Health outcomes of asthma and COPD patients: the evaluation of a project to implement guidelines in general practice

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1 International Journal for Quality in Health Care 2001; Volume 13, Number 1: pp Health outcomes of asthma and COPD patients: the evaluation of a project to implement guidelines in general practice M. P. JANS 1,2, F. G. SCHELLEVIS 1,3,E.M.LECOQ 1, P. D. BEZEMER 1,4 AND J. Th. M. van EIJK 5 1 Institute for Research in Extramural Medicine, Vrije Universiteit, Amsterdam, 2 Dutch National Institute of Allied Health Professions, Amersfoort, 3 Netherlands Institute of Primary Health Care (NIVEL), Utrecht, 4 Department of Epidemiology and Biostatistics, Vrije Universiteit, Amsterdam and 5 Department of Health Care Studies, Section of Medical Sociology, Universiteit Maastricht, Maastricht, the Netherlands Abstract Objective. To evaluate a project to implement guidelines on the management of patients with asthma or chronic obstructive pulmonary disease (COPD) in terms of the health outcomes of these patients. Design. A before-and-after study of 1 year with a non-randomized but comparable reference group. Setting. General practices in the Netherlands. Study participants. Two-hundred and eighty patients from 14 practices in the intervention group and 90 patients from five practices in the reference group (receiving usual care). Intervention. The project included a comprehensive implementation programme, involving identification of barriers, documentation of the care provided, specific education, feedback on compliance with the guidelines, and peer review. This project has been found to bring the process of care more in agreement with the guidelines. Main outcome measures. Mean peak expiratory flow rate (PEFR) as a percentage of the predicted value, number of days with a diurnal variation in PEFR [ 15%, number of days with respiratory symptoms (all recorded by patients for a period of 14 days), and perceived health status (Nottingham Health Profile). Results. After 1 year, the intervention group showed statistically significant improvements with regard to the mean PEFR, the diurnal variation in PEFR, respiratory symptoms and the pain score of the Nottingham Health Profile. Comparing the changes within the intervention group with the changes within the reference group, only a positive effect of the intervention on the mean PEFR was found. Conclusion. The comprehensive implementation programme improved the lung function and symptoms of asthma and COPD patients in the intervention group. However, in comparison with a reference group, the positive effect on the lung function was only small. Keywords: asthma, evaluation of guideline implementation, family practice, guidelines, health outcomes, obstructive lung diseases, quality of health care In recent years, the development and implementation of clinical guidelines has received increasing attention in general practice. Guidelines recommend the optimum management for a given condition. They are developed with the aim of improving the process of care and consequently, the health outcomes for patients. The publication of guidelines alone is poorly effective in changing clinical practice, and should therefore be accompanied by intensive implementation strategies in order to change the behaviour of general practitioners (GPs) [1 3]. In a systematic review of 61 studies, Wensing et al. concluded that combinations of three or more different implementation strategies, for example the combination of education, feedback and peer review, seemed to be more effective in improving the care provided by GPs than single Address reprint requests to M. P. Jans, Dutch National Institute of Allied Health Professions (NPi), P.O. Box 1161, 3800 BD Amersfoort, the Netherlands. g.van.oss@hccnet.nl 2001 International Society for Quality in Health Care and Oxford University Press 17

2 Health outcomes in asthma and COPD Figure 1 The components of the project to implement guidelines in the 14 intervention practices. Patients strategies [4]. In most of these studies only the effect on the process of care was studied; only eight studies assessed whether the implementation of guidelines had led to improvements in the health of patients. As most studies were carried out in the USA, the UK, and Canada, we replicated the introduction of a multifaceted implementation programme in the Dutch health care system. In the Netherlands, the GP is the gatekeeper of the health care system; he or she is able to deliver continuous care because patients have the same GP for many years. Patients with asthma or chronic obstructive pulmonary disease (COPD) are mainly diagnosed and treated in general practice. However, shortcomings have been reported in the care that GPs provide to patients with these disorders [5,6]. In the past decade, there has been increasing agreement on how these patients should be managed, as indicated by the publication of a considerable number of guidelines [7 10], including the guidelines on the management of asthma and COPD patients issued by the Dutch College of General Practitioners [11,12]. To implement these Dutch guidelines we carried out a project encompassing the following elements: identification of barriers, documentation, specific education, feedback, and peer review. In the evaluation, project elements of the process and outcome of care were included. As already described elsewhere, the