Reducing medication errors for hospital inpatients with Parkinsonism.

BACKGROUND: Patients with Parkinsonism are 1.5 times more likely than comparators to be hospitalised and have a significantly longer length of stay in hospital. Medication delays, inappropriate medication omission, and administration of contraindicated medications likely contribute to these poor outcomes. Education and hospital system interventions may reduce these errors. AIM: To determine the effectiveness of a multimodal education and awareness campaign in reducing medication errors in patients with Parkinsonism at Hutt Hospital. METHODS: We performed an audit of hospital medication charts to establish the baseline medication error rate and patient outcomes over a 3-month period. We then delivered an intervention consisting of staff education sessions, a sticker alert system and increased priority for pharmacist review of patient drug charts. We repeated the audit after the intervention. RESULTS: In the initial audit, the medication error rate was 22.5%, the clinical complication rate was 45% and one death was directly attributable to medication error. At follow up, the medication error and complication rates were 9.3% (absolute difference 13% (95% conflict of interest (CI) 10-16.4), P < 0.001) and 38% (absolute difference 7% (95% CI -19 to 34), P = 0.59), respectively, and there were no attributable deaths. The average length of stay before and after the intervention was 13 and 8 days respectively (absolute difference 5.7 days (95% CI -1.8 to 13.3), P = 0.135). CONCLUSIONS: There was a high in-hospital medication error rate for Parkinsonian patients. The intervention resulted in a statistically significantly improvement in the medication error rate. The estimated reductions in complication rate and length of stay may be clinically important. Similar interventions may be beneficial in other institutions.

Cognitive function during exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: The reported prevalence of cognitive impairment in patients with stable chronic obstructive pulmonary disease (COPD) ranges 36-77%. Few studies report the prevalence of cognitive impairment in acutely unwell COPD patients. AIMS: To determine the prevalence and time course of cognitive impairment in patients with COPD during and after an admission to hospital with an exacerbation of the disease. METHODS: Patients admitted to hospital with an exacerbation of COPD between October 2013 and November 2014 were administered the Montreal Cognitive Assessment tool, COPD assessment test and modified Borg dyspnoea scale at three points in time: within 24 h of admission, between 48 and 72 h after admission and 6 weeks post discharge. RESULTS: Twenty-five patients agreed to participate. Four withdrew from the study after the initial evaluation. The mean (range) COPD assessment test score 24 h after admission was 26 (18-37). Cognitive impairment was found in 19/25 (76%) patients at the initial evaluation, 16/21 (76%) patients at the second evaluation. Overall, 22/25 (88%) showed cognitive impairment within 72 h of an exacerbation of COPD. Fourteen out of 21 (66%) patients showed cognitive impairment at the final evaluation. The mean Montreal Cognitive Assessment scores improved from admission (22.6) to the second evaluation (23.3) to the final evaluation 3 (24.4), but this change was not statistically significant. CONCLUSION: Cognitive impairment is highly prevalent during hospital admissions with an exacerbation of COPD. This impairment does improve with time, but only a minority recover within a normal range. This will affect patients' abilities to understand and remember information given to them in hospital and adhere to medication regimens.

Serum periostin in obstructive airways disease.

Serum periostin is a potential biomarker of response to therapies that target type 2 inflammation in asthma. The objectives of this study were to describe: 1) the distribution of serum periostin levels in adults with symptomatic airflow obstruction; 2) its relationship with other variables, including type 2 biomarkers; and 3) the effect of inhaled corticosteroids on periostin levels.Serum periostin levels were measured in a cross-sectional study exploring phenotypes and biomarkers in 386 patients aged 18-75 years who reported wheeze and breathlessness in the past 12 months. In 49 ICS-naïve patients, periostin levels were measured again after 12 weeks of budesonide (800 µg·day(-1)).The distribution of serum periostin levels was right skewed (mean±sd 57.3±18.6 ng·mL(-1), median (interquartile range) 54.0 (45.1-65.6) ng·mL(-1), range 15.0-164.7 ng·mL(-1)). Periostin was positively associated with exhaled nitric oxide (Spearman's rho=0.22, p<0.001), blood eosinophil count (Spearman's rho=0.21, p<0.001), and total IgE (Spearman's rho=0.14, p=0.007). The Hodges-Lehmann estimator (95% CI) of change in periostin level after ICS therapy was -4.8 (-6.7- -3.2) ng·mL(-1) (p<0.001).These findings provide data on the distribution of serum periostin in adults with symptomatic airflow obstruction, the weak associations between periostin and other type 2 markers, and the reduction in periostin with inhaled corticosteroid therapy.

