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Open adherence monitoring using routine data download from an adaptive aerosol delivery nebuliser in children with cystic fibrosis
Abstract
Adaptive aerosol delivery (AAD) nebuliser devices can reduce treatment times whilst enabling adherence to be monitored using inbuilt data logs. Using one such device, we have monitored nebulised antibiotic adherence in children with Cystic Fibrosis (CF).
In CF children infected with Pseudomonas aeruginosa, downloaded data from an AAD device was used to calculate morning, evening and overall monthly adherence to antibiotic therapy over a year.
Overall monthly adherence to nebulised antibiotic therapy in 28 children was maintained between 60 and 70% over the year. Considerable variation in adherence, both between and within patients, was evident (Mean [SD] coefficient of variation, 37[44]%). Evening adherence (75[37]%) was better than morning adherence (58[34]%: p=0.012). Treatment regimens were changed in 8/28 patients based on adherence data.
Routine adherence monitoring can be implemented in an outpatient setting. Using this type of information it is possible to identify which aspects of treatment can be improved and to work together with families to individualize treatments.
... Much of the focus in research has been around time pressures. McNamara, McCormack, McDonald, Heaf, and Southern (2009) demonstrated that children with CF are more adherent to nebulised therapies in the evenings in comparison to the mornings, suggesting greater time pressures in the mornings (for both parents and children) (Latchford, Duff, Quinn, Conway, & Conner, 2009;McNamara et al., 2009). This is supported by Bregnballe et al. 's work (2011), with 60.00% of CF adolescents agreeing that one of the main adherence barriers is a lack of time. ...
... Much of the focus in research has been around time pressures. McNamara, McCormack, McDonald, Heaf, and Southern (2009) demonstrated that children with CF are more adherent to nebulised therapies in the evenings in comparison to the mornings, suggesting greater time pressures in the mornings (for both parents and children) (Latchford, Duff, Quinn, Conway, & Conner, 2009;McNamara et al., 2009). This is supported by Bregnballe et al. 's work (2011), with 60.00% of CF adolescents agreeing that one of the main adherence barriers is a lack of time. ...
... Adherence was measured utilising the DPD methodology. It was hypothesised that reported adherence would be higher during the weekend in comparison to weekdays, due to it being expected that the time pressures are less for adults during the weekend (Bregnballe et al., 2011;McNamara et al., 2009;Latchford et al., 2009). ...
Background
Treatment adherence is a major concern in cystic fibrosis (CF), with accumulating evidence that health outcomes are worse in patients with lower levels of adherence. This study investigates how adherence differs for adults with CF during a weekday and a weekend day by examining the roles of sex, anxiety, depression, and lung function as predictors of adherence.
Participants and procedure
Fifty-two adult participants with CF were recruited. Demographics and spirometry results were recorded. Participants completed the Hospital Anxiety and Depression Scale and two daily phone diaries in order to record their adherence to pancreatic enzymes, vitamins, physiotherapy and exercise. Based on previous findings, it was hypothesised that reported adherence would be higher during the weekend in comparison to weekdays, due to lower time pressure during the weekend.
Results
Paired sample t-tests indicated that overall participants had higher reported adherence during the weekend in comparison to weekdays, with sex, anxiety, depression and lung function being predictors of adherence.
Conclusions
Clinical implications and future directions are discussed, with an emphasis on the need for further qualitative research. We are now conducting another research project utilising qualitative interviews with participants to further investigate adherence within the CF population. Our aim is to identify the main adherence barriers and to develop interventions to improve treatment adherence in the CF population.
... Three studies were randomized controlled trials (RCTs), [20][21][22] three were prospective cohort studies, [23][24][25] and four retrospective studies [26][27][28][29] were also included. The population size varied between 28 28 and 832 29 subjects, with a mean age of 9.1 28 to 28.7 20 years. ...
... Three studies were randomized controlled trials (RCTs), [20][21][22] three were prospective cohort studies, [23][24][25] and four retrospective studies [26][27][28][29] were also included. The population size varied between 28 28 and 832 29 subjects, with a mean age of 9.1 28 to 28.7 20 years. Seven studies focused on measuring adherence to inhaled tobramycin, [21][22][23][24]26,27,29 one on inhaled colistimethate, 28 one on inhaled levofloxacin, 20 and one on inhaled aztreonam lysine. ...
... The population size varied between 28 28 and 832 29 subjects, with a mean age of 9.1 28 to 28.7 20 years. Seven studies focused on measuring adherence to inhaled tobramycin, [21][22][23][24]26,27,29 one on inhaled colistimethate, 28 one on inhaled levofloxacin, 20 and one on inhaled aztreonam lysine. 25 The general characteristics of the reviewed studies are summarized in Table 1. ...
Background:
Inhaled antibiotics (ABs) are recommended for use in the therapy of chronic Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF). The aim of this systematic literature review was to identify level of adherence to inhaled ABs and to determine predictors and consequences of nonadherence in CF.
Methods:
A systematic literature search of English-language articles was conducted in April 2015 using Medline and Embase. No publication date limit was applied. The literature screening was conducted by two independent reviewers. All of the included studies were assessed for quality.
Results:
The search yielded 193 publications, of which ten met the inclusion criteria and underwent data extraction. Seven studies focused on inhaled tobramycin, one on inhaled colistimethate, one on inhaled levofloxacin, and one on inhaled aztreonam lysine. Medication adherence to inhaled ABs was analyzed by pharmacy refill history, daily phone diary, parent and child self-reports, vials counting, or electronic monitoring. In randomized controlled trials (n=3), proportion of adherent patients (>75%-80% of required doses taken) ranged from 86% to 97%; in prospective cohort studies (n=3), adherence rates ranged between 36% and 92%, and in retrospective studies (n=4) it ranged between 60% and 70%. The adherence to inhaled ABs in CF was found to be associated with the complexity of treatment, time of drug administration, age of patients, treatment burden (adverse events, taste), and patient satisfaction.
Conclusion:
The high diversity of adherence data was because of the different study designs (randomized controlled trials vs real-world studies) and the lack of a commonly accepted consensus on the definition of adherence in the reviewed articles. Routine adherence monitoring during CF care, discussing the possible reasons of suboptimal adherence with the patient, and changing treatment regimens on the basis of patient burden can individualize CF therapy for patients and may improve the level of adherence.
... Three studies were randomized controlled trials (RCTs), [20][21][22] three were prospective cohort studies, [23][24][25] and four retrospective studies [26][27][28][29] were also included. The population size varied between 28 28 and 832 29 subjects, with a mean age of 9.1 28 to 28.7 20 years. ...
... Three studies were randomized controlled trials (RCTs), [20][21][22] three were prospective cohort studies, [23][24][25] and four retrospective studies [26][27][28][29] were also included. The population size varied between 28 28 and 832 29 subjects, with a mean age of 9.1 28 to 28.7 20 years. Seven studies focused on measuring adherence to inhaled tobramycin, [21][22][23][24]26,27,29 one on inhaled colistimethate, 28 one on inhaled levofloxacin, 20 and one on inhaled aztreonam lysine. ...
... The population size varied between 28 28 and 832 29 subjects, with a mean age of 9.1 28 to 28.7 20 years. Seven studies focused on measuring adherence to inhaled tobramycin, [21][22][23][24]26,27,29 one on inhaled colistimethate, 28 one on inhaled levofloxacin, 20 and one on inhaled aztreonam lysine. 25 The general characteristics of the reviewed studies are summarized in Table 1. ...
... Schedule: One follow-up study demonstrated that children with CF demonstrate greater adherence to therapies in the evening rather than the morning [29]. Adolescents' average weekday adherence was significantly greater than weekend adherence, and their average adherence on school days was greater than over the holidays, suggesting that having a structured schedule improves adherence [26]. ...
... Adolescents with CF value time as they become more aware of their shortened life expectancy [15]. Adolescents have higher rates of adherence on school days and in the evenings, whereas adherence decreases during the holidays and on weekends [29,26]. Balancing the time between treatments, educational, social, and personal commitments remain an ongoing challenge for CF care teams as forgetfulness and being busy are common excuses for missed treatments [27,21]. ...
... With others like TOBI Podhaler, it seems to be similar to what is produced with nebulizers, thanks to its formulation with PulmoSphere ® technology [31]. Moreover, microprocessor-controlled "smart" wet nebulizers, available for some antibiotics, use computer software that may be advantageous in some patients (i.e., for monitoring adherence to treatment) [32]. ...
The use of inhaled antibiotics was initially almost exclusively confined to patients with cystic fibrosis (CF). However, it has been extended in recent decades to patients with non-CF bronchiectasis or chronic obstructive pulmonary disease who present with chronic bronchial infection by potentially pathogenic microorganisms. Inhaled antibiotics reach high concentrations in the area of infection, which enhances their effect and enables their long-term administration to defeat the most resistant infections, while minimizing possible adverse effects. New formulations of inhaled dry powder antibiotics have been developed, providing, among other advantages, faster preparation and administration of the drug, as well as avoiding the requirement to clean nebulization equipment. In this review, we analyze the advantages and disadvantages of the different types of devices that allow the inhalation of antibiotics, especially dry powder inhalers. We describe their general characteristics, the different inhalers on the market and the proper way to use them. We analyze the factors that influence the way in which the dry powder drug reaches the lower airways, as well as aspects of microbiological effectiveness and risks of resistance development. We review the scientific evidence on the use of colistin and tobramycin with this type of device, both in patients with CF and with non-CF bronchiectasis. Finally, we discuss the literature on the development of new dry powder antibiotics.
... Less encouraging, only 50% reported using all their prescribed inhalations this frequently. This confirms trends described in earlier studies, 10,24 and may suggest that for a group of patients, inhaling twice daily is challenging to manage. Standardized use of dornase-alpha from early childhood may accustom all patients to once-daily inhalations, whereas more frequent inhalations require new habits. ...
Background:
Inhaled antibiotics are an important part of cystic fibrosis (CF) airway disease management and should be individualized to fit the microorganism and match patient needs. To investigate the implementation of personalised treatment, this study mapped the use of different types of inhaled antibiotics and adherence patterns.
Method:
We performed individual structured interviews in a cross-sectional study at the CF Centre in Copenhagen, Denmark. Patients with CF older than 15 years attending clinical consultations were included. Clinical data were obtained from centralized databases.
Results:
Among 149 participants, 107 (72%) had indication for treatment with inhaled antibiotics. In this group, 97 (91%) reported use of inhaled antibiotics within the last 12 months. Change from one inhaled antibiotic to another during that period was reported by 31 (29%), and 17 (25%) with Pseudomonas aeruginosa had used off-label antibiotics. Adherence to minimum one daily dose of antibiotic was reported by 78%, whilst adherence to all daily doses was 28 percentage-points lower. Skipping inhalations was due to side effects and doubt about the effect in less than 5% of cases.
Conclusion:
Change of inhaled antibiotics and use of off-label antibiotics for inhalation were common and side effects were a rare cause of non-adherence. This suggests satisfactory implementation of the principle of tailored antibiotic inhalation prescription in the Copenhagen CF-population. Adherence to at least one daily inhalation dose was markedly higher than adherence to multiple daily inhalations. This article is protected by copyright. All rights reserved.
... Nevertheless, the probably decreased adherence to therapy may be one of the reasons for the decrease in FEV 1 over time. This view is supported by the study results of McNamara et al., 27 which found that overall monthly adherence to nebulized therapy in children with CF was maintained between 60% and 70% over the year. The authors observed considerable variation in adherence, both between and within patients. ...