introduction of this project improved the process of care in terms of the compliance of GPs with the guidelines [13]. In addition, we investigated whether the introduction of this multifaceted implementation project res- ulted in improvements in the health of asthma and COPD patients. The present paper therefore evaluates a project to implement guidelines in general practice by examining the changes in the peak expiratory flow rate (PEFR), respiratory symptoms and perceived health status of these patients. All known asthma and COPD patients, as well as patients who had frequently presented respiratory symptoms in the previous 2 years or used asthma or COPD medication, were invited to visit the practice for assessment on whether they should be diagnosed as asthma or COPD patients. The patients with a confirmed diagnosis of asthma or COPD were invited to participate if they met the following inclusion criteria: between 16 and 70 years of age, not under the care of a chest physician, no disease with expected short-term death, no other disease affecting the lung function and capable Method of completing a questionnaire in the Dutch language. Of the 846 patients who were eligible, 607 patients were included Design (455 in the intervention group and 152 in the reference group); the other patients were not willing to participate. The The study was designed as a before-and-after study with a patients in the intervention group were included between non-randomized but comparable reference group. The project June 1993 and April 1994, but mainly between October 1993 was carried out in 14 general practices that were located in and January 1994; patients in the reference group were the north-western region of the Netherlands and included included between March and July GPs; these practices were the intervention practices. The GPs of these practices were recruited to participate in a new Intervention and control condition programme of the Vrije Universiteit Amsterdam on the quality of care for patients with chronic diseases in general practice. In 1993, a project was introduced in the intervention practices Within this group we compared the health of the asthma and that was directed towards the implementation of the guidelines COPD patients at baseline with their health 1 year later. of the Dutch College of General Practitioners [11,12] in daily To control for external factors, the change in health of care. In these guidelines no distinction has been made between patients in the intervention group was also compared with asthma and COPD care. The project involved a combination the change in health of patients in a reference group of GPs of the following components: identification of barriers, docu- who continued to provide their usual care. The five reference mentation, education, feedback, and peer review (Figure 1). practices with one GP per practice were located in the same We used questionnaires to identify the barriers and prob- region as the intervention practices. The reference group lems that GPs expected to encounter when adhering to the included the same variation as the intervention group with guidelines. These barriers and problems received special regard to type of practice (solo or group practice), urbanization attention in the project. level and previous education on asthma and COPD care. Documentation of the main aspects of diagnosis and The study was approved by the local medical ethics committee. treatment on standardized forms for each consultation was 18

3 M. P. Jans et al. an essential aspect of the project because it reminded GPs who gave a positive answer to one or more of these three to work in accordance with the guidelines and allowed us to questions was considered to have had symptoms on that day. provide feedback data. If the record contained data for less than 14 days the data Beginning in October 1993, minute educational were extrapolated to 14 days, provided that data for at least meetings were held in a 15-month period. The GPs received 10 days were available. education on diagnostics, treatment and follow-up visits. Controversial guideline recommendations were discussed in Perceived health status the group, sometimes with experts in the field of asthma and Perceived health status was measured according to the first COPD. During each meeting, GPs received personal feedback part of the Nottingham Health Profile (NHP) [17]. This on the care they had provided for their patients; the feedback instrument, measuring general health status, consists of 38 was related to the topic being discussed. This feedback was items about how people feel or function in daily life. The based on the data registered on the consultation forms. In items cover the following six dimensions: physical mobility, addition, the method of peer review [14] was used to share pain, sleep, energy, social isolation and emotional reactions. experiences, to gain support from colleagues, and to discuss Patients were asked whether or not each item applied to the discrepancies between the recommendations given in the them. Positive answers were given the appropriate weights; guidelines and the actual care provided. The GPs in the resulting in a score range from 0 to 100 for each dimension intervention group attended a mean of seven of eleven [18]. Higher scores correspond to a lower perceived health educational meetings (range, 4 11 meetings). status. Dimension scores were calculated only if no