Editorial
Current Status of Symptomatic Slow-acting Drugs for Osteoarthritis (SYSADOAs) in Spain
Situación actual de los SYSADOA en España
Miguel Bernad Pineda
Assitant, Servicio de Reumatología, Hospital Universitario La Paz, Madrid, Spain
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"contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Mónica Fernández Castro, Jose Luis Andreu, Carlos Sánchez-Piedra, Víctor Martínez Taboada, Alejandro Olivé, José Rosas, Fernando Sánchez-Alonso" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Mónica" "apellidos" => "Fernández Castro" ] 1 => array:2 [ "nombre" => "Jose Luis" "apellidos" => "Andreu" ] 2 => array:2 [ "nombre" => "Carlos" "apellidos" => "Sánchez-Piedra" ] 3 => array:2 [ "nombre" => "Víctor" "apellidos" => "Martínez Taboada" ] 4 => array:2 [ "nombre" => "Alejandro" "apellidos" => "Olivé" ] 5 => array:2 [ "nombre" => "José" "apellidos" => "Rosas" ] 6 => array:2 [ "nombre" => "Fernando" "apellidos" => "Sánchez-Alonso" ] 7 => array:1 [ "colaborador" => "on behalf of the working group on systemic autoimmune diseases (SAD-SER) of the Spanish Society of Rheumatology and the SER research unit (RU-SER) of the Spanish Society of the Rheumatology" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1699258X15001527" "doi" => "10.1016/j.reuma.2015.09.002" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X15001527?idApp=UINPBA00004M" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574316300302?idApp=UINPBA00004M" "url" => "/21735743/0000001200000004/v3_201704050048/S2173574316300302/v3_201704050048/en/main.assets" ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Current Status of Symptomatic Slow-acting Drugs for Osteoarthritis (SYSADOAs) in Spain" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "181" "paginaFinal" => "183" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Miguel Bernad Pineda" "autores" => array:1 [ 0 => array:3 [ "nombre" => "Miguel" "apellidos" => "Bernad Pineda" "email" => array:1 [ 0 => "mbernadp@hotmail.com" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Assitant, Servicio de Reumatología, Hospital Universitario La Paz, Madrid, Spain" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Situación actual de los SYSADOA en España" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Osteoarthritis is characterized by the degeneration and loss of joint cartilage. It is associated with hyperostosis (formation of osteophytes and subchondral bone sclerosis) and frequently with low-grade fever. The clinical features are pain, sensitivity, stiffness and crepitus in the affected joint, occasional effusion, and varying degrees of local inflammation. These changes result in functional limitation and a reduced quality of life.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Osteoarthritis can occur in any joint, but us most common in hips, knees, hands, feet and spine. It is the most widespread cause of chronic pain and disability in older individuals. The diagnosis of osteoarthritis is based on the clinical signs and radiological findings, although there is not always a good correlation between the two assessments.</p><p id="par0015" class="elsevierStylePara elsevierViewall">According to the ArtRoCad (Osteoarthritis in Knee and Hip) study,<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">2</span></a> the mean annual cost of knee and hip osteoarthritis in Spain amounts to € 1502 per patient, for a total cost of € 4738<span class="elsevierStyleHsp" style=""></span>million/year, that is, the equivalent to 0.5% of the Spanish gross domestic product. The direct costs range between € 40 and € 18,155 a year per patient. Regarding direct costs, the major part of the budget (47%) is allocated to medical expenses, especially the time spent by specialists in attending to patient visits (22%) and hospital admissions (13%). However, pharmaceuticals account for only 5% of the costs.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Traditionally, the treatment strategy has targeted pain relief and control using analgesics and nonsteroidal anti-inflammatory drugs (NSAID). The most widely employed analgesic has been paracetamol, but recent evidence of its toxicity<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">3</span></a> and inefficacy in the treatment of osteoarthritis<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">4</span></a> have led some authors to question its utility. Recently, Roberts et al.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">3</span></a> published a systematic review in which they demonstrate a relationship between paracetamol intake at the recommended analgesic doses and the incidence of adverse cardiovascular, gastrointestinal and renal effects in adults and, what's more, an increase in the rate of mortality. On the other hand, compared with placebo, doses of 3000–4000<span class="elsevierStyleHsp" style=""></span>mg/day of paracetamol produce slight, short-term pain reduction and disability in patients with osteoarthritis of the knee or hip.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">4</span></a> The evaluation of the adverse effects indicates that patients who take paracetamol quadruple their likelihood of having abnormal results on liver function tests compared to those taking placebo.