Treatment responsiveness of phenotypes of symptomatic airways obstruction in adults.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous disorders encompassing different phenotypes of airflow obstruction, which might differ in their response to treatment. OBJECTIVE: The aim of this study was to determine distinct phenotypes comprising the syndromes of asthma and COPD and the treatment responsiveness of these phenotypes to inhaled ß-agonist, antimuscarinic, and corticosteroid therapy. METHODS: We undertook a cross-sectional study with 3 phases. In phase 1, 1,264 participants aged 18 to 75 years with self-reported current wheeze and breathlessness were identified from a random population sample of 16,459. In phase 2, 451 participants attended for detailed assessment, including responsiveness to inhaled salbutamol and ipratropium bromide. In phase 3, 168 steroid-naive participants were enrolled in a 12-week trial of inhaled budesonide. Cluster analysis was performed in 389 participants who completed phase 2 with full data. Treatment responsiveness was compared between phenotypes. RESULTS: Cluster analysis identified 5 phenotypes: moderate-to-severe childhood-onset atopic asthma, asthma-COPD overlap, obese-comorbid, mild childhood-onset atopic asthma, and mild intermittent. Bronchodilation after salbutamol was equal to or greater than that after ipratropium for all phenotypes. The moderate-to-severe childhood-onset atopic asthma, asthma-COPD overlap, and obese-comorbid phenotypes had greater efficacy with inhaled corticosteroid treatment than the mild intermittent group. CONCLUSION: Cluster analysis of adults with symptomatic airflow obstruction identifies 5 disease phenotypes, including asthma-COPD overlap and obese-comorbid phenotypes, and provides evidence that patients with the asthma-COPD overlap syndrome might benefit from inhaled corticosteroid therapy.

Interventions for sexual dysfunction in people with chronic obstructive pulmonary disease (COPD).

BACKGROUND: People with chronic obstructive pulmonary disease (COPD) are believed be at higher risk of problems with sexual function than age-matched peers. Problems with sexuality or sexual function associated with COPD may arise as a results of hormonal, physiological, or psychological problems, or as a result of changes in intimate relationships arising from the chronic nature of the condition. OBJECTIVES: To evaluate the effectiveness of interventions for sexual dysfunction in people with COPD. SEARCH METHODS: We searched the Cochrane Airways Group's Specialised Register on 8 July 2015 and conducted supplementary searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, four other databases, and two trials registers to July 2015, together with reference checking, citation searching, and contact with study authors to identify additional studies. We used no language or date restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs), cluster RCTs, and quasi-RCTs evaluating the effects of pharmacological, mechanical, psychological, or educational interventions to address problems with sexual well-being in people with COPD and their partners. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed search results against predetermined inclusion criteria. Two review authors independently extracted data and assessed risk of bias for included studies. We contacted study authors for additional information. MAIN RESULTS: We included two studies involving a total of 48 participants. One of these studies (an RCT) investigated the effect of a pharmacological intervention (testosterone therapy) compared to a placebo over a four-month period. The other study (a quasi-RCT) compared one month of long-term oxygen therapy to a single 24-hour dose of oxygen therapy over a one-month period. Both studies only included men with moderate to very severe COPD (mean FEV1% across both studies 41%; standard deviation (SD) 11.7%) who were under the age of 74 (mean age across both studies 65 years; SD 7.1). We found low-quality evidence that testosterone therapy for men with COPD results in improvements in erectile function, but no evidence of effect regarding overall satisfaction with sexual function. There is insufficient data to draw conclusions regarding the possibility of adverse events arising from testosterone therapy for COPD or the effect of oxygen therapy on erectile dysfunction. Neither study provided additional data on sexual function, other than erectile function. AUTHORS' CONCLUSIONS: There is currently insufficient evidence from clinical trials at present to inform the best way of providing interventions to improve sexual function and sexual satisfaction for people with COPD and their partners. Consequently, clinicians need to rely on clinical trials involving people without COPD and expert opinion in order to guide clinical practice in this area. Considerably more trials need to be conducted in this area of clinical practice.

