Differences in outpatient antibiotic use between a Spanish region and a Nordic country | Enfermedades Infecciosas y Microbiología Clínica

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"tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "409" "paginaFinal" => "411" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Can the use of antibiotics be improved in outpatients in Spain?" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Carles Llor" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Carles" "apellidos" => "Llor" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213005X14001311?idApp=UINPBA00004N" "url" => "/0213005X/0000003200000007/v1_201408010904/S0213005X14001311/v1_201408010904/es/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Differences in outpatient antibiotic use between a Spanish region and a Nordic country" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "412" "paginaFinal" => "417" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Sara Malo-Fumanal, María José Rabanaque-Hernández, Cristina Feja-Solana, María Jesús Lallana-Alvarez, Javier Armesto-Gómez, Lars Bjerrum" "autores" => array:6 [ 0 => array:4 [ "nombre" => "Sara" "apellidos" => "Malo-Fumanal" "email" => array:1 [ 0 => "smalo@unizar.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "María José" "apellidos" => "Rabanaque-Hernández" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Cristina" "apellidos" => "Feja-Solana" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "María Jesús" "apellidos" => "Lallana-Alvarez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "Javier" "apellidos" => "Armesto-Gómez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 5 => array:3 [ "nombre" => "Lars" "apellidos" => "Bjerrum" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Departamento de Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza, Zaragoza, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Instituto Aragonés de Ciencias de la Salud, Zaragoza, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Farmacia de Atención Primaria, Servicio Aragonés de Salud, Zaragoza, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Farmacia, Servicio Aragonés de Salud, Zaragoza, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Section and Research Unit of General Practice, Department of Public Health, University of Copenhagen, Copenhagen K, Denmark" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Diferencias en el uso extrahospitalario de antibióticos entre una región española y un país nórdico" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 813 "Ancho" => 2236 "Tamanyo" => 128964 ] ] "descripcion" => array:1 [ "en" => "Overall prescription of antibiotics in 2010 in Aragón and Denmark segregated by ATC type." ] ] ] "textoCompleto" => "IntroductionAntimicrobial resistance threatens the effectiveness of successful treatment of infections. It is becoming a public health issue with local, national, and global dimensions. The outcomes are the increased morbidity, disease burden, and mortality.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Several studies have shown the relationship between antimicrobial drug use and the level of pathogen resistance at a national level in countries within the European Union. Antibiotic overuse and misuse have been recognised as important factors determining the development of antimicrobial resistance.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>Early studies showed striking geographical variations in the use of antibiotics between the Nordic and the southern European countries. Denmark had a low consumption, and the prescribing profile followed national guidelines. Conversely, Spain was one of the countries where antibiotics were most often used.<a class="elsevierStyleCrossRefs" href="#bib0010">2,3</a> However, and according to recent data, changes have been occurring. Antimicrobial drug consumption in the Danish Primary Health Care has increased notably during the latest decade.<a class="elsevierStyleCrossRefs" href="#bib0015">3,4</a> In Spain, not only at the national level but also regional, there have been several campaigns and interventions conducted in favour of a more rational, and prudent, use of antibiotics.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> These messages directed at physicians, drug companies, and patients may have had positive influence on the observed decrease in antibiotic use.<a class="elsevierStyleCrossRef" href="#bib0025">5</a>Awareness of outpatient antibiotic use and their regional differences are important tools for action and investigation, and should be a stimulus to improve the quality of prescription and, hopefully as a result, to reduce resistance levels.<a class="elsevierStyleCrossRef" href="#bib0015">3</a>The aim of the present study was to describe and compare antibiotic prescribing in Primary Care in Denmark and Aragón (an Autonomous Region in north-eastern Spain).MethodsThe data on consumption of antibiotics in Primary Care in the year 2010 were obtained from the National Institute for Health Data and Disease Control in Denmark<a class="elsevierStyleCrossRef" href="#bib0030">6</a> and the Information System for Medication Consumption in the Aragón Community. The Danish database is a public, open-access web that contains the following information: identification of the dispensed product according to the Anatomical Therapeutic Chemical (ATC) classification code defined by the World Health Organization (WHO), volume sold, volume sold per 1000 inhabitants, number of users per 1000 inhabitants; each one of these categories segregated by age and gender. The Aragón database contains: patient code to ensure anonymity, ATC code of the dispensed product, number of packages and defined daily dose (DDD) dispensed, prescription month, gender and date of birth of the patient. Permission to access this source of information was obtained from the Aragón Health Sciences Institute.In Denmark there were 5,534,738 inhabitants on the 1st of January 2010.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> It is mandatory to report the sale of these medicines and, therefore, the obtained data cover all sales to patients. Self-medication with antibiotics is rare in Denmark, and 97% of prescribed antibiotics were obtained after a clinical consultation.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> The population studied in Aragón were all those inhabitants of the Autonomous Region with cover under the National Health Service (NHS) of Aragón which, in 2010, were 1,327,827. All the antibiotic prescriptions dispensed in the pharmacies under the Aragon NHS were included. Not taken into account were private prescriptions and those covered by private insurances, hospital-based consumption, and drugs purchased without prescription.To compare antibiotic consumption (ATC code J01) we used the antibiotic prescription rates (number of individuals receiving at least one prescription in one year per 1000 inhabitants), unadjusted as well as adjusted for age by the direct method using the standard European population, with a confidence level of 95%. Data were broken down by gender and different age groups. In Aragón, 19.8% of the registered prescriptions in the database corresponded to non-identified patients whose patient code, gender, date of birth were not available. To preclude underestimation of the real rate of consumption and to facilitate comparisons of both populations in the two study areas, the number of patients that would correspond to these prescriptions was estimated based on the data of those for whom this information was available.Also, the technical unit suggested by the WHO was used i.e. the defined daily dose (DDD), which enables the population exposure to drug use to be calculated as number of DDD per 1000 inhabitants per day (DID), according to the ATC/DDD method.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> For the DID calculation, the DDD for each of the following groups was collated: tetracyclines (J01A), narrow spectrum penicillins (J01CE), broad spectrum penicillins (J01CA and J01CR), cephalosporins (J01D), sulphonamides and trimethoprim (J01E), macrolides (J01F), aminoglycosides (J01G), quinolones (J01M), combinations of antimicrobials (J01R) and other antimicrobials (J01X). To establish the consumption of DID by gender and by age, we calculated the new values of DID for each case in Aragón according to the same methodology as for the rates of prescription, which enables comparisons to be made with the data obtained from Denmark.ResultsThe antibiotic prescription rate in Denmark in 2010 was 315 per 1000 inhabitants per year (95% CI: 311–320) compared to that in Aragón, 407 per 1000 inhabitants per year (95% CI: 396–418). When adjusted for age, these rates were 311 in Denmark and 409 per 1000 inhabitants per year in Aragón. The prescription rate was higher in Aragón for all ages, except for those above 80 years of age where the prescription rate was higher in Denmark. The differences between the two study regions were statistically significant for the 0–19 and 55–79 year age groups. Also, in the two populations studied there were differences between the rate of prescriptions in women and in men (364 women versus 266 men in Denmark and 453 women versus 360 men/1000 inhabitants in Aragón). Females received more treatment at all ages except 0–4 years, in both study regions (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The general trend observed in prescription rates segregated by gender and age was similar in both populations.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>There were important differences between the two study regions in relation to the overall consumption of antibiotics; 23.2 DID in Aragón and 17.0 DID in Denmark. The volume of antibiotics used by the females was greater than that by the males; 19.3 versus 13.4 DID, respectively in Denmark and 24.9 versus 21.4 DID, respectively in Aragón.The election of therapeutic drug subgroups showed differences between the study regions (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Penicillins were the most prescribed antibiotics not only in Aragón but also in Denmark. A very high consumption of broad spectrum penicillins was registered in the Spanish region while, in Denmark, the most prescribed were the narrow spectrum penicillins. Also in Aragón there was a wide use of quinolones, macrolides and cephalosporins. In Denmark other groups being prescribed frequently were macrolides and tetracyclines. The consumption of aminoglucosides was insignificant in the two study regions. Of note in Aragón was the combination of antibiotics (principally spiramycin with metronidazol) and antibiotics of the J01X group that were, essentially, fosfomycin and nitrofurantoin. In Denmark, this group included antibiotics such as nitrofurantoin and methenamine.