Anticholinergic therapy for acute asthma in children.

Inhaled anticholinergics as single agent bronchodilators (or in combination with beta(2)-agonists) are one of the several medications available for the treatment of acute asthma in children

Usability and feasibility of consumer-facing technology to reduce unsafe medication use by older adults

Background Mobile health technology can improve medication safety for older adults, for instance, by educating patients about the risks associated with anticholinergic medication use. Objective This study's objective was to test the usability and feasibility of Brain Buddy, a consumer-facing mobile health technology designed to inform and empower older adults to consider the risks and benefits of anticholinergics. Methods Twenty-three primary care patients aged ≥60 years and using anticholinergic medications participated in summative, task-based usability testing of Brain Buddy. Self-report usability was assessed by the System Usability Scale and performance-based usability data were collected for each task through observation. A subset of 17 participants contributed data on feasibility, assessed by self-reported attitudes (feeling informed) and behaviors (speaking to a physician), with confirmation following a physician visit. Results Overall usability was acceptable or better, with 100% of participants completing each Brain Buddy task and a mean System Usability Scale score of 78.8, corresponding to “Good” to “Excellent” usability. Observed usability issues included higher rates of errors, hesitations, and need for assistance on three tasks, particularly those requiring data entry. Among participants contributing to feasibility data, 100% felt better informed after using Brain Buddy and 94% planned to speak to their physician about their anticholinergic related risk. On follow-up, 82% reported having spoken to their physician, a rate independently confirmed by physicians. Conclusion Consumer-facing technology can be a low-cost, scalable intervention to improve older adults’ medication safety, by informing and empowering patients. User-centered design and evaluation with demographically heterogeneous clinical samples uncovers correctable usability issues and confirms the value of interventions targeting consumers as agents in shared decision making and behavior change

OnabotulinumtoxinA 100U provides significant improvements in overactive bladder symptoms in patients with urinary incontinence regardless of the number of anticholinergic therapies used or reason for inadequate management of overactive bladder

INTRODUCTION: A prespecified pooled analysis of two placebo-controlled, phase 3 trials evaluated whether the number of prior anticholinergics used or reason for their discontinuation affected the treatment response to onabotulinumtoxinA 100U in overactive bladder (OAB) patients with urinary incontinence (UI). METHODS: Patients with symptoms of OAB received intradetrusor injections of onabotulinumtoxinA 100U or placebo, sparing the trigone. Change from baseline at week 12 in UI episodes/day, proportion of patients reporting a positive response (‘greatly improved’ or ‘improved’) on the treatment benefit scale (TBS), micturition and urgency were evaluated by number of prior anticholinergics (1, 2 or ≥ 3) and reason for their discontinuation (insufficient efficacy or side effects). Adverse events (AE) were assessed. RESULTS: Patients had taken an average of 2.4 anticholinergics before study enrolment. OnabotulinumtoxinA reduced UI episodes/day from baseline vs. placebo, regardless of the number of prior anticholinergics (−2.82 vs. −1.52 for one prior anticholinergic; −2.58 vs. −0.58 for two prior anticholinergics; and −2.92 vs. −0.73 for three or more prior anticholinergics; all p < 0.001). The proportion of TBS responders was higher with onabotulinumtoxinA vs. placebo (69.0% vs. 37.2% for one prior anticholinergic; 58.8% vs. 24.8% for two prior anticholinergics and 56.4% vs. 22.5% for three or more prior anticholinergics; all p < 0.001). Similar results were observed regardless of the reason for discontinuation. OnabotulinumtoxinA reduced the episodes of urgency and frequency of micturition vs. placebo in all groups. AEs were well tolerated, with a comparable incidence in all groups. CONCLUSION: In patients with symptoms of OAB who were inadequately managed by one or more anticholinergics, onabotulinumtoxinA 100U provided significant and similar treatment benefit and safety profile regardless of the number of prior anticholinergics used or reason for inadequate management of OAB. ClinicalTrials.gov: NCT00910845, NCT00910520

