The effect of varenicline and nicotine patch on smoking rate and satisfaction with smoking: an examination of the mechanism of action of two pre-quit pharmacotherapies.

OBJECTIVES: In recent years, there has been growing research interest in using nicotine replacement medications to aid smoking reduction prior to a quit attempt. Gaining a better understanding of how treatments influence smoking reduction may allow for better tailoring of treatments and, ultimately, better cessation outcomes. The objective of the current study was to test the effects of the pre-quit use of varenicline and nicotine patch on smoking rate and satisfaction with smoking. METHODS: All participants were required to attend up to five study visit sections. Participants (n = 213) who were interested in quitting were randomised (open-label) to receive either pre-quit patch or varenicline (both treatments started 2 weeks prior to an assigned quit day, followed by 10 weeks post-quit) or standard patch (10 weeks starting from an assigned quit day). Participants used modified smartphones to monitor their smoking in real time for 4 weeks. RESULTS: Participants in the two pre-quit treatment groups reported significant reductions in both their satisfaction with smoking (p < 0.001) and smoking rate (p < 0.001) from baseline to the end of pre-quit period; participants in the standard patch group did not. The observed reduction of smoking rate was associated with the satisfaction with smoking (p < 0.01), although the mediation effect of satisfaction was small. CONCLUSIONS: Pre-quit treatment caused reductions in satisfaction with smoking and smoking rate. Satisfaction was associated with changes in smoking rate, but the relationship was weak. As such, monitoring reductions in satisfaction do not appear to be a viable method of evaluating responsiveness to treatment.

Examination of the mechanism of action of two pre-quit pharmacotherapies for smoking cessation.

BACKGROUND: There is substantial scope for improvement in the current arsenal of smoking cessation methods and techniques: even when front-line cessation treatments are utilized, smokers are still more likely to fail than to succeed. Studies testing the incremental benefit of using nicotine patch for 1-4 weeks prior to quitting have shown pre-quit nicotine patch use produces a robust incremental improvement over standard post-quit patch treatment. The primary objective of the current study is to test the mechanism of action of two pre-quit smoking cessation medications-varenicline and nicotine patch-in order to learn how best to optimize these pre-quit treatments. METHODS/DESIGN: The study is a three group, randomized, open-label controlled clinical trial. Participants (n = 216 interested quitters) will be randomized to receive standard patch treatment (10 weeks of patch starting from a designated quit day), pre-quit patch treatment (two weeks of patch treatment prior to a quit day, followed by 10 weeks post-quit treatment) or varenicline (starting two weeks prior to quit day followed by 10 weeks post-quit). Participants will use study-specific modified smart-phones to monitor their smoking, withdrawal symptoms, craving, mood and social situations in near real-time over four weeks; two weeks prior to an assigned quit date and two weeks after this date. Smoking and abstinence will be assessed at regular study visits and biochemically verified. DISCUSSION: Understanding how nicotine patches and varenicline influence abstinence may allow for better tailoring of these treatments to individual smokers. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12614000329662 (Registered: 27 March 2014).

Platinum versus non-platinum chemotherapy regimens for small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) is a very fast growing form of cancer and is characterised by early metastasis. As a result, chemotherapy is the mainstay of treatment. A number of different platinum-based chemotherapy regimens and non-platinum-based chemotherapy regimens have been used for the treatment of SCLC, with varying results. This review was conducted to analyse the data from these studies in order to compare their effectiveness. OBJECTIVES: To determine the effectiveness of platinum chemotherapy regimens compared with non-platinum chemotherapy regimens in the treatment of SCLC with respect to survival, tumour response, toxicity and quality of life. SEARCH METHODS: We searched the biomedical literature databases CENTRAL (TheCochrane Library 2014, Issue 7), MEDLINE, EMBASE and CINAHL from 1966 to August 2014. In addition, we handsearched reference lists from relevant resources. SELECTION CRITERIA: All randomised controlled trials involving patients with pathologically confirmed SCLC (including both limited-stage disease and extensive-stage disease) and the use of a platinum-based chemotherapy regimen in at least one treatment arm and a non-platinum-based chemotherapy regimen in a separate arm. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by the Cochrane Collaboration. Two authors independently assessed search results. We assessed included studies for methodological quality and recorded the following outcome data: survival, tumour response, toxicity and quality of life. We combined the results of the survival, tumour response and toxicity data in a meta-analysis. Quality-of-life data were analysed individually. MAIN RESULTS: A total of 32 studies involving 6075 patients with SCLC were included in this systematic review. The majority of studies were multi-centre randomised controlled trials conducted throughout Europe, North America and Asia with the earliest study publishing data in 1981 and the latest in 2014. The duration of studies ranged from 12 to 72 months with a median of 32 months. The median age of patients in the vast majority of studies was between 60 and 65 years of age. Eighteen studies presented data on extensive-stage disease. Nine studies presented data on limited-stage disease. Eleven studies did not present data based on the disease stage. These data were analysed separately in subgroup analyses. Sixteen (50%) studies were of good quality with a low risk of bias and the data from these studies were analysed separately in a heterogeneity analysis.There was no statistically significant difference between treatment groups in terms of survival at 6 months, 12 months and 24 months. There was also no statistically significant difference in terms of overall tumour response. However, platinum-based treatment regimens did have a significantly higher rate of complete response. Platinum-based chemotherapy regimens had significantly higher rates of nausea and vomiting and thrombocytopenia toxicity. Four trials presented quality-of-life data, but, due to the different systems used to measure quality of life this data could not be combined in a meta-analysis. AUTHORS' CONCLUSIONS: Platinum-based chemotherapy regimens did not offer a statistically significant benefit in survival or overall tumour response compared with non-platinum-based regimens. However, platinum-based chemotherapy regimens did increase complete response rates, at the cost of higher adverse events including nausea and vomiting, anaemia and thrombocytopenia toxicity. These data suggest non-platinum chemotherapy regimens have a more advantageous risk-benefit profile. This systematic review highlights the lack of quality-of-life data in trials involving chemotherapy treatment for SCLC. With poor long-term survival associated with both treatment groups, the issue of the quality of the survival period takes on even more significance. It would be beneficial for future trials in this area to include a quality-of-life assessment.

