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Line Hust Storgaard,1 Hans-Ulrich Hockey,2 Birgitte Schantz Laursen,3,4 Ulla Møller Weinreich1,3 1Department of Respiratory Diseases, Aalborg University Hospital, Aalborg, Denmark; 2Biometrics Matters Limited, Hamilton, New Zealand; 3Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 4Clinical Nursing Research Unit, Aalborg University Hospital, Aalborg, Denmark Background: This study investigated the long-term effects of humidified high-flow nasal cannula (HFNC) in COPD patients with chronic hypoxemic respiratory failure treated with long-term oxygen therapy (LTOT).Patients and methods: A total of 200 patients were randomized into usual care ± HFNC. At inclusion, acute exacerbation of COPD (AECOPD) and hospital admissions 1 year before inclusion, modified Medical Research Council (mMRC) score, St George’s Respiratory Questionnaire (SGRQ), forced expiratory volume in 1 second (FEV1), 6-minute walk test (6MWT) and arterial carbon dioxide (PaCO2) were recorded. Patients completed phone interviews at 1, 3 and 9 months assessing mMRC score and AECOPD since the last contact. At on-site visits (6 and 12 months), mMRC, number of AECOPD since last contact and SGRQ were registered and FEV1, FEV1%, PaCO2 and, at 12 months, 6MWT were reassessed. Hospital admissions during the study period were obtained from hospital records. Hours of the use of HFNC were retrieved from the high-flow device.Results: The average daily use of HFNC was 6 hours/day. The HFNC group had a lower AECOPD rate (3.12 versus 4.95/patient/year, p

In this study, we evaluated the performance of a humidified nasal high-flow system (Optiflow, Fisher and Paykel Healthcare) by measuring delivered FiO, and airway pressures. Oxygraphy, capnography and measurement of airway pressures were performed through a hypopharyngeal catheter in healthy volunteers receiving Optiflow humidified nasal high flow therapy at rest and with exercise. The study was conducted in a non-clinical experimental setting. Ten healthy volunteers completed the study after giving informed written consent. Participants received a delivered oxygen fraction of 0.60 with gas flow rates of 10, 20, 30, 40 and 50 l/minute in random order FiO2, F(E)O2, F(E)CO2 and airway pressures were measured. Calculation of FiO2 from F(E)O2 and F(E)CO2 was later performed. Calculated FiO2 approached 0.60 as gas flow rates increased above 30 l/minute during nose breathing at rest. High peak inspiratory flow rates with exercise were associated with increased air entrainment. Hypopharyngeal pressure increased with increasing delivered gas flow rate. At 50 l/minute the system delivered a mean airway pressure of up to 7.1 cm H20. We believe that the high gas flow rates delivered by this system enable an accurate inspired oxygen fraction to be delivered. The positive mean airway pressure created by the high flow increases the efficacy of this system and may serve as a bridge to formal positive pressure systems. [ABSTRACT FROM AUTHOR]

Objective: To establish the cost-effectiveness of long-term humidification therapy (LTHT) added to usual care for patients with moderate or severe chronic obstructive pulmonary disease or bronchiectasis., Methods: Resource usage in a 12-month clinical trial of LTHT was estimated from hospital records, patient diaries, and the equipment supplier. Health state utility values were derived from the St. Georges Respiratory Questionnaire (SGRQ) total score. All patients who remained in the trial for 12 months and who had at least 90 days of diary records were included (87 of 108)., Results: Clinical costs were NZ $3973 (95% confidence interval [CI] $1614-$6332) for the control group and NZ $3331 (95% CI $948-$6920) for the intervention group. The mean health benefit per patient was -6.9 SGRQ units (95% CI -13.0 to -7.2; P < 0.05) or +0.0678 quality-adjusted life-years (95% CI 0.001-0.135). With the intervention costing NZ $2059 annually, the mean cost per quality-adjusted life-year was NZ $20,902 (US $18,907) and the bootstrap median was NZ $19,749 (2.5th percentile -$40,923, 97.5th percentile $221,275). At a willingness-to-pay (WTP) threshold of NZ $30,000, the probability of cost-effectiveness was 61%, ranging from 49% to 72% as the cost of LTHT was varied by ±30%. At a WTP of NZ $20,000, the probability was 49% (range 34%-61%)., Conclusions: LTHT is moderately cost-effective for patients with moderate to severe chronic obstructive pulmonary disease or bronchiectasis at a WTP threshold that is acceptable for public funding of medicines in New Zealand. These findings must be interpreted with caution because of the modest size of the clinical study, necessary lack of blinding in the clinical trial, and uncertainty in estimating health state utility from the SQRQ., (Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

