Addition of long-acting beta2-agonists to inhaled corticosteroids for chronic asthma in children

Background Long-acting beta2-agonists (LABA) in combination with inhaled corticosteroids (ICS) are increasingly prescribed for children with asthma. Objectives To assess the safety and efficacy of adding a LABA to an ICS in children and adolescents with asthma. To determine whether the benefit of LABA was influenced by baseline severity of airway obstruction, the dose of ICS to which it was added or with which it was compared, the type of LABA used, the number of devices used to deliver combination therapy and trial duration. Search methods We searched the Cochrane Airways Group Asthma Trials Register until January 2015. Selection criteria We included randomised controlled trials testing the combination of LABA and ICS versus the same, or an increased, dose of ICS for at least four weeks in children and adolescents with asthma. The main outcome was the rate of exacerbations requiring rescue oral steroids. Secondary outcomes included markers of exacerbation, pulmonary function, symptoms, quality of life, adverse events and withdrawals. Data collection and analysis Two review authors assessed studies independently for methodological quality and extracted data. We obtained confirmation from trialists when possible. Main results We included in this review a total of 33 trials representing 39 control-intervention comparisons and randomly assigning 6381 children. Most participants were inadequately controlled on their current ICS dose. We assessed the addition of LABA to ICS (1) versus the same dose of ICS, and (2) versus an increased dose of ICS. LABA added to ICS was compared with the same dose of ICS in 28 studies. Mean age of participants was 11 years, and males accounted for 59% of the study population. Mean forced expiratory volume in one second (FEV1) at baseline was ≥ 80% of predicted in 18 studies, 61% to 79% of predicted in six studies and unreported in the remaining studies. Participants were inadequately controlled before randomisation in all but four studies. There was no significant group difference in exacerbations requiring oral steroids (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.70 to 1.28, 12 studies, 1669 children; moderate-quality evidence) with addition of LABA to ICS compared with ICS alone. There was no statistically significant group difference in hospital admissions (RR 1.74, 95% CI 0.90 to 3.36, seven studies, 1292 children; moderate-quality evidence)nor in serious adverse events (RR 1.17, 95% CI 0.75 to 1.85, 17 studies, N = 4021; moderate-quality evidence). Withdrawals occurred significantly less frequently with the addition of LABA (23 studies, 471 children, RR 0.80, 95% CI 0.67 to 0.94; low-quality evidence). Compared with ICS alone, addition of LABA led to significantly greater improvement in FEV1 (nine studies, 1942 children, inverse variance (IV) 0.08 L, 95% CI 0.06 to 0.10; mean difference (MD) 2.99%, 95% CI 0.86 to 5.11, seven studies, 534 children; low-quality evidence), morning peak expiratory flow (PEF) (16 studies, 3934 children, IV 10.20 L/min, 95% CI 8.14 to 12.26), reduction in use of daytime rescue inhalations (MD -0.07 puffs/d, 95% CI -0.11 to -0.02, seven studies; 1798 children) and reduction in use of nighttime rescue inhalations (MD -0.08 puffs/d, 95% CI -0.13 to -0.03, three studies, 672 children). No significant group difference was noted in exercise-induced % fall in FEV1, symptom-free days, asthma symptom score, quality of life, use of reliever medication and adverse events. A total of 11 studies assessed the addition of LABA to ICS therapy versus an increased dose of ICS with random assignment of 1628 children. Mean age of participants was 10 years, and 64% were male. Baseline mean FEV1 was ≥ 80% of predicted. All trials enrolled participants who were inadequately controlled on a baseline inhaled steroid dose equivalent to 400 µg/d of beclomethasone equivalent or less. There was no significant group differences in risk of exacerbation requiring oral steroids with the combination of LABA and ICS versus a double dose of ICS (RR 1.69, 95% CI 0.85 to 3.32, three studies, 581 children; moderate-quality evidence) nor in risk of hospital admission (RR 1.90, 95% CI 0.65 to 5.54, four studies, 1008 children; moderate-quality evidence). No statistical significant group difference was noted in serious adverse events (RR 1.54, 95% CI 0.81 to 2.94, seven studies, N = 1343; moderate-quality evidence) and no statistically significant differences in overall risk of all-cause withdrawals (RR 0.96, 95% CI 0.67 to 1.37, eight studies, 1491 children; moderate-quality evidence). Compared with double the dose of ICS, use of LABA was associated with significantly greater improvement in morning PEF (MD 8.73 L/min, 95% CI 5.15 to 12.31, five studies, 1283 children; moderate-quality evidence), but data were insufficient to aggregate on other markers of asthma symptoms, rescue medication use and nighttime awakening. There was no group difference in risk of overall adverse effects, A significant group difference was observed in linear growth over 12 months, clearly indicating lower growth velocity in the higher ICS dose group (two studies: MD 1.21 cm/y, 95% CI 0.72 to 1.70). Authors' conclusions In children with persistent asthma, the addition of LABA to ICS was not associated with a significant reduction in the rate of exacerbations requiring systemic steroids, but it was superior for improving lung function compared with the same or higher doses of ICS. No differences in adverse effects were apparent, with the exception of greater growth with the use of ICS and LABA compared with a higher ICS dose. The trend towards increased risk of hospital admission with LABA, irrespective of the dose of ICS, is a matter of concern and requires further monitoring

