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Opioid consumption in the Community of Madrid (Spain) between 2004 and 2014
Consumo de opioides en la Comunidad de Madrid (España) entre 2004 y 2014
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Ruiz-López, A. Alonso-Babarro" "autores" => array:2 [ 0 => array:4 [ "nombre" => "D." "apellidos" => "Ruiz-López" "email" => array:2 [ 0 => "diego.ruiz@salud.madrid.org" 1 => "dieruizlopez@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "A." "apellidos" => "Alonso-Babarro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Equipo de Soporte Paliativo Domiciliario (ESAPD), Centro de Salud Legazpi, Dirección Asistencial Noroeste de Atención Primaria, Servicio Madrileño de Salud, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Cuidados Paliativos, Hospital Universitario La Paz, Servicio Madrileño de Salud, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Consumo de opioides en la Comunidad de Madrid (España) entre 2004 y 2014" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1129 "Ancho" => 2453 "Tamanyo" => 121155 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Total consumption of WHO step II and step III opioids in the Community of Madrid between 2004 and 2014.</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>: CM, Community of Madrid; DID, defined daily doses/1000 inhabitants/day; WHO, World Health Organization.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Pain is the most stressful and feared symptom for patients at the end-of-life.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">1</span></a> The treatment of cancer pain is based on a proper assessment and the rational use of analgesics and co-analgesics according to the ladder of the World Health Organization (WHO).<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">2</span></a> Opioids are essential drugs in treating cancer pain and intense pain in general.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Studies on the consumption and use of drugs have analyzed the marketing, distribution, prescription and use of drugs and their medical, societal and economic consequences.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">3</span></a> Daily defined dose (DDD)<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">4</span></a> is a measure that corresponds to the mean daily maintenance dose of a drug for adults for their main indication, through a specified administration route. The DDD helps describe the drug-treatment significance of consumption much better than other parameters such as the number of containers, prescriptions and economic cost.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Worldwide opioid consumption has increased since the publication of the WHO analgesic ladder in 1986, coinciding with the development of palliative care. However, the majority of opioid use has been concentrated in a small group of countries.<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">5,6</span></a> In recent years, the considerable majority of publications on opioids have focused on opioid abuse and the resulting deaths. This is a worldwide problem, although the highest figures have been reached by the United States, the largest consumer of opioids worldwide.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a> An authentic “opioid epidemic” has been described, with disastrous secondary effects on the population, which has set off alarms on the use of these drugs. Studies on opioid consumption could act as a public health alert if, as it seems, opioid abuse behaviors are closely related to a country's opioid consumption.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">8</span></a> Moreover, the opioid consumption profile at the international level is not correlated with that indicated by clinical practice guidelines. Factors such as the pharmaceutical industry, therapeutic novelty and a lack of training could influence the pattern of consumption.<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">9,10</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Studies on opioid consumption are scarce and show considerable heterogeneity. In the literature on opioid consumption in Spain, we found fairly fragmented data on the evolution of overall consumption in the various autonomous communities and on the relationship between opioid consumption in primary care and specialized care.<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">11,12</span></a> The main objective of our study was to report on the overall consumption of opioids and its evolution in the Community of Madrid (Spain) between 2004 and 2014.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">We conducted an analytical, observational, retrospective study of prescriptions performed in Madrid in all primary care and specialized care centers of Madrid's public health network between 2004 and 2014, as well as of the prescriptions of 3 large hospitals of Madrid's public health network to determine the influence of 3 hospital departments (palliative care, oncology and pain management) on the total hospital consumption of each opioid analyzed.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In 2004 at the start of the study, Madrid had a population of 5,804,829 inhabitants; by 2014 at the end of the study, it had 6,454,440 inhabitants.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">13</span></a> The raw data on opioid consumption between 2004 and 2014 was provided by General Deputy Directorate of Pharmacy and Healthcare Products of the Ministry of Health of Madrid. These data were converted to DDD for subsequent grouping and analysis.