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Oudbier SJ, Aarts JW, Kloes van der JM, Kuijvenhoven MA, Janssen SL, Hilhorst M, Nurmohamed SA, Smets EMA, Teeuwisse PJI, Dusseljee-Peute LW. Patient-reported usability challenges when implementing integrated EHR medication reminders for kidney transplant patients in a home setting: A pilot study. Int J Med Inform 2025; 201:105949. [PMID: 40318499 DOI: 10.1016/j.ijmedinf.2025.105949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 04/18/2025] [Accepted: 04/23/2025] [Indexed: 05/07/2025]
Abstract
BACKGROUND With an aging population and the increasing prevalence of chronic diseases such as chronic kidney disease (CKD), kidney transplantation is the preferred treatment for end-stage renal disease due to its superior clinical outcomes and cost-effectiveness compared to dialysis. Although EHR-integrated medication reminders have the potential to enhance adherence in transplant patients, their feasibility require further investigation. OBJECTIVE The objective of this pilot study was to assess the feasibility of an integrated medication reminder tool for kidney transplant patients in terms of experienced usability and satisfaction. METHODS A single-arm survey design was used to assess the usability and satisfaction in kidney transplant recipients using an EHR-integrated medication reminder tool through the patient portal at a large academic hospital in the Netherlands. Usability and satisfaction were evaluated using the validated Experienced Usability and Satisfaction with self-monitoring in the home Setting (GEMS) questionnaire comprising four subconstructs: Convenience of use, Perceived value, Efficiency of use, and Satisfaction. Quantitative data were analysed and assessed through descriptive statistics. Furthermore, six additional questions assessed logging into the system, ease of follow-up on reminder, satisfaction with reminder timing, perceived support for adherence, occurrence of incorrect reminders, and willingness to continue using the tool, using Likert scales and open-ended responses. RESULTS In total, forty-three patients participated in this study. The results showed mixed experienced usability and satisfaction, with a GEMS score of 65.0%. The Efficiency of use subconstruct revealed issues such as difficulties in checking off medication and accessing the patient portal. The Satisfaction subconstruct revealed limitations of the tool, as reminders cannot be customized, creating inconvenience for patients who had developed their own medication routines after transplantation. One third (35.7%) of the patients reported willingness to continue using the tool after the pilot program. CONCLUSION The experienced usability and satisfaction of an integrated EHR medication reminder tool were adequate for half of the patients. To facilitate large-scale implementation, improvements of the tool are needed to maximize its effectiveness for kidney transplant patients, particularly by enhancing customization of the notification system to better meet user needs and support medication adherence.
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Affiliation(s)
- S J Oudbier
- Amsterdam UMC Location University of Amsterdam, Outpatient Division, Amsterdam, the Netherlands; Amsterdam UMC Location University of Amsterdam, Medical Psychology, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands; Amsterdam Public Health Research Institute, Digital Health, Amsterdam, the Netherlands; Amsterdam Public Health Research Institute, Quality of Care, Amsterdam, the Netherlands.
