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Readmission to primary care is challenging for patients due to involvement of multiple healthcare providers across different settings and implementing new medicines into their daily routine. Elucidating patients' needs is crucial to tailor counseling support.To explore the patient perspectives on implementing a newly prescribed cardiovascular medicine into their daily routine at readmission to primary care.A qualitative study was performed within the outpatient pharmacy. Adult patients who were prescribed a new cardiovascular medicine by their treating hospital physician at hospital discharge or during an outpatient clinic visit were eligible to participate. Purposive sampling was applied to equally distribute adherence-influencing factors. Patients were interviewed by telephone and inclusion continued until theoretical data saturation. An adapted Greenhalgh framework for implementation research was used for a thematic content analysis by conceptualizing the new medicine as an innovation that requires implementation by a patient (adopter).Data saturation was reached at 44 patients of which 19 discontinued their new medicine at the time of the interview. Reasons for discontinuing included: side-effects, insufficient efficacy or negligence. Patients considered a lack of basic knowledge on their newly prescribed cardiovascular medicine as a major barrier for adopting it into their daily routine. They were in need of information on risks and benefits of their new medicine. A noticeable effect and tailored counseling facilitated patients in taking their medicine as prescribed. Patients mentioned personalized organizing tools and routinization of medication intake as important success factors for addressing their practical challenges with their new medicine.By applying the adapted Greenhalgh framework, this study provided a unique and structured insight in patients' barriers and facilitators that could influence their ability to implement a new cardiovascular medicine at readmission to primary care. This knowledge enables pharmacists to tailor their patient support and provide individualized patient counseling.

Introduction: In the past decade, prescription opioid use increased exponentially and concomitantly opioid use disorders (OUD) are becoming more common. Several risk factors for developing OUD have been identified, but little is known regarding the patients’ perspective on developing a prescription OUD. Methods: We recruited 25 adults undergoing treatment for prescription OUD. In-depth, semi-structured interviews focussed on experiences with long-term opioid use, knowledge and attitudes regarding opioids, and access to opioids. A directed content analysis was conducted on the transcribed interviews using NVivo. Results: Participants showed that the development of an OUD is affected by various factors which could be grouped into three themes: (1) experiences driving initiation, (2) experiences driving continuation, and (3) experiences with prescription OUD. Besides the need for pain management, the dynamics of patient-provider communication, care coordination, provider vigilance, and environmental support all contributed to the way patients used their opioids. Conclusion: Patients’ experiences illustrate that the first stage of the development of prescription OUD differs from the development of other substance addictions. Negative reinforcement might play a more prominent role in the early phase of prescription opioid use. Patients expressed a lack of guidance, both at the start of use and long-term use, easy access to new prescriptions and a lack of monitoring as main drivers of the development. Poorly controlled pain and subjective stress fuelled continuous opioid use.

Background: Non-medical medication switches, a change to another medicine or medication label not motivated by medical reasons, occur frequently. Switches often lead to negative patient emotions, such as confusion and anger. Pharmacy staff's communication, i.e. delivering the message and addressing patients' emotions is crucial, but experienced as difficult.Objective: To develop and test a communication training for the pharmacy team to facilitate medication switch conversations.Methods: A communication training was developed based on the 'breaking bad news model' and 'positive message framing' strategies, and incorporating needs and preferences from practice. The training consisted of an e-learning with theory and reflective exercises, a half-day live training session, and an online reflection session. The Kirkpatrick training evaluation model (levels one 'reaction' and two 'learning') was used to evaluate the training. Quantitative data were analyzed using descriptive statistics and interview data was transcribed verbatim and analyzed thematically.Results: Twelve pharmacists and 27 pharmacy technicians from 15 Dutch pharmacies participated in the training. According to Kirkpatrick's model level one, the major learning outcome was to give space to patients to express their emotions and/or concerns (e.g. more silences in the conversations). For level two, most participants valued practicing the conversations, role-playing, and receiving feedback. The majority of the participants indicated that they had sufficient tools and practice during the live training to apply the strategies in daily practice. A few participants still needed time and practice, or missed examples to apply the strategies.Conclusion: The communication training based on the two strategies was well-received and participants felt well-equipped post-training. The take-away for participants was to give space to patients to express their emotions. Using these strategies and skills, pharmacy teams can tailor their medication counseling to patients' emotions and concerns during non-medical medication switches to better support patients in proper medication use.

Background Community pharmacies are easily accessible for self-care advice. Guidelines for providing self-care advice were introduced in several countries, including the Netherlands in the 1990s. Previous studies have indicated room for improvement in self-care advice in daily pharmacy practice. Aim To identify barriers and facilitators for providing self-care advice. Method Semi-structured interviews were conducted face-to-face or online with pharmacists and pharmacy assistants using a topic guide based on the Theoretical Domains Framework. The interviews were audio-recorded and transcribed verbatim. The transcripts were deductively analysed to identify barriers and facilitators for self-care counselling. COREQ guidelines were followed. Results In total, 13 pharmacists and 12 pharmacy assistants were interviewed to reach data saturation. In general, most themes addressed by pharmacists and pharmacy assistants belonged to similar domains. The following domains were frequently mentioned: environmental context and resources (e.g. priority for prescription drugs, privacy, collaboration with general practitioners, access to patients’ records), intentions (providing reliable advice), skills (communication, decision-making), knowledge (ready guideline knowledge), beliefs about consequences (patient safety), social influences (patient awareness of pharmacist role), reinforcement (lack of reimbursement for relatively time-consuming advice). Conclusion This study identifies barriers and facilitators for evidence-based self-care advice. Pharmacists should first support pharmacy assistants by helping them keep their knowledge and skills up to date and creating suitable pharmacy preconditions to facilitate improvements in self-care counselling. Second, collaboration with general practitioners regarding minor ailments should be improved.