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The data on intrahospital opioid consumption was obtained from information from the hospital pharmacy departments of the 3 major public hospitals of Madrid (all with more than 700 hospital beds). The hospitals expressed their desire to keep their names confidential. Data were disaggregated by year (from 2009 to 2014) and by the various hospital departments. Two of the databases were Farmatools<span class="elsevierStyleSup">®</span> databases, and the other was an IFMS<span class="elsevierStyleSup">®</span> database, developed by INDRA Sistemas, S.A.</p><p id="par0040" class="elsevierStylePara elsevierViewall">For the household palliative care support teams (<span class="elsevierStyleItalic">Equipos de Soporte de Atención Paliativa Domiciliaria</span>, ESAPD), we could only analyze the consumption of morphine and methadone in 2014, given that they were the only opioids dispensed from the primary care pharmacy department and the only year for which data was available.</p><p id="par0045" class="elsevierStylePara elsevierViewall">We analyzed the data on the consumption of opioids available in Spain: morphine, fentanyl, buprenorphine, oxycodone, methadone, hydromorphone, meperidine, pentazocine and tapentadol within the opioid drug group that constitutes the WHO's analgesic step III, as well as tramadol, codeine, dihydrocodeine and dextropropoxyphene, in WHO's analgesic step II.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study methodology for opioid consumption</span><p id="par0050" class="elsevierStylePara elsevierViewall">Prescription drug consumption in primary care is expressed in doses per inhabitant per day (DID).<elsevierMultimedia ident="eq0005"></elsevierMultimedia></p><p id="par0055" class="elsevierStylePara elsevierViewall">We analyzed the variation between the starting and ending years of our study (2004 and 2014) to establish the annual and overall differences using the following formula:<elsevierMultimedia ident="eq0010"></elsevierMultimedia></p><p id="par0060" class="elsevierStylePara elsevierViewall">We also analyzed the percentage of DID of each opioid, compared with the total, to determine the specific weight of each opioid compared with the others, employing the following equation:<elsevierMultimedia ident="eq0015"></elsevierMultimedia></p><p id="par0065" class="elsevierStylePara elsevierViewall">For opioid consumption by department in the 3 large hospitals, we calculated the DDD per 1000 annual hospital stays with the formula indicated above. After calculating the total consumption of each opioid, we calculated the consumption of each opioid by study year in the hospital departments of palliative care, oncology and pain management.</p><p id="par0070" class="elsevierStylePara elsevierViewall">The project was approved by the Central Research Commission of Primary Care Management of the Ministry of Health of the Community of Madrid on the 17th of February 2016 (protocol code 01/16).</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Total opioid consumption in Madrid between 2004 and 2014</span><p id="par0075" class="elsevierStylePara elsevierViewall">We calculated opioid consumption by taking into account the sum of each opioid in primary care, specialized care and for patients hospitalized in the hospitals of the public health network of Madrid.</p><p id="par0080" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> shows the total data for each analgesic step. A sustained increase over the 11 years can be observed in both groups. The DIDs were 2.67 and 8.10 in 2004 and 2014, respectively. Total opioid consumption has increased almost 3-fold during this period, with a somewhat larger increase in step II opioid consumption than step III (step II: 1.49 DIDs in 2004 vs. 5.19 DIDs in 2014; step III: 1.19 DIDs in 2004 vs. 2.91 DIDS in 2014).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Tramadol was the most widely prescribed drug (4.12 DIDs in 2014). To appreciate this evolution in more detail, <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> shows only the step III opioids. Fentanyl (1.23 DIDs in 2014) and morphine (0.52 DIDs in 2014) were the most prescribed opioids, with a continuous annual increase. Oxycodone (0.31 DIDs in 2014) and buprenorphine (0.34 DIDs in 2014) were next in line. The use of oxycodone grew at rapid rate during the initial years of the study but has slowed in recent years.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarizes the interannual variation in opioid consumption between 2004 and 2014. The use of all step II analgesic opioids has declined, except for tramadol. The use of all step III opioids grew but in different proportions. The use of morphine and methadone increased the least. <a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a> shows the percentage of use of the various step III opioids compared with the total.