| | - J W Aarts
- Amsterdam UMC, Department of Clinical Pharmacology and Pharmacy, Amsterdam, the Netherlands
| | - J M Kloes van der
- Amsterdam UMC, Department of Clinical Pharmacology and Pharmacy, Amsterdam, the Netherlands
| | - M A Kuijvenhoven
- Amsterdam UMC, Department of Clinical Pharmacology and Pharmacy, Amsterdam, the Netherlands
| | - S L Janssen
- EvA Servicecentrum, Amsterdam UMC, Amsterdam, the Netherlands
| | - M Hilhorst
- Amsterdam UMC, Department of Nephrology, Amsterdam, the Netherlands
| | - S A Nurmohamed
- Amsterdam UMC, Department of Nephrology, Amsterdam, the Netherlands
| | - E M A Smets
- Amsterdam UMC Location University of Amsterdam, Medical Psychology, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands; Amsterdam Public Health Research Institute, Quality of Care, Amsterdam, the Netherlands
| | - P J I Teeuwisse
- Amsterdam UMC, Department of Clinical Pharmacology and Pharmacy, Amsterdam, the Netherlands
| | - L W Dusseljee-Peute
- Amsterdam UMC, Location University of Amsterdam, Department of Medical Informatics, Amsterdam, the Netherlands
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Maksyutynska K, Batoy B, Wei X, Shafei O, Li Y, Famure O, Kim SJ. Assessing Risk Factors and Posttransplant Outcomes of Nonadherence Among Kidney Transplant Recipients. Transplant Direct 2025; 11:e1799. [PMID: 40371057 PMCID: PMC12073937 DOI: 10.1097/txd.0000000000001799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 02/13/2025] [Accepted: 03/07/2025] [Indexed: 05/16/2025] Open
Abstract
Background Adherence of kidney transplant recipients (KTRs) to prescribed regimens is vital for long-term graft function. This study aimed to identify adherence rates using objective and composite measures, risk factors for nonadherence, and the latter's impact on posttransplant outcomes. Methods A retrospective single-center cohort study was conducted among KTR transplanted from January 1, 2003, to December 31, 2017. Overall nonadherence was defined as 1 or more of the following in the first-year posttransplant: (1) at least 1 missed clinic visit, (2) >30% missed laboratory visits, and (3) >40% coefficient of variation of calcineurin inhibitor levels. Logistic and Cox proportional hazards models were fitted to identify adherence risk factors and outcomes, respectively. Results Among the included 1803 KTR, overall nonadherence was identified in 34.9%; 11.2% were nonadherent to clinic visits, 5.4% to laboratory tests, and 25.2% to medications. Recipient history of psychiatric disorders (odds artio [OR], 1.57; 95% confidence interval [CI], 1.22-2.02) or pretransplant nonadherence (OR, 1.82; 95% CI, 1.31-2.54), and private drug coverage (OR, 0.62; 95% CI, 0.48-0.80) were associated with posttransplant nonadherence. Any episode of nonadherence over the first year after transplant was associated with an increased risk of total graft failure (hazard ratio [HR], 1.52; 95% CI, 1.20-1.91), death with graft function (HR, 1.51; 95% CI, 1.11-2.05), and biopsy-proven acute rejection (HR, 2.35; 95% CI, 1.38-3.99). Conclusions Adherence among KTR is influenced by both psychosocial and socioeconomic determinants which impact posttransplant outcomes. Our results emphasize feasible methods to monitor adherence and identify high-risk KTR.
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Affiliation(s)
- Kateryna Maksyutynska
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - Benedict Batoy
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - Xinyu Wei
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - Oswa Shafei
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - Yanhong Li
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - Olusegun Famure
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - S. Joseph Kim
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, ON, Canada
- Division of Nephrology, Department of Medicine, University of Toronto, Toronto, ON, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada
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Hansen CM, Bachmann S, Su M, Budde K, Choi M. Calcineurin Inhibitor Associated Nephrotoxicity in Kidney Transplantation-A Transplant Nephrologist's Perspective. Acta Physiol (Oxf) 2025; 241:e70047. [PMID: 40243357 PMCID: PMC12005075 DOI: 10.1111/apha.70047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 03/29/2025] [Accepted: 03/29/2025] [Indexed: 04/18/2025]
Abstract
AIM Calcineurin inhibitors (CNIs) have revolutionized transplant medicine, improving allograft survival but posing challenges like calcineurin inhibitor-induced nephrotoxicity (CNT). Acute CNT, often dose-dependent, leads to vasoconstriction and acute kidney injury, with treatment focusing on CNI exposure reduction. Chronic CNT manifests as progressive allograft function decline, with challenges in distinguishing it from nonspecific allograft nephropathy. METHODS This narrative review provides a concise overview of the clinical management of CNT, covering acute and chronic CNT. We reviewed original articles, landmark papers, and meta-analyses on CNT mitigation strategies, including CNI-sparing approaches. RESULTS Preventive measures include co-medications, CNI exposure monitoring, and CNI sparing strategies, such as reducing target trough levels and converting to mTOR inhibitors (mTORi) or belatacept. Despite improvements in graft function, challenges persist in demonstrating significant differences in allograft survival with CNI-sparing regimens. The paradigm shift from chronic CNT as the main cause of chronic allograft nephropathy toward rather immunologic triggered injuries and/or comorbidities as relevant contributors to allograft deterioration over time must be kept in mind. CONCLUSION CNIs have significantly improved kidney transplant outcomes, but their associated nephrotoxicity necessitates mitigation strategies. The decision to implement such regimens is always an individual choice balancing against the risk of immunologic injuries. Further long-term studies are needed to optimize immunosuppressive approaches and refine CNT management.
