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PURPOSE: Diagnosing asthma in children with asthmatic symptoms remains a challenge, particularly in preschool children. This challenge creates an opportunity for variability in prescribing. The aim of our study was to investigate how and to what degree patient, family, and physician characteristics influence prescribing of asthma medication in children. METHODS: We undertook a multilevel population-based study using the second Dutch national survey of general practice (DNSGP-2), 2001. Participants were 46,371 children aged 1 to 17 years belonging to 25,537 families registered with 109 general practitioners. Using a multilevel multivariate logistic regression analysis with 3 levels, our main outcome measure was the prescribing of asthma medication, defined as at least 1 prescription for beta(2)-adrenergic agonists, inhaled corticosteroids, cromones, or montelukast during the 1-year study period. RESULTS: We identified characteristics significantly associated with prescribing asthma medication on all 3 levels (child, family, and physician). The variance in prescribing among physicians was significantly higher with children who were younger than 6 years than with children aged 6 years and older (95% CI, 3.5%-25.2% vs 2.4%-13.4%). Several diagnoses other than asthma and asthmatic complaints were strongly associated with prescribing asthma medication, including bronchitis/bronchiolitis (OR = 9.04; 95% CI, 7.57-10.8) and cough (OR = 6.51; 95% CI, 5.68-7.47). CONCLUSIONS: Our study shows a much higher variance in prescribing patterns among general practitioners for children younger than 6 years compared with older children, which could be a direct result of the diagnostic complexities found in young children with asthmatic symptoms. Thus diagnostic gaps may lead to more physician-driven prescribing irrespective of the clinical context.

PURPOSE: Diagnosing asthma in children with asthmatic symptoms remains a challenge, particularly in preschool children. This challenge creates an opportunity for variability in prescribing. The aim of our study was to investigate how and to what degree patient, family, and physician characteristics influence prescribing of asthma medication in children. METHODS: We undertook a multilevel population-based study using the second Dutch national survey of general practice (DNSGP-2), 2001. Participants were 46,371 children aged 1 to 17 years belonging to 25,537 families registered with 109 general practitioners. Using a multilevel multivariate logistic regression analysis with 3 levels, our main outcome measure was the prescribing of asthma medication, defined as at least 1 prescription for beta(2)-adrenergic agonists, inhaled corticosteroids, cromones, or montelukast during the 1-year study period. RESULTS: We identified characteristics significantly associated with prescribing asthma medication on all 3 levels (child, family, and physician). The variance in prescribing among physicians was significantly higher with children who were younger than 6 years than with children aged 6 years and older (95% CI, 3.5%-25.2% vs 2.4%-13.4%). Several diagnoses other than asthma and asthmatic complaints were strongly associated with prescribing asthma medication, including bronchitis/bronchiolitis (OR = 9.04; 95% CI, 7.57-10.8) and cough (OR = 6.51; 95% CI, 5.68-7.47). CONCLUSIONS: Our study shows a much higher variance in prescribing patterns among general practitioners for children younger than 6 years compared with older children, which could be a direct result of the diagnostic complexities found in young children with asthmatic symptoms. Thus diagnostic gaps may lead to more physician-driven prescribing irrespective of the clinical context.

BACKGROUND: In pre-school children a diagnosis of asthma is not easily made and only a minority of wheezing children will develop persistent atopic asthma. According to the general consensus a diagnosis of asthma becomes more certain with increasing age. Therefore the congruence between asthma medication use and doctor-diagnosed asthma is expected to increase with age. The aim of this study is to evaluate the relationship between prescribing of asthma medication and doctor-diagnosed asthma in children age 0-17. METHODS: We studied all 74,580 children below 18 years of age, belonging to 95 GP practices within the second Dutch national survey of general practice (DNSGP-2), in which GPs registered all physician-patient contacts during the year 2001. Status on prescribing of asthma medication (at least one prescription for beta2-agonists, inhaled corticosteroids, cromones or montelukast) and doctor-diagnosed asthma (coded according to the International Classification of Primary Care) was determined. RESULTS: In total 7.5% of children received asthma medication and 4.1% had a diagnosis of asthma. Only 49% of all children receiving asthma medication was diagnosed as an asthmatic. Subgroup analyses on age, gender and therapy groups showed that the Positive Predictive Value (PPV) differs significantly between therapy groups only. The likelihood of having doctor-diagnosed asthma increased when a child received combination therapy of short acting beta2-agonists and inhaled corticosteroids (PPV = 0.64) and with the number of prescriptions (3 prescriptions or more, PPV = 0.66). Both prescribing of asthma medication and doctor-diagnosed asthma declined with age but the congruence between the two measures did not increase with age. CONCLUSION: In this study, less than half of all children receiving asthma medication had a registered diagnosis of asthma. Detailed subgroup analyses show that a diagnosis of asthma was present in at most 66%, even in groups of children treated intensively with asthma medication. Although age strongly influences the chance of being treated, remarkably, the congruence between prescribing of asthma medication and doctor-diagnosed asthma does not increase with age.