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Opioid consumption in primary care in Madrid between 2004 and 2014</span><p id="par0095" class="elsevierStylePara elsevierViewall">The step III opioid most often consumed in primary care by DID was fentanyl (0.92 DIDs in 2014). Morphine (0.12 DIDs in 2014) was exceeded by buprenorphine, oxycodone and, in 2014, tapentadol, with estimated DIDs in 2014 of 0.31, 0.20 and 0.14, respectively (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Opioid consumption in primary care in Madrid between 2004 and 2014</span><p id="par0100" class="elsevierStylePara elsevierViewall">In parallel with primary care opioid consumption, we studied opioid consumption resulting from prescriptions from public hospitals and specialized care institutions in Madrid. The step III opioid most often prescribed was fentanyl, with 0.05 DIDs in 2014. Oxycodone was more widely employed than in primary care, with a peak consumption in 2011 and 2012 (0.04 DIDs for both years) when it became the second most widely employed opioid globally after tramadol. Tapentadol was also more widely consumed in specialized care than in primary care (0.03 DIDs in 2014) The opioid consumption by hospital prescription of morphine was low, less than that of fentanyl, oxycodone and, in 2014, tapentadol.</p><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Intrahospital opioid consumption of the public health network of Madrid between 2004 and 2014</span><p id="par0105" class="elsevierStylePara elsevierViewall">Within the hospitals, morphine was the most consumed opioid (0.38 DIDs in 2014), even when considering step II opioids. The second most consumed opioids were tramadol and fentanyl (0.27 and 0.26 DIDs in 2014, respectively). The other opioids had anecdotal consumption, although methadone was more widely employed than in primary care, with 0.08 DIDs in hospitals and 0.01 DIDs in primary care. <a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a> shows only the consumption of WHO step III analgesic opioids.</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Opioid consumption in 3 large hospitals of the public health network of Madrid between 2009 and 2014</span><p id="par0110" class="elsevierStylePara elsevierViewall">We studied in detail the opioid consumption in 3 major public hospitals of the Community of Madrid. In the case of morphine, we observed that palliative care units and oncology departments prescribed 40–50% of all opioids in the 3 hospitals. Fentanyl presented a pattern different to the above and was employed mostly in oncology (25–35% of the total), while barely being employed in palliative care units (2–11%). Oxycodone reflected intermediate consumption levels between morphine and fentanyl; the oncology departments used 40% of the total in the hospitals. Lastly, methadone consumption was affected because it was included in the parenteral detoxification of patients with drug addiction. Methadone was the most widely used, in proportion, by palliative care units; in one of the hospitals, the consumption of methadone constituted 35% of the total for the hospital.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Opioid consumption in primary care home palliative care support teams (ESAPD) in Madrid in 2014</span><p id="par0115" class="elsevierStylePara elsevierViewall">We studied specific consumption in ESAPDs in 2014, with data on opioids supplied by the primary care pharmacy departments. The consumption of methadone in ESAPDs was 31.06% of the total for primary care, and the consumption of morphine was 2.31% of the total of the consumption in primary care.</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0120" class="elsevierStylePara elsevierViewall">Our study has provided a report on the evolution of opioid consumption in the Community of Madrid between 2004 and 2014. We have found no previous studies on opioid consumption as complete at the national or international level. The Spanish Agency for Medicines and Medical Devices (AEMPS) published an analysis between 1992 and 2006, using a similar methodology,<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">14</span></a> with 0.4 and 4.4 DIDs for opioids in 1992 and 2006, respectively. However, this study did not conduct a detailed analysis of the consumption. Various analyses at the regional level have been published.<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">15–17</span></a> In a study of Catalonia, the DIDs were 1.7 and 2.8 in 2009 and 2014, respectively; however, step II analgesic opioids were not included. In Navarra, opioid consumption data showed DIDs of 1.7 and 10.7 in 2000 and 2014, respectively, but only included opioids indicated for treating chronic nononcologic pain. These studies allow us to assume that the evolution in opioid consumption has proceeded in parallel in the various autonomous communities of Spain and therefore that many of our study's conclusions can be applied to the entire country.</p><p id="par0125" class="elsevierStylePara elsevierViewall">In the more developed countries, opioid consumption has increased in recent years.<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">18,19</span></a> According to data from the WHO collaborating center of the University of Wisconsin for the study of pain,<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">20</span></a> the countries with the greatest opioid consumption in 2014 were Canada (967.26 morphine equivalents [MEQs]), the US (700.78 MEQs) and Australia (494.69 MEQs). In the same year in Europe, Denmark had a consumption of 481.24 MEQs, the United Kingdom had 424.41 MEQs and Norway had 299.66 MEQs. However, the countries of southern Europe had a slightly lower consumption: Portugal with 230.34 MEQs, France with 213.57 MEQs and Italy with 155.55 MEQs. The data obtained on the Community of Madrid, expressed in the same manner as this study source, indicate a consumption of 103.73<span class="elsevierStyleHsp" style=""></span>mg/capita in 2014, having observed a highly pronounced growth from 2004, when opioid use was 43.96<span class="elsevierStyleHsp" style=""></span>mg/capita. In developing countries with little progress in healthcare systems, much lower opioid consumption figures have been published.