What constitutes brilliant aged care? : a qualitative study of practices that exceed expectation

Aim: This study aimed to explore what constitutes brilliant aged care. Background: Although many aged care services do not offer the care that older people and carers need and want, some perform better. Rather than focus on problems with aged care, this study examined brilliant aged care—practices that exceeded expectation. Design: The methodology for this study was informed by grounded theory, under-pinned by constructionism to socially construct meaning. Methods: This study invited nominations for a Brilliant Award via a survey, and inter-views with the nominees via web conference. After receiving survey responses from 10 nominators, interviews were conducted with 12 nominees. Data were analysed using reflexive thematic analysis and documented according to COREQ guidelines to optimise rigour and transparency. Results: According to participants, brilliant aged care involved being relationally at-tuned to older people, a deep understanding of the older person, recognition of aged care as more than a job, innovative practices and permission to reprioritise. Conclusions: This study suggests that, in aged care, brilliance happens. It emphasises the importance of meaningful connections and relationships in aged care, where thoughtful acts acknowledge an older person's value and humanity as well as creativity and innovation. Relevance to Clinical Practice: For those who manage and deliver aged care, the findings suggest that small practice changes can make a positive difference to older people. Brilliant aged care can involve acts of empathy; enthusiasm for aged care; innovative practices, even those that are small scale; and reprioritising workplace tasks to spend time with older people. For policymakers, this study highlights the need to recognise and raise the profile of the pockets of brilliance within the aged care sector. This might be achieved via awards and other initiatives that serve to celebrate and learn from brilliance in its myriad forms. Patient or Public Contribution: The nominees, who included carers, were invited to participate in workshops with other carers and older people to co-design a model of brilliant aged care, during which workshop participants discussed and critiqued the findings constructed from the data

The Feasibility of Deriving the Electronic Frailty Index from Australian General Practice Records

