Accuracy of patient self-report as a measure of inhaled asthma medication use.

BACKGROUND AND OBJECTIVE: Measuring adherence to inhaled asthma treatment is a key priority for asthma care. The aim of this study was to determine the relationship between self-report and actual medication use as measured by electronic monitoring for single and combination inhaled corticosteroid (ICS) and long-acting beta-agonist (LABA) metered-dose inhaler therapy. METHODS: In this retrospective analysis from a previously completed prospective 24-week randomized, controlled trial of single or combination ICS/LABA therapy, medication use in the week prior to study visits determined by self-report questionnaire and electronic monitoring was compared. One hundred eleven participants received 125 µg fluticasone dipropionate and 25 µg salmeterol, two actuations twice daily, by either separate or combination ICS/LABA inhalers. Paired data for self-report and electronic monitoring were analysed. Measurement of agreement was by Bland-Altman-like plots by visit with calculation of limits of agreement. RESULTS: For single and combination ICS/LABA therapy, self-report consistently overestimated actual inhaler use assessed by electronic monitoring by a mean of 2.2-8.4 inhalations over a 1-week period, with limits of agreement ranging from ±15.8 to 25.6 inhalations. Participants who underused their inhalers tended to overreport their use, while those who overused tended to underreport their medication use. The greater the degree of underuse, the greater the magnitude of overreport, and likewise, the greater the degree of overuse, the greater the magnitude of underreport. CONCLUSIONS: Self-report is inaccurate in measuring actual use of inhaled asthma treatment with patients who underuse their maintenance therapy overreporting their use and those who overuse their therapy underreporting their use.

Randomised controlled trial of high concentration versus titrated oxygen therapy in severe exacerbations of asthma.

BACKGROUND: The effect on Paco2 of high concentration oxygen therapy when administered to patients with severe exacerbations of asthma is uncertain. METHODS: 106 patients with severe exacerbations of asthma presenting to the Emergency Department were randomised to high concentration oxygen (8 l/min via medium concentration mask) or titrated oxygen (to achieve oxygen saturations between 93% and 95%) for 60 min. Patients with chronic obstructive pulmonary disease or disorders associated with hypercapnic respiratory failure were excluded. The transcutaneous partial pressure of carbon dioxide (Ptco2) was measured at 0, 20, 40 and 60 min. The primary outcome variable was the proportion of patients with a rise in Ptco2 ≥4 mm Hg at 60 min. RESULTS: The proportion of patients with a rise in Ptco2 ≥4 mm Hg at 60 min was significantly higher in the high concentration oxygen group, 22/50 (44%) vs. 10/53 (19%), RR 2.3 (95% CI 1.2 to 4.4, p<0.006). The high concentration group had a higher proportion of patients with a rise in Ptco2 ≥8 mm Hg, 11/50 (22%) vs. 3/53 (6%), RR 3.9 (95% CI 1.2 to 13.1, p=0.016). All 10 patients with a final Ptco2 ≥45 mm Hg received high concentration oxygen therapy, and in five there was an increase in Ptco2 ≥10 mm Hg. CONCLUSION: High concentration oxygen therapy causes a clinically significant increase in Ptco2 in patients presenting with severe exacerbations of asthma. A titrated oxygen regime is recommended in the treatment of severe asthma, in which oxygen is administered only to patients with hypoxaemia, in a dose that relieves hypoxaemia without causing hyperoxaemia. Clinical trial number ACTRN12607000131459.

The value of the CRB65 score to predict mortality in exacerbations of COPD requiring hospital admission.

BACKGROUND AND OBJECTIVE: The CRB65 score, a risk stratification method validated for use in community-acquired pneumonia, has recently been shown to have utility in acute exacerbations of COPD (AECOPD). The objective of this study was to independently validate the CRB65 score as a predictor of mortality in patients who required hospital admission with AECOPD. METHODS: The medical records of patients admitted to Wellington Hospital with AECOPD during a 12-month period from June 2006 were reviewed. Logistic regression was used to determine the strength of the association between the CRB65 score and death at three measurement times: in-hospital, 30days and 12months. RESULTS: Complete data were available in 133/174 patient admissions. In-hospital and 30-day mortality increased progressively with increasing CRB65 score and was markedly higher in the CRB 3-4 group (3%, 5%, 29%, and 4%, 9%, 43% for CRB65 scores 0-1, 2, 3-4 for in-hospital and 30-day mortality, respectively). Differences in 1-year mortality were less apparent (24%, 25%, 57% for CRB65 scores 0-1, 2, 3-4, respectively). The CRB65 score demonstrated a modest value for predicting in-hospital and 30-day mortality with a c statistic of 0.68 at both time points. CONCLUSIONS: The CRB65 score shows similar characteristics for predicting short-term mortality in AECOPD as its use in community-acquired pneumonia. We recommend its use in clinical practice, particularly in patients with a score ≥3, which is associated with a high risk of early mortality, and need for intensive hospital management.