<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">21</span></a> Uganda, for example, consumed 1.05 EM in 201420.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">20</span></a> Various published studies have revealed the barriers for access to opioids that determine their consumption.</p><p id="par0130" class="elsevierStylePara elsevierViewall">We found no studies that have compared the growth in the dispensing of step II and III analgesics. Our data show that step II opioids have grown in use much more quickly in recent years, revealing a clear increased concern for pain at all healthcare levels.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Morphine, as the best example of classical opioids, has undergone a clear reduction proportional to the overall opioid consumption in the Community of Madrid. This situation has been repeated in almost all countries in Europe and in studies published in Spain.<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">22,23</span></a> The new opioids (fentanyl, oxycodone, buprenorphine and tapentadol) have relegated morphine to a highly secondary role. Countries such as the United Kingdom, which has greater implementation of training in pain management and palliative care, and countries with economic difficulties in accessing all opioids have a different opioid consumption profile, where morphine occupies a central role among opioids.<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">9,24,25</span></a> Morphine remains the opioid of choice for moderate-severe oncologic pain and is the most cost-effective.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">9</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">The fentanyl “phenomenon” needs to be analyzed separately. The emergence of new transmucosal fentanyl formulations for breakthrough cancer pain has also been responsible for the growth in its consumption. In our study, fentanyl represented approximately 40% of the total consumption of step III analgesics.</p><p id="par0145" class="elsevierStylePara elsevierViewall">Palliative care units in Madrid started a little more than 25 years ago, and their development has been exponential, both at the home and hospital level. During the 11 years of our study, home and hospital coverage was completed throughout the region. Our data show that hospital and home palliative care teams employed morphine and methadone more often than other available opioids. This preference for the 2 opioids is similar to that observed in the United Kingdom,<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">26</span></a> the country with the greatest implementation of palliative care units.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">27</span></a> Therefore, the hypothesis that palliative care departments can positively influence the appropriateness and pattern of prescription of opioid consumption appears to be reasonable. A better understanding of clinical practice guidelines and greater experience in using opioids could explain these findings.<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">10,28–30</span></a> Moreover, dosage convenience and the persistence of a certain fear of morphine could also determine a different profile of use.</p><p id="par0150" class="elsevierStylePara elsevierViewall">Opioid misuse and abuse have reached epidemic levels in the US.<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">8,31–34</span></a> In Spain, opioid misuse and abuse has already been reported, especially regarding the emergence of “rapid fentanyls”, although concrete data are still not available. It seems clear that the higher the opioid consumption in a country, the greater the risk for opioid abuse.<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">6,26,27,30</span></a> In a large number of cases, these behaviors are associated with the consumption of other drugs such as benzodiazepines and psychostimulants.<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">30</span></a> The increase in opioid consumption in Spain is unquestionably linked to an increase in the risk of opioid abuse.<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">35–40</span></a> There should be a balance between preventive and corrective measures for these abusive practices and the elimination of barriers that prevent the correct use of opioids in patients with pain. We are currently immersed in a public health problem that requires the intervention of health authorities, although starting with each of the clinicians who prescribe opioids. Studies on opioid consumption could help define the risks in each region, although more studies are needed to relate the evolution of opioid consumption and aberrant opioid consumption.</p><p id="par0155" class="elsevierStylePara elsevierViewall">Our study has a number of limitations. Firstly, the prescriptions issued do not necessarily involve the consumption of that drug. Additionally, these prescriptions can be issued in the Community of Madrid and be consumed in other regions of Spain. However, this study methodology is accepted internationally as the most appropriate for studying drug consumption. Secondly, we do not know the actual indication for the prescribed opioids, and we cannot therefore make valid assumptions as to how the prescriptions are distributed between oncologic and nononcologic pain treatment. Thirdly, not all hospitals of the public health network of Madrid had all commercial opioids during the study period, Which limits the possible comparisons; in reality, however, this lack of access has not significantly affected the results. Lastly, methadone, in addition to its use as a WHO step III analgesic, is employed as parenteral detoxification for patients addicted to drugs. However, we observed that methadone was the least prescribed opioid among all marketed opioids, and its use appears to be very specifically related to palliative care teams.