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The toxicity of NSAID in the gastrointestinal tract is well known, and there are increasing warnings about the secondary effects associated with these drugs. Thus, patients are recommended to use them at the lowest dose and over the shortest possible period of time, and never as chronic treatment. In April 2015, the Spanish Agency of Medicines and Health Products (AEMPS) endorsed the recommendations of the European Pharmacovigilance Risk Assessment Committee (PRAC) and advised against administering high doses of ibuprofen (≥2400<span class="elsevierStyleHsp" style=""></span>mg/day) or dexibuprofen (≥1200<span class="elsevierStyleHsp" style=""></span>mg/day), as they are associated with a higher risk of arterial thrombosis, comparable to cyclooxygenase-2 (COX-2) inhibitors at standard doses.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">5</span></a> The United States Food and Drug Administration (FDA) has requested the update of NSAID labels to ensure that they indicate that these drugs increase the risk of myocardial infarction, and recommends that physicians remain alert to the possible presentation of adverse effects in patients who are receiving them. The FDA also advises patients who take NSAID to seek medical attention immediately if they experience the symptoms of myocardial infarction or stroke, such as chest pain, weakness, numbness or paralysis of any part of the body, difficulties in speaking or comprehension, and/or respiratory insufficiency.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The results of certain clinical trials suggest that treatment with symptomatic slow-acting drugs for osteoarthritis/disease modifying osteoarthritis drugs (SYSADOA/DMOAD) reduces pain and stiffness and increases functional capacity in patients with moderate to severe osteoarthritis,<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">7–9</span></a> even at the level of mechanisms of action.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> The Glucosamine/Chondroitin Arthritis Intervention (GAIT) Trial,<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">11</span></a> one of the largest trials conducted to date with these drugs, involved 1583 patients with knee osteoarthritis. It compared the drugs with placebo and celecoxib, and found no statistically significant effect for chondroitin sulfate (CS) or glucosamine hydrochloride, alone or in combination, after 6 months of treatment. The authors attributed these results in part to the elevated response rate in the placebo group (60%) and to the fact that the majority of the participants had mild pain at the start and, thus, a narrow margin for discernible improvement. On the other hand, in this trial, the analysis of the patients with moderate to severe pain did reveal a statistically significant effect for the combination of CS and glucosamine in terms of pain and functional capacity, among other parameters.</p><p id="par0035" class="elsevierStylePara elsevierViewall">In the continuation of the GAIT trial,<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">12</span></a> which included 662 of the initial 1583 participants, in whom the study was prolonged until the patients had completed 2 years of treatment, no significant differences were observed with respect to placebo for any of the treatment groups. Nor were significant differences found for the positive control using celecoxib, although there was an overall drop-out rate of around 50%, a circumstance that may have seriously compromised the statistical power of the study for the detection of significance.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">12</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Gabay et al.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">7</span></a> demonstrated that, after 6 months of treatment with CS, the patients with severe symptomatic hand osteoarthritis reported a reduction in the pain and in morning stiffness, in addition to improvement in functional activity, and experienced no important adverse effects.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Singh et al.,<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">8</span></a> authors of an extensive Cochrane review published in 2015, concluded that CS alone or in combination with glucosamine in patients with osteoarthrosis was superior to placebo, producing a statistically significant clinical improvement in joint pain. The findings in both the overall physical evaluation scores, like the Lequesne index, and the less marked reduction of the joint space width were better in the treatment groups than in the patients receiving placebo. The risk of serious secondary effects was lower in the group with CS than in the groups receiving other control drugs.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">8</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The treatment of osteoarthritis with SYSADOA has as strong an effect as treatment with celecoxib, as was demonstrated in the Multicentre Osteoarthritis intervention trial with SYSADOA (MOVES).