ANTECEDENTES: Se considera que los pacientes con enfermedad pulmonar obstructiva crónica (EPOC) tienen un mayor riesgo de problemas con la función sexual que sus pares igualados por la edad. Los problemas con la sexualidad o la función sexual asociados con la EPOC pueden surgir como resultado de problemas hormonales, fisiológicos o psicológicos, o como resultado de los cambios en las relaciones íntimas que aparecen por la naturaleza crónica de la afección. OBJETIVOS: Evaluar la efectividad de las intervenciones para la disfunción sexual en los pacientes con EPOC. MÉTODOS DE BÚSQUEDA: Se buscó en el registro especializado del Grupo Cochrane de Vías Respiratorias (Cochrane Airways Group) el 8 de julio de 2015 y se realizaron búsquedas suplementarias en el Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials) (CENTRAL), MEDLINE, EMBASE, en otras cuatro bases de datos y en otros dos registros hasta julio 2015, junto con la verificación de las referencias, la búsqueda de citas y el contacto con autores de estudios para identificar estudios adicionales. No se aplicó ninguna restricción de idioma o de fecha. CRITERIOS DE SELECCIÓN: Ensayos controlados aleatorios (ECA), ECA grupales y ensayos controlados cuasialeatorios que evaluaron los efectos de las intervenciones farmacológicas, mecánicas, psicológicas o educacionales para enfrentar los problemas con el bienestar sexual en pacientes con EPOC y sus parejas. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos revisores de manera independiente examinaron los resultados de la búsqueda contra los criterios predeterminados de inclusión. Dos autores de la revisión, de forma independiente, extrajeron los datos y evaluaron el riesgo de sesgo de los estudios incluidos. Se contactó con los autores de los estudios para obtener información adicional. RESULTADOS PRINCIPALES: Se incluyeron dos estudios con un total de 48 participantes. Uno de estos estudios (un ECA) investigó el efecto de una intervención farmacológica (tratamiento con testosterona) comparada con placebo durante un período de cuatro meses. El otro estudio (un ensayo controlado cuasialeatorio) comparó un mes de oxigenoterapia a largo plazo con una dosis única de 24 horas de oxigenoterapia durante un período de un mes. Ambos estudios solamente incluyeron hombres con EPOC moderada a muy grave (VEF1% medio en ambos estudios 41%; desviación estándar [DE] 11,7%) que tenían menos de 74 años (edad promedio en ambos estudios 65 años; DE 7,1). Se encontraron pruebas de baja calidad de que el tratamiento con testosterona en los hombres con EPOC da lugar a mejorías en la función eréctil, pero no se obtuvieron pruebas del efecto con respecto a la satisfacción general con la función sexual. No hay datos suficientes para establecer conclusiones con respecto a la posibilidad de eventos adversos con el tratamiento con testosterona para la EPOC o el efecto de la oxigenoterapia sobre la disfunción eréctil. Ningún estudio proporcionó datos adicionales sobre la función sexual, aparte de la función eréctil. CONCLUSIONES DE LOS AUTORES: Actualmente no hay pruebas suficientes de ensayos clínicos que informen la mejor manera de proporcionar intervenciones para mejorar la función sexual y la satisfacción sexual de los pacientes con EPOC y sus parejas. Por lo tanto, los médicos deben depender de ensayos clínicos que incluyen pacientes sin EPOC y de la opinión de expertos para guiar la práctica clínica en esta área. Es necesario realizar muchos más ensayos en esta área de la práctica clínica.