</p><p id="par0160" class="elsevierStylePara elsevierViewall">In conclusion, opioid consumption in the Community of Madrid between 2004 and 2014 increased more than 3-fold. Tramadol was the most widely prescribed opioid, followed by fentanyl, morphine, buprenorphine, oxycodone and tapentadol. The profile found in our study coincides with that in the reviewed literature in Spain and in other countries. Palliative care teams in Madrid showed a consumption of mostly morphine and methadone over the other opioids. According to the literature, this profile appears to be the most cost-effective and coincides with that of the United Kingdom, considered the pioneer and the most advanced in the development of palliative care.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Funding</span><p id="par0165" class="elsevierStylePara elsevierViewall">The research project received a Research Support Grant from the <span class="elsevierStyleGrantSponsor" id="gs1">Foundation for Biomedical Research and Innovation in Primary Care (FIIBAP) of the Madrid Health Department in the 2016 call</span> (protocol code 01/16).</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflicts of interest</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1276552" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1180653" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1276551" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Materiales y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1180652" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Background" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study methodology for opioid consumption" ] ] ] 6 => array:3 [ "identificador" => "sec0020" "titulo" => "Results" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Total opioid consumption in Madrid between 2004 and 2014" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Opioid consumption in primary care in Madrid between 2004 and 2014" ] 2 => array:3 [ "identificador" => "sec0035" "titulo" => "Opioid consumption in primary care in Madrid between 2004 and 2014" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Intrahospital opioid consumption of the public health network of Madrid between 2004 and 2014" ] ] ] 3 => array:2 [ "identificador" => "sec0045" "titulo" => "Opioid consumption in 3 large hospitals of the public health network of Madrid between 2009 and 2014" ] 4 => array:2 [ "identificador" => "sec0050" "titulo" => "Opioid consumption in primary care home palliative care support teams (ESAPD) in Madrid in 2014" ] ] ] 7 => array:2 [ "identificador" => "sec0055" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0060" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0065" "titulo" => "Conflicts of interest" ] 10 => array:2 [ "identificador" => "xack438435" "titulo" => "Acknowledgements" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-11-22" "fechaAceptado" => "2019-02-09" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1180653" "palabras" => array:4 [ 0 => "Opioids" 1 => "Drug consumption" 2 => "Pain" 3 => "Palliative care" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1180652" "palabras" => array:4 [ 0 => "Opioides" 1 => "Consumo fármacos" 2 => "Dolor" 3 => "Cuidados paliativos" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Opioid consumption is an appropriate indicator of pain treatment. In Spain, there are scarcely any studies on the evolution of the consumption of opioids and their detailed use in the various settings.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We conducted an analytical, observational, retrospective study of prescriptions performed in the Community of Madrid in all primary care and specialized care centers and the three major hospitals between 2004 and 2014 to determine the influence of the various departments on the prescription of opioids.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Opioid consumption in Madrid between 2004 and 2014 increased more than 3-fold (2.67 vs. 8.10 defined daily doses/1000 inhabitants/day [DIDs] for 2004 and 2014, respectively). Tramadol was the most widely prescribed opioid (4.12 DIDs in 2014). Among the step III opioids, the most widely employed was fentanyl (1.23 DIDs in 2014). In primary care, the most prescribed step III opioids were fentanyl (0.92 DIDs in 2014), buprenorphine (0.31 DIDs in 2014), oxycodone (0.20 DIDs in 2014) and tapentadol (0.14 DIDs in 2014). In specialized care, the most prescribed opioids were fentanyl (0.05 DIDs in 2014), oxycodone (0.03 DIDs in 2014) and tapentadol (0.02 DIDs in 2014). In both cases, morphine represented a tiny percentage (0.12 primary care and 0.02 specialized care DIDs in 2014). Lastly, the most widely used opioid in the hospitals was morphine (0.38 DIDs in 2014), fentanyl (0.27 DIDs in 2014) and oxycodone (0.04 DIDs in 2014). For the palliative care teams (both home and hospital), the most consumed opioids were morphine (40–50% of the total) and methadone (35% of the total).