<elsevierMultimedia ident="fig0010"></elsevierMultimedia>As shown in <a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>, consumption of broad spectrum penicillins was very high in Aragón in all age groups. Of note is that in children (0–4 years) the use was 23.9 DID. In Denmark the consumption of this therapeutic type was moderately high at 0–4 years (6.0 DID) and, as well, beyond the age of 65 years. Narrow spectrum penicillins, the prescription of which was non-significant in Aragón, had an increasing and notable use in Denmark beyond 15 years of age. Tetracyclines were highly prescribed in the 15–19 year old age group, especially among the Danes. In Aragón, the use of quinolones in the older age groups and cephalosporins in children and older age groups was of considerable note. The latter were not prescribed in Denmark. The use of macrolides showed a very similar pattern in both study areas, and in most age groups.<elsevierMultimedia ident="fig0015"></elsevierMultimedia>DiscussionThe present study provides relevant data on the use of antibiotics in Denmark and Aragón (Spain). In the past decade, Vaccheri et al.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> compared the prescription of antibiotics in Ravenna (Italy) with that in Funen (Denmark). The rate of prescription in the Italian region was higher than in the Danish region (400 inhabitants exposed versus 300/1000 inhabitants, respectively). Our results reflect a prescription rate in Aragón (407 exposed/1000 inhabitants) that is similar to the Italian population and, as such, represents an overall proportion of individuals exposed to antibiotics that is much higher than in Denmark (315 exposed/1000 inhabitants). In general, women were more exposed than males in both study areas. There are few studies that contain information on differences in the prescriptions of these drugs as a function of gender. Gulliford et al.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> observed that the prescriptions of antibiotics were about 30–50% higher in women than in men in the treatment of respiratory tract infections (RTIs). This was explained by the higher rate of consultations by the women. Other authors considered that the greater prescription of antibiotics in women was attributable, possibly, to their higher rate of urinary tract infections requiring treatment.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> The consumption (in terms of DID) obtained for both study regions was, as well, higher in women. Conversely, the prescription rate in children was much higher in Aragón than in Denmark. Two previous studies showed that antibiotic use in Danish children was substantially lower than that observed in children from a Canadian population<a class="elsevierStyleCrossRef" href="#bib0060">12</a> and that of another population in Italy.<a class="elsevierStyleCrossRef" href="#bib0065">13</a>The differences in our two study populations were important for the assessment of the consumption of antibiotics, as measured by DID. The value we obtained for the Danes was somewhat similar to that declared for the country in 2010 in the annual report of the European Surveillance of Antimicrobial Consumption Network (ESAC-Net) published by ECDC (17.0 DID versus 16.5 DID).<a class="elsevierStyleCrossRef" href="#bib0015">3</a> On the other hand, the level observed in Aragón (23.2 DID) was higher than that presented by the EDCD for Spain for the year 2010 (20.3 DID).<a class="elsevierStyleCrossRef" href="#bib0015">3</a> The Community of Aragón has been shown, already, to have a higher use of antibiotics compared to the mean of the rest of Spain.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> This could be due to factors related to a higher consumption of antibiotics such as by a higher older-aged population in Aragón<a class="elsevierStyleCrossRef" href="#bib0075">15</a> or of a rural population that is proportionally greater than the rest of Spain.<a class="elsevierStyleCrossRef" href="#bib0080">16</a>There are large variations in DID between countries. The consumption of antibiotics in Europe in 2010 varied between very high values (e.g. France; 28.2 DID) and others lower (e.g. Netherlands; 11.2 DID).<a class="elsevierStyleCrossRef" href="#bib0015">3</a> Analysis of antibiotic use, as measured by DID, is considered a relevant indicator of public health quality since it is, probably, the best marker of the pressures leading to bacterial resistance.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> Although the number of DID used in Denmark has increased,<a class="elsevierStyleCrossRef" href="#bib0020">4</a> it continues to be among the lowest in Europe, and with a lower proportion of antibiotic-resistant pathogens. On the other hand, Spain is positioned as a country with a higher rate of resistance to antibiotics.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> However, several of the comparative studies conducted to-date do not highlight Spain as being one of the regions with higher use. This is due, probably, to an underestimation of consumption. For example, the NHS in Spain estimated the total consumption of antibiotics in 2005 as 18.8 DID, a very low level compared with that obtained by Campos et al.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> who took into account the total sales of antibiotics (including private-health prescriptions as well as antibiotics purchased without a medical prescription). The DID, in this case, was equal to 28.93, which placed Spain among the countries with highest consumption in Europe.<a class="elsevierStyleCrossRef" href="#bib0085">17</a>There are other important differences in the choice of antibiotics between the two populations. Penicillins were the drugs most utilized in both areas, representing >60% of the total DID prescribed. However, while in Denmark 6 of every 10 prescriptions of penicillins correspond to narrow spectrum type, in Aragón almost all the prescriptions of penicillins were the broad spectrum type. The high prescription rate of broad spectrum penicillins in the Danish population >60 years of age is explained, in part, by the treatment with pivmecillinam of urinary tract infections in women. The use of tetracyclines, higher in Denmark, peaks in the 15–19 year age group which is reasonable since this is the antibiotic used in this age group to treat juvenile acne. On the other hand, the quinolones are observed among the most prescribed antibiotics in the adult Aragón population, while its use is sporadic in Denmark. Quinolones are among the antibiotics the WHO defines as Critically Important Antimicrobials (CIA) in medicine,<a class="elsevierStyleCrossRef" href="#bib0090">18</a> the use of which should be rational and reserved for the treatment of serious infections in humans. According to Spanish therapeutic recommendations, quinolones are recommended as second-line treatment in several specific infections, such as pneumonia or acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD).<a class="elsevierStyleCrossRef" href="#bib0095">19</a> Nevertheless, the high number of DDD obtained could exhibit a low adherence to recommendations. The use of cephalosporins represented around 8% of the total DID in Aragón, and was almost completely absent in Denmark. Oral cephalosporins are not funded by the Danish NHS, but they are funded by the NHS in Spain. However, these drugs are considered first-line neither in the treatment of RTIs, nor in the majority of infections at other sites<a class="elsevierStyleCrossRef" href="#bib0095">19</a> and, as such, its high use in Spain is not justified. The use of spiramycin with methronidazol, a combination that is used almost exclusively in odontology, was notable in Aragón while not being used in Denmark.Earlier studies<a class="elsevierStyleCrossRefs" href="#bib0045">9,20</a> had shown that there was a marked difference in the geographic pattern of north-south Europe in the outpatient consumption of antibiotics. It is difficult to explain the high variability, but some characteristics of both populations should be considered when trying to explicate the disparities observed.Our two study populations did not have important demographic differences, albeit the Aragón population showed an ageing that was slightly greater than the Danish population (the >80 age group was around 4% in Denmark compared to around 7% in Aragón).<a class="elsevierStyleCrossRefs" href="#bib0035">7,15</a> This does not appear to justify the differences observed, since these differences are maintained when the rates are adjusted for age.The type of health care organisation in both regions plays also an important role in the prescribing habits. Danish Primary Health Care resembles the Spanish one in some aspects. Both of them are mostly financed by public funds, being the regions governments who manage the health care. The two are based on a patient list system, i.e. citizens are assigned to a GP, who is responsible for serving the patients on his/her list. This system enables the GP to develop a better knowledge of the individual patient.<a class="elsevierStyleCrossRefs" href="#bib0105">21,22</a>On the other hand, some differences between the ambulatory systems can be described. Spanish GPs work within a team of GPs, receiving a fixed salary regardless of the number of patients attended. Nevertheless, Danish GPs run private practices (self-employed), either on their own as solo practitioners or in collaboration with a few GPs more. Two thirds of their incomes are fees for services rendered.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> This latter situation may sometimes cause that Danish GPs prescribe according to the patient's wishes, to ensure upcoming consultations.The number of inhabitants per GP in Denmark is not very distinct from that in Spain. However, in Spain there is in addition one paediatrician per 1029 inhabitants.<a class="elsevierStyleCrossRefs" href="#bib0105">21,22</a> Spanish children are normally treated by paediatricians, whereas in Denmark all patients, including children, are treated by the GP. Some authors noted that paediatricians may be more liberal prescribers than GPs, and were more likely to prescribe antibiotics inappropriately.<a class="elsevierStyleCrossRef" href="#bib0115">23</a>Furthermore, the number of pharmacies per inhabitant is about ten times higher in Spain than in Denmark.<a class="elsevierStyleCrossRefs" href="#bib0105">21,22</a> It should not be a negligible difference, if we take into account the obtained results.Some variables associated with an inappropriate prescription of antibiotics can be the fear of possible complications for the patients, and the desire on the part of the physician to satisfy the expectations of the patient (or their parents/guardians, in the case of children).<a class="elsevierStyleCrossRef" href="#bib0120">24</a> Until a few years ago, obtaining an antibiotic in a Spanish pharmacy without a medical prescription was not an unusual practice. As a consequence, Spanish patients could have greater expectations to receive an antibiotic when they attend the medical consultation by reason of an infection.The frequency of patients’ attendance in the outpatient clinic and/or the high clinical work-load could also be factors related to the prescription increase.<a class="elsevierStyleCrossRef" href="#bib0125">25</a> In Spain, citizens attend outpatient clinics more often than those residing in rest of Europe and the mean duration of the clinical visit in the Primary Care Centre is 5.4min.