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How to improve adherence the captors of phosphorus on hemodialysis: Experience in real life with sucroferric oxyhydroxide
Cómo mejorar la adherencia a los captores del fosforo en hemodiálisis: experiencia en vía real con oxihidróxido sucroférrico
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La alternativa a la biopsia percutánea en pacientes de alto riesgo" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Mónica Bolufer, Clara García-Carro, Irene Agraz, Iratxe Díez Miranda, Juliana Jaramillo, Karla Arredondo, Roxana Bury, Natalia Ramos, Maria A. Azancot, Alejandra Gabaldón, Mercedes Pérez Lafuente, Eugenia Espinel, Alfons Segarra, Daniel Serón, María José Soler" "autores" => array:15 [ 0 => array:2 [ "nombre" => "Mónica" "apellidos" => "Bolufer" ] 1 => array:2 [ "nombre" => "Clara" "apellidos" => "García-Carro" ] 2 => array:2 [ "nombre" => "Irene" "apellidos" => "Agraz" ] 3 => array:2 [ "nombre" => "Iratxe" "apellidos" => "Díez Miranda" ] 4 => array:2 [ "nombre" => "Juliana" "apellidos" => "Jaramillo" ] 5 => array:2 [ "nombre" => "Karla" "apellidos" => "Arredondo" ] 6 => array:2 [ "nombre" => "Roxana" "apellidos" => "Bury" ] 7 => array:2 [ "nombre" => "Natalia" "apellidos" => "Ramos" ] 8 => array:2 [ "nombre" => "Maria A." "apellidos" => "Azancot" ] 9 => array:2 [ "nombre" => "Alejandra" "apellidos" => "Gabaldón" ] 10 => array:2 [ "nombre" => "Mercedes" "apellidos" => "Pérez Lafuente" ] 11 => array:2 [ "nombre" => "Eugenia" "apellidos" => "Espinel" ] 12 => array:2 [ "nombre" => "Alfons" "apellidos" => "Segarra" ] 13 => array:2 [ "nombre" => "Daniel" "apellidos" => "Serón" ] 14 => array:2 [ "nombre" => "María José" "apellidos" => "Soler" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0211699520300801" "doi" => "10.1016/j.nefro.2020.04.018" "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/S0211699520300801?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251420301358?idApp=UINPBA000064" "url" => "/20132514/0000004000000006/v1_202012250708/S2013251420301358/v1_202012250708/en/main.assets" ] "en" => array:21 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "How to improve adherence the captors of phosphorus on hemodialysis: Experience in real life with sucroferric oxyhydroxide" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "640" "paginaFinal" => "646" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "M. Dolores Arenas Jiménez, Juan Francisco Navarro González" "autores" => array:2 [ 0 => array:4 [ "nombre" => "M. Dolores" "apellidos" => "Arenas Jiménez" "email" => array:1 [ 0 => "lola@olemiswebs.com" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "fn0005" ] 3 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Juan Francisco" "apellidos" => "Navarro González" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Nephrology Department, Hospital Vithas Perpetuo Internacional, Alicante, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Nephrolgy Department, Hospital del Mar, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Nephrology Department, Hospital Universitario Nuestra Señora de la Candelaria, RedinRen, Santa Cruz de Tenerife, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Cómo mejorar la adherencia a los captores del fosforo en hemodiálisis: experiencia en vía real con oxihidróxido sucroférrico" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1735 "Ancho" => 2500 "Tamanyo" => 163158 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Comparison between SUCROFERRIC OXYHYDROXIDE (SFOH) group and control group (phosphate serum levels).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The search for a phosphate binder (PB) that is effective, well-tolerated, overcomes the problem of non-adherence, and controls serum phosphorus (sP) in patients on hemodialysis (HD) in a stable and sustained manner, remains an open question. In controlled clinical trials, all currently available PB have demonstrated their effectiveness in lowering the sP,<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">1</span></a> and some of them have additional advantages in other aspects such as vascular calcification,<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">2</span></a> pleiotropic effects on cholesterol<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">3</span></a> or decrease in FGF 23.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">However, in actual clinical practice, results are not as favorable, and despite having sufficient tools, a large number of patients treated with PB fail to maintain sP within the ranges recommended by the different clinical guidelines.<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">5,6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Sucroferric oxyhydroxide (SFOH) is a non-calcium, iron-based PB that compared to sevelamer carbonate (“sevelamer®”), has demonstrated sustained Ps control, good tolerability, and lower pill burden in a Phase 3 study conducted in dialysis patients with hyperphosphatemia.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">7</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The main drawback of the treatment of hyperphosphatemia is that it must be controlled with drugs that depend tightly on adequate compliance of the patient: adherence to the drug is essential to obtain the expected results.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">8</span></a> PB probably are the group of drugs prescribed in HD with a higher non-adherence rate.