The acoustic features of inhalation can be used to quantify aerosol delivery from a Diskus™ dry powder inhaler.

PURPOSE: Some patients are unable to generate the peak inspiratory flow rate (PIFR) necessary to de-agglomerate drug particles from dry powder inhalers (DPIs). In this study we tested the hypothesis that the acoustic parameters of an inhalation are related to the PIFR and hence reflect drug delivery. METHODS: A sensitivity analysis of the relationship of the acoustics of inhalation to simultaneously recorded airflow, in a cohort of volunteers (n = 92) was performed. The Next Generation Impactor (NGI) was used to assess in vitro drug delivery from salmeterol/fluticasone and salbutamol Diskus™ DPIs. Fine particle fraction, FPF, (<5 µm) was measured at 30-90 l/min for 2-6 s and correlated with acoustically determined flow rate (IFRc). In pharmacokinetic studies using a salbutamol (200 µg) Diskus™, volunteers inhaled either at maximal or minimal effort on separate days. RESULTS: PIFRc was correlated with spirometrically determined values (R (2) = 0.88). In in vitro studies, FPF increased as both flow rate and inhalation duration increased for the salmeterol/fluticasone Diskus™ (Adjusted R (2) = 0.95) and was proportional to flow rate only for the salbutamol Diskus™ (Adjusted R (2) = 0.71). In pharmacokinetic studies, blood salbutamol levels measured at 20 min were significantly lower when PIFRc was less than 60 l/min, p < 0.0001. CONCLUSION: Acoustically-determined PIFR is a suitable method for estimating drug delivery and for monitoring inhalation technique over time.

Structured sedation programs in the emergency department, hospital and other acute settings: protocol for systematic review of effects and events.

BACKGROUND: The use of procedural sedation outside the operating theatre has increased in hospital settings and has gained popularity among non-anesthesiologists. Sedative agents used for procedural pain, although effective, also pose significant risks to the patient if used incorrectly. There is currently no universally accepted program of education for practitioners using or introducing procedural sedation into their practice. There is emerging literature identifying structured procedural sedation programs (PSPs) as a method of ensuring a standardized level of competency among staff and reducing risks to the patient. We hypothesize that programs of education for healthcare professionals using procedural sedation outside the operating theatre are beneficial in improving patient care, safety, practitioner competence and reducing adverse event rates. METHODS/DESIGN: Electronic databases will be systematically searched for studies (randomized and non-randomized) examining the effectiveness of structured PSPs from 1966 to present. Database searches will be supplemented by contact with experts, reference and citation checking, and a grey literature search. No language restriction will be imposed. Screening of titles and abstracts, and data extraction will be performed by two independent reviewers. All disagreements will be resolved by discussion with an independent third party. Data analysis will be completed adhering to procedures outlined in the Cochrane Handbook of Systematic Reviews of Interventions. If the data allows, a meta-analysis will be performed. DISCUSSION: This review will cohere evidence on the effectiveness of structured PSPs on sedation events and patient outcomes within the hospital and other acute care settings. In addition, it will examine key components identified within a PSP associated with patient safety and improved patient outcomes. TRIAL REGISTRATION: PROSPERO registration number: CRD42013003851.

A method of estimating inspiratory flow rate and volume from an inhaler using acoustic measurements.

Inhalers are devices employed to deliver medication to the airways in the treatment of respiratory diseases such as asthma and chronic obstructive pulmonary disease. A dry powder inhaler (DPI) is a breath actuated inhaler that delivers medication in dry powder form. When used correctly, DPIs improve patients' clinical outcomes. However, some patients are unable to reach the peak inspiratory flow rate (PIFR) necessary to fully extract the medication. Presently clinicians have no reliable method of objectively measuring PIFR in inhalers. In this study, we propose a novel method of estimating PIFR and also the inspiratory capacity (IC) of patients' inhalations from a commonly used DPI, using acoustic measurements. With a recording device, the acoustic signal of 15 healthy subjects using a DPI over a range of varying PIFR and IC values was obtained. Temporal and spectral signal analysis revealed that the inhalation signal contains sufficient information that can be employed to estimate PIFR and IC. It was found that the average power (Pave) in the frequency band 300-600 Hz had the strongest correlation with PIFR (R(2) = 0.9079), while the power in the same frequency band was also highly correlated with IC (R(2) = 0.9245). This study has several clinical implications as it demonstrates the feasibility of using acoustics to objectively monitor inhaler use.

Single dose oral dexamethasone versus multi-dose prednisolone in the treatment of acute exacerbations of asthma in children who attend the emergency department: study protocol for a randomized controlled trial.