The use of medicines in children has been receiving more attention during recent years. The aim of this thesis was to gain more insight in the process of medicines’ use in children by studying use of asthma medication. Evaluation of asthma medication use in children is challenging because of diagnostic difficulties in paediatric asthma and questions regarding effectiveness of medication. It thus requires a comprehensive approach taking into account the whole process of prescribing and treatment changes over time and family and prescriber influences as well as the age of the child. We found that the likelihood of receiving asthma medication is very high, especially in young children and is subject to physician and family influences. Uncertainties regarding diagnosis and treatment lead to use of trials of medication and may lead to more physician driven prescribing irrespective of the clinical context. Improvement of asthma medication therapy in children is warranted, but is highly dependent on better diagnostics and results from effectiveness studies. On the other hand the combined findings of our studies show that although many children receive asthma medication without an asthma diagnosis, use of these medicines is often a one-off event. We saw a clear difference in duration and intensity of treatment between children with and without asthma at a later age. Asthma medication use in children can be improved on many issues but is not as random as it may seem sometimes.

The use of medicines in children has been receiving more attention during recent years. The aim of this thesis was to gain more insight in the process of medicines’ use in children by studying use of asthma medication. Evaluation of asthma medication use in children is challenging because of diagnostic difficulties in paediatric asthma and questions regarding effectiveness of medication. It thus requires a comprehensive approach taking into account the whole process of prescribing and treatment changes over time and family and prescriber influences as well as the age of the child. We found that the likelihood of receiving asthma medication is very high, especially in young children and is subject to physician and family influences. Uncertainties regarding diagnosis and treatment lead to use of trials of medication and may lead to more physician driven prescribing irrespective of the clinical context. Improvement of asthma medication therapy in children is warranted, but is highly dependent on better diagnostics and results from effectiveness studies. On the other hand the combined findings of our studies show that although many children receive asthma medication without an asthma diagnosis, use of these medicines is often a one-off event. We saw a clear difference in duration and intensity of treatment between children with and without asthma at a later age. Asthma medication use in children can be improved on many issues but is not as random as it may seem sometimes.

In this thesis we aimed to further deepen knowledge on factors associated with nonadherence to provide means to improve adherence. We evaluated several methods of assessing adherence. At first, we evaluated the accuracy of the Medication Adherence Rating Scale (MARS), a structured method for eliciting patients’ reports of adherence, in identifying low adherence with ICS using prescription refill data as a reference. We found that the MARS as a self-reported measure of adherence is useful as a screening tool for identifying patients with low adherence to ICS. Furthermore, we investigated the use of ICS during a ten-year period to describe medication use as a continuum. With this approach we could expand research further than identifying those patients who persist and also investigate recurring episodes of non-persistence. We found that patients most frequently discontinued in the year after start. In conditions like asthma, self-management allows patients, depending on their severity of disease, to adjust the timing and dosing of inhaled corticosteroids (ICS). Why patients behave in a particular way or make certain decisions is not easy to deduce from the pharmacy records available in most studies on adherence. In Chapters 3 and 4 we evaluated possible driving forces behind certain adherence behaviour. Discontinuation of ICS treatment has been widely discussed and some investigators had found similar results as ours, in new users of other medication. However, few studies investigated diagnoses assigned to new users of medication by the physician and it’s influence on adherence. Furthermore to the best of our knowledge, patient and physician reasons for discontinuing have not been investigated in depth. Therefore we aimed to describe reasons for prescribing and discontinuing ICS from a patient perspective (Chapter 3.1) with clinical information, obtained from the GP, added (Chapter 3.2). To our surprise patients primarily mentioned a variety of self-limiting symptoms like cough and dyspnoea or conditions like common cold, acute bronchitis and pneumonia for which ICS are not indicated. General practitioners stated to be certain on a diagnosis of asthma in almost one quarter of their patients. Moreover, in almost 30% of their patients they had a suspicion of asthma. The discrepancy between the opinions of GPs and patients indicates that the communication of the reason for prescribing drugs like ICS should be improved. As knowledge of treatment and actions of a drug have been shown to influence adherence and self-management we investigated in chapter 3.3 the knowledge of ICS’ mode of actions among new users of ICS that discontinued, and whether they were instructed on the use of their inhaler. The majority of patients were not aware of ICS’ actions. The way in which patients are instructed on their inhalers should be improved, especially giving attention to knowledge on the anti-inflammatory effects of ICS. Previously the beliefs about medicines questionnaire (BMQ) was shown to correlate with self-reported adherence. In chapter 4.1 we investigated whether beliefs about ICS, measured by the BMQ (necessity and concerns), relate to adherence objectively measured by prescription refill records. Based on the relations found we conclude that the BMQ specific and general could be used to identify specific barriers on the use of medication of individual patients. For this purpose we defined four attitudinal groups, based on the BMQ necessity and concerns constructs, in an attempt to translate particular beliefs to certain types of patients and facilitate medical decision making by recognising patients who will most likely be non-adherent. The attitudinal groups differ in perceived harmfulness towards medicines in general and in adherence by self-report and pharmacy data. In chapter 4.2 we evaluated whether the level of disease control influenced the relation between the BMQ and adherence since it has been hypothesized, e.g. within Leventhal’s common-sense model, that symptom experience might influence adherence or mediate the relation between adherence and perception. We found that in patients with less adequate disease control more attention for beliefs and symptom control is needed, as the correlations between perceived need of ICS and adherence are weakest in patients with lowest disease control. Symptom control can be evaluated (in the pharmacy) by use of the Asthma Control Questionnaire (ACQ) and use of short-acting beta2-agonists (SABA). In this way it can be verified whether certain experienced symptoms are followed by the correct self-management actions or accompanied with a particular perception, e.g. whether a relatively high reported need for ICS is accompanied with a preference to use a SABA or even an ICS as needed when experiencing dyspnoea, rather than using the ICS for prevention. Based on our findings the effectiveness of interventions can be improved by tailoring to an individual patient’s needs. For this purpose we provide clinical implications of the findings in each chapter, including the general discussion.