Background: Cystic fibrosis (CF) is a genetic disorder, in which defective clearance of airway secretions leads to progressive lung function loss. Inhaled mannitol is used to increase sputum and mucociliary clearance. There are little data from real-world studies on the effectiveness of mannitol in children. Our objective was to evaluate the spirometry and clinical results of mannitol in pediatric patients. Methods: We retrospectively reviewed the records of 30 children and adolescents with CF receiving inhaled mannitol who were already on recombinant human deoxyribonuclease (rhDNase) treatment. The change in forced expiratory volume in 1 second (FEV 1) from baseline at 2-4 months was the primary outcome. Secondary measures were other spirometry results, body mass index (BMI), hospital admissions, sputum characteristics, and positive bacterial colonization. Results: Compared to baseline, we found significant improvement in percent predicted FEV 1 at 2-4 months of treatment; 84.50 (58.00-99.00) vs. 96.00 (66.00-106.00) (P = 0.0007). The absolute change in FEV 1 was +11.5% at 2-4 months, +6.5% at 5-7 months, and +4% at 8-12 months. Also, significant improvements in other spirometry results were observed. Adolescents had significantly lower FEV 1 results, but the improvement in their lung function was sustained for a more extended period than children. Mannitol provided easier sputum removal, increased sputum volume, significant decline in hospitalizations, and significantly fewer patients with positive sputum cultures. A significant increase in BMI at 8-12 months was observed. Cough was the most frequent adverse effect. Conclusion: In a real-world setting, our results demonstrated that adding mannitol to rhDNase therapy is tolerable in pediatric patients with CF and may provide improved spirometry and clinical outcomes. In addition, our results showed that mannitol provided recovery in overall lung function at 2-4 months, which was sustained up to 12 months together with improved BMI, easier sputum removal, and a decline in bacterial colonization and hospital admissions. However, cough was the most frequent side effect.
... The device can also be used to monitor the frequency and length of treatments. Adherence to the treatment was maintained between 60% and 70% over 1 year [31]. Insight Online is a home monitoring telehealth interface, which includes data from the I-Neb. ...
The limited resources and the practice of social distancing during the COVID pandemic create a paradigm shift in the utilization of telemedicine in healthcare. However, the implementation of best practices is hampered in part by a lack of literature devoted to telehealth in bronchiectasis. In this commentary, we examine multiple approaches to structuring of telemedicine care for patients with bronchiectasis, highlight current evidence-based interventions that can be incorporated into the management of bronchiectasis, and describe our experience with telemedicine at the University of Connecticut Center for Bronchiectasis Care during the COVID-19 pandemic. The structural model must be adapted to different local dynamics and available technologies with careful attention to patient characteristics and access to technology to avoid the potential paradoxical effects of increasing patients’ burden and healthcare disparities in underserved populations.
... Additional features of the app such as schedules and patient reminders can help participants build good self-care habits. Providing adherence feedback might also improve the quality of clinical consultations by enabling an open and honest discussion about adherence issues (35). Data tracking nebulizers form the basis of further ongoing trials evaluating different telehealth interventions aiming to increase adherence to nebulizer therapy (Tele-Coaching Intervention to Improve Treatment Adherence in Cystic Fibrosis, ClinicalTrials.gov ...
Background
The extend of lung disease remains the most important prognostic factor for survival in patients with cystic fibrosis (CF), and lack of adherence is the main reason for treatment failure. Early detection of deterioration in lung function and optimising adherence are therefore crucial in CF care. We implement a randomized controlled trial to evaluate efficacy of telemonitoring of adherence, lung function, and health condition in combination with behavior change interventions using innovative digital technologies.
Methods
This is a multi-centre, randomized, controlled, non-blinded trial aiming to include 402 patients ≥ 12 years-of-age with CF. A standard-of-care arm is compared to an arm receiving objective, continuous monitoring of adherence to inhalation therapies, weekly home spirometry using electronic devices with data transmission to patients and caring physicians combined with video-conferencing, a self-management app and professional telephone coaching. The duration of the intervention phase is 18 months. The primary endpoint is time to the first protocol-defined pulmonary exacerbation. Secondary outcome measures include number of and time between pulmonary exacerbations, adherence to inhalation therapy, changes in forced expiratory volume in 1 s from baseline, number of hospital admissions, and changes in health-related quality of life. CF-associated medical treatment and care, and health care related costs will be assessed by explorative analysis in both arms.
Discussion
This study offers the opportunity to evaluate the effect of adherence interventions using telemedicine capable devices on adherence and lung health, possibly paving the way for implementation of telemedicine in routine care for patients with CF.
Trial registration : This study has been registered with the German Clinical Trials Register (Identifier: DRKS00024642, date of registration 01 Mar 2021, URL: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00024642 ).
... As new life-prolonging treatments are discovered, adherence becomes an important consideration as patients are faced with increasingly complex treatment regimens. Adherence to CF treatments including inhaled therapies [15][16][17][18][19] and physiotherapy 20 has been shown to be variable and often suboptimal. Higher adherence to CF therapies is associated with improved outcomes including reduced 19 admissions to hospital 17 and length of inpatient stay. ...
Introduction
Ivacaftor was the first therapy licensed to address the underlying defect in cystic fibrosis (CF). The improvements in lung function, nutritional status and pulmonary exacerbations in patients carrying a Gly551Asp mutation were greater than previously seen in clinical trials for other therapies. Limited data are available regarding long-term outcomes and adherence to ivacaftor outside clinical trials.
Methods
We conducted a 5-year single-centre retrospective study of people with CF carrying the Gly 551 Asp mutation who received ivacaftor. Clinical outcome data were extracted from medical notes and databases. Drug delivery data were used to assess medicine possession ratio (MPR).
Results
35 people were included. After commencing ivacaftor, FEV 1 improved by 9.6% (SE±1.59%) predicted by 6 months. Thereafter, FEV 1 declined, and at 5 years had returned to pre-ivacaftor baseline. Ivacaftor did not alter annual rate of FEV 1 decline (1.57% pre vs 1.82% post, p=0.74). Body mass index (BMI) increased for 4 years. There was a significant reduction in inpatient and total intravenous antibiotic days sustained over 5 years. MPR remained high but declined over time (−2.5±0.9% per year, p=0.007). FEV 1 was better maintained in patients with higher MPRs.
Conclusion
The addition of ivacaftor provides acute benefits for people with the Gly551Asp mutation and established lung disease. We report a sustained reduction in intravenous antibiotic use but following acute improvement in lung function, decline continues, and patients will continue to require medical observation and optimisation. Strategies to maintain high adherence should be a priority to prolong the benefits of ivacaftor.
... For example: although one study found adherence was maintained between 60% and 70% over 1 year, diurnal variation was also noted; evening 70% versus 58% morning (p=0.012). 36 This allows for more realistic joint goal setting and changes to treatments based on the results. 35 36 However, this device is currently only available to a subset of patients prescribed Promixin (colistimethate sodium, Profile Therapeutics plc, West Sussex, UK) and although data logging devices may provide useful information to the CF team regarding adherence, some patients may find this level of monitoring intrusive. ...
Digital healthcare is a rapidly growing healthcare sector. Its importance has been recognised at both national and international level, with the WHO recently publishing its first global strategy for digital health. The use of digital technology within cystic fibrosis (CF) has also increased. CF is a chronic, life-limiting condition, in which the treatment burden is high and treatment regimens are not static. Digital technologies present an opportunity to support the lives of people with CF. We included 59 articles and protocols in this state-of-the-art review, relating to 48 studies from 1999 until 2019. This provides a comprehensive overview of the expansion and evolution of the use of digital technology. Technology has been used with the aim of increasing accessibility to healthcare, earlier detection of pulmonary exacerbations and objective electronic adherence monitoring. It may also be used to promote adherence and self-management through education, treatment management Apps and social media.
... Les résultats ont montrés de grandes différences entre chaque patients, mais de façon générale, la séance du soir était mieux respectée (75% en moyenne) que celle du matin (58% en moyenne). Leur conclusion était qu'une telle surveillance automatisée permettait d'identifier quels aspects du traitement peuvent être améliorés et de travailler ensuite avec les familles pour individualiser le traitement [13]. Concernant l'exercice respiratoire en soit, d'autres voies plus ludiques ont été essayées comme la pratique du chant ou d'instrument à vent. ...
Ce document fut réalisé en tant que projet d’approfondissement compris dans la formation "Master of science in engineering" en technologie de l’information et de la communication, orientation ingénierie logicielle proposée par la HES-SO.
Le but du projet était la réalisation d'un Serious Game (SG) pour les enfants atteints de la mucoviscidose aussi appelée fibrose kystique (CF), une maladie génétique mortelle affectant entre autres les voies respiratoires. Un SG est un jeu avec une intention sérieuse. Pour ce projet, c'est aspect sérieux se concrétise dans la réalisation d'exercice de physiothérapie respiration ainsi que dans l'augmentation de l'adhérence à ces exercices. En effet, les personnes atteintes de CF doivent afin d'améliorer leur espérance et qualité de vie réaliser des exercices quotidiens peu intéressants et souvent peu respectés. Le but de notre SG est donc de rendre cette tâche la plus ludique possible afin d'augmenter la motivation des patients.
Ce projet intervient dans un plus grand projet "jeuxmucoviscidose.net" qui a pour but la réalisation de plusieurs SG de façon open source pour les patients atteint de CF. Le but de ce projet est notamment l'ouverture à divers pratique thérapeutique dans le monde ainsi qu'une collaboration active de divers contributeurs directement concernés par la problématique ou non. D'autres projet antérieures avaient permis de définir et réaliser certains points notamment une première idée du jeu ou encore l'API permettant de récupérer les informations du périphérique respiratoire devant être utilisé : Le Flutter.
Ce document décrit les trois principales phases de ce projet étant l'analyse, la conception et l'implémentation. Comparés à d'autres projets, la phase d'analyse se devait d'être très importante et une grande proportion des heures y était consacrée. Ceci afin, de faire la synthèse de nombreux documents scientifiques, un entretien avec un physiothérapeute respiratoire ainsi qu'un état de l'art des projets existant.
... [8][9][10][11] Usage of the I-neb can reduce treatment burden and this nebulizer is already widely used in adults and increasingly in children. [12][13][14][15] However, the I-neb has not been tested in children and little is known about pharmacokinetics (PK) and safety of tobramycin delivered with this nebulizer. This lack of knowledge is especially a risk with drugs such as tobramycin, where high trough concentrations and cumulative exposure can lead to nephro-and ototoxicity. ...
Aims
We aimed to compare the pharmacokinetics (PK) and safety profile of tobramycin inhalation solution (TIS) using the I‐neb device to the standard PARI‐LC Plus nebulizer in children with cystic fibrosis.
Methods
A randomized, open‐label, crossover study was performed. In 2 separate study visits, blood samples from 22 children were collected following TIS nebulization with I‐neb (75 mg) and PARI‐LC Plus (300 mg). Study visits were separated by 1 month, in which 1 of the study nebulizers was used twice daily. Tobramycin PK for both nebulizers was established using measured tobramycin concentrations and Bayesian PK modelling software. Hearing and renal function tests were performed to test for aminoglycoside associated toxicity. In addition to standard estimated glomerular filtration rate values, biomarkers for tubular injury (KIM‐1 and NAG) were measured. Patient and nebulizer satisfaction were assessed.
Results
Inhalations were well tolerated and serum trough concentrations below the predefined toxic limit were reached with no significant differences in PK parameters between nebulizers. Results of audiometry and estimated glomerular filtration rate revealed no abnormalities. However, increased urinary NAG/creatinine ratios at visit 2 for both nebulizers suggest TIS‐induced subclinical tubular kidney injury. Nebulization time was 50% shorter and patient satisfaction was significantly higher with the I‐neb.
Conclusions
Nebulization of 75 mg TIS with the I‐neb in children with cystic fibrosis resulted in comparable systemic exposure to 300 mg TIS with the PARI‐LC Plus and was well tolerated and preferred over the PARI‐LC Plus. Long‐term safety of TIS nebulization should be monitored clinically, especially regarding the effects on tubular kidney injury.