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">8,9</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The causes of this low adherence are related to PB pill burden,<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">10</span></a> the complexity of the regimen (they must be taken in association with the intake),<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">11</span></a> their interference with the habits of the patient<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">8</span></a> and the high prevalence of gastrointestinal symptoms.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">12</span></a> Studies in real clinical practice are necessary to understand the influence of patients’ preferences in the acceptance of PB<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">13</span></a> and to design strategies associated with better compliance.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">14</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The development of the new PB must include not only the analysis of its clinical efficacy in achieving the phosphorus objective, but also to deepen in those aspects that may influence adherence in the medium-long term. In this sense, it is important to approach the opinions of patients regarding the new PB, their preferences and their degree of acceptance.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The objective of this study is to evaluate the efficacy of SFOH in hemodialysis patients, as well as adherence and acceptance by the patient and the strategies that favor a good compliance in real clinical practice.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0040" class="elsevierStylePara elsevierViewall">This was a prospective study carry out during 3 months in usual clinical practice at the Hemodialysis unit of Vithas Hospital Perpetuo Internacional, Alicante (Spain).</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study population</span><p id="par0045" class="elsevierStylePara elsevierViewall">All HD patients being currently treated at our unit with PB were included in the study. Eligible patients were between 18 and 90 years of age, and on renal replacement HD therapy (4<span class="elsevierStyleHsp" style=""></span>h/session, 3 days a week, with single pool dialyzer clearance time/volume of water in patient's body (Kt/V)<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>1.4) for at least 6 months before inclusion in the study.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Adherence, Ps levels, pill burden and the percentage of patients with sP levels <5<span class="elsevierStyleHsp" style=""></span>mg/dl were compared between the two groups of treatment (SFOH and control) at baseline and 1, 2 and 3 months. In SFOH group, preferences in the administration mode and side effects were recorded.</p><p id="par0055" class="elsevierStylePara elsevierViewall">All patients participating in the study signed an informed consent.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Study design</span><p id="par0060" class="elsevierStylePara elsevierViewall">57 patients were assigned to SFOH (SFHO group) and 48 patients maintained their baseline treatment (association of low doses of Ca acetate plus Mg carbonate (Osvaren®) (less than 440<span class="elsevierStyleHsp" style=""></span>mg of calcium element) with lanthanum carbonate (Fosrenol®) or carbonate of sevelamer (Renagel® or Renvela®) (control group).</p><p id="par0065" class="elsevierStylePara elsevierViewall">The inclusion criteria for assigning patients to the SFOH group were: sP higher than 5<span class="elsevierStyleHsp" style=""></span>mg/dl (46 patients) or sP lower than 5<span class="elsevierStyleHsp" style=""></span>mg/dl with a high number of pills (3 patients) or poor tolerance to PB and suspected non-adherence to PB (8 patients). Initially, all patients were asked through a one-to-one interview if they agreed to switch to this new alternative treatment. Those patients who did not wish to change maintained the same treatment even if they had sP poorly controlled.</p><p id="par0070" class="elsevierStylePara elsevierViewall">All patients received the instruction to split the tablets and distribute then during intakes, starting with one or two tablets daily.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Sampling for Ps levels was performed immediately before HD session the second day of the week (Wednesday or Thursday).</p><p id="par0080" class="elsevierStylePara elsevierViewall">Self-reported non-adherence to treatment to PB was estimated using the Simplified Medication Adherence Questionnaire (SMAQ), which has been validated in the Spanish population with Acquired Immune Deficiency Syndrome<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">15</span></a> and has shown sufficient internal consistency in HD patients.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">8,13,14</span></a> Patients were considered non-adherent when answering: 1: “Do you always take your medication at the appropriate time?” NO; 2: “When you feel bad, have you ever discontinued taking your medication? YES; 3: “Have you ever forgotten to take your medication?” YES; 4: “Have you ever forgotten to take your medications during the weekend? “YES; 5: “In the LAST WEEK, HOW MANY TIMES did you fail to take your prescribed dose?” C: 3–5 times, D: 6–0 times or E: more than 10 times; 6: “Since your last visit how many whole days have gone by in which you did not take your medication?” more than two days. The questionnaire is dichotomous; any response in the sense of non compliance is considered non adherent. SMAQ was collected baseline and at 2 months after starting the new treatment.