A common but not necessarily logical requirement in drug development is that a 'limit of quantitation' be set for chemical assays and that observations that fall below the limit should not be treated as real data but should be labelled as below the limit and set aside for special treatment. We examine five of seven approaches to analysing such data considered by Beal in 2001, concentrating in particular on two: one that treats the data as a truncated sample and another that treats them as a censored sample. In fact, using a pattern-mixture framework, one can show that the former consists of using the conditional distribution of the 'acceptable values' and the latter adds the information from the marginal mixing distribution. We illustrate these approaches with a real example, concentrating in particular on the two likelihood-based methods, provide various formulae that may be used to compare these and other approaches, check these formulae using simulations and make some recommendations as to which approach one should use., (Copyright © 2012 John Wiley & Sons, Ltd.)

Aim: Persistent airway inflammation with mucus retention in patients with chronic airway disorders such as COPD and bronchiectasis may lead to frequent exacerbations, reduced lung function and poor quality of life. This study investigates if long-term humidification therapy with high flow fully humidified air at 37 degrees C through nasal cannulae can improve these clinical outcomes in this group of patients., Method: 108 patients diagnosed with COPD or bronchiectasis were randomised to daily humidification therapy or usual care for 12 months over which exacerbations were recorded. Lung function, quality of life, exercise capacity, and measures of airway inflammation were also recorded at baseline, 3 and 12 months., Results: Patients on long-term humidification therapy had significantly fewer exacerbation days (18.2 versus 33.5 days; p = 0.045), increased time to first exacerbation (median 52 versus 27 days; p = 0.0495) and reduced exacerbation frequency (2.97/patient/year versus 3.63/patient/year; p = 0.067) compared with usual care. Quality of life scores and lung function improved significantly with humidification therapy compared with usual care at 3 and 12 months., Conclusion: Long-term humidification therapy significantly reduced exacerbation days, increased time to first exacerbation, improved lung function and quality of life in patients with COPD and bronchiectasis. Clinical trial registered with www.actr.org.au; Number ACTRN2605000623695., (Copyright 2010 Elsevier Ltd. All rights reserved.)

The susceptibility of 1763 yeast isolates (from 22 species and seven genera) was tested using Clinical and Laboratory Standards Institute M27-A2 microdilution methodology. Candida spp. predominated (97.1%), mainly C. albicans (51.4%), C. glabrata (16.4%) and C. tropicalis (13.7%), followed by Trichosporon spp. (1.1%) and Cryptococcus neoformans (1.0%). Most isolates came from blood/catheters (72.0%) or the oesophagus/oropharynx (11.3%). The voriconazole, itraconazole, fluconazole and amphotericin B MIC90 values (minimum inhibitory concentration for 90% of the isolates) for all isolates were 1.0, 2.0, 64 and 1.0 microg/mL, respectively. Voriconazole MICs correlated with those for fluconazole (r = 0.91) and itraconazole (r = 0.90). Only 109 isolates (6.2%) had voriconazole MICs > or = 4.0 microg/mL; all were C. albicans, C. glabrata or C. tropicalis resistant to itraconazole (and most to fluconazole). Isolates from 22 patients with amphotericin MICs > or = 2.0 microg/mL (range 2.0-16.0 microg/mL) were also cross-resistant to one or more of the triazoles. Patients (n = 34) with voriconazole-resistant isolates showed a 56% response to voriconazole therapy, and those patients (n = 261) with susceptible isolates showed a 71% response. Twenty-three voriconazole-treated patients had baseline resistant isolates, in eight patients voriconazole resistance developed during therapy and in three patients a different resistant species arose during therapy. Thus, voriconazole MICs correlate with those of fluconazole and itraconazole and may predict clinical outcome.

Weaned Romney ewe lambs were grazed at two levels of nutrition from 20 December to 12 April. Both groups were grazed together at a high level of nutrition thereafter. Vasectomized rams were introduced on 1 April. Oestrus occurred in 62/84 (74%) of the low nutrition group and in all 24 of the high nutrition group. The mean date of first oestrus was 3 June for the former and 28 May for the latter. The non-oestrous ewes were killed on 17 July and the others within 5 days of showing oestrus. From each carcass, certain organs (i.e. adrenals, ovaries, thyroid, heart, kidneys, liver, lungs, spleen, stomach and uterus) and various fat depots were dissected out and weighed. In addition, half of the carcass was minced and subsampled for protein and fat analysis. The weight of uterus discriminated between oestrous and non-oestrous animals, as did a linear combination of the weights of lungs, spleen and stomach. The data suggest that fatness or protein content, or the weights of the other organs, are not important indicators of sexual maturity in female sheep.