... In calculating the variability for time of use, it is impor- tant to consider that adults with CF may use their inhaled preventative therapies in two separate sessions because inhaled antibiotics, eg, colistin and tobramycin, are meant for twice daily use, with the UK CF Trust recommending a minimum interval of 6 hours between doses. 40 Both treatment sessions should be considered separately because behavior for one session may be discordant to the behavior in the other session (eg, adherence during "evening" sessions may be better compared to adherence during "morning" sessions 41 or vice versa). In considering the "morning" and "evening" sessions, using midnight-mid-day and mid-day-midnight scales is likely to be problematic. ...
Background
Habit, a psychological process that automatically generates urges to perform a behavior in associated settings, is potentially an important determinant of medication adherence. Habit is challenging to measure because, as a psychological construct, it cannot be directly observed. We describe a method of using routinely available objective adherence data from electronic data capture (EDC) to generate a behavior-based index of adherence habit and demonstrate how this index can be applied.
Methods to generate the habit index
Our proposed habit index is a “frequency in context” measure. It estimates habit as a multiplicative product of behavior frequency (generated from weekly percentage adherence) and context stability (inferred from time of nebulizer use). Although different timescales can be used, we chose to generate weekly habit scores since we believe that this is the most granular level at which context stability can be reasonably calculated.
An application of the habit index
A hallmark of habit is to predict future behavior, hence we used time series method to cross-correlate the habit index with nebulizer adherence in the subsequent week among 123 adults with cystic fibrosis (52, 42.3% female; median age 25 years) over a median duration of 153 weeks (IQR 74–198 weeks). The mean cross-correlation coefficient (R) between the habit index and subsequent adherence was 0.40 (95% CI 0.36–0.44). Adjusting for current adherence, the unstandardized regression coefficient (B) for the habit index was 0.30 (95% CI −1.04 to 1.65).
Conclusion
We have described a pragmatic method to infer “habit” from adherence data routinely captured with EDC and provided proof-of-principle evidence regarding the feasibility of this concept. The continuous stream of data from EDC allows the habit index to unobtrusively assess “habit” at various time points over prolonged periods, and hence the habit index may be applicable in habit formation studies.
... Over the last decade, investigations of treatment-specific adherence in CF care have shown different rates to different therapies (Quittner, Zhang, et al., 2014), with inhalation therapy being of particular interest due to its important role in preventing, eradicating, and treating lung infection (Bodnár, Mészáros, Oláh, & Ágh, 2016). Although measuring adherence to inhalation therapy has benefited significantly from Adaptive Aerosol Delivery™ (AAD) technology-which electronically records nebulizer use-the complex factors which influence the process of actually adhering remain largely elusive (McNamara, McCormack, McDonald, Heaf, & Southern, 2009). Variables known to be important in CF treatment adherence include age, beliefs about medication, and characteristics of the treatment (Duff & Latchford, 2010). ...
The benefits of improved treatments for cystic fibrosis (CF) depend on optimal adherence, which remains problematic, particularly to aerosol therapy. In this study, we explored the process of adhering to aerosol therapy from the perspective of both adolescents with CF and their parents. Interviews were conducted individually with six adolescents and six parents, informed by accurate adherence data from an electronically chipped, aerosol device. Interview transcripts from audio-recordings were analyzed using grounded theory method (GTM). Major themes revealed differences in perspective between parent and adolescent, with this relationship mediating the cognitive and emotional processes that play a significant role in adherence behavior. These processes are further influenced by interactions with the aerosol therapy treatment regimen, device characteristics, and the context in which adherence is taking place. Parents and adolescents have different views of treatment and how to manage it. Both need to be addressed if optimal adherence is to be achieved.
... In addition, understanding nebuliser adherence requires focusing not only on those with low adherence, but those who consistently adhere. Some people can maintain consistently high adherence for many years (McNamara, McCormack, McDonald, Heaf, & Southern, 2009). 'High adherers' may have better self-regulatory skills or resources (i.e. ...
Objectives: Adherence to nebulised treatment is typically low among people with cystic fibrosis (CF). This study sought to identify factors differentiating high or low nebuliser adherence patterns (i.e. ≥80% or <50% of all nebulised treatments over one year) among adults with CF.
Design: A mixed methods cross-sectional exploratory comparison of low and high adherers to nebulised medications.
Methods: Of 36 eligible adults invited from a UK CF centre, 20 were recruited (10 high, 10 low adherers). Adherence was objectively measured using electronic data capture. Participants completed a self-report questionnaire comprising measures of hypothesised predictors (habit, self-control, life chaos, perceived treatment burden, capability, motivation and opportunity), then took part in a semi-structured interview. Quantitative data were compared between groups, and interview data were thematically analysed.
Results: High adherers reported stronger habit and greater opportunities, though habit and perceived opportunity scores were highly positively correlated. No other quantitative measure distinguished between groups. Habitual instigation tendency attenuated the relationship between treatment complexity and perceived treatment burden. Indeed, in interviews, high adherers reported that routinisation and greater automaticity made treatment burden more manageable.
Conclusions: High adherers seized more opportunities for nebuliser use, adapted their lives more effectively to using nebulisers and were more likely to make nebuliser use habitual. Nebuliser adherence interventions among adults with CF might usefully target development of routines for instigating nebuliser use, and identification of opportune moments for nebuliser use.
... The development of Adaptive Aerosol Delivery (AAD) devices has enabled adherence rates to be electronically monitored, with the exact date and time of all doses logged. The I-neb (Philips Respironics, Guildford, UK) uses this technology to enable electronic adherence data to be downloaded and reviewed with patients in clinic, which is now becoming standard practice in the UK. 4 Using this method, rates of adherence to nebulized therapy in children with CF have been recorded at around 65%. 5,6 Doubts about the need or effect of regular medication, concerns about the burden of medication for children with CF, and oppositional behavior (defiant and disruptive behavior toward parents/carers) are classified as intentional adherence barriers. 7 These barriers may be identified and addressed by having open discussions about electronically monitored adherence rates. ...
Background
Children with cystic fibrosis (CF) often have suboptimal adherence rates to nebulized medication. Adherence barriers cited include forgetting to take the nebulizers, due to busy home and social lives. Text message reminders have been shown to be effective at improving adherence rates in other chronic diseases such as asthma and diabetes.
Objective
The objective of this study was to assess the feasibility and efficacy of sending text reminders for a prolonged period of time to children with CF.
Materials and methods
Children with CF aged 5–16 years taking at least one medication via a nebulizer with an electronic adherence monitor were consented for the study. Text message reminders were sent to participants and/or parents via the hospital’s automated text service, up to twice a day, for 6 months. The adherence rates for the 6-month text period were compared to the previous 6 months before the study. Rates were calculated for weekdays, weekends, and school holidays.
Results
Seventeen participants were recruited to the study, with a mean age of 12 years and a mean forced expiratory volume in 1 second (FEV1) of 81% predicted. Fifteen children completed the 6-month text period, and I-neb data were accurately analyzed for 13 participants. The mean adherence rate in the 6 months receiving texts was 80%, compared to 81% in the prior 6 months. Overall adherence rates on weekdays, weekends, and school holidays were equivalent during the 2 time periods. A subgroup of patients with moderate baseline adherence showed increased adherence during the text period, particularly at weekends.
Conclusion
It is feasible to send text message reminders to children with CF, and they are amenable to this approach. Although text reminders do not increase rates in patients with existing optimal adherence, they may be of value in patients with more moderate baseline rates.
... Patient knowledge and medication adherence in cF of your medication did you take?" 16 They were considered adherent if they self-reported taking their medications more than 80% in the past three months and missing less than 20% in an average week, as commonly classified in adherence research. 17 Responses that showed discrepancies between the self-reported doses missed and percentage of doses taken were considered discordant responses for that particular individual medication and excluded from the primary analysis. ...
Background and objectives
Patient knowledge of lung function (ie, forced expiratory volume in 1 s [FEV1]% predicted) and the intended benefits of their prescribed pulmonary medications might play an important role in medication adherence, but this relationship has not been examined previously in patients with cystic fibrosis (CF).
Methods
All patients diagnosed with CF and without prior lung transplantation were invited to complete knowledge and self-reported medication adherence questionnaires during routine outpatient visits to the Adult CF Clinic, St Paul’s Hospital, Vancouver, Canada from June 2013 to August 2014.
Results
A total of 142 out of 167 (85%) consecutive adults attending CF clinic completed patient knowledge and medication adherence survey questionnaires. Sixty-four percent of the patients recalled their last FEV1% predicted value within 5%, and 70% knew the intended benefits of all their prescribed medications. Self-reported adherence rates were highest for inhaled antibiotics (81%), azithromycin (87%), and dornase alpha (76%) and lowest for hypertonic saline (47%). Individuals who knew their FEV1% predicted value within 5% were more likely to self-report adherence to dornase alpha (84% vs 62%, P=0.06) and inhaled antibiotics (88% vs 64%, P=0.06) compared to those who did not, but these associations were not statistically significant. There were no significant associations observed between patient knowledge of intended medication benefits and self-reported medication adherence.
Conclusion
Contrary to our hypothesis, disease- and treatment-related knowledge was not associated with self-reported medication adherence. This suggests other barriers to medication adherence should be targeted in future studies aiming to improve medication adherence in adults with CF.
... 88 In addition, EMDs provide opportunity for face-to-face discussion of adherence data, to facilitate shared decision-making (SDM) and improve treatment outcomes. 89 Unfortunately, while EMDs have demonstrated significantly improved adherence to inhalers in clinical trials, this has not translated into improved clinical outcomes or reduced health care costs. 88,90 This may be a result of highly motivated volunteers in the control groups, leading to increased awareness and heightened medication adherence. ...
Robert Barrons,1 James Wheeler,2 J Andrew Woods1 1Wingate University School of Pharmacy, Wingate, NC, USA; 2University of Tennessee Health Science Center, Nashville, TN, USA Abstract: An anticipated surge in the elderly population will be accompanied by a rise in aging patients with asthma or COPD. Clinician selection of inhalers needs to address the unique challenges to elderly patients. These challenges to the use of inhalers include diminished physical and cognitive abilities, as well as cost reimbursement issues associated with polypharmacy and the Medicare gap. Clinicians should consider patient preferences for an inhaler device that provides ease of administration, and addresses conveniences such as portability, visual, and auditory indicators of dosing completion. The addition of spacer devices resolves hand-breath coordination difficulty with pressurized metered dose inhalers, but reduces overall inhaler convenience. Soft mist inhalers (Respimat®) improve ease of administration, but use may be limited by cost and formulary availability. Multiple dose dry powder inhalers provide convenience and simplified use by requiring only one to two steps prior to administration, but concerns of peak inspiratory flow requirements remain among patients with advanced age and severity of COPD. If unaddressed, these challenges to inhaler selection contribute to inappropriate use of inhalers in 41% to 69% of patients, accompanied by at least 51% non-adherence to treatment. Clinicians must first avail themselves of reputable educational resources regarding new inhaler developments and administration, for competent patient instruction. Patient education should include a checklist of inhaler technique, with physical demonstration of each device by the patient and provider. Device demonstration significantly improves inhaler technique and identifies the need for nebulization therapy. Clinician and patient knowledge of available inhalers and their administration should initiate shared decision-making involving patient and provider medication preferences and choices. Patient education and shared decision-making should be longstanding and opportunistic, addressing failed inhaler adherence in the outpatient setting, and the contribution of inhaler non-adherence to hospital admissions and emergency department visits. Keywords: elderly patients, asthma, COPD, non-adherence, patient education, inhaler
... Several studies have evaluated self-or clinician-reported adherence compared with objective electronic monitoring [45,46]. Objective recording is only possible through specific nebuliser devices (Ineb) and it has already been discussed that these do not permit use of all nebulised medications. ...