Combination budesonide/formoterol inhaler as maintenance and reliever therapy in Maori with asthma.

BACKGROUND AND OBJECTIVE: There are significant health disparities between Maori and non-Maori with asthma, a pattern seen between other ethnic populations. This study investigates outcomes for Maori in a randomized controlled trial (RCT) of combination budesonide/formoterol inhaler therapy in asthma. METHODS: This 24-week multicentre RCT recruited 303 adult asthma patients, 44 of whom were Maori. Participants were randomized to the single combination budesonide/formoterol inhaler as maintenance and reliever therapy ('SMART') regimen or 'standard' regimen (combination budesonide/formoterol inhaler for maintenance and salbutamol as reliever). Outcomes included patterns of beta-agonist inhaler use including 'high use' of reliever therapy (>8 actuations of budesonide/formoterol in excess of four maintenance doses per day for SMART and >16 actuations per day of salbutamol for standard). Differences in outcomes for Maori versus non-Maori were assessed using an interaction term between ethnicity and treatment. RESULTS: With adjustment for ethnicity, the SMART group had fewer days of high use (relative rate (RR) 0.57 (95% confidence interval (CI): 0.38-0.85)), days of high use without medical review within 48 h (RR 0.49 (95% CI: 0.32-0.75)) and severe exacerbations (RR 0.54 (95% CI: 0.36-0.81)) compared with standard. The magnitude of the benefit from the SMART regimen was similar in Maori and non-Maori. Regardless of treatment regimen, Maori demonstrated more days of high use, high use without medical review and underuse of maintenance therapy. CONCLUSIONS: The SMART regimen has a favourable risk/benefit profile in Maori. Days of high use, days of high use without medical review and underuse of maintenance treatment were greater in Maori, regardless of treatment regimen.

The multiple dimensions of airways disease: targeting treatment to clinical phenotypes.

PURPOSE OF REVIEW: The recognition that asthma and chronic obstructive pulmonary disease (COPD) are not single diseases, but syndromes made up of multiple separate disorders that overlap, has led to attempts to develop a new taxonomy for the disorders of airflow obstruction. A better understanding of the distinct disorders of airways disease has the potential to inform on underlying mechanisms, risk factors, natural history, monitoring and treatment. RECENT FINDINGS: Recent attempts to describe the different phenotypes have largely been based on cluster analysis. Preliminary evidence suggests that there may be five distinct phenotypes of airways disease. To date, however, no simple allocation criteria have been validated that enable clinicians to allocate individual patients to specific phenotypic groups. The concept of differential treatment responses in different phenotypes of airways disease has been established with the demonstration that eosinophilic asthma preferentially responds to inhaled corticosteroid therapy or monoclonal antibody against interleukin-5, and severe refractory noneosinophilic asthma to macrolide antibiotics. SUMMARY: The priority is to further define the distinct phenotypes that make up the syndromes of asthma and COPD. This knowledge could lead to treatments specifically targeted for defined phenotypic groups, rather than for asthma and COPD in general, which represents the current management approach.

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

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

New Zealand COPD Guidelines: Quick Reference Guide.

The purpose of the Asthma and Respiratory Foundation of New Zealand's COPD Guidelines: Quick Reference Guide is to provide simple, practical, evidence-based recommendations for the diagnosis, assessment, and management of chronic obstructive pulmonary disease (COPD) in clinical practice. The intended users are health professionals responsible for delivering acute and chronic COPD care in community and hospital settings, and those responsible for the training of such health professionals.

Expiratory reactance abnormalities in patients with expiratory dynamic airway collapse: a new application of impulse oscillometry.