Purpose: Frailty is a prevalent condition in older adults. Identification of frailty using an electronic Frailty Index (eFI) has been successfully implemented across general practices in the United Kingdom. However, in Australia, the eFI remains understudied. Therefore, we aimed to (i) examine the feasibility of deriving an eFI from Australian general practice records and (ii) describe the prevalence of frailty as measured by the eFI and the prevalence with socioeconomic status and geographic remoteness. Participants and Methods: This retrospective analysis included patients (≥70 years) attending any one of >700 general practices utilizing the Australian MedicineInsight data platform, 2017–2018. A 36-item eFI was derived using standard methodology, with frailty classified as mild (scores 0.13–0.24); moderate (0.25–0.36) or severe (≥0.37). Socioeconomic status (Socio-Economic Indexes for Areas (SEIFA) index)) and geographic remoteness (Australian Statistical Geography Standard (ASGC) remoteness areas) were also examined. Results: In total, 79,251 patients (56% female) were included, mean age 80.0 years (SD 6.5); 37.4% (95% CI 37.0–37.7) were mildly frail, 16.7% (95% CI 16.4–16.9) moderately frail, 4.8% (95% CI 4.7–5.0) severely frail. Median eFI score was 0.14 (IQR 0.08 to 0.22); maximum eFI score was 0.69. Across all age groups, moderate and severe frailty was significantly more prevalent in females (P < 0.001). Frailty severity increased with increasing age (P < 0.001) and was strongly associated with socioeconomic disadvantage (P < 0.001) but not with geographic remoteness. Conclusion: Frailty was identifiable from routinely collected general practice data. Frailty was more prevalent in socioeconomically disadvantaged groups, women and older patients and existed in all levels of remoteness. Routine implementation of an eFI could inform interventions to prevent or reduce frailty in all older adults, regardless of location

Statins versus placebo for people with chronic obstructive pulmonary disease

Background: Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable respiratory disease. COPD exacerbations are associated with worse quality of life, increased hospitalisations, and increased mortality. Currently available pharmacological interventions have variable impact on exacerbation frequency. The anti‐inflammatory effects of statins may lead to decreased pulmonary and systemic inflammation, resulting in fewer exacerbations of COPD. Several observational studies have shown potential benefits of statins for patients with COPD. Objectives: This review aims to evaluate available evidence on benefits and harms associated with statin therapy compared with placebo as adjunct therapy for patients with COPD. Primary objectives include the following • To determine whether statins reduce mortality rates in COPD • To determine whether statins reduce exacerbation frequency, improve quality of life, or improve lung function in COPD • To determine whether statins are associated with adverse effects. Search methods: We identified trials from the Cochrane Airways Trials Register, which contains studies identified through multiple electronic searches and handsearches of other sources. We also searched trial registries and reference lists of primary studies. We conducted the most recent search on 20 May 2019. Selection criteria: Parallel, randomised controlled trials recruiting adults with COPD. Data collection and analysis: We used standard methods as expected by Cochrane. Prespecified primary outcomes were number of exacerbations, all‐cause mortality, and COPD‐specific mortality. Main results: Eight studies including 1323 participants with COPD were included in the review. Participants had a mean age of 61.4 to 72 years, and most were male (median 73.4%). Mean baseline forced expiratory volume in one second (FEV₁) ranged from 41% to 90% predicted. All studies compared moderate‐ or high‐intensity statin therapy versus placebo. The duration of treatment ranged from 12 weeks to 36 months. We found no statistically significant difference between statins and placebo in our primary outcome of number of exacerbations per person‐year (mean difference (MD) ‐0.03, 95% confidence interval (CI) ‐0.25 to 0.19, 1 trial, 877 participants), including number of exacerbations requiring hospitalisation per person‐year (MD 0.00, 95% CI ‐0.10 to 0.10, 1 trial, 877 exacerbations). This evidence was of moderate quality after downgrading for unclear risk of bias. Our primary outcomes of all‐cause mortality (odds ratio (OR) 1.03, 95% CI 0.61 to 1.74, 2 trials, 952 participants) and COPD‐specific mortality (OR 1.25, 95% CI 0.38 to 4.13, 1 trial, 877 participants) showed no significant difference between statins and placebo, with wide confidence intervals suggesting uncertainty about the precision of the results. This evidence was of low quality after downgrading for unclear risk of bias and imprecision. Results of the secondary outcomes analysis showed no clear differences between statins and placebo for FEV₁ (% predicted) (MD 1.18, 95% CI ‐2.6 to 4.97, 6 trials, 325 participants) but did show a statistically significant improvement in FEV₁/forced vital capacity (FVC) (MD 2.66, 95% CI 0.12 to 5.2; P = 0.04; 6 trials, 325 participants). A sensitivity analysis excluding two trials at high risk of bias showed no statistically significant difference in FEV₁/FVC (MD 2.05, 95% CI ‐0.87 to ‐4.97; P = 0.17; 4 trials, 255 participants). We also found no significant differences between the two groups in functional capacity measured by six‐minute walk distance in metres (MD 1.79, 95% CI ‐52.51 to 56.09, 3 trials, 71 participants), with wide confidence intervals suggesting uncertainty about the precision of the results. Results show no clear difference in quality of life, which was reported in three trials, and a slight reduction in C‐reactive protein (CRP) in the intervention group, which was statistically significant (MD ‐1.03, 95% CI ‐1.95 to ‐0.11; I² = 0%, P = 0.03; 3 trials, 142 participants). We noted a significant reduction in interleukin (IL)‐6 in the intervention group (MD ‐2.11, 95% CI ‐2.65 to ‐1.56; I² = 0%, P ≤ 0.00001; 2 trials, 125 participants). All trials mentioned adverse events and indicated that statins were generally well tolerated. One study reported adverse events in detail and indicated that rates of all non‐fatal adverse events (the number of serious adverse events per person‐year) were similar in both groups (0.63 ± 1.56 events (intervention group) and 0.62 ± 1.48 events (control group); P > 0.20) for all comparisons, except for non‐fatal serious adverse events involving the gastrointestinal tract, which were more frequent in the intervention group (in 30 patients (0.05 events per person‐year) vs 17 patients (0.02 events per person‐year); P = 0.02). Another trial lists the total numbers and percentages of adverse events in the intervention group (12 (26%)) and in the control group (21 (43%)) and of serious adverse events in the intervention group (4 (9%)) and in the control group (3 (6%)).The other trials stated that researchers found no significant adverse effects of statins but did not report adverse events in detail. Authors' conclusions: A small number of trials providing low‐ or moderate‐quality evidence were suitable for inclusion in this review. They showed that use of statins resulted in a reduction in CRP and IL‐6, but that this did not translate into clear clinical benefit for people with COPD. Further randomised controlled trials are needed to explore this topic