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The overall consumption of opioids in Madrid tripled between 2004 and 2014. Tramadol and fentanyl were the most prescribed of the step II and III analgesics, respectively. The role of morphine is diminishing in the prescription of opioids.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes y objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El consumo de opioides es un indicador adecuado de cómo se trata el dolor. En España apenas existen estudios de la evolución del consumo y de su utilización pormenorizada en los distintos ámbitos.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Materiales y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio analítico, observacional, retrospectivo de las prescripciones realizadas en la Comunidad de Madrid (CM) en toda la atención primaria (AP) y la atención especializada (AE) entre 2004 y 2014 y de tres grandes hospitales, para determinar la influencia de los distintos servicios en su prescripción.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El consumo de opioides en la CM entre 2004 y 2014 aumentó más de tres veces (DHD 2004: 2,67; 2014: 8,10). El tramadol fue el opioide globalmente más prescrito (DHD 2014: 4,12). Entre los de tercer escalón, el más utilizado fue el fentanilo (DHD 2014: 1,23). En AP los opioides más prescritos de tercer escalón fueron el fentanilo (DHD 2014: 0,92), seguido de la buprenorfina (DHD 2014: 0,31), la oxicodona (DHD 2014: 0,20) y el tapentadol (DHD 2014: 0,14). En AE los opioides más prescritos fueron el fentanilo (DHD 2014: 0,05), la oxicodona (DHD 2014: 0,03) y el tapentadol (DHD 2014: 0,02). En ambos casos la morfina representaba un porcentaje muy reducido (DHD 2014: AP 0,12 y AE 0,02). Por último, el opioide más utilizado en los hospitales fue la morfina (DHD 2014: 0,38), seguido del fentanilo (DHD 2014: 0,27) y la oxicodona (DHD 2014: 0,04). Los equipos de cuidados paliativos, tanto domiciliarios como hospitalarios, mostraron un consumo mayoritario de morfina (40-50% del total) y de metadona (35% del total).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El consumo global de opioides en la CM se triplicó entre 2004 y 2014. El tramadol y el fentanilo fueron los más prescritos del segundo y tercer escalón analgésico, respectivamente. La morfina está teniendo un papel residual en la prescripción de opioides.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Materiales y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Ruiz-López D, Alonso-Babarro A. Consumo de opioides en la Comunidad de Madrid (España) entre 2004 y 2014. Rev Clin Esp. 2019. <span class="elsevierStyleInterRef" id="intr0005" href="https://doi.org/10.1016/j.rce.2019.02.002">https://doi.org/10.1016/j.rce.2019.02.002</span></p>" ] ] "multimedia" => array:9 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1129 "Ancho" => 2453 "Tamanyo" => 121155 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Total consumption of WHO step II and step III opioids in the Community of Madrid between 2004 and 2014.</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>: CM, Community of Madrid; DID, defined daily doses/1000 inhabitants/day; WHO, World Health Organization.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1459 "Ancho" => 2496 "Tamanyo" => 178918 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Consumption of WHO step III analgesic opioids in the Community of Madrid between 2004 and 2014.</p> <p id="spar0060" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>: CM, Community of Madrid; DID, defined daily doses/1000 inhabitants/day.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1107 "Ancho" => 2288 "Tamanyo" => 132834 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Percentage use of step III opioids compared with all opioids.</p> <p id="spar0070" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>: WHO, World Health Organization.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 890 "Ancho" => 2434 "Tamanyo" => 132030 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Consumption of WHO step III analgesic opioids in primary care in the Community of Madrid between 2004 and 2014 expressed in defined daily doses/1000 inhabitants/day.</p> <p id="spar0080" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>: DID, defined daily doses/1000 inhabitants/day; PC, primary care.</p>" ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 965 "Ancho" => 2301 "Tamanyo" => 142725 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Intrahospital consumption of WHO step III analgesic opioids of the public health network of the Community of Madrid between 2004 and 2014 expressed in defined daily doses per 1000 annual hospital stays.</p> <p id="spar0090" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>: AHS, annual hospital stays; DDD, daily defined dose; WHO, World Health Organization.