Expiratory dynamic airways collapse (EDAC) is a condition that affects the central airways; it is not well characterised physiologically, with relatively few studies. We sought to characterise impulse oscillometry (IOS) features of EDAC in patients with normal spirometry. Expiratory data were hypothesised to be the most revealing. In addition, we compared IOS findings in chronic obstructive pulmonary disease (COPD) patients with and without EDAC. EDAC was identified at bronchoscopy as 75-100% expiratory closure at the carina or bilateral main bronchi. Four patient groups were compared: controls with no EDAC and normal lung function; lone EDAC with normal lung function; COPD-only patients; and COPD patients with EDAC. 38 patients were studied. Mean IOS data z-scores for EDAC compared to controls showed significantly higher reactance (X) values including X at 5 Hz, resonance frequency and area under the reactance curve (AX). EDAC showed significantly greater expiratory/inspiratory differences in all IOS data compared to controls. Stepwise logistic regression showed that resonant frequency best discriminated between EDAC and normal control, whereas classification and regression tree analysis found AX ≥3.523 to be highly predictive for EDAC in cases with normal lung function (14 out of 15 cases, and none out of eight controls). These data show a new utility of IOS: detecting EDAC in patients with normal lung function.

External validity of randomized controlled trials in COPD.

BACKGROUND: COPD is a heterogeneous disease comprising a wide range of clinical phenotypes, depending on the degree to which emphysema, chronic bronchitis, reversible bronchospasm and small airways inflammation are present. Not all of these phenotypes may be represented among the subjects included in randomized controlled drug trials (RCTs) in COPD, making it difficult for doctors to know to what extent RCT evidence applies to individual patients. From a respiratory health survey of adults randomly selected from the community, we have estimated the proportion of subjects with COPD who would have been eligible for inclusion in major COPD RCTs. METHODS: A postal survey was sent to 3500 randomly selected individuals aged 25-75 years. Respondents were invited to complete a detailed respiratory questionnaire and pulmonary function tests. Subjects with COPD defined by post-bronchodilator spirometry were assessed against the eligibility criteria of 18 major RCTs cited in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. FINDINGS: Of 749 subjects completing the full survey, 117 had COPD. Of these, a median of 5% (range 0-20%) of subjects met inclusion criteria for the major RCTs. Of 55 subjects with COPD receiving treatment, 0-9% (median 5%) met inclusion criteria for the major RCTs. INTERPRETATION: The major COPD RCTs on which the GOLD treatment guidelines are based may have limited external validity. Over 90% of the COPD subjects in the community who were taking medication, did so on the basis of RCTs for which they would not have been eligible.

The effect of 1g of acetaminophen twice daily for 12 weeks on alanine transaminase levels--A randomized placebo-controlled trial.

OBJECTIVE: Acetaminophen is often used on a regular, daily basis for the treatment of chronic pain; however, the safety of regular acetaminophen is still debated. This study determined whether 12 weeks of treatment with acetaminophen at half the maximum recommended daily dose causes an increase in alanine transaminase (ALT) in healthy adults participating in a clinical trial of the effect of acetaminophen on asthma control and severity. DESIGN AND METHODS: 94 healthy adults aged 18-65 years with mild to moderate asthma and with no history of previous liver dysfunction and an ALT within 1.5 times the upper limit of normal at baseline participated in a randomized, double-blind, placebo-controlled, parallel-group, clinical trial of 1g of acetaminophen twice daily or placebo twice daily for 12 weeks. Liver function monitoring was undertaken at baseline, weeks 2, 4, 6 and 12. The primary outcome variable was mean ALT levels at week 12 compared to baseline in the acetaminophen group versus placebo group. RESULTS: 94 participants were randomized and commenced study treatment. One participant in each treatment group was withdrawn due to an increase in ALT to greater than three times the upper limit of normal. Mean ALT at week 12 was 25.4I U/L (SD 9.7) in the acetaminophen group (N=31) and 19.0 IU/L (SD 6.0) in the placebo group (N=54). After controlling for baseline this represented a statistically significant difference of 3.6 IU/L (95% CI 1.3 to 6.0, P=0.003). There was no progressive increase in ALT demonstrated throughout the trial. CONCLUSIONS: Regular, daily use of acetaminophen at half the maximum recommended daily dose for 12 weeks in a healthy adult population is associated with a small elevation in mean ALT of no probable clinical significance. Further assessment of the effects on liver function of the maximum recommended dose of acetaminophen is required.