<a class="elsevierStyleCrossRef" href="#bib0130">26</a> Contrarily, in Denmark, the mean duration of a consultation is 10–15min. Time constraint is a risk factor for antibiotic overprescribing. It takes longer time to explain a patient the reasons for not prescribing an antibiotic than it takes to make a prescription.Llor et al.<a class="elsevierStyleCrossRef" href="#bib0135">27</a> compared GPs prescription of antibiotics for RTIs in Denmark and Spain. These authors showed the different approaches to the choice of antibiotics for RTIs existing in both countries. Danish GPs used primarily narrow spectrum penicillin for most of the RTIs, while Spanish GPs preferred broad spectrum penicillins either alone or in combination with clavulanic acid. Current Spanish guidelines recommend the use of broad spectrum antibiotics as first-line treatment in some urinary tract infections, exacerbation of COPD or pneumonia in the elderly.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> National guidelines are developed considering the different resistance patterns existing in each country. Given that bacterial resistance to the most used antimicrobials is clearly distinct in the two study areas,<a class="elsevierStyleCrossRef" href="#bib0005">1</a> the recommendations for some of the most frequent infections are different.The utilization of different diagnostic methods in general practice may influence on the prescription of antibiotics as well.<a class="elsevierStyleCrossRef" href="#bib0135">27</a> Most Danish GPs use a rapid antigen test (strep A) or a C-reactive protein (CRP) as a support to verify the diagnoses of bacterial tonsillitis or lower respiratory infection. These tests have been shown to reduce the number of patients treated with antibiotics.<a class="elsevierStyleCrossRefs" href="#bib0140">28,29</a> In Spain, none of these tests are used routinely in general practice. It could explain, at least partially, the higher antibiotic prescription rates obtained in the Spanish region.Some previous studies<a class="elsevierStyleCrossRefs" href="#bib0100">20,27</a> highlighted that there is a low probability that the differences existing between the prescription habits of the Danish and Spanish physicians could be due to the unequal prevalence of RTIs receiving attention in Primary Care. Also the pressure exerted by the pharmaceutical industry to the GPs plays an important part in the choice of the antibiotic.<a class="elsevierStyleCrossRef" href="#bib0135">27</a> In Denmark, there are strict rules to avoid doctors’ potential influence of economic incentives from pharmaceutical companies.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> The situation is more liberal in Spain, where drug companies are one of the main sources of information for physicians.<a class="elsevierStyleCrossRef" href="#bib0150">30</a>As previously mentioned, all these factors affecting the use of antibiotics in the two study populations such as different social and cultural traditions, marketing policies of pharmaceutical companies, organisation of the NHS, or the national recommendations should be taken into account when comparing antibiotic use.One of the principal limitations of our study is that the Danish database included all the outpatient prescriptions of antibiotics in the country while, in Aragón, only the outpatient consumption funded by the NHS was taken into account i.e. no account was taken of the consumption in the Spanish region associated with other administrative/funding entities such as private health prescriptions, or drugs acquired without prescription, or self-medication. As has been highlighted, these practices would have a significant impact on the overall consumption, and could represent up to 30% of actual utilization of antibiotics.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> Therefore, although the words “outpatient use”, “utilisation” and “consumption” have been used all through the paper, the analysis performed only included those antibiotics being prescribed in a medical prescription and funded by the NHS. As such, the data from our present study could be an underestimation of the real antibiotic utilisation, particularly in Aragón.Another limitation is that the consumption databases do not contain information on the clinical indication for which the antibiotic was prescribed. As such, the appropriateness of the prescription could not be evaluated.In conclusion, the present study is useful in increasing the knowledge of outpatient antibiotic use in the two populations studied. The data obtained suggest that, in general, women in both regions received a higher volume more frequently. In Aragón, the use of antibiotics in the population is very high, while the data in Denmark indicate a more moderate use. The different traditions, habits, pressures and recommendations existing in both countries should be considered when comparing these data. The obtained results should be a starting point in the search for possible explanations for these variations, and of solutions, or updates on recommendations and prescription guidelines. The misuse of antimicrobial drugs, or their abuse, favours the development and propagation of resistant bacteria, which implies a health threat for the population. Hence, we consider it necessary to conduct interventions at national as well as international level to promote a rational use of antibiotics.FundingS. Malo was supported by a grant from the Programa Europa XXI, funded by the DGA (CONAID) and the Inmaculada Savings Bank [Grant number CM 8/12 to S.M].The work received external funding from the Proyecto del Fondo de Investigación Sanitaria (Instituto de Salud Carlos III, Spanish Ministry of Science, Grant PI10/01048).Conflict of interestThe authors have no conflict of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:2 [ "identificador" => "xres358026" "titulo" => array:5 [ 0 => "Abstract" 1 => "Introduction" 2 => "Methods" 3 => "Results" 4 => "Conclusion" ] ] 1 => array:2 [ "identificador" => "xpalclavsec338008" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres358027" "titulo" => array:5 [ 0 => "Resumen" 1 => "Introducción" 2 => "Métodos" 3 => "Resultados" 4 => "Conclusión" ] ] 3 => array:2 [ "identificador" => "xpalclavsec338009" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflict of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-07-10" "fechaAceptado" => "2013-10-01" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec338008" "palabras" => array:3 [ 0 => "General practice" 1 => "Antibacterial prescription" 2 => "International comparison" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec338009" "palabras" => array:3 [ 0 => "Atención primaria" 1 => "Prescripción antibiótica" 2 => "Comparación internacional" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "IntroductionAntibiotic use and misuse are linked to pathogen resistance and, as such, both constitute a public health issue with local, national, and global dimensions. Early studies have shown striking variations in the use of these drugs between Nordic and Mediterranean countries. The aim of the present study was to describe and compare antibiotic prescribing in Primary Care in Denmark and Aragón (a North-eastern Spanish region). MethodsOutpatient antibiotic prescription data (2010) were obtained from the National Institute for Health Data and Disease Control (Denmark), and the Information System on Medication Consumption in Aragón. The consumption of antibiotics (ATC J01) was analyzed from the prescription rates and the number of defined daily dose (DDD) per 1000 inhabitants/day (DID). ResultsThe rate of antibiotic prescription in 2010 in Aragón was greater than in Denmark (407 compared to 315 exposed individuals/1000 inhabitants). There were significant differences as regards overall consumption of antibiotics (23.2 DID in Aragón and 17.0 DID in Denmark), as well as the therapeutic group selection. There was an elevated use of broad spectrum penicillins, quinolones and cephalosporins in the Spanish region while, in Denmark, the most-consumed antibiotic was narrow spectrum penicillin. ConclusionThe use of antibiotics in the Spanish region is very high, and there are marked differences in the choice of drug between this region and Denmark. Interventions are needed that promote the rational use of these drugs to reduce potential bacterial resistance, and to avoid unnecessary risks to patients." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "IntroducciónEl uso inadecuado de antibióticos se ha relacionado con la aparición de resistencias microbianas, constituyendo así un problema de salud pública de dimensiones locales, nacionales y globales. Estudios previos han mostrado importantes diferencias en el uso de estos fármacos entre los países nórdicos y los mediterráneos. El objetivo de este estudio fue describir y comparar la prescripción antibiótica en atención primaria en Dinamarca y Aragón. MétodosLos datos de utilización extrahospitalaria de antibióticos (2010) se obtuvieron del National Institute for Health Data and Disease Control (Dinamarca) y del Sistema de Información de Consumo Farmacéutico de Aragón. El consumo de antibióticos (ATC J01) se analizó mediante las tasas de prescripción y el número de dosis diaria definida por 1.000 habitantes/día (DHD). ResultadosLa tasa de prescripción antibiótica en 2010 en Aragón fue superior a la de Dinamarca (407 frente a 315 expuestos/1.000 habitantes). Se observaron diferencias significativas en cuanto al consumo total de antibióticos (23,2 DHD en Aragón y 17 DHD en Dinamarca), así como en la elección del grupo terapéutico. La utilización de penicilinas de amplio espectro, quinolonas y cefalosporinas en la región española fue elevada, mientras que en Dinamarca el antibiótico más consumido fue una penicilina de espectro reducido. ConclusiónEl uso de antibióticos en Aragón es elevado, y existen importantes diferencias en la elección del tipo de fármaco entre esta región y Dinamarca. Sería conveniente desarrollar intervenciones que promuevan el uso racional de estos fármacos, para reducir las resistencias bacterianas y evitar riesgos innecesarios a los pacientes." ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1202 "Ancho" => 2181 "Tamanyo" => 165660 ] ] "descripcion" => array:1 [ "en" => "Overall prescription of antibiotics in Aragón and Denmark in 2010, segregated by gender and age. Data are expressed as gender- and age-specific antibiotic prescription rates (number of individuals with one or more prescriptions per 1000 inhabitants for each condition per year)." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 813 "Ancho" => 2236 "Tamanyo" => 128964 ] ] "descripcion" => array:1 [ "en" => "Overall prescription of antibiotics in 2010 in Aragón and Denmark segregated by ATC type." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1590 "Ancho" => 3167 "Tamanyo" => 338566 ] ] "descripcion" => array:1 [ "en" => "Comparison of antibiotic prescriptions segregated by most-frequently prescribed ATC type and age-group, in Aragón and Denmark. The X-axis represents the age groups; Y-axis represents DDD/1000 inhabitants/day. Black circles, Aragón; grey circles, Denmark." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antimicrobial resistance surveillance in Europe 2010. 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Differences in outpatient antibiotic use between a Spanish region and a Nordic country