There have been significant advances in both inhalation medicines and delivery devices with "intelligent nebulisers" and "dry-powder inhalers" becoming commonplace in CF care.Inhaled medicines generate high levels of a drug within the airways with limited systemic effects, offering safe and convenient antibiotic and mucolytic therapy for individuals with CF.Variations in adherence are not unique to CF; however, treatment burden is high and therefore fast inhaled drug delivery devices may assist individuals in completing the prescribed treatment regimes.Prescribers of inhaled medicines have a responsibility to consider, in addition to efficacy, the appropriated drug/device combination for each individual in order to promote adherence and achieve the desired clinical benefit.
The recognised mainstay daily treatments for cystic fibrosis (CF) focus on inhaled and oral medications, airway clearance and optimised nutrition. This review discusses recent advances in inhaled therapies for the management of CF, including devices such as intelligent nebulisers, drug formulations and supporting evidence for inhaled antibiotics (for the management of chronic Pseudomonas aeruginosa) and muco-active drugs. We include practical advice for clinicians regarding the optimisation of inhalation technique and education. The influence of adherence on the use of inhaled therapies in CF is also reviewed.
To inform readers about the history and progression of inhaled therapies for people with CF with reference to the literature supporting current practice.To highlight the factors that may impact the success of inhaled therapies, including those which are device specific such as drug deposition and those which influence adherence.
... Electronic monitoring has been used in clinical settings as part of adherence-promoting interventions 54,55 to provide accurate, objective, and detailed information on adherence patterns, without significant disruption to patients' natural medicationtaking behavior. 56,57 When used appropriately, EMD data can be a powerful tool to engage patients in active discussions about their unique medication-taking behaviors, beliefs about their disease, and attitudes to their prescribed treatment. ...
Use of electronic monitoring devices (EMDs) for inhalers is growing rapidly because of their ability to provide objective and detailed adherence data to support clinical decision making. There is increasing potential for the use of EMDs in clinical settings, especially as cost-effectiveness is realized and device costs reduce. However, it is important for clinicians to know about the attributes of different EMDs so that they can select the right device for their patients and understand the factors that affect the reliability and accuracy of the data EMDs record. This article gives information on where to obtain EMDs, describes device specifications, and highlights useful features for the clinician and the patient, including user feedback data. We discuss the benefits and potential drawbacks of data collected by EMDs and provide device users with a set of tools to optimize the use of EMDs in clinical settings, such as advice on how to carry out brief EMD checks to ensure data quality and device reliability. New EMDs on the market require pretesting before use by patients. We provide information on how to carry out EMD pretesting in the clinic and patients' homes, which can be carried out by health professionals or in collaboration with researchers or manufacturers. Strategies for interpreting and managing common device malfunctions are also discussed.
Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
... Chip-based recording nebulizers can store data such as treatment date, time, duration and completeness of dose, that can then be downloaded to generate an accurate report of adherence [88]. Using this type of information, it is possible to provide patients with feedback and adjust treatment schedules to hopefully improve compliance [89]. ...
Much of the improvement in the survival of individuals with cystic fibrosis (CF) is due to advancements in antimicrobial treatments. New aerosolized antibiotic formulations have recently been introduced (such as inhaled aztreonam), and others are in development (inhaled levofloxacin and liposomal amikacin). Licensed dry powder formulations include tobramycin inhalation powder and dry powder colistimethate (available in Europe). Although inhaled antibiotics have the advantage of being able to deliver high intrapulmonary concentrations of drug, antimicrobial resistance can still develop and is a concern in CF. Antimicrobial resistance might be mitigated by using non-antibiotic treatments, antibiotic adjuvants, which have activity against bacteria. Examples include agents such as gallium, antimicrobial peptides and anti-biofilm compounds such as alginate oligosaccharides (OligoG) and garlic. Vaccination strategies and antibody therapy (IgY) against Pseudomonas aeruginosa have also been attempted to prevent initial infection with this organism in CF. Although aggressive and long-term use of antibiotics has been crucial in slowing lung function decline and improving survival in people with CF, it has added a significant burden of care and associated toxicities in these individuals. Careful surveillance and the use of preventative strategies for antibiotic related toxicity (such as nephrotoxicity and ototoxicity) are essential. Continued development of effective antimicrobial agents that can function in the conditions encountered in the CF lung, such as against bacterial biofilm growth and under anaerobic conditions, is needed.
Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
... For instance, studies have demonstrated that children with CF adhere more to their nebulized medications on evenings versus mornings, weekdays versus weekends, and during the school year versus while on vacation. 14,15 The level of adherence does affect pulmonary health outcomes and frequency of hospitalizations due to more frequent pulmonary exacerbations requiring intravenous antibiotics and lower baseline lung function. 16 The commonly identified barriers are the complexity of the treatment regimen, poor health/fatigue, lack of perceived benefit, competing social and work demands, stigma/embarrassment, frequency of interaction with the healthcare team, financial barriers, amount of family/ significant other support, and depression/anxiety. 1 It is clear that the people with CF face a wide variety of challenges and potentially several barriers concurrently, therefore, an individualized approach should be utilized to reduce these barriers. ...
... 4) Over the last few decades, smart nebulisers such as the I-neb and Akita have been developed that allow electronic data logging. This supplies objective information for patient and CF team on treatment adherence [44,45]. 5) Smart nebulisers such as the Akita allow the control of inhalation competence. ...
Dry powder inhalers (DPIs) delivering antibiotics for the suppressive treatment of Pseudomonas aeruginosa in cystic fibrosis patients were developed recently and are now increasingly replacing time-consuming nebuliser therapy. Noninferiority studies have shown that the efficacy of inhaled tobramycin delivered by DPI was similar to that of wet nebulisation. However, there are many differences between inhaled antibiotic therapy delivered by DPI and by nebuliser. The question is whether and to what extent inhalation technique and other patient-related factors affect the efficacy of antibiotics delivered by DPI compared with nebulisers. Health professionals should be aware of the differences between dry and wet aerosols, and of patient-related factors that can influence efficacy, in order to personalise treatment, to give appropriate instructions to patients and to better understand the response to the treatment after switching.
In this review, key issues of aerosol therapy are discussed in relation to inhaled antibiotic therapy with the aim of optimising the use of both nebulised and DPI antibiotics by patients. An example of these issues is the relationship between airway generation, structural lung changes and local concentrations of the inhaled antibiotics. The pros and cons of dry and wet modes of delivery for inhaled antibiotics are discussed.
... Twenty papers assessed participants' adherence to medication (male, n ϭ 916; female, n ϭ 855; unspecified, n ϭ 69). 3,10,11,20,[22][23][24][25][27][28][29][31][32][33][34][35][36][37][38][39] Eighteen papers were of low quality, and 2 were of moderate quality. The categories of medications are summarized below (Table 3). ...
Background:
The management of cystic fibrosis (CF) includes adherence to a home management program (airway clearance, medication, nutritional advice, and exercise). This has led to an increase in life expectancy, although the benefits depend greatly on a patient's level of adherence to daily treatments at home. To date, no systematic review has established adherence rates to all World Health Organization guidelines in the home setting; hence, this review was undertaken.
Methods:
The review comprised 3 phases. A methodological assessment of databases (Embase, CINAHL, PsychINFO, PEDro, PubMed, Cochrane Central Register of Controlled Trials) identified potentially relevant papers. These papers were screened for inclusion criteria by 2 independent reviewers, data were extracted, and the internal validity was rated using a valid and reliable scale. Results were categorized into 4 themes: medication, nutrition, airway clearance techniques, and exercise.
Results:
The search generated a total of 26 papers, 24 of which were rated as being poor quality. Adherence to a treatment program for CF patients is generally low (from 22% for nutritional guidelines to 130% for oral antibiotics), and it varies greatly depending on the type of treatment and the method of assessment employed (objective tool vs self-reported questionnaires).
Conclusions:
Consensus on how to measure adherence is lacking, and the quality of studies addressing adherence in this population is generally poor. Overall, studies using self-reported measures yielded higher adherence scores than those that used objective measures, suggesting that current efforts to improve methods of adherence are appropriate. The prevalence of non-adherence remains unclear due to these limitations.
... It remains to be seen whether telehealth will improve adherence in the real-world setting. In one study, adherence for CF patients with the I-neb device was found to be 60-70% [105]. Patients were more compliant on weekdays than on weekends, and less compliant over holidays when their routine was broken. ...
Inhaled antibiotics dramatically improve targeting of drug to the site of respiratory infections, while simultaneously minimizing systemic exposure and associated toxicity. The high local concentrations of antibiotic may enable more effective treatment of multi-drug resistant pathogens. This review explores barriers to effective treatment with inhaled antibiotics. In addition, potential opportunities for improvements in treatment are reviewed.
... For instance, studies have demonstrated that children with CF adhere more to their nebulized medications on evenings versus mornings, weekdays versus weekends, and during the school year versus while on vacation. 14,15 The level of adherence does affect pulmonary health outcomes and frequency of hospitalizations due to more frequent pulmonary exacerbations requiring intravenous antibiotics and lower baseline lung function. 16 The commonly identified barriers are the complexity of the treatment regimen, poor health/fatigue, lack of perceived benefit, competing social and work demands, stigma/embarrassment, frequency of interaction with the healthcare team, financial barriers, amount of family/ significant other support, and depression/anxiety. 1 It is clear that the people with CF face a wide variety of challenges and potentially several barriers concurrently, therefore, an individualized approach should be utilized to reduce these barriers. ...
Primary ciliary dyskinesia (PCD) is a genetic condition affecting approximately 1 in 15,000-20,000 individuals, and the majority of cases exhibit an autosomal recessive inheritance pattern. However, genetic heterogenicity is seen in PCD and reflects the complexity of ciliary structure and biogenesis. There have been many recent advances in the diagnosis and management of PCD in the last few years, including advanced genetic sequencing, nasal nitric oxide assay, and ciliary motility tests. This article focuses on the ultrastructure and pathophysiology of ciliary dyskinesias, along with a review of clinical features, screening, and diagnostic tests. It also reflects upon the diagnostic challenge caused by the diverse clinical presentation, which will be of great value to pediatricians for considering PCD in their differential list, henceforth leading to early recognition and management, along with awareness of the recent advances in the field of genetics and other techniques for diagnosis of this condition.
... Using objective data such as pharmacy refill history and electronic medication monitors, it is now possible to more accurately record adherence discretely and without further inconvenience to the individual. Analysis has shown that factors such as age, time of day, weekdays versus weekends, school routine versus holidays, can cause substantial variation even within individuals in terms of daily adherence, (49,50) with an average of 50% adherence reported. (51) This can have a significant impact on clinical outcome, increased risk of hospitalisation and increased health care costs. ...
The pharmacological treatment of cystic fibrosis, together with implications for health economics, therapeutic monitoring and adherence, are discussed.
Key points:
Airways disease in CF is progressive and requires intensive management to reduce frequency of exacerbation and risk of hospitalisation with care focused on keeping the lungs healthy to maintain good lung function for as long as possible.
Episodes of acute pulmonary exacerbation in particular, contribute to long-term deterioration in lung function as many individuals will fail to recover to baseline even months after IV antibiotic treatment.
Medical advances have improved survival with medications now accounting for 65% of costs. Hospitalisation is the second highest expenditure and can range from £8000-20,000 per stay depending on the level of care required.
The development of inhaled antibiotics has undoubtedly contributed to improved life expectancy. The approval of dry powder inhalers for tobramycin and several other drugs may now improve adherence.
Novel therapies such as CFTR potentiators and correctors signal an important advance in the treatment of CF lung disease as early treatment may stall the progression of the disease, improving patient outcome and overall health costs.
