array:23 [
  "pii" => "S2173574310700435"
  "issn" => "21735743"
  "doi" => "10.1016/S2173-5743(10)70043-5"
  "estado" => "S300"
  "fechaPublicacion" => "2010-07-01"
  "aid" => "70043"
  "copyright" => "Sociedad Española de Reumatología and Colegio Mexicano de Reumatología"
  "copyrightAnyo" => "2010"
  "documento" => "article"
  "crossmark" => 0
  "subdocumento" => "fla"
  "cita" => "Reumatol Clin. 2010;6:187-95"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:2 [
    "total" => 2597
    "formatos" => array:3 [
      "EPUB" => 46
      "HTML" => 1707
      "PDF" => 844
    ]
  ]
  "itemSiguiente" => array:18 [
    "pii" => "S2173574310700447"
    "issn" => "21735743"
    "doi" => "10.1016/S2173-5743(10)70044-7"
    "estado" => "S300"
    "fechaPublicacion" => "2010-07-01"
    "aid" => "70044"
    "copyright" => "Sociedad Española de Reumatología and Colegio Mexicano de Reumatología"
    "documento" => "article"
    "crossmark" => 0
    "subdocumento" => "fla"
    "cita" => "Reumatol Clin. 2010;6:196-8"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 2937
      "formatos" => array:3 [
        "EPUB" => 45
        "HTML" => 1489
        "PDF" => 1403
      ]
    ]
    "en" => array:10 [
      "idiomaDefecto" => true
      "titulo" => "Diffuse alveolar hemorrhage: Causes and outcomes in a referral center"
      "tienePdf" => "en"
      "tieneTextoCompleto" => 0
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "196"
          "paginaFinal" => "198"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Hemorragia alveolar difusa: causas y desenlaces en un instituto de tercer nivel"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Ivette Buendía-Roldán, Carmen Navarro, Jorge Rojas-Serrano"
          "autores" => array:3 [
            0 => array:2 [
              "nombre" => "Ivette"
              "apellidos" => "Buendía-Roldán"
            ]
            1 => array:2 [
              "nombre" => "Carmen"
              "apellidos" => "Navarro"
            ]
            2 => array:2 [
              "nombre" => "Jorge"
              "apellidos" => "Rojas-Serrano"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574310700447?idApp=UINPBA00004M"
    "url" => "/21735743/0000000600000004/v1_201305061610/S2173574310700447/v1_201305061610/en/main.assets"
  ]
  "itemAnterior" => array:18 [
    "pii" => "S2173574310700423"
    "issn" => "21735743"
    "doi" => "10.1016/S2173-5743(10)70042-3"
    "estado" => "S300"
    "fechaPublicacion" => "2010-07-01"
    "aid" => "70042"
    "copyright" => "Sociedad Española de Reumatología and Colegio Mexicano de Reumatología"
    "documento" => "simple-article"
    "crossmark" => 0
    "subdocumento" => "edi"
    "cita" => "Reumatol Clin. 2010;6:185-6"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 1493
      "formatos" => array:3 [
        "EPUB" => 45
        "HTML" => 1037
        "PDF" => 411
      ]
    ]
    "en" => array:8 [
      "idiomaDefecto" => true
      "titulo" => "Understanding chronic fatigue syndrome"
      "tienePdf" => "en"
      "tieneTextoCompleto" => 0
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "185"
          "paginaFinal" => "186"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Entendiendo el síndrome de fatiga crónica"
        ]
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Javier Rivera Redondo"
          "autores" => array:1 [
            0 => array:2 [
              "nombre" => "Javier"
              "apellidos" => "Rivera Redondo"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574310700423?idApp=UINPBA00004M"
    "url" => "/21735743/0000000600000004/v1_201305061610/S2173574310700423/v1_201305061610/en/main.assets"
  ]
  "en" => array:15 [
    "idiomaDefecto" => true
    "titulo" => "An economic evaluation of chondroitin sulfate and non-steroidal anti-inflammatory drugs for the treatment of osteoarthritis. Data from the VECTRA study"
    "tieneTextoCompleto" => 0
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "187"
        "paginaFinal" => "195"
      ]
    ]
    "autores" => array:1 [
      0 => array:3 [
        "autoresLista" => "Carlos Rubio-Terrés"
        "autores" => array:2 [
          0 => array:3 [
            "nombre" => "Carlos"
            "apellidos" => "Rubio-Terrés"
            "email" => array:1 [
              0 => "crubioterres@healthvalue.org"
            ]
          ]
          1 => array:2 [
            "colaborador" => "Grupo del estudio VECTRA"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#9674;</span>"
                "identificador" => "fn0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:1 [
          0 => array:1 [
            "entidad" => "Health Value&#44; Health Economics and Research Outcomes Consulting&#44; Madrid&#44; Spain"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Evaluaci&#243;n econ&#243;mica del uso de condroit&#237;n sulfato y antiinflamatorios no esteroideos en el tratamiento de la artrosis&#46; Datos del estudio VECTRA"
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2009-05-21"
    "fechaAceptado" => "2009-12-02"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec112482"
          "palabras" => array:7 [
            0 => "Chondroitin sulphate"
            1 => "Non-steroidal antiinflammatory drugs"
            2 => "Antirheumatic drugs"
            3 => "Osteoarthritis"
            4 => "Knee osteoarthritis"
            5 => "Hip osteoarthritis"
            6 => "Costs"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec112483"
          "palabras" => array:7 [
            0 => "Condroit&#237;n sulfato"
            1 => "Agentes antiinflamatorios no esteroideos"
            2 => "Agentes antirreum&#225;ticos"
            3 => "Artrosis"
            4 => "Artrosis de rodilla"
            5 => "Artrosis de cadera"
            6 => "Costes"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Our aim was to investigate&#58; 1&#41; the average cost per patient with osteoarthritis treated with chondroitin sulfate compared with NSAIDs for 6 months and 2&#41; the possible impact that the reduction NSAID use due to monotherapy with or combined administration of chondroitin sulfate treatment may have on the budget of the Spanish National Health System&#46;</p> <span class="elsevierStyleSectionTitle">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A cost-minimization model compared both treatments &#40;efficacy equivalence assumption&#41;&#44; used at the recommended doses and regimens during a 6-month period&#46; Data used in the model was obtained from the VECTRA study&#44; a retrospective study of 530 patients with osteoarthritis treated with chondroitin sulfate or NSAIDs that was conducted to determine the consumption of health care resources&#46; The efficacy and incidence of adverse events was estimated from meta-analysis based on randomized clinical trials&#46; Univariate sensitivity analysis was performed for the base case scenario&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The overall 6-month cost per patient given chondroitin sulfate was 141 &#8364; compared with 182 &#8364; when treated with NSAIDs&#46; If during the forthcoming 3 years&#44; 5&#37;&#44; 10&#37;&#44; and 15&#37; of patients currently treated with NSAIDs would gradually be replaced by treatment with chondroitin sulfate&#44; the expected savings for the Spanish National Health System during these 3 years would be over 38&#44;700&#44;000 &#8364;&#46; In addition&#44; 2&#44;666 cases of gastrointestinal adverse events &#40;including 90 serious adverse events&#41; will have been avoided for every 10&#44;000 patients treated with chondroitin sulfate instead of NSAID&#46; Sensitivity analysis confirmed the strength of base-case in all scenarios&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">On the basis of these findings&#44; chondroitin sulfate is a treatment for osteoarthritis with a lesser cost and better gastrointestinal tolerability compared with NSAIDs&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El