Drug Prescription Strategies in the Treatment of Patients With Fibromyalgia

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The different treatments being used have not yet obtained the satisfactory results expected which is why patients with FM continue to maintain the same clinical manifestations even many years after being diagnosed.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>Pharmacological treatment options are quite broad because many drugs that act on the central nervous system may have beneficial effects in these patients.<a class="elsevierStyleCrossRefs" href="#bib0010">2,3</a> Analgesic, anti-inflammatory drugs (NSAIDs), antidepressants, anticonvulsants, benzodiazepines and other drugs that act on the central nervous system are used as the first line treatment in patients with FM, although in most cases are not directed towards the treatment overall disease, but only to address some of the symptoms.However, due to the many adverse effects of these drugs also, one must be aware of what they can each contribute to the treatment of fibromyalgia and prevent overmedication, a problem often seen in these patients.On the other hand, there are no studies to determine what type of drug is most effective, or what sequence or association should be used to obtain the best possible results.Therefore, in this situation, when administering a drug to treat fibromyalgia not only choosing among several possibilities is the responsibility of the physician, but also knowing what strategy is the most effective.The aim of this paper is to analyze the different strategies of drug treatment followed by rheumatologists specializing in the treatment of patients with FM and determine which ones are most effective.MethodsPatientsMen and women over 18 years with the diagnosis of FM according to the criteria of the American College of Rheumatology<a class="elsevierStyleCrossRef" href="#bib0020">4</a> were consecutively included, between January and April 2007. The patients came from the outpatient clinics of rheumatology of 15 different centers throughout Spain (project ICAF).All physicians who participated in the study were selected for their special dedication to the treatment of patients with fibromyalgia. Before the study began, there was a meeting with all participating centers to standardize performance criteria between different doctors, as recommended by the consensus document of the Spanish Society of Rheumatology on fibromyalgia.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>Exclusion criteria were cardiopulmonary or other crippling diseases, morbid obesity, inflammatory rheumatic diseases and unbalanced psychiatric diseases. We also excluded those patients involved in reporting disability claims, litigation or any type of compensation processes.The study protocol was approved by the ethics committee of clinical research at the Hospital General Universitario Gregorio Marañón in Madrid.Study DesignThis is a prospective study with 2 separate visits over a period of 3 months for establishing a drug treatment in routine clinical practice conditions.At the initial visit, after signing the informed consent document, the patient was interviewed face to face and sociodemographic, clinical variables were collected, as were drugs currently being used to treat fibromyalgia.Clinical evaluation was performed using the recently validated ICAF questionnaire for our population.<a class="elsevierStyleCrossRefs" href="#bib0025">5,6</a> It consists of 4 factors: emotional, physical, active coping and passive coping as well as an overall score. ICAF assesses emotional aspects, such as anxiety and depression, and the impact they have on the patient's social environment (emotional factor). It also assesses the patient's functional capacity, fatigue, sleep quality and pain (physical factor) and the way in which the patient confronts her illness (factors of active and passive coping). As for how to score: the higher the score of each factor and the overall score, the worse the patient's clinical condition except in active coping indicating that the patient has more resources to address the disease (<a class="elsevierStyleCrossRef" href="#sec0055">Annex 2 “Combined allocation index in patients with fibromyalgia (ICAF). Spanish version”</a>).The evaluation of drugs mainly included is that acts on the central nervous system: benzodiazepines, hypnotics, antidepressants, anticonvulsants, antihistamines, antipsychotics, and analgesics, opioids and NSAIDs.Then the new treatment was prescribed according to usual clinical practice conditions, with the physician specialist modifying the treatment that the patient had been undergoing if they felt ill. The specialist advised all patients to undergo physical exercise in a generic way, but other non-pharmacological treatments such as psychological therapy, relaxation techniques, acupuncture, or massage diets were kept in the same preconditions that the patient had been subjected to. No other recommendation was performed and there was neither special treatment nor any limitation for prescription drug treatment in any of the centers where the study was undertaken.At the final visit the same evaluations were performed again, same as were made at the first visit and the drugs the patient was taking again quantified.Statistical AnalysisBefore beginning the analysis, patient data were carefully reviewed to study the distribution of frequencies and detect defects collection. Data for ICAF scores are expressed in scores T, as previously described in the work original.<a class="elsevierStyleCrossRef" href="#bib0025">5</a>In the statistical analysis compared the number and type of drugs used in the initial visit compared to the final visit, as well as differences in the overall score and each of the factors of the ICAF.Missing data were resolved following 2 strategies: data for the initial visit were used as vertical median for each group, and lost data from the final visit were completed by dragging the data from the initial visit, considering more conservative procedure.We performed a descriptive statistical analysis of data on both visits and compared it using the t-test for related samples for the differences between the scores of the initial and final views.To evaluate treatment efficacy between the two visits we calculated the effect size. The effect size is an index that expresses the magnitude of a change<a class="elsevierStyleCrossRef" href="#bib0035">7</a>; that is, an index of how much the difference between two groups is. The magnitude of the effect size is measured according to the categories proposed by Cohen, which considers a value >0.8–0.5 as large, between 0.5 and 0.2 as moderate and <0.2 as small.We used the statistical software version 17.0 SPSS WIN for statistical analysis and considered significant a P<.05.ResultsWe included 232 patients in the analysis, 98% women, mean age 47.7±8.6 years and duration of disease 4.3±4.0 years. All physicians provided approximately the same number of patients per study.The number of drugs to treat FM was 3.1±1.6 drugs/patient at the initial visit, with the distribution shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. After treatment the number of drugs rose to 3.4±1.9 drugs/patient (P<.017) in the final visit. The major changes between the two visits occurred between NSAIDs, antidepressants, benzodiazepines and anticonvulsants (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>For further analysis we only took into account drugs that act directly on the central nervous system and analgesics and NSAIDs were discarded. Moreover, the consumption of hypnotics has added the use of benzodiazepines, since in many cases they are also used to induce sleep.The most significant changes were: an increase in the number of antidepressants, from 0.50±0.50 to 0.71±0.45 (P<.0001) antidepressants/patient an increase number of anticonvulsants, from 0.14±0.35 to 0.41±0.49 (P<.0001) anticonvulsants/patient, and a reduction in the number of benzodiazepines, from 0.48±0.50 to 0.38±0.48 (P<.001) benzodiazepines/patient. Regarding the number of drugs introduced into treatment only one was introduced in 87 patients in 15 patients 2 were entered and in 4 patients 3 drugs were introduced simultaneously.From the point of view of clinical manifestations, there was a significant improvement between the initial and the final visits affecting the emotional and physical factors, active coping and overall score in the total group of patients.Specific Strategies for Change in Treatment and its ConsequencesSpecific strategies for change in the treatment followed by physicians in the study were to add an anticonvulsant alone (17.7% patients), adding an antidepressant alone (14.7% patients) or add both drugs simultaneously (6.5% of patients).However, it is noteworthy that the most common strategy was to stop all treatment in 35.8% of patients. Within this group, 26% of patients not taking medication for central nervous system, but 25% of them took one, 36% took 2 and 11% took 3 of the drugs.The remaining strategies were varied and were used in 25.3% of patients. In many cases, the strategy involved the suspension of a drug replaced by the introduction of another, so it was difficult to assess their effectiveness individually.At the initial visit, we found no statistically significant differences between treatment groups in the baseline variables studied: age, sex, duration of disease, time since diagnosis or employment status. There were also no differences in baseline total score of ICAF or any of its four factors (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>When considering the therapeutic measures taken subsequently, we analyzed two situations: the presence or absence of changes. When comparing patients in which a drug was discontinued (n=26) with those where a drug was introduced (n=102), the only significant difference was that the emotional factor scored higher (worse emotional score) compared to the group of patients where a drug was introduced (49.77±8.87 vs 54.45±9.92, P=.021), but no significant differences in other factors or the overall score.The group of patients who underwent the strategy and in whom the treatment was not modified, there was no additional benefits for patients. Overall ICAF score and its factors were not significantly changed in this group of patients between the initial and final visits.In the group of patients in whom the strategy was to add only an anticonvulsant, there were significant differences in emotional and physical factors as well as the overall score with a moderate effect size (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).At the other group of patients in which only an antidepressant was added, there were also significant differences in the overall score and the emotional and physical factors with a slightly higher effect size than in the previous group (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Note that the greatest effect among the factors was achieved in the physical component of ICAF.Finally, in the patient group in which the strategy was the introduction of both drugs, antidepressant and anticonvulsant effects were the greatest of all figures with effect size close to 1 (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).While the strategy of adding an antidepressant or an anticonvulsant was generally made exclusively, a change in strategy with benzodiazepines was not as smooth. These were added and suspended exclusively in about the same number of patients, but also changes in benzodiazepines more often accompanied the introduction or withdrawal of the other 2 drugs. Regardless of changes in the other 2 drugs, overall benzodiazepines were discontinued in 36 patients and were added as new drug in only 3 patients. The analysis of the strategy to discontinue benzodiazepines produced an improvement in the overall score and in all factors except passive coping (data not shown).DiscussionIn this paper we have analyzed some of the most common strategies of drug administration followed by a group of physicians with special attention to the treatment of patients with FM, in conditions of medical practice. The results suggest that certain changes in the drug delivery strategy are accompanied by significant changes in clinical status of patients.As a general strategy, there was a significant increase in the total number of drugs used to treat patients and more often involve the introduction of a single drug.Some of the treatment strategies were used more often than others by the physicians of this study, and among them, strategies to individually incorporate an antidepressant, an anticonvulsant or both drugs simultaneously were clearly more frequent. Other strategies, for example stopping benzodiazepines, were used, and although there were indications that it may also be beneficial, it could not be tested due to the small number of patients in this situation since this strategy was accompanied, often, in exchange for some other drugs.However, the strategy of not making changes to the treatment was the most frequent of all affecting 36% of patients. However, in these patients the clinical evaluation of the initial and final visits showed no significant differences in the clinical situation of patients.There remains considerable skepticism regarding FM<a class="elsevierStyleCrossRef" href="#bib0040">8</a> and a fairly widespread opinion among physicians is that drug treatment does not provide much benefit so the patients are often only treated with drugs to treat symptoms of pain, mainly analgesics and NSAIDs.One possible explanation may lie in the fact that in the European Union there is no indication of drug treatment in FM, while in the U.S., the FDA3 has approved 2 drugs, dual antidepressants and inhibitors of serotonin and norepinephrine (duloxetine and milnacipram), and an anticonvulsant drug (pregabalin) for this indication. Therefore, in the European Union, these drugs can only be given when dealing with clinical manifestations for which they are approved; however, in many FM patients these clinical manifestations are not exactly the most relevant.In this sense, the finding in our study that the only difference between patients to whom drugs were introduced and those to which the drug was discontinued, emotional factors, which measure anxiety and depression, confirm that these drugs were prescribed to treat these symptoms and not others such as pain, fatigue, and functional capacity as measured by the physical factor.A meta-analysis has shown that various recent<a class="elsevierStyleCrossRef" href="#bib0045">9</a> antidepressants produce a particularly favorable effect on pain, sleep, mood, fatigue and mood status changes, but with a low effect size in relation to perceived quality of life. Something similar happens with anticonvulsants, which have also shown that there is a degree of hard evidence that pregabalin and gabapentin produced improvement in pain and sleep, but not on fatigue or mood alterations.