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Study variables</span><p id="par0085" class="elsevierStylePara elsevierViewall">Ps levels and the percentage of patients with sP levels <5<span class="elsevierStyleHsp" style=""></span>mg/dl were the primary study variable. Secondary study variables were number of pills of PB, adherence, preferences in the administration mode and side effects.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Additional information included age; gender and HD vintage.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical methods</span><p id="par0095" class="elsevierStylePara elsevierViewall">Data were analyzed using SPSS software, version 17.0. First, we obtained a descriptive analysis of all variables collected. The qualitative variables are described as absolute frequencies and percentages, while quantitative variables were analyzed using the mean, standard deviation (SD), and range (maximum and minimum values). Independent <span class="elsevierStyleItalic">t</span>-tests or chi-square tests were used. ANOVA was performed for repeated measurements, and the Friedman Test was used to evaluate the differences observed in quantitative variables at different study stages. The level of significance was established at <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05.</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Population characteristics</span><p id="par0100" class="elsevierStylePara elsevierViewall">A total of 105 patients were enrolled. Mean (DS) age of patients was 63.39 (13.8), being 63.7% males. Mean (SD) time on HD replacement was 7.13 (7.17) years. Mean time of follow-up 3 (SD 1.4) months. The baseline patient's characteristics in the 2 groups are in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">The percentage of patients with controlled sP (<5<span class="elsevierStyleHsp" style=""></span>mg/dl) increased significantly in the SFOH users’ group (62.1–92.9%, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001), but not in the control group (83–83.3%, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>NS) at 3 months (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The average of daily tablets decreased significantly in the SFOH group (7.2–2.3 comp, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001), but not in the control group (5.6 to 5.6, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>NS) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>) and 100% of the patients used only one PB in SFOH group. The use of SFOH increased the adherence according to the SMAQ questionnaire (57.8% to 84.3%; OR 13.1, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001) at 3 months. Adherence in the control group did not change (81–82.3%; <span class="elsevierStyleItalic">p</span>: NS) Patients were informed about the various modes of administration (swallow/chew), and adapting it to the preferences of the patient (split-swallowing 89% compared to chewing 11%) improved the acceptance (44.7–78%) (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). No changes in efficacy between the two modes of administration was observed. Eight of the patients (14.0%) experienced side effects: 4 diarrhea, 1 constipation and 3 thirst. 3 patients (5.2%) discontinued SFOH because they did not like the medication even after changing the way of administration, and 4 patients (7%) SFOH were discontinued as a consequence of gastrointestinal adverse events</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0110" class="elsevierStylePara elsevierViewall">The main findings of this study are that the introduction of a new PB (SFOH) achieves an improvement in the control of phosphorus (it goes from 62% to 93% of controlled patients) with a lower number of tablets per day (of 7.2–2.3 tablets daily), while the group that was kept receiving basal treatment did not show significant differences in the control of phosphorus or in the number of daily tablets during the observation period. These results are consistent with those previously seen in controlled clinical trials<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">7</span></a> and in other real-world studies<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">16</span></a> in which SFOH was able to control a greater number of patients with a lower number of tablets.</p><p id="par0115" class="elsevierStylePara elsevierViewall">It is important to highlight the fact that, in our study, patients in the group that changed to SFOH were worse controlled and less adherent to the PB than those in the control group and the results might affected by a selection bias. In spite of this, a greater percentage of these patients had their Ps controlled at the end of the observation period, what still shows a more striking result, being the group worse controlled at baseline. Even patients who had the worst controlled phosphorus get better results (92.9%) than patients who did not change treatment (83%).</p><p id="par0120" class="elsevierStylePara elsevierViewall">Lack of adherence to PB is probably the most important factor for not achieving the objectives of P recommended in clinical guidelines, and it is estimated that it affects up to 50% of hemodialysis patients treated.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">8–12</span></a> In this study, the non-adherence rate measured by the SMAQ questionnaire decreased significantly after the introduction of SFOH. It is important to use tools to measure therapeutic adherence. Some studies show that the assessment of adherence directly and subjectively underestimates the non-adherence of patients.