Randomised placebo-controlled study of the effect of paracetamol on asthma severity in adults.

OBJECTIVE: To investigate the effect of regular paracetamol on bronchial hyper-responsiveness (BHR) and asthma control in adult asthma. SETTING: Single research-based outpatient clinic. PARTICIPANTS: 94 adults with mild-to-moderate asthma received randomised treatment; 85 completed the study. Key inclusion criteria were age 18-65 years, forced expiratory volume in 1 s (FEV1) >70% predicted, provocation concentration of methacholine causing a 20% reduction in FEV1 (PC20) between 0.125 and 16 mg/mL. Key exclusion criteria included an asthma exacerbation within the previous 2 months, current regular use of paracetamol, use of high-dose aspirin or non-steroidal anti-inflammatory drugs, current or past cigarette smoking >10 pack-years. INTERVENTIONS: In a 12-week randomised, double-blind, placebo-controlled, parallel-group study, participants received 12 weeks of 1 g paracetamol twice daily or placebo twice daily. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome variable was BHR, measured as the PC20 at week 12. Secondary outcome variables included FEV1, fractional exhaled nitric oxide (FeNO) and asthma control questionnaire (ACQ) score. RESULTS: At 12 weeks, the mean (SD) logarithm base two PC20 was 1.07 (2.36) in the control group (N=54) and 0.62 (2.09) in the paracetamol group (N=31). After controlling for baseline PC20, the mean difference (paracetamol minus placebo) was -0.48 doubling dose worsening in BHR in the paracetamol group (95% CI -1.28 to 0.32), p=0.24. There were no statistically significant differences (paracetamol minus placebo) in log FeNO (0.09 (95% CI -0.097 to 0.27)), FEV1 (-0.07 L (95% CI -0.15 to 0.01)) or ACQ score (-0.04 (95% CI -0.27 to 0.18)). CONCLUSIONS: There was no significant effect of paracetamol on BHR and asthma control in adults with mild-to-moderate asthma. However, the study findings are limited by low power and the upper confidence limits did not rule out clinically relevant adverse effects. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry Number: NZCTR12609000551291.

Occupational risk factors for chronic respiratory disease in a New Zealand population using lifetime occupational history.

OBJECTIVES: To investigate associations between respiratory disease and occupational exposures in a New Zealand urban population, the Wellington Respiratory Survey. METHODS: Multiple regression analyses in a population sample of 1017 individuals aged 25 to 74 years with spirometry and questionnaire information, including a lifetime occupational history. RESULTS: Chronic bronchitis symptoms were associated with self-reported exposure to hairdressing, paint manufacturing, insecticides, welding, detergents and with ALOHA Job Exposure Matrix-assessed gases/fumes exposure. The strongest association was for hairdressing (odds ratio 6.91; 95% confidence interval: 2.02 to 23.70). Cumulative exposure to mineral dust and gases/fumes was associated with higher FEV1% (forced expiratory volume in the first second of expiration) predicted. Analyses were limited by relatively small numbers of cases. CONCLUSIONS: Increased risks of objectively defined respiratory disease, which have been previously documented, were not seen. Nevertheless, the study suggested increased risk of respiratory symptoms with various occupational exposures as well as likely healthy worker effect.

Use of metered-dose inhaler electronic monitoring in a real-world asthma randomized controlled trial.