presente estudio <span class="elsevierStyleItalic">a</span>&#41; estima el coste medio de un paciente con artrosis tratado durante 6 meses con condroit&#237;n sulfato &#40;CS&#41; o antiinflamatorios no esteroideos &#40;AINE&#41;&#44; y <span class="elsevierStyleItalic">b</span>&#41; eval&#250;a el impacto presupuestario para el Sistema Nacional de Salud que causar&#237;a la disminuci&#243;n del consumo de AINE con la administraci&#243;n en monoterapia o conjunta de CS&#46;</p> <span class="elsevierStyleSectionTitle">Material y m&#233;todo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Modelo de minimizaci&#243;n de costes que compar&#243; ambos tratamientos &#40;asumiendo igualdad de eficacia&#41;&#44; a las dosis y las pautas recomendadas&#44; durante un per&#237;odo de seis meses&#46; Los datos utilizados en el modelo se obtuvieron del estudio VECTRA&#44; un estudio retrospectivo en el que se recogi&#243; el consumo de recursos sanitarios de 530 pacientes con artrosis tratados con CS o AINE&#46; La eficacia y la incidencia de efectos adversos se estimaron a partir del metaan&#225;lisis de ensayos cl&#237;nicos aleatorizados&#46; Se hicieron an&#225;lisis de sensibilidad simples univariantes del caso b&#225;sico&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El coste semestral por paciente tratado con CS fue de 141 &#8364;&#44; y de 182 &#8364; en el caso de los AINE&#46; Esto significa que&#44; si durante los 3 pr&#243;ximos a&#241;os el 5&#44; el 10 y el 15&#37; de los pacientes con artrosis tratados actualmente con AINE fueran tratados con CS&#44; se generar&#237;an ahorros para el Sistema Nacional de Salud de m&#225;s de 38&#44;7 millones de euros durante este per&#237;odo&#46; Adem&#225;s&#44; por cada 10&#46;000 pacientes tratados con CS en lugar de AINE se evitar&#237;an 2&#46;666 efectos adversos gastrointestinales&#44; de los que 90 ser&#237;an graves&#46; Los an&#225;lisis de sensibilidad confirmaron la estabilidad del caso b&#225;sico en todos los supuestos considerados&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Comparado con los AINE&#44; el CS es un tratamiento con menores costes y con mejor tolerancia gastrointestinal en el manejo de la artrosis&#46;</p>"
      ]
    ]
    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9674;"
        "nota" => "<p class="elsevierStyleNotepara">The list of the VECTRA study researchers is shown in Annex I&#46;</p>"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara">VECTRA is the acronym for the &#8220;Economic and Health Evaluation of Chondroitin Sulphate for the Treatment of Osteoarthritis&#8221;&#46;</p>"
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:36 [
            0 => array:3 [
              "identificador" => "bib1"
              "etiqueta" => "1&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Direct and indirect costs attributable to osteoarthritis in active subjects"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "V&#46; Rabenda"
                            1 => "C&#46; Manette"
                            2 => "R&#46; Lemmens"
                            3 => "A&#46;M&#46; Mariani"
                            4 => "N&#46; Struvay"
                            5 => "J&#46;Y&#46; Reginster"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Rheumatol"
                        "fecha" => "2006"
                        "volumen" => "33"
                        "paginaInicial" => "1152"
                        "paginaFinal" => "1158"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16755664"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib2"
              "etiqueta" => "2&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Health-related quality of life in older adults with symptomatic hip and knee osteoarthritis&#58; a comparison with matched healthy controls"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "F&#46; Salaffi"
                            1 => "M&#46; Carotti"
                            2 => "A&#46; Stancati"
                            3 => "W&#46; Grassi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Aging Clin Exp Res"
                        "fecha" => "2005"
                        "volumen" => "17"
                        "paginaInicial" => "255"
                        "paginaFinal" => "263"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16285189"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib3"
              "etiqueta" => "3&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Direct and indirect costs of osteoarthritis of the knee"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "Italian Group for Study of the Costs of Arthritis"
                          "etal" => false
                          "autores" => array:6 [
                            0 => "G&#46; Leardini"
                            1 => "F&#46; Salaffi"
                            2 => "R&#46; Caporali"
                            3 => "B&#46; Canesi"
                            4 => "L&#46; Rovati"
                            5 => "R&#46; Montanelli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Rheumatol"
                        "fecha" => "2004"
                        "volumen" => "22"
                        "paginaInicial" => "699"
                        "paginaFinal" => "706"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15638043"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib4"
              "etiqueta" => "4&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence&#44; risk factors&#44; and impact of knee pain suggesting osteoarthritis in Spain"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "Behalf of the EPISER Study Group"
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46;C&#46; Fern&#225;ndez-L&#243;pez"
                            1 => "A&#46; Laffon"
                            2 => "F&#46;J&#46; Blanco"
                            3 => "L&#46; Carmona"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Rheumatol"
                        "fecha" => "2008"
                        "volumen" => "26"
                        "paginaInicial" => "324"
                        "paginaFinal" => "332"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18565256"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib5"
              "etiqueta" => "5&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An international comparison of the estimated effect of the aging of the population on the major cause of disablement&#44; musculoskeletal disorders"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "E&#46;M&#46; Badley"
                            1 => "M&#46; Crotty"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Rheumatol"
                        "fecha" => "1995"
                        "volumen" => "22"
                        "paginaInicial" => "1934"
                        "paginaFinal" => "1940"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8991994"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib6"
              "etiqueta" => "6&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence of symptomatic knee&#44; hand&#44; and hip osteoarthritis in Greece&#46; The ESORDIG study"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "ESORDIG Study Group"
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;A&#46; Andrianakos"
                            1 => "L&#46;K&#46; Kontelis"
                            2 => "D&#46;G&#46; Karamitsos"
                            3 => "S&#46;I&#46; Aslanidis"
                            4 => "A&#46;I&#46; Georgountzos"
                            5 => "G&#46;O&#46; Kaziolas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Rheumatol"
                        "fecha" => "2006"
                        "volumen" => "33"
                        "paginaInicial" => "2507"
                        "paginaFinal" => "2513"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17143985"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib7"