<a class="elsevierStyleCrossRef" href="#bib0050">10</a>In our work we found that administration of an antidepressant or an anticonvulsant individually improves the patient's general condition with a moderate effect size. However, when added both at the same time the effect size increases by almost 50% compared to antidepressants and up to 100% with respect to anticonvulsants. This finding is consistent with that recently suggested by some authors.<a class="elsevierStyleCrossRef" href="#bib0055">11</a>However, we cannot rule that the mere change of drug treatment, adding 2 new drugs, could have a positive impact beyond their specific effect. The change itself and the expectations of the patient before can have a therapeutic effect.<a class="elsevierStyleCrossRef" href="#bib0060">12</a>It is noteworthy that the major effect of these drugs occurs precisely on the physical factor of ICAF followed the emotional factor. The factors of active and passive coping did not change significantly, as there are ways in which patients cope with the disease and are not modified in the short term by the introduction of a drug.<a class="elsevierStyleCrossRef" href="#bib0030">6</a>The criterion to follow a particular strategy has not been entirely uniform among physicians in the study. Thus, the strategy to not modify the treatment was followed by physicians in 36% of patients despite their clinical situation in terms of degree of impairment was similar to that of other patients who used other strategies. However, within this group of patients, 74% were receiving one or more drugs so the scope for any type of change was large.Moreover, there was a similar number of patients to whom only benzodiazepines were suspended or added, suggesting that some strategies are not shared unanimously by all physicians.The main limitation of this study is that it has not been able to evaluate all possible strategies of drug administration but only those most frequently followed by doctors, and we cannot conclude on which is the most effective strategy. Originally the study was not designed for it so the results are only for guidelines on clinical practice in the sample of clinical units involved in the study.Another limitation is that some variables were not analyzed in this study and yet may behave as potential confounders. Variables such as comorbidity, or treatment followed for this, and were not evaluated in our study and may affect results obtained in relation to the effectiveness of different strategies.Although it initially was not recommended that researchers change the preconditions of psychological therapy or physical exercise, it is possible that over the 3-month follow-up study period there was some sort of modification that may have influenced the results.We note that the importance of this study is that it allows us to know which are the main strategies of prescription drugs for fibromyalgia patients followed in our environment and in conditions of medical practice. Although data from our study cannot ensure the best possible strategy, we found some evidence to suggest that among the most common strategies some of them might be superior to others. These findings should be tested in future studies.FinancingThis study was financed by the Fondo de Investigación Sanitaria (FIS)PI 07/0202, of the Health and Consumption ministry.Conflict of InterestsPfizer Pharmaceuticals contributed economically to the development of the ICAF project as a research Project of the Spanish Foundation for Rheumatology. The 3 authors of the study have been principal investigators of the ICAF project." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:2 [ "identificador" => "xres125852" "titulo" => array:5 [ 0 => "Abstract" 1 => "Objective" 2 => "Methods" 3 => "Results" 4 => "Conclusion" ] ] 1 => array:2 [ "identificador" => "xpalclavsec113147" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres125851" "titulo" => array:5 [ 0 => "Resumen" 1 => "Objetivo" 2 => "Métodos" 3 => "Resultados" 4 => "Conclusión" ] ] 3 => array:2 [ "identificador" => "xpalclavsec113146" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Study Design" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical Analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0030" "titulo" => "Results" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Specific Strategies for Change in Treatment and its Consequences" ] ] ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0045" "titulo" => "Financing" ] 9 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflict of Interests" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-01-24" "fechaAceptado" => "2012-02-01" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec113147" "palabras" => array:7 [ 0 => "Fibromyalgia" 1 => "Antidepressive agents" 2 => "Anticonvulsants" 3 => "Benzodiazepines" 4 => "Therapeutics" 5 => "Questionnaires" 6 => "Outcome assessment (health care)" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec113146" "palabras" => array:7 [ 0 => "Fibromialgia" 1 => "Antidepresivos" 2 => "Anticonvulsivante" 3 => "Benzodiacepinas" 4 => "Tratamiento" 5 => "Cuestionarios" 6 => "Evaluación de medidas de desenlace" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo analyze prescription strategies followed by rheumatologist specialized in fibromyalgia (FM) treatment. MethodsA prospective, multicentric, 3-month follow-up study with two visits. The drug treatment was started following usual clinical practice conditions. Prescription of benzodiazepines, hypnotics, anticonvulsants and antidepressants were those mainly studied. Clinical evaluation was performed by the ICAF (combined index of affection in patients with fibromyalgia) questionnaire. The most frequent strategies and their size effect were calculated. ResultsA total of 232 patients attending 15 rheumatology centers were included. The introduction of an anticonvulsant or an antidepressant was the most common drug strategies followed in 17.7% and 14.7% of patients, respectively. Both strategies produced a statistically significant clinical improvement. The most effective strategy (with an effect size of nearly 1) was the introduction of both drugs (6.5% patients), which increased the antidepressants effect size in 50% and 100% for anticonvulsants. The strategy of not changing the number of drug prescriptions was the most frequent (35.8% patients) but no significant clinical improvement was found in these patients. Some other strategies were very uncommon and have not been analyzed in this study. ConclusionThe introduction of anticonvulsants or antidepressants, in an isolated or combined form, produces a significant clinical improvement in FM patients. The most effective drug strategy is the introduction of both drugs at the same time. The least effective strategy is not to change the number of drug prescriptions." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "ObjetivoAnalizar las diferentes estrategias de prescripción seguidas por reumatólogos especializados en FM. MétodosEstudio prospectivo, multicéntrico, con 2 visitas separadas 3 meses en el que se instaura un tratamiento farmacológico en condiciones de práctica clínica habitual. Se analizó fundamentalmente la prescripción de benzodiacepinas, hipnóticos, antidepresivos y anticonvulsivantes. La evaluación clínica se realizó mediante el cuestionario ICAF (Índice combinado de afectación en pacientes con fibromialgia). Se determinaron las estrategias más frecuentes y se calculó el tamaño del efecto para analizar su eficacia. ResultadosSe incluyó a 232 pacientes con FM atendidos en 15 consultas de reumatología. Las estrategias más comunes fueron la introducción aislada de un anticonvulsivante (17,7%) o un antidepresivo (14,7), que produjeron mejorías clínicas estadísticamente significativas. La estrategia más eficaz (tamaño del efecto próximo a 1) fue la introducción simultánea de ambos fármacos (6,5%), que aumentó en un 50% el tamaño del efecto de antidepresivos y en un 100% el de anticonvulsivantes. La estrategia de no realizar ningún cambio en el número de fármacos fue la más frecuente (35,8%) pero no mostró mejoría clínica significativa. Otras estrategias fueron muy poco frecuentes y no han sido analizadas. ConclusiónLas estrategias de prescripción de fármacos anticonvulsivantes o antidepresivos de manera aislada o en combinación producen una mejoría clínica significativa en los pacientes con FM. La estrategia más eficaz es la introducción de ambos fármacos simultáneamente. La menos eficaz es no realizar ningún cambio." ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Rivera J, et al. Estrategias de prescripción de fármacos en el tratamiento de pacientes con fibromialgia. Reumatol Clin. 2012;8:184–8." ] 1 => array:2 [ "etiqueta" => "◊" "nota" => "The names of the components of the Group ICAF are listed in Annex 1." ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:3 [ "apendice" => "ICAF group: Alegre C. (Hospital Vall de Hebrón, Barcelona), Belenguer R. (Hospital 9 de Octubre, Valencia), Belmonte M. (Hospital General de Castellón, Castellón), Beltrán J. (Hospital General de Castellón, Castellón), Blanch J. (Hospital IMAS, Barcelona), Collado A. (Hospital Clínic, Barcelona), Fernández Dapica P. (Hospital Universitario 12 de Octubre, Madrid), Francisco Hernández F.M. (Hospital Dr. Negrín, Gran Canaria), García Monforte A. (Hospital Universitario Gregorio Marañón, Madrid), González Hernández T. (IPR, Madrid), González Polo J. (Hospital Universitario La Paz, Madrid), Hidalgo C. (Centro Reumatológico, Salamanca), Mundo J. (Hospital Clínic, Barcelona), Muñoz Carreño P. (Hospital General, Guadalajara), Vallejo I. (Hospital Clínic, Barcelona), Vidal J. (Hospital General, Guadalajara)." "etiqueta" => "Annex 1" "identificador" => "sec0055" ] ] ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "ns=non significant." "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"><td class="td" title="\n \t\t\t\t\ttable-head\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-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Initial Visit</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Final Visit</td><td 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">Dif. % \t\t\t\t\t\t\n \t\t\t\t</td><td 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">P \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-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Patients \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Patients \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">Analgesics \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">148 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63.8 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">136 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58.6 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−5.2 \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">ns \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NSAID \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">132 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56.9 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">105 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45.3 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−11.6 \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">.0001 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antidepressants \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">118 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50.9 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">167 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72.0 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+21.1 \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">.0001 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Benzodiazepines \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">104 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">44.8 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32.3 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−12.5 \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">.0001 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anticonvulsants \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.7 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">96 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41.4 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+26.7 \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">.0001 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypnotics \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.0 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.6 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+2.6 \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">ns \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.4 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.6 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+2.2 \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">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab212348.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Type of Drug Employed in 232 Patients With FM and Individual Changes Produced After Treatment in Everyday Clinical Practice Conditions." ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "ACO: anticonvulsant; ADE: antidepressant; Cop.: coping; SD: standard deviation; ns: non significant." "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"><td 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">Factors \t\t\t\t\t\t\n \t\t\t\t</td><td 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">Groups \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Initial Visit</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Final Visit</td><td 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">P<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td 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">Size of the Effect \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Confidence Interval</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Mean \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">SD \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Mean \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Sup. \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Inf. \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Emotional</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">ACO \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">50.52 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.53 \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">46.52 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.02 \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">.005 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.50 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.94 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.06 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ADE \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">47.53 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.67 \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">43.55 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.97 \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">.001 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.58 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−1.06 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.09 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ACO+ADE \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">48.51 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.80 \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">42.83 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.94 \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">.006 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.92 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−1.64 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.14 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">P<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \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">ns \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="" 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">0.033 \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="" 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="" 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="" 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="" 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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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 " colspan="10" align="left" valign="\n \t\t\t\t\ttop\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 " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Physical</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">ACO \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">51.73 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.74 \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">44.12 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.92 \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">.003 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.73 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−1.17 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.27 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ADE \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">48.36 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.30 \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">38.90 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.30 \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">.0001 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.90 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−1.39 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.39 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ACO+ADE \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">46.79 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.91 \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">37.56 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.87 \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">.008 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.98 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−1.71 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.20 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">P<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \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">ns \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="" 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">ns \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="" 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="" 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="" 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="" 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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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 " colspan="10" align="left" valign="\n \t\t\t\t\ttop\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 " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cop. active</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">ACO \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">49.50 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.13 \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">48.14 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.38 \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">ns \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.16 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.59 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.28 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ADE \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">50.02 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.27 \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">52.08 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.83 \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">ns \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.19 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.29 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.66 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ACO+ADE \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">47.01 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.62 \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">53.35 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.64 \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">.002 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.65 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.10 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.37 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">P<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \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">ns \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="" 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">ns \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="" 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="" 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="" 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="" 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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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 " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cop. passive</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">ACO \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">52.45 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.85 \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">51.62 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.35 \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">ns \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.08 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.51 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.35 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ADE \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">50.14 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.30 \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">49.36 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.42 \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">ns \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.08 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.55 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.40 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ACO+ADE \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">49.95 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.22 \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">49.85 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.79 \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">ns \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.01 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.73 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.70 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">P<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \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">ns \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="" 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">ns \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="" 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="" 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="" 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="" 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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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 " colspan="10" align="left" valign="\n \t\t\t\t\ttop\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 " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Global ICAF</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">ACO \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">51.57 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.56 \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">47.25 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.78 \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">.003 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.48 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.91 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.03 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ADE \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">48.29 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.75 \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">42.23 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.03 \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">.0001 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.68 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−1.16 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.19 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ACO+ADE \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">49.36 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.34 \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">41.04 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.94 \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">.003 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.99 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−1.72 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.20 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">P<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \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">ns \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="" 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">0.013 \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="" 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="" 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="" 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="" 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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab212349.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Value of P for intragroup differences between initial and final visit." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "Value of P for differences among groups of each one of the factors." ] ] ] "descripcion" => array:1 [ "en" => "Differences in Factors and Global ICAF Scores Between Groups of Patients in Which an Anticonvulsant (ACO; n=41), an Antidepressant (ADE; n=34) or Both Drugs Simultaneously Were Introduced (ACO+ADE; n=15). The Table Shows Values at the Initial Visit, Final Visit and the Size of the Effect Between Both." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:12 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The longitudinal outcome of fibromyalgia: a study of 1555 patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "B. Walitt" 1 => "M.A. Fitzcharles" 2 => "A.L. Hassett" 3 => "R.S. Katz" 4 => "W. Hauser" 5 => "F. Wolfe" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3899/jrheum.110026" "Revista" => array:5 [ "tituloSerie" => "J Rheumatol" "fecha" => "2011" "volumen" => "38" "paginaInicial" => "10" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20952462" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Documento consenso de Sociedad Española de Reumatología sobre la fibromialgia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Rivera" 1 => "C. Alegre" 2 => "F. Ballina" 3 => "J. Carbonell" 4 => "L. Carmona" 5 => "B. 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Buskila" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2007.071522" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2008" "volumen" => "67" "paginaInicial" => "536" "paginaFinal" => "541" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17644548" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The American college of rheumatology 1990 criteria for the classification of fibromialgia. Report of the multicenter criteria committee" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Wolfe" 1 => "H.A. Smythe" 2 => "M.B. Yunus" 3 => "R.M. Bennett" 4 => "C. Bombardier" 5 => "D.L. 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Original Article