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Affiliation(s)
- Carla M. Hansen
- Department of Nephrology and Medical Intensive CareCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität Zu BerlinBerlinGermany
| | - Sebastian Bachmann
- Department of Nephrology and Medical Intensive CareCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität Zu BerlinBerlinGermany
| | - Mingzhen Su
- Department of Nephrology and Medical Intensive CareCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität Zu BerlinBerlinGermany
| | - Klemens Budde
- Department of Nephrology and Medical Intensive CareCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität Zu BerlinBerlinGermany
| | - Mira Choi
- Department of Nephrology and Medical Intensive CareCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität Zu BerlinBerlinGermany
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Bul KCM, Bannon C, Krishnan N, Dunlop A, Szczepura A. Can eHealth applications improve renal transplant outcomes for adolescents and young adults? A systematic review. Transplant Rev (Orlando) 2023; 37:100760. [PMID: 37172527 DOI: 10.1016/j.trre.2023.100760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 03/20/2023] [Accepted: 04/01/2023] [Indexed: 05/15/2023]
Abstract
BACKGROUND AND OBJECTIVES Adherence to medical treatment following a kidney transplant is particularly challenging during adolescence and young adulthood. There is increasing evidence of the benefits of the use of computer and mobile technology (labelled as eHealth hereafter) including serious gaming and gamification in many clinical areas. We aimed to conduct a systematic review of such interventions designed to improve self-management skills, treatment adherence and clinical outcomes in young kidney transplant recipients aged 16 to 30 years. METHOD The Cochrane Library, MEDLINE, EMBASE, PsychINFO, SCOPUS and CINAHL databases were searched for studies published between 01 January 1990 and 20 October 2020. Articles were short-listed by two independent reviewers based on pre-defined inclusion/exclusion criteria. Reference lists were screened and authors of published conference abstracts contacted. Two reviewers independently appraised selected articles, systematically extracted data and assessed the quality of individual studies (CASP and SORT). Thematic analysis was used for evidence synthesis; quantitative meta-analysis was not possible. RESULTS A total of 1098 unique records were identified. Short-listing identified four eligible studies, all randomized controlled trials (n = 266 participants). Trials mainly focused on mHealth applications or electronic pill dispensers (mostly for patients >18 years old). Most studies reported on clinical outcome measures. All showed improved adherence but there were no differences in the number of rejections. Study quality was low for all four studies. CONCLUSIONS The findings of this review suggest that eHealth interventions can improve treatment adherence and clinical outcomes for young kidney transplant patients. More robust and high-quality studies are now needed to validate these findings. Future studies should also extend beyond short-term outcomes, and consider cost of implementation. The review was registered with PROSPERO (CRD42017062469).