Older patients' prescriptions screening in the community pharmacy: development of the Ghent Older People's Prescriptions community Pharmacy Screening (GheOP3S) tool

Background: Ageing of the population often leads to polypharmacy. Consequently, potentially inappropriate prescribing (PIP) becomes more frequent. Systematic screening for PIP in older patients in primary care could yield a large improvement in health outcomes, possibly an important task for community pharmacists. In this article, we develop an explicit screening tool to detect relevant PIP that can be used in the typical community pharmacy practice, adapted to the European market. Methods: Eleven panellists participated in a two-round RAND/UCLA (Research and Development/University of California, Los Angeles) process, including a round zero meeting, a literature review, a first written evaluation round, a second face-to-face evaluation round and, finally, a selection of those items that are applicable in the contemporary community pharmacy. Results: Eighteen published lists of PIP for older patients were retrieved from the literature, mentioning 398 different items. After the two-round RAND/UCLA process, 99 clinically relevant items were considered suitable to screen for in a community pharmacy practice. A panel of seven community pharmacists selected 83 items, feasible in the contemporary community pharmacy practice, defining the final GheOP3S tool. Conclusion: A novel explicit screening tool (GheOP3S) was developed to be used for PIP screening in the typical community pharmacy practice

Guideline on management of the acute asthma attack in children by Italian Society of Pediatrics.

BACKGROUND: Acute asthma attack is a frequent condition in children. It is one of the most common reasons for emergency department (ED) visit and hospitalization. Appropriate care is fundamental, considering both the high prevalence of asthma in children, and its life-threatening risks. Italian Society of Pediatrics recently issued a guideline on the management of acute asthma attack in children over age 2, in ambulatory and emergency department settings. METHODS: The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was adopted. A literature search was performed using the Cochrane Library and Medline/PubMed databases, retrieving studies in English or Italian and including children over age 2 year. RESULTS: Inhaled ß2 agonists are the first line drugs for acute asthma attack in children. Ipratropium bromide should be added in moderate/severe attacks. Early use of systemic steroids is associated with reduced risk of ED visits and hospitalization. High doses of inhaled steroids should not replace systemic steroids. Aminophylline use should be avoided in mild/moderate attacks. Weak evidence supports its use in life-threatening attacks. Epinephrine should not be used in the treatment of acute asthma for its lower cost / benefit ratio, compared to β2 agonists. Intravenous magnesium solphate could be used in children with severe attacks and/or forced expiratory volume1 (FEV1) lower than 60% predicted, unresponsive to initial inhaled therapy. Heliox could be administered in life-threatening attacks. Leukotriene receptor antagonists are not recommended. CONCLUSIONS: This Guideline is expected to be a useful resource in managing acute asthma attacks in children over age 2

Potentially inappropriate prescribing in nursing home residents detected with the community pharmacist specific GheOP3S-tool

Background: The Ghent Older People’s Prescriptions community Pharmacy Screening (GheOP3S-)tool was recently developed to screen for potentially inappropriate prescribing (PIP). Objective: We aimed (1) to determine PIP prevalence in older nursing home (NH) residents with polypharmacy using the GheOP3S-tool and (2) to identify those PIPs that are most frequently detected. Method: A cross-sectional study was carried out between February and June 2014 in 10 NHs in Belgium, supplied by a community pharmacy chain. For each NH, 40 residents (>70 years, using >5 chronic drugs) were included. PIP prevalence was determined using the GheOP3S-tool. Results: 400 NH residents were included [mean age (±SD) 86.2 (±6.3) years; median number of drugs (±IQR) 10 (7–12)]. A total of 1728 PIPs were detected in 387 (97 %) participants (Median 4; IQR 2–6). The most prevalent items can be assigned to three categories: long-term use of central nervous system drugs (i.e. benzodiazepines, antidepressants and antipsychotics), use of anticholinergic drugs (mutual combinations and with underlying constipation/dementia) and underuse of osteoporosis prophylaxis. Conclusion: Screening for PIP by means of the GheOP3S-tool revealed a high prevalence of PIP among older NH residents with polypharmacy. This finding urges for initiatives on the patient-level, but also on a broader, institutional level

Long-acting inhaled therapy (beta-agonists, anticholinergics and steroids) for COPD: a network meta-analysis.

