Incidence, presentation and management of Lyme disease in Dutch general practice

Incidence, presentation and management of Lyme disease in Dutch general practice Abstract Background Little is known about the presentation and management of Lyme disease in general practice. Objective To investigate the incidence of Lyme disease over a 6-year period, and its presentation and management in Dutch general practice. Methods Observational study using routine data from a practice-based research network in the Netherlands with 7 practices, 24 GPs and 30000 registered patients. From 2009 to 2014, we calculated the incidence of patients presenting with Lyme disease in general practice. We analysed patient characteristics and symptoms that patients presented with at first visit. Furthermore, we analysed General Practitioners’ (GPs’) diagnostic and therapeutic strategies, and adherence to the national guideline. Results Over a 6-year period, we found 212 episodes with clinical- or laboratory-based diagnosed Lyme disease, resulting in a mean incidence of 117 cases per 100000 patients per year. We did not identify a significant linear trend over time. The most frequently reported symptoms at first visit were rash (77%) and/or insect bite (58%). In 25% of patients, GPs performed a serological test, in 99% an antibiotic was prescribed and 11% were referred to a medical specialist. Frequently (in 46% of patients), the GP did not adhere to the guideline completely. Conclusion This study shows that there is no linear trend in the incidence of Lyme disease over a 6-year period and that most patients present to GPs with unspecific symptoms like rash or insect bites. We show that GPs frequently (in 46% of patients) do not fully adhere to recommendations stated in the national guideline. Bacterial infections, disease management, general practice, guideline adherence, incidence, Lyme disease Introduction Lyme disease is an infectious disease caused by Borrelia burgdorferi. It is transmitted to humans by infected ticks (1). The risk of getting Lyme disease after a tick bite is relatively small (lower than 3%). However, about 10% of patients develop local reactions or systemic symptoms after a tick bite (2–4). The most common manifestation of Lyme disease is erythema migrans, a skin disorder which is characterised by a macula or papule, sometimes with a central clearing, which extends over a period of days or weeks (5,6). The infecting pathogen can also spread to other tissues and organs, sometimes causing severe manifestations like neuroborreliosis, Lyme arthritis or Lyme carditis (7–9). From the 1990s to 2009, the number of infections with the Borrelia bacteria increased in the Netherlands and the rest of the world (10–13), but it seems to have stabilised in the last few years (14). This information is, however, based on rough annual estimates by general practitioners (GPs). As there is no International Classification of Primary Care (ICPC) code for Lyme disease, it is complex to use electronic patient records and analyse the incidence more accurately for surveillance purposes. The Dutch National Organization for Quality Assurance in Hospitals (CBO) developed a guideline for Lyme disease in 2004 (15), including recommendations on diagnostics and treatment for medical specialists and GPs. The guideline was revised in 2013 (16). The level of adherence of Dutch GPs to these guidelines is unknown. Furthermore, characteristics of patients with Lyme disease are unknown. In this study, we therefore aim to investigate the incidence of Lyme disease as presented at Dutch general practices between 2009 and 2014 using electronic patient records. Furthermore, we aim to analyse the characteristics of patients with Lyme disease, their initial symptoms with which they present to GPs and the diagnostic and therapeutic strategies performed by the GP. Finally, we aim to assess to what extent GPs adhere to the national guideline for patients with Lyme disease. Methods Design In this observational study, electronic patient data from the Family Medicine Network (FaMe-Net) were used, this is a practice-based research network from the Radboud university medical centre in Nijmegen, the Netherlands. FaMe-Net is a fusion between two former high quality registration networks in general practice, the Continuous Morbidity Registration (17) and the Transition Project (18). GPs from this network have registered all patient encounters since 1971. GPs code each episode of care according to ICPC and the International Classification of Diseases (ICD10) (19,20). An episode of care is defined as a health problem in an individual from the first to the last visit related to the specified health problem. All actions from the GP, including physical examination, diagnostic tests and prescriptions, are systematically coded. The validity of registration is high, as participating GPs meet regularly to discuss registration and diagnostic criteria. Moreover, the system warns the GP in case of error or inconsistency in registration. Patients In the absence of a specific ICPC or ICD10-code for Lyme disease, all patients with Lyme disease were identified by one investigator (MM) using the following two steps: first, all patients with one of the following ICPC-codes were selected: S12 (insect bite); A78 (other infectious disease) in combination with ICD10-code A69.2 or A26.0 (Lyme disease or cutaneous erysipeloid); L70 in combination with ICD10-code M01.2 (arthritis in Lyme disease); N71 in combination with ICD10-code G01 (meningitis in Lyme disease); and N94 in combination with ICD10-code G63.0 (polyneuropathy in Lyme disease). Second, the electronic patient files of all selected patients were examined including free text written by the GP and letters from medical specialists. Patients were identified as having Lyme disease when the GP or specialist specified the diagnosis of Lyme or erythema migrans in the electronic patient file or referral letter. Selection of patients was performed for the years 2009–2014. Guideline for Lyme disease The Dutch guideline for Lyme disease (2004) provides information on the diagnostic and therapeutic strategies for patients with (suspected) Lyme disease (15). GPs can use a decision tree to determine if a serological test or antibiotic treatment is indicated (see Figure 1). Diagnostic and therapeutic strategies depend on symptom duration and the initial risk of Lyme disease, which is categorised as high, intermediate, low or very low, based on the presence of Lyme disease symptoms (such as erythema migrans or joint complaints, see explanation in footnote of Figure 1). The 2004 guideline for Lyme disease was revised in 2013, leading to the inclusion of a new recommendation to optionally prescribe antibiotic prophylaxis after a tick bite (16). The new guideline did not contain relevant changes to diagnostic or treatment strategies for Lyme disease and therefore its introduction does not affect our analyses. Figure 1. View largeDownload slide Decision tree for a patient with Lyme disease symptoms. aHigh risk: presence of a cutaneous manifestation, such as erythema migrans, acrodermatitis chronic atroficans or lymphocytoma. Intermediate risk: presence of a Lyme disease appropriate extracutaneous manifestation (e.g. joint complaints) in combination with another indication of Lyme disease in the previous three months (i.e. the possibility that the patient had a tick bite or a possible untreated cutaneous manifestation [such as erythema migrans)]. Low risk: presence of a Lyme disease appropriate extracutaneous manifestation without any other indication of Lyme disease in the previous 3 months. Very low risk: patients not fulfilling any of the above descriptions. bSymptom duration since the onset of first symptoms. cNo serology: in these cases a serology to confirm Lyme disease is not indicated. Serology +: serology test is recommended and a positive test result confirms Lyme disease. Serology −: serology test is recommended and a negative test result rules out Lyme disease. dRepeated serology +: repeated serology is recommended and a positive test result confirms Lyme disease. Repeated serology −: repeated serology is recommended and a negative test result rules out Lyme disease. eTreat: antibiotic treatment is recommended in these cases. The type of antibiotic treatment depends on the symptoms and patient characteristics. In case of erythema migrans the advice is to give doxycycline 100 mg twice a day, for 10 days. For pregnant women: amoxicilline 500 mg three times a day, for 14 days. In children <9 years: amoxicilline 50 mg/kg/day, three times a day, for 14 days (maximum of 500mg three times a day). For treatment of all other manifestations of Lyme disease see CBO guideline (16). Figure 1. View largeDownload slide Decision tree for a patient with Lyme disease symptoms. aHigh risk: presence of a cutaneous manifestation, such as erythema migrans, acrodermatitis chronic atroficans or lymphocytoma. Intermediate risk: presence of a Lyme disease appropriate extracutaneous manifestation (e.g. joint complaints) in combination with another indication of Lyme disease in the previous three months (i.e. the possibility that the patient had a tick bite or a possible untreated cutaneous manifestation [such as erythema migrans)]. Low risk: presence of a Lyme disease appropriate extracutaneous manifestation without any other indication of Lyme disease in the previous 3 months. Very low risk: patients not fulfilling any of the above descriptions. bSymptom duration since the onset of first symptoms. cNo serology: in these cases