data were The GPs in the reference group continued to provide their missing on the dimension concerned. usual care and were not involved in organized education, documentation or feedback regarding asthma and COPD care. They were, however, aware of the existence of the Potentially confounding and modifying variables guidelines, as they had been published in a GP journal 1 year The following variables at patient level were considered: age, before the start of this study [11,12]. sex, highest educational level, allergy, current smoking (yes/ no), prescribed medication, comorbidity and type of disease (asthma versus COPD). Information on these variables was recorded on inclusion by the GP in the intervention group Measurements and by a researcher in the reference group on a standardized Outcome measures form. Allergy was considered to be present if the total IgEtest was positive or, if this test was not available (23%), a At baseline (T0) and one year later (T1) all patients were positive history of allergy for at least one of the following issued with forms, on which they were asked to record data allergens: house dust mite, animals or pollens. Medication on PEFR measurements and respiratory symptoms during a prescribed at the time of inclusion was classified into three 2-week period. Furthermore they were asked to fill in a categories: no medication, bronchodilators only (short-acting questionnaire about their perceived health status. β 2 -agonists, anticholinergics or theophyllines) and inhaled anti-inflammatory agents (corticosteroids or sodium cromoglycates) Peak expiratory flow rate with or without bronchodilators. Comorbidity was Lung function was determined in two ways: by the mean defined as the presence of one or more of the following morning PEFR of 14 days as a percentage of the predicted diseases according to the medical record: diabetes mellitus, value [15], and by the number of days with a diurnal variation hypertension, myocardial infarction, angina pectoris, conin PEFR of more than 15%. Patients measured their PEFR gestive heart failure, cerebrovascular disease, transient ischtwice a day, using a mini-wright meter, and recorded the aemic attack, dementia, osteoarthritis of the hip or knee, highest value of a triple measurement in the morning and in rheumatoid arthritis or any malignancy. the evening. Diurnal variation in PEFR was defined as the Until recently in the Netherlands it was commonly thought difference between the morning and the evening PEFR, that asthma and COPD should be considered as different expressed as a percentage of the mean value of that day; expressions of the same disease [19]. Therefore, at the time diurnal variation was calculated per day [16]. If the record of this study it was not common practice for Dutch GPs to contained data for less than 14 days, the data were extrapolated make a distinction between asthma and COPD. Nowadays, to 14 days, provided that data for at least 10 days were the importance of making a distinction is becoming more available. widely recognized in view of the differences in treatment and prognosis. To diagnose asthma, information is needed on the Respiratory symptoms reversibility or variability of the lung function before the Another outcome measure was the number of days with prescription of medication; to diagnose COPD, more than respiratory symptoms. Patients recorded daily whether their one FEV 1 measurement is required to establish chronic sleep had been disturbed due to coughing, wheezing or obstructive lung function [20]. Because these measurements dyspnoea (yes/no), whether they had had symptoms lasting were not included in the routine practice of Dutch GPs at almost all day (yes/no) and whether the symptoms had the time of the present study, no such data were available. interfered with their normal daily activities (yes/no). A patient To get an idea whether the effects of the intervention are 19

4 Health outcomes in asthma and COPD related to the kind of disease we made a rough distinction between asthma and COPD patients on the basis of the age of onset of the disease (< 40 versus [ 40 years of age) [20]. Analyses variation of more than 15%, the number of days with symptoms and the score on the pain dimension of the NHP were all statistically significant (Table 2). The multiple linear regression analyses showed that asthma patients responded better to the intervention with regard to the outcome measures PEFR (P=0.01) and diurnal variation in PEFR (P=0.04) than COPD patients. The other variables showed no re- lationship with the outcome measures after adjusting for the baseline value of the outcome measure concerned. Paired t-tests were used to test whether the patients within the intervention group improved significantly. In order to investigate whether the changes within the intervention group varied between specific subgroups of patients, we conducted multiple linear regression analysis with the potentially modifying variables as independent variables, and the change in PEFR as the dependent variable. In this analysis we adjusted for the baseline value of the PEFR. The same analyses were conducted with respect to the outcome measures diurnal variation in PEFR and respiratory symptoms. The comparability at baseline between the patients in the intervention and the reference group was assessed for the baseline values of the outcome measures and for potentially confounding variables. The intervention