BACKGROUND: Electronic monitoring of inhaled asthma medications is one method to measure medication adherence and patterns of use. Information on the performance of monitors in a randomized controlled trial allows researchers and clinicians to understand their utility and limitations. The Smartinhaler Tracker is an electronic monitor for metered-dose inhalers (MDIs) that records the date, time, and number of actuations. OBJECTIVE: To determine the performance of the Smartinhaler monitors used in a 24-week randomized controlled trial of 303 patients with asthma in a real-world setting. METHODS: Prestudy use checks involved 2 actuations of the MDI, with a further 2 performed 2 hours later. Within-study monitor checks, performed before dispensing at clinic visits 2 to 4, included a computerized check of monitor clock function, actuation accuracy, and battery life. Within-study data checks involved computerized checks of monitor clock function before data upload. RESULTS: Two thousand six hundred seventy-eight of 2728 monitors (98.2%) passed prestudy use checks. Seventy-six of 2642 monitors (2.9%) dispensed to participants failed within-study monitor checks. Fifty-one of 2642 monitors (1.9%) malfunctioned before data upload, mostly as a result of fluid immersion. Ninety-three of 2642 monitors (3.5%) were lost or thrown away by participants. Complete data was available from 2498 of 2642 dispensed monitors (94.5%) and 2498 of 2549 returned monitors (98.0%). CONCLUSIONS: The Smartinhaler Tracker is a reliable monitor for measuring MDI use in a real-world setting. Use of extensive monitor and data-checking protocols reduces data loss. In a research or clinical setting, the use of a validated and reliable electronic monitor represents the reference standard for assessing patterns of medication use.

Efficacy and safety of maintenance and reliever combination budesonide-formoterol inhaler in patients with asthma at risk of severe exacerbations: a randomised controlled trial.

BACKGROUND: The Single combination budesonide-formoterol inhaler Maintenance And Reliever Therapy (SMART) regimen reduces severe asthma exacerbations in patients, but whether the high doses of corticosteroid and ß agonist increase the risk of adverse effects with both short-term and cumulative exposure is not certain. Our aim was to investigate whether the SMART regimen would reduce the risk of overuse of ß agonist, reduce the likelihood of patients to seek medical review when such episodes occurred, and if any reduction in severe asthma exacerbations would be at the cost of a higher burden of systemic corticosteroid. METHODS: In this 24-week trial undertaken at four primary health-care practices and one hospital in New Zealand, patients (aged 16-65 years) with a recent asthma exacerbation were randomly assigned in a 1:1 ratio to the SMART or standard fixed-dose regimen. Treatment in the SMART group consisted of two actuations of budesonide-formoterol (200 µg and 6 µg, respectively, per actuation) twice daily, delivered through a combination metered dose inhaler (MDI), with one extra actuation as needed for relief of symptoms; treatment in the standard group consisted of two actuations of budesonide-formoterol (200 µg and 6 µg, respectively, per actuation) twice daily through a combination MDI with one to two actuations of salbutamol (100 µg per actuation) by MDI as needed for relief of symptoms. MDIs were monitored electronically to measure actual use of medication. The allocation sequence for randomisation was computer generated, with a block size of eight per site. Participants, investigators, and the statistician were not masked to group assignment. The primary outcome was the proportion of participants with at least one high-use episode of ß agonist (more than eight actuations per day of budesonide-formoterol in addition to the four maintenance doses in the SMART group or more than 16 actuations per day of salbutamol in the standard group). Analysis was by intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12610000515099. FINDINGS: 303 patients were randomly assigned to the SMART (n=151) or standard group (n=152). No significant difference was noted between the SMART and standard groups in the proportion of participants with at least one high-use episode of ß agonist (84 [56%] vs 68 [45%], respectively, relative risk 1·24 [95% CI 0·99-1·56]; p=0·058). There were fewer days of high use in the SMART group (mean 5·1 days [SD 14·3] vs 8·9 days [20·9], relative rate 0·58 [0·39-0·88]; p=0·01). Of the patients who had at least one high-use episode, those in the SMART group had fewer days of high use without medical review (8·5 days [17·8] vs 18·3 days [24·8], 0·49 [0·31-0·75]; p=0·001). The SMART regimen resulted in higher inhaled corticosteroid exposure (943·5 µg budesonide per day [1502·5] vs 684·3 µg budesonide per day [390·5], respectively; ratio of means 1·22 [1·06-1·41]; p=0·006), but reduced oral corticosteroid exposure (77·5 mg prednisone [240·5] vs 126·6 mg prednisone [382·1], respectively; p=0·011), with no significant difference in composite systemic corticosteroid exposure (793·7 mg prednisone equivalent per year [893·1] vs 772·1 mg prednisone equivalent per year [1062·7], respectively; 1·03 [0·86-1·22]; p=0·76). Participants in the SMART group had fewer severe asthma exacerbations (35 [weighted mean rate per year 0·53] vs 66 [0·97]; relative rate 0·54 [0·36-0·82]; p=0·004). INTERPRETATION: The SMART regimen has a favourable risk-to-benefit profile and can be recommended for use in adults at risk of severe asthma exacerbations. FUNDING: Health Research Council of New Zealand.