Drug Prescription Strategies in the Treatment of Patients With Fibromyalgia

Estrategias de prescripción de fármacos en el tratamiento de pacientes con fibromialgia

Javier Riveraa,

Corresponding author

javierrivera@ser.es

Corresponding author.

, Miguel Ángel Vallejob, Joaquim Esteve-Vivesc, ICAF Grupo ◊

a Unidad de Reumatología, Instituto Provincial de Rehabilitación, Hospital Universitario Gregorio Marañón, Madrid, Spain

b Departamento de Psicología de la Personalidad, Evaluación y Tratamientos Psicológicos, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain

c Sección Reumatología, Hospital General Universitari d’Alacant, Alicante, Spain

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    "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>"
    "titulo" => "Drug Prescription Strategies in the Treatment of Patients With Fibromyalgia"
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        "autoresLista" => "Javier Rivera, Miguel &#193;ngel Vallejo, Joaquim Esteve-Vives"
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                "identificador" => "fn0005"
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            "entidad" => "Unidad de Reumatolog&#237;a&#44; Instituto Provincial de Rehabilitaci&#243;n&#44; Hospital Universitario Gregorio Mara&#241;&#243;n&#44; Madrid&#44; Spain"
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            "entidad" => "Departamento de Psicolog&#237;a de la Personalidad&#44; Evaluaci&#243;n y Tratamientos Psicol&#243;gicos&#44; Universidad Nacional de Educaci&#243;n a Distancia &#40;UNED&#41;&#44; Madrid&#44; Spain"
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        "titulo" => "Estrategias de prescripci&#243;n de f&#225;rmacos en el tratamiento de pacientes con fibromialgia"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Treatment of patients with fibromyalgia &#40;FM&#41; is currently showing difficulties&#46; The different treatments being used have not yet obtained the satisfactory results expected which is why patients with FM continue to maintain the same clinical manifestations even many years after being diagnosed&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Pharmacological treatment options are quite broad because many drugs that act on the central nervous system may have beneficial effects in these patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> Analgesic&#44; anti-inflammatory drugs &#40;NSAIDs&#41;&#44; antidepressants&#44; anticonvulsants&#44; benzodiazepines and other drugs that act on the central nervous system are used as the first line treatment in patients with FM&#44; although in most cases are not directed towards the treatment overall disease&#44; but only to address some of the symptoms&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">However&#44; due to the many adverse effects of these drugs also&#44; one must be aware of what they can each contribute to the treatment of fibromyalgia and prevent overmedication&#44; a problem often seen in these patients&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">On the other hand&#44; there are no studies to determine what type of drug is most effective&#44; or what sequence or association should be used to obtain the best possible results&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Therefore&#44; in this situation&#44; when administering a drug to treat fibromyalgia not only choosing among several possibilities is the responsibility of the physician&#44; but also knowing what strategy is the most effective&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The aim of this paper is to analyze the different strategies of drug treatment followed by rheumatologists specializing in the treatment of patients with FM and determine which ones are most effective&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Patients</span><p id="par0035" class="elsevierStylePara elsevierViewall">Men and women over 18 years with the diagnosis of FM according to the criteria of the American College of Rheumatology<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> were consecutively included&#44; between January and April 2007&#46; The patients came from the outpatient clinics of rheumatology of 15 different centers throughout Spain &#40;project ICAF&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">All physicians who participated in the study were selected for their special dedication to the treatment of patients with fibromyalgia&#46; Before the study began&#44; there was a meeting with all participating centers to standardize performance criteria between different doctors&#44; as recommended by the consensus document of the Spanish Society of Rheumatology on fibromyalgia&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Exclusion criteria were cardiopulmonary or other crippling diseases&#44; morbid obesity&#44; inflammatory rheumatic diseases and unbalanced psychiatric diseases&#46; We also excluded those patients involved in reporting disability claims&#44; litigation or any type of compensation processes&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The study protocol was approved by the ethics committee of clinical research at the Hospital General Universitario Gregorio Mara&#241;&#243;n in Madrid&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Study Design</span><p id="par0055" class="elsevierStylePara elsevierViewall">This is a prospective study with 2 separate visits over a period of 3 months for establishing a drug treatment in routine clinical practice conditions&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">At the initial visit&#44; after signing the informed consent document&#44; the patient was interviewed face to face and sociodemographic&#44; clinical variables were collected&#44; as were drugs currently being used to treat fibromyalgia&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Clinical evaluation was performed using the recently validated ICAF questionnaire for our population&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> It consists of 4 factors&#58; emotional&#44; physical&#44; active coping and passive coping as well as an overall score&#46; ICAF assesses emotional aspects&#44; such as anxiety and depression&#44; and the impact they have on the patient&#39;s social environment &#40;emotional factor&#41;&#46; It also assesses the patient&#39;s functional capacity&#44; fatigue&#44; sleep quality and pain &#40;physical factor&#41; and the way in which the patient confronts her illness &#40;factors of active and passive coping&#41;&#46; As for how to score&#58; the higher the score of each factor and the overall score&#44; the worse the patient&#39;s clinical condition except in active coping indicating that the patient has more resources to address the disease &#40;<a class="elsevierStyleCrossRef" href="#sec0055">Annex 2 &#8220;Combined allocation index in patients with fibromyalgia &#40;ICAF&#41;&#46; Spanish version&#8221;</a>&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The evaluation of drugs mainly included is that acts on the central nervous system&#58; benzodiazepines&#44; hypnotics&#44; antidepressants&#44; anticonvulsants&#44; antihistamines&#44; antipsychotics&#44; and analgesics&#44; opioids and NSAIDs&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Then the new treatment was prescribed according to usual clinical practice conditions&#44; with the physician specialist modifying the treatment that the patient had been undergoing if they felt ill&#46; The specialist advised all patients to undergo physical exercise in a generic way&#44; but other non-pharmacological treatments such as psychological therapy&#44; relaxation techniques&#44; acupuncture&#44; or massage diets were kept in the same preconditions that the patient had been subjected to&#46; No other recommendation was performed and there was neither special treatment nor any limitation for prescription drug treatment in any of the centers where the study was undertaken&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">At the final visit the same evaluations were performed again&#44; same as were made at the first visit and the drugs the patient was taking again quantified&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Statistical Analysis</span><p id="par0085" class="elsevierStylePara elsevierViewall">Before beginning the analysis&#44; patient data were carefully reviewed to study the distribution of frequencies and detect defects collection&#46; Data for ICAF scores are expressed in scores T&#44; as previously described in the work original&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">In the statistical analysis compared the number and type of drugs used in the initial visit compared to the final visit&#44; as well as differences in the overall score and each of the factors of the ICAF&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Missing data were resolved following 2 strategies&#58; data for the initial visit were used as vertical median for each group&#44; and lost data from the final visit were completed by dragging the data from the initial visit&#44; considering more conservative procedure&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">We performed a descriptive statistical analysis of data on both visits and compared it using the <span class="elsevierStyleItalic">t</span>-test for related samples for the differences between the scores of the initial and final views&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">To evaluate treatment efficacy between the two visits we calculated the effect size&#46; The effect size is an index that expresses the magnitude of a change<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#59; that is&#44; an index of how much the difference between two groups is&#46; The magnitude of the effect size is measured according to the categories proposed by Cohen&#44; which considers a value &#62;0&#46;8&#8211;0&#46;5 as large&#44; between 0&#46;5 and 0&#46;2 as moderate and &#60;0&#46;2 as small&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">We used the statistical software version 17&#46;0 SPSS WIN for statistical analysis and considered significant a <span class="elsevierStyleItalic">P</span>&#60;&#46;05&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0115" class="elsevierStylePara