The association between a genetic risk score for allergy and the risk of developing allergies in childhood-Results of the WHISTLER cohort.

BACKGROUND: Several genetic variants have been associated with the susceptibility to allergic disease in adults, but it remains unclear whether these genetic variants are also associated with the onset of allergic disease early in life. The aim of this study was to develop a genetic risk score (GRS) for allergy based on findings in adults and study its predictive capacity for allergy in children. METHODS: A GRS was constructed based on 10 SNPs previously associated with allergies in adults. The GRS was tested in children who participated in a population-based newborn cohort (WHISTLER) and were followed from birth to school age. Logistic regression analysis was used to study the association between the GRS and the parental-reported allergies at age 5 (based on a reported allergy to ≥1 of the following allergens: pollen, house dust mites, or pets). A Cox regression model was used to study the association between GRS and a physician-diagnosed allergy during follow-up (allergic conjunctivitis, allergic rhinitis, and eczema/dermatitis). Cohen's kappa coefficient was calculated to study the agreement between physician-diagnosed allergy and parental-reported allergy at age 5. RESULTS: The GRS was significantly associated with parental-reported allergy (odds ratio: 15.9, 95% confidence interval (CI): 1.07-233.73) at age 5, as well as with a physician-diagnosed allergy during follow-up (hazard ratio: 1.89, 95% CI: 1.05-3.41). The overall agreement between physician-diagnosed and parental-reported allergies was 70.5% (kappa: 0.10, 95% CI: 0.03-0.18). CONCLUSIONS: An adult-derived GRS for allergy predicts the risk of developing allergies in childhood.

High incidence of oral corticosteroids prescriptions in children with asthma in early childhood.

OBJECTIVE: Severe asthma exacerbations are often treated with short courses of oral corticosteroids (OCS). This study assessed the incidence of OCS being prescribed in asthmatic children of various age groups and calculated their chances of receiving subsequent OCS prescriptions. METHODS: Longitudinal Dutch community pharmacy data of 2272 children who were regular users of asthma medication was analyzed retrospectively. Incidence rates for first, second and third prescriptions of OCS were calculated, stratified by age and sex. Probabilities of receiving first, second or third OCS prescriptions were assessed with Kaplan-Meier analysis. RESULTS: Incidence rates for first OCS prescriptions were 4.5 for the 1(st) year of life per 100 person-years (100PY); 3.9 for the 2(nd); 4.6 for the 3(rd); 4.2 for the 4(th), and 4.7 for the 5(th) year of life per 100PY. This was relatively high compared to incidence rates for children between the ages of 6 and 11 (ranging between 2.2 per 100PY (age 9) and 3.7(age 11)). Incidence rates for second and third OCS prescriptions were very high: 78.2(95%CI: 45.0-123.7) and 241.2(95%CI: 81.2-583.4) per 100PY for infants, respectively. The chances of receiving a first OCS prescription was higher in males (P value < 0.01). CONCLUSIONS: In the Netherlands, the incidence of OCS being prescribed to children being treated with asthma medication in early childhood is relatively high for first OCS prescriptions and extremely high for second and third OCS prescriptions compared to other ages. Furthermore, there is a high probability of receiving a further OCS prescription shortly after an OCS prescription.

Characteristics and severity of asthma in children with and without atopic conditions: a cross-sectional study.