<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">9</span></a> After 6 months of treatment with CS<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>glucosamine hydrochloride, the patients with knee osteoarthritis and moderate to severe pain experienced pain relief, reduced stiffness, inflammation and joint effusion, and increased mobility. These results confirm the observation that the combination of CS<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>glucosamine hydrochloride constitutes a therapeutic alternative for the patients with comorbidities and, thus, taking multiple medications, given that the safety profile is superior to that of NSAID.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">9</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The authors of a recently published clinical trial<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">13</span></a> observed a reduction in the narrowing of the joint space measured in patients with knee osteoarthritis who received CS<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>glucosamine sulfate for 2 years, compared to placebo. Both this group of patients and those who received only CS, glucosamine sulfate or placebo reported a reduction in knee pain after 1 year of treatment.</p><p id="par0060" class="elsevierStylePara elsevierViewall">The controversy arises with studies like the meta-analysis published in the British Medical Journal,<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">14</span></a> which concludes that neither CS nor glucosamine, nor the combination of the two, are clinically effective in the treatment of osteoarthritis. That study was the object of several letters to the editor in which there were comments on the methodology used, mainly concerning the inclusion of studies in which the only aim was to assess the modifying effect of the drugs (in patients with little pain) to determine their effects on the symptoms. The editors of the British Medical Journal themselves published an online communiqué in which they retracted some of the affirmations in the article and suggested that some of the conclusions could have been erroneous or biased.</p><p id="par0065" class="elsevierStylePara elsevierViewall">A more recent meta-analysis<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">15</span></a> that also analyzes the effect of chondroitin and glucosamine, alone and in combination, concludes that the 3 alternatives produce clinically significant pain relief in osteoarthritis. The authors also question the conclusions of the aforementioned meta-analysis of Wandel et al., citing methodological biases.</p><p id="par0070" class="elsevierStylePara elsevierViewall">In Spain, the VECTRA (Valoración Económica y Sanitaria de Condroitín Sulfato en el Tratamiento de la Artrosis) study (<span class="elsevierStyleItalic">Economic Evaluation of Chondroitin Sulfate and Non-steroidal Anti-inflammatory Drugs for the Treatment of Osteoarthritis</span>) demonstrated that the treatment of osteoarthritis with CS is associated with lower costs and a better gastrointestinal tolerance than NSAID, which results in a decrease in the use of gastroprotective agents.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">16</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Chondroitin sulfate and glucosamine have different mechanisms of action that explain why the combined treatment is more effective than the use of each drug alone. The absorption of CS is immediate and is produced in the segment proximal to the small intestine, and its highest plasma concentration is found 2–3<span class="elsevierStyleHsp" style=""></span>h after administration. When it reaches the joint, it is distributed in cartilage and subchondral bone tissue, but its penetration in chondrocytes is limited. It is most effective in the early stages of osteoarthritis, when fragments of the extracellular matrix trigger the inflammatory response. Chondroitin sulfate has been shown to reduce synovitis and subchondral bone lesions.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> Concerning the importance of the use of the two glucosamine salts, glucosamine sulfate and hydrochloride, the European Medicines Agency considers that either can be utilized without distinction, given that the pharmacologically active molecule is glucosamine. However, some reports mention the possible interference with glucosamine sulfate absorption when administered in combination with CS.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">17</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">The safety profile of chondroitin and glucosamine is an important aspect. Among other advantages, they are safe in terms of cardiovascular health, as they do not increase the risk of myocardial infarction or stroke, even in patients with high cardiovascular risk,<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">18</span></a> in contrast to NSAID, especially in prolonged treatments, at high doses<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">19</span></a> and in combination with opiates.