elsevierViewall">We included 232 patients in the analysis&#44; 98&#37; women&#44; mean age 47&#46;7&#177;8&#46;6 years and duration of disease 4&#46;3&#177;4&#46;0 years&#46; All physicians provided approximately the same number of patients per study&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The number of drugs to treat FM was 3&#46;1&#177;1&#46;6 drugs&#47;patient at the initial visit&#44; with the distribution shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; After treatment the number of drugs rose to 3&#46;4&#177;1&#46;9 drugs&#47;patient &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;017&#41; in the final visit&#46; The major changes between the two visits occurred between NSAIDs&#44; antidepressants&#44; benzodiazepines and anticonvulsants &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">For further analysis we only took into account drugs that act directly on the central nervous system and analgesics and NSAIDs were discarded&#46; Moreover&#44; the consumption of hypnotics has added the use of benzodiazepines&#44; since in many cases they are also used to induce sleep&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The most significant changes were&#58; an increase in the number of antidepressants&#44; from 0&#46;50&#177;0&#46;50 to 0&#46;71&#177;0&#46;45 &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;0001&#41; antidepressants&#47;patient an increase number of anticonvulsants&#44; from 0&#46;14&#177;0&#46;35 to 0&#46;41&#177;0&#46;49 &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;0001&#41; anticonvulsants&#47;patient&#44; and a reduction in the number of benzodiazepines&#44; from 0&#46;48&#177;0&#46;50 to 0&#46;38&#177;0&#46;48 &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41; benzodiazepines&#47;patient&#46; Regarding the number of drugs introduced into treatment only one was introduced in 87 patients in 15 patients 2 were entered and in 4 patients 3 drugs were introduced simultaneously&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">From the point of view of clinical manifestations&#44; there was a significant improvement between the initial and the final visits affecting the emotional and physical factors&#44; active coping and overall score in the total group of patients&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Specific Strategies for Change in Treatment and its Consequences</span><p id="par0140" class="elsevierStylePara elsevierViewall">Specific strategies for change in the treatment followed by physicians in the study were to add an anticonvulsant alone &#40;17&#46;7&#37; patients&#41;&#44; adding an antidepressant alone &#40;14&#46;7&#37; patients&#41; or add both drugs simultaneously &#40;6&#46;5&#37; of patients&#41;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">However&#44; it is noteworthy that the most common strategy was to stop all treatment in 35&#46;8&#37; of patients&#46; Within this group&#44; 26&#37; of patients not taking medication for central nervous system&#44; but 25&#37; of them took one&#44; 36&#37; took 2 and 11&#37; took 3 of the drugs&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">The remaining strategies were varied and were used in 25&#46;3&#37; of patients&#46; In many cases&#44; the strategy involved the suspension of a drug replaced by the introduction of another&#44; so it was difficult to assess their effectiveness individually&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">At the initial visit&#44; we found no statistically significant differences between treatment groups in the baseline variables studied&#58; age&#44; sex&#44; duration of disease&#44; time since diagnosis or employment status&#46; There were also no differences in baseline total score of ICAF or any of its four factors &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0160" class="elsevierStylePara elsevierViewall">When considering the therapeutic measures taken subsequently&#44; we analyzed two situations&#58; the presence or absence of changes&#46; When comparing patients in which a drug was discontinued &#40;n&#61;26&#41; with those where a drug was introduced &#40;n&#61;102&#41;&#44; the only significant difference was that the emotional factor scored higher &#40;worse emotional score&#41; compared to the group of patients where a drug was introduced &#40;49&#46;77&#177;8&#46;87 vs 54&#46;45&#177;9&#46;92&#44; <span class="elsevierStyleItalic">P</span>&#61;&#46;021&#41;&#44; but no significant differences in other factors or the overall score&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">The group of patients who underwent the strategy and in whom the treatment was not modified&#44; there was no additional benefits for patients&#46; Overall ICAF score and its factors were not significantly changed in this group of patients between the initial and final visits&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">In the group of patients in whom the strategy was to add only an anticonvulsant&#44; there were significant differences in emotional and physical factors as well as the overall score with a moderate effect size &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">At the other group of patients in which only an antidepressant was added&#44; there were also significant differences in the overall score and the emotional and physical factors with a slightly higher effect size than in the previous group &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Note that the greatest effect among the factors was achieved in the physical component of ICAF&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Finally&#44; in the patient group in which the strategy was the introduction of both drugs&#44; antidepressant and anticonvulsant effects were the greatest of all figures with effect size close to 1 &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">While the strategy of adding an antidepressant or an anticonvulsant was generally made exclusively&#44; a change in strategy with benzodiazepines was not as smooth&#46; These were added and suspended exclusively in about the same number of patients&#44; but also changes in benzodiazepines more often accompanied the introduction or withdrawal of the other 2 drugs&#46; Regardless of changes in the other 2 drugs&#44; overall benzodiazepines were discontinued in 36 patients and were added as new drug in only 3 patients&#46; The analysis of the strategy to discontinue benzodiazepines produced an improvement in the overall score and in all factors except passive coping &#40;data not shown&#41;&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0190" class="elsevierStylePara elsevierViewall">In this paper we have analyzed some of the most common strategies of drug administration followed by a group of physicians with special attention to the treatment of patients with FM&#44; in conditions of medical practice&#46; The results suggest that certain changes in the drug delivery strategy are accompanied by significant changes in clinical status of patients&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">As a general strategy&#44; there was a significant increase in the total number of drugs used to treat patients and more often involve the introduction of a single drug&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Some of the treatment strategies were used more often than others by the physicians of this study&#44; and among them&#44; strategies to individually incorporate an antidepressant&#44; an anticonvulsant or both drugs simultaneously were clearly more frequent&#46; Other strategies&#44; for example stopping benzodiazepines&#44; were used&#44; and although there were indications that it may also be beneficial&#44; it could not be tested due to the small number of patients in this situation since this strategy was accompanied&#44; often&#44; in exchange for some other drugs&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">However&#44; the strategy of not making changes to the treatment was the most frequent of all affecting 36&#37; of patients&#46; However&#44; in these patients the clinical evaluation of the initial and final visits showed no significant differences in the clinical situation of patients&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">There remains considerable skepticism regarding FM<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> and a fairly widespread opinion among physicians is that drug treatment does not provide much benefit so the patients are often only treated with drugs to treat symptoms of pain&#44; mainly analgesics and NSAIDs&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">One possible explanation may lie in the fact that in the European Union there is no indication of drug treatment in FM&#44; while in the U&#46;S&#46;&#44; the FDA3 has approved 2 drugs&#44; dual antidepressants and inhibitors of serotonin and norepinephrine &#40;duloxetine and milnacipram&#41;&#44; and an anticonvulsant drug &#40;pregabalin&#41; for this indication&#46; Therefore&#44; in the European Union&#44; these drugs can only be given when dealing with clinical manifestations for which they are approved&#59; however&#44; in many FM patients these clinical manifestations are not exactly the most relevant&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">In this sense&#44; the finding in our study that the only difference between patients to whom drugs were introduced and those to which the drug was discontinued&#44; emotional factors&#44; which measure anxiety and depression&#44; confirm that these drugs were prescribed to treat these symptoms and not others such as pain&#44; fatigue&#44; and functional capacity as measured by the physical factor&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">A meta-analysis has shown that various recent<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> antidepressants produce a particularly favorable effect on pain&#44; sleep&#44; mood&#44; fatigue and mood status changes&#44; but with a low effect size in relation to perceived quality of life&#46; Something similar happens with anticonvulsants&#44; which have also shown that there is a degree of hard evidence that pregabalin and gabapentin produced improvement in pain and sleep&#44; but not on fatigue or mood