              "etiqueta" => "7&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence and burden of osteoarthritis&#58; results from a population survey in Norway"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46; Grotle"
                            1 => "K&#46;B&#46; Hagen"
                            2 => "B&#46; Natvig"
                            3 => "F&#46;A&#46; Dahl"
                            4 => "T&#46;K&#46; Kvien"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Rheumatol"
                        "fecha" => "2008"
                        "volumen" => "35"
                        "paginaInicial" => "677"
                        "paginaFinal" => "684"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18278832"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib8"
              "etiqueta" => "8&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Screening for hip and knee osteoarthritis in the general population&#58; predictive value of a questionnaire and prevalence estimates"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "KHOALA Osteoarthritis Group"
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46;H&#46; Roux"
                            1 => "A&#46; Saraux"
                            2 => "B&#46; Mazieres"
                            3 => "J&#46; Pouchot"
                            4 => "J&#46; Morvan"
                            5 => "B&#46; Fautrel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2007.075952"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2008"
                        "volumen" => "67"
                        "paginaInicial" => "1406"
                        "paginaFinal" => "1411"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18077540"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib9"
              "etiqueta" => "9&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "GP and patient perspectives on treatment with non-steroidal anti-inflammatory drugs for the treatment of pain in osteoarthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "B&#46; Crichton"
                            1 => "M&#46; Green"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Med Res Opin"
                        "fecha" => "2002"
                        "volumen" => "18"
                        "paginaInicial" => "92"
                        "paginaFinal" => "96"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12017216"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib10"
              "etiqueta" => "10&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nonsteroidal antiinflammatory drug discontinuation in patients with osteoarthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "D&#46; Scholes"
                            1 => "A&#46; Stergachis"
                            2 => "P&#46;M&#46; Penna"
                            3 => "E&#46;H&#46; Normand"
                            4 => "P&#46;D&#46; Hansten"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Rheumatol"
                        "fecha" => "1995"
                        "volumen" => "22"
                        "paginaInicial" => "708"
                        "paginaFinal" => "712"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7791168"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib11"
              "etiqueta" => "11&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Non-steroidal anti-inflammatory drugs&#44; including cyclo-oxygenase-2 inhibitors&#44; in osteoarthritic knee pain&#58; metaanalysis of randomised placebo controlled trials"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46;M&#46; Bjordal"
                            1 => "A&#46;E&#46; Ljunggren"
                            2 => "A&#46; Klovning"
                            3 => "L&#46; Sl&#248;rdal"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/bmj.38273.626655.63"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMJ"
                        "fecha" => "2004"
                        "volumen" => "329"
                        "paginaInicial" => "1317"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15561731"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib12"
              "etiqueta" => "12&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chondroitin sulphate for symptomatic osteoarthritis&#58; critical appraisal of meta-analyses"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46; Monfort"
                            1 => "J&#46; Martel-Pelletier"
                            2 => "J&#46;P&#46; Pelletier"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1185/030079908X297231"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Med Res Opin"
                        "fecha" => "2008"
                        "volumen" => "24"
                        "paginaInicial" => "1303"
                        "paginaFinal" => "1308"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18416884"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib13"
              "etiqueta" => "13&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Standing Committee for International Clinical Studies Including Therapeutic Trials ESCISIT&#46; EULAR recommendations 2003&#58; an evidence based approach to the management of knee osteoarthritis&#58; report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials &#40;ESCISIT&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;M&#46; Jordan"
                            1 => "N&#46;K&#46; Arden"
                            2 => "M&#46; Doherty"
                            3 => "B&#46; Bannwarth"
                            4 => "J&#46;W&#46; Bijlsma"
                            5 => "P&#46; Dieppe"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2003"
                        "volumen" => "62"
                        "paginaInicial" => "1145"
                        "paginaFinal" => "1155"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14644851"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib14"
              "etiqueta" => "14&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "OARSI recommendations for the management of hip and knee osteoarthritis&#44; part I&#58; critical appraisal of existing treatment guidelines and systematic review of current research evidence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46; Zhang"
                            1 => "R&#46;W&#46; Moskowitz"
                            2 => "G&#46; Nuki"
                            3 => "S&#46; Abramson"
                            4 => "R&#46;D&#46; Altman"
                            5 => "N&#46; Arden"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.joca.2007.06.014"
                      "Revista" => array:6 [
                        "tituloSerie" => "Osteoarthritis Cartilage"
                        "fecha" => "2007"
                        "volumen" => "15"
                        "paginaInicial" => "981"
                        "paginaFinal" => "1000"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17719803"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib15"
              "etiqueta" => "15&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chondroitin sulfates &#40;CS 4&#38;6&#41;&#58; practical applications and economic impact"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "T&#46; Conrozier"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Presse Med"
                        "fecha" => "1998"
                        "volumen" => "27"
                        "paginaInicial" => "1866"
                        "paginaFinal" => "1868"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9856137"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib16"
              "etiqueta" => "16&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Less use of NSAIDs in long-term than in recent chondroitin sulphate users in osteoarthritis&#58; a pharmacy-based observational study in France"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Lagnaoui"
