Longitudinal observational studies and causality
Estudios observacionales longitudinales y causalidad
Read
13690
Timeswas read the article
2910
Total PDF
10780
Total HTML
Share statistics
array:21 [ "pii" => "X201325141200061X" "issn" => "20132514" "doi" => "10.3265/Nefrologia.pre2011.Nov.11167" "estado" => "S300" "fechaPublicacion" => "2012-01-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Nefrologia (English Version). 2012;32:12-4" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 5983 "formatos" => array:3 [ "EPUB" => 334 "HTML" => 4874 "PDF" => 775 ] ] "Traduccion" => array:1 [ "es" => array:17 [ "pii" => "X0211699512000612" "issn" => "02116995" "doi" => "10.3265/Nefrologia.pre2011.Nov.11167" "estado" => "S300" "fechaPublicacion" => "2012-01-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Nefrologia. 2012;32:12-4" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 8396 "formatos" => array:3 [ "EPUB" => 279 "HTML" => 7463 "PDF" => 654 ] ] "es" => array:9 [ "idiomaDefecto" => true "titulo" => "Estudios observacionales longitudinales y causalidad" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "12" "paginaFinal" => "14" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Longitudinal observational studies and causality" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Alfonso Muriel, Domingo Hernández-Marrero, Víctor Abraira" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Alfonso" "apellidos" => "Muriel" ] 1 => array:2 [ "nombre" => "Domingo" "apellidos" => "Hernández-Marrero" ] 2 => array:2 [ "nombre" => "Víctor" "apellidos" => "Abraira" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "X201325141200061X" "doi" => "10.3265/Nefrologia.pre2011.Nov.11167" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X201325141200061X?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X0211699512000612?idApp=UINPBA000064" "url" => "/02116995/0000003200000001/v0_201502091357/X0211699512000612/v0_201502091357/es/main.assets" ] ] "itemSiguiente" => array:17 [ "pii" => "X2013251412000601" "issn" => "20132514" "doi" => "10.3265/Nefrologia.pre2011.Nov.11098" "estado" => "S300" "fechaPublicacion" => "2012-01-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Nefrologia (English Version). 2012;32:15-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 9531 "formatos" => array:3 [ "EPUB" => 309 "HTML" => 8324 "PDF" => 898 ] ] "en" => array:10 [ "idiomaDefecto" => true "titulo" => "The value of serum free light chain assay in patients with monoclonal gammopathies and renal failure" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "15" "paginaFinal" => "19" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Valor del ensayo de las cadenas ligeras libres en suero para los pacientes de gammapatías monoclonales e insuficiencia renal" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11098_16025_25688_en_f1_11098.jpg" "Alto" => 1311 "Ancho" => 2089 "Tamanyo" => 1893534 ] ] "descripcion" => array:1 [ "en" => "Free light chains and the kidney" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. Luisa Campos, Nuno M. Barbosa-de Carvalho, Guillermo Martín-Reyes" "autores" => array:3 [ 0 => array:2 [ "nombre" => "M. Luisa" "apellidos" => "Campos" ] 1 => array:2 [ "nombre" => "Nuno M." "apellidos" => "Barbosa-de Carvalho" ] 2 => array:2 [ "nombre" => "Guillermo" "apellidos" => "Martín-Reyes" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "X0211699512000604" "doi" => "10.3265/Nefrologia.pre2011.Nov.11098" "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/X0211699512000604?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251412000601?idApp=UINPBA000064" "url" => "/20132514/0000003200000001/v0_201502091620/X2013251412000601/v0_201502091620/en/main.assets" ] "itemAnterior" => array:17 [ "pii" => "X2013251412000628" "issn" => "20132514" "doi" => "10.3265/Nefrologia.pre2011.Dec.11258" "estado" => "S300" "fechaPublicacion" => "2012-01-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Nefrologia (English Version). 2012;32:7-11" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 11392 "formatos" => array:3 [ "EPUB" => 335 "HTML" => 10047 "PDF" => 1010 ] ] "en" => array:10 [ "idiomaDefecto" => true "titulo" => "Carotid ultrasound for the early diagnosis of atherosclerosis in chronic kidney disease" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "7" "paginaFinal" => "11" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La ecografía carotídea en el diagnóstico precoz de enfermedad arterial ateromatosa en la enfermedad renal crónica" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11258_16025_26277_en_figura_1_a_y_figura_b_11258.jpg" "Alto" => 842 "Ancho" => 2121 "Tamanyo" => 595821 ] ] "descripcion" => array:1 [ "en" => "Ultrasound image of carotid arteries" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Àngels Betriu-Bars, Elvira Fernández-Giráldez" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Àngels" "apellidos" => "Betriu-Bars" ] 1 => array:2 [ "nombre" => "Elvira" "apellidos" => "Fernández-Giráldez" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "X0211699512000620" "doi" => "10.3265/Nefrologia.pre2011.Dec.11258" "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/X0211699512000620?