a serology to confirm Lyme disease is not indicated. Serology +: serology test is recommended and a positive test result confirms Lyme disease. Serology −: serology test is recommended and a negative test result rules out Lyme disease. dRepeated serology +: repeated serology is recommended and a positive test result confirms Lyme disease. Repeated serology −: repeated serology is recommended and a negative test result rules out Lyme disease. eTreat: antibiotic treatment is recommended in these cases. The type of antibiotic treatment depends on the symptoms and patient characteristics. In case of erythema migrans the advice is to give doxycycline 100 mg twice a day, for 10 days. For pregnant women: amoxicilline 500 mg three times a day, for 14 days. In children <9 years: amoxicilline 50 mg/kg/day, three times a day, for 14 days (maximum of 500mg three times a day). For treatment of all other manifestations of Lyme disease see CBO guideline (16). Measures The following data were collected for patients with Lyme disease from the electronic patient files: start date of the episode, all face-to-face contacts, the total number of contacts within this episode, any referral to a specialist, information on Lyme serology, drug prescriptions and patient characteristics such as sex and birth year. The general practice where the patient was enrolled was also recorded. Free text written by the GPs was used to categorise presented symptoms at first visit according to ICPC-codes (performed by MM and AU) and to determine the duration of these symptoms. To evaluate if diagnostic and therapeutic strategies in patients were performed according to national guideline, the following information was retrieved from free text fields in the electronic patient files: initial risk of Lyme disease based on the presence of Lyme disease related symptoms (high, intermediate, low or very low risk) (see footnote Figure 1) and symptom duration (< or > than 8 weeks). In addition, the diagnostic and therapeutic strategies lead to the following six variables: serology performed (yes, no), repeated serology performed (yes, no), antibiotic treatment prescribed (yes, no), type of antibiotic prescribed, antibiotic dosage, and antibiotic treatment duration. Based on these data, additional variables were created: serology according to guideline recommendations (yes, no); antibiotic treatment following guideline (yes, no); and overall adherence (adherence to all advices in the guideline: yes, no). When patient record data was unclear, variables were coded as unknown. If the type of antibiotic treatment did not adhere to the guideline because of antibiotic allergies or pregnancy it was recoded as ‘according to the guideline’. Analyses The incidence was expressed as the number of episodes per 100000 patients per year and calculated annually from 2009 to 2014. A regression coefficient was calculated to test for a significant linear trend over time. Descriptive analyses (combining data across the study years) were performed for the following demographic and disease-associated patient characteristics: sex, age grouped into categories of 20 years, number of contacts within the episode, the involved practice, symptom duration, initial risk of Lyme disease, symptoms presented by the patient at first visit, and whether the patient was referred to a specialist at a hospital. We assessed guideline adherence separately for advice regarding serology, antibiotic type, antibiotic dose and antibiotic duration. In addition, we calculated the overall frequency of non-adherence to the guideline (defined as: one or more diagnostic or treatment recommendations not in line with the guideline) as a percentage of all episodes of Lyme disease. The association between GPs’ adherence to the guideline and patient’s age category, sex, symptom duration, initial risk of Lyme disease, referral to a specialist and the GP practice was analysed using a chi-square test. In addition, the association between GPs’ adherence to the guideline and total number of GP consultations was analysed using a t-test. Results Study population Patients with Lyme disease were identified in FaMe-Net. This network consists of 24 GPs with ~30000 registered patients (from seven general practices). Three practices are located in Nijmegen (urban and semi-urban area), two practices in Amstelveen (semi-urban area, one practice in Olst (rural area) and one practice in Franeker (rural area). The study practices are representative to Dutch practices in terms of average patient population size, male to female GP ratio, and proportion of practices that include GP trainees (21–23). However, the majority of our study practices are group practices consisting of three or more GPs, while fewer solo or duo practices are included in comparison to the general practices across the Netherlands. Moreover, participating GPs have special interest in primary care research. The patient population in this network is representative of the general Dutch population in terms of age and sex (21). Incidence In total, we identified 212 patients with diagnosed Lyme disease. Figure 2 shows the calculated incidences of Lyme disease per 100000 patients for all years between 2009 and 2014. The mean incidence was 117 (SD = 24.9) per 100000 per year. The incidence varied from 74 in 2012 to 145 in 2011. There was no significant linear trend over time (β = −3.2; 95% CI −21.1 to 14.7, P = 0.65). Figure 2. View largeDownload slide Incidence of Lyme disease in Dutch general practice (2009–2014). Figure 2. View largeDownload slide Incidence of Lyme disease in Dutch general practice (2009–2014). Characteristics of patients with Lyme disease Table 1 shows the characteristics of all identified patients with Lyme disease. The mean age was 46.1 years (SD = 20.5), with 16% of patients under the age of 20 and 27% over the age of 60. Just over half of the patients were female. Compared to the total patient population of these practices, Lyme disease occurred relatively more often among those aged 41–80 years, while there were no major sex differences. Most patients were classified as having high initial risk of Lyme disease (93%) and symptoms for less than 8 weeks (75%). In total, 23 patients (10.8%) were referred to a medical specialist. Patients’ age and sex were not related to referral (P = 0.97 and P = 0.19, respectively). Table 1. Characteristics of patients with Lyme disease (n = 212) and total practice population (n = 29371) from 2009 to 2014 Patient characteristics Patients with Lyme disease (n = 212) n (%) Total practice populationa (n = 29371) n (%) Age in years  0–20 33 (15.6) 8476 (28.9)  21–40 35 (16.5) 7635 (26.0)  41–60 86 (40.6) 8464 (28.8)  61–80 56 (26.4) 3946 (13.4)  ≥81 2 (0.9) 850 (2.9) Sex  Male 101 (47.6) 14451 (49.2)  Female 111 (52.4) 14920 (50.8) Initial risk of Lyme disease (see footnote Figure 1)  Very low 0 (0)  Low 5 (2.4)  Intermediate 2 (0.9)  High 198 (93.4)  Unknown 7 (3.3) Symptom duration at presentation to GP  < 8 weeks 158 (74.5)  > 8 weeks 14 (6.6)  Unknown 40 (18.9) Initial referral to a specialist  Referral 23 (10.8)   Dermatologist 11 (5.2)   Internist 5 (2.4)   Haematologist 2 (1.0)   Neurologist 1 (0.5)   Otorhinolaryngologist 1 (0.5)   Orthopaedist 1 (0.5)   Emergency department 1 (0.5)   Unknown specialism 1 (0.5)  No referral 189 (89.2) Symptoms presented at first visit to the GPb  Localised rash 164 (77.4)b  Insect bite 124 (58.5)b  Musculoskeletal symptoms 16 (7.5)  Fear of Lyme disease 11 (5.2)  Other skin symptoms (pain, pruritus or swelling) 11 (5.2)  Fever, general weakness or feeling ill 8 (3.8)  Neurological symptoms (headache or tingling fingers) 4 (1.9)  Ear symptoms 1 (0.5)  Swallowing problems 1 (0.5)  Throat symptoms 1 (0.5)  Unknown 10 (4.7) Patient characteristics Patients with Lyme disease (n = 212) n (%) Total practice populationa (n = 29371) n (%) Age in years  0–20 33 (15.6) 8476 (28.9)  21–40 35 (16.5) 7635 (26.0)  41–60 86 (40.6) 8464 (28.8)  61–80 56 (26.4) 3946 (13.4)  ≥81 2 (0.9) 850 (2.9) Sex  Male 101 (47.6) 14451 (49.2)  Female 111 (52.4) 14920 (50.8) Initial risk of Lyme disease (see footnote Figure 1)  Very low 0 (0)  Low 5 (2.4)  Intermediate 2 (0.9)  High 198 (93.4)  Unknown 7 (3.3) Symptom duration at presentation to GP  < 8 weeks 158 (74.5)  > 8 weeks 14 (6.6)  Unknown 40 (18.9) Initial referral to a specialist  Referral 23 (10.8)   Dermatologist 11 (5.2)   Internist 5 (2.4)   Haematologist 2 (1.0)   Neurologist 1 (0.5)   Otorhinolaryngologist 1 (0.5)   Orthopaedist 1 (0.5)   Emergency department 1 (0.5)   Unknown specialism 1 (0.5)  No referral 189 (89.2) Symptoms presented at first visit to the GPb  Localised rash 164 (77.4)b  Insect bite 124 (58.5)b  Musculoskeletal symptoms 16 (7.5)  Fear of Lyme disease 11 (5.2)  Other skin symptoms (pain, pruritus or swelling) 11 (5.2)  Fever, general weakness or feeling ill 8 (3.8)  Neurological symptoms (headache or tingling fingers) 4 (1.9)  Ear symptoms 1 (0.5)  Swallowing problems 1 (0.5)  Throat symptoms 1 (0.5)  Unknown 10 (4.7) aTotal practice population average from 2009 to 2014. bPatients could present with multiple symptoms. In total, 201 out of 212 patients (95%) presented with either localised rash or an insect bite and 77 patients (36%) presented with a combination of both. View Large Table 1. Characteristics of patients with Lyme disease (n = 212) and total practice population (n = 29371) from 2009 to 2014 Patient characteristics Patients with Lyme disease (n = 212) n (%) Total practice populationa (n = 29371) n (%) Age in years  0–20 33 (15.6) 8476 (28.9)  21–40 35 (16.5) 7635 (26.0)  