The burden of peripheral intravenous catheters in older hospital inpatients : a national cross-sectional study part of the One Million Global Peripheral Intravenous Catheters Collaboration

Objectives: To investigate the burden of peripheral intravenous catheters (PIVCs) in older hospitalised patients. Methods: A cross-sectional prospective observational study (2014/2015) to describe the characteristics, indications and outcomes of PIVCs among patients aged ≥65 from 65 Australian hospitals. Results: Amongst 2179 individual PIVCs (in 2041 patients, mean age 77.6 years, 45% female, 58% in NSW), 43% were inserted by doctors and 74% used that day, meaning 25% were ‘idle’. Overall, 18% (393/2179) exhibited signs of PIVC-related complications. Most commonly exhibited PIVC-related complications were tenderness (4.1%) and local redness (1.8%). Nearly one in three (29.1%) dressings was soiled, loosened or had come off, and only 36.8% had the time and date documented on the dressing. Both infusing IV medications (aOR 1.74, 95% CI 1.28–2.38, p 84 years) was independently associated with lower likelihood of a high score (aOR 0.71, 95% CI 0.54–0.94, p = 0.02). Conclusions: Given 1 in 5 PIVCs were identified with having complications, further research should focus on optimising PIVC use in older patients

A review of standard pharmacological therapy for adult asthma - Steps 1 to 5

The aim of pharmacological therapy for asthma is to improve symptoms and lung function and minimise the risk of asthma attacks. The intensity of treatment is based on the level of asthma control and the potential risk of future deterioration. In the British asthma guidelines, treatments are divided into Step One to Five, with each Step signifying a need for an increase in therapy in response to symptoms or to prevent exacerbations. Treatments comprise of inhaled or systemic medications. Inhaled therapy includes short-acting and long-acting medication to improve symptoms and inhaled corticosteroids which reduce airway inflammation. Systemic treatments include medications which act on specific biological pathways, such as the leukotriene or IgE pathways, or systemic corticosteroids. In choosing a particular therapy, treatment benefits are balanced by the potential risks of medication-related adverse effects. This review will provide a practical guide to the key pharmacological therapies for adult asthma at Steps One to Five based on British guidelines and consider future options for new treatments