and reference groups were compared with regard to the change in the outcome measures, using stepwise multiple linear regression analyses with adjustments for baseline differences on the outcome measure concerned and for potential confounders. Variables with P-values greater than 0.2 in the univariate analyses were included in these multiple regression analyses. All analyses were performed at patient level. To check dependencies among patients within the same practice, which would make the results too optimistic, we investigated whether the standardized residuals, resulting from the regression analyses, clustered per practice. For all analyses we used a significance level of 5%. Results Study population We introduced a project involving the identification of bar- riers, documentation, education, feedback, and peer review, to implement guidelines on the management of asthma and COPD patients in general practice. After 1 year, this comprehensive implementation programme resulted in improvements of the lung function and the respiratory symptoms of the patients within the intervention group. However, in comparison with a reference group, we only found a During the year of the intervention 104 (23%) patients in the intervention group and 40 (26%) in the reference group withdrew from the study (moved, no time, no longer willing to participate). Seventy-one (16%) patients in the intervention group and 22 (14%) in the reference group did not complete the symptom and PEFR records at both T0 and T1, or the period between both records was less than 9 months or more than 15 months. This resulted in a study population of 370 patients, 280 in the intervention group and 90 in the reference group. The mean number of patients per practice was 20 (range, 9 42) in the intervention group and 18 (range, 10 29) in the reference group. The patients included in the study population did not differ at baseline from the patients who withdrew or had incomplete data (Table 1), except with regard to age and sex: the study population was older, and more were women. Changes within intervention group Within the intervention group the 1-year improvements in the mean PEFR, the number of days with a diurnal PEFR Comparability of intervention and reference group at baseline Our efforts to make the intervention and reference group comparable with respect to variation in practice and GP characteristics were successful (Table 3). Before the start of the study there were also no significant differences between the care in the intervention and the reference group, as measured by the percentage of patients with two or more consultations and the percentage of patients with at least one measurement of PEFR in the previous year [13]. As is shown in Table 1, the patients in the intervention group had a lower level of education and less often had comorbidity than the patients in the reference group. Moreover, the patients in the intervention group showed a higher number of days with respiratory symptoms (P=0.01; Mann Whitney test) and a higher pain score on the NHP (P=0.01; Mann Whitney test) at baseline than the patients in the reference group (Table 2). Differences between intervention and reference group Table 2 presents the outcome measures at baseline and 1 year later, and the regression coefficients, which indicate the differences in the changes in the outcome measures between the intervention group and the reference group, after adjusting for baseline differences of the outcome measure concerned and for confounders. As evident from the regression coefficient, the intervention group showed a significantly greater improvement in the mean morning PEFR than the reference group. With regard to the emotional reactions score of the NHP, however, the intervention group showed a significantly greater deterioration than the reference group. No effects were found for the other outcome measures. The standardized residuals resulting from the regression analyses were not clustered per practice. Discussion 20

5 M. P. Jans et al. Table 1 Patient characteristics at baseline of the study population and the dropouts in the intervention and reference group Intervention group Reference group Difference in study Study Study population between population Dropouts population Dropouts intervention and... (n = 280) (n = 175) P (n = 90) (n = 62) P reference group (P) Age (years) [mean (SD)] 42 (15) 40 (14) (15) 39 (14) Sex (% men) < Highest educational level No education/primary school (%) Secondary school (%) University (%) Age at onset of disease (years) 28 (19) 26 (16) (18) 31 (17) [mean (SD)] Type of disease Asthma (%) COPD (%) Allergy (%) Smoking (%) Prescription of anti-inflammatory (%) agents Comorbidity (%) < t-test. 2 Chi-square test. 21