... Establish a supportive, collaborative relationship with patients and families Maintain an open and honest dialog to identify opportunities for improvement Consider the use of motivational interviewing, various teaching modalities, and the teach-back method Establish effective communication between patients, families, and healthcare professionals Review pharmacy refill information to assess adherence Consider use of a novel delivery device for inhaled therapy monitor treatment adherence through electronic data capture in nebulizers [McNamara et al. 2009;Daniels et al. 2011;McCormack et al. 2012]. Nurses and allied health professionals can be instrumental in making patients aware of the technologies that are available and should encourage patients and parents to utilize appropriate tools. ...
Nonadherence to inhaled therapies is a major problem in the treatment of cystic fibrosis that can influence lung function and health outcomes. Potential contributors to nonadherence have been identified, including demographic and psychosocial factors, time and convenience of inhaled therapy, and treatment beliefs. Additional research is clearly needed to clarify the contributors and to determine which interventions and technological advances will enhance adherence to inhaled therapies in patients with cystic fibrosis. Nurses and allied health professionals are ideally positioned to assist patients and families with adherence to inhaled therapies through monitoring, communication, and education about the available therapies and their proper use. This review briefly summarizes the available evidence about contributors to nonadherence, potential interventions, novel delivery devices for inhaled therapies, and opportunities for additional research.
... Objective, personalized, feedback data on patterns of medication use provided by EMDs can open discussions between the health professional and the patient, 24 and when feedback is given sensitively and with respect for the patient's autonomy, 15,29 it can facilitate shared decision making and optimize treatment routines. 30 A number of trials, from 2 to 18 months' duration, have examined the use of adherence feedback as a strategy to improve adherence of patients with asthma, either alone or in conjunction with a behavioral intervention. 2,10,23,[31][32][33][34] Feedback generally took the form of reviewing printouts of inhaler use, with constructive and positive discussion and suggestions, and with problem-solving or goalsetting sessions. ...
In the past decade, rapid technological developments have advanced electronic monitoring devices (EMD) for asthma inhalers beyond simple recording of actuations to providing adherence promotion features and detailed information about patterns of medication use. This article describes currently available EMDs, discusses their utility and limitations in assessing adherence, and describes the potential for EMD-based adherence promotion interventions in clinical settings. To date, the main use of EMDs has been in clinical research. In selected populations, simple EMD-based adherence interventions, delivered either through clinician-to-patient feedback about medication use or by direct-to-patient reminders for missed doses, can significantly improve adherence. Further work is now needed to determine the impact of EMDs on clinical outcomes and their cost-effectiveness and feasibility for different clinical settings, including in disadvantaged populations. If this evidence can be provided, then the use of EMDs could expand into the management of asthma in populations with high health care costs, eg, severe asthma. In the future, medication monitoring could help distinguish poor treatment response from poor adherence, guide prescribing decisions, and prompt providers to discuss barriers to adherence; electronic health records may provide the gateway for integrating medication-use monitoring into digital chronic care management.
Background:
Adherence to treatment, including inhaled therapies, is low in people with cystic fibrosis (CF). Although psychological interventions for improving adherence to inhaled therapies in people with CF have been developed, no previous published systematic review has evaluated the evidence for efficacy of these interventions.
Objectives:
The primary objective of the review was to assess the efficacy of psychological interventions for improving adherence to inhaled therapies in people with cystic fibrosis (CF). The secondary objective was to establish the most effective components, or behaviour change techniques (BCTs), used in these interventions.
Search methods:
We searched the Cochrane Cystic Fibrosis Trials Register, which is compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched databases (PubMed; PsycINFO; EBSCO; Scopus; OpenGrey), trials registries (World Health Organization International Clinical Trials Registry Platform; US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov), and the reference lists of relevant articles and reviews, with no restrictions on language, year or publication status. Date of search: 7 August 2022.
Selection criteria:
We included randomised controlled trials (RCTs) comparing different types of psychological interventions for improving adherence to inhaled therapies in people with CF of any age, or comparing psychological interventions with usual care. We included quasi-RCTs if we could reasonably assume that the baseline characteristics were similar in both groups.
Data collection and analysis:
Two review authors independently assessed trial eligibility and completed data extraction, risk of bias assessments, and BCT coding (using the BCT Taxonomy v1) for all included trials. We resolved any discrepancies by discussion, or by consultation with a third review author as necessary. We assessed the certainty of the evidence using GRADE.
Main results:
We included 10 trials (1642 participants) in the review (children and adolescents in four trials; adults in five trials; and children and adults in one trial). Nine trials compared a psychological intervention with usual care; we could combine data from some of these in a number of quantitative analyses. One trial compared a psychological intervention with an active comparator (education plus problem-solving (EPS)). We identified five ongoing trials. Psychological interventions were generally multi-component and complex, containing an average of 9.6 BCTs (range 1 to 28). The two most commonly used BCTs included 'problem-solving' and 'instruction on how to perform the behaviour'. Interventions varied in their type, content and mode of delivery. They included a problem-solving intervention; a paper-based self-management workbook; a telehealth intervention; a group training programme; a digital intervention comprising medication reminders and lung function self-monitoring; a life-coaching intervention; a motivational interviewing (MI) intervention; a brief MI intervention (behaviour change counselling); and a digital intervention combined with behaviour change sessions. Intervention duration ranged from 10 weeks to 12 months. Assessment time points ranged from six to eight weeks up to 23 months. Psychological interventions compared with usual care We report data here for the 'over six months and up to 12 months' time point. We found that psychological interventions probably improve adherence to inhaled therapies (primary outcome) in people with CF compared with usual care (mean difference (MD) 9.5, 95% confidence interval (CI) 8.60 to 10.40; 1 study, 588 participants; moderate-certainty evidence). There was no evidence of a difference between groups in our second primary outcome, treatment-related adverse events: anxiety (MD 0.30, 95% CI -0.40 to 1.00; 1 study, 535 participants), or depression (MD -0.10, 95% CI -0.80 to 0.60; 1 study, 534 participants), although this was low-certainty evidence. For our secondary outcomes, there was no evidence of a difference between groups in terms of lung function (forced expiratory volume in one second (FEV1) % predicted MD 1.40, 95% CI -0.20 to 3.00; 1 study, 556 participants; moderate-certainty evidence); number of pulmonary exacerbations (adjusted rate ratio 0.96, 95% CI 0.83 to 1.11; 1 study, 607 participants; moderate-certainty evidence); or respiratory symptoms (MD 0.70, 95% CI -2.40 to 3.80; 1 study, 534 participants; low-certainty evidence). However, psychological interventions may improve treatment burden (MD 3.90, 95% CI 1.20 to 6.60; 1 study, 539 participants; low-certainty evidence). The overall certainty of the evidence ranged from low to moderate across these outcomes. Reasons for downgrading included indirectness (current evidence included adults only whereas our review question was broader and focused on people of any age) and lack of blinding of outcome assessors. Psychological interventions compared with an active comparator For this comparison the overall certainty of evidence was very low, based on one trial (n = 128) comparing an MI intervention to EPS for 12 months. We are uncertain whether an MI intervention, compared with EPS, improves adherence to inhaled therapies, lung function, or quality of life in people with CF, or whether there is an effect on pulmonary exacerbations. The included trial for this comparison did not report on treatment-related adverse events (anxiety and depression). We downgraded all reported outcomes due to small participant numbers, indirectness (trials included only adults), and unclear risk of bias (e.g. selection and attrition bias).
Authors' conclusions:
Due to the limited quantity of trials included in this review, as well as the clinical and methodological heterogeneity, it was not possible to identify an overall intervention effect using meta-analysis. Some moderate-certainty evidence suggests that psychological interventions (compared with usual care) probably improve adherence to inhaled therapies in people with CF, without increasing treatment-related adverse events, anxiety and depression (low-certainty evidence). In future review updates (with ongoing trial results included), we hope to be able to establish the most effective BCTs (or 'active ingredients') of interventions for improving adherence to inhaled therapies in people with CF. Wherever possible, investigators should make use of the most objective measures of adherence available (e.g. data-logging nebulisers) to accurately determine intervention effects. Outcome reporting needs to be improved to enable combining or separation of measures as appropriate. Likewise, trial reporting needs to include details of intervention content (e.g. BCTs used); duration; intensity; and fidelity. Large trials with a longer follow-up period (e.g. 12 months) are needed in children with CF. Additionally, more research is needed to determine how to support adherence in 'under-served' CF populations.
Background:
Improved understanding and treatment of cystic fibrosis (CF) has led to longer life expectancy, which is accompanied by an increasingly complex regimen of treatments. Suboptimal adherence to the treatment plan, in the context of respiratory disease, has been found to be associated with poorer health outcomes. With digital technology being more accessible, it can be used to monitor adherence to inhaled therapies via chipped nebulisers, mobile phone apps and web-based platforms. This technology can allow monitoring of adherence as well as clinical outcomes, and allow feedback to both the person with CF and their healthcare team.
Objectives:
To assess the effects of using digital technology to monitor adherence to inhaled therapies and health status in adults and children with CF.
Search methods:
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 28 October 2021. We also searched Embase and three clinical trial registries and checked references of included studies. Date of last search: 9 November 2021.
Selection criteria:
We searched for randomised controlled trials (RCTs) looking at the effects of a digital technology for monitoring adherence of children and adults with CF to inhaled therapies.
Data collection and analysis:
Two review authors screened the search results for studies eligible for inclusion in the review and extracted their data. We used Risk of Bias 2 for assessing study quality. We assessed the overall certainty of the evidence using GRADE.
Main results:
We included two studies in our review, with 628 participants aged five to 41 years. There was one study each for two different comparisons. Nebuliser target inhalation mode versus standard inhalation mode The included parallel study was carried out over 10 weeks after a run-in period of four to six weeks. The study compared the effects of a digitally enhanced inhalation mode (target inhalation mode) for nebulised antibiotics compared to standard mode in children attending a regional CF clinic in the United Kingdom. The study's primary outcome was the time taken to complete the inhaled treatment, but investigators also reported on adherence to therapy. The results showed that there may be an improvement in adherence with the target inhalation mode when this intervention is used (mean difference (MD) 24.0%, 95% confidence interval (CI) 2.95 to 45.05; low-certainty evidence). The target inhalation mode may make little or no difference to forced expiratory volume in one second (FEV1) % predicted (MD 1.00 % predicted, 95% CI -9.37 to 11.37; low-certainty evidence). The study did not report on treatment burden, quality of life (QoL) or pulmonary exacerbations. eNebuliser with digital support versus eNebuliser without support One large multicentre RCT monitored adherence via data-tracking nebulisers. The intervention group also receiving access to an online web-based platform, CFHealthHub, which offered tailored, flexible support from the study interventionist as well as access to their adherence data, educational and problem-solving information throughout the 12-month trial period. We graded all evidence as moderate certainty. Compared to usual care, the digital intervention probably improves adherence to inhaled therapy (MD 18%, 95% CI 12.90 to 23.10); probably leads to slightly reduced treatment burden (MD 5.1, 95% CI 1.79 to 8.41); and may lead to slightly improved FEV1 % predicted (MD 3.70, 95% CI -0.23 to 7.63). There is probably little or no difference in the incidence of pulmonary exacerbations or QoL between the two groups.
Authors' conclusions:
Digital monitoring plus tailored support via an online platform probably improves adherence to inhaled therapies and reduces treatment burden (but without a corresponding change in QoL) in the medium term (low- and moderate-certainty evidence). In a shorter time frame, technological enhancement of inhaling antibiotics may improve adherence to treatment (low-certainty evidence). There may be little or no effect on lung function with either intervention, and online monitoring probably makes no difference to pulmonary exacerbations. Future research should assess the effect of digital technology on adherence in both children and adults. Consideration of adherence to the total treatment regimen is also important, as an improvement in adherence to inhaled therapies could come at the cost of adherence to other parts of the treatment regimen.