IntroductionAbout 70% of patients with asthma and/or chronic obstructive pulmonary disease (COPD) use their inhaled medication incorrectly, leading to reduced disease control, higher healthcare use and costs. Adequate guidance from the pharmacy team from first dispense onwards can benefit patients in the long run. We propose an intervention (‘On TRACk’) to improve medication adherence and inhaler technique of adult patients with asthma and/or COPD. This intervention focuses on training pharmacy technicians (PTs) in patient-centred communication and inhalation instruction skills. In addition, patients are actively involved in refill consultations at the pharmacy. The aim of this study is to improve inhaler technique and better inhaled medication adherence among patients with asthma and/or COPD. This paper describes the study protocol.Methods and analysisA cluster randomised controlled trial (RCT) with an intervention and control group of 15 pharmacies each will be conducted. Per intervention pharmacy, two PTs will be trained online. Each PT will include five patients who will prepare their second and third dispense counselling sessions by selecting three topics they wish to discuss. Pharmacies in the control cluster provide usual care. In total, 300 patients (150 per group) will be included. Up to 12 months after inclusion, patients complete 3-monthly follow-up questionnaires. Both a process evaluation and a cost-effectiveness analysis will be performed alongside the trial. Trial effectiveness on the patient level will be evaluated after the 12-month follow-up period.Patient data will be collected through questionnaires and pharmacy refill data. Patients’ inhaler technique will be visually assessed by PTs. Semistructured interviews with PTs and patients will be conducted regarding implementation and fidelity. Direct and indirect health costs will be collected to assess cost-effectiveness.The primary outcome is adherence to inhalation maintenance medication measured with pharmacy refill data. Secondary outcomes are inhaler technique, persistence, patients’ attitudes towards medication, self-efficacy in medication use and communication with their PTs.Ethics and disseminationThe study was approved by the Vrije Universiteit Amsterdam Ethics Committee (number: 2020.358). Results will be presented at (inter)national conferences and published in peer-reviewed journals. If proven to be (cost-)effective, the intervention should be considered for reimbursement and implementation in Dutch community pharmacies.Trial registration numberNL9750.

The pharmacy counter is a good place to identify and discuss medication-related problems. However, there is a lack of practical communication tools to support pharmacy technicians (PTs) in initiating a conversation with patients. This study aimed to develop and test a practical set of questions for PTs, called TRIAGE, to identify problems during encounters. TRIAGE was developed based on insight from the literature, focus groups with PTs and pharmacists, and input from patients and experts. In 10 community pharmacies, 17 PTs used TRIAGE during encounters with patients who collected their cardiovascular medication. For each encounter, PTs registered the identified problems and suggested solutions. A total of 105 TRIAGE conversations were held, 66 for first refill and 39 for follow-up refill prescriptions. In 15 (23%) first refill prescription encounters, a problem was identified. These problems concerned forgetting to take the medication, a complex medication regime or (fear of) side effects. In three (8%) follow-up refill prescription encounters, a problem was identified. Most of the problems were solved on the spot. Pharmacy technicians indicated that they identified medication-related problems with TRIAGE that otherwise would be left unnoticed. They appreciated TRIAGE as a useful instrument for starting the conversation with patients about medication use.

Background Adherence rates among asthma patients are generally low and decrease during adolescence, resulting in poorly controlled asthma. The aim of our study was to evaluate the effectiveness of the ADolescent Adherence Patient Tool (ADAPT), an interactive mobile health (mHealth) intervention, in supporting self-management and improving inhaled corticosteroid adherence in adolescents with asthma. Methods We conducted a cluster randomized controlled trial in 66 Dutch community pharmacies. Asthma patients aged 12–18 years were invited to participate, based on pharmacy medication refill records. The main study outcome was self-reported medication adherence, measured with the Medication Adherence Report Scale (MARS). Secondary outcomes were asthma control and quality of life. Outcomes were measured at start (t = 0 months) and at the end of follow-up (t = 6 months). Mixed-effects models were used to analyze the effect. Results In total, 234 adolescents (147 in the control group and 87 in the intervention group) completed the study; mean age 15.1 ± 1.9 years and 52.6% females. Adherence rates of patients with low baseline adherence (MARS scores ≤19; n = 76) increased with 1.42 points in the intervention group (n = 26). Adherence rates of patients in the control group (n = 50) decreased with 0.70 points. Thus there was a positive effect of the intervention on medication adherence (MARS +2.12, p = 0.04). This effect was stronger (MARS +2.52, p = 0.02) in poor adherent adolescents with uncontrolled asthma (n = 74). No effect of the intervention was observed on asthma control or quality of life. Conclusions The ADAPT intervention increases medication adherence in adolescents with asthma having poor adherence rates at baseline. Healthcare providers should consider a tailored mHealth approach to improve the asthma treatment.