BACKGROUND: Childhood allergic diseases have a major impact on a child's quality of life, as well as that of their parents. We studied the coexistence of reported allergies in children who use asthma medication. Additionally, we tested the hypothesis that asthma severity is greater among children with certain combinations of co-morbid allergic conditions. METHODS: For this cross-sectional study, 703 children (ages 4 to 12 years) from the PACMAN cohort study were selected. All of the children were regular users of asthma medication. The study population was divided into nine subgroups according to parental-reported allergies of the child (hay fever, eczema, food allergy or combinations of these). In order to assess whether these subgroups differed clinically, the groups were compared for child characteristics (age, gender, family history of asthma), asthma exacerbations in the past year (oral corticosteroids (OCS) use; asthma-related emergency department (ED) visits), asthma control, fractional exhaled nitric oxide level (FeNO), and antihistaminic usage. RESULTS: In our study, 79.0% of the parents reported that their child suffered from at least one atopic condition (hay fever, food allergy and eczema), and one quarter of the parents (25.6%) reported that their child suffered from all three atopic conditions. Having more than one atopic condition was associated with an increased risk of OCS use (OR = 3.3, 95% CI = 1.6 - 6.6), ED visits (OR = 2.3, 95% CI = 1.2 - 4.6) in the past year and inadequate short term asthma control (OR = 1.9, 95% CI = 1.3 - 2.8). CONCLUSIONS: Children who use asthma medication often also have other allergic conditions. Parental reported allergies were associated with a higher risk of more severe asthma (more asthma complaints and more asthma exacerbations).

The fiduciary obligation of the physician-researcher in phase IV trials.

BACKGROUND: In this manuscript, we argue that within the context of phase IV, physician-researchers retain their fiduciary obligation to treat the patient-participants. DISCUSSION: We first clarify why the perspective that research ethics ought to be differentiated from clinical ethics is not applicable in phase IV, and therefore, why therapeutic orientation is most convivial in this phase. Next, assuming that ethics guidelines may be representative of common morality, we show that ethics guidelines see physician-researchers primarily as physicians and only secondarily as researchers. We then elaborate on what a fiduciary obligation is and how some of the obligations are default duties. Lastly, we look at the fiduciary obligation of the physician-researcher in phase IV interventional trials. CONCLUSION: The fiduciary obligation to treat is not as easily waived as in earlier trials. Assuming the entwinement of research and practice in phase IV, physician-researchers, in collaboration with other researchers, investigators, and research ethics committees, should ensure that in terms of study design, methodology, and research practice, the therapeutic value of the research to the patient-participants is not diminished.

The cloudy crystal ball of cost-effectiveness studies.

Despite the use of identical clinical trial data (Anastrazole, Tamoxifen, Alone or in Combination for the adjuvant treatment of postmenopausal women with localised hormone receptor-positive breast cancer data), not dependent on differences between countries, the outcome of 11 published cost-effectiveness analyses varied more than 20-fold. The observed wide variation in predicted life-years gained (a parameter derived from clinical trial data) demonstrates that authors used substantially different methods for handling the same data. We therefore consider it to be of utmost importance to strive for standardization of and better guidance for disease-specific modeling in economic evaluations.

Phase IV non-inferiority trials and additional claims of benefit.

BACKGROUND: Non-inferiority (NI) trials in drug research are used to demonstrate that a new treatment is not less effective than an active comparator. Since phase IV trials typically aim at informing a clinical decision, the value of a phase IV non-inferiority trial hinges also on its clinical relevance. In such trials, clinical relevance would refer to the added benefit claims of a specific drug, apart from efficacy, relative to its comparator drug in the trial. METHODS: In this study, we reviewed 41 phase IV trials and extracted information on whether the authors mentioned any additional benefit beyond the NI (efficacy) claim of the drug and whether the additional benefit was proven in the trial. We checked whether the additional claim was based on descriptions only or on formal statistical analyses. RESULTS: Our results showed that 22 out of the 41 NI trials mentioned additional benefit of the test drug and most of these claims were related to the safety profile. Of all the post-authorization NI trials that claimed additional benefit, 10 out of 22 NI trials used formal statistical analyses to show additional benefit, and only one included a sample size calculation for the additional benefit prior to the trial. CONCLUSION: We conclude that there is room for improvement in terms of designing phase IV NI trials with added benefit claims and in proving these additional claims.

Inflammatory phenotypes underlying uncontrolled childhood asthma despite inhaled corticosteroid treatment: rationale and design of the PACMAN2 study.