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Affiliation(s)
- Kim C M Bul
- Coventry University, Institute for Health and Wellbeing, Centre for Intelligent Healthcare, West Midlands, Coventry, United Kingdom.
| | - Christopher Bannon
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Nithya Krishnan
- University Hospital Coventry and Warwickshire NHS Trust, Renal, West Midlands, Coventry, United Kingdom
| | - Amber Dunlop
- University Hospital Coventry and Warwickshire NHS Trust, Library & Knowledge Services, West Midlands, Coventry, United Kingdom
| | - Ala Szczepura
- Coventry University, Institute for Health and Wellbeing, Centre for Healthcare and Communities, West Midlands, Coventry, United Kingdom
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Mella A, Torazza MC, Finocchietti D, Fop F, Allesina A, Dolla C, Giraudi R, Biancone L. Non-adherence assessment to immunosuppressant therapy with a self-report questionnaire and intra-patient variability in renal transplantation: risk factors and clinical correlations. Minerva Urol Nephrol 2023; 75:92-98. [PMID: 33781021 DOI: 10.23736/s2724-6051.21.04244-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Non-adherence (NA) to immunosuppressive drugs is to date considered a crucial issue in kidney transplanted patients (KTRs), leading to de-novo donor-specific anti-HLA antibodies (dnDSA) development, acute and chronic rejection, and at least graft loss. However, NA assessment is challenging, often leading to underestimation in real-life settings. METHODS NA evaluation in all KTRs referred to our post-transplantation clinic in the period between 01/01-15/07/2018 with self-report questionnaire combined to intra-patient variability (IPV) of the pivotal immunosuppressive drug (based on trough levels of tacrolimus/mTOR inhibitor). RESULTS Based on both questionnaire and IPV, 86 out of the 504 tested KTRs (17%) were classified as NA. Male gender (OR, 2.0; 95% confidence interval [CI], 1.2 to 3.4), high educational level (OR for KTRs with a degree, 1.8 [95% CI, 1.0 to 3.1]), employment (OR, 2.0 [95% CI, 1.2 to 3.3]), young age at transplantation (P=0.017), longer time on the waiting list and after transplantation (P=0.027 and 0.049 respectively) were all associated with NA. High IPV was mostly documented in KTRs treated with the twice-daily formulation of the immunosuppressive drug (OR, 1.5 [95% CI, 1.0 to 2.1]) and better associated with dnDSA appearance (OR, 2.1 [95% CI, 1.1 to 3.9]). CONCLUSIONS NA is a significant problem, difficult to assess, and can lead to dnDSA development also in our population. Identifying risk factors for NA might be an underestimated tool to improve graft and patient outcome in KTRs.
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Affiliation(s)
- Alberto Mella
- Division of Nephrology Dialysis and Transplantation, Department of Medical Sciences, "A. Vercellone" Renal Transplantation Center, Città della Salute e della Scienza, Turin, Italy
| | - Maria C Torazza
- Division of Nephrology Dialysis and Transplantation, Department of Medical Sciences, "A. Vercellone" Renal Transplantation Center, Città della Salute e della Scienza, Turin, Italy
| | - Daniela Finocchietti
- Division of Nephrology Dialysis and Transplantation, Department of Medical Sciences, "A. Vercellone" Renal Transplantation Center, Città della Salute e della Scienza, Turin, Italy.,Department of Nephrology and Dialysis, Maggiore Hospital, Chieri, Turin, Italy
| | - Fabrizio Fop
- Division of Nephrology Dialysis and Transplantation, Department of Medical Sciences, "A. Vercellone" Renal Transplantation Center, Città della Salute e della Scienza, Turin, Italy
| | - Anna Allesina
- Division of Nephrology Dialysis and Transplantation, Department of Medical Sciences, "A. Vercellone" Renal Transplantation Center, Città della Salute e della Scienza, Turin, Italy
| | - Caterina Dolla
- Division of Nephrology Dialysis and Transplantation, Department of Medical Sciences, "A. Vercellone" Renal Transplantation Center, Città della Salute e della Scienza, Turin, Italy
| | - Roberta Giraudi
- Division of Nephrology Dialysis and Transplantation, Department of Medical Sciences, "A. Vercellone" Renal Transplantation Center, Città della Salute e della Scienza, Turin, Italy