BACKGROUND Mobile health (mHealth) apps have the potential to support patients’ medication use and are therefore increasingly used. Apps with broad functionality are suggested to be more effective; however, not much is known about the actual use of different functionalities and the effective engagement. OBJECTIVE The aim of this study was to explore the use and the effective engagement of adolescents (aged 12 to 18 years) with the Adolescent Adherence Patient Tool (ADAPT). METHODS The ADAPT intervention consisted of an app for patients, which was connected to a management system for their pharmacist. The aim of the ADAPT intervention was to improve medication adherence and, therefore, the app contained multiple functionalities: questionnaires to monitor symptoms and adherence, medication reminders, short movies, pharmacist chat, and peer chat. For this study, data of the ADAPT study and a cluster randomized controlled trial were used. Adolescents with asthma had 6 months’ access to the ADAPT intervention, and all app usage was securely registered in a log file. RESULTS In total, 86 adolescents (mean age 15.0, SD 2.0 years) used the ADAPT app 17 times (range 1-113) per person. Females used the app more often than males (P=.01) and for a longer period of time (P=.03). On average, 3 different functionalities were used, and 13% of the adolescents used all functionalities of the app. The questionnaires to monitor symptoms and adherence were used by most adolescents. The total app use did not affect adherence; however, activity in the pharmacist chat positively affected medication adherence (P=.03), in particular, if patients sent messages to their pharmacist (P=.01). CONCLUSIONS mHealth apps for adolescents with asthma should contain different functionalities to serve the diverging needs and preferences of individual patients. Suggested key functionalities to promote use and effectiveness in adolescents with asthma are questionnaires to monitor symptoms and a health care provider chat.

Purpose: Health literacy is defined as the ability to obtain, understand and apply information to make appropriate health decisions. Most health literacy research has been performed in the USA. Our objective was to study the prevalence of limited health literacy among adult pharmacy visitors in the Netherlands and to assess the association between health literacy and understanding of drug label information. Methods: A cross-sectional study was performed in community pharmacies belonging to the Utrecht Pharmacy Practice network for Education and Research. Adult pharmacy visitors (aged ≥18years) were approached in the pharmacy waiting area and invited for a brief interview including the newest vital sign, a validated health literacy assessment measure and questions about understanding of standard drug label instructions. Results: A total of 984 pharmacy visitors were included in the study: 63% were women, mean age was 56years and the majority was of native origin (84%). Based on newest vital sign scores, 52% had limited health literacy skills. Pharmacy visitors with limited health literacy skills had significantly lower understanding of drug label instructions (p

Background Since January 2012 the Dutch Medicines Act has been changed to enable medication monitoring and counselling for individual patients. Prescribers of medicines are now obliged to record the indication on the prescription of medicines mentioned in this law. Objective To assess patients’ opinion about recording of the indication on prescription and to explore the uptake of alterations in the medicines act in clinical practice. Methods The study was conducted in a sample of 57 community pharmacies belonging to the Utrecht Pharmacy Practice Network for Education and Research. In total, 528 patients were interviewed in these pharmacies and automated dispensing records were obtained from 22 community pharmacies to check prescriptions for linking of diagnosis codes (indications). Results For 12.5 % of the prescriptions that required notification of the indication, a diagnosis code was mentioned. For all other medicines, 15.1 % of the prescriptions were provided with diagnosis codes. There was large variation between different drugs. Only 11.7 % of the interviewed patients were familiar with the law. The majority of patients (91.1 %) had no objections with mentioning the indication for use on the prescription. Conclusion Indications are insufficiently mentioned on prescriptions while the majority of patients are generally positive about the law.

Adolescents are becoming more independently responsible for their medication regimen; therefore, adolescence is a crucial period to address medication beliefs, as many of the beliefs may persist into adulthood and can impair adherence and willingness to continue a prescribed therapy. Within this study, we aimed to explore adolescents’ general perceptions towards medicines. Adolescent students attending secondary schools in the Netherlands were invited through the school’s virtual learning environment to fill in an online questionnaire. Medication beliefs were assessed using the Beliefs About Medicines Questionnaire—General assessing general harm and general overuse beliefs. Within a 2-week period, 434 adolescent students responded to the questionnaire; 47.2 % thought that doctors overprescribed medication, and 20.5 % perceived medication as harmful in general. Being religious was associated with stronger harm (odds ratio (OR) 2.0, 95 % confidence interval (CI) 1.2–3.2) and overuse beliefs (OR 1.4, 95 % CI 0.9–2.1). Adolescents of native background had less concerns about overuse (OR 0.4, 95 % CI 0.2–0.8). Adolescents who actually consulted physicians had lower overuse beliefs (OR 0.6, 95 % CI 0.4–1.0). Conclusion: Adolescents more strongly believe in the general overuse of medicines than in general harm. Religious and ethnic background influence medication beliefs, as does previous experiences with the health-care system. Gaining more insight in adolescent patients’ medication use behavior and identifying patients at risk for negative medication beliefs associated with poor adherence in clinical practice might be a first step towards a lifelong good medication use.