                            1 => "M&#46; Baumevielle"
                            2 => "B&#46; B&#233;gaud"
                            3 => "P&#46; Pouyanne"
                            4 => "G&#46; Maurice"
                            5 => "F&#46; Depont"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Th&#233;rapie"
                        "fecha" => "2006"
                        "volumen" => "61"
                        "paginaInicial" => "341"
                        "paginaFinal" => "346"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17124950"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib17"
              "etiqueta" => "17&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Osteoarthritis&#58; chondroitin sulfate long term utilization reduces consumption of coxibs&#44; NSAIDs and analgesics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "C&#46; Taieb"
                            1 => "C&#46; Huichard"
                            2 => "L&#46; Didier"
                            3 => "R&#46; Roche"
                            4 => "D&#46; Labed"
                            5 => "E&#46; Myon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2005"
                        "volumen" => "64"
                        "paginaInicial" => "483"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib18"
              "etiqueta" => "18&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An&#225;lisis farmacoecon&#243;mico del tratamiento de la artrosis con condroit&#237;n sulfato en comparaci&#243;n con AINE"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "C&#46; Rubio-Terr&#233;s"
                            1 => "I&#46; M&#246;ller Parera"
                            2 => "E&#46; Tom&#225;s Campeny"
                            3 => "J&#46; Verg&#233;s Milano"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Atenc Farm"
                        "fecha" => "2004"
                        "volumen" => "6"
                        "paginaInicial" => "15"
                        "paginaFinal" => "27"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib19"
              "etiqueta" => "19&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Maetzel A&#44; Krahn M&#44; Naglie G&#46; The cost-effectiveness of celecoxib and rofecoxib in patients with osteoarthritis or rheumatoid arthritis&#46; Ottawa&#58; Canadian Coordinating Office for Health Technology Assessment&#59; 2002&#46; Technology report no&#46; 23&#46;"
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib20"
              "etiqueta" => "20&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparison of the antiinflammatory efficacy of chondroitin sulfate and diclofenac sodium in patients with knee osteoarthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "P&#46; Morreale"
                            1 => "R&#46; Manopulo"
                            2 => "M&#46; Galati"
                            3 => "L&#46; Boccanera"
                            4 => "G&#46; Saponati"
                            5 => "L&#46; Bocchi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Rheumatol"
                        "fecha" => "1996"
                        "volumen" => "23"
                        "paginaInicial" => "1385"
                        "paginaFinal" => "1391"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8856618"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib21"
              "etiqueta" => "21&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The efficacy of chondroitin sulfate in the treatment of knee osteoarthritis&#58; a meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "R&#46;M&#46; Eugenio-Sarmiento"
                            1 => "B&#46;H&#46;D&#46; Manapat"
                            2 => "E&#46;O&#46; Salido"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Osteoarthritis Cartilage"
                        "fecha" => "1999"
                        "volumen" => "7"
                        "paginaInicial" => "S35"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib22"
              "etiqueta" => "22&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A metaanalysis of chondroitin sulfate in the treatment of osteoarthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "B&#46;F&#46; Leeb"
                            1 => "H&#46; Schweitzer"
                            2 => "K&#46; Montag"
                            3 => "J&#46;S&#46; Smolen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Rheumatol"
                        "fecha" => "2000"
                        "volumen" => "27"
                        "paginaInicial" => "205"
                        "paginaFinal" => "211"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10648040"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib23"
              "etiqueta" => "23&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Glucosamine and chondroitin for treatment of osteoarthritis&#58; a systematic quality assessment and meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "T&#46;E&#46; McAlindon"
                            1 => "M&#46;P&#46; La Valley"
                            2 => "J&#46;P&#46; Gulin"
                            3 => "D&#46;T&#46; Felson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "2000"
                        "volumen" => "283"
                        "paginaInicial" => "1469"
                        "paginaFinal" => "1475"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10732937"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib24"
              "etiqueta" => "24&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Meta-analysis&#58; chondroitin for osteoarthritis of the knee or hip"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Reichenbach"
                            1 => "R&#46; Sterchi"
                            2 => "M&#46; Scherer"
                            3 => "S&#46; Trelle"
                            4 => "E&#46; B&#252;rgi"
                            5 => "U&#46; B&#252;rgi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Intern Med"
                        "fecha" => "2007"
                        "volumen" => "146"
                        "paginaInicial" => "580"
                        "paginaFinal" => "590"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17438317"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib25"
              "etiqueta" => "25&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis&#58; a comprehensive meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "F&#46; Richy"
                            1 => "O&#46; Bruyere"
                            2 => "O&#46; Ethgen"
                            3 => "M&#46; Cucherat"
                            4 => "Y&#46; Henrotin"
                            5 => "J&#46;Y&#46; Reginster"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/archinte.164.14.1514"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Intern Med"
                        "fecha" => "2003"
                        "volumen" => "164"
                        "paginaInicial" => "1514"
                        "paginaFinal" => "1522"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15277281"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib26"
              "etiqueta" => "26&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate&#58; a oneyear&#44; randomized&#44; double-blind&#44; multicenter study versus placebo"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Uebelhart"
                            1 => "M&#46; Malaise"
                            2 => "R&#46; Marcolongo"
                            3 => "F&#46; De Vathaire"
                            4 => "M&#46; Piperno"
                            5 => "E&#46; Mailleux"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.joca.2004.01.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Osteoarthritis Cartilage"
                        "fecha" => "2004"