Patient Anxiety and Depression Moderate the Effects of Increased Self-management Knowledge on Physical Activity: A Secondary Analysis of a Randomised Controlled Trial on Health-Mentoring in COPD.

OBJECTIVE: Anxiety and depression are common comorbidities in people with chronic obstructive pulmonary disease (COPD). While these comorbidities could potentially lead to a higher motivation to learn about self-management, they could also inhibit patients from translating this knowledge into appropriate self-management behaviours. This paper explores the moderating effects of anxiety and depression on a health-mentoring intervention, focusing on mechanisms of change (mediation). METHODS: 182 COPD patients participated in an RCT, with anxiety and depression assessed by the Hospital Anxiety and Depression Scale (HADS), self-management knowledge by the Partners in Health Scale, and spontaneous physical activity using accelerometers, all measured at baseline, 6 and 12 months. The moderated mediation model tested the intervention's effect on physical activity, mediated via changes in self-management knowledge, at different levels of anxiety and depression. RESULTS: Knowledge mediated the effect of the intervention on changes in physical activity only for participants reporting low levels of anxiety or depression. Both acted as moderators: Increased knowledge led to more physical activity among participants reporting low anxiety or depression and to less activity among highly anxious or depressed participants. CONCLUSION: Although health-mentoring interventions can be an effective tool to increase knowledge and physical activity among COPD patients, it is essential to take anxiety and depression into account, as increased knowledge may have detrimental effects in highly anxious or depressed participants. This suggests that patients with elevated anxiety or depression may need to be treated appropriately before engaging in chronic disease self-management interventions.

Diagnosis and early detection of COPD using spirometry.

The standard respiratory function test for case detection of chronic obstructive pulmonary disease (COPD) is spirometry. The criterion for diagnosis defined in guidelines is based on the FEV1/FVC ratio forced expiratory ratio (FER) and its severity is based on forced expiratory volume in one second (FEV1) from measurements obtained during maximal forced expiratory manoeuvres. Spirometry is a safe and practical procedure, and when conducted by a trained operator using a spirometer that provides quality feedback, the majority of patients can be coached to provide acceptable and repeatable results. This allows potentially wide application of testing to improve recognition and diagnosis of COPD, such as for case finding in primary care. However, COPD remains substantially under diagnosed in primary care and a major reason for this is underuse of spirometry. The presence of symptoms is not a reliable indicator of disease and diagnosis is often delayed until more severe airflow obstruction is present. Early diagnosis is worthwhile, as it allows risk factors for COPD such as smoking to be addressed promptly and treatment optimised. Paradoxically, investigation of the patho-physiology in COPD has shown that extensive small airway disease exists before it is detectable with conventional spirometric indices, and methods to detect airway disease earlier using the flow-volume curve are discussed.

Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Current guidelines recommend that patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) should be treated with systemic corticosteroid for seven to 14 days. Intermittent systemic corticosteroid use is cumulatively associated with adverse effects such as osteoporosis, hyperglycaemia and muscle weakness. Shorter treatment could reduce adverse effects. OBJECTIVES: To compare the efficacy of short-duration (seven or fewer days) and conventional longer-duration (longer than seven days) systemic corticosteroid treatment of adults with acute exacerbations of COPD. SEARCH METHODS: Searches were carried out using the Cochrane Airways Group Specialised Register of Trials, MEDLINE and CENTRAL (Cochrane Central Register of Controlled Trials) up to June 2014 and ongoing trials registers up to July 2014. SELECTION CRITERIA: Randomised controlled trials comparing different durations of systemic corticosteroid defined as short (i.e. seven or fewer days) or longer (i.e. longer than seven days). Other interventions-bronchodilators and antibiotics-were standardised. Studies with participants requiring assisted ventilation were excluded. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by The Cochrane Collaboration. MAIN RESULTS: Eight studies with 582 participants met the inclusion criteria, of which five studies conducted in hospitals with 519 participants (range 28 to 296) contributed to the meta-analysis. Mean ages of study participants were 65 to 73 years, the proportion of male participants varied (58% to 84%) and COPD was classified as severe or very severe. Corticosteroid treatment was given at equivalent daily doses for three to seven days for short-duration treatment and for 10 to 15 days for longer-duration treatment. Five studies administered oral prednisolone (30 mg in four, tapered in one), and two studies provided intravenous corticosteroid treatment. Studies contributing to the meta-analysis were at low risk of selection, performance, detection and attrition bias. In four studies we did not find a difference in risk of treatment failure between short-duration and longer-duration systemic corticosteroid treatment (n = 457; odds ratio (OR) 0.72, 95% confidence interval (CI) 0.36 to 1.46)), which was equivalent to 22 fewer per 1000 for short-duration treatment (95% CI 51 fewer to 34 more). No difference in risk of relapse (a new event) was observed between short-duration and longer-duration systemic corticosteroid treatment (n = 457; OR 1.04, 95% CI 0.70 to 1.56), which was equivalent to nine fewer per 1000 for short-duration treatment (95% CI 68 fewer to 100 more). Time to the next COPD exacerbation did not differ in one large study that was powered to detect non-inferiority and compared five days versus 14 days of systemic corticosteroid treatment (n = 311; hazard ratio 0.95, 95% CI 0.66 to 1.37). In five studies no difference in the likelihood of an adverse event was found between short-duration and longer-duration systemic corticosteroid treatment (n = 503; OR 0.89, 95% CI 0.46 to 1.69, or nine fewer per 1000 (95% CI 44 fewer to 51 more)). Length of hospital stay (n = 421; mean difference (MD) -0.61 days, 95% CI -1.51 to 0.28) and lung function at the end of treatment (n = 185; MD FEV1 -0.04 L; 95% CI -0.19 to 0.10) did not differ between short-duration and longer-duration treatment. AUTHORS' CONCLUSIONS: Information from a new large study has increased our confidence that five days of oral corticosteroids is likely to be sufficient for treatment of adults with acute exacerbations of COPD, and this review suggests that the likelihood is low that shorter courses of systemic corticosteroids (of around five days) lead to worse outcomes than are seen with longer (10 to 14 days) courses. We graded most available evidence as moderate in quality because of imprecision; further research may have an important impact on our confidence in the estimates of effect or may change the estimates. The studies in this review did not include people with mild or moderate COPD; further studies comparing short-duration systemic corticosteroid versus conventional longer-duration systemic corticosteroid for treatment of adults with acute exacerbations of COPD are required.