To cite this article: Vijverberg SJH, Koster ES, Koenderman L, Arets HGM, van der Ent CK, Postma DS, Koppelman GH, Raaijmakers JAM, Maitland-van der Zee A-H. Exhaled NO is a poor marker of asthma control in children with a reported use of asthma medication: a pharmacy-based study. Pediatr Allergy Immunol 2012: 23: 529536. Abstract Background: A high fraction of nitric oxide in exhaled breath (FeNO) has been suggested to be a marker of ongoing airway inflammation and poorly controlled disease in asthma. The usefulness of FeNO to monitor asthma control is still debated today. Aim: To assess the validity of FeNO as a marker of asthma control in children with reported use of asthma medication. Methods: Fraction of nitric oxide in exhaled breath was measured in 601 children (aged 412 yr) with reported use of asthma medication in the past 6 months and in 63 healthy non-asthmatic children (aged 512). Asthma control was assessed by the Asthma Control Questionnaire (ACQ). A receiver-operator characteristics (ROC) curve was generated to assess the accuracy of FeNO as a marker for asthma control. Logistic regression analysis was used to study whether clinical, healthcare, medication, and environmental factors are associated with high FeNO levels (>25 ppb). Results: Fraction of nitric oxide in exhaled breath had a poor accuracy to discriminate well-controlled from not well-controlled asthma [area under the ROC curve: 0.56 (95% CI: 0.520.61, p = 0.008)]. In addition, high FeNO (>25 ppb) was associated with lower medication adherence rates (OR: 0.4; 95% CI 0.30.6), fewer antibiotic courses in the past year (OR: 0.6; 95% CI: 0.40.9), fewer leukotriene antagonists use in the past year (OR: 0.4; 95% CI: 0.20.9), and fewer visits to a (pulmonary) pediatrician (OR: 0.6; 95% CI: 0.40.9). Children living in a non-urban environment had more often high FeNO levels (OR: 1.7; 95% CI: 1.12.6). Conclusion: High FeNO is a poor marker of asthma control in children with reported use of asthma medication. Various other factors, including medication adherence and medication use, are associated with increased FeNO levels.

BACKGROUND: The T2206C FCER2 variant was found previously to be associated with IgE levels, exacerbation rates and decreased FCER2 expression in children on inhaled corticosteroids (ICS) participating in a clinical trial. This finding has not been replicated. We sought to replicate the association between the FCER2 gene and exacerbations in children with asthma. In addition, we tested the hypothesis that the T2206C variant may be associated with other markers of steroid resistance such as asthma symptom scores and asthma medication use. METHODS: The influence of the T2206C variant on asthma exacerbations (emergency department visits or hospitalization), symptoms scores and medication use was explored using data from two populations of asthmatic children using ICS: Pharmacogenetics of Asthma medication in Children: Medication with ANti-inflammatory effects study (n = 386) and BREATHE study (n = 939). RESULTS: The T2206C variant was associated with increased risk of asthma-related hospital visits in both cohorts (OR: 1.91, 95% CI: 1.08-3.40), and meta-analysis with previously published results was highly significant (OR: 2.38, 95% CI: 1.47-3.85, P = 0.0004). The FCER2 variant was also associated with increased risk of uncontrolled asthma measured by Asthma Control Questionnaire (OR: 2.64, 95% CI: 1.00-6.98) and was associated with increased daily steroid dose (OR: 2.46, 95% CI: 1.38-4.39). CONCLUSION: The association between the FCER2 T2206C variant and asthma-related hospitalizations in steroid-treated asthma appears robust and may also be associated with other indicators of lack of ICS efficacy such as asthma symptoms and a requirement for higher daily doses of ICS. Our results suggest that the FCER2 T2206C variant might be a useful pharmacogenetic predictor of steroid refractory patients.

Aims Poor adherence with inhaled corticosteroids (ICSs) has been reported frequently and may be associated with uncontrolled asthma. A better understanding of factors influencing adherence may help to achieve higher adherence rates for a larger part of the population, which will eventually lead to better asthma control. The aim of this study was to investigate factors associated with adherence in paediatric ICS users. Methods We included 527 children using ICSs who participated in the Pharmacogenetics of Asthma Medication in Children: Medication with Anti-inflammatory Effects (PACMAN) cohort study. The outcome, a parent-reported adherence, was assessed by using the Medication Adherence Report Scale. Four categories of determinants were studied: child characteristics, family characteristics, medication use (parental beliefs towards medication; using Beliefs about Medicines Questionnaire) and environmental factors. Results Good adherence was observed in 302 children (57%). Increased fractional exhaled nitric oxide values (indication for airway inflammation) were associated with a lower chance of good adherence (OR = 0.25, 95%CI = 0.15–0.41). Parental necessity beliefs about medication were associated with higher adherence (OR = 2.32, 95%CI = 1.59–3.39). Dutch origin was also associated with higher adherence rates (OR = 2.11, 95%CI = 1.09–4.07). Furthermore, younger age (

Seasonal variation in asthma has been widely recognized. The aim of this study was to describe seasonal patterns of asthma symptoms and asthma medication use in a cohort of pediatric asthma medication users and to study determinants of seasonal childhood asthma.For this study, 602 children participating in the Pharmacogenetics of Asthma medication in Children: Medication with Anti-inflammatory effects) cohort were included. Parents were asked about their child's respiratory symptoms and quick-reliever medication use over the past year. Logistic regression analysis was used to study determinants of seasonality in asthma control (the level of disease control based on symptoms, limitations in activities, and rescue medication use).There was a decline in asthma symptoms and asthma medication use during the summer period and a peak occurred from autumn to spring. The prevalence of wheeze ranged from 32% in summer to 56% in autumn. The prevalence of respiratory symptoms and medication use was significantly lower during summer (p.0001). Oral steroids and antibiotics use and strong parental necessity beliefs were associated with uncontrolled asthma, regardless of seasonality. Allergic rhinitis was associated with an increased risk of uncontrolled asthma during spring [odds ratio (OR): 1.9; 95% confidence interval (CI): 1.3-2.8] and summer (OR: 1.9; 95% CI: 1.2-3.0). Eczema was associated with a higher risk of uncontrolled asthma during autumn (OR: 1.5; 95% CI: 1.0-2.2) and winter (OR: 1.3; 95% CI: 1.0-1.9).We showed seasonal patterns in asthma symptoms and medication use. Associations were shown between allergic rhinitis and asthma control during spring/summer and eczema was associated with uncontrolled asthma during autumn/winter. Seasonality in asthma morbidity and health-care use is most likely associated with atopic constitution and viral infections, which are common during fall, winter, and spring.