Diferencias en el uso extrahospitalario de antibióticos entre una región española y un país nórdico

Sara Malo-Fumanala,

Corresponding author

smalo@unizar.es

Corresponding author.

, María José Rabanaque-Hernándeza, Cristina Feja-Solanab, María Jesús Lallana-Alvarezc, Javier Armesto-Gómezd, Lars Bjerrume

a Departamento de Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza, Zaragoza, Spain

b Instituto Aragonés de Ciencias de la Salud, Zaragoza, Spain

c Servicio de Farmacia de Atención Primaria, Servicio Aragonés de Salud, Zaragoza, Spain

d Servicio de Farmacia, Servicio Aragonés de Salud, Zaragoza, Spain

e Section and Research Unit of General Practice, Department of Public Health, University of Copenhagen, Copenhagen K, Denmark

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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Overall prescription of antibiotics in 2010 in Arag&#243;n and Denmark segregated by ATC type&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Antimicrobial resistance threatens the effectiveness of successful treatment of infections&#46; It is becoming a public health issue with local&#44; national&#44; and global dimensions&#46; The outcomes are the increased morbidity&#44; disease burden&#44; and mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Several studies have shown the relationship between antimicrobial drug use and the level of pathogen resistance at a national level in countries within the European Union&#46; Antibiotic overuse and misuse have been recognised as important factors determining the development of antimicrobial resistance&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Early studies showed striking geographical variations in the use of antibiotics between the Nordic and the southern European countries&#46; Denmark had a low consumption&#44; and the prescribing profile followed national guidelines&#46; Conversely&#44; Spain was one of the countries where antibiotics were most often used&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> However&#44; and according to recent data&#44; changes have been occurring&#46; Antimicrobial drug consumption in the Danish Primary Health Care has increased notably during the latest decade&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> In Spain&#44; not only at the national level but also regional&#44; there have been several campaigns and interventions conducted in favour of a more rational&#44; and prudent&#44; use of antibiotics&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> These messages directed at physicians&#44; drug companies&#44; and patients may have had positive influence on the observed decrease in antibiotic use&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Awareness of outpatient antibiotic use and their regional differences are important tools for action and investigation&#44; and should be a stimulus to improve the quality of prescription and&#44; hopefully as a result&#44; to reduce resistance levels&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The aim of the present study was to describe and compare antibiotic prescribing in Primary Care in Denmark and Arag&#243;n &#40;an Autonomous Region in north-eastern Spain&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">The data on consumption of antibiotics in Primary Care in the year 2010 were obtained from the National Institute for Health Data and Disease Control in Denmark<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and the Information System for Medication Consumption in the Arag&#243;n Community&#46; The Danish database is a public&#44; open-access web that contains the following information&#58; identification of the dispensed product according to the Anatomical Therapeutic Chemical &#40;ATC&#41; classification code defined by the World Health Organization &#40;WHO&#41;&#44; volume sold&#44; volume sold per 1000 inhabitants&#44; number of users per 1000 inhabitants&#59; each one of these categories segregated by age and gender&#46; The Arag&#243;n database contains&#58; patient code to ensure anonymity&#44; ATC code of the dispensed product&#44; number of packages and defined daily dose &#40;DDD&#41; dispensed&#44; prescription month&#44; gender and date of birth of the patient&#46; Permission to access this source of information was obtained from the Arag&#243;n Health Sciences Institute&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In Denmark there were 5&#44;534&#44;738 inhabitants on the 1st of January 2010&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> It is mandatory to report the sale of these medicines and&#44; therefore&#44; the obtained data cover all sales to patients&#46; Self-medication with antibiotics is rare in Denmark&#44; and 97&#37; of prescribed antibiotics were obtained after a clinical consultation&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The population studied in Arag&#243;n were all those inhabitants of the Autonomous Region with cover under the National Health Service &#40;NHS&#41; of Arag&#243;n which&#44; in 2010&#44; were 1&#44;327&#44;827&#46; All the antibiotic prescriptions dispensed in the pharmacies under the Aragon NHS were included&#46; Not taken into account were private prescriptions and those covered by private insurances&#44; hospital-based consumption&#44; and drugs purchased without prescription&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">To compare antibiotic consumption &#40;ATC code J01&#41; we used the antibiotic prescription rates &#40;number of individuals receiving at least one prescription in one year per 1000 inhabitants&#41;&#44; unadjusted as well as adjusted for age by the direct method using the standard European population&#44; with a confidence level of 95&#37;&#46; Data were broken down by gender and different age groups&#46; In Arag&#243;n&#44; 19&#46;8&#37; of the registered prescriptions in the database corresponded to non-identified patients whose patient code&#44; gender&#44; date of birth were not available&#46; To preclude underestimation of the real rate of consumption and to facilitate comparisons of both populations in the two study areas&#44; the number of patients that would correspond to these prescriptions was estimated based on the data of those for whom this information was available&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Also&#44; the technical unit suggested by the WHO was used i&#46;e&#46; the defined daily dose &#40;DDD&#41;&#44; which enables the population exposure to drug use to be calculated as number of DDD per 1000 inhabitants per day &#40;DID&#41;&#44; according to the ATC&#47;DDD method&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> For the DID calculation&#44; the DDD for each of the following groups was collated&#58; tetracyclines &#40;J01A&#41;&#44; narrow spectrum penicillins &#40;J01CE&#41;&#44; broad spectrum penicillins &#40;J01CA and J01CR&#41;&#44; cephalosporins &#40;J01D&#41;&#44; sulphonamides and trimethoprim &#40;J01E&#41;&#44; macrolides &#40;J01F&#41;&#44; aminoglycosides &#40;J01G&#41;&#44; quinolones &#40;J01M&#41;&#44; combinations of antimicrobials &#40;J01R&#41; and other antimicrobials &#40;J01X&#41;&#46; To establish the consumption of DID by gender and by age&#44; we calculated the new values of DID for each case in Arag&#243;n according to the same methodology as for the rates of prescription&#44; which enables comparisons to be made with the data obtained from Denmark&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">The antibiotic prescription rate in Denmark in 2010 was 315 per 1000 inhabitants per year &#40;95&#37; CI&#58; 311&#8211;320&#41; compared to that in Arag&#243;n&#44; 407 per 1000 inhabitants per year &#40;95&#37; CI&#58; 396&#8211;418&#41;&#46; When adjusted for age&#44; these rates were 311 in Denmark and 409 per 1000 inhabitants per year in Arag&#243;n&#46; The prescription rate was higher in Arag&#243;n for all ages&#44; except for those above 80 years of age where the prescription rate was higher in Denmark&#46; The differences between the two study regions were statistically significant for the 0&#8211;19 and 55&#8211;79 year age groups&#46; Also&#44; in the two populations studied there were differences between the rate of prescriptions in women and in men &#40;364 women versus 266 men in Denmark and 453 women versus 360 men&#47;1000 inhabitants in Arag&#243;n&#41;&#46; Females received more treatment at all ages except 0&#8211;4 years&#44; in both study regions &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The general trend observed in