                        "volumen" => "12"
                        "paginaInicial" => "269"
                        "paginaFinal" => "276"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15023378"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib27"
              "etiqueta" => "27&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The cost-effectiveness of acetaminophen&#44; NSAIDs&#44; and selective COX-2 inhibitors in the treatment of symptomatic knee osteoarthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "C&#46;C&#46; Kamath"
                            1 => "H&#46;M&#46; Kremers"
                            2 => "D&#46;J&#46; Vanness"
                            3 => "W&#46;M&#46; O&#8217;Fallon"
                            4 => "R&#46;L&#46; Cabanela"
                            5 => "S&#46;E&#46; Gabriel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1046/j.1524-4733.2003.00215.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Value Health"
                        "fecha" => "2003"
                        "volumen" => "6"
                        "paginaInicial" => "144"
                        "paginaFinal" => "157"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12641865"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib28"
              "etiqueta" => "28&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cost-effectiveness analysis of the use of celecoxib for the treatment of osteoarthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46; Moreno"
                            1 => "E&#46; Vargas"
                            2 => "J&#46; Soto"
                            3 => "J&#46; Rejas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Gac Sanit"
                        "fecha" => "2003"
                        "volumen" => "17"
                        "paginaInicial" => "27"
                        "paginaFinal" => "36"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12605743"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib29"
              "etiqueta" => "29&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "US Food and Drug Administration&#46; VIOxx gastrointestinal safety &#91;accessed 31&#47;7&#47;2008&#93;&#46; Available from&#58; <a class="elsevierStyleInterRef" href="http://www.fda.gov/medwatch/SAFETY/2002/vioxx_deardoc.pdf">http&#58;&#47;&#47;www&#46;fda&#46;gov&#47;medwatch&#47;SAFETY&#47;2002&#47;vioxx&#95;deardoc&#46;pdf</a>"
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib30"
              "etiqueta" => "30&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "National Institute for Health and Clinical Excellence &#40;NICE&#41;&#46; TA27 Osteoarthritis and rheumatoid arthritis-COX II inhibitors&#58; guidance &#91;accessed 31&#47;7&#47;2008&#93;&#46; Available from&#58; <a class="elsevierStyleInterRef" href="http://www.nice.org.uk/nicemedia/pdf/coxiifullguidance.pdf">http&#58;&#47;&#47;www&#46;nice&#46;org&#46;uk&#47;nicemedia&#47;pdf&#47;coxiifullguidance&#46;pdf</a>"
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib31"
              "etiqueta" => "31&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Centro Nacional de Epidemiolog&#237;a&#46; Mortalidad por causa&#44; sexo y grupo de edad &#40;1996&#8211;2005&#41; &#91;accessed 31&#47;7&#47;2008&#93;&#46; Available from&#58; <a class="elsevierStyleInterRef" href="http://www.isciii.es/htdocs/centros/epidemiologia/anexos/ww9201_ed_cau_tasa.htm">http&#58;&#47;&#47;www&#46;isciii&#46;es&#47;htdocs&#47;centros&#47;epidemiologia&#47;anexos&#47;ww9201&#95;ed&#95;cau&#95;tasa&#46;htm</a>"
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib32"
              "etiqueta" => "32&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Economic evaluation of nimesulide versus diclofenac in the treatment of osteoarthritis in France&#44; Italy and Spain"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "R&#46; Tarricone"
                            1 => "E&#46; Martelli"
                            2 => "F&#46; Parazzini"
                            3 => "J&#46; Darb&#224;"
                            4 => "C&#46; Le Pen"
                            5 => "J&#46; Rovira"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Drug Investig"
                        "fecha" => "2001"
                        "volumen" => "21"
                        "paginaInicial" => "453"
                        "paginaFinal" => "457"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib33"
              "etiqueta" => "33&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lesiones eritematosas y escamosas de la piel"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "K&#46; Aso"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:4 [
                        "titulo" => "Gu&#237;a de actuaci&#243;n en atenci&#243;n primaria"
                        "fecha" => "2002"
                        "editorial" => "Sociedad Espa&#241;ola de Medicina Familiar y Comunitaria"
                        "editorialLocalizacion" => "Barcelona"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib34"
              "etiqueta" => "34&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Direcci&#243;n General de Farmacia y Productos Sanitarios&#46; Base de datos del medicamento &#91;accessed 31&#47;7&#47;2008&#93;&#46; Available from&#58; <a class="elsevierStyleInterRef" href="http://www.portalfarmacom/">www&#46;portalfarmacom</a>"
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib35"
              "etiqueta" => "35&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Base de datos de costes sanitarios&#46; Versi&#243;n 2&#46;2"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46; Gisbert"
                            1 => "M&#46; Brosa"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:3 [
                        "fecha" => "2005"
                        "editorial" => "SOIKOS"
                        "editorialLocalizacion" => "Barcelona"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib36"
              "etiqueta" => "36&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pharmacoeconomic analysis in new drug development&#58; a pragmatic approach to efficiency studies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "C&#46; Rubio Terr&#233;s"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/1054773815575074"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Res &#38; REg Affairs"
                        "fecha" => "1998"
                        "volumen" => "15"
                        "paginaInicial" => "209"
                        "paginaFinal" => "223"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25784149"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/21735743/0000000600000004/v1_201305061610/S2173574310700435/v1_201305061610/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "17338"
    "tipo" => "SECCION"
    "es" => array:2 [
      "titulo" => "Original Article"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "es"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/21735743/0000000600000004/v1_201305061610/S2173574310700435/v1_201305061610/en/main.pdf?idApp=UINPBA00004M&text.app=https://reumatologiaclinica.org/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574310700435?idApp=UINPBA00004M"
]
Share
Journal Information
Vol. 6. Issue 4.
Pages 187-195 (July - August 2010)
Share
Share
Download PDF
More article options
Vol. 6. Issue 4.
Pages 187-195 (July - August 2010)
Full text access
An economic evaluation of chondroitin sulfate and non-steroidal anti-inflammatory drugs for the treatment of osteoarthritis. Data from the VECTRA study
Evaluación económica del uso de condroitín sulfato y antiinflamatorios no esteroideos en el tratamiento de la artrosis. Datos del estudio VECTRA
Visits
6366
Carlos Rubio-Terrés, Grupo del estudio VECTRA
Health Value, Health Economics and Research Outcomes Consulting, Madrid, Spain
This item has received
Article information
Abstract
Bibliography
Download PDF
Statistics
Abstract
Objective