<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">17,18</span></a> This does not allow identifying many non-adherent patients, which means that the opportunity to intervene on them is lost and therapeutic decisions can be adopted with a high degree of empiricism that lead us to unnecessarily increase the doses of the drugs.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Several studies have shown an association between larger number of tablets and non-adherence.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">10,12</span></a> SFOH has been shown to be able to control sP with a lower number of tablets per day (less than 1 tablet per meal, average 2.3 tablets/day) in patients who previously were taking an average of 7.2 tablets per day (more than 2 tablets per intake). This lower need for tablets may influence the better adherence observed in our study when switching to SFOH, but also can mean better compliance with less need for pills.</p><p id="par0130" class="elsevierStylePara elsevierViewall">The effectiveness of a PB relies not only on its ability to bind Ps but also on its ability to be accepted by the patient who makes the final decision to take it or not. Patient's preferences and adherence to the prescribed PB are, at least, as important as their effectiveness. In clinical practice, the least effective PB is the one that the patient does not want to take: “Drugs do not work in patients who do not take them.”<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">19</span></a> SFOH was well accepted initially, but when we explore the degree of acceptance of “chew” instruction as a mode of intake, more than half of the patients admitted that they did not like it. However, when they were offered another possibility of administration, Split-swallow, the percentage of acceptance increased from 44% to 78%, and 89% of patients chose this option as the mode of administration. Good short-term results in the control of phosphorus and adherence are not enough, as they may be motivated by the novelty of the new PB itself, but it is important to know the degree of acceptance of the prescribed PB to ensure long-term compliance. This will allow us to adapt to difficulties and anticipate the possibility of future non-adherence. Physicians may be able to improve adherence by selecting a PB or the mode of intake according to patient's preferences.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">13</span></a> Assessing patient beliefs and preferences about medications (form, size, unpalatable taste, number of tablets) is a reliable way of finding out intentional non-adherence to treatment with PB and may help to identify ways in which adherence rates can be improved.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">13</span></a> In a previous study, the percentage of patients prescribed PB that they did not like was 54.5%, and those patients had a greater risk of not meeting the goal of sP <5.5<span class="elsevierStyleHsp" style=""></span>mg/dl.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">8</span></a> The change in the mode of administration (chew/Split-swallow) according to the preference of the patient could help us to maintain the treatment and control of phosphorus in the long term. In this study, 3 patients (5.2%) discontinued SFOH because they did not like the medication even after changing the way of administration. Individualization of treatment could be rewarded with increased medication adherence and, potentially, improved outcomes.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Intolerance to drugs and their side-effects are frequent causes of non-adherence.<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">20,21</span></a> 14% of the patients treated with SFOH experienced side effects (none serious): diarrhea, constipation and thirst and in 7% SFOH was discontinued for this reason. Intentional non-adherence to therapy may be modified with a closer consideration of the side effects of any particular binder. In a previous study, initial changes of PB, considering patient's preferences, were due to immediate intolerance to the new PB, while long-term changes were caused by fatigue and boredom with the PB they were taking.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">13</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">In our experience, starting with a slow and progressive increase of the dose of SFOH minimizes initial side effects. As we have seen in this study, most of the patients are controlled with less than 1 tablet per intake. The instruction to split the tablets and distribute then during intakes, starting with one or two tablets daily, favors a lower occurrence of side effects, and, therefore, reduces the abandonment of SFOH by the patient.</p><p id="par0145" class="elsevierStylePara elsevierViewall">The type of relationship/communication established between doctor and patient is essential in intentional non-adherent patients and influences the improvement of self-motivation.<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">22,23</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">In conclusion, SFOH is a potent BP that controlled sP in monotherapy in 93% of our patients short term. It improves adherence and has good acceptance due to its tolerability, the lower number of tablets it requires and its intake flexibility that allows it to be adapted to the patient's preferences.</p><p id="par0155" class="elsevierStylePara elsevierViewall">Combination between good tools (well tolerated PB, well accepted, flexible in the taking, etc.) together with a close doctor and patient relationship with respect to the patient's preferences and opinions manages to improve the results in the control of sP.