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251412000628?idApp=UINPBA000064" "url" => "/20132514/0000003200000001/v0_201502091620/X2013251412000628/v0_201502091620/en/main.assets" ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "Longitudinal observational studies and causality" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "12" "paginaFinal" => "14" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Alfonso Muriel, Domingo Hernández-Marrero, Víctor Abraira" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Alfonso" "apellidos" => "Muriel" "email" => array:1 [ 0 => "alfonso.muriel@hrc.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 1 => array:3 [ "nombre" => "Domingo" "apellidos" => "Hernández-Marrero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] 2 => array:3 [ "nombre" => "Víctor" "apellidos" => "Abraira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Unidad de Bioestadística Clínica, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERESP, Madrid, " "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Universitario Carlos Haya, Málaga, " "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Estudios observacionales longitudinales y causalidad" ] ] "textoCompleto" => "<p class="elsevierStylePara">Results from randomised clinical trials (CT) and CT meta-analyses provide the best scientific evidence for evaluating the effect of a treatment according to the hierarchical rankings for clinical research methods. Observational studies (OS) hold a lower position in the evidence rankings, and are considered to have less probative force for the following reasons: a) they may overestimate the effects of the treatment due to patient heterogeneity; b) they may contain biases that are inherent to their design and nature; and c) on some occasions, the interpretation of results may be confusing. However, the controlled conditions found in a CT mean that their results may not be directly applicable to patients in clinical practice. An OS, on the other hand, measures effectiveness that cannot feasibly be obtained in any other way. In clinical research, and in the field of nephrology in particular, the analysis of large patient registers or clinical databases provides information whose usefulness should not be underestimated,<span class="elsevierStyleSup">1,2</span> and which may complement CT results. Using this strategy, we can perform  medical research that is closer to daily clinical practice, and focuses on the normal conditions experienced by the patients themselves.<span class="elsevierStyleSup">3</span></p><p class="elsevierStylePara">Generally speaking, OS, and cohort studies in particular, are useful for assessing the effect of a treatment that was not assigned at random. Here, treatment is established based on common medical practice or on the patient’s individual characteristics. Establishing a link between a treatment and a certain result may depend on a number of biases, including confounding by indication, since in this type of study, treatment is not assigned at random and may be related to health results. One obvious example is when the indication for the treatment in some situations is determined based on clinical guidelines or consensus for a specific disease.</p><p class="elsevierStylePara">A number of statistical models have been created to assess the effect of a treatment and to check for potentially confounding co-variables. For example, regression models can offer measures to associate a treatment with a result, but they cannot establish causality measures due to the lack of interchangeability among patients. Causal relationships can be established in a CT, since the patients are interchangeable and assigned to different groups at random. Interchangeability cannot be assumed in an OS, since the assigned group depends on the patient's conditions, expressed as co-variables that change over time, and on the treatment the patient receives according to the co-variables that were analysed. It may therefore occur that time-dependent variables are affected by the treatment itself. This means that both the co-variables and the treatment may change the patient’s prognosis.