Conservative versus interventional management for primary spontaneous pneumothorax in adults.

BACKGROUND: Primary spontaneous pneumothorax is widely managed according to size with interventional techniques based on practice guidelines. Interventional management is not without complications and observational data suggest conservative management works. The current guidelines are based on expert consensus rather than evidence, and a systematic review may help in identifying evidence for this practice. OBJECTIVES: The objective of the review is to compare conservative and interventional treatments of adult primary spontaneous pneumothorax for outcomes of clinical efficacy, tolerability and safety. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 6, 2014); MEDLINE via Ovid SP (1920 to 26th June 2014); EMBASE via Ovid SP (1947 to 26th June 2014); CINAHL via EBSCO host (1980 to 26th June 2014); and ISI Web of Science (1945 to 26th June 2014). We searched ongoing trials via the relevant databases and contacted authors. We also searched the 'grey literature'. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and we accepted quasi-RCTs if a systematic method of allocation was used. Participants were limited to adults aged 18 to 50 years, with their first symptomatic primary spontaneous pneumothorax with radiological evidence and no underlying lung disease. DATA COLLECTION AND ANALYSIS: Two of five authors independently reviewed all studies in the search criteria and made inclusions and exclusions according to the selection criteria. No statistical methods were necessary as there were no included trials. MAIN RESULTS: We identified 358 studies with duplicates removed. There were three potentially relevant studies that we excluded as they were not randomized controlled trials. There was one ongoing trial that was relevant and we contacted the authors and confirmed the study is ongoing at June 2014. We will update this review when this ongoing study is completed. AUTHORS' CONCLUSIONS: There are no completed randomized controlled trials comparing conservative and interventional management for primary spontaneous pneumothorax in adults. There is a lack of high-quality evidence for current guidelines in management and a need for randomized controlled trials comparing conservative and interventional management for this condition.

Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of hospital admission and mortality. They contribute to long-term decline in lung function, physical capacity and quality of life. The most common causes are infective, and treatment includes antibiotics, bronchodilators and systemic corticosteroids as anti-inflammatory agents. OBJECTIVES: To assess the effects of corticosteroids administered orally or parenterally for treatment of acute exacerbations of COPD, and to compare the efficacy of parenteral versus oral administration. SEARCH METHODS: We carried out searches using the Cochrane Airways Group Specialised Register of Trials, MEDLINE and CENTRAL (Cochrane Central Register of Controlled Trials), and checked references of included studies and trials registries. We conducted the last search in May 2014. SELECTION CRITERIA: Randomised controlled trials comparing corticosteroids administered orally or parenterally with an appropriate placebo, or comparing oral corticosteroids with parenteral corticosteroids in the treatment of people with acute exacerbations of COPD. Other interventions (e.g. bronchodilators and antibiotics) were standardised for both groups. We excluded clinical studies of acute asthma. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: Sixteen studies (n = 1787) met inclusion criteria for the comparison systemic corticosteroid versus placebo and 13 studies contributed data (n = 1620). Four studies (n = 298) met inclusion criteria for the comparison oral corticosteroid versus parenteral corticosteroid and three studies contributed data (n = 239). The mean age of participants with COPD was 68 years, median proportion of males 82% and mean forced expiratory volume in one second (FEV1) per cent predicted at study admission was 40% (6 studies; n = 633). We judged risk of selection, detection, attrition and reporting bias as low or unclear in all studies. We judged risk of performance bias high in one study comparing systemic corticosteroid with control and in two studies comparing intravenous corticosteroid versus oral corticosteroid.Systemic corticosteroids reduced the risk of treatment failure by over half compared with placebo in nine studies (n = 917) with median treatment duration 14 days, odds ratio (OR) 0.48 (95% confidence interval (CI) 0.35 to 0.67). The evidence was graded as high quality and it would have been necessary to treat nine people (95% CI 7 to 14) with systemic corticosteroids to avoid one treatment failure. There was moderate-quality evidence for a lower rate of relapse by one month for treatment with systemic corticosteroid in two studies (n = 415) (hazard ratio (HR) 0.78; 95% CI 0.63 to 0.97). Mortality up to 30 days was not reduced by treatment with systemic corticosteroid compared with control in 12 studies (n = 1319; OR 1.00; 95% CI 0.60 to 1.66).FEV1, measured up to 72 hours, showed significant treatment benefits (7 studies; n = 649; mean difference (MD) 140 mL; 95% CI 90 to 200); however, this benefit was not observed at later time points. The likelihood of adverse events increased with corticosteroid treatment (OR 2.33; 95% CI 1.59 to 3.43). Overall, one extra adverse effect occurred for every six people treated (95% CI 4 to 10). The risk of hyperglycaemia was significantly increased (OR 2.79; 95% CI 1.86 to 4.19). For general inpatient treatment, duration of hospitalisation was significantly shorter with corticosteroid treatment (MD -1.22 days; 95% CI -2.26 to -0.18), with no difference in length of stay the intensive care unit (ICU) setting.Comparison of parenteral versus oral treatment showed no significant difference in the primary outcomes of treatment failure, relapse or mortality or for any secondary outcomes. There was a significantly increased rate of hyperglycaemia in one study (OR 4.89; 95% CI 1.20 to 19.94). AUTHORS' CONCLUSIONS: There is high-quality evidence to support treatment of exacerbations of COPD with systemic corticosteroid by the oral or parenteral route in reducing the likelihood of treatment failure and relapse by one month, shortening length of stay in hospital inpatients not requiring assisted ventilation in ICU and giving earlier improvement in lung function and symptoms. There is no evidence of benefit for parenteral treatment compared with oral treatment with corticosteroid on treatment failure, relapse or mortality. There is an increase in adverse drug effects with corticosteroid treatment, which is greater with parenteral administration compared with oral treatment.