prescription rates segregated by gender and age was similar in both populations&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">There were important differences between the two study regions in relation to the overall consumption of antibiotics&#59; 23&#46;2 DID in Arag&#243;n and 17&#46;0 DID in Denmark&#46; The volume of antibiotics used by the females was greater than that by the males&#59; 19&#46;3 versus 13&#46;4 DID&#44; respectively in Denmark and 24&#46;9 versus 21&#46;4 DID&#44; respectively in Arag&#243;n&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The election of therapeutic drug subgroups showed differences between the study regions &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Penicillins were the most prescribed antibiotics not only in Arag&#243;n but also in Denmark&#46; A very high consumption of broad spectrum penicillins was registered in the Spanish region while&#44; in Denmark&#44; the most prescribed were the narrow spectrum penicillins&#46; Also in Arag&#243;n there was a wide use of quinolones&#44; macrolides and cephalosporins&#46; In Denmark other groups being prescribed frequently were macrolides and tetracyclines&#46; The consumption of aminoglucosides was insignificant in the two study regions&#46; Of note in Arag&#243;n was the combination of antibiotics &#40;principally spiramycin with metronidazol&#41; and antibiotics of the J01X group that were&#44; essentially&#44; fosfomycin and nitrofurantoin&#46; In Denmark&#44; this group included antibiotics such as nitrofurantoin and methenamine&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">As shown in <a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#44; consumption of broad spectrum penicillins was very high in Arag&#243;n in all age groups&#46; Of note is that in children &#40;0&#8211;4 years&#41; the use was 23&#46;9 DID&#46; In Denmark the consumption of this therapeutic type was moderately high at 0&#8211;4 years &#40;6&#46;0 DID&#41; and&#44; as well&#44; beyond the age of 65 years&#46; Narrow spectrum penicillins&#44; the prescription of which was non-significant in Arag&#243;n&#44; had an increasing and notable use in Denmark beyond 15 years of age&#46; Tetracyclines were highly prescribed in the 15&#8211;19 year old age group&#44; especially among the Danes&#46; In Arag&#243;n&#44; the use of quinolones in the older age groups and cephalosporins in children and older age groups was of considerable note&#46; The latter were not prescribed in Denmark&#46; The use of macrolides showed a very similar pattern in both study areas&#44; and in most age groups&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">The present study provides relevant data on the use of antibiotics in Denmark and Arag&#243;n &#40;Spain&#41;&#46; In the past decade&#44; Vaccheri et al&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> compared the prescription of antibiotics in Ravenna &#40;Italy&#41; with that in Funen &#40;Denmark&#41;&#46; The rate of prescription in the Italian region was higher than in the Danish region &#40;400 inhabitants exposed versus 300&#47;1000 inhabitants&#44; respectively&#41;&#46; Our results reflect a prescription rate in Arag&#243;n &#40;407 exposed&#47;1000 inhabitants&#41; that is similar to the Italian population and&#44; as such&#44; represents an overall proportion of individuals exposed to antibiotics that is much higher than in Denmark &#40;315 exposed&#47;1000 inhabitants&#41;&#46; In general&#44; women were more exposed than males in both study areas&#46; There are few studies that contain information on differences in the prescriptions of these drugs as a function of gender&#46; Gulliford et al&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> observed that the prescriptions of antibiotics were about 30&#8211;50&#37; higher in women than in men in the treatment of respiratory tract infections &#40;RTIs&#41;&#46; This was explained by the higher rate of consultations by the women&#46; Other authors considered that the greater prescription of antibiotics in women was attributable&#44; possibly&#44; to their higher rate of urinary tract infections requiring treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> The consumption &#40;in terms of DID&#41; obtained for both study regions was&#44; as well&#44; higher in women&#46; Conversely&#44; the prescription rate in children was much higher in Arag&#243;n than in Denmark&#46; Two previous studies showed that antibiotic use in Danish children was substantially lower than that observed in children from a Canadian population<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> and that of another population in Italy&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">The differences in our two study populations were important for the assessment of the consumption of antibiotics&#44; as measured by DID&#46; The value we obtained for the Danes was somewhat similar to that declared for the country in 2010 in the annual report of the European Surveillance of Antimicrobial Consumption Network &#40;ESAC-Net&#41; published by ECDC &#40;17&#46;0 DID versus 16&#46;5 DID&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> On the other hand&#44; the level observed in Arag&#243;n &#40;23&#46;2 DID&#41; was higher than that presented by the EDCD for Spain for the year 2010 &#40;20&#46;3 DID&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The Community of Arag&#243;n has been shown&#44; already&#44; to have a higher use of antibiotics compared to the mean of the rest of Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> This could be due to factors related to a higher consumption of antibiotics such as by a higher older-aged population in Arag&#243;n<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> or of a rural population that is proportionally greater than the rest of Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">There are large variations in DID between countries&#46; The consumption of antibiotics in Europe in 2010 varied between very high values &#40;e&#46;g&#46; France&#59; 28&#46;2 DID&#41; and others lower &#40;e&#46;g&#46; Netherlands&#59; 11&#46;2 DID&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Analysis of antibiotic use&#44; as measured by DID&#44; is considered a relevant indicator of public health quality since it is&#44; probably&#44; the best marker of the pressures leading to bacterial resistance&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Although the number of DID used in Denmark has increased&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> it continues to be among the lowest in Europe&#44; and with a lower proportion of antibiotic-resistant pathogens&#46; On the other hand&#44; Spain is positioned as a country with a higher rate of resistance to antibiotics&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> However&#44; several of the comparative studies conducted to-date do not highlight Spain as being one of the regions with higher use&#46; This is due&#44; probably&#44; to an underestimation of consumption&#46; For example&#44; the NHS in Spain estimated the total consumption of antibiotics in 2005 as 18&#46;8 DID&#44; a very low level compared with that obtained by Campos et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> who took into account the total sales of antibiotics &#40;including private-health prescriptions as well as antibiotics purchased without a medical prescription&#41;&#46; The DID&#44; in this case&#44; was equal to 28&#46;93&#44; which placed Spain among the countries with highest consumption in Europe&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">There are other important differences in the choice of antibiotics between the two populations&#46; Penicillins were the drugs most utilized in both areas&#44; representing &#62;60&#37; of the total DID prescribed&#46; However&#44; while in Denmark 6 of every 10 prescriptions of penicillins correspond to narrow spectrum type&#44; in Arag&#243;n almost all the prescriptions of penicillins were the broad spectrum type&#46; The high prescription rate of broad spectrum penicillins in the Danish population &#62;60 years of age is explained&#44; in part&#44; by the treatment with pivmecillinam of urinary tract infections in women&#46; The use of tetracyclines&#44; higher in Denmark&#44; peaks in the 15&#8211;19 year age group which is reasonable since this is the antibiotic used in this age group to treat juvenile acne&#46; On the other hand&#44; the quinolones are observed among the most prescribed antibiotics in the adult Arag&#243;n