BACKGROUND: The diagnosis of childhood asthma covers a broad spectrum of pathological mechanisms that can lead to similarly presenting clinical symptoms, but may nonetheless require different treatment approaches. Distinct underlying inflammatory patterns are thought to influence responsiveness to standard asthma medication. METHODS/DESIGN: The purpose of the PACMAN2 study is to identify inflammatory phenotypes that can discriminate uncontrolled childhood asthma from controlled childhood asthma by measures in peripheral blood and exhaled air. PACMAN2 is a nested, case-control follow-up study to the ongoing pharmacy-based "Pharmacogenetics of Asthma medication in Children: Medication with Anti-inflammatory effects" (PACMAN) study. The original PACMAN cohort consists of children aged 4-12 years with reported use of asthma medication. The PACMAN2 study will be conducted within the larger PACMAN cohort, and will focus on detailed phenotyping of a subset of the PACMAN children. The selected participants will be invited to a follow-up visit in a clinical setting at least six months after their baseline visit based on their adherence to usage of inhaled corticosteroids, their asthma symptoms in the past year, and their age (≥ 8 years). During the follow-up visit, current and long-term asthma symptoms, medication use, environmental factors, medication adherence and levels of exhaled nitric oxide will be reassessed. The following measures will also be examined: pulmonary function, exhaled volatile organic compounds, as well as inflammatory markers in peripheral blood and blood plasma. Comparative analysis and cluster-analyses will be used to identify markers that differentiate children with uncontrolled asthma despite their use of inhaled corticosteroids (ICS) (cases) from children whose asthma is controlled by the use of ICS (controls). DISCUSSION: Asthmatic children with distinct inflammatory phenotypes may respond differently to anti-inflammatory therapy. Therefore, by identifying inflammatory phenotypes in children with the PACMAN2 study, we may greatly impact future personalised treatment strategies, uncover new leads for therapeutic targets and improve the design of future clinical studies in the assessment of the efficacy of novel therapeutics.

Exhaled NO is a poor marker of asthma control in children with a reported use of asthma medication: a pharmacy-based study.

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 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). 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: 0.52-0.61, 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). 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.

Reviewing the cost-effectiveness of endocrine early breast cancer therapies: influence of differences in modeling methods on outcomes.

OBJECTIVES: The purpose of this systematic review is primarily to identify published cost-effectiveness analyses and cost-utility analyses of endocrine therapies for the treatment of early breast cancer. A secondary objective is to identify whether differences in seven modeling characteristics are related to differences in outcome of these cost-effectiveness and cost-utility analyses. METHODS: A systematic literature review was conducted to identify peer-reviewed full economic evaluations of endocrine treatments of early breast cancer published in the English language between 2000 and December 2010. Information from these publications was abstracted regarding outcome, quality, and modeling methods. RESULTS: We identified 20 economic evaluations comprising 5 different endocrine therapeutic strategies, which are all assessed more then once. The incremental cost-effectiveness ratios (ICERs) of the reported outcomes varied widely for identical therapies. For anastrazole compared to tamoxifen, incremental life-years gained even ranged from 0.16 to 0.550 with an ICER ranging from €3,958 to €75,331. Incremental quality-adjusted life-years (QALYs) gained ranged from 0.092 to 0.378 with a cost per QALY gained varying from €3,696 to €120,265. These large differences in outcome were related to different modeling methods, with differences in time horizon and use of a carryover effect as most prominent causes. CONCLUSION: Despite similar comparators and logical differences due to transferability issues, the outcomes of the included studies varied widely. To increase comparability and transparency of pharmacoeconomic evaluations, standardization of modeling methods for different therapeutic groups/diseases and the availability of a detailed and complete description of the model used in the evaluation is advocated. Recommendations for standardization in modeling treatment strategies in early breast cancer are presented.

The risk-benefit task of research ethics committees: an evaluation of current approaches and the need to incorporate decision studies methods.