| | - Luigi Biancone
- Division of Nephrology Dialysis and Transplantation, Department of Medical Sciences, "A. Vercellone" Renal Transplantation Center, Città della Salute e della Scienza, Turin, Italy -
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6
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Morizawa Y, Satoh H, Arai M, Iwasa S, Sato A, Fujimoto K. Association Between Nonadherence and Transient Hyperuricemia in Pediatric Kidney Transplantation. Transplant Proc 2023; 55:129-133. [PMID: 36581508 DOI: 10.1016/j.transproceed.2022.09.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 08/29/2022] [Accepted: 09/20/2022] [Indexed: 12/29/2022]
Abstract
BACKGROUND Nonadherence among pediatric transplant recipients is a significant problem that reduces graft survival and leads to poor kidney graft outcomes. It is, however, extremely difficult to detect during a regular follow-up. This study, therefore, aimed to investigate the risk factors involved in nonadherence, focusing on unexplained transient hyperuricemia in pediatric kidney transplant (KTx) recipients at a single pediatric center. METHODS This retrospective study included 167 patients who underwent KTx at our pediatric center. A Cox proportional hazards analysis was performed to evaluate the risk of nonadherence using the following factors: age, sex, body mass index SD score, transient hyperuricemia, hypertension, and follow-up period. RESULTS Nonadherence was identified in 19 patients (11%), with the average (SD) age and post-KTx duration at diagnosis being 17.21 (4.73) years and 79.21 (38.77) months, respectively. Thirty-four patients (20%) were diagnosed with transient hyperuricemia at a median of 14 months after KTx. On multivariate Cox regression analysis, transient hyperuricemia was the only independent risk factor for nonadherence after KTx. CONCLUSIONS Transient hyperuricemia was identified as one of the risk factors for nonadherence after KTx; therefore, careful monitoring for transient hyperuricemia may allow early detection of nonadherence.
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Affiliation(s)
- Y Morizawa
- Department of Urology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan; Department of Urology, Nara Medical University, Kashihara, Nara, Japan.
| | - H Satoh
- Department of Urology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan
| | - M Arai
- Department of Urology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan
| | - S Iwasa
- Department of Urology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan
| | - A Sato
- Department of Urology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan
| | - K Fujimoto
- Department of Urology, Nara Medical University, Kashihara, Nara, Japan
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Oomen L, Bootsma-Robroeks C, Cornelissen E, de Wall L, Feitz W. Pearls and Pitfalls in Pediatric Kidney Transplantation After 5 Decades. Front Pediatr 2022; 10:856630. [PMID: 35463874 PMCID: PMC9024248 DOI: 10.3389/fped.2022.856630] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 02/15/2022] [Indexed: 11/13/2022] Open
Abstract
Worldwide, over 1,300 pediatric kidney transplantations are performed every year. Since the first transplantation in 1959, healthcare has evolved dramatically. Pre-emptive transplantations with grafts from living donors have become more common. Despite a subsequent improvement in graft survival, there are still challenges to face. This study attempts to summarize how our understanding of pediatric kidney transplantation has developed and improved since its beginnings, whilst also highlighting those areas where future research should concentrate in order to help resolve as yet unanswered questions. Existing literature was compared to our own data of 411 single-center pediatric kidney transplantations between 1968 and 2020, in order to find discrepancies and allow identification of future challenges. Important issues for future care are innovations in immunosuppressive medication, improving medication adherence, careful donor selection with regard to characteristics of both donor and recipient, improvement of surgical techniques and increased attention for lower urinary tract dysfunction and voiding behavior in all patients.