Randomized controlled trial of adherence with single or combination inhaled corticosteroid/long-acting beta-agonist inhaler therapy in asthma.

BACKGROUND: The inhaled corticosteroid (ICS)/long-acting beta-agonist (LABA) combination inhaler has the potential to improve adherence with ICS therapy in asthma. OBJECTIVE: To determine whether ICS/LABA combination inhaler therapy improves adherence compared with separate inhaler use. METHODS: In a 24-week randomized controlled parallel group study, 111 subjects were prescribed 125 microg fluticasone dipropionate (FP) and 25 microg salmeterol, 2 actuations twice daily through either a combination inhaler or separate inhalers concurrently. Medication use was recorded by covert electronic monitors. The primary outcome variable was adherence during the final 6-week period, defined as the number of doses taken as a percentage of those prescribed. RESULTS: Complete adherence data from the final 6-week period were available for 49 and 54 subjects in the separate and combination groups, respectively. The mean (SD) adherence was 73.7% (36.0) for FP, 76.7% (30.5) for salmeterol, and 82.4% (24.5) for FP/salmeterol. There were no significant differences in adherence between FP/salmeterol and FP (-8.7%; 95% CI, -10.6 to 3.3) and salmeterol (-5.6%; 95% CI, -16.4 to 5.1). There was no significant difference in overuse among the FP, salmeterol, or FP/salmeterol groups. In 2 (4%) of 49 subjects, salmeterol was effectively taken as monotherapy during a 6-week period. CONCLUSION: In the setting of a randomized controlled trial, use of a combination ICS/LABA inhaler does not markedly increase adherence above that observed with separate inhaler use. LABA monotherapy was observed in a small proportion of patients prescribed ICS and LABA therapy via separate inhalers.

Long-acting beta-agonists and asthma death: how useful are different study designs to evaluate the potential association?

BACKGROUND AND OBJECTIVE: There is uncertainty whether long-acting beta-agonist (LABA) drugs may increase the risk of asthma mortality. This uncertainty is partly due to the difficulty in estimating the risk of rare adverse outcomes. The aim of this paper is to consider the utility of three approaches to determine the magnitude and statistical significance of this potential association. METHODS: Using a death rate of 9 per 10,000 subjects with asthma, derived from a meta-analysis of randomized controlled trials (RCTs) of formoterol, power calculations for a single RCT, a case-control study, and a meta-analysis of RCTs were determined. RESULTS: For each study design, the number of subjects and events required to have adequate statistical power to detect a 1.5- and 2.0-fold increased risk of death were calculated. For a single RCT, or meta-analyses of RCTs, very large sample sizes are required. In contrast, case-control methodology represents a realistic method of estimating the risk of rare serious adverse events. CONCLUSIONS: Major practical limitations exist in the use of RCTs to determine the potential risk of death with LABAs in the treatment of asthma. Case-control methodology may be more effective in establishing causation; however, if selection bias occurs, estimates of risk may be inaccurate.

An audit of the effect of oxygen prescription charts on clinical practice.

PROBLEM: The need to improve the prescription, administration and monitoring of oxygen therapy. DESIGN: An interventional, prospective audit. BACKGROUND AND SETTING: Wellington Hospital, a teaching and tertiary referral hospital in New Zealand in 2007 and 2008. KEY MEASURES FOR IMPROVEMENT: Demonstration of adequate oxygen prescribing, administration and monitoring of oxygen therapy. STRATEGIES FOR IMPROVEMENT: The introduction of a new drug chart with a specific oxygen prescription section. Targeted educational lectures primarily to medical staff. EFFECTS OF CHANGE: 610 and 566 patients were reviewed in the first and second audits. After introduction of the new oxygen prescription section on the drug chart the proportion of patients whose oxygen therapy was prescribed increased from 15/85 (17.6%) to 39/98 (39.8%), relative risk 2.3 (95% CI 1.3 to 3.9). The proportion with adequate oxygen prescription, with documentation of device, flow rate or inspired oxygen concentration, and the target oxygen saturation increased from 5/85 (5.9%) to 36/98 (36.7%), relative risk 6.2 (95% CI 2.5 to 15.0). Introduction of the new charts was not associated with changes in clinical practice in terms of assessment of oxygen saturations on room air and commencement if < or = 92%, or the titration of oxygen therapy in response to oxygen saturations < or = 92%. LESSONS LEARNT: An oxygen prescription section on hospital drug charts improved the prescription of oxygen but did not improve clinical practice. Additional strategies are required to improve the administration of oxygen therapy in hospitals.

