formation of ferropseudobrookite and higher yields of 4.42 ± 0.18 wt % O2 can be obtained