Our aim was to investigate: 1) the average cost per patient with osteoarthritis treated with chondroitin sulfate compared with NSAIDs for 6 months and 2) the possible impact that the reduction NSAID use due to monotherapy with or combined administration of chondroitin sulfate treatment may have on the budget of the Spanish National Health System.

Methods

A cost-minimization model compared both treatments (efficacy equivalence assumption), used at the recommended doses and regimens during a 6-month period. Data used in the model was obtained from the VECTRA study, a retrospective study of 530 patients with osteoarthritis treated with chondroitin sulfate or NSAIDs that was conducted to determine the consumption of health care resources. The efficacy and incidence of adverse events was estimated from meta-analysis based on randomized clinical trials. Univariate sensitivity analysis was performed for the base case scenario.

Results

The overall 6-month cost per patient given chondroitin sulfate was 141 € compared with 182 € when treated with NSAIDs. If during the forthcoming 3 years, 5%, 10%, and 15% of patients currently treated with NSAIDs would gradually be replaced by treatment with chondroitin sulfate, the expected savings for the Spanish National Health System during these 3 years would be over 38,700,000 €. In addition, 2,666 cases of gastrointestinal adverse events (including 90 serious adverse events) will have been avoided for every 10,000 patients treated with chondroitin sulfate instead of NSAID. Sensitivity analysis confirmed the strength of base-case in all scenarios.

Conclusions

On the basis of these findings, chondroitin sulfate is a treatment for osteoarthritis with a lesser cost and better gastrointestinal tolerability compared with NSAIDs.

Keywords:
Chondroitin sulphate
Non-steroidal antiinflammatory drugs
Antirheumatic drugs
Osteoarthritis
Knee osteoarthritis
Hip osteoarthritis
Costs
Resumen
Objetivo

El presente estudio a) estima el coste medio de un paciente con artrosis tratado durante 6 meses con condroitín sulfato (CS) o antiinflamatorios no esteroideos (AINE), y b) evalúa el impacto presupuestario para el Sistema Nacional de Salud que causaría la disminución del consumo de AINE con la administración en monoterapia o conjunta de CS.

Material y método

Modelo de minimización de costes que comparó ambos tratamientos (asumiendo igualdad de eficacia), a las dosis y las pautas recomendadas, durante un período de seis meses. Los datos utilizados en el modelo se obtuvieron del estudio VECTRA, un estudio retrospectivo en el que se recogió el consumo de recursos sanitarios de 530 pacientes con artrosis tratados con CS o AINE. La eficacia y la incidencia de efectos adversos se estimaron a partir del metaanálisis de ensayos clínicos aleatorizados. Se hicieron análisis de sensibilidad simples univariantes del caso básico.