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">20</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Finally, recent international guidelines have proposed that chondroitin and glucosamine, together with paracetamol, be the treatment of choice in osteoarthritis,<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">21</span></a> especially in patients with comorbidities taking multiple medications.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Bernad Pineda M. Situación actual de los SYSADOA en España. Reumatol Clin. 2016;12:181–183.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:21 [ 0 => array:3 [ "identificador" => "bib0110" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Burden of major musculoskeletal conditions" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.D. Woolf" 1 => "B. Pfleger" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Bull World Health Organ" "fecha" => "2003" "volumen" => "81" "paginaInicial" => "646" "paginaFinal" => "656" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14710506" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0115" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Implementación y características de la población del estudio ArtRoCad, una aproximación al consumo de recursos y repercusión socioeconómica de la artrosis de rodilla y cadera en atención primaria" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Batlle-Gualda" 1 => "L. Carmona" 2 => "D. Gavrila" 3 => "E.I. García Criado" 4 => "R. Ruiz Miravalles" 5 => "J. Carbonell Abelló" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1699-258X(06)73052-2" "Revista" => array:6 [ "tituloSerie" => "Reumatol Clin" "fecha" => "2006" "volumen" => "2" "paginaInicial" => "224" "paginaFinal" => "234" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21794334" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0120" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Paracetamol: not as safe as we thought? A systematic literature review of observational studies" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Roberts" 1 => "V. Delgado Nunes" 2 => "S. Buckner" 3 => "S. Latchem" 4 => "M. Constanti" 5 => "P. Miller" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/annrheumdis-2014-206914" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2016" "volumen" => "75" "paginaInicial" => "552" "paginaFinal" => "559" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25732175" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0125" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomized placebo controlled trials" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G.C. Machado" 1 => "C.G. Maher" 2 => "P.H. Ferreira" 3 => "M.B. Pinheiro" 4 => "C.W.C. Lin" 5 => "R.O. Day" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Br Med J" "fecha" => "2014" "volumen" => "350" "paginaInicial" => "h1225" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0130" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "Available from: <span class="elsevierStyleInterRef" id="intr0010" href="http://www.aemps.gob.es/">www.aemps.gob.es</span> [accessed 10.10.15]" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Riesgo cardiovascular de dosis altas de ibuprofeno o dexibuprofeno: recomendaciones de uso" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2015" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0135" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "Available from <span class="elsevierStyleInterRef" id="intr0015" href="http://www.fda.gov/Drugs/DrugSafety/ucm451800.htm">http://www.fda.gov/Drugs/DrugSafety/ucm451800.htm</span> [accessed 10.10.15]" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Food and Drug Administration" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:2 [ "fecha" => "2015" "editorial" => "Drug Safety Communications" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0140" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Symptomatic effects of chondroitin 4 and chondroitin 6 sulfate on hand osteoarthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "C. Gabay" 1 => "C. Medinger-Sadowski" 2 => "D. Gascon" 3 => "F. Kolo" 4 => "A. Finckh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.30574" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "2011" "volumen" => "63" "paginaInicial" => "3383" "paginaFinal" => "3391" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21898340" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0145" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chondroitin for osteoarthritis (Review)" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "The Cochrane Collaboration" "etal" => false "autores" => array:4 [ 0 => "J.A. Singh" 1 => "S. Noorbaloochi" 2 => "R. MacDonald" 3 => "L.J. Maxwell" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "Cochrane Libr" "fecha" => "2015" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0150" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomized, double-blind, non-inferiority trial versus celecoxib" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.C. Hochberg" 1 => "J. Martel-Pelletier" 2 => "J. Monfort" 3 => "I. Möller" 4 => "J.R. Castillo" 5 => "N. Arden" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/annrheumdis-2014-206792" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2015" "volumen" => "75" "paginaInicial" => "37" "paginaFinal" => "44" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25589511" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0155" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Absorption, distribution