BACKGROUND: Asthma is a major cause of pediatric morbidity and mortality. In acute exacerbations of asthma, corticosteroids reduce relapses, subsequent hospital admission and the need for ß2-agonist therapy. Prednisolone is relatively short-acting with a half-life of 12 to 36 hours, thereby requiring daily dosing. Prolonged treatment course, vomiting and a bitter taste may reduce patient compliance with prednisolone. Dexamethasone is a long-acting corticosteroid with a half-life of 36 to 72 hours. It is used frequently in children with croup and bacterial meningitis, and is well absorbed orally. The purpose of this trial is to examine whether a single dose of oral dexamethasone (0.3 mg/kg) is clinically non-inferior to prednisolone (1 mg/kg/day for three days) in the treatment of exacerbations of asthma in children who attend the Emergency Department. METHODS/DESIGN: This is a randomized, non-inferiority, open-label clinical trial. After informed consent with or without assent, patients will be randomized to either oral dexamethasone 0.3 mg/kg stat or prednisolone 1 mg/kg/day for three days. The primary outcome measure is the comparison between the Pediatric Respiratory Assessment Measure (PRAM) across both groups on Day 4. The PRAM score, a validated, responsive and reliable tool to determine asthma severity in children aged 2 to 16 years, will be performed by a clinician blinded to treatment allocation. Secondary outcomes include relapse, hospital admission and requirement for further steroid therapy. Data will be analyzed on an intention-to-treat and a per protocol basis. With a sample size of 232 subjects (105 in each group with an estimated 10% loss to follow-up), we will be able to reject the null hypothesis - that the population means of the experimental and control groups are equal with a probability (power) of 0.9. The Type I error probability associated with this test (of the null hypothesis) is 0.05. DISCUSSION: This clinical trial may provide evidence that a shorter steroid course using dexamethasone can be used in the treatment of acute pediatric asthma, thus eliminating the issue of compliance to treatment. REGISTRATION: ISRCTN26944158 and EudraCT Number 2010-022001-18.

Improved late survival and disability after stroke with therapeutic anticoagulation for atrial fibrillation: a population study.

BACKGROUND AND PURPOSE: Although therapeutic anticoagulation improves early (within 1 month) outcomes after ischemic stroke in hospital-admitted patients with atrial fibrillation, no information exists on late outcomes in unselected population-based studies, including patients with all stroke (ischemic and hemorrhagic). METHODS: We identified patients with atrial fibrillation and stroke in a prospective, population-based study in North Dublin. Clinical characteristics, stroke subtype, stroke severity (National Institutes of Health Stroke Scale), prestroke antithrombotic medication, and International Normalized Ratio (INR) at onset were documented. Modified Rankin Scale (mRS) score was measured before stroke and at 7, 28, and 90 days; 1 year; and 2 years after stroke. RESULTS: One hundred seventy-five patients had atrial fibrillation-associated stroke and medication data at stroke onset (159 ischemic, 16 hemorrhagic); 17% of those with ischemic stroke were anticoagulated before stroke (27 of 159.) On multivariable analysis, therapeutic INR was associated with improved late survival after ischemic stroke (adjusted 2-year odds ratio for death=0.08; 95% CI, 0.01 to 0.78; P=0.03). This survival benefit persisted when patients with hemorrhagic stroke were included (2-year survival; 70.5% therapeutic INR, 14.3% nontherapeutic INR; log-rank P<0.001; odds ratio for death=0.27; 95% CI, 0.09 to 0.88; P=0.03). Admission INR was inversely correlated with early and late modified Rankin Scale score (2-year Spearman ρ=-0.65; P<0.0003). An INR of 2 to 3 at ischemic stroke onset was associated with greater early (72 hours to 28 days) modified Rankin Scale score improvement (P=0.04) and good functional outcome (modified Rankin Scale score=0 to 2) at 1 year (adjusted odds ratio=4.8; 95% CI, 1.45 to 23.8; P=0.04). CONCLUSIONS: In addition to improving short-term outcome in selected hospital-treated patient groups, therapeutic anticoagulation may provide important benefits for long-term stroke outcomes in unselected populations.

Stroke subtype classification to mechanism-specific and undetermined categories by TOAST, A-S-C-O, and causative classification system: direct comparison in the North Dublin population stroke study.

BACKGROUND AND PURPOSE: Reliable etiologic classification of ischemic stroke may enhance clinical trial design and identification of subtype-specific environmental and genetic risk factors. Although new classification systems (Causative Classification System [CCS] and ASCO [A for atherosclerosis, S for small vessel disease, C for cardiac source, O for other cause]) have been developed to improve subtype assignment, few comparative data exist from large studies. We hypothesized that both CCS and ASCO would reduce the proportion of patients classified as cause undetermined compared with the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) scheme in a large population-based stroke study. METHODS: A single rater classified all first-ever ischemic strokes in the North Dublin Population Stroke Study, a population-based study of 294 529 North Dublin residents. Published algorithms for TOAST, CCS, and ASCO were applied. RESULTS: In 381 first-ever ischemic stroke patients, CCS assigned fewer patients as cause undetermined (26.2% versus 39.4%; P<0.000001), with increased assignment of cardio-aortic embolism (relative increase 6.9%; P=0.004), large artery atherosclerosis (relative increase 44.1%; P=0.00006), small artery occlusion (relative increase 27.3%; P=0.00006), and other causes (relative increase 91.7%; P=0.001) compared with TOAST. When ASCO grade 1 evidence was applied, fewer patients were classified as small artery disease (relative decrease 29.1%; P=0.007) and more as large artery/atherothrombotic (relative increase 17.6%; P=0.03). ASCO grade 1 did not reduce the proportion of cause undetermined cases compared with TOAST (42.3% versus 39.4%; P=0.2). Agreement between systems ranged from good (kappa=0.61 for TOAST/ASCO grade 1 small artery category) to excellent (kappa=0.95 for TOAST/CCS and ASCO grade 1/CCS cardio/aorto-embolism category). Application of ASCO grades 1 to 3 indicated evidence of large artery/atherosclerosis (73.3%), cardio-embolism (31.3%), small artery (64.7%), and other cause (12%) in TOAST-undetermined cases. CONCLUSIONS: Both CCS and ASCO schemes showed good-to-excellent agreement with TOAST, but each had specific characteristics compared with TOAST for subtype assignment and data retention. The feasibility of a single combined classification system should be considered.