</p>" ] ] 5 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ATC code \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug name \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">% Variation 2004–2014 \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N02aa01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Buprenorphine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">251.40 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N02aa03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dextropropoxyphene \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−100.00 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N02aa05/N02aa55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dihydrocodeine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−100.00 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N02aa08 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fentanyl \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">137.80 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N02ab02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hydromorphone (2009–2014) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.04 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N02ab91 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Meperidine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40.32 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N02ac04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Morphine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27.74 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N02ad01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Oxycodone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14,172.59 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N02ae01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pentazocine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−100.00 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N02ax02/N02ax52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tapentadol (2011–2014) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">217.92 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N02aa59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tramadol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">304.91 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N07bc02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Codeine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">99.77 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N02ax06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Methadone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27.42 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total WHO step II opioids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">248.57 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total WHO step III opioids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">145.40 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total opioids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">202.77 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2183514.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Interannual variation of the opioids studied between 2004 and 2014 in the Community of Madrid.</p>" ] ] 6 => array:5 [ "identificador" => "eq0005" "tipo" => "MULTIMEDIAFORMULA" "mostrarFloat" => false "mostrarDisplay" => true "Formula" => array:5 [ "Matematica" => "DID=DDD by primary care prescription×1000number of inhabitants×365   days" "Fichero" => "STRIPIN_si1.jpeg" "Tamanyo" => 4842 "Alto" => 35 "Ancho" => 311 ] ] 7 => array:5 [ "identificador" => "eq0010" "tipo" => "MULTIMEDIAFORMULA" "mostrarFloat" => false "mostrarDisplay" => true "Formula" => array:5 [ "Matematica" => "Percentage increase in   2014   compared with   2004=DID2014−DID2004DID2004×100" "Fichero" => "STRIPIN_si2.jpeg" "Tamanyo" => 5315 "Alto" => 59 "Ancho" => 343 ] ] 8 => array:5 [ "identificador" => "eq0015" "tipo" => "MULTIMEDIAFORMULA" "mostrarFloat" => false "mostrarDisplay" => true "Formula" => array:5 [ "Matematica" => "Percentage use compared with the total   (%   total)=DID of each opioidDID of all opioids" "Fichero" => "STRIPIN_si3.jpeg" "Tamanyo" => 5877 "Alto" => 60 "Ancho" => 337 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:40 [ 0 => array:3 [ "identificador" => "bib0205" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Palliative care: the World Health Organization's global perspective" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "C. Sepúlveda" 1 => "A. Marlin" 2 => "T. Yoshida" 3 => "A. Ullrich" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Pain Symptom Manag" "fecha" => "2002" "volumen" => "24" "paginaInicial" => "91" "paginaFinal" => "96" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0210" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cancer pain management according to WHO analgesic guidelines" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S.A. Schug" 1 => "D. Zech" 2 => "U. 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Solano Garzón" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Med Paliat" "fecha" => "2018" "volumen" => "25" "paginaInicial" => "175" "paginaFinal" => "183" ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack438435" "titulo" => "Acknowledgements" "texto" => "<p id="par0175" class="elsevierStylePara elsevierViewall">We would like to thank Technical Support for the <span class="elsevierStyleGrantSponsor" id="gs2">Research Unit of the Deputy Management of Primary Care of the Community of Madrid</span> for their methodology support. We would also like to thank the Deputy directorate General of Pharmacy and Healthcare Products of the Community of Madrid and the hospital pharmacy departments of the hospitals that were part of the study for providing the data on opioid consumption.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/22548874/0000021900000007/v1_201912172116/S2254887419300815/v1_201912172116/en/main.assets" "Apartado" => array:4 [ "identificador" => "1901" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/22548874/0000021900000007/v1_201912172116/S2254887419300815/v1_201912172116/en/main.pdf?idApp=WRCEE&text.app=https://revclinesp.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887419300815?idApp=WRCEE" ]
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