High-flow nasal cannula therapy for infants with bronchiolitis.

BACKGROUND: Bronchiolitis is a common lower respiratory tract illness, usually of viral aetiology, affecting infants younger than 24 months of age and is a frequent cause of hospitalisation. It causes airway inflammation, mucus production and mucous plugging, resulting in airway obstruction. Effective pharmacotherapy is lacking and bronchiolitis is a major cause of morbidity and mortality.Conventional treatment consists of supportive therapy in the form of fluids, supplemental oxygen and respiratory support. Traditionally oxygen delivery is as a dry gas at 100% concentration via low-flow nasal prongs. However, the use of heated, humidified, high-flow nasal cannula (HFNC) therapy enables delivery of higher inspired gas flows of an air/oxygen blend, up to 12 L/min in infants and 30 L/min in children. Its use provides some level of continuous positive airway pressure to improve ventilation in a minimally invasive manner. This may reduce the need for invasive respiratory support thus potentially lowering costs, with clinical advantages and fewer adverse effects. OBJECTIVES: To assess the effects of HFNC therapy compared with conventional respiratory support in the treatment of infants with bronchiolitis. SEARCH METHODS: We searched CENTRAL (2013, Issue 4), MEDLINE (1946 to May week 1, 2013), EMBASE (January 2010 to May 2013), CINAHL (1981 to May 2013), LILACS (1982 to May 2013) and Web of Science (1985 to May 2013). In addition we consulted ongoing trial registers and experts in the field to identify ongoing studies, checked reference lists of relevant articles and searched conference abstracts. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs which assessed the effects of HFNC (delivering oxygen or oxygen/room air blend at flow rates greater than 4 L/min) compared to conventional treatment in infants (< 24 months) with a clinical diagnosis of bronchiolitis. DATA COLLECTION AND ANALYSIS: Two review authors independently used a standard template to assess trials for inclusion and extract data on study characteristics, 'Risk of bias' elements and outcomes. We contacted trial authors to request missing data. Outcome measures included the need for invasive respiratory support and time until discharge, clinical severity measures, oxygen saturation, duration of oxygen therapy and adverse events. MAIN RESULTS: We included one RCT which was a pilot study with 19 participants that compared HFNC therapy with oxygen delivery via a head box. In this study, we judged the risk of selection, attrition and reporting bias to be low, and we judged the risk of performance and detection bias to be unclear due to lack of blinding. The median oxygen saturation (SpO2) was higher in the HFNC group at eight hours (100% versus 96%, P = 0.04) and at 12 hours (99% versus 96%, P = 0.04) but similar at 24 hours. There was no clear evidence of a difference in total duration of oxygen therapy, time to discharge or total length of stay between groups. No adverse events were reported in either group and no participants in either group required further respiratory support. Five ongoing trials were identified but no data were available in May 2013. We were not able to perform a meta-analysis. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine the effectiveness of HFNC therapy for treating infants with bronchiolitis. The current evidence in this review is of low quality, from one small study with uncertainty about the estimates of effect and an unclear risk of performance and detection bias. The included study provides some indication that HFNC therapy is feasible and well tolerated. Further research is required to determine the role of HFNC in the management of bronchiolitis in infants. The results of the ongoing studies identified will contribute to the evidence in future updates of this review.

Compliance with an EMA monitoring protocol and its relationship with participant and smoking characteristics.

INTRODUCTION: Arguably, the greatest advantage of ecological momentary assessment (EMA) studies is that data are collected repeatedly in real-time and real-world situations, which reduces recall and situational biases and thus improves the accuracy and validity of the data collected. However, the validity of EMA data is contingent upon compliance rates. If participant characteristics are related to missing data, analyses should control for these factors, or they should be targeted in EMA training sessions. This study evaluates the impact of demographic and smoking-related participant characteristics on compliance to an EMA smoking study protocol. METHODS: Prequit-day data were taken from the control arm of an ongoing randomized controlled trial of a smoking-cessation program. After training, 119 participants were asked to carry a mobile device with them at all times for ~6 days and to log every cigarette they smoked in addition to completing randomly scheduled assessments. Different types of compliance were assessed: the percentage of completed random prompts (signal-contingent compliance), the percentage of logged cigarettes per day compared to a timeline follow-back measure, and the correlation between logged cigarettes and a carbon monoxide assessment 2 hr later (both event-contingent compliance). RESULTS: Overall compliance rates were 78.48% for event-contingent and 72.17% for signal-contingent compliance. None of the demographic or smoking-related participant characteristics predicted signal-contingent compliance; however, female participants showed higher event-contingent compliance than male participants, and Caucasian participants showed higher event-contingent compliance than non-Caucasian participants. CONCLUSIONS: Compliance did not depend on smoking-related characteristics. EMA is a valid method for assessing smoking behavior in real-time and real-world settings.