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflict of interests</span><p id="par0160" class="elsevierStylePara elsevierViewall">Dra Arenas and Navarro F have given conferences sponsored by Abbott (Abbvie), Amgen, Genzyme, Shire and Vifor Fresenius. They had also participated in national advisory committees of Abbott (Abbvie), Amgen and Vifor Fresenius.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1440711" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1314982" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1440710" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1314981" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study population" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Study design" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Study variables" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical methods" ] ] ] 6 => array:3 [ "identificador" => "sec0035" "titulo" => "Results" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Population characteristics" ] ] ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflict of interests" ] 9 => array:2 [ "identificador" => "xack502885" "titulo" => "Acknowledgements" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-10-19" "fechaAceptado" => "2020-04-03" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1314982" "palabras" => array:4 [ 0 => "Adherence" 1 => "Phosphate binders" 2 => "Patient–physician relationship" 3 => "Patient preferences" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1314981" "palabras" => array:4 [ 0 => "Adherencia" 1 => "Aglutinantes de fosfato" 2 => "Relación médico-paciente" 3 => "Preferencias del paciente" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The lack of adherence to phosphate -binders (PB) is the most important factor in not achieving the objectives of serum phosphorus (sP). Studies in the real-world population are needed to understand the influence of PBs on adherence and how to modify it.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Prospective study conducted during 3 months in usual clinical practice. Out of 105 hemodialysis patients, 57 were switched to SFOH and 48 maintained their baseline treatment (control group). sP levels and the percentage of patients with sP levels <5<span class="elsevierStyleHsp" style=""></span>mg/dl were compared. Adherence before and after introduction of SFOH, number of pills of PB, preferences in the administration mode and side effects were analyzed.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The percentage of patients with controlled sP (<5<span class="elsevierStyleHsp" style=""></span>mg/dl) increased significantly in the SFOH users’ group (62.1–92.9%, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001), but not in the control group (83–83.3%, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>NS). The average of daily tablets decreased significantly in the SFOH group (7.2–2.3 comp, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001), but not in the control group (5.6–5.6, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>NS) and 100% of the patients used only one PB in SFOH group. The use of SFOH increased the adherence according to the SMAQ questionnaire (57.8–84.3%; OR 13.1, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001). The possibility to choose the preferred mode of administration (split-swallowing 89% compared to chewing 11%), improved the acceptance (44.7–78%). 14% of the patients experienced side effects and in 5.2% SFOH was discontinued for this reason.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">SFOH controlled serum sP in 93% of patients, 100% in monotherapy, and with fewer tablets. The exploration and adaptation of preferences in the mode of administration influenced the acceptance of the drug by the patient and, probably, the future adherence.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La falta de adherencia a los captores del fósforo es el factor más importante para no lograr los objetivos del fósforo sérico (Ps). Se necesitan estudios en la población del mundo real para comprender la influencia de los CP sobre la adherencia y como modificarla.</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Objetivos Evaluar la eficacia y la adherencia de un nuevo CP, oxihidróxido sucroférrico (OHSF) en pacientes en hemodiálisis y la influencia de un cambio en el modo de administración del fármaco sobre la aceptación del mismo.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo realizado durante 3 meses en práctica clínica habitual. De 105 pacientes de hemodiálisis, 57 pacientes con P mal controlado (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>mg/dl) fueron cambiados a OHSF y 48 mantuvieron su tratamiento inicial (grupo control). Se compararon los niveles de Ps y el porcentaje de pacientes con niveles de Ps<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>mg/dl. Se analizó la adherencia antes y después de la introducción de OHSF, el número de comprimidos de captores del P, los efectos secundarios y el grado de aceptación del fármaco tras ofrecer varias alternativas en el modo de administración.