</p><p class="elsevierStylePara">Marginal structural models (MSM) were proposed in the late 1990s by members of the Harvard School of Public Health<span class="elsevierStyleSup">3,4 </span>to evaluate causal relationships and avoid biases in longitudinal studies. MSM are an alternative to classical regression models when there is a time-dependent confounder that is associated with the event in question, but it is also related to the treatment being evaluated. These models are called “structural” because they study causality, rather than simple association. Causal inference is performed by means of comparing, theoretically, the results of treating all patients with the results of treating none of the patients. Marginal structural models use a weighted form of the propensity score, called IPTW (inverse probability of treatment weight), in such a way as to simulate a population in which treated and untreated patients do not differ in any of their co-variables, therefore allowing us to assume interchangeability for treated and untreated patients. MSM are used in clinical research in order to resolve questions of causality. As noted by Hernan, the scenario is typically represented by observational studies that are analysed like CT.<span class="elsevierStyleSup">5</span> This type of model can be implemented by using common statistical software applications. The journal NBE published an article entitled “<span class="elsevierStyleItalic">Modelos estructurales marginales: una herramienta útil que proporciona evidencia a los estudios observacionales</span>” (marginal structural models: a tool for studying causal relationships in observational studies)<span class="elsevierStyleSup">6</span> which provides practical information about this type of statistical tool. This article also provides an in-depth account of the conceptual bases of an MSM, the assumptions and conditions it must contain, and the way to implement it by using specifically designed statistical software.</p><p class="elsevierStylePara">In many medical specialties, including nephrology, patients are monitored over long periods of time as part of their care requirements, and they receive a number of treatments that are added according to their condition at a specific time. An MSM is ideal in this type of situation for avoiding confounding by indication biases. To cite an example, MSM were applied in OS of HIV-positive patients receiving anti-retroviral drugs<span class="elsevierStyleSup">7-10</span>; in patients taking aspirin due for cardiovascular disease<span class="elsevierStyleSup">11</span>; and in patients who received corticosteroids for asthma<span class="elsevierStyleSup">12</span> or rheumatoid arthritis.<span class="elsevierStyleSup">13</span></p><p class="elsevierStylePara">In nephrology, MSM have also been used to determine the causal relationship between multiple treatments or exposures and the final outcome of a disease. In this respect, multiple OS have shown that patients on high doses of erythropoietin (EPO) could have higher mortality rates, although it was also suspected that patients requiring higher doses of EPO could have more co-morbidities. Likewise, the efficacy of restricting phosphorus in a diet or using a certain dialysis technique (haemodialysis vs peritoneal dialysis) to decrease mortality in kidney patients are also topics of considerable debate.</p><p class="elsevierStylePara">Although a preliminary analysis shows that very high doses of EPO are associated with higher mortality, this effect disappeared with the implementation of a more complete MSM.<span class="elsevierStyleSup">14</span> Use of MSM also revealed that neither restricting dietary phosphate in these patients nor the type of dialysis (haemodialysis or peritoneal dialysis) had a decisive influence on mortality in this patient group.<span class="elsevierStyleSup">15,16</span> Lastly, the use of MSM in a multi-centre OS from the Netherlands showed that loss of residual renal function was associated with higher mortality rate,<span class="elsevierStyleSup">17</span> which supports the possibility of implementing kidney replacement therapy that is personalised according to the urinary volume of the patient at the start of chronic dialysis.</p><p class="elsevierStylePara">In the field of kidney transplantation, the main purpose of MSM is to estimate the impact of metabolic changes on mortality and to evaluate the efficacy of immunosuppressive and cardioprotective drugs on both patient and kidney graft survival. In fact, the use of Cox regression models and MSM, adjusted for confounders, showed that high glycaemia and more intense insulin treatment was associated with higher mortality.<span class="elsevierStyleSup">18</span> At the same time, with the help of MSM, it was shown that the use of mycophenolate mofetil was a more effective aid to kidney graft survival than azathioprine.<span class="elsevierStyleSup">19</span> Lastly, a recent OS performed by our group by MSM found that the use of renin-angiotensin system blockers in kidney transplant patients is associated with a lower risk of mortality, but does not guard against losing the graft.