and mechanism of action of SYSADOAS" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "P. Du Souich" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.pharmthera.2014.01.002" "Revista" => array:6 [ "tituloSerie" => "Pharmacol Ther" "fecha" => "2014" "volumen" => "142" "paginaInicial" => "362" "paginaFinal" => "374" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24457028" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0160" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.O. Clegg" 1 => "D.J. Reda" 2 => "C.L. Harris" 3 => "M.A. Klein" 4 => "J.R. O’Dell" 5 => "M.M. Hooper" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa052771" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2006" "volumen" => "354" "paginaInicial" => "795" "paginaFinal" => "808" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16495392" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0165" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical efficacy and safety over two years use of glucosamine, chondroitin sulfate, their combination, celecoxib or placebo taken to treat osteoarthritis of the knee: a GAIT report" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.D. Sawitzke" 1 => "H. Shi" 2 => "M.F. Finco" 3 => "D.D. Dunlop" 4 => "C.L. Harris" 5 => "N.G. Singer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2009.120469" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2010" "volumen" => "69" "paginaInicial" => "1459" "paginaFinal" => "1464" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20525840" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0170" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Glucosamine and chondroitin for knee osteoarthritis: a double-blind randomized placebo-controlled trial evaluating single and combination regimens" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Fransen" 1 => "M. Agaliotis" 2 => "L. Nairn" 3 => "M. Votrubec" 4 => "L. Bridgett" 5 => "S. Su" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/annrheumdis-2013-203954" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2015" "volumen" => "74" "paginaInicial" => "851" "paginaFinal" => "858" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24395557" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0175" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Wandel" 1 => "P. Jüni" 2 => "B. Tendal" 3 => "E. Nüesch" 4 => "P.M. Villiger" 5 => "N.J. Welton" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Br Med J" "fecha" => "2010" "volumen" => "341" "paginaInicial" => "c4675" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0180" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effectiveness and safety of glucosamine, chondroitin, the two in combination, or celecoxib in the treatment of osteoarthritis of the knee" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Zeng" 1 => "J. Wei" 2 => "H. Li" 3 => "Y. Wang" 4 => "D. Xie" 5 => "T. Yang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/srep16827" "Revista" => array:5 [ "tituloSerie" => "Sci Rep" "fecha" => "2015" "volumen" => "5" "paginaInicial" => "16827" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26576862" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0185" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evaluación económica del uso de condroitín sulfato y antiinflamatorios no esteroides en el tratamiento de la artrosis. Datos del estudio VECTRA" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "Grupo del estudio VECTRA" "etal" => false "autores" => array:1 [ 0 => "C. Rubio-Terés" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Reum Clin" "fecha" => "2010" "volumen" => "6" "paginaInicial" => "187" "paginaFinal" => "195" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0190" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The human pharmacokinetics of oral ingestion of glucosamine and chondroitin sulfate taken separately or in combination" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.G. Jackson" 1 => "A.H. Plaas" 2 => "J.D. Sandy" 3 => "C. Hua" 4 => "S. Kim-Rolands" 5 => "J.G. Barnhill" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.joca.2009.10.013" "Revista" => array:6 [ "tituloSerie" => "Osteoarthr Cartil" "fecha" => "2010" "volumen" => "18" "paginaInicial" => "297" "paginaFinal" => "302" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19912983" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0195" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk of nonfatal acute myocardial infarction associated with non-steroidal antiinflammatory drugs, non-narcotic analgesics and other drugs used in osteoarthritis: a nested case-control study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.J. De Abajo" 1 => "M.J. Gil" 2 => "P. García Poza" 3 => "V. Bryant" 4 => "B. Oliva" 5 => "J. Timoner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/pds.3617" "Revista" => array:6 [ "tituloSerie" => "Pharmacoepidemiol Drug