Background: Cystic fibrosis (CF) is a genetic disorder, in which defective clearance of airway secretions leads to progressive lung function loss. Inhaled mannitol is used to increase sputum and mucociliary clearance. There are little data from real-world studies on the effectiveness of mannitol in children. Our objective was to evaluate the spirometry and clinical results of mannitol in pediatric patients. Methods: We retrospectively reviewed the records of 30 children and adolescents with CF receiving inhaled mannitol who were already on recombinant human deoxyribonuclease (rhDNase) treatment. The change in forced expiratory volume in 1 second (FEV1) from baseline at 2-4 months was the primary outcome. Secondary measures were other spirometry results, body mass index (BMI), hospital admissions, sputum characteristics, and positive bacterial colonization. Results: Compared to baseline, we found significant improvement in percent predicted FEV1 at 2-4 months of treatment; 84.50 (58.00-99.00) vs. 96.00 (66.00-106.00) (P = 0.0007). The absolute change in FEV1 was +11.5% at 2-4 months, +6.5% at 5-7 months, and +4% at 8-12 months. Also, significant improvements in other spirometry results were observed. Adolescents had significantly lower FEV1 results, but the improvement in their lung function was sustained for a more extended period than children. Mannitol provided easier sputum removal, increased sputum volume, significant decline in hospitalizations, and significantly fewer patients with positive sputum cultures. A significant increase in BMI at 8-12 months was observed. Cough was the most frequent adverse effect. Conclusion: In a real-world setting, our results demonstrated that adding mannitol to rhDNase therapy is tolerable in pediatric patients with CF and may provide improved spirometry and clinical outcomes. In addition, our results showed that mannitol provided recovery in overall lung function at 2-4 months, which was sustained up to 12 months together with improved BMI, easier sputum removal, and a decline in bacterial colonization and hospital admissions. However, cough was the most frequent side effect.
Background
People with cystic fibrosis frequently have low levels of adherence to inhaled medications.
Objectives
The objectives were to develop and evaluate an intervention for adults with cystic fibrosis to improve adherence to their inhaled medication.
Design
We used agile software methods to develop an online platform. We used mixed methods to develop a behaviour change intervention for delivery by an interventionist. These were integrated to become the CFHealthHub intervention. We undertook a feasibility study consisting of a pilot randomised controlled trial and process evaluation in two cystic fibrosis centres. We evaluated the intervention using an open-label, parallel-group randomised controlled trial with usual care as the control. Participants were randomised in a 1 : 1 ratio to intervention or usual care. Usual care consisted of clinic visits every 3 months. We undertook a process evaluation alongside the randomised controlled trial, including a fidelity study, a qualitative interview study and a mediation analysis. We undertook a health economic analysis using both a within-trial and model-based analysis.
Setting
The randomised controlled trial took place in 19 UK cystic fibrosis centres.
Participants
Participants were people aged ≥ 16 years with cystic fibrosis, on the cystic fibrosis registry, not post lung transplant or on the active transplant list, who were able to consent and not using dry-powder inhalers.
Intervention
People with cystic fibrosis used a nebuliser with electronic monitoring capabilities. This transferred data automatically to a digital platform. People with cystic fibrosis and clinicians could monitor adherence using these data, including through a mobile application (app). CFHealthHub displayed graphs of adherence data as well as educational and problem-solving information. A trained interventionist helped people with cystic fibrosis to address their adherence.
Main outcome measures
Randomised controlled trial – adjusted incidence rate ratio of pulmonary exacerbations meeting the modified Fuchs criteria over a 12-month follow-up period (primary outcome); change in percentage adherence; and per cent predicted forced expiratory volume in 1 second (key secondary outcomes). Process evaluation – percentage fidelity to intervention delivery, and participant and interventionist perceptions of the intervention. Economic modelling – incremental cost per quality-adjusted life-year gained.
Results
Randomised controlled trial – 608 participants were randomised to the intervention ( n = 305) or usual care ( n = 303). To our knowledge, this was the largest randomised controlled trial in cystic fibrosis undertaken in the UK. The adjusted rate of exacerbations per year (primary outcome) was 1.63 in the intervention and 1.77 in the usual-care arm (incidence rate ratio 0.96, 95% confidence interval 0.83 to 1.12; p = 0.638) after adjustment for covariates. The adjusted difference in mean weekly normative adherence was 9.5% (95% confidence interval 8.6% to 10.4%) across 1 year, favouring the intervention. Adjusted mean difference in forced expiratory volume in 1 second (per cent) predicted at 12 months was 1.4% (95% confidence interval –0.2% to 3.0%). No adverse events were related to the intervention. Process evaluation – fidelity of intervention delivery was high, the intervention was acceptable to people with cystic fibrosis, participants engaged with the intervention [287/305 (94%) attended the first intervention visit], expected mechanisms of action were identified and contextual factors varied between randomised controlled trial sites. Qualitative interviews with 22 people with cystic fibrosis and 26 interventionists identified that people with cystic fibrosis welcomed the objective adherence data as proof of actions to self and others, and valued the relationship that they built with the interventionists. Economic modelling – the within-trial analysis suggests that the intervention generated 0.01 additional quality-adjusted life-years at an additional cost of £865.91 per patient, leading to an incremental cost-effectiveness ratio of £71,136 per quality-adjusted life-year gained. This should be interpreted with caution owing to the short time horizon. The health economic model suggests that the intervention is expected to generate 0.17 additional quality-adjusted life-years and cost savings of £1790 over a lifetime (70-year) horizon; hence, the intervention is expected to dominate usual care. Assuming a willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained, the probability that the intervention generates more net benefit than usual care is 0.89. The model results are dependent on assumptions regarding the duration over which costs and effects of the intervention apply, the impact of the intervention on forced expiratory volume in 1 second (per cent) predicted and the relationship between increased adherence and drug-prescribing levels.
Limitations
Number of exacerbations is a sensitive and valid measure of clinical change used in many trials. However, data collection of this outcome in this context was challenging and could have been subject to bias. It was not possible to measure baseline adherence accurately. It was not possible to quantify the impact of the intervention on the number of packs of medicines prescribed.
Conclusions
We developed a feasible and acceptable intervention that was delivered to fidelity in the randomised controlled trial. We observed no statistically significant difference in the primary outcome of exacerbation rates over 12 months. We observed an increase in normative adherence levels in a disease where adherence levels are low. The magnitude of the increase in adherence may not have been large enough to affect exacerbations.
Future work
Given the non-significant difference in the primary outcome, further research is required to explore why an increase in objective normative adherence did not reduce exacerbations and to develop interventions that reduce exacerbations.
Trial registration
Work package 3.1: Current Controlled Trials ISRCTN13076797. Work packages 3.2 and 3.3: Current Controlled Trials ISRCTN55504164.
Funding
This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research ; Vol. 9, No. 11. See the NIHR Journals Library website for further project information.
Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. The primary objective of the review is to assess the efficacy of psychological interventions for improving adherence to inhaled therapies in people with cystic fibrosis (CF). A secondary objective is to establish the most effective components, or behaviour change techniques (BCTs), of interventions for improving adherence to inhaled therapies in people with CF, using the BCT Taxonomy version 1 (Michie 2013). Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Significant advancements in the treatment of cystic fibrosis (CF) have led to drastically improved medical outcomes for those living with this illness. While these improvements have increased life expectancy and resulted in better quality of life, managing the daily care required to stay healthy is burdensome and complex. A time-intensive daily CF treatment regimen may be difficult to maintain and can interfere with many aspects of one’s life. Many factors impact how well an individual adheres to recommendations of their healthcare team. Understanding the barriers and facilitators of treatment adherence in CF is critical as well as the interventions available to help those with this disease live better lives while managing their health.
Non-adherence to prescribed treatment is considered the foremost cause of treatment failure in chronic medical conditions. Airway clearance techniques (ACT) play a key role in the management of chronic suppurative lung disease yet, along with inhaled therapies such as nebulised antibiotics, adherence to these is often lower than to other treatments. In this review we discuss methods of monitoring adherence to these therapies and potential barriers and outline suggestions for improving adherence in the paediatric population.
There are many and varied devices currently approved for the administration of inhaled treatments for use in different parts of the world. Well-developed national and local guidelines and training programs for health professionals are important in ensuring that patients are prescribed the best available devices and formulations for their age and disease condition, as well as being trained adequately in their optimal use. Despite training, surveys have shown diverging practices between health care centers for using and testing efficacy of inhaled treatments. This demonstrates the confusion that arises due to the lack of consistency concerning advice from trained therapists and prescribers about the use of devices to administer inhaled treatments. This review aims to provide a summary of current inhalation devices, with advantages and caveats of each. This is done within the context of device development and how device options can be considered for appropriate treatment delivery for children with airway disease, such as asthma.
Objective:
To compare medication adherence, pulmonary exacerbations, healthcare utilization, and costs for patients with cystic fibrosis (CF) who utilized a pharmacy-based therapy management program to a matched control group. We hypothesized that patient management services would be associated with better medication adherence, and thus require fewer visits to the emergency room or hospitalizations.
Methods:
This retrospective, observational cohort study used claims data from the MORE2claims Registry®. The sample consisted of CF patients, aged 6+, who had ≥1 pharmacy claim for inhaled tobramycin, inhaled aztreonam, ivacaftor, or dornase alfa from 6/2/2014-5/31/2015. Adherence was measured as proportion of days covered (PDC). Propensity score matching and multivariable regression techniques were used to compare outcomes in program participants to matched controls.
Results:
Of the 236 intervention and 724 control patients meeting selection criteria, 202 were propensity-matched from each cohort. Relative to the control cohort, program patients had 23% higher mean PDC for tobramycin (IRR = 1.23, P = 0.01) and were twice as likely to be adherent to tobramycin (PDC ≥ 80%) than matched controls (OR = 2.14, P = 0.04). Program patients had fewer ER visits (IRR = 0.52, P < 0.01) and slightly lower ER costs (IRR = 0.66, P = 0.06) than the control patients.
Conclusion:
A pharmacy-based therapy management program for CF patients was associated with higher adherence to inhaled tobramycin and lower ER rates. Pharmacies that provide therapy management can support effective CF care management.
This is the protocol for a review and there is no abstract. The objectives are as follows:
The review aims to assess interventions aimed at promoting adherence to treatment in people with CF. Since there are various methods for measuring adherence, each with varying degrees of objectivity and accuracy, the review will also assess the effects of these interventions on clinical measures, such as lung function and quality of life, to allow a broader appraisal of efficacy. The review will also assess the disadvantages of the interventions such as cost and the length of time required to perform the intervention.
Shortcomings of conventional nebulizers in terms of drug delivery have led to the development of "intelligent" nebulizers. Based on the Adaptive Aerosol Delivery technology, the I-neb AAD System has been designed with vibrating mesh technology and a unique metering chamber design for precise drug delivery with minimal waste of aerosol. Two breathing pattern algorithms are built into the device, one for the Tidal Breathing Mode (TBM), and one for slow and deep inhalations, the Target Inhalation Mode (TIM). A key feature of the AAD technology is the patient feedback mechanisms that are provided to guide the patient on delivery performance.
Cystic fibrosis (CF) is a common autosomal recessive inherited disorder affecting 1 in 2,500 births and similar to 75,000 people in North America, Europe, and Australia. The purpose of this review is to discuss the most recent advances in therapies for CF patients. The CF drug development pipeline provides information regarding the phase of each new therapy and those that are already in use by patients. The ultimate goal of therapy will be to deliver tailored individualized therapies to those who need it the most. This review will focus on new research on CF transmembrane conductance regulator protein modulator agents and the effort of gene therapy.
Suboptimum adherence to preventive asthma treatment is associated with substantial morbidity and mortality, yet adherence often remains poor. We aimed to investigate whether use of an inhaler with audiovisual reminders leads to improved adherence and asthma outcomes in school-aged children who presented to the emergency department with an asthma exacerbation.