alterations&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">In our work we found that administration of an antidepressant or an anticonvulsant individually improves the patient&#39;s general condition with a moderate effect size&#46; However&#44; when added both at the same time the effect size increases by almost 50&#37; compared to antidepressants and up to 100&#37; with respect to anticonvulsants&#46; This finding is consistent with that recently suggested by some authors&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">However&#44; we cannot rule that the mere change of drug treatment&#44; adding 2 new drugs&#44; could have a positive impact beyond their specific effect&#46; The change itself and the expectations of the patient before can have a therapeutic effect&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">It is noteworthy that the major effect of these drugs occurs precisely on the physical factor of ICAF followed the emotional factor&#46; The factors of active and passive coping did not change significantly&#44; as there are ways in which patients cope with the disease and are not modified in the short term by the introduction of a drug&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0245" class="elsevierStylePara elsevierViewall">The criterion to follow a particular strategy has not been entirely uniform among physicians in the study&#46; Thus&#44; the strategy to not modify the treatment was followed by physicians in 36&#37; of patients despite their clinical situation in terms of degree of impairment was similar to that of other patients who used other strategies&#46; However&#44; within this group of patients&#44; 74&#37; were receiving one or more drugs so the scope for any type of change was large&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Moreover&#44; there was a similar number of patients to whom only benzodiazepines were suspended or added&#44; suggesting that some strategies are not shared unanimously by all physicians&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">The main limitation of this study is that it has not been able to evaluate all possible strategies of drug administration but only those most frequently followed by doctors&#44; and we cannot conclude on which is the most effective strategy&#46; Originally the study was not designed for it so the results are only for guidelines on clinical practice in the sample of clinical units involved in the study&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">Another limitation is that some variables were not analyzed in this study and yet may behave as potential confounders&#46; Variables such as comorbidity&#44; or treatment followed for this&#44; and were not evaluated in our study and may affect results obtained in relation to the effectiveness of different strategies&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">Although it initially was not recommended that researchers change the preconditions of psychological therapy or physical exercise&#44; it is possible that over the 3-month follow-up study period there was some sort of modification that may have influenced the results&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">We note that the importance of this study is that it allows us to know which are the main strategies of prescription drugs for fibromyalgia patients followed in our environment and in conditions of medical practice&#46; Although data from our study cannot ensure the best possible strategy&#44; we found some evidence to suggest that among the most common strategies some of them might be superior to others&#46; These findings should be tested in future studies&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Financing</span><p id="par0275" class="elsevierStylePara elsevierViewall">This study was financed by the <span class="elsevierStyleGrantSponsor" id="gs0005">Fondo de Investigaci&#243;n Sanitaria &#40;FIS&#41;</span><span class="elsevierStyleGrantNumber" refid="gs0005">PI 07&#47;0202</span>&#44; of the Health and Consumption ministry&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of Interests</span><p id="par0280" class="elsevierStylePara elsevierViewall">Pfizer Pharmaceuticals contributed economically to the development of the ICAF project as a research Project of the Spanish Foundation for Rheumatology&#46; The 3 authors of the study have been principal investigators of the ICAF project&#46;</p></span></span>"
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          "identificador" => "xpalclavsec113147"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "xres125851"
          "titulo" => array:5 [
            0 => "Resumen"
            1 => "Objetivo"
            2 => "M&#233;todos"
            3 => "Resultados"
            4 => "Conclusi&#243;n"
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec113146"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
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        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Methods"
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            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Patients"
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            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Study Design"
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            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Statistical Analysis"
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          ]
        ]
        6 => array:3 [
          "identificador" => "sec0030"
          "titulo" => "Results"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Specific Strategies for Change in Treatment and its Consequences"
            ]
          ]
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        7 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Discussion"
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        8 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Financing"
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        9 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Conflict of Interests"
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        10 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2012-01-24"
    "fechaAceptado" => "2012-02-01"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec113147"
          "palabras" => array:7 [
            0 => "Fibromyalgia"
            1 => "Antidepressive agents"
            2 => "Anticonvulsants"
            3 => "Benzodiazepines"
            4 => "Therapeutics"
            5 => "Questionnaires"
            6 => "Outcome assessment &#40;health care&#41;"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec113146"
          "palabras" => array:7 [
            0 => "Fibromialgia"
            1 => "Antidepresivos"
            2 => "Anticonvulsivante"
            3 => "Benzodiacepinas"
            4 => "Tratamiento"
            5 => "Cuestionarios"
            6 => "Evaluaci&#243;n de medidas de desenlace"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To analyze prescription strategies followed by rheumatologist specialized in fibromyalgia &#40;FM&#41; treatment&#46;</p> <span class="elsevierStyleSectionTitle">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A prospective&#44; multicentric&#44; 3-month follow-up study with two visits&#46; The drug treatment was started following usual clinical practice conditions&#46; Prescription of benzodiazepines&#44; hypnotics&#44; anticonvulsants and antidepressants were those mainly studied&#46; Clinical evaluation was performed by the ICAF &#40;combined index of affection in patients with fibromyalgia&#41; questionnaire&#46; The most frequent strategies and their size effect were calculated&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A total of 232 patients attending 15 rheumatology centers were included&#46; The introduction of an anticonvulsant or an antidepressant was the most common drug strategies followed in 17&#46;7&#37; and 14&#46;7&#37; of patients&#44; respectively&#46; Both strategies produced a statistically significant clinical improvement&#46; The most effective strategy &#40;with an effect size of nearly 1&#41; was the introduction of both drugs &#40;6&#46;5&#37; patients&#41;&#44; which increased the antidepressants effect size in 50&#37; and 100&#37; for anticonvulsants&#46; The strategy of not changing the number of drug prescriptions was the most frequent &#40;35&#46;8&#37; patients&#41; but no significant clinical improvement was found in these patients&#46; Some other strategies were very uncommon and have not been analyzed in this study&#46;</p> <span class="elsevierStyleSectionTitle">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The introduction of anticonvulsants or antidepressants&#44; in an isolated or combined form&#44; produces a significant clinical improvement in FM patients&#46; The most effective drug strategy is the introduction of both drugs at the same time&#46; The least effective strategy is not to change the number of drug prescriptions&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Analizar las diferentes estrategias de prescripci&#243;n seguidas por reumat&#243;logos especializados en FM&#46;</p> <span class="elsevierStyleSectionTitle">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo&#44; multic&#233;ntrico&#44; con 2 visitas separadas 3 meses en el que se instaura un tratamiento farmacol&#243;gico en condiciones de pr&#225;ctica cl&#237;nica habitual&#46; Se analiz&#243; fundamentalmente la prescripci&#243;n de benzodiacepinas&#44; hipn&#243;ticos&#44; antidepresivos y anticonvulsivantes&#46; La evaluaci&#243;n cl&#237;nica se realiz&#243; mediante el cuestionario ICAF &#40;&#205;ndice combinado de afectaci&#243;n en pacientes con fibromialgia&#41;&#46; Se determinaron las estrategias m&#225;s frecuentes y se calcul&#243; el tama&#241;o del efecto para analizar su eficacia&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se incluy&#243; a 232 pacientes con FM atendidos en 15 consultas de reumatolog&#237;a&#46; Las estrategias m&#225;s comunes fueron la introducci&#243;n aislada de un anticonvulsivante &#40;17&#44;7&#37;&#41; o un antidepresivo &#40;14&#44;7&#41;&#44; que produjeron mejor&#237;as cl&#237;nicas estad&#237;sticamente significativas&#46; La estrategia m&#225;s eficaz &#40;tama&#241;o del efecto pr&#243;ximo a 1&#41; fue la introducci&#243;n simult&#225;nea de ambos f&#225;rmacos &#40;6&#44;5&#37;&#41;&#44; que aument&#243; en un 50&#37; el tama&#241;o del efecto de antidepresivos y en un 100&#37; el de anticonvulsivantes&#46; La estrategia de no realizar ning&#250;n cambio en el n&#250;mero de f&#225;rmacos fue la m&#225;s frecuente &#40;35&#44;8&#37;&#41; pero no mostr&#243; mejor&#237;a cl&#237;nica significativa&#46; Otras estrategias fueron muy poco frecuentes y no han sido analizadas&#46;</p> <span class="elsevierStyleSectionTitle">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Las estrategias de prescripci&#243;n de f&#225;rmacos anticonvulsivantes o antidepresivos de manera aislada o en combinaci&#243;n producen una mejor&#237;a cl&#237;nica significativa en los pacientes con FM&#46; La estrategia m&#225;s eficaz es la introducci&#243;n de ambos f&#225;rmacos simult&#225;neamente&#46; La menos eficaz es no realizar ning&#250;n cambio&#46;</p>"