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Affiliation(s)
- Loes Oomen
- Division of Pediatric Urology, Department of Urology, Radboudumc Amalia Children's Hospital, Nijmegen, Netherlands
| | - Charlotte Bootsma-Robroeks
- Department of Pediatric Nephrology, Radboudumc Amalia Children's Hospital, Nijmegen, Netherlands
- Department of Pediatrics, Pediatric Nephrology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
| | - Elisabeth Cornelissen
- Department of Pediatric Nephrology, Radboudumc Amalia Children's Hospital, Nijmegen, Netherlands
| | - Liesbeth de Wall
- Division of Pediatric Urology, Department of Urology, Radboudumc Amalia Children's Hospital, Nijmegen, Netherlands
| | - Wout Feitz
- Division of Pediatric Urology, Department of Urology, Radboudumc Amalia Children's Hospital, Nijmegen, Netherlands
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Zachciał J, Uchmanowicz I, Krajewska M, Banasik M. Adherence to Immunosuppressive Therapies after Kidney Transplantation from a Biopsychosocial Perspective: A Cross-Sectional Study. J Clin Med 2022; 11:jcm11051381. [PMID: 35268471 PMCID: PMC8910970 DOI: 10.3390/jcm11051381] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 02/24/2022] [Accepted: 02/28/2022] [Indexed: 12/02/2022] Open
Abstract
Kidney transplantation (KT) is the best method for kidney replacement therapy (KRT) because of patient survival rates and quality of life (QoL). Nowadays, the main cause of graft loss is antibody-mediated rejection. The treatment of humoral injury is difficult with uncertain results and still not firmly established. Therefore, appropriate adherence is crucial to prolong graft and patient survival. This study aims to evaluate the association of transplant patients’ acceptance of illness, symptoms of anxiety and depression, frailty, and QoL with medication adherence in KT recipients. A total of 210 patients after KT completed the surveys. The instruments were distributed during patients’ admission at the clinic by a qualified nurse, who assisted the patients’ in completing the questionnaires. A cross-sectional study of KT recipients 9.45 ± 7.26 years after KT was performed. Patient adherence with medications was assessed using the Adherence to Refills and Medications Scale (ARMS). Explanatory variables were examined with validated instruments, such as the World Health Organization Quality of Life (WHOQoL-BREF) questionnaire, The Mini-Mental State Examination (MMSE), the Acceptance of Illness Scale (AIS), the Hospital Anxiety and Depression Scale (HADS), and the Tilburg Frailty Indicator (TFI) scale, respectively. Simple linear and multiple regression analyses demonstrated the positive correlation between acceptance of illness and adherence to immunosuppressive medications in a patient sample of KT recipients. The other important factor facilitating adherence to medications was linked with physical and environmental dimensions. On the other hand, frail kidney transplant patients were more likely to be non-adherent. In conclusion, identifying contributors to better medication adherence in immunosuppressive therapy is crucial in preventing transplant rejection or graft loss. In the kidney transplant population, the acceptance of illness, selected dimensions of QoL, and demographic variables associated with rural living and vocational education favored adherence behaviors.
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Affiliation(s)
- Justyna Zachciał
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, 50-556 Wroclaw, Poland; (J.Z.); (M.K.); (M.B.)
- Department of Clinical Nursing, Wroclaw Medical University, 51-618 Wroclaw, Poland
| | - Izabella Uchmanowicz
- Department of Clinical Nursing, Wroclaw Medical University, 51-618 Wroclaw, Poland
- Correspondence: ; Tel.: +48-71-784-18-24
| | - Magdalena Krajewska
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, 50-556 Wroclaw, Poland; (J.Z.); (M.K.); (M.B.)
| | - Mirosław Banasik
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, 50-556 Wroclaw, Poland; (J.Z.); (M.K.); (M.B.)