Background: Several studies have shown that predictors of asthma treatment outcomes differ depending on the definition of the outcome chosen. This provides evidence that different outcomes studied may reflect distinct aspects of asthma control. To assess predictors of asthma control, we need firm outcome phenotypes. The aim of this study was to investigate the association between measurements of current and long-term asthma control. Methods: We included 527 children using inhaled corticosteroids participating in the Pharmacogenetics of Asthma medication in Children: Medication with ANti-inflammatory effects cohort. Current asthma control (previous week) was defined using the Asthma Control Questionnaire. Long-term asthma control was based on Global Initiative for Asthma guidelines. Not well-controlled asthma in a season was defined as =3 of the following items present in a season: (i) day-time or (ii) night-time symptoms, (iii) limitations in activities, and (iv) rescue medication use. Asthma control during (i) the previous season and (ii) the year preceding the pharmacy visit was used as long-term asthma control definitions. Current and long-term asthma control were compared to investigate agreement. Results: Long-term uncontrolled asthma rates were highest in autumn and winter (50%) and lowest in summer (32%) (p

Summary Asthma is one of the most common chronic diseases worldwide. There is a large interindividual variability in response to asthma treatment. Most patients respond well to standard therapy; however, a small proportion of the patients remain symptomatic despite treatment with high dosages of corticosteroids. Uncontrolled asthma leads to a decreased quality of life. Therefore, it is important to identify individuals who will respond poorly to standard asthma medication, especially to standard maintenance therapy with inhaled corticosteroids, at an early stage. Response to anti-inflammatory therapy is generally monitored by the assessment of clinical symptoms, which only partially correlates with underlying airway inflammation. The identification of specific inflammatory biomarkers might help to guide treatment or predict a corticosteroid response more accurately. Some inflammatory biomarkers are already finding their way into clinical practice (e.g. fraction of nitric oxide in exhaled breath), whereas others are predominantly used as a research tool (e.g. profiles of volatile organic compounds). Currently, there is no inflammatory biomarker used in routine clinical practice to predict a corticosteroid response. More knowledge on the underlying biological mechanism(s) of heterogeneous therapeutic responses could help to identify novel biomarkers. This review will focus on inflammatory patterns and genetic variations that may underlie differences in treatment response in patients with asthma, and will provide an overview of inflammatory biomarkers that could potentially serve as response predictors.

Background: Despite existing effective treatment options, asthma is uncontrolled in a considerable proportion of patients. The aim of this study was to identify determinants of uncontrolled asthma at age 8 in children participating in the PIAMA birth cohort study. Methods: One hundred seventy children using inhaled corticosteroids in the previous 12 months at age 8 were included. Uncontrolled asthma was defined as: >= 3 items present in the past month: (1) day-time or (2) night-time asthma symptoms, (3) limitations in activities, (4) rescue medication use, (5) FEV(1)

PURPOSE: This study was conducted to assess the validity of parental reported use of inhaled corticosteroids (ICS) in children. METHODS: ICS users were identified within the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study and the PIAMA pharmacy sub-cohort which is nested within the PIAMA study. Complete medication histories were available for the first 8 years of life for children within the PIAMA pharmacy sub-cohort. Parental reported ICS use was measured by using data from questionnaires. ICS use in the pharmacy records was determined by using the Anatomical Therapeutic Chemical (ATC) codes. The proportion of overall agreement and kappa statistics with their corresponding 95% confidence intervals were calculated to quantify agreement between self-reported medication use and pharmacy prescription data. RESULTS: At all ages overall agreement was very high (>97%) and Cohen's kappa's ranged from 0.80 to 0.88 which also reflects excellent agreement between parental reported use of ICS and pharmacy prescription data. CONCLUSIONS: Our finding suggests that parental report of medication use is a reliable source of data to asses ICS use in children. The questionnaire-based medication data collected within the PIAMA study can be used to study asthma medication use in a large group of children.

The detailed knowledge of the human genome has not fulfilled its promise as yet. It seems fair to say that we are far from treating existing diseases by therapeutic interventions developed on the basis of genetic knowledge. However, pharmacogenetics has shown to be useful in improving our understanding of pharmacotherapy. Industry is starting to embed this knowledge in the design of innovative drugs and there are three important areas of interest: safety, efficacy and target identification. Application of pharmacogenetics e.g. in patient selection are leading to the direction of more personalised medicine. The future will bring more of such applications. However, current knowledge also leads to a more integrated approach of pharmacogenetics as part of systems biology, providing an even more complete image of reality surrounding disease and therapy, including for example environmental factors and behaviour. In addition, collaborative efforts with academic partners are very much welcomed by the pharmaceutical industry and are expected to have a synergistic effect on progression in this field.