Long-acting beta2-agonists for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a respiratory disease that causes progressive symptoms of breathlessness, cough and mucus build-up. It is the fourth or fifth most common cause of death worldwide and is associated with significant healthcare costs.Inhaled long-acting beta2-agonists (LABAs) are widely prescribed to manage the symptoms of COPD when short-acting agents alone are no longer sufficient. Twice-daily treatment with an inhaled LABA is aimed at relieving symptoms, improving exercise tolerance and quality of life, slowing decline and even improving lung function and preventing and treating exacerbations. OBJECTIVES: To assess the effects of twice-daily long-acting beta2-agonists compared with placebo for patients with COPD on the basis of clinically important endpoints, primarily quality of life and COPD exacerbations. SEARCH METHODS: We searched the Cochrane Airways Group trials register, ClinicalTrials.gov and manufacturers' websites in June 2013. SELECTION CRITERIA: Parallel, randomised controlled trials (RCTs) recruiting populations of patients with chronic obstructive pulmonary disease. Studies were required to be at least 12 weeks in duration and designed to assess the safety and efficacy of a long-acting beta2-agonist against placebo. DATA COLLECTION AND ANALYSIS: Data and characteristics were extracted independently by two review authors, and each study was assessed for potential sources of bias. Data for all outcomes were pooled and subgrouped by LABA agent (formoterol 12 µg, formoterol 24 µg and salmeterol 50 µg) and then were separately analysed by LABA agent and subgrouped by trial duration. Sensitivity analyses were conducted for the proportion of participants taking inhaled corticosteroids and for studies with high or uneven rates of attrition. MAIN RESULTS: Twenty-six RCTs met the inclusion criteria, randomly assigning 14,939 people with COPD to receive twice-daily LABA or placebo. Study duration ranged from three months to three years; the median duration was six months. Participants were more often male with moderate to severe symptoms at randomisation; mean forced expiratory volume in 1 second (FEV1) was between 33% and 55% predicted normal in the studies, and mean St George's Respiratory Questionnaire score (SGRQ) ranged from 44 to 55 when reported.Moderate-quality evidence showed that LABA treatment improved quality of life on the SGRQ (mean difference (MD) -2.32, 95% confidence interval (CI) -3.09 to -1.54; I(2) = 50%; 17 trials including 11,397 people) and reduced the number of exacerbations requiring hospitalisation (odds ratio (OR) 0.73, 95% CI 0.56 to 0.95; I(2) = 10%; seven trials including 3804 people). In absolute terms, 18 fewer people per 1000 were hospitalised as the result of an exacerbation while receiving LABA therapy over a weighted mean of 7 months (95% CI 3 to 31 fewer). Scores were also improved on the Chronic Respiratory Disease Questionnaire (CRQ), and more people receiving LABA treatment showed clinically important improvement of at least four points on the SGRQ.The number of people who had exacerbations requiring a course of oral steroids or antibiotics was also lower among those taking LABA (52 fewer per 1000 treated over 8 months; 95% CI 24 to 78 fewer, moderate quality evidence).Mortality was low, and combined findings of all studies showed that LABA therapy did not significantly affect mortality (OR 0.90, 95% CI 0.75 to 1.08; I(2) = 21%; 23 trials including 14,079 people, moderate quality evidence). LABA therapy did not affect the rate of serious adverse events (OR 0.97, 95% CI 0.83 to 1.14; I(2) = 34%, moderate quality evidence), although there was significant unexplained heterogeneity, especially between the two formoterol doses.LABA therapy improved predose FEV1 by 73 mL more than placebo (95% CI 48 to 98; I(2) = 71%, low quality evidence), and people were more likely to withdraw from placebo than from LABA therapy (OR 0.74, 95% CI 0.69 to 0.80; I(2) = 0%). Higher rates of withdrawal in the placebo arm may reduce our confidence in some results, but the disparity is more likely to reduce the magnitude of difference between LABA and placebo than inflate the true effect; removing studies at highest risk of bias on the basis of high and unbalanced attrition did not change conclusions for the primary outcomes. AUTHORS' CONCLUSIONS: Moderate-quality evidence from 26 studies showed that inhaled long-acting beta2-agonists are effective over the medium and long term for patients with moderate to severe COPD. Their use is associated with improved quality of life and reduced exacerbations, including those requiring hospitalisation. Overall, findings showed that inhaled LABAs did not significantly reduce mortality or serious adverse events.

Swimming training for asthma in children and adolescents aged 18 years and under.