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El porcentaje de pacientes con P controlado (<5<span class="elsevierStyleHsp" style=""></span>mg/dl) aumentó significativamente a los 3 meses de seguimiento en el grupo de pacientes con OHSF (62,1 al 92,9%; p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,001), pero no en el grupo de control (83 al 83,3%; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>NS). El promedio de comprimidos diarios disminuyó significativamente en el grupo OHSF (7,2 a 2,3 comprimidos; p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,001), pero no en el grupo control (5,6 a 5,6; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>NS) y todos los pacientes en tratamiento con OHSF se controlaron con monoterapia. El uso de OHSF aumentó la adherencia según el cuestionario SMAQ (57,8 al 84,3%; OR: 13,1; p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,001). La posibilidad de elegir el modo de administración preferido (cortar-tragar 89% en comparación con masticar 11%) mejoró la aceptación (44,7 al 78%) de los pacientes. El 14% de los pacientes experimentaron efectos secundarios y en 5,2% se suspendió el OHSF por esta razón.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">OHSF controló el P sérico en el 93% de los pacientes, siendo la totalidad de ellos en monoterapia, y con menor número de comprimidos a corto plazo. La exploración y adaptación de las preferencias en el modo de administración influyó en la aceptación del fármaco por parte del paciente y, probablemente en la adherencia futura.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "d" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">(Previous).</p>" "identificador" => "fn0005" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1735 "Ancho" => 2500 "Tamanyo" => 163158 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Comparison between SUCROFERRIC OXYHYDROXIDE (SFOH) group and control group (phosphate serum levels).</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1646 "Ancho" => 2503 "Tamanyo" => 109208 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Comparison between SUCROFERRIC OXYHYDROXIDE SFOH group and control group (tablets/day).</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1397 "Ancho" => 2294 "Tamanyo" => 129971 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Patient's acceptance before and after the change in the mode of administration adapting it to the patient's preferences.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">SFOH group (<span class="elsevierStyleItalic">N</span>: 57) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control group (<span class="elsevierStyleItalic">N</span>:48) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age, mean years (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">65.8 (13.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72.6 (12.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35.3% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33.5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dialysis vintage, mean years (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (9.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Primary cause of ESRD, diabetes mellitus % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23.7% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Baseline P (mg/dL), mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.0 (1.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.3 (1.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Baseline albumin cCa (mg/dL), mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.9 (0.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.7 (0.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Baseline PTH (pg/mL), mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">423.0 (325.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">334.5 (432.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2478257.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Baseline patient characteristics.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:23 [ 0 => array:3 [ "identificador" => "bib0120" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The phosphate binder equivalent dose" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.T. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 3 | 7 |
| 2024 October | 57 | 45 | 102 |
| 2024 September | 58 | 32 | 90 |
| 2024 August | 76 | 63 | 139 |
| 2024 July | 39 | 25 | 64 |
| 2024 June | 46 | 40 | 86 |
| 2024 May | 61 | 36 | 97 |
| 2024 April | 53 | 35 | 88 |
| 2024 March | 55 | 31 | 86 |
| 2024 February | 48 | 39 | 87 |
| 2024 January | 52 | 26 | 78 |
| 2023 December | 26 | 20 | 46 |
| 2023 November | 46 | 50 | 96 |
| 2023 October | 41 | 39 | 80 |
| 2023 September | 29 | 31 | 60 |
| 2023 August | 39 | 27 | 66 |
| 2023 July | 42 | 26 | 68 |
| 2023 June | 30 | 25 | 55 |
| 2023 May | 43 | 33 | 76 |
| 2023 April | 34 | 17 | 51 |
| 2023 March | 65 | 24 | 89 |
| 2023 February | 46 | 19 | 65 |
| 2023 January | 24 | 35 | 59 |
| 2022 December | 61 | 33 | 94 |
| 2022 November | 45 | 38 | 83 |
| 2022 October | 63 | 55 | 118 |
| 2022 September | 57 | 44 | 101 |
| 2022 August | 41 | 38 | 79 |
| 2022 July | 35 | 51 | 86 |
| 2022 June | 27 | 52 | 79 |
| 2022 May | 42 | 32 | 74 |
| 2022 April | 28 | 46 | 74 |
| 2022 March | 36 | 63 | 99 |
| 2022 February | 35 | 42 | 77 |
| 2022 January | 33 | 45 | 78 |
| 2021 December | 25 | 43 | 68 |
| 2021 November | 43 | 43 | 86 |
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| 2021 September | 58 | 39 | 97 |
| 2021 August | 50 | 35 | 85 |
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| 2021 June | 52 | 21 | 73 |
| 2021 May | 69 | 47 | 116 |
| 2021 April | 121 | 64 | 185 |
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| 2021 February | 63 | 39 | 102 |
| 2021 January | 42 | 21 | 63 |
| 2020 December | 10 | 4 | 14 |
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