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9
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Gandolfini I, Palmisano A, Fiaccadori E, Cravedi P, Maggiore U. Detecting, preventing, and treating non-adherence to immunosuppression after kidney transplantation. Clin Kidney J 2022; 15:1253-1274. [PMID: 35756738 PMCID: PMC9217626 DOI: 10.1093/ckj/sfac017] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Indexed: 11/12/2022] Open
Abstract
Medication non-adherence (MNA) is a major issue in kidney transplantation and it is associated with increased risk of rejection, allograft loss, patients’ death and higher healthcare costs. Despite its crucial importance, it is still unclear what are the best strategies to diagnose, prevent and treat MNA. MNA can be intentional (deliberate refusal to take the medication as prescribed) or unintentional (non-deliberate missing the prescribed medication). Its diagnosis may rely on direct methods, aiming at measuring drug ingestions, or indirect methods that analyse the habits of patients to adhere to correct drug dose (taking adherence) and interval (time adherence). Identifying individual risk factors for MNA may provide the basis for a personalized approach to the treatment of MNA. Randomized control trials performed so far have tested a combination of strategies, such as enhancing medication adherence through the commitment of healthcare personnel involved in drug distribution, the use of electronic reminders, therapy simplification or various multidisciplinary approaches to maximize the correction of individual risk factors. Although most of these approaches reduced MNA in the short-term, the long-term effects on MNA and, more importantly, on clinical outcomes remain unclear. In this review, we provide a critical appraisal of traditional and newer methods for detecting, preventing and treating non-adherence to immunosuppression after kidney transplantation from the perspective of the practising physician.
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Affiliation(s)
- Ilaria Gandolfini
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Nephrology Unit, University Hospital of Parma, Parma, Italy
| | | | - Enrico Fiaccadori
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Nephrology Unit, University Hospital of Parma, Parma, Italy
| | - Paolo Cravedi
- Department of Medicine, Division of Nephrology and Translational Transplant Research Center, Recanati Miller Transplant Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Umberto Maggiore
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Nephrology Unit, University Hospital of Parma, Parma, Italy
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10
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Bailey P, Vergis N, Allison M, Riddell A, Massey E. Psychosocial Evaluation of Candidates for Solid Organ Transplantation. Transplantation 2021; 105:e292-e302. [PMID: 33675318 DOI: 10.1097/tp.0000000000003732] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Transplant candidates should undergo an assessment of their mental health, social support, lifestyle, and behaviors. The primary aims of this "psychosocial evaluation" are to ensure that transplantation is of benefit to life expectancy and quality of life, and to allow optimization of the candidate and transplant outcomes. The content of psychosocial evaluations is informed by evidence regarding pretransplant psychosocial predictors of transplant outcomes. This review summarizes the current literature on pretransplant psychosocial predictors of transplant outcomes across differing solid organ transplants and discusses the limitations of existing research. Pretransplant depression, substance misuse, and nonadherence are associated with poorer posttransplant outcomes. Depression, smoking, and high levels of prescription opioid use are associated with reduced posttransplant survival. Pretransplant nonadherence is associated with posttransplant rejection, and nonadherence may mediate the effects of other psychosocial variables such as substance misuse. There is evidence to suggest that social support is associated with likelihood of substance misuse relapse after transplantation, but there is a lack of consistent evidence for an association between social support and posttransplant adherence, rejection, or survival across all organ transplant types. Psychosocial evaluations should be undertaken by a trained individual and should comprise multiple consultations with the transplant candidate, family members, and healthcare professionals. Tools exist that can be useful for guiding and standardizing assessment, but research is needed to determine how well scores predict posttransplant outcomes. Few studies have evaluated interventions designed to improve psychosocial functioning specifically pretransplant. We highlight the challenges of carrying out such research and make recommendations regarding future work.