41–60 86 (40.6) 8464 (28.8)  61–80 56 (26.4) 3946 (13.4)  ≥81 2 (0.9) 850 (2.9) Sex  Male 101 (47.6) 14451 (49.2)  Female 111 (52.4) 14920 (50.8) Initial risk of Lyme disease (see footnote Figure 1)  Very low 0 (0)  Low 5 (2.4)  Intermediate 2 (0.9)  High 198 (93.4)  Unknown 7 (3.3) Symptom duration at presentation to GP  < 8 weeks 158 (74.5)  > 8 weeks 14 (6.6)  Unknown 40 (18.9) Initial referral to a specialist  Referral 23 (10.8)   Dermatologist 11 (5.2)   Internist 5 (2.4)   Haematologist 2 (1.0)   Neurologist 1 (0.5)   Otorhinolaryngologist 1 (0.5)   Orthopaedist 1 (0.5)   Emergency department 1 (0.5)   Unknown specialism 1 (0.5)  No referral 189 (89.2) Symptoms presented at first visit to the GPb  Localised rash 164 (77.4)b  Insect bite 124 (58.5)b  Musculoskeletal symptoms 16 (7.5)  Fear of Lyme disease 11 (5.2)  Other skin symptoms (pain, pruritus or swelling) 11 (5.2)  Fever, general weakness or feeling ill 8 (3.8)  Neurological symptoms (headache or tingling fingers) 4 (1.9)  Ear symptoms 1 (0.5)  Swallowing problems 1 (0.5)  Throat symptoms 1 (0.5)  Unknown 10 (4.7) Patient characteristics Patients with Lyme disease (n = 212) n (%) Total practice populationa (n = 29371) n (%) Age in years  0–20 33 (15.6) 8476 (28.9)  21–40 35 (16.5) 7635 (26.0)  41–60 86 (40.6) 8464 (28.8)  61–80 56 (26.4) 3946 (13.4)  ≥81 2 (0.9) 850 (2.9) Sex  Male 101 (47.6) 14451 (49.2)  Female 111 (52.4) 14920 (50.8) Initial risk of Lyme disease (see footnote Figure 1)  Very low 0 (0)  Low 5 (2.4)  Intermediate 2 (0.9)  High 198 (93.4)  Unknown 7 (3.3) Symptom duration at presentation to GP  < 8 weeks 158 (74.5)  > 8 weeks 14 (6.6)  Unknown 40 (18.9) Initial referral to a specialist  Referral 23 (10.8)   Dermatologist 11 (5.2)   Internist 5 (2.4)   Haematologist 2 (1.0)   Neurologist 1 (0.5)   Otorhinolaryngologist 1 (0.5)   Orthopaedist 1 (0.5)   Emergency department 1 (0.5)   Unknown specialism 1 (0.5)  No referral 189 (89.2) Symptoms presented at first visit to the GPb  Localised rash 164 (77.4)b  Insect bite 124 (58.5)b  Musculoskeletal symptoms 16 (7.5)  Fear of Lyme disease 11 (5.2)  Other skin symptoms (pain, pruritus or swelling) 11 (5.2)  Fever, general weakness or feeling ill 8 (3.8)  Neurological symptoms (headache or tingling fingers) 4 (1.9)  Ear symptoms 1 (0.5)  Swallowing problems 1 (0.5)  Throat symptoms 1 (0.5)  Unknown 10 (4.7) aTotal practice population average from 2009 to 2014. bPatients could present with multiple symptoms. In total, 201 out of 212 patients (95%) presented with either localised rash or an insect bite and 77 patients (36%) presented with a combination of both. View Large The mean number of GP consultations within one episode of Lyme disease was 2.1 (SD = 2.5). In 13 patients (6.1%), the number of GP contacts was five or more, with a maximum of 27 contacts. The number of contacts was not related to patient’s age (P = 0.57) or sex (P = 0.35). The symptom(s) patients presented with at their first GP visit for Lyme disease are shown in the bottom half of Table 1. The mean number of presented symptoms at first visit is 1.77 (SD = 0.80). In total, 201 patients (95%) presented with either a rash or an insect bite and 77 patients (36%) presented with a combination of both. Other symptoms, including musculoskeletal symptoms and fear of Lyme disease, were presented by a minority of cases (<8%). GPs’ diagnostic and therapeutic strategies Table 2 summarises the diagnostic and therapeutic strategies performed by the GP within an episode of Lyme disease. In 25% of patients, GPs performed a serological test and in 99% an antibiotic was prescribed. As the majority of patients (n = 154) in our study were classified as having high initial risk of Lyme disease and had had symptoms for less than 8 weeks, antibiotic treatment was according to guidelines in these patients (see also Figure 1). Table 2. Diagnostic and therapeutic strategies by GPs in 212 patients with Lyme disease from 2009 to 2014 Performed strategy Number (%) Initial serological test  Performed 52 (24.5)   Positive 32 (15.1)   Negative 20 (9.4)  Not performed 159 (75.0)  Unknown 1 (0.5) Repeated serological test  Performed 4 (1.9)   Positive 0 (0)   Negative 4 (1.9)  Not performed 207 (97.6)  Unknown 1 (0.5) Antibiotic treatment  Prescribed 210 (99.1)  Not prescribed 1 (0.5)  Unknown 1 (0.5) Performed strategy Number (%) Initial serological test  Performed 52 (24.5)   Positive 32 (15.1)   Negative 20 (9.4)  Not performed 159 (75.0)  Unknown 1 (0.5) Repeated serological test  Performed 4 (1.9)   Positive 0 (0)   Negative 4 (1.9)  Not performed 207 (97.6)  Unknown 1 (0.5) Antibiotic treatment  Prescribed 210 (99.1)  Not prescribed 1 (0.5)  Unknown 1 (0.5) View Large Table 2. Diagnostic and therapeutic strategies by GPs in 212 patients with Lyme disease from 2009 to 2014 Performed strategy Number (%) Initial serological test  Performed 52 (24.5)   Positive 32 (15.1)   Negative 20 (9.4)  Not performed 159 (75.0)  Unknown 1 (0.5) Repeated serological test  Performed 4 (1.9)   Positive 0 (0)   Negative 4 (1.9)  Not performed 207 (97.6)  Unknown 1 (0.5) Antibiotic treatment  Prescribed 210 (99.1)  Not prescribed 1 (0.5)  Unknown 1 (0.5) Performed strategy Number (%) Initial serological test  Performed 52 (24.5)   Positive 32 (15.1)   Negative 20 (9.4)  Not performed 159 (75.0)  Unknown 1 (0.5) Repeated serological test  Performed 4 (1.9)   Positive 0 (0)   Negative 4 (1.9)  Not performed 207 (97.6)  Unknown 1 (0.5) Antibiotic treatment  Prescribed 210 (99.1)  Not prescribed 1 (0.5)  Unknown 1 (0.5) View Large Table 3 shows GPs’ adherence to the guideline recommendations published in 2013. Overall, GPs did not fully adhere to the guideline in 97 patients (46%), and in 29 patients (14%) the adherence to the guideline was unknown. Non-adherence was mainly due to GPs’ prescribing antibiotics for more than 10 days (30%) and performing a serological test when not recommended by the guideline (14%). Of all 55 patients with a longer antibiotic prescription than the recommended 10 days, 39 patients (71%) received a prescription for 14–17 days, 4 patients (7%) for 21 days and 8 patients (15%) for 28–30 days. In 82% of non-adherence cases it was due to one factor, in 17% of cases there were two factors and in 1% of patients the GP did not adhere to three factors in the guideline. Table 3. Non-adherence to Lyme disease guideline by GPs in 212 patients with Lyme disease Strategies Not according to guideline: n (%) Serological test (n = 212) 34 (16.0)  Performed 30 (14.2)a  Not performed 4 (1.9) Repeated serological test (n = 212) 3 (1.4)  Performed 3 (1.4)  Not performed 0 (0) Antibiotic treatment (n = 210) 84 (39.6)  Antibiotic type (n = 210) 9 (4.3)  Antibiotic dosage (n = 186)b 7 (3.8)   Higher 2 (1.1)   Lower 4 (2.2)   Frequency 1 (0.5) Antibiotic length (n = 186)b 68 (36.6)   Longer 55 (29.6)   Shorter 13 (7.0) Overall (one or more of the above strategies that were not according to guideline) (n = 212) 97 (45.8) Strategies Not according to guideline: n (%) Serological test (n = 212) 34 (16.0)  Performed 30 (14.2)a  Not performed 4 (1.9) Repeated serological test (n = 212) 3 (1.4)  Performed 3 (1.4)  Not performed 0 (0) Antibiotic treatment (n = 210) 84 (39.6)  Antibiotic type (n = 210) 9 (4.3)  Antibiotic dosage (n = 186)b 7 (3.8)   Higher 2 (1.1)   Lower 4 (2.2)   Frequency 1 (0.5) Antibiotic length (n = 186)b 68 (36.6)   Longer 55 (29.6)   Shorter 13 (7.0) Overall (one or more of the above strategies that were not according to guideline) (n = 212) 97 (45.8) aThe serological test was not recommended in the guideline for patients at high risk of Lyme disease with a symptom duration <8 weeks. bFor children (n = 24), the dosage and length of the antibiotic treatment were not adequately registered (15,16). View Large Table 3. Non-adherence to Lyme disease guideline by GPs in 212 patients with Lyme disease Strategies Not according to guideline: n (%) Serological test (n = 212) 34 (16.0)  Performed 30 (14.2)a  Not performed 4 (1.9) Repeated serological test (n = 212) 3 (1.4)  Performed 3 (1.4)  Not performed 0 (0) Antibiotic treatment (n = 210) 84 (39.6)  Antibiotic type (n = 210) 9 (4.3)  Antibiotic dosage (n = 186)b 7 (3.8)   Higher 2 (1.1)   Lower 4 (2.2)   Frequency 1 (0.5) Antibiotic length (n = 186)b 68 (36.6)   Longer 55 (29.6)   Shorter 13 (7.0) Overall (one or more of the above strategies that were not according to guideline) (n = 212) 97 (45.8) Strategies Not according to guideline: n (%) Serological test (n = 212) 34 (16.0)  Performed 30 (14.2)a  Not performed 4 (1.9) Repeated serological test (n = 212) 3 (1.4)  Performed 3 (1.4)  Not performed 0 (0) Antibiotic treatment (n = 210) 84 (39.6)  Antibiotic type (n = 210) 9 (4.3)  Antibiotic dosage (n = 186)b 7 (3.8)   Higher 2 (1.1)   Lower 4 (2.2)   Frequency 1 (0.5) Antibiotic length (n = 186)b 68 (36.6)   Longer 55 (29.6)   Shorter 13 (7.0) Overall (one or more of the above strategies that were not according to guideline) (n = 212) 97 (45.8) aThe serological test was not recommended in the guideline for patients at high risk of Lyme disease with a symptom duration <8 weeks. bFor children (n = 24), the dosage and length of the antibiotic treatment were not adequately registered (15,16). View Large Determinants for not adhering to Lyme disease guidelines Non-adherence was related to the number of GP contacts: with higher non-adherence for patients with three or more GP contacts (P = 0.04). We found no relation between adherence to the guideline and patient’s age (P = 0.76), sex (P = 0.27), symptom duration (P = 0.56), initial risk of Lyme disease (P = 