BACKGROUND: Research ethics committees (RECs) are tasked to assess the risks and the benefits of a trial. Currently, two procedure-level approaches are predominant, the Net Risk Test and the Component Analysis. DISCUSSION: By looking at decision studies, we see that both procedure-level approaches conflate the various risk-benefit tasks, i.e., risk-benefit assessment, risk-benefit evaluation, risk treatment, and decision making. This conflation makes the RECs' risk-benefit task confusing, if not impossible. We further realize that RECs are not meant to do all the risk-benefit tasks; instead, RECs are meant to evaluate risks and benefits, appraise risk treatment suggestions, and make the final decision. CONCLUSION: As such, research ethics would benefit from looking beyond the procedure-level approaches and allowing disciplines like decision studies to be involved in the discourse on RECs' risk-benefit task.

Uncontrolled asthma at age 8: the importance of parental perception towards medication.

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) <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). RESULTS: 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). CONCLUSIONS: 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.

Limited agreement between current and long-term asthma control in children: the PACMAN cohort study.

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 < 0.05). Overall agreement between current and long-term asthma control was limited (66% for previous season and 68% for previous year). CONCLUSION: 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.

Asthma symptoms in pediatric patients: differences throughout the seasons.

INTRODUCTION: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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.

Inhaled corticosteroid adherence in paediatric patients: the PACMAN cohort study.

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 (< 6 years) was associated with better adherence (OR = 1.62, 95%CI = 1.02-2.59). CONCLUSIONS: Increased airway inflammation was associated with lower ICS adherence, which underlines the need of good adherence to reach disease control. Our results suggest that by improving knowledge, especially in ethnic minorities, and by stimulating positive parental perception towards the nature of the disease, the characteristics of the prescribed drugs and the use of medications, better adherence and as a result better asthma control could be reached.

Asthma medication use in infancy: determinants related to prescription of drug therapy.

BACKGROUND: Little is known about factors that determine prescribing of asthma therapy in infancy. OBJECTIVE: To describe factors related to the initiation and refill of asthma therapy in infancy. METHODS: This study included 1202 infants who participated in a prospective birth cohort study: the 'Wheezing Illnesses Study Leidsche Rijn (WHISTLER)'. Outcomes, asthma therapy initiation and refill, were assessed using prescription data. Logistic regression analysis was used to study determinants of therapy initiation in two groups: total population and infants with a respiratory system symptom diagnosis. In addition, determinants of refilling prescriptions were studied in infants who started therapy in their first year of life. RESULTS: Fifteen per cent of all infants started asthma therapy in their first year of life. Respiratory symptoms were an important driver of both initiation and refill of prescriptions. In the total population, therapy initiation was associated with male gender [odds ratio (OR): 1.6, 95% confidence interval (CI): 1.1-2.6], day-care attendance (OR: 1.6, 95% CI: 1.0-2.5) and breastfeeding (OR: 0.6, 95% CI: 0.3-1.0). For infants with a respiratory system symptom diagnosis, day-care attendance was associated with an increased chance of therapy initiation (OR: 5.3, 95% CI: 1.8-16.2) and breastfeeding was associated with a lower chance of starting therapy (OR: 0.4, 95% CI: 0.1-1.1). Dutch children had a higher chance of refilling prescriptions in infancy (OR: 5.3, 95% CI: 1.1-26.8). CONCLUSIONS: Apart from other factors involved, the principal reason for initiation and refill of asthma therapy in infancy was the presence of respiratory symptoms. This appeared the only reason to prescribe medication and physicians are not distracted by other factors.

Patterns of asthma medication use: early asthma therapy initiation and asthma outcomes at age 8.

Wheeze has many underlying pathophysiologies in childhood, but is the main reason for anti-asthma drugs prescription. This study was conducted to describe asthma medication use patterns among children in their first eight years of life. Longitudinal medication use data from 777 children participating in the PIAMA study were used. Medication patterns were described for four groups that started therapy before the third birthday, when the peak in prescriptions occurred in our cohort; short-acting ß-agonists (SABA), inhaled corticosteroids (ICS), SABA + ICS or none of these. One third (n = 255) of the children received a first SABA or ICS prescription before age 8. Only three children (1.2%) used medication continuously during follow-up. Of the children who started SABA, 53.8% discontinued within 1-2 years. Of the children who started ICS before age 3, 42.1% discontinued within 1-2 years and 31.6% received additional SABA. 41.5% of the children who started SABA + ICS used this short-term (≤1 -2 years) and 21.5% long-term (≥ 3 years). Fifteen percent of children who did not start asthma therapy in their first 3 years of life did receive prescriptions between age 3 and 8. Children prescribed SABA + ICS before age 3 had the highest prevalence of hyper responsiveness at age 8, and similar prevalence of atopy as the other groups. Asthma medication is prescribed frequently in the first 8 years of life, particularly before age 3, and only few children use it continuously. ICS and SABA prescription occurs especially in those who were more likely to develop signs of asthma at age 8.