Aims: To investigate the effects of genetic variation on treatment response to asthma medication in children and to identify (profiles of) SNPs that characterize response phenotypes. Material & methods: The Pharmacogenetics of Asthma medication in Children: Medication with Anti-inflammatory effects (PACMAN) study was initiated in April 2009 as an observational retrospective pharmacy-based study, including at least 1000 children with asthma medication (aged 4–12 years). Data on respiratory symptoms and medication use behavior will be collected using a questionnaire; complete medication histories will be extracted from the pharmacy information system; additional health information will be requested from the general practitioner; quality of inhalation technique and lung function measurements will be performed and saliva samples for DNA extraction and genotyping will be collected. Two groups of patients will be defined based on questionnaire data and lung function measurements: responders and nonresponders to anti-inflammatory asthma treatment. These two groups will be compared with respect to genetic variation. Corrections will be made for potential confounding factors. Results: The main study end point is treatment response, including asthma control, medication use and exhaled nitric oxide as a measure of airway inflammation. Whilst our focus is on genetic factors, this study allows us to also investigate other treatment response determinants, such as inhalation technique and therapy adherence. Conclusion: Results from the PACMAN study could eventually lead to a more individualized therapy approach. PACMAN will focus on pharmacogenetics of asthma medication in children, while knowledge will be gained of relevant interest to the treatment of the asthma population at large.

Background: Inhaled corticosteroid (ICS) adherence is often suboptimal. Adherence can be estimated using electronic medical records, but studies seldom consider changes over time or distinguish between ICS persistence (duration of use) and implementation (used versus prescribed). Aim: To better understand real-life ICS adherence patterns and how they vary over time within and between patients. Methods: Records were extracted from the Optimum Patient Care Research Database for patients initiating ICS at an index date (ID). Eligible patients (≥6yrs) had ≥3-yrs9 continuous data (1 baseline; 2 outcome); asthma diagnosed ≥1yr before ID, & ≥2 separate ICS and/or SABA prescriptions in each outcome yr. ICS persistence & implementation were estimated over consecutive 6-month intervals. Treatment episodes (persistent use) were calculated in each interval and implementation (MPR) for each episode then examined longitudinally. Results: 13,922 patients received 112,984 ICS prescriptions over 2yrs. For the subgroup of patients with ≥1 ICS prescription in all intervals (52.1%): median(IQR) treatment episode duration was 148(104)days; mean(±SD) MPR was high in the 0-6mnth interval (89.02±0.24%) and decreased on average 0.89±0.08% over the successive intervals, and substantial intra- & interpersonal MPR variance was found (64% & 36%, respectively). Conclusions: Defining ICS adherence as implementation during treatment episodes accounts for non-persistence and results in higher MPRs than typically reported. Consideration must be given to the appropriate definition of adherence when designing adherence studies. The variation in MPR detected over time may allow causal modelling of adherence determinants and effects.

Patients with atopic dermatitis (AD) have a defective skin barrier that even exists in nonlesional skin and is characterized by increased transepidermal water loss (TEWL) as well as enhanced percutaneous penetration of both lipophilic and hydrophilic compounds. The well-established association between filaggrin gene (FLG) loss-of-function mutations and AD supports the hypothesis that an intrinsically impaired skin barrier may be a primary step in the development of AD. To assess the barrier function of uninvolved skin in AD patients carriers of FLG mutations, the percutaneous penetration of polyethylene glycols (PEGs) of various molecular sizes was determined in vivo in AD patients and control subjects using tape stripping of the stratum corneum (SC). The study demonstrated a reduced skin barrier in AD patients, irrespective of FLG genotype, implying that other factors besides FLG loss-offunction mutations modulate skin barrier integrity.

BACKGROUND: The number of patients using methotrexate (MTX) has increased during the last decade. Because of the narrow therapeutic range and potential risks of incorrect use, vigilance is required when dispensing MTX. In 2009, the Royal Dutch Pharmacists Society, in accordance with the Dutch Health Care Inspectorate, published safe MTX dispensing recommendations for community pharmacies. OBJECTIVE: To examine adherence to recommendations aimed at safe MTX dispensing. METHODS: This study was conducted within a convenience sample of 78 community pharmacies belonging to the Utrecht Pharmacy Practice Network for Education and Research (UPPER). Data were collected in May 2011. RESULTS: 95 pharmacists and 337 pharmacy technicians were interviewed to assess self-reported adherence with dispensing recommendations. In addition, medication records for patients using MTX were extracted in 52 pharmacies in order to objectively assess adoption of recommendations. More than 75% of the pharmacists and pharmacy technicians reported to be adherent to 6 of the 11 recommendations. There are variations in reported adherence between team members working in 1 pharmacy; higher adherence rates (> 75%) for the pharmacy team as a whole were only shown for 2 recommendations (recording of day of intake on the label and moment of authorization by the pharmacist). The medication records showed that adherence with working procedures significantly increased: The number of dispensed records with notification of the day of intake on the medication label increased from 9.9% of the records per pharmacy in 2008 to 77.1% in 2010 (P < 0.001). CONCLUSIONS: Dutch community pharmacies seem to be adherent to most safe dispensing recommendations. However, inconsistencies exist between team members that emphasize the importance of addressing this issue and discussing recommendations within the team, as there is still room for improvement to ensure safe dispensing. J Manag Care Pharm. 2014;20(2):194-200