BACKGROUND: Pharmacological therapy for chronic obstructive pulmonary disease (COPD) is aimed at relieving symptoms, improving quality of life and preventing or treating exacerbations.Treatment tends to begin with one inhaler, and additional therapies are introduced as necessary. For persistent or worsening symptoms, long-acting inhaled therapies taken once or twice daily are preferred over short-acting inhalers. Several Cochrane reviews have looked at the risks and benefits of specific long-acting inhaled therapies compared with placebo or other treatments. However for patients and clinicians, it is important to understand the merits of these treatments relative to each other, and whether a particular class of inhaled therapies is more beneficial than the others. OBJECTIVES: To assess the efficacy of treatment options for patients whose chronic obstructive pulmonary disease cannot be controlled by short-acting therapies alone. The review will not look at combination therapies usually considered later in the course of the disease.As part of this network meta-analysis, we will address the following issues.1. How does long-term efficacy compare between different pharmacological treatments for COPD?2. Are there limitations in the current evidence base that may compromise the conclusions drawn by this network meta-analysis? If so, what are the implications for future research? SEARCH METHODS: We identified randomised controlled trials (RCTs) in existing Cochrane reviews by searching the Cochrane Database of Systematic Reviews (CDSR). In addition, we ran a comprehensive citation search on the Cochrane Airways Group Register of trials (CAGR) and checked manufacturer websites and reference lists of other reviews. The most recent searches were conducted in September 2013. SELECTION CRITERIA: We included parallel-group RCTs of at least 6 months' duration recruiting people with COPD. Studies were included if they compared any of the following treatments versus any other: long-acting beta2-agonists (LABAs; formoterol, indacaterol, salmeterol); long-acting muscarinic antagonists (LAMAs; aclidinium, glycopyrronium, tiotropium); inhaled corticosteroids (ICSs; budesonide, fluticasone, mometasone); combination long-acting beta2-agonist (LABA) and inhaled corticosteroid (LABA/ICS) (formoterol/budesonide, formoterol/mometasone, salmeterol/fluticasone); and placebo. DATA COLLECTION AND ANALYSIS: We conducted a network meta-analysis using Markov chain Monte Carlo methods for two efficacy outcomes: St George's Respiratory Questionnaire (SGRQ) total score and trough forced expiratory volume in one second (FEV1). We modelled the relative effectiveness of any two treatments as a function of each treatment relative to the reference treatment (placebo). We assumed that treatment effects were similar within treatment classes (LAMA, LABA, ICS, LABA/ICS). We present estimates of class effects, variability between treatments within each class and individual treatment effects compared with every other.To justify the analyses, we assessed the trials for clinical and methodological transitivity across comparisons. We tested the robustness of our analyses by performing sensitivity analyses for lack of blinding and by considering six- and 12-month data separately. MAIN RESULTS: We identified 71 RCTs randomly assigning 73,062 people with COPD to 184 treatment arms of interest. Trials were similar with regards to methodology, inclusion and exclusion criteria and key baseline characteristics. Participants were more often male, aged in their mid sixties, with FEV1 predicted normal between 40% and 50% and with substantial smoking histories (40+ pack-years). The risk of bias was generally low, although missing information made it hard to judge risk of selection bias and selective outcome reporting. Fixed effects were used for SGRQ analyses, and random effects for Trough FEV1 analyses, based on model fit statistics and deviance information criteria (DIC). SGRQ SGRQ data were available in 42 studies (n = 54,613). At six months, 39 pairwise comparisons were made between 18 treatments in 25 studies (n = 27,024). Combination LABA/ICS was the highest ranked intervention, with a mean improvement over placebo of -3.89 units at six months (95% credible interval (CrI) -4.70 to -2.97) and -3.60 at 12 months (95% CrI -4.63 to -2.34). LAMAs and LABAs were ranked second and third at six months, with mean differences of -2.63 (95% CrI -3.53 to -1.97) and -2.29 (95% CrI -3.18 to -1.53), respectively. Inhaled corticosteroids were ranked fourth (MD -2.00, 95% CrI -3.06 to -0.87). Class differences between LABA, LAMA and ICS were less prominent at 12 months. Indacaterol and aclidinium were ranked somewhat higher than other members of their classes, and formoterol 12 mcg, budesonide 400 mcg and formoterol/mometasone combination were ranked lower within their classes. There was considerable overlap in credible intervals and rankings for both classes and individual treatments. Trough FEV1 Trough FEV1 data were available in 46 studies (n = 47,409). At six months, 41 pairwise comparisons were made between 20 treatments in 31 studies (n = 29,271). As for SGRQ, combination LABA/ICS was the highest ranked class, with a mean improvement over placebo of 133.3 mL at six months (95% CrI 100.6 to 164.0) and slightly less at 12 months (mean difference (MD) 100, 95% CrI 55.5 to 140.1). LAMAs (MD 103.5, 95% CrI 81.8 to 124.9) and LABAs (MD 99.4, 95% CrI 72.0 to 127.8) showed roughly equivalent results at six months, and ICSs were the fourth ranked class (MD 65.4, 95% CrI 33.1 to 96.9). As with SGRQ, initial differences between classes were not so prominent at 12 months. Indacaterol and salmeterol/fluticasone were ranked slightly better than others in their class, and formoterol 12, aclidinium, budesonide and formoterol/budesonide combination were ranked lower within their classes. All credible intervals for individual rankings were wide. AUTHORS' CONCLUSIONS: This network meta-analysis compares four different classes of long-acting inhalers for people with COPD who need more than short-acting bronchodilators. Quality of life and lung function were improved most on combination inhalers (LABA and ICS) and least on ICS alone at 6 and at 12 months. Overall LAMA and LABA inhalers had similar effects, particularly at 12 months. The network has demonstrated the benefit of ICS when added to LABA for these outcomes in participants who largely had an FEV1 that was less than 50% predicted, but the additional expense of combination inhalers and any potential for increased adverse events (which has been established by other reviews) require consideration. Our findings are in keeping with current National Institute for Health and Care Excellence (NICE) guidelines