BACKGROUND: Asthma is the most common chronic medical condition in children and a common reason for hospitalisation. Observational studies have suggested that swimming, in particular, is an ideal form of physical activity to improve fitness and decrease the burden of disease in asthma. OBJECTIVES: To determine the effectiveness and safety of swimming training as an intervention for asthma in children and adolescents aged 18 years and under. SEARCH METHODS: We searched the Cochrane Airways Group's Specialised Register of trials (CENTRAL), MEDLINE , EMBASE, CINAHL, in November 2011, and repeated the search of CENTRAL in July 2012. We also handsearched ongoing Clinical Trials Registers. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) and quasi-RCTs of children and adolescents comparing swimming training with usual care, a non-physical activity, or physical activity other than swimming. DATA COLLECTION AND ANALYSIS: We used standard methods specified in the Cochrane Handbook for Systematic reviews of Interventions. Two review authors used a standard template to independently assess trials for inclusion and extract data on study characteristics, risk of bias elements and outcomes. We contacted trial authors to request data if not published fully. When required, we calculated correlation coefficients from studies with full outcome data to impute standard deviation of changes from baseline. MAIN RESULTS: Eight studies involving 262 participants were included in the review. Participants had stable asthma, with severity ranging from mild to severe. All studies were randomised trials, three studies had high withdrawal rates. Participants were between five to 18 years of age, and in seven studies swimming training varied from 30 to 90 minutes, two to three times a week, over six to 12 weeks. The programme in one study gave 30 minutes training six times per week. The comparison was usual care in seven studies and golf in one study. Chlorination status of swimming pool was unknown for four studies. Two studies used non-chlorinated pools, one study used an indoor chlorinated pool and one study used a chlorinated but well-ventilated pool.No statistically significant effects were seen in studies comparing swimming training with usual care or another physical activity for the primary outcomes; quality of life, asthma control, asthma exacerbations or use of corticosteroids for asthma. Swimming training had a clinically meaningful effect on exercise capacity compared with usual care, measured as maximal oxygen consumption during a maximum effort exercise test (VO2 max) (two studies, n = 32), with a mean increase of 9.67 mL/kg/min; 95% confidence interval (CI) 5.84 to 13.51. A difference of equivalent magnitude was found when other measures of exercise capacity were also pooled (four studies, n = 74), giving a standardised mean difference (SMD) 1.34; 95% CI 0.82 to 1.86. Swimming training was associated with small increases in resting lung function parameters of varying statistical significance; mean difference (MD) for FEV1 % predicted 8.07; 95% CI 3.59 to 12.54. In sensitivity analyses, by risk of attrition bias or use of imputed standard deviations, there were no important changes on effect sizes. Unknown chlorination status of pools limited subgroup analyses.Based on limited data, there were no adverse effects on asthma control or occurrence of exacerbations. AUTHORS' CONCLUSIONS: This review indicates that swimming training is well-tolerated in children and adolescents with stable asthma, and increases lung function (moderate strength evidence) and cardio-pulmonary fitness (high strength evidence). There was no evidence that swimming training caused adverse effects on asthma control in young people 18 years and under with stable asthma of any severity. However whether swimming is better than other forms of physical activity cannot be determined from this review. Further adequately powered trials with longer follow-up periods are needed to better assess the long-term benefits of swimming.

Supporting health behaviour change in chronic obstructive pulmonary disease with telephone health-mentoring: insights from a qualitative study.

BACKGROUND: Adoption and maintenance of healthy behaviours is pivotal to chronic disease self-management as this influences disease progression and impact. This qualitative study investigated health behaviour changes adopted by participants with moderate or severe chronic obstructive pulmonary disease (COPD) recruited to a randomised controlled study of telephone-delivered health-mentoring. METHODS: Community nurses trained as health-mentors used a patient-centred approach with COPD patients recruited in general practice to facilitate behaviour change, using a framework of health behaviours; 'SNAPPS' Smoking, Nutrition, Alcohol, Physical activity, Psychosocial well-being, and Symptom management, through regular phone calls over 12 months. Semi-structured interviews in a purposive sample sought feedback on mentoring and behaviour changes adopted. Interviews were analysed using iterative thematic and interpretative content approaches by two investigators. RESULTS: Of 90 participants allocated to health-mentoring, 65 (72%) were invited for interview at 12-month follow up. The 44 interviewees, 75% with moderate COPD, had a median of 13 mentor contacts over 12 months, range 5-20. Interviewed participants (n=44, 55% male, 43% current smokers, 75% moderate COPD) were representative of the total group with a mean age 65 years while 82% had at least one additional co-morbid chronic condition. Telephone delivery was highly acceptable and enabled good rapport. Participants rated 'being listened to by a caring health professional' as very valuable. Three participant groups were identified by attitude to health behaviour change: 14 (32%) actively making changes; 18 (41%) open to and making some changes and 12 (27%) more resistant to change. COPD severity or current smoking status was not related to group category. Mentoring increased awareness of COPD effects, helping develop and personalise behaviour change strategies, even by those not actively making changes. Physical activity was targeted by 43 (98%) participants and smoking by 14 (74%) current smokers with 21% reporting quitting. Motivation to maintain changes was increased by mentor support. CONCLUSIONS: Telephone delivery of health-mentoring is feasible and acceptable to people with COPD in primary care. Health behaviours targeted by this population, mostly with moderate disease, were mainly physical activity and smoking reduction or cessation. Health-mentoring increased motivation and assisted people to develop strategies for making and sustaining beneficial change. TRIAL REGISTRATION: ACTR12608000112368.