      ]
    ]
    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara">Please cite this article as&#58; Rivera J&#44; et al&#46; Estrategias de prescripci&#243;n de f&#225;rmacos en el tratamiento de pacientes con fibromialgia&#46; Reumatol Clin&#46; 2012&#59;8&#58;184&#8211;8&#46;</p>"
      ]
      1 => array:2 [
        "etiqueta" => "&#9674;"
        "nota" => "<p class="elsevierStyleNotepara">The names of the components of the Group ICAF are listed in Annex 1&#46;</p>"
      ]
    ]
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:3 [
            "apendice" => "<p id="par0285" class="elsevierStylePara elsevierViewall">ICAF group&#58; Alegre C&#46; &#40;Hospital Vall de Hebr&#243;n&#44; Barcelona&#41;&#44; Belenguer R&#46; &#40;Hospital 9 de Octubre&#44; Valencia&#41;&#44; Belmonte M&#46; &#40;Hospital General de Castell&#243;n&#44; Castell&#243;n&#41;&#44; Beltr&#225;n J&#46; &#40;Hospital General de Castell&#243;n&#44; Castell&#243;n&#41;&#44; Blanch J&#46; &#40;Hospital IMAS&#44; Barcelona&#41;&#44; Collado A&#46; &#40;Hospital Cl&#237;nic&#44; Barcelona&#41;&#44; Fern&#225;ndez Dapica P&#46; &#40;Hospital Universitario 12 de Octubre&#44; Madrid&#41;&#44; Francisco Hern&#225;ndez F&#46;M&#46; &#40;Hospital Dr&#46; Negr&#237;n&#44; Gran Canaria&#41;&#44; Garc&#237;a Monforte A&#46; &#40;Hospital Universitario Gregorio Mara&#241;&#243;n&#44; Madrid&#41;&#44; Gonz&#225;lez Hern&#225;ndez T&#46; &#40;IPR&#44; Madrid&#41;&#44; Gonz&#225;lez Polo J&#46; &#40;Hospital Universitario La Paz&#44; Madrid&#41;&#44; Hidalgo C&#46; &#40;Centro Reumatol&#243;gico&#44; Salamanca&#41;&#44; Mundo J&#46; &#40;Hospital Cl&#237;nic&#44; Barcelona&#41;&#44; Mu&#241;oz Carre&#241;o P&#46; &#40;Hospital General&#44; Guadalajara&#41;&#44; Vallejo I&#46; &#40;Hospital Cl&#237;nic&#44; Barcelona&#41;&#44; Vidal J&#46; &#40;Hospital General&#44; Guadalajara&#41;&#46;</p>"
            "etiqueta" => "Annex 1"
            "identificador" => "sec0055"
          ]
        ]
      ]
    ]
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        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">ns&#61;non significant&#46;</p>"
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " colspan="2" align="center" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Initial Visit</td><td class="td" title="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Final Visit</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Dif&#46; &#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">P</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Patients&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Analgesics&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">148&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">63&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">136&nbsp;\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="char" valign="\n
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                  \t\t\t\t">58&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">&#8722;5&#46;2&nbsp;\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">ns&nbsp;\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="left" valign="\n
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                  \t\t\t\t">NSAID&nbsp;\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="char" valign="\n
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                  \t\t\t\t">132&nbsp;\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="char" valign="\n
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                  \t\t\t\t">56&#46;9&nbsp;\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="char" valign="\n
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                  \t\t\t\t">105&nbsp;\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="char" valign="\n
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                  \t\t\t\t">45&#46;3&nbsp;\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="char" valign="\n
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                  \t\t\t\t">&#8722;11&#46;6&nbsp;\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
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                  \t\t\t\t">&#46;0001&nbsp;\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="left" valign="\n
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                  \t\t\t\t">Antidepressants&nbsp;\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="char" valign="\n
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                  \t\t\t\t">118&nbsp;\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">167&nbsp;\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="char" valign="\n
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                  \t\t\t\t">72&#46;0&nbsp;\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="char" valign="\n
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                  \t\t\t\t">&#43;21&#46;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#46;0001&nbsp;\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="left" valign="\n
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                  \t\t\t\t">Benzodiazepines&nbsp;\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="char" valign="\n
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                  \t\t\t\t">104&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">44&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">75&nbsp;\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#46;3&nbsp;\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;12&#46;5&nbsp;\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">&#46;0001&nbsp;\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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anticonvulsants&nbsp;\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="char" valign="\n
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                  \t\t\t\t">34&nbsp;\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;7&nbsp;\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">96&nbsp;\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="char" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">&#43;26&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Hypnotics&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">6&#46;0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Other&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">3&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;6&nbsp;\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;2&#46;2&nbsp;\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">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab212348.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Type of Drug Employed in 232 Patients With FM and Individual Changes Produced After Treatment in Everyday Clinical Practice Conditions&#46;</p>"
        ]
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      1 => array:7 [
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        "tabla" => array:3 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">ACO&#58; anticonvulsant&#59; ADE&#58; antidepressant&#59; Cop&#46;&#58; coping&#59; SD&#58; standard deviation&#59; ns&#58; non significant&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " colspan="2" align="center" valign="\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Mean&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">SD&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Mean&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">SD&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Sup&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Inf&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \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">ACO&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">50&#46;52&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">9&#46;53&nbsp;\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">46&#46;52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;005&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ADE&nbsp;\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">47&#46;53&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">7&#46;67&nbsp;\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">43&#46;55&nbsp;\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;97&nbsp;\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">&#46;001&nbsp;\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;0&#46;58&nbsp;\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;1&#46;06&nbsp;\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;0&#46;09&nbsp;\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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ACO&#43;ADE&nbsp;\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">48&#46;51&nbsp;\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;80&nbsp;\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">42&#46;83&nbsp;\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;94&nbsp;\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">&#46;006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">P</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
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Article information