6 Health outcomes in asthma and COPD Table 2 Change of the mean PEFR, the number of days with a diurnal PEFR variation of more than 15%, the number of days with respiratory symptoms, and the perceived health status in the intervention and reference group Intervention group Reference group (n = 280) 1 (n = 90) Difference between T1 T1 Change (95% CI) T0 T1 Change (95% CI) groups β (95% CI)... 2 PEFR (% of predicted value) [mean (SD)] 78.5 (17.1) 81.0 (17.5) (1.5, 3.5) (19.1) 75.6 (20.1) ( 1.5, 1.9) 2.3 (0.3, 4.2) 4 Number of days with diurnal variation in PEFR [ 15% in 2- week period Mean (SD) 2.7 (3.3) 1.6 (3.0) 1.0 ( 1.4, 0.6) (3.0) 1.9 (3.4) 0.3 ( 1.0,0.3) 0.5 ( 0.2, 1.2) Median Number of days with respiratory symptoms in 2-week period Mean (SD) 4.4 (4.8) 3.2 (4.3) 1.2 ( 1.8, 0.6) (4.0) 2.8 (4.3) 0.2 ( 1.2, 0.9) 0.1 ( 0.9, 1.0) Median Nottingham Health Profile (0 100) Physical mobility Mean (SD) 7 (13) 6 (13) 1 ( 2, 1) 4 (9) 4 (9) 0 ( 2, 2) 0.6 ( 3.0, 1.7) Pain Mean (SD) 5 (14) 3 (12) 2 ( 4, 0) 3 1 (3) 2 (7) +1 (0,2) 0.9 ( 1.3, 3.2) Median Sleep Mean (SD) 11 (19) 11 (21) 0 ( 2, 3) 9 (16) 12 (22) +3 ( 1, 7) 0.1 ( 4.3, 4.5) Energy Mean (SD) 22 (28) 22 (32) 1 ( 3, 4) 22 (31) 20 (31) 1 ( 7, 5) 3.0 ( 9.5, 3.6) Social isolation Mean (SD) 6 (17) 7 (16) 0 ( 1, 2) 2 (8) 3 (9) 0 ( 1, 2) 1.9 ( 4.6, 0.8) Emotional reactions Mean (SD) 10 (17) 11 (19) +2 (0, 4) 5 (9) 5 (10) 0 ( 2, 2) 3.4 ( 6.7, 0.1) 1 With regard to the NHP: n = Regression coefficient β (95% confidence interval) of variable group, adjusted for the baseline value of the outcome measure concerned and for confounders. A positive β means a better result in intervention group than in reference group. 3 Paired t-test: P Ζ Multiple regression analysis: P <

7 M. P. Jans et al. Table 3 GP and practice characteristics, and care provided in the year before the start of the study in the intervention and reference group Intervention group Reference group... (n = 14) (n = 5) GP and practice characteristics: Age of GPs [mean (SD)] 41 (5) 43 (5) Number of years working as a GP [mean (SD)] 11 (7) 13 (4) Working part-time (%) Attended a course on asthma and COPD care in previous 2 years (%) Solo practice (%) Location of practice City (%) Small city (%) Rural (%) Care during previous year: Percentage of patients per practice with more 30 (0 74) 30 (14 59) than two consultations [median (range)] Percentage of patients per practice with more than 5 (0 90) 20 (0 58) one PEFR measurement [median (range)] positive, though small, effect on the mean PEFR. The difference in PEFR between both groups was 2.5% of the predicted value; whether this is a clinically significant improvement can be questioned. In addition, the implementation programme was shown to have a negative effect on the emotional reactions score of the NHP. Sources of bias First, bias might have been caused by the selection of motivated patients. All asthma and COPD patients of the participating GPs had been called up to participate in this project. Lack of motivation to visit the GP or researcher and to fill in questionnaires was the main reason for not taking part or for withdrawing from the study. However, this problem is inherent to research into the implementation of guidelines. The co-operation of the patient is essential for the GP to provide optimal care. The high rate of dropout might have resulted in an overestimation of the differences between the intervention and reference group, as the effects of the intervention were greater for older patients and for women, who were over represented in the study population. Second, it is possible that the month of inclusion might have biased the results. Most patients in the intervention group were enrolled in the fall and winter, whereas most patients in the reference group were enrolled in spring. As could be expected, therefore, the patients in the intervention group showed a higher number of days with respiratory symptoms at inclusion. In order to minimize the bias caused by the month of inclusion, we used in the paired analyses the change in outcome measures and adjusted for the baseline value. A point under discussion is whether the measuring instruments were able to detect clinically relevant changes over time. With regard to symptoms, we asked patients whether they had had symptoms or not, but we did not ask to what extent. In the case of asthma patients, the 2-week registration period of the symptom and PEFR record might have been too short to provide insight into the degree of symptoms, because of the variable nature of asthma. Although little is known on the validity of PEFR measurements, it has been recommended in guidelines as an important parameter to measure control of especially asthma. PEFR measurements are most valuable in individual follow-up; therefore we used paired comparisons in our study. Since the PEFR is a less valid measure for COPD, its use as an outcome measure in COPD can be questioned. Furthermore, the perceived health status of most asthma and COPD patients in our study, as measured according to the NHP, seemed to be comparable with that of healthy people [21], thus leaving little room for improvement. A disease-specific quality-of-life questionnaire might have been more appropriate. However, at the time of the study no such ques- tionnaire was available in the Dutch language. As mentioned before, the intervention resulted in an improvement in lung function parameters, which was not accompanied by an improvement in the perceived health status. This finding is consistent with that of van Schayck et al. who found no correlation between the decline in FEV 1 and changes in NHP scores [22,23]. In addition to the possibly low responsiveness of the NHP, another explanation for these findings could be that patients soon get used to different levels of lung function and continue to assess their health status as normal [23]. Difficulty of research into the implementation of guidelines One of the difficulties of studying the effect of a project to implement guidelines on improvements in the health of 23