High agreement between parental reported inhaled corticosteroid use and pharmacy prescription data.

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.

Patients' understanding of the reasons for starting and discontinuing inhaled corticosteroids.

AIM: Although early discontinuation of treatment in new users of inhaled corticosteroids (ICS) has been widely discussed, the reasons for stopping have not been investigated in depth. We aimed to describe reasons for discontinuation from a patient's perspective in relation to their experience of symptoms at the time of the investigation. METHODS: A cross-sectional study among new users that discontinued ICS use in the Netherlands was performed. Patients were interviewed by telephone, aiming to identify the symptoms for which they were prescribed ICS, the reasons for discontinuing treatment and the respiratory symptoms patients still experienced at the time of the survey. In addition, automated dispensing records of all patients were retrieved. RESULTS: From 287 eligible patients, 230 (80.1%) were interviewed. Only 22 patients (9.6%) mentioned asthma as the reason for a first ICS prescription. A decrease in symptoms was the main reason for discontinuation (45%). Thirty patients (13%) reported clinically significant residual symptoms. These patients reported more seasonal variation of symptoms and were more often prescribed short-acting beta(2)-agonists. CONCLUSIONS: The majority of patients mentioned a wide range of symptoms and conditions, other than asthma or chronic obstructive pulmonary disease, as the reason for the start of ICS therapy. Most of these conditions may be expected to be of short duration. Not surprisingly a decrease in symptoms was the main, and justifiable, reason for discontinuing ICS. However, a non-negligible proportion of patients reported residual symptoms that suggest the need of continued ICS use. Physicians and pharmacists could cooperate in identifying those patients for which ICS are really indicated and motivate them to continue the use of ICS.

Beliefs about medicines predict refill adherence to inhaled corticosteroids.

OBJECTIVE: Despite the importance of the chronic use of inhaled corticosteroids (ICS) in maintaining asthma control, reported adherence varies between 40% and 60%. The Beliefs about Medicines Questionnaire (BMQ) has been shown to correlate with self-reported adherence. The aim of this study is to investigate whether beliefs about ICS (necessity and concerns), as measured by the BMQ, relate to adherence objectively measured by prescription-refill records. METHODS: In a cross-sectional study of patients aged 18-45 years who filled at least two ICS prescriptions in 11 community pharmacies in The Netherlands, perceptions of ICS were assessed using the BMQ. Additionally, self-reported adherence was assessed using the Medication Adherence Report Scale. ICS prescription-refill adherence rates for a 12-month period prior to the survey were obtained from automated pharmacy dispensing records. Four attitudinal groups were defined using the necessity and concerns constructs. Statistical tests were used to examine associations between ICS adherence (assessed by subjective self-report and objective pharmacy records), specific beliefs about and attitudes towards ICS, and more general beliefs about pharmaceuticals. RESULTS: Questionnaires were returned by 238 patients (51.1%). Both self-reported adherence (r=.38) and adherence by pharmacy records (rho=0.32) correlated with ICS necessity beliefs and concerns. Patients defined as skeptical, indifferent, ambivalent, or accepting, on the basis of these constructs, differed with respect to both their attitudes towards medicines in general and their adherence to medication. CONCLUSIONS: Patients' beliefs about ICS correlate not only with adherence by self-report but also with a more objective measure of medication adherence calculated by pharmacy dispensing records. The necessity-concerns constructs offer a potentially useful framework to help clinicians elicit key treatment beliefs influencing adherence to ICS.