population&#44; while its use is sporadic in Denmark&#46; Quinolones are among the antibiotics the WHO defines as Critically Important Antimicrobials &#40;CIA&#41; in medicine&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> the use of which should be rational and reserved for the treatment of serious infections in humans&#46; According to Spanish therapeutic recommendations&#44; quinolones are recommended as second-line treatment in several specific infections&#44; such as pneumonia or acute exacerbation of Chronic Obstructive Pulmonary Disease &#40;COPD&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Nevertheless&#44; the high number of DDD obtained could exhibit a low adherence to recommendations&#46; The use of cephalosporins represented around 8&#37; of the total DID in Arag&#243;n&#44; and was almost completely absent in Denmark&#46; Oral cephalosporins are not funded by the Danish NHS&#44; but they are funded by the NHS in Spain&#46; However&#44; these drugs are considered first-line neither in the treatment of RTIs&#44; nor in the majority of infections at other sites<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> and&#44; as such&#44; its high use in Spain is not justified&#46; The use of spiramycin with methronidazol&#44; a combination that is used almost exclusively in odontology&#44; was notable in Arag&#243;n while not being used in Denmark&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Earlier studies<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;20</span></a> had shown that there was a marked difference in the geographic pattern of north-south Europe in the outpatient consumption of antibiotics&#46; It is difficult to explain the high variability&#44; but some characteristics of both populations should be considered when trying to explicate the disparities observed&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Our two study populations did not have important demographic differences&#44; albeit the Arag&#243;n population showed an ageing that was slightly greater than the Danish population &#40;the &#62;80 age group was around 4&#37; in Denmark compared to around 7&#37; in Arag&#243;n&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;15</span></a> This does not appear to justify the differences observed&#44; since these differences are maintained when the rates are adjusted for age&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The type of health care organisation in both regions plays also an important role in the prescribing habits&#46; Danish Primary Health Care resembles the Spanish one in some aspects&#46; Both of them are mostly financed by public funds&#44; being the regions governments who manage the health care&#46; The two are based on a patient list system&#44; i&#46;e&#46; citizens are assigned to a GP&#44; who is responsible for serving the patients on his&#47;her list&#46; This system enables the GP to develop a better knowledge of the individual patient&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#44;22</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">On the other hand&#44; some differences between the ambulatory systems can be described&#46; Spanish GPs work within a team of GPs&#44; receiving a fixed salary regardless of the number of patients attended&#46; Nevertheless&#44; Danish GPs run private practices &#40;self-employed&#41;&#44; either on their own as solo practitioners or in collaboration with a few GPs more&#46; Two thirds of their incomes are fees for services rendered&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> This latter situation may sometimes cause that Danish GPs prescribe according to the patient&#39;s wishes&#44; to ensure upcoming consultations&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The number of inhabitants per GP in Denmark is not very distinct from that in Spain&#46; However&#44; in Spain there is in addition one paediatrician per 1029 inhabitants&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#44;22</span></a> Spanish children are normally treated by paediatricians&#44; whereas in Denmark all patients&#44; including children&#44; are treated by the GP&#46; Some authors noted that paediatricians may be more liberal prescribers than GPs&#44; and were more likely to prescribe antibiotics inappropriately&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Furthermore&#44; the number of pharmacies per inhabitant is about ten times higher in Spain than in Denmark&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#44;22</span></a> It should not be a negligible difference&#44; if we take into account the obtained results&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Some variables associated with an inappropriate prescription of antibiotics can be the fear of possible complications for the patients&#44; and the desire on the part of the physician to satisfy the expectations of the patient &#40;or their parents&#47;guardians&#44; in the case of children&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Until a few years ago&#44; obtaining an antibiotic in a Spanish pharmacy without a medical prescription was not an unusual practice&#46; As a consequence&#44; Spanish patients could have greater expectations to receive an antibiotic when they attend the medical consultation by reason of an infection&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The frequency of patients&#8217; attendance in the outpatient clinic and&#47;or the high clinical work-load could also be factors related to the prescription increase&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> In Spain&#44; citizens attend outpatient clinics more often than those residing in rest of Europe and the mean duration of the clinical visit in the Primary Care Centre is 5&#46;4<span class="elsevierStyleHsp" style=""></span>min&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Contrarily&#44; in Denmark&#44; the mean duration of a consultation is 10&#8211;15<span class="elsevierStyleHsp" style=""></span>min&#46; Time constraint is a risk factor for antibiotic overprescribing&#46; It takes longer time to explain a patient the reasons for not prescribing an antibiotic than it takes to make a prescription&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Llor et al&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> compared GPs prescription of antibiotics for RTIs in Denmark and Spain&#46; These authors showed the different approaches to the choice of antibiotics for RTIs existing in both countries&#46; Danish GPs used primarily narrow spectrum penicillin for most of the RTIs&#44; while Spanish GPs preferred broad spectrum penicillins either alone or in combination with clavulanic acid&#46; Current Spanish guidelines recommend the use of broad spectrum antibiotics as first-line treatment in some urinary tract infections&#44; exacerbation of COPD or pneumonia in the elderly&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> National guidelines are developed considering the different resistance patterns existing in each country&#46; Given that bacterial resistance to the most used antimicrobials is clearly distinct in the two study areas&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> the recommendations for some of the most frequent infections are different&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The utilization of different diagnostic methods in general practice may influence on the prescription of antibiotics as well&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> Most Danish GPs use a rapid antigen test &#40;strep A&#41; or a C-reactive protein &#40;CRP&#41; as a support to verify the diagnoses of bacterial tonsillitis or lower respiratory infection&#46; These tests have been shown to reduce the number of patients treated with antibiotics&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;29</span></a> In Spain&#44; none of these tests are used routinely in general practice&#46; It could explain&#44; at least partially&#44; the higher antibiotic prescription rates obtained in the Spanish region&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Some previous studies<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;27</span></a> highlighted that there is a low probability that the differences existing between the prescription habits of the Danish and Spanish physicians could be due to the unequal prevalence of RTIs receiving attention in Primary Care&#46; Also the pressure exerted by the pharmaceutical industry to the GPs plays an important part in the choice of the antibiotic&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> In