Resultados

El coste semestral por paciente tratado con CS fue de 141 €, y de 182 € en el caso de los AINE. Esto significa que, si durante los 3 próximos años el 5, el 10 y el 15% de los pacientes con artrosis tratados actualmente con AINE fueran tratados con CS, se generarían ahorros para el Sistema Nacional de Salud de más de 38,7 millones de euros durante este período. Además, por cada 10.000 pacientes tratados con CS en lugar de AINE se evitarían 2.666 efectos adversos gastrointestinales, de los que 90 serían graves. Los análisis de sensibilidad confirmaron la estabilidad del caso básico en todos los supuestos considerados.

Conclusiones

Comparado con los AINE, el CS es un tratamiento con menores costes y con mejor tolerancia gastrointestinal en el manejo de la artrosis.

Palabras clave:
Condroitín sulfato
Agentes antiinflamatorios no esteroideos
Agentes antirreumáticos
Artrosis
Artrosis de rodilla
Artrosis de cadera
Costes
Full text is only aviable in PDF
References
[1.]
V. Rabenda, C. Manette, R. Lemmens, A.M. Mariani, N. Struvay, J.Y. Reginster.
Direct and indirect costs attributable to osteoarthritis in active subjects.
J Rheumatol, 33 (2006), pp. 1152-1158
[2.]
F. Salaffi, M. Carotti, A. Stancati, W. Grassi.
Health-related quality of life in older adults with symptomatic hip and knee osteoarthritis: a comparison with matched healthy controls.
Aging Clin Exp Res, 17 (2005), pp. 255-263
[3.]
G. Leardini, F. Salaffi, R. Caporali, B. Canesi, L. Rovati, R. Montanelli, Italian Group for Study of the Costs of Arthritis.
Direct and indirect costs of osteoarthritis of the knee.
Clin Exp Rheumatol, 22 (2004), pp. 699-706
[4.]
J.C. Fernández-López, A. Laffon, F.J. Blanco, L. Carmona, Behalf of the EPISER Study Group.
Prevalence, risk factors, and impact of knee pain suggesting osteoarthritis in Spain.
Clin Exp Rheumatol, 26 (2008), pp. 324-332
[5.]
E.M. Badley, M. Crotty.
An international comparison of the estimated effect of the aging of the population on the major cause of disablement, musculoskeletal disorders.
J Rheumatol, 22 (1995), pp. 1934-1940
[6.]
A.A. Andrianakos, L.K. Kontelis, D.G. Karamitsos, S.I. Aslanidis, A.I. Georgountzos, G.O. Kaziolas, ESORDIG Study Group, et al.
Prevalence of symptomatic knee, hand, and hip osteoarthritis in Greece. The ESORDIG study.
J Rheumatol, 33 (2006), pp. 2507-2513
[7.]
M. Grotle, K.B. Hagen, B. Natvig, F.A. Dahl, T.K. Kvien.
Prevalence and burden of osteoarthritis: results from a population survey in Norway.
J Rheumatol, 35 (2008), pp. 677-684
[8.]
C.H. Roux, A. Saraux, B. Mazieres, J. Pouchot, J. Morvan, B. Fautrel, KHOALA Osteoarthritis Group, et al.
Screening for hip and knee osteoarthritis in the general population: predictive value of a questionnaire and prevalence estimates.
Ann Rheum Dis, 67 (2008), pp. 1406-1411
[9.]
B. Crichton, M. Green.
GP and patient perspectives on treatment with non-steroidal anti-inflammatory drugs for the treatment of pain in osteoarthritis.
Curr Med Res Opin, 18 (2002), pp. 92-96
[10.]
D. Scholes, A. Stergachis, P.M. Penna, E.H. Normand, P.D. Hansten.
Nonsteroidal antiinflammatory drug discontinuation in patients with osteoarthritis.
J Rheumatol, 22 (1995), pp. 708-712
[11.]
J.M. Bjordal, A.E. Ljunggren, A. Klovning, L. Slørdal.
Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritic knee pain: metaanalysis of randomised placebo controlled trials.
[12.]
J. Monfort, J. Martel-Pelletier, J.P. Pelletier.
Chondroitin sulphate for symptomatic osteoarthritis: critical appraisal of meta-analyses.
Curr Med Res Opin, 24 (2008), pp. 1303-1308
[13.]
K.M. Jordan, N.K. Arden, M. Doherty, B. Bannwarth, J.W. Bijlsma, P. Dieppe, et al.
Standing Committee for International Clinical Studies Including Therapeutic Trials ESCISIT. EULAR recommendations 2003: an evidence based approach to the management of knee osteoarthritis: report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT).
Ann Rheum Dis, 62 (2003), pp. 1145-1155
[14.]
W. Zhang, R.W. Moskowitz, G. Nuki, S. Abramson, R.D. Altman, N. Arden, et al.
OARSI recommendations for the management of hip and knee osteoarthritis, part I: critical appraisal of existing treatment guidelines and systematic review of current research evidence.
Osteoarthritis Cartilage, 15 (2007), pp. 981-1000
[15.]
T. Conrozier.
Chondroitin sulfates (CS 4&6): practical applications and economic impact.
Presse Med, 27 (1998), pp. 1866-1868
[16.]
R. Lagnaoui, M. Baumevielle, B. Bégaud, P. Pouyanne, G. Maurice, F. Depont, et al.