Saf" "fecha" => "2014" "volumen" => "23" "paginaInicial" => "1128" "paginaFinal" => "1138" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24692325" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0200" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk of ischemic stroke associated with non-steroidal anti-inflammatory drugs and paracetamol: a population-based case-control study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "P. García-Poza" 1 => "F.J. de Abajo" 2 => "M.J. Gil" 3 => "A. Chacón" 4 => "V. Bryant" 5 => "L.A. García-Rodríguez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jth.12855" "Revista" => array:6 [ "tituloSerie" => "J Thromb Haemost" "fecha" => "2015" "volumen" => "13" "paginaInicial" => "708" "paginaFinal" => "718" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25611553" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0205" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "[abstract]" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Searching for evidence to support clinical practice- using non-steroidals as an example" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Pontes" 1 => "R. Morros" 2 => "J.R. Marsal" 3 => "F. de Abajo" 4 => "J.R. Castillo" 5 => "J. Ríos" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/annrheumdis-2015-eular.4380" "Libro" => array:1 [ "fecha" => "2015" ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0210" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An algorithm recommendations for the management of knee osteoarthritis in Europe and internationally: a report from a task force of the Europe Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "O. Bruyère" 1 => "C. Cooper" 2 => "J.P. Pelletier" 3 => "J. Branco" 4 => "M.L. Brandi" 5 => "F. Guillemin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.semarthrit.2014.05.014" "Revista" => array:6 [ "tituloSerie" => "Semin Arthritis Rheum" "fecha" => "2014" "volumen" => "44" "paginaInicial" => "253" "paginaFinal" => "263" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24953861" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735743/0000001200000004/v3_201704050048/S2173574316300533/v3_201704050048/en/main.assets" "Apartado" => array:4 [ "identificador" => "17335" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Editorial" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/21735743/0000001200000004/v3_201704050048/S2173574316300533/v3_201704050048/en/main.pdf?idApp=UINPBA00004M&text.app=https://reumatologiaclinica.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574316300533?idApp=UINPBA00004M" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 37 | 18 | 55 |
| 2024 October | 455 | 90 | 545 |
| 2024 September | 316 | 54 | 370 |
| 2024 August | 292 | 72 | 364 |
| 2024 July | 315 | 59 | 374 |
| 2024 June | 259 | 58 | 317 |
| 2024 May | 220 | 52 | 272 |
| 2024 April | 250 | 30 | 280 |
| 2024 March | 210 | 44 | 254 |
| 2024 February | 260 | 41 | 301 |
| 2024 January | 329 | 43 | 372 |
| 2023 December | 158 | 38 | 196 |
| 2023 November | 169 | 28 | 197 |
| 2023 October | 184 | 37 | 221 |
| 2023 September | 150 | 41 | 191 |
| 2023 August | 139 | 23 | 162 |
| 2023 July | 141 | 23 | 164 |
| 2023 June | 129 | 40 | 169 |
| 2023 May | 150 | 29 | 179 |
| 2023 April | 112 | 20 | 132 |
| 2023 March | 137 | 22 | 159 |
| 2023 February | 151 | 45 | 196 |
| 2023 January | 124 | 39 | 163 |
| 2022 December | 128 | 40 | 168 |
| 2022 November | 222 | 47 | 269 |
| 2022 October | 193 | 50 | 243 |
| 2022 September | 188 | 44 | 232 |
| 2022 August | 128 | 44 | 172 |
| 2022 July | 154 | 47 | 201 |
| 2022 June | 156 | 43 | 199 |
| 2022 May | 202 | 56 | 258 |
| 2022 April | 189 | 48 | 237 |
| 2022 March | 221 | 69 | 290 |
| 2022 February | 156 | 31 | 187 |
| 2022 January | 141 | 47 | 188 |
| 2021 December | 121 | 37 | 158 |
| 2021 November | 130 | 59 | 189 |
| 2021 October | 143 | 67 | 210 |
| 2021 September | 104 | 50 | 154 |
| 2021 August | 91 | 45 | 136 |
| 2021 July | 98 | 24 | 122 |
| 2021 June | 153 | 60 | 213 |
| 2021 May | 173 | 67 | 240 |
| 2021 April | 406 | 151 | 557 |
| 2021 March | 220 | 46 | 266 |
| 2021 February | 122 | 39 | 161 |
| 2021 January | 145 | 23 | 168 |
| 2020 December | 105 | 29 | 134 |
| 2020 November | 139 | 22 | 161 |
| 2020 October | 90 | 27 | 117 |
| 2020 September | 120 | 38 | 158 |
| 2020 August | 97 | 30 | 127 |
| 2020 July | 79 | 25 | 104 |
| 2020 June | 85 | 30 | 115 |
| 2020 May | 71 | 22 | 93 |
| 2020 April | 54 | 29 | 83 |
| 2020 March | 61 | 11 | 72 |
| 2020 February | 2 | 0 | 2 |
| 2018 May | 9 | 2 | 11 |
| 2018 April | 119 | 11 | 130 |
| 2018 March | 106 | 5 | 111 |
| 2018 February | 50 | 14 | 64 |
| 2018 January | 60 | 8 | 68 |
| 2017 December | 80 | 14 | 94 |
| 2017 November | 68 | 12 | 80 |
| 2017 October | 70 | 12 | 82 |
| 2017 September | 59 | 20 | 79 |
| 2017 August | 70 | 24 | 94 |
| 2017 July | 57 | 32 | 89 |
| 2017 June | 66 | 28 | 94 |
| 2017 May | 71 | 23 | 94 |
| 2017 April | 48 | 19 | 67 |
| 2017 March | 49 | 19 | 68 |
| 2017 February | 41 | 22 | 63 |
| 2017 January | 31 | 13 | 44 |
| 2016 December | 67 | 23 | 90 |
| 2016 November | 84 | 27 | 111 |
| 2016 October | 81 | 22 | 103 |
| 2016 September | 91 | 13 | 104 |
| 2016 August | 135 | 89 | 224 |
| 2016 July | 68 | 42 | 110 |
| 2016 June | 0 | 9 | 9 |
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