Hospital at home for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Hospital at home schemes are a recently adopted method of service delivery for the management of acute exacerbations of chronic obstructive pulmonary disease (COPD) aimed at reducing demand for acute hospital inpatient beds and promoting a patient-centred approach through admission avoidance. However, evidence in support of such a service is contradictory. OBJECTIVES: To evaluate the efficacy of hospital at home compared to hospital inpatient care in acute exacerbations of COPD. SEARCH METHODS: Trials were identified from searches of electronic databases, including CENTRAL, MEDLINE, EMBASE, and the Cochrane Airways Group Register (CAGR). The review authors checked the reference lists of included trials. The CAGR was searched up to February 2012. The additional databases were searched up to October 2010. SELECTION CRITERIA: We considered randomised controlled trials where patients presented to the emergency department with an exacerbation of their COPD. Studies must not have recruited patients for whom treatment at home is usually not viewed as an responsible option (e.g. patients with an impaired level of consciousness, acute confusion, acute changes on the radiograph or electrocardiogram, arterial pH less than 7.35, concomitant medical conditions). DATA COLLECTION AND ANALYSIS: Two review authors independently selected articles for inclusion, assessed the risk of bias and extracted data for each of the included trials. MAIN RESULTS: Eight trials with 870 patients were included in the review and showed a significant reduction in readmission rates for hospital at home compared with hospital inpatient care of acute exacerbations of COPD (risk ratio (RR)0.76; 95% confidence interval (CI) from 0.59 to 0.99; P=0.04). Moreover, we observed a trend towards lower mortality in the hospital at home group, but the pooled effect estimate did not reach statistical significance (RR 0.65, 95% CI 0.40 to 1.04, P = 0.07). For health-related quality of life, lung function (FEV1) and direct costs, the quality of the available evidence is in general too weak to make firm conclusions. AUTHORS' CONCLUSIONS: Selected patients presenting to hospital emergency departments with acute exacerbations of COPD can be safely and successfully treated at home with support from respiratory nurses. We found evidence of moderate quality that hospital at home may be advantageous with respect to readmission rates in these patients. Treatment of acute exacerbation of COPD in hospital at home also show a trend towards reduced mortality rate when compared with conventional inpatient treatment, but these results did not reach statistical significance (moderate quality evidence). For other outcomes than readmission and mortality rate, we assessed the evidence to be of low or very low quality.

Engaging general practice nurses in chronic disease self-management support in Australia: insights from a controlled trial in chronic obstructive pulmonary disease.

The growing burden of chronic disease will increase the role of primary care in supporting self-management and health behaviour change. This role could be undertaken to some extent by the increased practice nurse workforce that has occurred over recent years. Mixed methods were used to investigate the potential for general practice nurses to adopt this role during a 12-month randomised controlled study of telephone-delivered health mentoring in Tasmanian practices. Nurses (general practice and community health) were trained as health mentors to assist chronic obstructive pulmonary disease patients to identify and achieve personal health related goals through action plans. Of 21% of invited practices that responded, 19 were allocated to health mentoring; however, general practice nurses were unable to train as health mentors in 14 (74%), principally due to lack of financial compensation and/or workload pressure. For five general practice nurses trained as health mentors, their roles had previously included some chronic disease management, but training enhanced their understanding and skills of self-management approaches and increased the focus on patient partnership, prioritising patients' choices and achievability. Difficulties that led to early withdrawal of health mentors were competing demands, insufficient time availability, phone calls having lower priority than face-to-face interactions and changing employment. Skills gained were rated as valuable, applicable to all clinical practice and transferable to other health care settings. Although these results suggest that training can enhance general practice nurses' skills to deliver self-management support in chronic disease, there are significant system barriers that need to be addressed through funding models and organisational change.

Erythropoietin as a treatment of anemia in heart failure: systematic review of randomized trials.

BACKGROUND: Anemia in heart failure is both common and associated with worse symptoms and increased mortality. Several small randomized controlled trials (RCTs) have assessed erythropoiesis-stimulating agents (ESAs), but definitive evaluation and clinical guidance are required. We sought to systematically review the effects of ESAs in chronic heart failure. METHODS: An extensive search strategy identified 11 RCTs with 794 participants comparing any ESA with control over 2 to 12 months of follow-up. Published and additionally requested data were incorporated into a Cochrane systematic review (CD007613). RESULTS: Nine studies were placebo controlled, and 5, double blinded. Erythropoiesis-stimulating agent treatment significantly improved exercise duration by 96.8 seconds (95% CI 5.2-188.4, P = .04) and 6-minute walk distance by 69.3 m (95% CI 17.0-121.7, P = .009) compared with control. Benefit was also noted for peak oxygen consumption (+2.29 mL/kg per minute, P = .007), New York Heart Association class (-0.73, P < .001), ejection fraction (+5.8%, P < .001), B-type natriuretic peptide (-226.99 pg/mL, P < .001), and quality-of-life indicators with a mean increase in hemoglobin level of 2 g/dL. There was a significantly lower rate of heart failure-related hospitalizations with ESA therapy (odds ratio 0.56, 95% CI 0.37-0.84, P = .005). No associated increase in adverse events or mortality (odds ratio 0.58, 95% CI 0.34-0.99, P = .047) was observed, although the number of events was limited. CONCLUSION: Meta-analysis of small RCTs suggests that ESA treatment can improve exercise tolerance, reduce symptoms, and have benefits on clinical outcomes in anemic patients with heart failure. Confirmation requires larger, well-designed studies with careful attention to dose, attained hemoglobin level, and long-term outcomes.