ISSN: 21735743
Original language: English

DOI:10.1016/j.reumae.2012.06.016

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Year/Month	Html	Pdf	Total

2024 October	36	35	71
2024 September	39	19	58
2024 August	49	31	80
2024 July	41	35	76
2024 June	44	29	73
2024 May	45	30	75
2024 April	40	26	66
2024 March	30	31	61
2024 February	36	36	72
2024 January	31	17	48
2023 December	21	35	56
2023 November	52	48	100
2023 October	67	45	112
2023 September	91	52	143
2023 August	134	22	156
2023 July	49	32	81
2023 June	31	22	53
2023 May	56	30	86
2023 April	38	15	53
2023 March	91	29	120
2023 February	43	32	75
2023 January	29	30	59
2022 December	73	32	105
2022 November	64	47	111
2022 October	31	43	74
2022 September	48	47	95
2022 August	35	40	75
2022 July	31	54	85
2022 June	33	35	68
2022 May	44	38	82
2022 April	37	41	78
2022 March	30	67	97
2022 February	40	38	78
2022 January	36	53	89
2021 December	31	46	77
2021 November	30	40	70
2021 October	53	54	107
2021 September	35	48	83
2021 August	37	58	95
2021 July	26	39	65
2021 June	34	52	86
2021 May	44	46	90
2021 April	93	108	201
2021 March	55	47	102
2021 February	48	30	78
2021 January	44	23	67
2020 December	39	21	60
2020 November	21	32	53
2020 October	19	16	35
2020 September	45	36	81
2020 August	16	28	44
2020 July	19	39	58
2020 June	29	45	74
2020 May	48	21	69
2020 April	29	19	48
2020 March	13	11	24
2020 February	2	0	2
2020 January	4	0	4
2019 September	6	0	6
2019 June	2	0	2
2019 March	2	0	2
2019 January	1	0	1
2018 May	5	0	5
2018 April	52	4	56
2018 March	105	7	112
2018 February	30	2	32
2018 January	18	8	26
2017 December	28	9	37
2017 November	29	5	34
2017 October	25	3	28
2017 September	22	6	28
2017 August	24	7	31
2017 July	24	9	33
2017 June	54	7	61
2017 May	50	12	62
2017 April	29	24	53
2017 March	32	11	43
2017 February	14	5	19
2017 January	30	3	33
2016 December	50	8	58
2016 November	28	6	34
2016 October	62	13	75
2016 September	65	5	70
2016 August	61	5	66
2016 July	32	4	36
2015 December	3	0	3
2015 October	2	0	2
2015 September	5	0	5
2015 July	21	7	28
2015 June	34	6	40
2015 May	38	14	52
2015 April	35	12	47
2015 March	30	8	38
2015 February	25	9	34
2015 January	32	8	40
2014 December	35	11	46
2014 November	30	14	44
2014 October	30	8	38
2014 September	26	13	39
2014 August	34	13	47
2014 July	35	13	48
2014 June	45	8	53
2014 May	56	16	72
2014 April	53	9	62
2014 March	57	13	70
2014 February	40	16	56
2014 January	42	12	54
2013 December	37	12	49
2013 November	24	10	34
2013 October	48	17	65
2013 September	54	18	72
2013 August	41	13	54
2013 July	33	25	58
2013 June	44	25	69
2013 May	44	18	62
2013 April	45	18	63
2013 March	36	19	55
2013 February	42	17	59
2013 January	35	19	54
2012 December	34	17	51
2012 November	35	29	64
2012 October	24	18	42
2012 September	27	14	41

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