0.95), referral to a specialist (P = 0.89) or practice (P = 0.17). The proportion of patients that was not treated according to the guideline varied only from 39 to 53% between the study practices. Discussion We found a mean incidence of 117 cases of Lyme disease per 100000 patients from 2009 to 2014. We did not identify a significant linear trend over time, suggesting that the incidence was stable between 2009 and 2014. The most frequently reported symptoms at first visit were rash and/or insect bite (in 95% of patients). In 25% of patients GPs performed a serological test, in 99% an antibiotic was prescribed and 11% of patients were referred to a medical specialist. GPs frequently did not fully adhere to the guideline. Non-adherence was mainly due to prescribing antibiotics for more than 10 days and performing a serological test when not recommended by the guideline. It seems that GPs’ non-adherence is related to number of patient–physician contacts. Non-adherence to the guideline may be due to the fact that GPs are not familiar with its content as GPs only diagnose Lyme disease a few times each year. Patients’ expectations, wishes or uncertainties about whether Lyme disease has been treated sufficiently (e.g. when the rash did not completely disappear after 10 days of antibiotic treatment) can be other explanations for non-adherence (24–27). Strengths and limitations To our knowledge, this is the first study analysing the incidence of Lyme disease using data from GP electronic patient files. Previously, incidence was calculated using survey-based annual estimations by GPs as there is no ICPC code for Lyme disease (14,15). The data for this study were extracted from a robust source of seven general practices participating in FaMe-Net, in which Lyme disease is registered using specific ICPC and ICD10-codes. This is more reliable than previous estimations. Another strength is that the study practices are located in both areas with a relatively low and a relatively high incidence of erythrema migrans, which is important given the geographical variation in incidence (28). A limitation of this study is that we had to depend on the completeness and accuracy of the texts written by the GPs in electronic patient files. Particularly when analysing adherence to the guideline, we sometimes missed important information. However, as non-adherence to the guideline was observed in all study practices with comparable rates, it is unlikely that findings were created by only some practices. Another limitation is that GPs working with FaMe-Net have special affinity with medical research and may therefore exhibit higher levels of adherence to the guideline than GPs working in other practices. However, the symptoms that patients present with at first visit and determinants of GPs’ non-adherence are unlikely to be affected by this. Comparison with existing literature We observed that the incidence of Lyme disease was stable between 2009 and 2014. Hofhuis et al. (14). also found a stagnation in the rise of the incidence rate of Lyme disease in the last 5 years. We found a mean incidence of 117 (SD = 24.9) per 100000 patients per year, which is somewhat lower than the incidence rate reported by Hofhuis et al. (140 per 100000 patients). Hofhuis et al. based their incidence rates on a brief postal questionnaire sent to Dutch GPs asking them to estimate their number of patients with Lyme disease. Another explanation for the difference in incidence rate might be the geographical variation in general practices: in some areas in the Netherlands tick bites and Lyme disease are more prevalent. The incidence of Lyme disease in the Netherlands is much higher than in the UK with an incidence rate of 1.73 per 100000 patients in 2011 (29). But the incidence data of the UK study are incomplete because they are only based on laboratory-confirmed Lyme cases. We found that patients most frequently present with a localised rash (77%) or an insect bite (59%), while musculoskeletal symptoms were reported by only 8% of all patients. This corresponds with previous studies reporting relatively high occurrence of a rash (77–92%) and insect/tick bite (60–79%), and low occurrence of musculoskeletal symptoms (5–7%) (5,7,9,30). Implications for research and practice Based on the mean incidence, an average GP with a population of 2250 patients will diagnose three cases of Lyme disease each year. Lyme disease patients often present to their GP with a localised rash and/or an insect bite at first contact. Musculoskeletal symptoms, fear of Lyme disease or pain, pruritus or swelling of the skin are less frequently mentioned symptoms that patients with Lyme disease may initially present with. Our study showed that GPs do not perform a serological test in most patients with Lyme disease and prescribe antibiotics for almost all patients, which is according to the guideline. However, GPs frequently did not fully adhere to the guideline. Better guideline adherence may be accomplished by making the guideline more easily accessible during GP-patient encounters and by making GPs more familiar with its content (e.g. by e-learning). Non-adherence was higher for patients with three or more GP contacts related to the episode of Lyme disease, but no other determinants of non-adherence were found. We recommend further research in which GPs are asked to explain non-adherence to the guideline in specific patients. This additional information is of great importance for future research into potential areas in which care for patients with Lyme disease could be improved. Declarations Funding: none. Ethical approval: none. Conflict of interest: none. Acknowledgements We thank all GPs from FaMe-Net for enabling research with data from their electronic patient files and the staff from MIMS Radboudumc for providing this data. References 1. van den Wijngaard CC , Hofhuis A , Harms MG et al. The burden of Lyme borreliosis expressed in disability-adjusted life years . Eur J Public Health 2015 ; 25 : 1071 – 8 . Google Scholar CrossRef Search ADS PubMed 2. Tijsse-Klasen E , Jacobs JJ , Swart A et al. Small risk of developing symptomatic tick-borne diseases following a tick bite in The Netherlands . Parasit Vectors 2011 ; 4 : 17 . Google Scholar CrossRef Search ADS PubMed 3. Jacobs JJ , Noordhoek GT , Brouwers JM , Wielinga PR , Jacobs JP , Brandenburg AH . Small risk of developing Lyme borreliosis following a tick bite on Ameland: research in a general practice . Ned Tijdschr Geneeskd 2008 ; 152 : 2022 – 6 . Google Scholar PubMed 4. Hofhuis A , van de Kassteele J , Sprong H et al. Predicting the risk of Lyme borreliosis after a tick bite, using a structural equation model . PLoS One 2017 ; 12 : e0181807 . Google Scholar CrossRef Search ADS PubMed 5. Berglund J , Eitrem R , Ornstein K et al. An epidemiologic study of Lyme disease in southern Sweden . N Engl J Med 1995 ; 333 : 1319 – 27 . Google Scholar CrossRef Search ADS PubMed 6. Wormser GP , Dattwyler RJ , Shapiro ED et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America . Clin Infect Dis 2006 ; 43 : 1089 – 134 . Google Scholar CrossRef Search ADS PubMed 7. Stanek G , Wormser GP , Gray J , Strle F . Lyme borreliosis . Lancet 2012 ; 379 : 461 – 73 . Google Scholar CrossRef Search ADS PubMed 8. Nadelman RB , Nowakowski J , Forseter G et al. The clinical spectrum of early Lyme borreliosis in patients with culture-confirmed erythema migrans . Am J Med 1996 ; 100 : 502 – 8 . Google Scholar CrossRef Search ADS PubMed 9. Huppertz HI , Böhme M , Standaert SM , Karch H , Plotkin SA . Incidence of Lyme borreliosis in the Würzburg region of Germany . Eur J Clin Microbiol Infect Dis 1999 ; 18 : 697 – 703 . Google Scholar CrossRef Search ADS PubMed 10. Hofhuis A , Harms M , van den Wijngaard C , Sprong H , van Pelt W . Continuing increase of tick bites and Lyme disease between 1994 and 2009 . Ticks Tick Borne Dis 2015 ; 6 : 69 – 74 . Google Scholar CrossRef Search ADS PubMed 11. Bacon RM , Kugeler KJ , Mead PS ; Centers for Disease Control and Prevention (CDC) . Surveillance for Lyme disease–United States, 1992-2006 . MMWR Surveill Summ 2008 ; 57 : 1 – 9 . Google Scholar PubMed 12. Fulop B , Poggensee G . Epidemiological situation of Lyme borreliosis in germany: surveillance data from six Eastern German States, 2002 to 2006 . Parasitol Res 2008 ; 103 ( Suppl 1 ): S117 – 20 . Google Scholar CrossRef Search ADS PubMed 13. Dubrey SW , Bhatia A , Woodham S , Rakowicz W . Lyme disease in the United Kingdom . Postgrad Med J 2014 ; 90 : 33 – 42 . Google Scholar CrossRef Search ADS PubMed 14. Hofhuis A , Bennema S , Harms M et al. Decrease in tick bite consultations and stabilization of early Lyme borreliosis in the Netherlands in 2014 after 15 years of continuous increase . BMC Public Health 2016 ; 16 : 425 . Google Scholar CrossRef Search ADS PubMed 15. Dutch guideline for Lyme disease [Richtlijn Lyme-borreliose] . Dutch National Organization for Quality Assurance in Hospitals (Centraal BegeleidingsOrgaan); Van Zuiden Communications, Alphen aan den Rijn, The Netherlands , 2004 . https://www.huidziekten.nl/richtlijnen/richtlijn-lymeborreliose-2004.pdf (accessed 8 May 2018) . 16. Dutch guideline for Lyme disease [Richtlijn Lymeziekte] . Dutch National Organization for Quality Assurance in Hospitals (Centraal BegeleidingsOrgaan); 2013 . https://www.rivm.nl/Documenten_en_publicaties/Algemeen_Actueel/Nieuwsberichten/2013/CBO_richtlijn_Lymeziekte_definitief (accessed 8 May 2018) . 