In this thesis we aimed to further deepen knowledge on factors associated with nonadherence to provide means to improve adherence. We evaluated several methods of assessing adherence. At first, we evaluated the accuracy of the Medication Adherence Rating Scale (MARS), a structured method for eliciting patients’ reports of adherence, in identifying low adherence with ICS using prescription refill data as a reference. We found that the MARS as a self-reported measure of adherence is useful as a screening tool for identifying patients with low adherence to ICS. Furthermore, we investigated the use of ICS during a ten-year period to describe medication use as a continuum. With this approach we could expand research further than identifying those patients who persist and also investigate recurring episodes of non-persistence. We found that patients most frequently discontinued in the year after start. In conditions like asthma, self-management allows patients, depending on their severity of disease, to adjust the timing and dosing of inhaled corticosteroids (ICS). Why patients behave in a particular way or make certain decisions is not easy to deduce from the pharmacy records available in most studies on adherence. In Chapters 3 and 4 we evaluated possible driving forces behind certain adherence behaviour. Discontinuation of ICS treatment has been widely discussed and some investigators had found similar results as ours, in new users of other medication. However, few studies investigated diagnoses assigned to new users of medication by the physician and it’s influence on adherence. Furthermore to the best of our knowledge, patient and physician reasons for discontinuing have not been investigated in depth. Therefore we aimed to describe reasons for prescribing and discontinuing ICS from a patient perspective (Chapter 3.1) with clinical information, obtained from the GP, added (Chapter 3.2). To our surprise patients primarily mentioned a variety of self-limiting symptoms like cough and dyspnoea or conditions like common cold, acute bronchitis and pneumonia for which ICS are not indicated. General practitioners stated to be certain on a diagnosis of asthma in almost one quarter of their patients. Moreover, in almost 30% of their patients they had a suspicion of asthma. The discrepancy between the opinions of GPs and patients indicates that the communication of the reason for prescribing drugs like ICS should be improved. As knowledge of treatment and actions of a drug have been shown to influence adherence and self-management we investigated in chapter 3.3 the knowledge of ICS’ mode of actions among new users of ICS that discontinued, and whether they were instructed on the use of their inhaler. The majority of patients were not aware of ICS’ actions. The way in which patients are instructed on their inhalers should be improved, especially giving attention to knowledge on the anti-inflammatory effects of ICS. Previously the beliefs about medicines questionnaire (BMQ) was shown to correlate with self-reported adherence. In chapter 4.1 we investigated whether beliefs about ICS, measured by the BMQ (necessity and concerns), relate to adherence objectively measured by prescription refill records. Based on the relations found we conclude that the BMQ specific and general could be used to identify specific barriers on the use of medication of individual patients. For this purpose we defined four attitudinal groups, based on the BMQ necessity and concerns constructs, in an attempt to translate particular beliefs to certain types of patients and facilitate medical decision making by recognising patients who will most likely be non-adherent. The attitudinal groups differ in perceived harmfulness towards medicines in general and in adherence by self-report and pharmacy data. In chapter 4.2 we evaluated whether the level of disease control influenced the relation between the BMQ and adherence since it has been hypothesized, e.g. within Leventhal’s common-sense model, that symptom experience might influence adherence or mediate the relation between adherence and perception. We found that in patients with less adequate disease control more attention for beliefs and symptom control is needed, as the correlations between perceived need of ICS and adherence are weakest in patients with lowest disease control. Symptom control can be evaluated (in the pharmacy) by use of the Asthma Control Questionnaire (ACQ) and use of short-acting beta2-agonists (SABA). In this way it can be verified whether certain experienced symptoms are followed by the correct self-management actions or accompanied with a particular perception, e.g. whether a relatively high reported need for ICS is accompanied with a preference to use a SABA or even an ICS as needed when experiencing dyspnoea, rather than using the ICS for prevention. Based on our findings the effectiveness of interventions can be improved by tailoring to an individual patient’s needs. For this purpose we provide clinical implications of the findings in each chapter, including the general discussion.