Background: Pharmacy technicians seem to be well equipped to engage in conversations with patients about their experiences and problems with medication, but it is unclear whether or not they systematically explain or demonstrate to patients how to use medication packaging. Objective: To explore to what extent pharmacy technicians identify problems with opening medicine packaging and how they assist patients in solving these problems. Methods: We conducted a cross-sectional study that comprised semistructured interviews, with 31 pharmacy technicians in 31 pharmacies, to assess the occurrence and type of difficulties with packagings and to suggest solutions. Results: All pharmacy technicians recognize the occurrence of packaging problems, though patients rarely report them at the pharmacy counter. Not all pharmacy technicians are familiar with opening all packaging forms, but they all describe ways to find out how to open them, which usually only happens after patients bring up problems. Solutions suggested by the pharmacy technicians include informing and counseling, changing or manipulating the packaging, and providing assisting tools. Conclusions: This study shows that although pharmacy technicians are aware that medication packaging can cause problems and are able to name or find out solutions to all these problems, there is no systematic attention for packaging at drug dispensation in most pharmacies. Discussing the handling of medication packaging should become a fixed part of drug dispensation counseling. Pharmacists should draw up working procedures to support pharmacy technicians in their counseling activities.

Background: Poor understanding of medical instructions or misinterpretations can be a cause for not using medication as prescribed. Previous studies reported misunderstanding of instructions and warnings on drug labels by up to 50 % of the adult population. Objective: The aim of this study was to assess interpretation of drug label instructions in different migrant populations living in the Netherlands. Methods: Interpretation of drug label instructions was examined in four populations of first-generation immigrants from the Antilles (n = 168), Iran (n = 180), Surinam (n = 155), and Turkey (n = 188). Participants were recruited at meeting places (e.g., mosques and educational or cultural centers) for the particular ethnic group. First-year pharmacy students (n = 153) born in the Netherlands were included as reference group. Correct interpretation of drug label instructions was assessed using a survey with questions about five instructions. Results: Only two out of five presented instructions were interpreted correctly by the majority of the respondents of all groups. Higher levels of education, longer duration of stay, and native ethnicity were positively associated with correct interpretation of drug labels (p

A high fraction of nitric oxide in exhaled breath (FeNO) has been suggested to be a marker of ongoing airway inflammation and poorly controlled disease in asthma. The usefulness of FeNO to monitor asthma control is still debated today.To assess the validity of FeNO as a marker of asthma control in children with reported use of asthma medication.Fraction of nitric oxide in exhaled breath was measured in 601 children (aged 4-12 yr) with reported use of asthma medication in the past 6 months and in 63 healthy non-asthmatic children (aged 5-12). Asthma control was assessed by the Asthma Control Questionnaire (ACQ). A receiver-operator characteristics (ROC) curve was generated to assess the accuracy of FeNO as a marker for asthma control. Logistic regression analysis was used to study whether clinical, healthcare, medication, and environmental factors are associated with high FeNO levels (25 ppb).Fraction of nitric oxide in exhaled breath had a poor accuracy to discriminate well-controlled from not well-controlled asthma [area under the ROC curve: 0.56 (95% CI: 0.52-0.61, p = 0.008)]. In addition, high FeNO (25 ppb) was associated with lower medication adherence rates (OR: 0.4; 95% CI 0.3-0.6), fewer antibiotic courses in the past year (OR: 0.6; 95% CI: 0.4-0.9), fewer leukotriene antagonists use in the past year (OR: 0.4; 95% CI: 0.2-0.9), and fewer visits to a (pulmonary) pediatrician (OR: 0.6; 95% CI: 0.4-0.9). Children living in a non-urban environment had more often high FeNO levels (OR: 1.7; 95% CI: 1.1-2.6).High FeNO is a poor marker of asthma control in children with reported use of asthma medication. Various other factors, including medication adherence and medication use, are associated with increased FeNO levels.

Several studies have shown that predictors of asthma treatment outcomes differ depending on the definition of the outcome chosen. This provides evidence that different outcomes studied may reflect distinct aspects of asthma control. To assess predictors of asthma control, we need firm outcome phenotypes. The aim of this study was to investigate the association between measurements of current and long-term asthma control.We included 527 children using inhaled corticosteroids participating in the Pharmacogenetics of Asthma medication in Children: Medication with ANti-inflammatory effects cohort. Current asthma control (previous week) was defined using the Asthma Control Questionnaire. Long-term asthma control was based on Global Initiative for Asthma guidelines. Not well-controlled asthma in a season was defined as ≥ 3 of the following items present in a season: (i) day-time or (ii) night-time symptoms, (iii) limitations in activities, and (iv) rescue medication use. Asthma control during (i) the previous season and (ii) the year preceding the pharmacy visit was used as long-term asthma control definitions. Current and long-term asthma control were compared to investigate agreement.Long-term uncontrolled asthma rates were highest in autumn and winter (50%) and lowest in summer (32%) (p0.05). Overall agreement between current and long-term asthma control was limited (66% for previous season and 68% for previous year).Congruence between current and long-term asthma control was limited. Furthermore, we showed significant seasonal differences. It is therefore important to calculate asthma control over a longer period of time, instead of using current asthma control as indicator.