17. Van Weel C . The Continuous Morbidity Registration Nijmegen: background and history of a Dutch general practice database . Eur J Gen Pract 2008 ; 14 ( Suppl 1 ): 5 – 12 . Google Scholar CrossRef Search ADS PubMed 18. Okkes IM , Oskam SK , Van Boven K , Lamberts H . Episodes of care in Dutch Family Practice . Epidemiological data based on the routine use of the International Classification of Primary Care (ICPC) in the Transition Project of the Academic Medical Center/University of Amsterdam (1995–2003) . In: Okkes IM , Oskam SK , Lamberts H (ed). ICPC in the Amsterdam Transition Project . CD-Rom. Amsterdam : Academic Medical Center/University of Amsterdam, Department of Family Medicine , 2005 . 19. Hofmans-Okkes IM , Lamberts H . The International Classification of Primary Care (ICPC): new applications in research and computer-based patient records in family practice . Fam Pract 1996 ; 13 : 294 – 302 . Google Scholar CrossRef Search ADS PubMed 20. Lamberts H , Okkes I . Sense and specificity in computer based patient records in general practice. The ICPC-ICD-10 conversion structure as the Holy Grail . Aust Fam Physician 1997 ; 26 ( Suppl 2 ): S57 – 9 . Google Scholar PubMed 21. CBS Statistics Netherlands . Statline: The Electronic Databank of Statistics Netherlands . http://statline.cbs.nl/Statweb/publication/?DM=SLNL&PA=7461BEV (accessed 8 May 2018 ). 22. Netherlands Institute for Health Services Research (NIVEL) . https://www.nivel.nl/nl/databank ( accessed 8 May 2018 ). 23. The Royal Dutch Medical Association (KNMG) . https://www.knmg.nl/opleiding-herregistratie-carriere/rgs/registers/aantal-registraties-specialistenaois/overzicht-aantal-aois-specialismeprofiel.htm ( accessed 8 May 2018 ). 24. Coumou J , Hovius JW , van Dam AP . Borrelia burgdorferi sensu lato serology in the Netherlands: guidelines versus daily practice . Eur J Clin Microbiol Infect Dis 2014 ; 33 : 1803 – 8 . Google Scholar CrossRef Search ADS PubMed 25. Cranney M , Warren E , Barton S , Gardner K , Walley T . Why do GPs not implement evidence-based guidelines? A descriptive study . Fam Pract 2001 ; 18 : 359 – 63 . Google Scholar CrossRef Search ADS PubMed 26. Grol R , Dalhuijsen J , Thomas S , Veld C , Rutten G , Mokkink H . Attributes of clinical guidelines that influence use of guidelines in general practice: observational study . BMJ 1998 ; 317 : 858 – 61 . Google Scholar CrossRef Search ADS PubMed 27. Bloemendal E , JW , Weenink M , Mistiaen Harmsen P. Naleving van Nederlandse richtlijnen . Utrecht, The Netherlands : NIVEL , 2011 . 28. Tick radar . Wageningen University, National Institute for Public Health and the Environment (RIVM) and Nature Today . https://www.tekenradar.nl/over-tekenradar-nl/cijfers-en-onderzoeksresultaten (accessed 8 May 2018 ). 29. Lyme Borreliosis Epidemiology and Surveillance: Public Health England ; 2013https://www.gov.uk/government/publications/lyme-borreliosis-epidemiology/lyme-borreliosis-epidemiology-and-surveillance (accessed 8 May 2018) 30. Hengge UR , Tannapfel A , Tyring SK , Erbel R , Arendt G , Ruzicka T . Lyme borreliosis . Lancet Infect Dis 2003 ; 3 : 489 – 500 . Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Family Practice Oxford University Press

Incidence, presentation and management of Lyme disease in Dutch general practice

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Abstract Background Little is known about the presentation and management of Lyme disease in general practice. Objective To investigate the incidence of Lyme disease over a 6-year period, and its presentation and management in Dutch general practice. Methods Observational study using routine data from a practice-based research network in the Netherlands with 7 practices, 24 GPs and 30000 registered patients. From 2009 to 2014, we calculated the incidence of patients presenting with Lyme disease in general practice. We analysed patient characteristics and symptoms that patients presented with at first visit. Furthermore, we analysed General Practitioners’ (GPs’) diagnostic and therapeutic strategies, and adherence to the national guideline. Results Over a 6-year period, we found 212 episodes with clinical- or laboratory-based diagnosed Lyme disease, resulting in a mean incidence of 117 cases per 100000 patients per year. We did not identify a significant linear trend over time. The most frequently reported symptoms at first visit were rash (77%) and/or insect bite (58%). In 25% of patients, GPs performed a serological test, in 99% an antibiotic was prescribed and 11% were referred to a medical specialist. Frequently (in 46% of patients), the GP did not adhere to the guideline completely. Conclusion This study shows that there is no linear trend in the incidence of Lyme disease over a 6-year period and that most patients present to GPs with unspecific symptoms like rash or insect bites. We show that GPs frequently (in 46% of patients) do not fully adhere to recommendations stated in the national guideline. Bacterial infections, disease management, general practice, guideline adherence, incidence, Lyme disease Introduction Lyme disease is an infectious disease caused by Borrelia burgdorferi. It is transmitted to humans by infected ticks (1). The risk of getting Lyme disease after a tick bite is relatively small (lower than 3%). However, about 10% of patients develop local reactions or systemic symptoms after a tick bite (2–4). The most common manifestation of Lyme disease is erythema migrans, a skin disorder which is characterised by a macula or papule, sometimes with a central clearing, which extends over a period of days or weeks (5,6). The infecting pathogen can also spread to other tissues and organs, sometimes causing severe manifestations like neuroborreliosis, Lyme arthritis or Lyme carditis (7–9). From the 1990s to 2009, the number of infections with the Borrelia bacteria increased in the Netherlands and the rest of the world (10–13), but it seems to have stabilised in the last few years (14). This information is, however, based on rough annual estimates by general practitioners (GPs). As there is no International Classification of Primary Care (ICPC) code for Lyme disease, it is complex to use electronic patient records and analyse the incidence more accurately for surveillance purposes. The Dutch National Organization for Quality Assurance in Hospitals (CBO) developed a guideline for Lyme disease in 2004 (15), including recommendations on diagnostics and treatment for medical specialists and GPs. The guideline was revised in 2013 (16). The level of adherence of Dutch GPs to these guidelines is unknown. Furthermore, characteristics of patients with Lyme disease are unknown. In this study, we therefore aim to investigate the incidence of Lyme disease as presented at Dutch general practices between 2009 and 2014 using electronic patient records. Furthermore, we aim to analyse the characteristics of patients with Lyme disease, their initial symptoms with which they present to GPs and the diagnostic and therapeutic strategies performed by the GP. Finally, we aim to assess to what extent GPs adhere to the national guideline for patients with Lyme disease. Methods Design In this observational study, electronic patient data from the Family Medicine Network (FaMe-Net) were used, this is a practice-based research network from the Radboud university medical centre in Nijmegen, the Netherlands. FaMe-Net is a fusion between two former high quality registration networks in general practice, the Continuous Morbidity Registration (17) and the Transition Project (18). GPs from this network have registered all patient encounters since 1971. GPs code each episode of care according to ICPC and the International Classification of Diseases (ICD10) (19,20). An episode of care is defined as a health problem in an individual from the first to the last visit related to the specified health problem. All actions from the GP, including physical examination, diagnostic tests and prescriptions, are systematically coded. The validity of registration is high, as participating GPs meet regularly to discuss registration and diagnostic criteria. Moreover, the system warns the GP in case of error or inconsistency in registration. Patients In the absence of a specific ICPC or ICD10-code for Lyme disease, all patients with Lyme disease were identified by one investigator (MM) using the following two steps: first, all patients with one of the following ICPC-codes were selected: S12 (insect bite); A78 (other infectious disease) in combination with ICD10-code A69.2 or A26.0 (Lyme disease or cutaneous erysipeloid); L70 in combination with ICD10-code M01.2 (arthritis in Lyme disease); N71 in combination with ICD10-code G01 (meningitis in Lyme disease); and N94 in combination with ICD10-code G63.0 (polyneuropathy in Lyme disease). Second, the electronic patient files of all selected patients were examined including free text written by the GP and letters from medical specialists. Patients were identified as having Lyme disease when the GP or specialist specified the diagnosis of Lyme or erythema migrans in the electronic patient file or referral letter. Selection of patients was performed for the years 2009–2014. Guideline for Lyme disease The Dutch guideline for Lyme disease (2004) provides information on the diagnostic and therapeutic strategies for patients with (suspected) Lyme disease (15). GPs can use a decision tree to determine if a serological test or antibiotic treatment is indicated (see Figure 1). Diagnostic and therapeutic strategies depend on symptom duration and the initial risk of Lyme disease, which is categorised as high, intermediate, low or very low, based on the presence of Lyme disease symptoms (such as erythema