Platinum versus non-platinum chemotherapy regimens for small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) is a very fast growing form of cancer and is characterised by early metastasis. As a result, chemotherapy is the mainstay of treatment. A number of different platinum-based chemotherapy regimens and non-platinum-based chemotherapy regimens have been used for the treatment of SCLC, with varying results. This review was conducted to analyse the data from these trials in order to compare their effectiveness. OBJECTIVES: To determine the effectiveness of platinum chemotherapy regimens compared with non-platinum chemotherapy regimens in the treatment of SCLC with respect to survival, tumour response, toxicity and quality of life. SEARCH STRATEGY: We searched the biomedical literature databases CENTRAL (The Cochrane Library 2007, Issue 2), MEDLINE, EMBASE and CINAHL from 1966 to April 2007. In addition, we handsearched reference lists from relevant resources. SELECTION CRITERIA: All randomised controlled trials involving patients with pathologically confirmed (cytological or histological) SCLC and the use of a platinum-based chemotherapy regimen in at least one treatment arm and a non-platinum-based chemotherapy regimen in a separate arm. DATA COLLECTION AND ANALYSIS: Two authors independently assessed search results. We assessed included studies for methodological quality and recorded the following outcome data: survival, tumour response, toxicity and quality of life. We combined the results of the survival, tumour response and toxicity data in a meta-analysis. MAIN RESULTS: A total of 29 trials involving 5530 patients were included in this systematic review. There was no statistically significant difference between treatment groups in terms of survival at 6 months, 12 months and 24 months. There was also no statistically significant difference in terms of overall tumour response. However, platinum-based treatment regimens did have a significantly higher rate of complete response. Platinum-based chemotherapy regimens had significantly higher rates of nausea and vomiting, anaemia and thrombocytopenia toxicity. Three trials presented quality of life data but the data presented were not complete and therefore could not be combined in a meta-analysis. AUTHORS' CONCLUSIONS: Platinum-based chemotherapy regimens did not offer a statistically significant benefit in survival or overall tumour response compared with non-platinum-based regimens. However, platinum-based chemotherapy regimens did increase complete response rates, at the cost of higher adverse events including nausea and vomiting, anaemia and thrombocytopenia toxicity. These data suggest non-platinum chemotherapy regimens have a more advantageous risk-benefit profile. This systematic review highlights the lack of quality of life data in trials involving chemotherapy treatment for SCLC. With poor long-term survival associated with both treatment groups, the issue of the quality of the survival period takes on even more significance. It would be beneficial for future trials in this area to include a quality of life assessment.

National survey of spirometer ownership and usage in general practice in Australia.

OBJECTIVES AND BACKGROUND: Despite the lack of data, it is believed that spirometry is underutilized in general practice. The aim of the present study was to determine the availability of spirometry and the level of spirometry training in general practice throughout Australia and compare with international data. METHODS: In total, 5976 general practices throughout Australia were sent a questionnaire requesting details of spirometer ownership, usage and the level and source of spirometry training. To exclude response bias, a follow-up telephone survey was conducted of 160 practices that did not respond to the initial survey. RESULTS: Of practices 19.5% (1125) responded to the initial survey with 64.2% (722) of these owning a spirometer and 83.9% in the follow-up sample. Common reasons for not owning a spirometer were equipment cost (53.3%) and insufficient remuneration (32.8%). Most practices (67.0%) performed one or more tests per week. Practices commonly used spirometry to diagnose (89.5%) and manage (93.9%) asthma, assess breathlessness (83.4%) and to detect and manage other diseases such as COPD (77.7%). Spirometer accuracy was never checked using a syringe 77.8% of practices and 40% did not test a healthy subject as part of their quality assurance programme. Spirometry training was received most commonly through courses run by general practice organizations (38.2%), and the duration of training courses was <2 h in 40% of cases. CONCLUSION: Despite high spirometer ownership in general practice, the frequency of use is low. Low rates of verification of spirometer accuracy and performance suggest the need for reliable, stable spirometers to be available to general practitioners. Regular and more comprehensive training in spirometry is needed.

Stability of the EasyOne ultrasonic spirometer for use in general practice.

OBJECTIVE AND BACKGROUND: Spirometry is recommended for the diagnosis and management of chronic respiratory diseases in the community. Spirometer accuracy is critical, but few general practitioners meet the American Thoracic Society and European Respiratory Society (ATS/ERS) recommendation for daily calibration. The aim of this study was to assess the accuracy and stability of a portable ultrasonic spirometer (EasyOne) that the manufacturer claims does not require regular calibration. METHODS: Six EasyOne spirometers were used in a practice-based spirometry study. Inspiratory and expiratory accuracy was checked periodically using a certified 3-L syringe. Paired calibration checks were performed using a dedicated mouthpiece assembly (spirette) and randomly selected spirettes. RESULTS: The six spirometers were used for up to 26 weeks (mean 23.9 weeks) and a total of 1041 spirometry tests and 75 syringe calibrations were performed. All inspiratory and expiratory calibration checks using a dedicated or randomly selected spirette met the ATS/ERS accuracy criterion (3.00+/-0.105 L). The mean (range) expiratory volume deviation from target volume (3.00 L) was 0.011 L (-0.06-0.09 L) using a dedicated spirette and 0.046 L (-0.09-0.10 L) using randomly selected spirettes. The deviation from target was not affected by the mean flow generated during the calibration procedure. There was no change in calibration during the study. CONCLUSIONS: This study supports the manufacturer's claim that the EasyOne spirometer maintains its calibration during routine clinical use in general practice and does not require daily calibration as specified in international spirometry guidelines.

Barriers to the use of spirometry in general practice.

BACKGROUND: Guidelines advise chronic obstructive pulmonary disease (COPD) should be diagnosed and managed by using spirometry to demonstrate irreversible airflow limitation and monitor change in smokers and ex-smokers aged over 35 years. METHODS: A cross-sectional study of patients and their general practitioners investigating use of spirometry in COPD in two practices by lung function assessment, review of practice records, interviews and focus groups. RESULTS: Sixteen GPs, and 38 patients with a diagnosis of COPD participated. At diagnosis, although 72% had spirometry, this occurred in only 41% of 17 patients diagnosed by a GP; but in all 19 cases when a specialist was involved. Diagnosis often occurred late, despite all patients having previously recorded symptoms typical of COPD. General practitioners expressed a preference to diagnose COPD on clinical grounds. Although 58% of patients had recent spirometry for current management, only 32% were performed by their GP. There were organisational and technical barriers to spirometry and poor recognition of the essential role of spirometry in the diagnosis of COPD. DISCUSSION: There are a number of potentially reversible factors that hinder practice recommendations regarding the use of spirometry in general practice to diagnose and manage COPD.