Less use of NSAIDs in long-term than in recent chondroitin sulphate users in osteoarthritis: a pharmacy-based observational study in France.
Thérapie, 61 (2006), pp. 341-346
[17.]
C. Taieb, C. Huichard, L. Didier, R. Roche, D. Labed, E. Myon.
Osteoarthritis: chondroitin sulfate long term utilization reduces consumption of coxibs, NSAIDs and analgesics.
Ann Rheum Dis, 64 (2005), pp. 483
[18.]
C. Rubio-Terrés, I. Möller Parera, E. Tomás Campeny, J. Vergés Milano.
Análisis farmacoeconómico del tratamiento de la artrosis con condroitín sulfato en comparación con AINE.
Atenc Farm, 6 (2004), pp. 15-27
[19.]
Maetzel A, Krahn M, Naglie G. The cost-effectiveness of celecoxib and rofecoxib in patients with osteoarthritis or rheumatoid arthritis. Ottawa: Canadian Coordinating Office for Health Technology Assessment; 2002. Technology report no. 23.
[20.]
P. Morreale, R. Manopulo, M. Galati, L. Boccanera, G. Saponati, L. Bocchi.
Comparison of the antiinflammatory efficacy of chondroitin sulfate and diclofenac sodium in patients with knee osteoarthritis.
J Rheumatol, 23 (1996), pp. 1385-1391
[21.]
R.M. Eugenio-Sarmiento, B.H.D. Manapat, E.O. Salido.
The efficacy of chondroitin sulfate in the treatment of knee osteoarthritis: a meta-analysis.
Osteoarthritis Cartilage, 7 (1999), pp. S35
[22.]
B.F. Leeb, H. Schweitzer, K. Montag, J.S. Smolen.
A metaanalysis of chondroitin sulfate in the treatment of osteoarthritis.
J Rheumatol, 27 (2000), pp. 205-211
[23.]
T.E. McAlindon, M.P. La Valley, J.P. Gulin, D.T. Felson.
Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis.
JAMA, 283 (2000), pp. 1469-1475
[24.]
S. Reichenbach, R. Sterchi, M. Scherer, S. Trelle, E. Bürgi, U. Bürgi, et al.
Meta-analysis: chondroitin for osteoarthritis of the knee or hip.
Ann Intern Med, 146 (2007), pp. 580-590
[25.]
F. Richy, O. Bruyere, O. Ethgen, M. Cucherat, Y. Henrotin, J.Y. Reginster.
Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis.
Arch Intern Med, 164 (2003), pp. 1514-1522
[26.]
D. Uebelhart, M. Malaise, R. Marcolongo, F. De Vathaire, M. Piperno, E. Mailleux, et al.
Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a oneyear, randomized, double-blind, multicenter study versus placebo.
Osteoarthritis Cartilage, 12 (2004), pp. 269-276
[27.]
C.C. Kamath, H.M. Kremers, D.J. Vanness, W.M. O’Fallon, R.L. Cabanela, S.E. Gabriel.
The cost-effectiveness of acetaminophen, NSAIDs, and selective COX-2 inhibitors in the treatment of symptomatic knee osteoarthritis.
Value Health, 6 (2003), pp. 144-157
[28.]
A. Moreno, E. Vargas, J. Soto, J. Rejas.
Cost-effectiveness analysis of the use of celecoxib for the treatment of osteoarthritis.
Gac Sanit, 17 (2003), pp. 27-36
[29.]
US Food and Drug Administration. VIOxx gastrointestinal safety [accessed 31/7/2008]. Available from: http://www.fda.gov/medwatch/SAFETY/2002/vioxx_deardoc.pdf
[30.]
National Institute for Health and Clinical Excellence (NICE). TA27 Osteoarthritis and rheumatoid arthritis-COX II inhibitors: guidance [accessed 31/7/2008]. Available from: http://www.nice.org.uk/nicemedia/pdf/coxiifullguidance.pdf
[31.]
Centro Nacional de Epidemiología. Mortalidad por causa, sexo y grupo de edad (1996–2005) [accessed 31/7/2008]. Available from: http://www.isciii.es/htdocs/centros/epidemiologia/anexos/ww9201_ed_cau_tasa.htm
[32.]
R. Tarricone, E. Martelli, F. Parazzini, J. Darbà, C. Le Pen, J. Rovira.
Economic evaluation of nimesulide versus diclofenac in the treatment of osteoarthritis in France, Italy and Spain.
Clin Drug Investig, 21 (2001), pp. 453-457
[33.]
K. Aso.
Lesiones eritematosas y escamosas de la piel.
Guía de actuación en atención primaria, Sociedad Española de Medicina Familiar y Comunitaria, (2002),
[34.]
Dirección General de Farmacia y Productos Sanitarios. Base de datos del medicamento [accessed 31/7/2008]. Available from: www.portalfarmacom
[35.]
R. Gisbert, M. Brosa.
Base de datos de costes sanitarios. Versión 2.2.
SOIKOS, (2005),
[36.]
C. Rubio Terrés.
Pharmacoeconomic analysis in new drug development: a pragmatic approach to efficiency studies.
Clin Res & REg Affairs, 15 (1998), pp. 209-223

The list of the VECTRA study researchers is shown in Annex I.

VECTRA is the acronym for the “Economic and Health Evaluation of Chondroitin Sulphate for the Treatment of Osteoarthritis”.

Copyright © 2010. Sociedad Española de Reumatología and Colegio Mexicano de Reumatología
Download PDF
Idiomas
Reumatología Clínica (English Edition)
Article options
Tools
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?