Systematic review of studies of the effect of hyperoxia on coronary blood flow.

BACKGROUND: International guidelines recommend the routine use of oxygen in the initial treatment of myocardial infarction, yet it is uncertain what effect this might have on physiologic and clinical outcomes. METHODS: We undertook a systematic search of Medline, Cochrane Database of Systematic Reviews, EMBASE, and CINHAL using the key words "oxygen," "coronary blood flow," "hyperoxia," and "coronary circulation" to identify human studies involving a measure of coronary blood flow while breathing oxygen and room air. The primary outcome measure was coronary blood flow; secondary outcomes included coronary vascular resistance and myocardial oxygen consumption. RESULTS: From 2,072 potential publications, there were 6 studies from 4 publications that met the inclusion criteria, with 6 healthy subjects and 61 subjects with cardiac disease. It was not possible to undertake a meta-analysis due to methodological limitations. In the 6 studies, high-concentration oxygen therapy resulted in hyperoxia, with a range in mean Pao(2) of 273 to 425 mm Hg. Hyperoxia caused a significant reduction in coronary blood flow (mean change -7.9% to -28.9%, n = 6 studies). Hyperoxia caused a significant increase in coronary vascular resistance (mean change 21.5% to 40.9%, n = 4 studies) and a significant reduction in myocardial oxygen consumption (mean change -15.3% to -26.9%, n = 3 studies). CONCLUSIONS: Hyperoxia from high-concentration oxygen therapy causes a marked reduction in coronary blood flow and myocardial oxygen consumption. These physiologic effects may have the potential to cause harm and are relevant to the use of high-concentration oxygen therapy in the treatment of cardiac and other disorders.

British Thoracic Society quality standards for home oxygen use in adults.

INTRODUCTION: The purpose of the quality standards document is to provide healthcare professionals, commissioners, service providers and patients with a guide to standards of care that should be met for home oxygen provision in the UK, together with measurable markers of good practice. Quality statements are based on the British Thoracic Society (BTS) Guideline for Home Oxygen Use in Adults. METHODS: Development of BTS Quality Standards follows the BTS process of quality standard production based on the National Institute for Health and Care Excellence process manual for the development of quality standards. RESULTS: 10 quality statements have been developed, each describing a key marker of high-quality, cost-effective care for home oxygen use, and each statement is supported by quality measures that aim to improve the structure, process and outcomes of healthcare. DISCUSSION: BTS Quality Standards for home oxygen use in adults form a key part of the range of supporting materials that the society produces to assist in the dissemination and implementation of a guideline's recommendations.

Randomized controlled trial of high concentration oxygen in suspected community-acquired pneumonia.

OBJECTIVE: To determine whether high concentration oxygen increases the PaCO(2) in the treatment of community-acquired pneumonia. DESIGN: Randomized controlled clinical trial in which patients received high concentration oxygen (8 L/min via medium concentration mask) or titrated oxygen (to achieve oxygen saturations between 93 and 95%) for 60 minutes. Transcutaneous CO(2) (PtCO(2)) was measured at 0, 20, 40 and 60 minutes. SETTING: The Emergency Departments at Wellington, Hutt and Kenepuru Hospitals. PARTICIPANTS: 150 patients with suspected community-acquired pneumonia presenting to the Emergency Department. Patients with chronic obstructive pulmonary disease (COPD) or disorders associated with hypercapnic respiratory failure were excluded. MAIN OUTCOME VARIABLES: The primary outcome variable was the proportion of patients with a rise in PtCO(2) ≥4 mmHg at 60 minutes. Secondary outcome variables included the proportion of patients with a rise in PtCO(2) ≥8 mmHg at 60 minutes. RESULTS: The proportion of patients with a rise in PtCO(2) ≥4 mmHg at 60 minutes was greater in the high concentration oxygen group, 36/72 (50.0%) vs 11/75 (14.7%), relative risk (RR) 3.4 (95% CI 1.9 to 6.2), P < 0.001. The high concentration group had a greater proportion of patients with a rise in PtCO(2) ≥8 mmHg, 11/72 (15.3%) vs 2/75 (2.7%), RR 5.7 (95% CI 1.3 to 25.0), P = 0.007. Amongst the 74 patients with radiological confirmation of pneumonia, the high concentration group had a greater proportion with a rise in PtCO(2) ≥4 mmHg, 20/35 (57.1%) vs 5/39 (12.8%), RR 4.5 (95% CI 1.9 to 10.6) P < 0.001. CONCLUSIONS: We conclude that high concentration oxygen therapy increases the PtCO(2) in patients presenting with suspected community-acquired pneumonia. This suggests that the potential increase in PaCO(2) with high concentration oxygen therapy is not limited to COPD, but may also occur in other respiratory disorders with abnormal gas exchange.

