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      Mensuração da não-adesão aos medicamentos imunossupressores em receptores de transplante de fígado Translated title: Medición de la no adhesión a los medicamentos inmunosupresores en receptores de trasplante de hígado Translated title: Measurement of non-adherence to immunosuppressive medication in liver transplantation recipients

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          Abstract

          Resumo Objetivo Avaliar os níveis de não-adesão à terapia imunossupressora em uma amostra de receptores de transplante de fígado utilizando a Basel Assessment of Adherence with Immunosuppressive Medication Scale; correlacionar as características sociodemográficas e os fatores clínicos à não-adesão medicamentosa. Métodos Estudo epidemiológico e transversal, realizado entre março 2016 e março 2018 no ambulatório de transplante de fígado da Universidade Federal de São Paulo. Resultados Foram avaliados 49 pacientes. O nível de não-adesão medicamentosa no transplante de fígado foi de 49% e esteve diretamente relacionado ao uso do ácido micofenólico (p=0,007) e à administração de múltiplas doses de imunossupressores diariamente (p=0,004). Não foram encontradas correlações estatisticamente significativas entre a não-adesão à terapia imunossupressora e as características sociodemográficas e demais variáveis clínicas analisadas. Conclusão Este estudo mostrou que quase a metade dos pacientes deixaram de aderir à terapia imunossupressora no pós transplante de fígado. Uma vez que os desfechos desfavoráveis no transplante estão intimamente relacionados à falhas na adesão, é importante os enfermeiros avaliarem esse comportamento durante o seguimento ambulatorial dos receptores de transplante de fígado.

          Translated abstract

          Resumen Objetivo Analizar los niveles de no adhesión a la terapia inmunosupresora en una muestra de receptores de trasplante de hígado utilizando la Basel Assessment of Adherence with Immunosuppressive Medication Scale y correlacionar las características sociodemográficas y los factores clínicos con la no adhesión a los medicamentos. Métodos Estudio epidemiológico y transversal realizado entre marzo de 2016 y marzo de 2018 en los consultorios externos de trasplante de hígado de la Universidad Federal de São Paulo. Resultados Fueron analizados 49 pacientes. El nivel de no adhesión a los medicamentos del trasplante de hígado fue de 49% y está directamente relacionado con el uso de ácido micofenólico (p=0,007) y con la administración de varias dosis inmunosupresoras diariamente (p=0,004). No se encontró correlación estadísticamente significativa entre la no adhesión a la terapia inmunosupresora y las características sociodemográficas y demás variables clínicas analizadas. Conclusión Este estudio mostró que casi la mitad de los pacientes dejó de realizar la terapia inmunosupresora en el postrasplante de hígado. Dado que los desenlaces desfavorables del trasplante están íntimamente relacionados con fallas en la adhesión, es importante que los enfermeros evalúen ese comportamiento durante el seguimiento ambulatorio de los receptores de trasplante de hígado.

          Translated abstract

          Abstract Objective Assessing the level of non-adherence to immunosuppressive therapy in a sample of liver transplantation recipients using the Basel Assessment of Adherence with Immunosuppressive Medication Scale; correlating socio-demographic features and clinical factors to medication non-adherence. Methods This cross-sectional epidemiological study was conducted between March 2016 and March 2018 at the outpatient service for liver transplantations of the Federal University of São Paulo. Results Forty-nine patients were assessed. The level of medication non-adherence after liver transplantation was 49%. It was directly correlated to the use of mycophenolic acid (p=0.007) and to multiple daily dosing of immunosuppressant medication (p=0.004). No statistically significant correlations were found between non-adherence to immunosuppressive therapy, socio-demographic features, and the remaining clinical variables assessed. Conclusion This study shows that nearly half of all patients are not compliant with immunosuppressive therapy after liver transplantation. Given poor liver transplantation outcomes are intimately related to adherence failure, nurses need to assess this behavior in outpatient follow-up of liver transplantation recipients.

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          Most cited references30

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          Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation

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            Transplant outcomes and economic costs associated with patient noncompliance to immunosuppression.