8 Health outcomes in asthma and COPD In conclusion, the introduction of the project to implement guidelines improved the health of asthma and COPD patients, especially the lung function, although the contrast with the reference group was small and might be not clinically relevant to GPs. In the long term, this might result in fewer ex- acerbations, less absence through illness and less hos- pitalization. The project demanded much time and energy from the GPs, tutors and researchers. Therefore, to be feasible on a broad scale, quality improvement activities must be integrated, as far as possible, into normal practice care. From that per- spective, the recent introduction of computerization in general practice might facilitate more detailed registration and con- tinuous data collection, which make it easier to provide GPs with feedback data on their performance. It would seem worthwhile to undertake additional research to obtain insight in more detail: what are the effects of a less intensive approach? what degree of compliance with the guidelines should be pursued to retain a balance between feasibility and health effects? how is the cost-effectiveness in the long term? In the meantime, as long as these questions remain unanswered, our study confirms that a comprehensive implementation programme can be used to change the behaviour of GPs, and consequently improve the health of patients. patients is the fact that the intervention is on GP level and the outcome measures are on patient level. Randomization at patient level is not applicable; a GP cannot apply guidelines for one patient and provide usual care for another. In order to avoid such contamination, the GP or the practice has to be the unit of allocation [24]. This requires a much more comprehensive study at far greater costs [25]. The nonrandomized allocation of practices to the intervention and the reference condition and the small number of practices in our study might have introduced potentially confounding factors that have not been taken into account and could have biased the results. For practical reasons, however, the number of GPs included in this study was small, especially in the reference group. Randomization of a small number of practices results in less chance that the groups are comparable with respect to potentially confounding factors, which is the reason for randomization. Another limitation of the randomized controlled trial design is that randomization may lead to GPs being allocated to an intervention that they would not normally accept [26]. GPs in the intervention group have to be motivated to change their daily practice; otherwise it is useless to measure the effect on health outcomes. Allocating motivated GPs to a reference group would introduce a serious risk of loss of contrast between the study groups, or to demotivation which would result in low quality data and/or loss of patients to follow-up. Finally, 1 year may be too short a period to be able to measure changes in health outcomes of asthma and COPD patients. It may take some time before practice routines really change, and the effects on health outcomes may be delayed. On the other hand, it is uncertain whether the changes in behaviour that have taken place will be maintained over a longer period of time, also when meetings are no longer held. Relationship between process and outcome of care of the patient with the advice given, which was not included in the subject of our research. Distinction between asthma and COPD In September 1997 a revised version of the guidelines was published [16,28,29]. The main difference in the revision is that an explicit distinction has been made between asthma and COPD. In retrospect, the version we used seems to be more appropriate for asthma patients than for COPD patients. The results of the regression analyses within the intervention group, which showed a greater improvement in lung function for asthma patients, support our view. In any case, in COPD patients fewer health benefits are to be expected in view of the kind of the disease. Although we endorse the revision of the guidelines, it is questionable whether the results would have been totally different if we had used these new guidelines in our project. Implications As we studied previously, the introduction of this project resulted in increased compliance with the guidelines [13], thus showing a positive effect on the process of care. The number of follow-up visits clearly increased, as did the percentage of patients who had at least one measurement of PEFR. GPs in the intervention group were more likely to monitor medication compliance and inhalation technique than the GPs in the reference group. We therefore assume that Acknowledgement the changes in the care provided have led to improvements in the health of the patients, which is the ultimate objective of The authors wish to thank the general practitioners and the implementation of guidelines. More details on the degree practice assistants who participate in the Vrije Universiteit s of GP compliance with the individual items of the guidelines Extramural Clinic for their co-operation in this study, and have been described in Jans et al. [27]. also for the kind hospitality shown to the researchers during The validity of the guidelines has been questioned by their visits to the practices. the participating GPs, because most recommendations were consensus based. It was therefore unrealistic to expect full implementation of the guidelines. 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