We did a randomised controlled trial in patients aged 6-15 years who attended the regional emergency department in Auckland, New Zealand with an asthma exacerbation and were on regular inhaled corticosteroids. Using a simple, unrestricted block randomisation with block sizes of 200, we randomly assigned patients to receive an electronic monitoring device for use with their preventer inhaler with the audiovisual reminder functions either enabled to support adherence to inhaled corticosteroids (intervention group) or disabled (control group). Participants were followed up every 2 months for 6 months. The primary outcomes were adherence to preventive inhaled corticosteroids and number of days absent from school for any reason. Asthma control was assessed as a secondary outcome. All analyses were done in the intention-to-treat population. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12613001353785.
The study took place between May 10, 2010, and Feb 26, 2012. We randomly assigned 220 patients, 110 to the intervention group and 110 to the control group. Median percentage adherence was 84% (10th percentile 54%, 90th percentile 96%) in the intervention group, compared with 30% (8%, 68%) in the control group (p<0·0001). The proportion of days absent from school for any reason was 1·9% (10th percentile 0·0%, 90th percentile 7·9%) in the intervention group and 1·7% (0·0%, 8·6%) in the control group. The change in asthma morbidity score from baseline to 6 months was significantly greater in the intervention group than in the control group (p=0·008), with a reduction of 2·0 points from a mean baseline score of 9·3 (SD 2·2) to 7·3 (2·1) in the intervention group, compared with a reduction of 1·2 points from a baseline of 9·2 (2·5) to 8·0 (2·2) in the control group.
Use of an electronic monitoring device with an audiovisual reminder led to significant improvements in adherence to inhaled corticosteroids in school-aged children with asthma. This intervention could be beneficial for the improvement of asthma control in patients for whom poor asthma control is related to poor adherence.
Health Research Council of New Zealand and Cure Kids.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Background:
Nebulised medicines contribute to the high treatment burden experienced by patients with cystic fibrosis (CF).
Objectives:
This study explored experiences of adult patients with CF when using nebulised medicines, factors impacting on their adherence to nebulised therapy and strategies they used to facilitate adherence.
Setting:
Community setting, in Sydney, Australia.
Methods:
Ten patients with CF were recruited through a CF patient organisation. Semi-structured face-to-face interviews were conducted, addressing the study objectives. Interviews were audio-recorded, transcribed verbatim and content analysed for anticipated and emergent themes.
Main outcome measure:
Experiences with using nebulised medicines; and barriers and facilitators of adherence to nebulised medicines.
Results:
Participants' age ranged from 22 to 45 years, with half being male. Four broad themes (with more specific sub-themes) were identified from the interviews: experiences with using nebulised medicines (cleaning nebuliser, time taken to use nebuliser medicine, flexibility in use of nebuliser); feelings about using nebulised medicines (necessary/important, dislike, part of life); factors impacting non-adherence (time consuming therapy, side effects/effects of medicine, work/social demands, lack of perceived importance); factors and strategies facilitating adherence (perceived medicine importance, habit/routine, support, health benefits, technology/medicine dose form, timetabling).
Conclusions:
Nebulised therapy for cystic fibrosis patients takes a substantial amount of time, with patients trying to alter their routine to incorporate nebulising into their daily lives. However there are still many factors that lead to low adherence, including work/social demands and travelling. Patients balance the necessity for nebulised therapy against the barriers, and engage in intentional non-adherence at times. Future strategies and resources should target and address specific factors identified by patients with CF as being important and impacting their adherence to nebulised medicines.
Patients with tracheostomies, those requiring mechanical ventilation, and those too small or compromised for conventional devices, are realizing the benefits of increasingly sophisticated aerosol delivery systems. New medicines and novel aerosol formulations, have enhanced our ability to treat lung disease, and are opening the doors for therapy to treat diseases like diabetes, pulmonary hypertension, and cancer. Progress in the aerosol delivery of drugs has been spurred by the significant benefits, including ease of use, patient comfort, greater selectivity of effect, and the potential to decrease side effects.
An increasing number of patients are dependent on aerosolized therapy to manage pulmonary diseases, including asthma, cystic fibrosis, and pulmonary arterial hypertension. An aerosol therapy is only useful if it can be appropriately and consistently delivered in the desired dose to the lower respiratory tract. Many factors affect this deposition in young children, including anatomical and physiologic differences between adults and children, patient-mask interface issues, the challenge of administering medication to uncooperative children, and behavioral adherence. Moreover, the techniques used to assess aerosol delivery to pediatric patients need to be carefully evaluated as new therapies and drug-device combinations are tested. In this review, we will address some of the challenges of delivering aerosolized medications to pediatric patients.
To measure drug adherence in children with mild asthma receiving long term prophylactic treatment.
Double blind randomised placebo controlled trial. Patients received inhaled budesonide 100 microg or 200 microg daily, or placebo for 27 months. All participants were asked to inhale medication or placebo from two different Turbuhalers (morning and evening) during the study. A total of 122 children (80 boys, 42 girls) aged 7-16 years with mild asthma (mean FEV(1) 103.7% of predicted) were included in the trial. Drug adherence was assessed by counting the number of remaining doses in the inhaler when study medication was returned at six month intervals.
A statistically significant and continuing decrease in measured drug adherence was found from three to nine months and then to 27 months, reaching mean values of 40.6% and 46. 9% for inhaled morning and evening medication respectively. Drug adherence declined more rapidly in the placebo group (compared to active treatment); this difference became significant after two years of treatment. Children aged 9 years or less had better drug adherence during the entire study period, but the difference was only significant for the first three months of the study. Measured drug adherence was significantly higher for evening medication compared to morning medication for all study intervals after nine months.
Measured drug adherence diminishes significantly when treating children with mild asthma in a long term trial. This emphasises the importance of monitoring compliance in clinical trials.
Cystic fibrosis (CF) is now as much a disease of adults as of children and adolescents. An important focus of recent research has been the impact of the complex, expensive, and time consuming routine of self-care and medical treatment that is required by adults with CF to maintain health. A growing concern for medical and allied health teams is the issue of patient adherence to prescribed health management plans. A summary of the particular medical and treatment context of CF is followed by a review of adherence measurement issues and the determinants of adherence to treatment regimens in people with CF, primarily adults. Evidence for factors which influence adherence decisions of people with CF is examined. The medical and psychological aspects of this complex problem have not been adequately addressed because of difficulties with definition and measurement. Only a small proportion of the variance in adherence has been accounted for in the literature. New measurement technologies and new theoretical directions offer promise for a better understanding of this complex and important issue and may result in more effective intervention strategies to improve adherence.
The objectives of this study were to describe and pilot-test a theory- and evidence-based intervention to improve adherence of HIV-infected patients with antiretroviral medication. Twenty-six treatment-experienced patients (>6 months on treatment) participated in a within-subject comparison design. Adherence was measured electronically with Medication Event Monitoring System (MEMS) caps for at least 5 months: 2 months before the intervention and 3 months during the intervention. MEMS data were used to measure the outcome of the intervention, but also served as feedback to participants during the intervention. Mean adherence during the month before intervention was compared to mean adherence during the third month of intervention. Data for the process evaluation were gathered through direct observation and semi-structured interviews. Adherence improved significantly during the intervention (Z = -2.1, p < 0.05). Mean adherence (percentage of prescribed doses taken within correct time interval) before the intervention was 81.8% compared to 92.5% during the third month of the intervention. More than 65% of the nonadherent patients (<95% adherence) before the intervention were adherent during the third month of the intervention. Both health care professionals and patients positively evaluated the intervention protocol and the electronic measurement of adherence. The only critique from some patients was the lack of userfriendliness of the MEMS cap and its medication container (size and shape). It can be concluded that the proposed intervention fits in standard care procedures, can be executed by trained HIV nurses, seems to improve adherence to antiretroviral medication, and is positively evaluated by the users. Large-scale and long-term research is warranted.
Chest physiotherapy (CP) is seen as a cornerstone of Cystic Fibrosis (CF) treatment. However, previous studies have suggested that adherence to CP is low. This study of adults with CF (N = 563) investigated CP adherence and associated factors. Only 29.5 per cent reported undertaking daily CP. Predictors of adherence included problems with fitting CP into lifestyle, a perception that CP does not help, physical consequences of CP, doing exercises instead and doing CP as and when necessary. These variables accounted for 45 per cent of the variance in adherence. Content analysis revealed a number of themes related to adherence to CP. Future studies should explore the benefits of daily CP and attempt to devise simple interventions to maximize adherence to CP.
Although there is general agreement from studies demonstrating that adherence to inhaled corticosteroid therapy is often inadequate to establish consistent control, relatively little concurrence exists in reports of interventions to correct the problem. Half of the studies reviewed found that the experimental intervention did not change adherence, and behavior change reported by patients was often not accompanied by changes in treatment success. Studies used a variety of methods that differed in quality with findings that were often contradictory. Key limitations in many studies included reliance on inadequate adherence measures, inclusion of convenience samples of well-motivated patients, and assessments of intervention outcomes artificially boosted by attrition of least adherent participants. Research is encouraged into innovative interventions that are brief, easily implemented, and can be tailored to individual patients and diverse clinical settings. Of particular importance is inclusion of hard-to-reach patients, including urban and rural poor and the use of valid measures of adherence at intervals sufficient to establish enduring benefit.
The objective of this study was to analyze data on parents' adherence to their child's prescribed nebulizer treatment regimen and compliance with the demands of the nebulizer and the face mask. Data on adherence and compliance were recorded in a 24-week double-blind, randomized, parallel-group study with budesonide inhalation suspension in 125 young children with mild to moderate asthma. Budesonide was administered with an Adaptive Aerosol Delivery (AAD) system, which recorded adherence to treatment and compliance with the AAD system. A total of 35,481 treatments were recorded and analyzed. A study questionnaire regarding the parents' and children's acceptance of the AAD system has also been analyzed. The adherence to the treatment regimen was 91.3%, and the compliance with the AAD system was 90.4%. True adherence, the product of adherence and compliance, was 82.5%. Approximately 90% of the parents found the face mask easy to seal and the AAD equipment easy to use, and over 90% of the children accepted it within 1 week. In conclusion, the results indicate that the AAD system could be of real clinical advantage for treatment of asthma in young children.
Cystic fibrosis is the most common genetically inherited disease in the Caucasian population, with approximately 30,000 patients in the USA and more than 50,000 patients worldwide. The primary defect in the cystic fibrosis transmembrane regulator gene affects the production and/or function of the cystic fibrosis transmembrane regulator protein. Depending on the severity of the genetic defect, patients may have minimal disease expression (e.g., male infertility) or multisystem involvement, including recurrent respiratory infection progressing to respiratory failure, hepatobiliary disease, exocrine pancreatic insufficiency, diabetes mellitus and gastrointestinal tract motility problems. Pseudomonas aeruginosa is commonly isolated from the lower respiratory tract in early childhood. Chronic infection is associated with increased morbidity and mortality. P. aeruginosa infection may be acquired from the environment or by person-to-person contact. Clinicians should adopt a proactive protocol to prevent chronic infection. The cornerstones of such a policy are microbiological surveillance, infection control and antibiotic-based eradication regimens.
The clinical records of 1187 patients starting antihypertensive treatment during the period 1969-1979 were reviewed at the end of 1983. The annual drop-out rate was 21.0% in the first year, decreased in subsequent years and was about 1% after five years. The medication compliance of 381 patients was estimated by interview in 1980. Of all 381 patients, 243 (63.8%) reported taking 95-100% of prescribed drugs. Medication compliance was related to the frequency and timing of dosing rather than to the number of drugs. Once daily regimens had better compliance than three times daily ones, and medication compliance was greatest for morning dosing, second greatest for evening dosing, and least for dosing at noon. Repeated assessment of medication compliance on three successive years was followed by gradual improvement of compliance without any other intervention.