External validity of randomised controlled trials in asthma: to whom do the results of the trials apply?

BACKGROUND: Asthma is a heterogeneous disease with a wide range of clinical phenotypes, not all of which may be encompassed in the subjects included in randomised controlled trials (RCTs). This makes it difficult for clinicians to know to what extent the evidence derived from RCTs applies to a given patient. AIM: To calculate the proportion of individuals with asthma who would have been eligible for the major asthma RCTs from the data of a random community survey of respiratory health. METHODS: A postal survey was sent to 3500 randomly selected individuals aged 25-75 years. Respondents were invited to complete a detailed respiratory questionnaire and pulmonary function testing. Participants with current asthma were assessed against the eligibility criteria of the 17 major asthma RCTs cited in the Global Initiative for Asthma (GINA) guidelines. FINDINGS: A total of 749 participants completed the full survey, of whom 179 had current asthma. A median 4% of participants with current asthma (range 0-36%) met the eligibility criteria for the included RCTs. A median 6% (range 0-43%) of participants with current asthma on treatment met the eligibility criteria. INTERPRETATION: This study shows that the major asthma RCTs on which the GINA guidelines are based may have limited external validity as they have been performed on highly selected patient populations. Most of the participants with current asthma on treatment in the community would not have been eligible for these RCTs.

Reference ranges for exhaled nitric oxide derived from a random community survey of adults.

RATIONALE: Measurement of the fraction of nitric oxide in exhaled breath (Fe(NO)) has been proposed as a noninvasive marker of airway inflammation. Before the widespread use of this test, there is a need to develop reference ranges to allow clinicians to interpret Fe(NO) measurements. OBJECTIVES: To derive reference ranges for Fe(NO) and to determine which factors in health and disease influence Fe(NO) levels. METHODS: Subjects aged between 25 and 75 years were drawn from a random sample of the predominantly white population of Wellington, New Zealand. MEASUREMENTS AND MAIN RESULTS: Fe(NO) was measured using an online nitric oxide monitor in accordance with international guidelines. A detailed respiratory questionnaire and pulmonary function tests were performed. The geometric mean Fe(NO) was 17.9 parts per billion (ppb) with a 90% confidence interval for an individual prediction (reference range) for normal subjects of 7.8 to 41.1 ppb. Sex, atopy, and smoking status significantly affected Fe(NO) levels, and several reference ranges are presented adjusting for these factors. Asthma and allergic rhinitis were associated with higher Fe(NO). Measurement of Fe(NO) had poor discriminant ability to identify steroid-naive subjects with asthma. CONCLUSIONS: The reference ranges presented may be used to assist in the interpretation of Fe(NO) measurements in white adults.