migrans or joint complaints, see explanation in footnote of Figure 1). The 2004 guideline for Lyme disease was revised in 2013, leading to the inclusion of a new recommendation to optionally prescribe antibiotic prophylaxis after a tick bite (16). The new guideline did not contain relevant changes to diagnostic or treatment strategies for Lyme disease and therefore its introduction does not affect our analyses. Figure 1. View largeDownload slide Decision tree for a patient with Lyme disease symptoms. aHigh risk: presence of a cutaneous manifestation, such as erythema migrans, acrodermatitis chronic atroficans or lymphocytoma. Intermediate risk: presence of a Lyme disease appropriate extracutaneous manifestation (e.g. joint complaints) in combination with another indication of Lyme disease in the previous three months (i.e. the possibility that the patient had a tick bite or a possible untreated cutaneous manifestation [such as erythema migrans)]. Low risk: presence of a Lyme disease appropriate extracutaneous manifestation without any other indication of Lyme disease in the previous 3 months. Very low risk: patients not fulfilling any of the above descriptions. bSymptom duration since the onset of first symptoms. cNo serology: in these cases a serology to confirm Lyme disease is not indicated. Serology +: serology test is recommended and a positive test result confirms Lyme disease. Serology −: serology test is recommended and a negative test result rules out Lyme disease. dRepeated serology +: repeated serology is recommended and a positive test result confirms Lyme disease. Repeated serology −: repeated serology is recommended and a negative test result rules out Lyme disease. eTreat: antibiotic treatment is recommended in these cases. The type of antibiotic treatment depends on the symptoms and patient characteristics. In case of erythema migrans the advice is to give doxycycline 100 mg twice a day, for 10 days. For pregnant women: amoxicilline 500 mg three times a day, for 14 days. In children <9 years: amoxicilline 50 mg/kg/day, three times a day, for 14 days (maximum of 500mg three times a day). For treatment of all other manifestations of Lyme disease see CBO guideline (16). Figure 1. View largeDownload slide Decision tree for a patient with Lyme disease symptoms. aHigh risk: presence of a cutaneous manifestation, such as erythema migrans, acrodermatitis chronic atroficans or lymphocytoma. Intermediate risk: presence of a Lyme disease appropriate extracutaneous manifestation (e.g. joint complaints) in combination with another indication of Lyme disease in the previous three months (i.e. the possibility that the patient had a tick bite or a possible untreated cutaneous manifestation [such as erythema migrans)]. Low risk: presence of a Lyme disease appropriate extracutaneous manifestation without any other indication of Lyme disease in the previous 3 months. Very low risk: patients not fulfilling any of the above descriptions. bSymptom duration since the onset of first symptoms. cNo serology: in these cases a serology to confirm Lyme disease is not indicated. Serology +: serology test is recommended and a positive test result confirms Lyme disease. Serology −: serology test is recommended and a negative test result rules out Lyme disease. dRepeated serology +: repeated serology is recommended and a positive test result confirms Lyme disease. Repeated serology −: repeated serology is recommended and a negative test result rules out Lyme disease. eTreat: antibiotic treatment is recommended in these cases. The type of antibiotic treatment depends on the symptoms and patient characteristics. In case of erythema migrans the advice is to give doxycycline 100 mg twice a day, for 10 days. For pregnant women: amoxicilline 500 mg three times a day, for 14 days. In children <9 years: amoxicilline 50 mg/kg/day, three times a day, for 14 days (maximum of 500mg three times a day). For treatment of all other manifestations of Lyme disease see CBO guideline (16). Measures The following data were collected for patients with Lyme disease from the electronic patient files: start date of the episode, all face-to-face contacts, the total number of contacts within this episode, any referral to a specialist, information on Lyme serology, drug prescriptions and patient characteristics such as sex and birth year. The general practice where the patient was enrolled was also recorded. Free text written by the GPs was used to categorise presented symptoms at first visit according to ICPC-codes (performed by MM and AU) and to determine the duration of these symptoms. To evaluate if diagnostic and therapeutic strategies in patients were performed according to national guideline, the following information was retrieved from free text fields in the electronic patient files: initial risk of Lyme disease based on the presence of Lyme disease related symptoms (high, intermediate, low or very low risk) (see footnote Figure 1) and symptom duration (< or > than 8 weeks). In addition, the diagnostic and therapeutic strategies lead to the following six variables: serology performed (yes, no), repeated serology performed (yes, no), antibiotic treatment prescribed (yes, no), type of antibiotic prescribed, antibiotic dosage, and antibiotic treatment duration. Based on these data, additional variables were created: serology according to guideline recommendations (yes, no); antibiotic treatment following guideline (yes, no); and overall adherence (adherence to all advices in the guideline: yes, no). When patient record data was unclear, variables were coded as unknown. If the type of antibiotic treatment did not adhere to the guideline because of antibiotic allergies or pregnancy it was recoded as ‘according to the guideline’. Analyses The incidence was expressed as the number of episodes per 100000 patients per year and calculated annually from 2009 to 2014. A regression coefficient was calculated to test for a significant linear trend over time. Descriptive analyses (combining data across the study years) were performed for the following demographic and disease-associated patient characteristics: sex, age grouped into categories of 20 years, number of contacts within the episode, the involved practice, symptom duration, initial risk of Lyme disease, symptoms presented by the patient at first visit, and whether the patient was referred to a specialist at a hospital. We assessed guideline adherence separately for advice regarding serology, antibiotic type, antibiotic dose and antibiotic duration. In addition, we calculated the overall frequency of non-adherence to the guideline (defined as: one or more diagnostic or treatment recommendations not in line with the guideline) as a percentage of all episodes of Lyme disease. The association between GPs’ adherence to the guideline and patient’s age category, sex, symptom duration, initial risk of Lyme disease, referral to a specialist and the GP practice was analysed using a chi-square test. In addition, the association between GPs’ adherence to the guideline and total number of GP consultations was analysed using a t-test. Results Study population Patients with Lyme disease were identified in FaMe-Net. This network consists of 24 GPs with ~30000 registered patients (from seven general practices). Three practices are located in Nijmegen (urban and semi-urban area), two practices in Amstelveen (semi-urban area, one practice in Olst (rural area) and one practice in Franeker (rural area). The study practices are representative to Dutch practices in terms of average patient population size, male to female GP ratio, and proportion of practices that include GP trainees (21–23). However, the majority of our study practices are group practices consisting of three or more GPs, while fewer solo or duo practices are included in comparison to the general practices across the Netherlands. Moreover, participating GPs have special interest in primary care research. The patient population in this network is representative of the general Dutch population in terms of age and sex (21). Incidence In total, we identified 212 patients with diagnosed Lyme disease. Figure 2 shows the calculated incidences of Lyme disease per 100000 patients for all years between 2009 and 2014. The mean incidence was 117 (SD = 24.9) per 100000 per year. The incidence varied from 74 in 2012 to 145 in 2011. There was no significant linear trend over time (β = −3.2; 95% CI −21.1 to 14.7, P = 0.65). Figure 2. View largeDownload slide Incidence of Lyme disease in Dutch general practice (2009–2014). Figure 2. View largeDownload slide Incidence of Lyme disease in Dutch general practice (2009–2014). Characteristics of patients with Lyme disease Table 1 shows the characteristics of all identified patients with Lyme disease. The mean age was 46.1 years (SD = 20.5), with 16% of patients under the age of 20 and 27% over the age of 60. Just over half of the patients were female. Compared to the total patient population of these practices, Lyme disease occurred relatively more often among those aged 41–80 years, while there were no major sex differences. Most patients were classified as having high initial risk of Lyme disease (93%) and symptoms for less than 8 weeks (75%). In total, 23 patients (10.8%) were referred to a medical specialist. Patients’ age and sex were not related to referral (P = 0.97 and P = 0.19, respectively). Table 1. Characteristics of patients with Lyme disease (n = 212) and total practice population (n = 29371) from 2009 to 2014 Patient characteristics Patients with Lyme disease (n = 212) n (%) Total practice populationa (n = 29371) n (%) Age in years  0–20 33 (15.6) 8476 (28.9)  21–40 35 (16.5) 7635 (26.0)  41–60 86 (40.6) 8464 (28.8)  61–80 56 (26.4) 3946 (13.4)  ≥81 2 (0.9) 850 (2.9) Sex  Male 101 (47.6) 14451 (49.2)  Female 111 (52.4) 14920 (50.8) Initial risk of Lyme disease (see footnote Figure 1)  Very low 0 (0)  Low 5 (2.4)  Intermediate 2 (0.9)  High 198 (93.4)  Unknown 7 (3.3) Symptom duration at presentation to GP  < 8 weeks 158 (74.5)  > 8 weeks 14 (6.6)  Unknown 40 (18.9) Initial referral to a specialist  Referral 23 (10.8)   Dermatologist 11 (5.2)   Internist 5 (2.4)   Haematologist 2 (1.0)   Neurologist 1 (0.5)   Otorhinolaryngologist 1 (0.5)   Orthopaedist 1 (0.5)   Emergency department 1 (0.5)   Unknown specialism 1 (0.5)  No referral 189 (89.2) Symptoms presented at first visit to the GPb  Localised rash 164 (77.4)b  Insect bite 124 (58.5)b  Musculoskeletal symptoms 16 (7.5)  Fear of Lyme disease 11 (5.2)  Other skin symptoms (pain, pruritus or swelling) 11 (5.2)  Fever, general weakness or feeling ill 8 (3.8)  Neurological symptoms (headache or tingling fingers) 4 (1.9)  Ear symptoms 1 (0.5)  Swallowing problems 1 (0.5)  Throat symptoms 1 (0.5)  Unknown 10 (4.7) Patient characteristics Patients with Lyme disease (n = 212) n (%) Total practice populationa (n = 29371) n (%) Age in years  0–20 33 (15.6) 8476 (28.9)  21–40 35 (16.5) 7635 (26.0)  41–60 86 (40.6) 8464 (28.8)  61–80 56 (26.4) 3946 (13.4)  ≥81 2 (0.9) 850 (2.9) Sex  Male 101 (47.6) 14451 (49.2)  Female 111 (52.4) 14920 (50.8) Initial risk of Lyme disease (see footnote Figure 1)  Very low 0 (0)  Low 5 (2.4)  Intermediate 2 (0.9)  High 198 (93.4)  Unknown 7 (3.3) Symptom duration at presentation to GP  < 8 weeks 158 (74.5)  > 8 weeks 14 (6.6)  Unknown 40 (18.9) Initial referral to a specialist  Referral 23 (10.8)   Dermatologist 11 (5.2)   Internist 5 (2.4)   Haematologist 2 (1.0)   Neurologist 1 (0.5)   Otorhinolaryngologist 1 (0.5)   Orthopaedist 1 (0.5)   Emergency department 1 (0.5)   Unknown specialism 1 (0.5)  No referral 189 (89.2) Symptoms presented at first visit to the GPb  Localised rash 164 (77.4)b  Insect bite 124 (58.5)b  Musculoskeletal symptoms 16 (7.5)  Fear of Lyme disease 11 (5.2)  Other skin symptoms (pain, pruritus or swelling) 11 (5.2)  Fever, general weakness or feeling ill 8 (3.8)  Neurological symptoms (headache or tingling fingers) 4 (1.9)  Ear symptoms 1 (0.5)  Swallowing problems 1 (0.5)  Throat symptoms 1 (0.5)  Unknown 10 (4.7) aTotal practice population average from 2009 to 2014. bPatients could present with multiple symptoms. In total, 201 out of 212 patients (95%) presented with either localised rash or an insect bite and 77 patients (36%) presented with a combination of both. View Large Table 1. Characteristics of patients with Lyme disease (n = 212) and total practice population (n = 29371) from 2009 to 2014 Patient characteristics Patients with Lyme disease (n = 212) n (%) Total practice populationa (n = 29371) n (%) Age in years  0–20 33 (15.6) 8476 (28.9)  21–40 35 (16.5) 7635 (26.0)  41–60 86 (40.6) 8464 (28.8)  61–80 56 (26.4) 3946 (13.4)  ≥81 2 (0.9) 850 (2.9) Sex  Male 101 (47.6) 14451 (49.2)  Female 111 (52.4) 14920 (50.8) Initial risk of Lyme disease (see footnote Figure 1)  Very low 0 (0)  Low 5 (2.4)  Intermediate 2 (0.9)  High 198 (93.4)  Unknown 7 (3.3) Symptom duration at presentation to GP  < 8 weeks 158 (74.5)  > 8 weeks 14 (6.6)  Unknown 40 (18.9) Initial referral to a specialist  Referral 23 (10.8)   Dermatologist 11 (5.2)   Internist 5 (2.4)   Haematologist 2 (1.0)   Neurologist 1 (0.5)   Otorhinolaryngologist 1 (0.5)   Orthopaedist 1 (0.5)   Emergency department 1 (0.5)   Unknown specialism 1 (0.5)  No referral 189 (89.2) Symptoms presented at first visit to the GPb  Localised rash 164 (77.4)b  Insect bite 124 (58.5)b  Musculoskeletal symptoms 16 (7.5)  Fear of Lyme disease 11 (5.2)  Other skin symptoms (pain, pruritus or swelling) 11 (5.2)  Fever, general weakness or feeling ill 8 (3.8)  Neurological symptoms (headache or tingling fingers) 4 (1.9)  Ear symptoms 1 (0.5)  Swallowing problems 1 (0.5)  Throat symptoms 1 (0.5)  Unknown 10 (4.7) Patient characteristics Patients with Lyme disease (n = 212) n (%) Total practice populationa (n = 29371) n (%) Age in years  0–20 33 (15.6) 8476 (28.9)  21–40 35 (16.5) 7635 (26.0)  41–60 86 (40.6) 8464 (28.8)  61–80 56 (26.4) 3946 (13.4)  ≥81 2 (0.9) 850 (2.9) Sex  Male 101 (47.6) 14451 (49.2)  Female 111 (52.4) 14920 (50.8) Initial risk of Lyme disease (see footnote Figure 1)  Very low 0 (0)  Low 5 (2.4)  Intermediate 2 (0.9)  High 198 (93.4)  Unknown 7 (3.3) Symptom duration at presentation to GP  < 8 weeks 158 (74.5)  > 8 weeks 14 (6.6)  Unknown 40 (18.9) Initial referral to a specialist  Referral 23 (10.8)   Dermatologist 11 (5.2)   Internist 5 (2.4)   Haematologist 2 (1.0)   Neurologist 1 (0.5)   Otorhinolaryngologist 1 (0.5)   Orthopaedist 1 (0.5)   Emergency department 1 (0.5)   Unknown specialism 1 (0.5)  No referral 189 (89.2) Symptoms presented at first visit to the GPb  Localised rash 164 (77.4)b  Insect bite 124 (58.5)b  Musculoskeletal symptoms 16 (7.5)  Fear of Lyme disease 11 (5.2)  Other skin symptoms (pain, pruritus or swelling) 11 (5.2)  Fever, general weakness or feeling ill 8 (3.8)  Neurological symptoms (headache or tingling fingers) 4 (1.9)  Ear symptoms 1 (0.5)  Swallowing problems 1 (0.5)  Throat symptoms 1 (0.5)  Unknown 10 (4.7) aTotal practice population average from 2009 to 2014. bPatients could present with multiple symptoms. In total, 201 out of 212 patients (95%) presented with either localised rash or an insect bite and 77 patients (36%) presented with a combination of both. View Large The mean number of GP consultations within one episode of Lyme disease was 2.1 (SD = 2.5). In 13 patients (6.1%), the number of GP contacts was five or more, with a maximum of 27 contacts. The number of contacts was not related to patient’s age (P = 0.57) or sex (P = 0.35). The symptom(s) patients presented with at their first GP visit for Lyme disease are shown in the bottom half of Table 1. The mean number of presented symptoms at first visit is 1.77 (SD = 0.80). In total, 201 patients (95%) presented with either a rash or an insect bite and 77 patients (36%) presented with a combination of both. Other symptoms, including musculoskeletal symptoms and fear of Lyme disease, were presented by a minority of cases (<8%). GPs’ diagnostic and therapeutic strategies Table 2 summarises the diagnostic and therapeutic strategies performed by the GP within an episode of Lyme disease. In 25% of patients, GPs performed a serological test and in 99% an antibiotic was prescribed. As the majority of patients (n = 154) in our study were classified as having high initial risk of Lyme disease and had had symptoms for less than 8 weeks, antibiotic treatment was according to guidelines in these patients (see also Figure 1). Table 2. Diagnostic and therapeutic strategies by GPs in 212 patients with Lyme disease from 2009 to 2014 Performed strategy Number (%) Initial serological test  Performed 52 (24.5)   Positive 32 (15.1)   Negative 20 (9.4)  Not performed 159 (75.0)  Unknown 1 (0.5) Repeated serological test  Performed 4 (1.9)   Positive 0 (0)   Negative 4 (1.9)  Not performed 207 (97.6)  Unknown 1 (0.5) Antibiotic treatment  Prescribed 210 (99.1)  Not prescribed 1 (0.5)  Unknown 1 (0.5) Performed strategy Number (%) Initial serological test  Performed 52 (24.5)   Positive 32 (15.1)   Negative 20 (9.4)  Not performed 159 (75.0)  Unknown 1 (0.5) Repeated serological test  Performed 4 (1.9)   Positive 0 (0)   Negative 4 (1.9)  Not performed 207 (97.6)  Unknown 1 (0.5) Antibiotic treatment  Prescribed 210 (99.1)  Not prescribed 1 (0.5)  Unknown 1 (0.5) View Large Table 2. Diagnostic and therapeutic strategies by GPs in 212 patients with Lyme disease from 2009 to 2014 Performed strategy Number (%) Initial serological test  Performed 52 (24.5)   Positive 32 (15.1)   Negative 20 (9.4)  Not performed 159 (75.0)  Unknown 1 (0.5) Repeated serological test  Performed 4 (1.9)   Positive 0 (0)   Negative 4 (1.9)  Not performed 207 (97.6)  Unknown 1 (0.5) Antibiotic treatment  Prescribed 210 (99.1)  Not prescribed 1 (0.5)  Unknown 1 (0.5) Performed strategy Number (%) Initial serological test  Performed 52 (24.5)   Positive 32 (15.1)   Negative 20 (9.4)  Not performed 159 (75.0)  Unknown 1 (0.5) Repeated serological test  Performed 4 (1.9)   Positive 0 (0)   Negative 4 (1.9)  Not performed 207 (97.6)  Unknown 1 (0.5) Antibiotic treatment  Prescribed 210 (99.1)  Not prescribed 1 (0.5)  Unknown 1 (0.5) View Large Table 3 shows GPs’ adherence to the guideline recommendations published in 2013. Overall, GPs did not fully adhere to the guideline in 97 patients (46%), and in 29 patients (14%) the adherence to the guideline was unknown. Non-adherence was mainly due to GPs’ prescribing antibiotics for more than 10 days (30%) and performing a serological test when not recommended by the guideline (14%). Of all 55 patients with a longer antibiotic prescription than the recommended 10 days, 39 patients (71%) received a prescription for 14–17 days, 4 patients (7%) for 21 days and 8 patients (15%) for 28–30 days. In 82% of non-adherence cases it was due to one factor, in 17% of cases there were two factors and in 1% of patients the GP did not adhere to three factors in the guideline. Table 3. Non-adherence to Lyme disease guideline by GPs in 212 patients with Lyme disease Strategies Not according to guideline: n (%) Serological test (n = 212) 34 (16.0)  Performed 30 (14.2)a  Not performed 4 (1.9) Repeated serological