To test whether the time of administration influences the therapeutic response to a calcium antagonist taken once a day. Also, the dynamics of drug compliance and its impact on blood pressure control were investigated.
Twenty outpatients with mild-to-moderate hypertension were included in a randomized, placebo-controlled open study. In a crossover design, all of the patients received 5 mg amlodipine, either in the morning or in the evening, during two consecutive 4-week treatment periods.
Blood pressure was taken by casual measurement, ambulatory 24-h monitoring (SpaceLabs 90202) and self-measurement at home, performed with a semi-automatic oscillometric device during the whole study period. Compliance was assessed using the Medication-Event-Monitoring System (MEMS).
Neither casual nor ambulatory day- or night-time readings detected a significant difference between morning and evening administration. However, self-measurement documented significantly greater blood pressure reductions for morning than for evening administration. The MEMS showed different compliance on the days of ambulatory monitoring (100% with both drug regimens) compared with the whole treatment period. The number of days with missed medication was thus significantly higher for the evening dosing regimen. The difference in self-measured blood pressure between the two regimens was lost if the days with missed medication were removed from the statistical analysis.
Time of once-a-day amlodipine administration does not influence its efficacy for 24-h blood pressure control. Furthermore, the use of self-measurement and the MEMS may provide useful additional information on the pharmacodynamic impact of different dosing patterns in hypertensive patients.
Unlabelled:
Twenty-four pediatric patients with acute lymphoblastic leukemia (ALL) on maintenance therapy were evaluated for their compliance with taking their prescribed doses of oral mercaptopurine (6-MP).
Procedure and results:
We utilized the Medication Event Monitoring System (MEMS; Aprex Corporation, Fremont, CA) for the study. Compliance was defined as the number of days doses were taken as a percentage of the total number of days doses were prescribed during the study period. The mean age of the patients was 7.3 years (range 2.6-17.2 (years). Patients were evaluated for a mean of 44 days (range 15-94 days). Thirty-three percent of patients (8) took less than 90% and 17% (4) took less than 80% of their prescribed pills. Eight patients were also evaluated for a difference in compliance between morning and evening administration. For the comparison of compliance between a morning vs. an evening schedule a tren toward improved compliance in the evening was found. Five patients had an increase and one patient a decrease in compliance with an evening schedule (differences ranged from 0.2% to 51.3%), with two patients having 100% compliance on both schedules.
Conclusions:
Our data raise concern that a significant proportion of pediatric patients are non-compliant with pill taking and demonstrate that the timing of administration of 6-MP in children with ALL may be crucial in some patients and supports the hypothesis that evening administration of 6-MP is associated with a lower risk of relapse.
Accurate assessment of medication adherence has been difficult to achieve but is essential to drug evaluation in clinical trials and improved outcomes in clinical care.
This study was conducted to compare four adherence assessment methods: child report, mother report, canister weight, and electronic measurements of metered dose inhaler (MDI) actuation.
Participants included 27 children with mild-to-moderate asthma who were followed prospectively for 6 months. All patients used an MDI equipped with an electronic Doser attached to their inhaled steroid. At each 2-month follow-up visit, Doser and canister weight data were recorded, while child and mother were interviewed separately regarding medication use.
Children and mothers reported, on average, over 80% adherence with the prescribed inhaled steroid. Canister weight revealed, on average, adherence of 69%, significantly lower than self-report. When adherence recorded by the electronic Doser was truncated to no more than 100% of prescribed daily use, average adherence was 50%. Older children and adolescents, nonwhite children, and those from poorer functioning families were least adherent.
Electronic adherence monitoring was significantly more accurate than self-report or canister weight measures. Such accuracy is an essential prerequisite to increasing understanding of the treatment, setting, and patient factors that influence adherence, and to the consequent design of effective intervention strategies.
Although there is general agreement from studies demonstrating that adherence to inhaled corticosteroid therapy is often inadequate to establish consistent control, relatively little concurrence exists in reports of interventions to correct the problem. Half of the studies reviewed found that the experimental intervention did not change adherence, and behavior change reported by patients was often not accompanied by changes in treatment success. Studies used a variety of methods that differed in quality with findings that were often contradictory. Key limitations in many studies included reliance on inadequate adherence measures, inclusion of convenience samples of well-motivated patients, and assessments of intervention outcomes artificially boosted by attrition of least adherent participants. Research is encouraged into innovative interventions that are brief, easily implemented, and can be tailored to individual patients and diverse clinical settings. Of particular importance is inclusion of hard-to-reach patients, including urban and rural poor and the use of valid measures of adherence at intervals sufficient to establish enduring benefit.
Dornase alpha improves sputum clearance and pulmonary function in patients with moderate bronchiectasis and cystic fibrosis (CF). Several studies have demonstrated variable adherence to treatment regimens in patients with CF. We aimed to compare self-reported adherence with computer based dispensing records of dornase alpha.
Direct interview of adherence to dornase alpha was compared with pharmacy-dispensing records during a 12-month period. The reasons for dornase alpha usage, and change in lung function in three groups of patients were compared (group 1 (n=42): positive trial, continuing therapy; group 2 (n=13): positive trial, ceased therapy; group 3 (n=22): negative trial). Ninety patients with CF were surveyed. Patients who had ceased dornase alpha provided reasons for drug cessation. Lung function and anthropometric data were collected prior to dornase alpha treatment and at 3 years. Health care professionals rated adherence to therapy.
Of the 42 patients on dornase alpha, the average utilisation was 197 days (54%). From dispensing records, 24% of patients were classified as good adherence, 46% as moderate adherence and 30% as poor adherence. Eighty-two percent claimed to use dornase alpha therapy more than 20 days/month, whereas dispensing records showed that only 24% of collected sufficient drug supplies. Health professionals' assessment of adherence of therapy was often incorrect and an overestimation was more common than underestimation. The change in FEV(1) 3 years after trial was not significantly different between groups. There was a negative correlation between initial response to dornase alpha and baseline FEV(1) (r=-0.44, P=0.001), however, initial response was not related to the change in FEV(1) over 3 years (r=0.20, P=0.16).
There is variability in adherence to dornase alpha in adults with CF and patient self-reporting is likely to over-estimate drug collection from the pharmacy. Further study of the long-term effects of dornase alpha is required. To date, proven interventions to enhance adherence are limited and require investigation in CF.
The morbidity and mortality associated with asthma are suspected to be a result, in part, of poor adherence to inhaled corticosteroid regimens. One influence on adherence may be the perception of symptoms. Because symptoms and adherence affect each other over time, a conventional statistical approach for studying these relationships may provide biased results.
To understand the influence of previous asthma symptoms and previous adherence on current symptoms.
A total of 76 adults, mean age 48 years +/- 15 years, with moderate or severe persistent asthma underwent 6 weeks of electronic monitoring of their use of inhaled corticosteroids and completed a daily symptom diary. We estimated the effect of earlier adherence on final symptoms by using marginal structural models, estimated by using a weighted estimation technique.
Morning was better than evening adherence, which declined over the observation period. The variability of adherence appeared to increase over the observation period. In addition, earlier adherence predicted current adherence more strongly than earlier symptoms predicted current adherence. There was no overall significant relationship between cumulative adherence and final symptoms.
These data indicate that accurately determining past adherence will help identify patients to target to improve their future adherence. These analyses are important for understanding time-varying measures in the clinical setting.
The purpose of this study was to monitor medication adherence in cystic fibrosis (CF) patients and its correlation with disease severity and patient age.
Children less than 12 years of age (group 1) and adolescents 12 years of age and older (group 2) were recruited from the University of Michigan CF Center. The study duration was 3 months. A total of 22 patients per group were enrolled. Adherence to ADEKs, an oral multivitamin, and dornase alfa, a nebulized mucolytic medication, was monitored. Adherence to ADEKs was monitored by using the Medication Event Monitoring System (MEMS) SmartCaps (APREX, AARDx, Inc., Union City, California). Dornase alfa adherence rate was monitored by counting empty medication vials.
Thirty-three patients completed the study, 15 patients in group 1 and 18 patients in group 2. The overall mean adherence rates for ADEKs and dornase alfa were (+/- SD) 63.6% +/- 24.0% and 66.5% +/- 31.2%, respectively. The median ADEKs and dornase alfa adherence rate for group 1 was 84.6% and 79.1%, respectively (p = .08); and for group 2 was 56.7% vs. 78.4%, respectively (p = .07). There was a trend toward significance, suggesting that the adherence rate for ADEKs was higher than for dornase alfa (p = .08) in group 1. Group 2 showed a trend toward adherence to dornase alfa than to ADEKs (p = .07). There was a trend for ADEKs adherence between groups 1 and 2 (p = .09), but not for dornase alfa (p = .93).
Parental supervision and disease severity are likely to play a major role in adherence to medical management. Partnership with patients and families about the treatment plan might be important for improving adherence rate. The MEMS SmartCaps is an electronic monitoring technology that should be used to measure drug adherence objectively both in further larger clinical trials and in the outpatient setting.
Adherence rates for chronic pediatric conditions are approximately 50%. The primary objective of the study was to assess rates of adherence using four different measurement methods for children with cystic fibrosis (CF).
Participants included 37 children with CF between 6 and 13 years of age and their primary caregivers. Adherence measures included parent and child self-reports, diary data, pharmacy refill history, and electronic monitors.
Results suggested that rates of adherence varied by treatment component and across measurement methods. However, when examining more objective measures, rates of overall adherence were below 50% for children with CF, indicating generally poor adherence to the treatment regimen. For example, rates of adherence to enzyme medications, using electronic and diary measures, ranged from 27% to 46%.
The multi-method measurement approach provided unique information regarding rates of adherence for each disease condition by type of treatment component. Accurately measuring rates of treatment adherence for children with CF is an important step in developing effective interventions to influence these behaviors.
In the past decade, the introduction of electronic monitoring systems for monitoring medication adherence has contributed to the dialog about what works and what does not work in monitoring adherence. The purpose of this article is to describe the use of the Medication Event Monitoring System (MEMS) in a study of patients receiving isoniazid for latent tuberculosis infection. Three case examples from the study illustrate the data that are obtained from the electronic device compared to self-reports and point to the disparities that may occur in electronic monitoring. The strengths and limitations of using the MEMS and ethical issues in utilizing this technology are discussed. Nurses need to be aware of these challenges when using electronic measuring devices to monitor medication adherence in clinical nursing practice and research.
The aim of this pilot study was to compare a the HaloLite Paediatric Nebulizer (HPN) with a pressurized metered dose inhaler and valved holding chamber (pMDI VHC, Aerochamber) in terms of drug delivery, adherence to treatment, compliance with device, true adherence, and acceptability. Fourteen children aged 11-36 months with asthma on regular treatment with inhaled corticosteroids were enrolled into an open, randomized, crossover trial. They received budesonide for 2 weeks with each delivery system. Both devices incorporated a datalogger which recorded information on how the device was used. The HPN was preprogrammed to deliver 25 microg of budesonide to the patient. A single actuation of budesonide 200 microg was used with the pMDI VHC. The median delivered dose of budesonide was 36 microg (range, 31-45 microg; CV, 15%) for the HPN and 53 microg (range, 17-85 microg; CV, 47%) for the pMDI VHC. The median adherence was 68% (range, 11-96%) with the HPN and 71% (range, 11-100%) with the pMDI VHC. The median device compliance was 30% and 51% and the median true adherence was 23% and 36%, respectively. The shape, size, and weight of the HaloLite Paediatric Nebulizer were generally less acceptable than the shape, size, and weight of the pMDI VHC with datalogger. These results indicate that reproducible quantities of drug can be delivered to very young children using AAD technology such as that incorporated into the HPN. Drug delivery with the pMDI VHC was more variable, but parents preferred this device.
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