<span class="elsevierStyleSup">20</span> These findings confirm the usefulness of implementing an MSM in cohort OS of renal patients, but it remains unclear whether carrying out randomised CT on these patients will support these results.</p><p class="elsevierStylePara">As we await new evidence, use of MSM in cohort OS employing time-dependent variables provides results that are valid and complementary to CT results for evaluating the clinical efficacy of specific treatments.</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Acknowledgements </span></p><p class="elsevierStylePara">The authors would like to thank Ramón y Cajal University Hospital’s Biostatistics Unit (IRYCIS, Madrid, Spain; CIBER Epidemiology and Public Health CIBERESP) and the kidney transplant teams at University Hospital of the Canary Islands (Tenerife) and Carlos Haya Hospital (Málaga) for their participation.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Key concepts</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">1. </span>OS results may be comparable to those from clinical trials in terms of therapeutic efficacy, given adequate, rigorous OS design and data analysis methods.</p><p class="elsevierStylePara"><span class="elsevierStyleBold">2. </span>The presence of time-dependent clinical confounders can result in overestimating or underestimating the effect of treatment when conventional regression models are used, due to confounding by indication.</p><p class="elsevierStylePara"><span class="elsevierStyleBold">3. </span>MSM can prevent confounding by indication biases, but their assumptions and conditions must be verified.</p><p class="elsevierStylePara"><span class="elsevierStyleBold">4. </span>The choice of confounders for implementing MSM must be done from a clinical standpoint, using the appropriate statistical support. Faulty choice of these variables can result in a bias that changes the estimator variance.</p><p class="elsevierStylePara"><span class="elsevierStyleBold">5. </span>When using an OS to assess the efficacy of a treatment, employing MSM can increase the level of evidence, making it applicable and extendable to daily clinical practice.</p>" "pdfFichero" => "P1-E532-S3380-A11167-EN.pdf" "tienePdf" => true "PalabrasClave" => array:1 [ "en" => array:4 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec439002" "palabras" => array:1 [ 0 => "Survival analysis" ] ] 1 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec439004" "palabras" => array:1 [ 0 => "Observational Study" ] ] 2 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec439006" "palabras" => array:1 [ 0 => "Regression" ] ] 3 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec439008" "palabras" => array:1 [ 0 => "Causal models" ] ] ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:20 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Dreyer NA, Garner S. Registries for robust evidence. JAMA 2009;302(7):790-1. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19690313" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Hernández D, Pascual J, Abraira V, Lorenzo V, Quereda C. Estudios observacionales y registros como fuentes de evidencia en el trasplante renal. Nefrologia 2006;26 Suppl 5:66-76." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Hernán MA. With great data comes great responsibility: publishing comparative effectiveness research in epidemiology. Epidemiology 2011;22(3):290-1. <a href="http://www.ncbi.nlm.nih.gov/pubmed/21464646" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Robins JM, Hernán MA, Brumback B. Marginal structural models and causal inference in epidemiology. Epidemiology 2000;11(5):550-60. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10955408" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Hernán MA, Alonso A, Logan R, Grodstein F, Michels KB, Willett WC, et al.\u{A0}Observational studies analyzed like randomized experiments: an application to postmenopausal hormone therapy and coronary heart disease. Epidemiology 2008;19(6):766-79. <a href="http://www.ncbi.nlm.nih.gov/pubmed/18854702" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 5 => array:3 [ "identificador" => "bib6" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Muriel A, Hernández D, Abraira V. Modelos estructurales marginales: una herramienta útil que proporciona evidencia a los estudios observacionales. Nefrologia Sup Ext 2011;2(7):7-13." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 6 => array:3 [ "identificador" => "bib7" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Edmonds A, Yotebieng M, Lusiama J, Matumona Y, Kitetele F, Napravnik S, et al.