test (n = 212) 3 (1.4)  Performed 3 (1.4)  Not performed 0 (0) Antibiotic treatment (n = 210) 84 (39.6)  Antibiotic type (n = 210) 9 (4.3)  Antibiotic dosage (n = 186)b 7 (3.8)   Higher 2 (1.1)   Lower 4 (2.2)   Frequency 1 (0.5) Antibiotic length (n = 186)b 68 (36.6)   Longer 55 (29.6)   Shorter 13 (7.0) Overall (one or more of the above strategies that were not according to guideline) (n = 212) 97 (45.8) Strategies Not according to guideline: n (%) Serological test (n = 212) 34 (16.0)  Performed 30 (14.2)a  Not performed 4 (1.9) Repeated serological test (n = 212) 3 (1.4)  Performed 3 (1.4)  Not performed 0 (0) Antibiotic treatment (n = 210) 84 (39.6)  Antibiotic type (n = 210) 9 (4.3)  Antibiotic dosage (n = 186)b 7 (3.8)   Higher 2 (1.1)   Lower 4 (2.2)   Frequency 1 (0.5) Antibiotic length (n = 186)b 68 (36.6)   Longer 55 (29.6)   Shorter 13 (7.0) Overall (one or more of the above strategies that were not according to guideline) (n = 212) 97 (45.8) aThe serological test was not recommended in the guideline for patients at high risk of Lyme disease with a symptom duration <8 weeks. bFor children (n = 24), the dosage and length of the antibiotic treatment were not adequately registered (15,16). View Large Table 3. Non-adherence to Lyme disease guideline by GPs in 212 patients with Lyme disease Strategies Not according to guideline: n (%) Serological test (n = 212) 34 (16.0)  Performed 30 (14.2)a  Not performed 4 (1.9) Repeated serological test (n = 212) 3 (1.4)  Performed 3 (1.4)  Not performed 0 (0) Antibiotic treatment (n = 210) 84 (39.6)  Antibiotic type (n = 210) 9 (4.3)  Antibiotic dosage (n = 186)b 7 (3.8)   Higher 2 (1.1)   Lower 4 (2.2)   Frequency 1 (0.5) Antibiotic length (n = 186)b 68 (36.6)   Longer 55 (29.6)   Shorter 13 (7.0) Overall (one or more of the above strategies that were not according to guideline) (n = 212) 97 (45.8) Strategies Not according to guideline: n (%) Serological test (n = 212) 34 (16.0)  Performed 30 (14.2)a  Not performed 4 (1.9) Repeated serological test (n = 212) 3 (1.4)  Performed 3 (1.4)  Not performed 0 (0) Antibiotic treatment (n = 210) 84 (39.6)  Antibiotic type (n = 210) 9 (4.3)  Antibiotic dosage (n = 186)b 7 (3.8)   Higher 2 (1.1)   Lower 4 (2.2)   Frequency 1 (0.5) Antibiotic length (n = 186)b 68 (36.6)   Longer 55 (29.6)   Shorter 13 (7.0) Overall (one or more of the above strategies that were not according to guideline) (n = 212) 97 (45.8) aThe serological test was not recommended in the guideline for patients at high risk of Lyme disease with a symptom duration <8 weeks. bFor children (n = 24), the dosage and length of the antibiotic treatment were not adequately registered (15,16). View Large Determinants for not adhering to Lyme disease guidelines Non-adherence was related to the number of GP contacts: with higher non-adherence for patients with three or more GP contacts (P = 0.04). We found no relation between adherence to the guideline and patient’s age (P = 0.76), sex (P = 0.27), symptom duration (P = 0.56), initial risk of Lyme disease (P = 0.95), referral to a specialist (P = 0.89) or practice (P = 0.17). The proportion of patients that was not treated according to the guideline varied only from 39 to 53% between the study practices. Discussion We found a mean incidence of 117 cases of Lyme disease per 100000 patients from 2009 to 2014. We did not identify a significant linear trend over time, suggesting that the incidence was stable between 2009 and 2014. The most frequently reported symptoms at first visit were rash and/or insect bite (in 95% of patients). In 25% of patients GPs performed a serological test, in 99% an antibiotic was prescribed and 11% of patients were referred to a medical specialist. GPs frequently did not fully adhere to the guideline. Non-adherence was mainly due to prescribing antibiotics for more than 10 days and performing a serological test when not recommended by the guideline. It seems that GPs’ non-adherence is related to number of patient–physician contacts. Non-adherence to the guideline may be due to the fact that GPs are not familiar with its content as GPs only diagnose Lyme disease a few times each year. Patients’ expectations, wishes or uncertainties about whether Lyme disease has been treated sufficiently (e.g. when the rash did not completely disappear after 10 days of antibiotic treatment) can be other explanations for non-adherence (24–27). Strengths and limitations To our knowledge, this is the first study analysing the incidence of Lyme disease using data from GP electronic patient files. Previously, incidence was calculated using survey-based annual estimations by GPs as there is no ICPC code for Lyme disease (14,15). The data for this study were extracted from a robust source of seven general practices participating in FaMe-Net, in which Lyme disease is registered using specific ICPC and ICD10-codes. This is more reliable than previous estimations. Another strength is that the study practices are located in both areas with a relatively low and a relatively high incidence of erythrema migrans, which is important given the geographical variation in incidence (28). A limitation of this study is that we had to depend on the completeness and accuracy of the texts written by the GPs in electronic patient files. Particularly when analysing adherence to the guideline, we sometimes missed important information. However, as non-adherence to the guideline was observed in all study practices with comparable rates, it is unlikely that findings were created by only some practices. Another limitation is that GPs working with FaMe-Net have special affinity with medical research and may therefore exhibit higher levels of adherence to the guideline than GPs working in other practices. However, the symptoms that patients present with at first visit and determinants of GPs’ non-adherence are unlikely to be affected by this. Comparison with existing literature We observed that the incidence of Lyme disease was stable between 2009 and 2014. Hofhuis et al. (14). also found a stagnation in the rise of the incidence rate of Lyme disease in the last 5 years. We found a mean incidence of 117 (SD = 24.9) per 100000 patients per year, which is somewhat lower than the incidence rate reported by Hofhuis et al. (140 per 100000 patients). Hofhuis et al. based their incidence rates on a brief postal questionnaire sent to Dutch GPs asking them to estimate their number of patients with Lyme disease. Another explanation for the difference in incidence rate might be the geographical variation in general practices: in some areas in the Netherlands tick bites and Lyme disease are more prevalent. The incidence of Lyme disease in the Netherlands is much higher than in the UK with an incidence rate of 1.73 per 100000 patients in 2011 (29). But the incidence data of the UK study are incomplete because they are only based on laboratory-confirmed Lyme cases. We found that patients most frequently present with a localised rash (77%) or an insect bite (59%), while musculoskeletal symptoms were reported by only 8% of all patients. This corresponds with previous studies reporting relatively high occurrence of a rash (77–92%) and insect/tick bite (60–79%), and low occurrence of musculoskeletal symptoms (5–7%) (5,7,9,30). Implications for research and practice Based on the mean incidence, an average GP with a population of 2250 patients will diagnose three cases of Lyme disease each year. Lyme disease patients often present to their GP with a localised rash and/or an insect bite at first contact. Musculoskeletal symptoms, fear of Lyme disease or pain, pruritus or swelling of the skin are less frequently mentioned symptoms that patients with Lyme disease may initially present with. Our study showed that GPs do not perform a serological test in most patients with Lyme disease and prescribe antibiotics for almost all patients, which is according to the guideline. However, GPs frequently did not fully adhere to the guideline. Better guideline adherence may be accomplished by making the guideline more easily accessible during GP-patient encounters and by making GPs more familiar with its content (e.g. by e-learning). Non-adherence was higher for patients with three or more GP contacts related to the episode of Lyme disease, but no other determinants of non-adherence were found. We recommend further research in which GPs are asked to explain non-adherence to the guideline in specific patients. This additional information is of great importance for future research into potential areas in which care for patients with Lyme disease could be improved. Declarations Funding: none. Ethical approval: none. Conflict of interest: none. Acknowledgements We thank all GPs from FaMe-Net for enabling research with data from their electronic patient files and the staff from MIMS Radboudumc for providing this data. References 1. van den Wijngaard CC , Hofhuis A , Harms MG et al. The burden of Lyme borreliosis expressed in disability-adjusted life years . Eur J Public Health 2015 ; 25 : 1071 – 8 . Google Scholar CrossRef Search ADS PubMed 2. Tijsse-Klasen E , Jacobs JJ , Swart A et al. Small risk of developing symptomatic tick-borne diseases following a tick bite in The Netherlands . Parasit Vectors 2011 ; 4 : 17 . Google Scholar CrossRef Search ADS PubMed 3. 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Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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Family PracticeOxford University Press

Published: May 14, 2018

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