Despite existing effective treatment options, asthma is uncontrolled in a considerable proportion of patients. The aim of this study was to identify determinants of uncontrolled asthma at age 8 in children participating in the PIAMA birth cohort study.One hundred seventy children using inhaled corticosteroids in the previous 12 months at age 8 were included. Uncontrolled asthma was defined as: ≥3 items present in the past month: (1) day-time or (2) night-time asthma symptoms, (3) limitations in activities, (4) rescue medication use, (5) FEV(1)0% predicted and (6) unscheduled physician visits because of asthma. Binomial regression was performed to study five groups of determinants representing asthma control: child and parental characteristics, environmental factors, therapy adherence and parental perception towards medication use (Beliefs about Medicines Questionnaire).Seventy seven children (45%) had uncontrolled asthma. Low maternal education (RR 1.6, 95% CI: 1.0-2.4) was associated with uncontrolled asthma. Parental necessity beliefs about medication use to maintain present and future health and parental concerns about potential adverse consequences of medication were also associated with uncontrolled asthma (RR 1.6, 95% CI: 1.1-2.2; and 1.6, 95% CI: 1.0-2.5, respectively).Environmental factors and therapy adherence were not associated with asthma control. In our cohort, uncontrolled asthma is associated with low maternal education and with strong parental beliefs about medication necessity and higher concern about potential side effects of medication.

Asthma is a chronic airway disease with a relatively high prevalence. Although the etiology of asthma is still not fully clear, there are effective treatments available. The treatment strategy for asthma consists of two steps: maintenance therapy with anti-inflammatory agents (inhaled corticosteroids and/or leukotriene antagonists) to reduce airway inflammation and retain proper lung function and secondly, the use of beta-agonists for quick symptomatic relief. Furthermore, oral steroids are used to treat acute exacerbations. There are large differences in response to drug therapy. This may be due to many factors, such as severity and type of disease, compliance, co-morbidity, co-medication (drug-drug interactions), environmental exposures and age. However, calculations of repeatability of treatment response suggest that part of this variance in response to pharmacotherapy could be due to genetic factors. Pharmacogenetics may explain the inter-individual variability in drug response due to genetic variation. Pharmacogenetics is a relatively new emerging research field that provides the opportunity to discover associations between genetic variation and response to a variety of drugs. This review will discuss the pharmacogenetics of antiinflammatory agents (corticosteroids and leukotriene antagonists) used in the treatment of asthma.

Response to pharmacotherapy can be highly variable amongst individuals. Pharmacogenomics may explain the interindividual variability in drug response due to genetic variation. However, besides genetics, many other factors can play a role in the response to pharmacotherapy, including disease severity, co-morbidity, environmental factors, therapy adherence and co-medication use. Better understanding of these factors and inter-relationships should bring about a much more effective approach to disease management. Systems biology that studies organisms as integrated and interacting networks of genes, proteins and biochemical reactions can contribute to this. Organisms are no longer studied part by part, but in a more integral manner. Integration of the genetic data with intermediate and end point phenotypic characterization may prove essential to define the inherent nature of drug effects. Therefore, in the future, a multidisciplinary systems-based approach will be necessary to deal with the bulk of the biological data that is available and, ultimately, to reach the goal of personalized prescribing.

Rapid response systems (RRSs) have been introduced in hospitals to prevent delays in medical management of care for patients whose clinical status deteriorates unexpectedly. An RRS consists of three limbs and its implementation affects the entire hospital organisation. This paper aims to provide insights into the approaches used by Dutch hospitals for RRS implementation and the factors influencing the approaches chosen. Starting from a conceptual framework emphasising the importance of the process, content and context for innovation implementation, our qualitative study shows the breadth of approaches used in practice. In-depth insights into the implementation process, content and context – as well as the relationships between them – extend existing theory on RRS implementation and will help hospitals tailor their implementation approach to organisational characteristics.

Background: Filaggrin (FLG) mutations result in reduced stratum corneum (SC) natural moisturizing factor (NMF) components and consequent increased SC pH. Because higher pH activates SC protease activity, we hypothesized an enhanced release of proinflammatory IL-1 cytokines from corneocytes in patients with atopic dermatitis (AD) with FLG mutations (AD(FLG)) compared with that seen in patients with AD without these mutations (AD(NON-FLG)). Objectives: We sought to investigate SC IL-1 cytokine profiles in the uninvolved skin of controls and patients with AD(FLG) versus patients with AD(NON-FLG). We also sought to examine the same profiles in a murine model of filaggrin deficiency (Flg(ft)/Flg(ft) [Flg(delAPfal)] mice). Methods: One hundred thirty-seven patients were studied. NMF levels were ascertained using confocal Raman spectroscopy; transepidermal water loss and skin surface pH were measured. IL-1 alpha, IL-1 beta, IL-18, IL-1 receptor antagonist (IL-1RA), and IL-8 levels were determined in SC tape strips from 93 patients. All subjects were screened for 9 FLG mutations. Flg(ft)/Flg(ft) (Flg(delAPfal)) mice, separated from maFlg(ft)/maFlg(ft) (flaky tail) mice, were used for the preparation and culture of primary murine keratinocytes and as a source of murine skin. RT-PCR was performed using primers specific for murine IL-1 alpha, IL-1 beta, and IL-1RA. Results: SC IL-1 levels were increased in patients with AD(FLG); these levels were inversely correlated with NMF levels. NMF values were also inversely correlated with skin surface pH. Skin and keratinocytes from Flg(ft)/Flg(ft) mice had upregulated expression of IL-1 beta and IL-1RA mRNA. Conclusions: AD(FLG) is associated with an increased SC IL-1 cytokine profile; this profile is also seen in a murine homologue of filaggrin deficiency. These findings might have importance in understanding the influence of FLG mutations on the inflammasome in the pathogenesis of AD and help individualize therapeutic approaches. (J Allergy Clin Immunol 2012;129:1031-9.)