Online versus paper-based screening for depression and anxiety in adults with cystic fibrosis in Ireland: a cross-sectional exploratory study

Objective: To compare online and paper-based screening for depression and anxiety in adults with cystic fibrosis (CF). Design and setting: Cross-sectional study in CF clinics in Ireland and through the Cystic Fibrosis Ireland online community. Participants: 160 adult patients aged 18 or above were recruited. Of these, 147 were included in the analysis; 83 online and 64 paper-based. The remaining 13 were excluded because of incomplete data. Measures: Depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS). Data on pulmonary function (forced expiratory volume in 1 s %) and body mass index were self-reported based on clinical assessments. Sociodemographic data were collected. Results: Compared with the paper-based participants, the online participants were more likely to be female (61.7% vs 48.4%), older (mean 32.2 vs 28.2 years) and were more likely to be married (32.5% vs 15.6%), living with their spouse or partner (42.5% vs 22.6%) and working either full time (33.7% vs 15.9%) or part time (30.1%vs 17.5%). The prevalence rates of elevated anxiety and depression were not significantly different (P=0.71 and P=0.56). HADS anxiety and depression scores were not statistically different between online (P=0.83) and paper-based (P=0.92) participants based on Mann-Whitney U test. A significant negative correlation was found between depression and pulmonary function (r=−0.39, P=0.01) and anxiety and pulmonary function (r=−0.36, P=0.02). Based on Cronbach’s alpha, there were no statistically significant differences between the online and paper-based participants on the internal consistency of the HADS anxiety (P=0.073) and depression (P=0.378) scales. Conclusions: Our findings suggest that online and paper-based screening for depression and anxiety in adult patients with CF yield comparable findings on prevalence rates and scores, associations with health and internal consistency of subscales. This study highlights that online screening offers an alternative method to paper-based screening. Further research with a larger sample and assessment of measurement equivalence between online and paper based screening is needed to confirm our results

Many continuous variables should be analyzed using the relative scale: a case study of β2-agonists for preventing exercise-induced bronchoconstriction

BACKGROUND: The relative scale adjusts for baseline variability and therefore may lead to findings that can be generalized more widely. It is routinely used for the analysis of binary outcomes but only rarely for continuous outcomes. Our objective was to compare relative vs absolute scale pooled outcomes using data from a recently published Cochrane systematic review that reported only absolute effects of inhaled β2-agonists on exercise-induced decline in forced-expiratory volumes in 1 s (FEV1). METHODS: From the Cochrane review, we selected placebo-controlled cross-over studies that reported individual participant data (IPD). Reversal in FEV1 decline after exercise was modeled as a mean uniform percentage point (pp) change (absolute effect) or average percent change (relative effect) using either intercept-only or slope-only, respectively, linear mixed-effect models. We also calculated the pooled relative effect estimates using standard random-effects, inverse-variance-weighting meta-analysis using study-level mean effects. RESULTS: Fourteen studies with 187 participants were identified for the IPD analysis. On the absolute scale, β2-agonists decreased the exercise-induced FEV1 decline by 28 pp., and on the relative scale, they decreased the FEV1 decline by 90%. The fit of the statistical model was significantly better with the relative 90% estimate compared with the absolute 28 pp. estimate. Furthermore, the median residuals (5.8 vs. 10.8 pp) were substantially smaller in the relative effect model than in the absolute effect model. Using standard study-level meta-analysis of the same 14 studies, β2-agonists reduced exercise-induced FEV1 decline on the relative scale by a similar amount: 83% or 90%, depending on the method of calculating the relative effect. CONCLUSIONS: Compared with the absolute scale, the relative scale captures more effectively the variation in the effects of β2-agonists on exercise-induced FEV1-declines. The absolute scale has been used in the analysis of FEV1 changes and may have led to sub-optimal statistical analysis in some cases. The choice between the absolute and relative scale should be determined based on biological reasoning and empirical testing to identify the scale that leads to lower heterogeneity.Peer reviewe