            We describe factors associated with immunosuppression compliance after kidney transplantation and examine relationships between compliance with allograft outcomes and costs. Medicare claims for immunosuppression in 15 525 renal transplant recipients with at least 1 year of graft function were used to calculate compliance as medication possession ratio. Compliance was categorized by quartiles as poor, fair, good and excellent. We modeled adjusted associations of clinical factors with the likelihood of persistent compliance by multiple logistic regressions (aOR), and estimated associations of compliance with subsequent graft and patient survival with Cox proportional hazards (aHR). Adolescent recipients aged 19-24 years were more likely to be persistently noncompliant compared to patients aged 24-44 years (aOR 1.49 [1.06-2.10]). Poor (aHR 1.80 [1.52-2.13]) and fair (aHR 1.63[1.37-1.93]) compliant recipients were associated with increased risks of allograft loss compared to the excellent compliant recipients. Persistent low compliance was associated with a $12 840 increase in individual 3-year medical costs. Immunosuppression medication possession ratios indicative of less than the highest quartile of compliance predicted increased risk of graft loss and elevated costs. These findings suggest that interventions to improve medication compliance among kidney transplant recipients should emphasize the benefits of maximal compliance, rather than discourage low compliance.
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              Pharmacology and toxicology of mycophenolate in organ transplant recipients: an update.

              This review aims to provide an update of the literature on the pharmacology and toxicology of mycophenolate in solid organ transplant recipients. Mycophenolate is now the antimetabolite of choice in immunosuppressant regimens in transplant recipients. The active drug moiety mycophenolic acid (MPA) is available as an ester pro-drug and an enteric-coated sodium salt. MPA is a competitive, selective and reversible inhibitor of inosine-5'-monophosphate dehydrogenase (IMPDH), an important rate-limiting enzyme in purine synthesis. MPA suppresses T and B lymphocyte proliferation; it also decreases expression of glycoproteins and adhesion molecules responsible for recruiting monocytes and lymphocytes to sites of inflammation and graft rejection; and may destroy activated lymphocytes by induction of a necrotic signal. Improved long-term allograft survival has been demonstrated for MPA and may be due to inhibition of monocyte chemoattractant protein 1 or fibroblast proliferation. Recent research also suggested a differential effect of mycophenolate on the regulatory T cell/helper T cell balance which could potentially encourage immune tolerance. Lower exposure to calcineurin inhibitors (renal sparing) appears to be possible with concomitant use of MPA in renal transplant recipients without undue risk of rejection. MPA displays large between- and within-subject pharmacokinetic variability. At least three studies have now reported that MPA exhibits nonlinear pharmacokinetics, with bioavailability decreasing significantly with increasing doses, perhaps due to saturable absorption processes or saturable enterohepatic recirculation. The role of therapeutic drug monitoring (TDM) is still controversial and the ability of routine MPA TDM to improve long-term graft survival and patient outcomes is largely unknown. MPA monitoring may be more important in high-immunological recipients, those on calcineurin-inhibitor-sparing regimens and in whom unexpected rejection or infections have occurred. The majority of pharmacodynamic data on MPA has been obtained in patients receiving MMF therapy in the first year after kidney transplantation. Low MPA area under the concentration time from 0 to 12 h post-dose (AUC0-12) is associated with increased incidence of biopsy-proven acute rejection although AUC0-12 optimal cut-off values vary across study populations. IMPDH monitoring to identify individuals at increased risk of rejection shows some promise but is still in the experimental stage. A relationship between MPA exposure and adverse events was identified in some but not all studies. Genetic variants within genes involved in MPA metabolism (UGT1A9, UGT1A8, UGT2B7), cellular transportation (SLCOB1, SLCO1B3, ABCC2) and targets (IMPDH) have been reported to effect MPA pharmacokinetics and/or response in some studies; however, larger studies across different ethnic groups that take into account genetic linkage and drug interactions that can alter a patient's phenotype are needed before any clinical recommendations based on patient genotype can be formulated. There is little data on the pharmacology and toxicology of MPA in older and paediatric transplant recipients.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                ape
                Acta Paulista de Enfermagem
                Acta paul. enferm.
                Escola Paulista de Enfermagem, Universidade Federal de São Paulo (São Paulo, SP, Brazil )
                0103-2100
                1982-0194
                June 2019
                : 32
                : 3
                : 319-326
                Affiliations
                [1] São Paulo orgnameUniversidade Federal de São Paulo orgdiv1Escola Paulista de Enfermagem Brazil
                Article
                S0103-21002019000300319
                10.1590/1982-0194201900044
                7578dc05-d2ca-4f8a-a20d-69352ddff19d

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 11 February 2019
                : 08 April 2019
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 37, Pages: 8
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                SciELO Brazil

                Categories
                Artigos Originais

                Nursing care,Cuidados de enfermagem,Assistência integral à saúde,Transplante de fígado,Adesão à medicação,Cooperação e adesão ao tratamento,Comprehensive health care,Liver transplantation,Medication adherence,Treatment adherence and compliance,Atención de Enfermería,Atención integral de salud,Trasplante de hígado,Cumplimiento de la medicación,Cumplimiento y adherencia al tratamento

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