Pharmacokinetics and pharmacodynamics of tiotropium solution and tiotropium powder in chronic obstructive pulmonary disease

The aim of the study was to characterize pharmacokinetics of tiotropium solution 5 µg compared to powder 18 µg and assess dose-dependency of tiotropium solution pharmacodynamics in comparison to placebo. In total 154 patients with chronic obstructive pulmonary disease (COPD) were included in this multicenter, randomized, double-blind within-solution (1.25, 2.5, 5 µg, and placebo), and open-label powder 18 µg, crossover study, including 4-week treatment periods. Primary end points were peak plasma concentration (Cmax,ss ), and area under the plasma concentration-time profile (AUC0-6h,ss ), both at steady state. The pharmacodynamic response was assessed by serial spirometry (forced expiratory volume in 1 second/forced vital capacity). Safety was evaluated as adverse events and by electrocardiogram/Holter. Tiotropium was rapidly absorbed with a median tmax,ss of 5-7 minutes postdosing for both devices. The gMean ratio of solution 5 µg over powder 18 µg was 81% (90% confidence interval, 73-89%) for Cmax,ss and 76% (70-82%) for AUC0-6h,ss , indicating that bioequivalence was not established. Dose ordering for bronchodilation was observed. Powder 18 µg and solution 5 µg were most effective, providing comparable bronchodilation. All treatments were well tolerated with no apparent relation to dose or device. Comparable bronchodilator efficacy to powder18 µg at lower systemic exposure supports tiotropium solution 5 µg for maintenance treatment of COPD

Is there a rationale and role for long-acting anticholinergic bronchodilators in asthma?

The authors acknowledge the medical writing assistance received from Sam Yarwood, PhD, of Complete HealthVizion, in the form of literature searches and preparation and revision of the draft manuscript.Peer reviewedPublisher PD