Denmark&#44; there are strict rules to avoid doctors&#8217; potential influence of economic incentives from pharmaceutical companies&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> The situation is more liberal in Spain&#44; where drug companies are one of the main sources of information for physicians&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">As previously mentioned&#44; all these factors affecting the use of antibiotics in the two study populations such as different social and cultural traditions&#44; marketing policies of pharmaceutical companies&#44; organisation of the NHS&#44; or the national recommendations should be taken into account when comparing antibiotic use&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">One of the principal limitations of our study is that the Danish database included all the outpatient prescriptions of antibiotics in the country while&#44; in Arag&#243;n&#44; only the outpatient consumption funded by the NHS was taken into account i&#46;e&#46; no account was taken of the consumption in the Spanish region associated with other administrative&#47;funding entities such as private health prescriptions&#44; or drugs acquired without prescription&#44; or self-medication&#46; As has been highlighted&#44; these practices would have a significant impact on the overall consumption&#44; and could represent up to 30&#37; of actual utilization of antibiotics&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Therefore&#44; although the words &#8220;outpatient use&#8221;&#44; &#8220;utilisation&#8221; and &#8220;consumption&#8221; have been used all through the paper&#44; the analysis performed only included those antibiotics being prescribed in a medical prescription and funded by the NHS&#46; As such&#44; the data from our present study could be an underestimation of the real antibiotic utilisation&#44; particularly in Arag&#243;n&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Another limitation is that the consumption databases do not contain information on the clinical indication for which the antibiotic was prescribed&#46; As such&#44; the appropriateness of the prescription could not be evaluated&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">In conclusion&#44; the present study is useful in increasing the knowledge of outpatient antibiotic use in the two populations studied&#46; The data obtained suggest that&#44; in general&#44; women in both regions received a higher volume more frequently&#46; In Arag&#243;n&#44; the use of antibiotics in the population is very high&#44; while the data in Denmark indicate a more moderate use&#46; The different traditions&#44; habits&#44; pressures and recommendations existing in both countries should be considered when comparing these data&#46; The obtained results should be a starting point in the search for possible explanations for these variations&#44; and of solutions&#44; or updates on recommendations and prescription guidelines&#46; The misuse of antimicrobial drugs&#44; or their abuse&#44; favours the development and propagation of resistant bacteria&#44; which implies a health threat for the population&#46; Hence&#44; we consider it necessary to conduct interventions at national as well as international level to promote a rational use of antibiotics&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Funding</span><p id="par0160" class="elsevierStylePara elsevierViewall">S&#46; Malo was supported by a grant from the <span class="elsevierStyleGrantSponsor" id="gs0005">Programa Europa XXI</span>&#44; funded by the <span class="elsevierStyleGrantSponsor" id="gs0010">DGA &#40;CONAID&#41;</span> and the <span class="elsevierStyleGrantSponsor" id="gs0015">Inmaculada Savings Bank</span> &#91;Grant number <span class="elsevierStyleGrantNumber" refid="gs0015">CM 8&#47;12</span> to S&#46;M&#93;&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">The work received external funding from the <span class="elsevierStyleGrantSponsor" id="gs0020">Proyecto del Fondo de Investigaci&#243;n Sanitaria</span> &#40;Instituto de Salud Carlos III&#44; Spanish Ministry of Science&#44; Grant <span class="elsevierStyleGrantNumber" refid="gs0020">PI10&#47;01048</span>&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflict of interest</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Antibiotic use and misuse are linked to pathogen resistance and&#44; as such&#44; both constitute a public health issue with local&#44; national&#44; and global dimensions&#46; Early studies have shown striking variations in the use of these drugs between Nordic and Mediterranean countries&#46; The aim of the present study was to describe and compare antibiotic prescribing in Primary Care in Denmark and Arag&#243;n &#40;a North-eastern Spanish region&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Outpatient antibiotic prescription data &#40;2010&#41; were obtained from the National Institute for Health Data and Disease Control &#40;Denmark&#41;&#44; and the Information System on Medication Consumption in Arag&#243;n&#46; The consumption of antibiotics &#40;ATC J01&#41; was analyzed from the prescription rates and the number of defined daily dose &#40;DDD&#41; per 1000 inhabitants&#47;day &#40;DID&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The rate of antibiotic prescription in 2010 in Arag&#243;n was greater than in Denmark &#40;407 compared to 315 exposed individuals&#47;1000 inhabitants&#41;&#46; There were significant differences as regards overall consumption of antibiotics &#40;23&#46;2 DID in Arag&#243;n and 17&#46;0 DID in Denmark&#41;&#44; as well as the therapeutic group selection&#46; There was an elevated use of broad spectrum penicillins&#44; quinolones and cephalosporins in the Spanish region while&#44; in Denmark&#44; the most-consumed antibiotic was narrow spectrum penicillin&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The use of antibiotics in the Spanish region is very high&#44; and there are marked differences in the choice of drug between this region and Denmark&#46; Interventions are needed that promote the rational use of these drugs to reduce potential bacterial resistance&#44; and to avoid unnecessary risks to patients&#46;</p>"
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        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El uso inadecuado de antibi&#243;ticos se ha relacionado con la aparici&#243;n de resistencias microbianas&#44; constituyendo as&#237; un problema de salud p&#250;blica de dimensiones locales&#44; nacionales y globales&#46; Estudios previos han mostrado importantes diferencias en el uso de estos f&#225;rmacos entre los pa&#237;ses n&#243;rdicos y los mediterr&#225;neos&#46; El objetivo de este estudio fue describir y comparar la prescripci&#243;n antibi&#243;tica en atenci&#243;n primaria en Dinamarca y Arag&#243;n&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Los datos de utilizaci&#243;n extrahospitalaria de antibi&#243;ticos &#40;2010&#41; se obtuvieron del National Institute for Health Data and Disease Control &#40;Dinamarca&#41; y del Sistema de Informaci&#243;n de Consumo Farmac&#233;utico de Arag&#243;n&#46; El consumo de antibi&#243;ticos &#40;ATC J01&#41; se analiz&#243; mediante las tasas de prescripci&#243;n y el n&#250;mero de dosis diaria definida por 1&#46;000 habitantes&#47;d&#237;a &#40;DHD&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La tasa de prescripci&#243;n antibi&#243;tica en 2010 en Arag&#243;n fue superior a la de Dinamarca &#40;407 frente a 315 expuestos&#47;1&#46;000 habitantes&#41;&#46; Se observaron diferencias significativas en cuanto al consumo total de antibi&#243;ticos &#40;23&#44;2 DHD en Arag&#243;n y 17 DHD en Dinamarca&#41;&#44; as&#237; como en la elecci&#243;n del grupo terap&#233;utico&#46; La utilizaci&#243;n de penicilinas de amplio espectro&#44; quinolonas y cefalosporinas en la regi&#243;n espa&#241;ola fue elevada&#44; mientras que en Dinamarca el antibi&#243;tico m&#225;s consumido fue una penicilina de espectro reducido&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El uso de antibi&#243;ticos en Arag&#243;n es elevado&#44; y existen importantes diferencias en la elecci&#243;n del tipo de f&#225;rmaco entre esta regi&#243;n y Dinamarca&#46; Ser&#237;a conveniente desarrollar intervenciones que promuevan el uso racional de estos f&#225;rmacos&#44; para reducir las resistencias bacterianas y evitar riesgos innecesarios a los pacientes&#46;</p>"
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Article information