\u{A0}The effect of highly active antiretroviral therapy on the survival of HIV-infected children in a resource-deprived setting: a cohort study. PLoS Med 2011;8(6):e1001044. <a href="http://www.ncbi.nlm.nih.gov/pubmed/21695087" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 7 => array:3 [ "identificador" => "bib8" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Petersen ML, Wang Y, van der Laan MJ, Guzman D, Riley E, Bangsberg DR. Pillbox organizers are associated with improved adherence to HIV antiretroviral therapy and viral suppression: a marginal structural model analysis. Clin Infect Dis 2007;45(7):908-15. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17806060" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 8 => array:3 [ "identificador" => "bib9" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Petersen ML, Wang Y, van der Laan MJ, Rhee SY, Shafer RW, Fessel WJ. Virologic efficacy of boosted double versus boosted single protease inhibitor therapy. AIDS 2007;21(12):1547-54. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17630549" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 9 => array:3 [ "identificador" => "bib10" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Hernan MA, Brumback BA, Robins JM. Estimating the causal effect of zidovudine on CD4 count with a marginal structural model for repeated measures. Stat Med 2002;21(12):1689-709. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12111906" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 10 => array:3 [ "identificador" => "bib11" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Cook NR, Cole SR, Hennekens CH. Use of a marginal structural model to determine the effect of aspirin on cardiovascular mortality in the Physicians' Health Study. Am J Epidemiol 2002;155(11):1045-53. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12034583" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 11 => array:3 [ "identificador" => "bib12" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Kim C, Feldman HI, Joffe M, Tenhave T, Boston R, Apter AJ. Influences of earlier adherence and symptoms on current symptoms: a marginal structural models analysis. J Allergy Clin Immunol 2005;115(4):810-4. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15806003" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 12 => array:3 [ "identificador" => "bib13" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Choi HK, Hernan MA, Seeger JD, Robins JM, Wolfe F. Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 2002;359(9313):1173-7. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11955534" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 13 => array:3 [ "identificador" => "bib14" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Wang O, Kilpatrick RD, Critchlow CW, Ling X, Bradbury BD, Gilbertson DT, et al.\u{A0}Relationship between epoetin alfa dose and mortality: findings from a marginal structural model. Clin J Am Soc Nephrol 2010;5(2):182-8. <a href="http://www.ncbi.nlm.nih.gov/pubmed/20019122" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 14 => array:3 [ "identificador" => "bib15" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Lynch KE, Lynch R, Curhan GC, Brunelli SM. Prescribed dietary phosphate restriction and survival among hemodialysis patients. Clin J Am Soc Nephrol 2011;6(3):620-9. <a href="http://www.ncbi.nlm.nih.gov/pubmed/21148246" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 15 => array:3 [ "identificador" => "bib16" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Mehrotra R, Chiu YW, Kalantar-Zadeh K, Bargman J, Vonesh E. Similar outcomes with hemodialysis and peritoneal dialysis in patients with end-stage renal disease. Arch Intern Med 2011;171(2):110-8. <a href="http://www.ncbi.nlm.nih.gov/pubmed/20876398" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 16 => array:3 [ "identificador" => "bib17" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "van der Wal WM, Noordzij M, Dekker FW, Boeschoten EW, Krediet RT, Korevaar JC, et al.\u{A0}Full loss of residual renal function causes higher mortality in dialysis patients; findings from a marginal structural model. Nephrol Dial Transplant 2011;26(9):2978-83. <a href="http://www.ncbi.nlm.nih.gov/pubmed/21317411" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 17 => array:3 [ "identificador" => "bib18" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Wiesbauer F, Heinze G, Regele H, Horl WH, Schernthaner GH, Schwarz C, et al.\u{A0}Glucose control is associated with patient survival in diabetic patients after renal transplantation. Transplantation 2010;89(5):612-9. <a href="http://www.ncbi.nlm.nih.gov/pubmed/20110856" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 18 => array:3 [ "identificador" => "bib19" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Kainz A, Heinze G, Korbely R, Schwarz C, Oberbauer R. Mycophenolate mofetil use is associated with prolonged graft survival after kidney transplantation. Transplantation 2009;88(9):1095-100. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19898205" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 19 => array:3 [ "identificador" => "bib20" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Hernández D, Muriel A, Abraira V, Pérez G, Porrini E, Marrero D, et al.\u{A0}Renin-angiotensin system blockade and kidney transplantation: longitudinal cohort study. Nephrol Dial Transplant. 2011 May 28.doi:10.193/ndt/gfr276. [Epub ahead of print]. <a href="http://www.ncbi.nlm.nih.gov/pubmed/22773240" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/20132514/0000003200000001/v0_201502091620/X201325141200061X/v0_201502091620/en/main.assets" "Apartado" => array:4 [ "identificador" => "35428" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Editorial Comments" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/20132514/0000003200000001/v0_201502091620/X201325141200061X/v0_201502091620/en/P1-E532-S3380-A11167-EN.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X201325141200061X?idApp=UINPBA000064" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 3 | 6 | 9 |
| 2024 October | 89 | 34 | 123 |
| 2024 September | 83 | 28 | 111 |
| 2024 August | 106 | 52 | 158 |
| 2024 July | 84 | 26 | 110 |
| 2024 June | 103 | 49 | 152 |
| 2024 May | 109 | 34 | 143 |
| 2024 April | 89 | 39 | 128 |
| 2024 March | 71 | 22 | 93 |
| 2024 February | 63 | 27 | 90 |
| 2024 January | 100 | 28 | 128 |
| 2023 December | 57 | 34 | 91 |
| 2023 November | 89 | 53 | 142 |
| 2023 October | 79 | 51 | 130 |
| 2023 September | 64 | 37 | 101 |
| 2023 August | 54 | 18 | 72 |
| 2023 July | 80 | 38 | 118 |
| 2023 June | 92 | 23 | 115 |
| 2023 May | 103 | 45 | 148 |
| 2023 April | 51 | 19 | 70 |
| 2023 March | 94 | 24 | 118 |
| 2023 February | 62 | 31 | 93 |
| 2023 January | 59 | 28 | 87 |
| 2022 December | 88 | 37 | 125 |
| 2022 November | 96 | 36 | 132 |
| 2022 October | 112 | 66 | 178 |
| 2022 September | 134 | 33 | 167 |
| 2022 August | 102 | 49 | 151 |
| 2022 July | 83 | 48 | 131 |
| 2022 June | 104 | 48 | 152 |
| 2022 May | 122 | 44 | 166 |
| 2022 April | 107 | 69 | 176 |
| 2022 March | 101 | 64 | 165 |
| 2022 February | 110 | 47 | 157 |
| 2022 January | 152 | 38 | 190 |
| 2021 December | 81 | 36 | 117 |
| 2021 November | 73 | 35 | 108 |
| 2021 October | 134 | 50 | 184 |
| 2021 September | 131 | 51 | 182 |
| 2021 August | 109 | 53 | 162 |
| 2021 July | 109 | 45 | 154 |
| 2021 June | 106 | 48 | 154 |
| 2021 May | 120 | 52 | 172 |
| 2021 April | 280 | 81 | 361 |
| 2021 March | 175 | 46 | 221 |
| 2021 February | 166 | 28 | 194 |
| 2021 January | 155 | 30 | 185 |
| 2020 December | 105 | 16 | 121 |
| 2020 November | 127 | 26 | 153 |
| 2020 October | 98 | 28 | 126 |
| 2020 September | 84 | 15 | 99 |
| 2020 August | 117 | 31 | 148 |
| 2020 July | 114 | 22 | 136 |
| 2020 June | 125 | 27 | 152 |
| 2020 May | 145 | 24 | 169 |
| 2020 April | 100 | 31 | 131 |
| 2020 March | 110 | 23 | 133 |
| 2020 February | 94 | 31 | 125 |
| 2020 January | 102 | 30 | 132 |
| 2019 December | 100 | 30 | 130 |
| 2019 November | 99 | 23 | 122 |
| 2019 October | 108 | 31 | 139 |
| 2019 September | 123 | 28 | 151 |
| 2019 August | 129 | 19 | 148 |
| 2019 July | 127 | 29 | 156 |
| 2019 June | 95 | 19 | 114 |
| 2019 May | 68 | 19 | 87 |
| 2019 April | 108 | 35 | 143 |
| 2019 March | 68 | 21 | 89 |
| 2019 February | 54 | 18 | 72 |
| 2019 January | 63 | 19 | 82 |
| 2018 December | 98 | 44 | 142 |
| 2018 November | 130 | 24 | 154 |
| 2018 October | 80 | 21 | 101 |
| 2018 September | 79 | 19 | 98 |
| 2018 August | 63 | 19 | 82 |
| 2018 July | 56 | 18 | 74 |
| 2018 June | 65 | 16 | 81 |
| 2018 May | 49 | 14 | 63 |
| 2018 April | 75 | 12 | 87 |
| 2018 March | 66 | 6 | 72 |
| 2018 February | 70 | 8 | 78 |
| 2018 January | 162 | 7 | 169 |
| 2017 December | 68 | 9 | 77 |
| 2017 November | 52 | 17 | 69 |
| 2017 October | 39 | 10 | 49 |
| 2017 September | 44 | 18 | 62 |
| 2017 August | 33 | 24 | 57 |
| 2017 July | 37 | 16 | 53 |
| 2017 June | 34 | 10 | 44 |
| 2017 May | 56 | 15 | 71 |
| 2017 April | 38 | 17 | 55 |
| 2017 March | 28 | 6 | 34 |
| 2017 February | 23 | 15 | 38 |
| 2017 January | 18 | 17 | 35 |
| 2016 December | 84 | 9 | 93 |
| 2016 November | 93 | 10 | 103 |
| 2016 October | 108 | 9 | 117 |
| 2016 September | 137 | 13 | 150 |
| 2016 August | 218 | 7 | 225 |
| 2016 July | 168 | 5 | 173 |
| 2016 June | 129 | 0 | 129 |
| 2016 May | 111 | 0 | 111 |
| 2016 April | 97 | 0 | 97 |
| 2016 March | 103 | 0 | 103 |
| 2016 February | 108 | 0 | 108 |
| 2016 January | 98 | 0 | 98 |
| 2015 December | 112 | 0 | 112 |
| 2015 November | 106 | 0 | 106 |
| 2015 October | 95 | 0 | 95 |
| 2015 September | 82 | 0 | 82 |
| 2015 August | 85 | 0 | 85 |
| 2015 July | 57 | 0 | 57 |
| 2015 June | 42 | 0 | 42 |
| 2015 May | 77 | 0 | 77 |
| 2015 April | 10 | 0 | 10 |
Show all