The effect of supplemental oxygen on hypercapnia in subjects with obesity-associated hypoventilation: a randomized, crossover, clinical study.

BACKGROUND: It is unknown whether oxygen therapy causes worsening hypercapnia in patients with obesity-associated hypoventilation (OAH), similar to the response observed in COPD. The objectives of this study were to investigate whether breathing 100% oxygen results in an increase in hypercapnia in patients with OAH and the mechanisms of any effect. METHODS: In this double-blind, randomized, controlled, crossover trial, 24 outpatients with newly diagnosed OAH inhaled 100% oxygen or room air for 20 min on 2 separate days. Transcutaneous CO(2) tension (Ptco(2)), minute ventilation, and volume of dead space to tidal volume ratio were measured at baseline and at 20 min. A mixed linear model was used to determine differences between the two treatments. RESULTS: The study was terminated in three subjects breathing 100% oxygen due to a Ptco(2) increase ≥ 10 mm Hg, which occurred after 10:35, 13:20, and 15:51 min. Ptco(2) increased by 5.0 mm Hg (95% CI, 3.1-6.8; P < .001) with oxygen compared with room air. Minute ventilation decreased by 1.4 L/min (95% CI, 0.11-2.6 L/min; P = .03), and volume of dead space to tidal volume ratio increased by 0.067 (95% CI, 0.035-0.10; P < .001) with oxygen compared with room air. CONCLUSIONS: Breathing 100% oxygen causes worsening hypercapnia in stable patients with OAH. TRIAL REGISTRY: Australia New Zealand Clinical Trials Registry; No.: ACTRN 12608000592347; URL: www.anzctr.org.au.

Honey in the treatment of burns: a systematic review and meta-analysis of its efficacy.

AIM: To determine the efficacy of honey in burn wound management. METHODS: A systematic review and meta-analysis of randomised controlled trials which compared the efficacy of honey with a comparator dressing treatment in the management of burns. The main outcome measure was the proportion of subjects with wounds healed at 15 days. RESULTS: Eight studies with 624 subjects were included in the meta-analysis. The quality of the studies was poor with each study having a Jadad score of 1. Six studies were undertaken by the same investigator. In most studies unprocessed honey covered by sterile gauze was compared with silver sulphadiazine-impregnated gauze. The fixed effects odds ratio for healing at 15 days was 6.1 (95% CI 3.7 to 9.9) in favour of honey having a superior effect. The random effects pooled odds ratio was 6.7 (95% CI 2.8 to 15.8) in favour of honey treatment. The secondary outcome variables all showed significantly greater efficacy for honey treatment. CONCLUSION: Available evidence indicates markedly greater efficacy of honey compared with alternative dressing treatments for superficial or partial thickness burns, although the limitations of the studies included in the meta-analysis restrict the clinical application of these findings. Further studies are urgently required to determine the role of honey in the management of superficial or partial thickness burns.

International trends in asthma mortality rates in the 5- to 34-year age group: a call for closer surveillance.

BACKGROUND: International time trends in asthma mortality have played an important sentinel role in the identification of two epidemics of asthma mortality in some countries in the 1960s and the 1970s and 1980s. Since then, little attention has been paid to the ongoing international time trends. METHODS: Country-specific data on asthma mortality rates since 1960 in the 5- to 34-year-old age group were collated. To be included in the analysis, countries were required to have data available prior to 1980. A scatter plot smoothing technique was used to model the change in asthma mortality rates with time. RESULTS: Asthma mortality rates from 20 countries were included in the analysis. An increase in asthma mortality rates was found in the 1960s, with a mean increase of 53% from 0.55 per 100,000 in 1960 and 1961 to a peak of 0.84 in 1966 and 1967. This trend was followed by a progressive decline to a nadir of 0.45 per 100,000 in 1974 and 1975. A gradual increase was then found in asthma mortality rates to a peak of 0.62 per 100,000 in 1985 and 1986, with a mean increase of 38% during this period. Since the late 1980s, there has been a widespread and progressive reduction in mortality rates to a level of 0.23 per 100,000 in 2004 and 2005, with a mean reduction of 63% during this period. CONCLUSIONS: The widespread increase in asthma mortality in the 1980s and the subsequent, even greater reduction has largely gone unrecognized. We propose that awareness of such trends and their causes is important and that they are investigated contemporaneously.