ISSN: 0213005X
Original language: English

DOI:10.1016/j.eimc.2013.10.002

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Year/Month	Html	Pdf	Total

2024 October	35	5	40
2024 September	66	19	85
2024 August	39	5	44
2024 July	55	6	61
2024 June	39	9	48
2024 May	26	21	47
2024 April	21	21	42
2024 March	34	14	48
2024 February	40	8	48
2024 January	40	12	52
2023 December	44	27	71
2023 November	33	25	58
2023 October	38	33	71
2023 September	24	16	40
2023 August	18	6	24
2023 July	22	27	49
2023 June	18	4	22
2023 May	16	3	19
2023 April	24	1	25
2023 March	20	8	28
2023 February	20	8	28
2023 January	12	13	25
2022 December	32	10	42
2022 November	62	32	94
2022 October	72	22	94
2022 September	71	16	87
2022 August	35	25	60
2022 July	21	12	33
2022 June	23	17	40
2022 May	30	8	38
2022 April	38	22	60
2022 March	41	16	57
2022 February	74	4	78
2022 January	48	10	58
2021 December	48	33	81
2021 November	39	13	52
2021 October	54	13	67
2021 September	47	10	57
2021 August	32	12	44
2021 July	43	10	53
2021 June	40	10	50
2021 May	29	8	37
2021 April	58	27	85
2021 March	56	10	66
2021 February	37	9	46
2021 January	36	4	40
2020 December	39	13	52
2020 November	42	15	57
2020 October	30	13	43
2020 September	51	16	67
2020 August	33	16	49
2020 July	34	18	52
2020 June	27	19	46
2020 May	46	21	67
2020 April	60	13	73
2020 March	51	15	66
2020 February	40	8	48
2020 January	32	16	48
2019 December	51	23	74
2019 November	29	21	50
2019 October	29	10	39
2019 September	35	15	50
2019 August	35	10	45
2019 July	49	22	71
2019 June	64	27	91
2019 May	181	88	269
2019 April	76	51	127
2019 March	36	7	43
2019 February	43	12	55
2019 January	40	8	48
2018 December	60	10	70
2018 November	56	15	71
2018 October	61	9	70
2018 September	107	5	112
2018 August	62	0	62
2018 July	18	5	23
2018 June	15	0	15
2018 May	19	10	29
2018 April	35	2	37
2018 March	19	1	20
2018 February	16	5	21
2018 January	28	1	29
2017 December	19	3	22
2017 November	21	2	23
2017 October	29	4	33
2017 September	10	17	27
2017 August	32	3	35
2017 July	26	3	29
2017 June	41	11	52
2017 May	59	9	68
2017 April	32	4	36
2017 March	28	28	56
2017 February	38	4	42
2017 January	40	1	41
2016 December	47	3	50
2016 November	42	3	45
2016 October	90	12	102
2016 September	61	5	66
2016 August	46	2	48
2016 July	28	1	29
2016 June	33	5	38
2016 May	30	4	34
2016 April	30	6	36
2016 March	55	13	68
2016 February	43	19	62
2016 January	39	16	55
2015 December	41	14	55
2015 November	37	9	46
2015 October	37	17	54
2015 September	46	20	66
2015 August	55	8	63
2015 July	42	3	45
2015 June	28	5	33
2015 May	47	10	57
2015 April	36	12	48
2015 March	36	9	45
2015 February	73	3	76
2015 January	37	11	48
2014 December	61	11	72
2014 November	43	16	59
2014 October	62	25	87
2014 September	83	70	153
2014 August	29	49	78

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