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Affiliation(s)
- Pippa Bailey
- Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
- Renal and Transplant Service, Southmead Hospital, North Bristol NHS Trust, Bristol, UK
| | - Nikhil Vergis
- Liver Services Department, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK
- Department of Metabolism Digestion and Reproduction, Imperial College London, UK
| | - Michael Allison
- Cambridge Liver Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Amy Riddell
- Renal and Transplant Service, Southmead Hospital, North Bristol NHS Trust, Bristol, UK
- University of Exeter Medical School, Exeter, UK
| | - Emma Massey
- Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, The Netherlands
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11
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Pourrat X, Berthy E, Dupuis A, Barbier L, Buchler M, Guillon LG, Monmousseau F, Ruspini E, Salamé E, Houdard SB, Giraudeau B. Implementing a personalized pharmaceutical plan in kidney or liver transplant patients: study protocol for a stepped-wedge cluster randomized trial (GRePH). Trials 2021; 22:782. [PMID: 34749777 PMCID: PMC8573912 DOI: 10.1186/s13063-021-05749-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 10/25/2021] [Indexed: 11/10/2022] Open
Abstract
Background Nowadays, the main challenge of transplantation is the improvement of long-term care, aiming at reducing treatment-related complications and at decreasing rejection rates. Patients’ adherence to both treatment and hygienic-dietary measures is mandatory to achieve these objectives. Adherence to immunosuppressive drugs is estimated to be only 70%. We hypothesized that the implementation of a personalized pharmaceutical plan (PPP) would increase adherence and therefore graft survival. Methods/design This study is a stepped-wedge cluster randomized trial with transplantation units defining clusters. Twelve clusters from 10 university hospitals were recruited. All centres started on the same day in the control phase. Every 7 weeks, one centre will switch to the intervention phase and remain there until the end of inclusions. We plan to recruit 1716 kidney and/or liver transplant patients. The intervention phase consists in setting up the PPP: development of the patient’s hospital and community pharmaceutical follow-up. In the hospital, the pharmacist will carry out drug reconciliation upon admission, daily pharmaceutical follow-up of prescriptions and pharmaceutical interviews with the patient in order to explain the modalities of taking immunosuppressive drugs and hygienic-dietary measures. After hospitalization, during the post-transplantation year, pharmaceutical meetings will take place, prior to medical consultations in order to check the patient’s understanding of the prescription, his adherence, to remind them of hygienic-dietary measures and to look for adverse effects. The hospital pharmacist will also be in charge of establishing a close link with the community pharmacist (CP) and general practitioner, especially providing discharge medication reconciliation, an e-learning and a checklist. Moreover, prior to each pharmaceutical consultation, the hospital pharmacist will contact the CP to discuss patient adherence. The primary outcome is adherence to immunosuppressive treatments 1 year post-transplantation assessed by using the BAASIS questionnaire and the health insurance data from the national health data system. A medico-economic study will measure the efficiency of this plan. Discussion GRePH aims to increase adherence of liver and/or kidney transplant patients to their immunosuppressive therapies in order to reduce transplant rejections. To this end, a new clinical pharmacy model, the PPP, will be set up in 10 university hospitals. Trial registration ClinicalTrials.gov NCT04295928. Registered on 5 March 2020 Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05749-w.
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Affiliation(s)
- Xavier Pourrat
- Pharmacy Department, Pharm D, Tours University Hospital, 2 boulevard Tonnelle, 37044, 09, Tours Cedex, France
| | - Elise Berthy
- Pharmacy Department, Pharm D, Tours University Hospital, 2 boulevard Tonnelle, 37044, 09, Tours Cedex, France.
| | - Antoine Dupuis
- Biology-Pharmacy-Public Health Department, University Hospital of Poitiers, 2 rue de la 9 Milétrie, 86021, Poitiers Cedex, France
| | - Louise Barbier
- Digestive Surgery and Liver Transplantation, Tours University Hospital, Tours, France
| | - Matthias Buchler
- Nephrology Department, Tours University Hospital, 2 boulevard Tonnelle, 37044, 09, Tours Cedex, France
| | - Leslie Grammatico Guillon
- Department of Medical Information, Epidemiology and Medical Economy, Tours University Hospital, Tours, France.,INSERM U966, University of Tours, Tours, France
| | - Fanny Monmousseau
- Health-economic Evaluation Unit, University Hospital of Tours, Tours, France.,EA 7505 Education, Ethics, Health, University of Tours, Tours, France
| | - Eric Ruspini
- Regional Union of Healthcare Professionals Pharmacists of the Greater East of France, 4 rue Piroux, Nancy, France
| | - Ephrem Salamé
- Digestive Surgery and Liver Transplantation, Tours University Hospital, Tours, France
| | - Solène Brunet Houdard
- Health-economic Evaluation Unit, University Hospital of Tours, Tours, France.,EA 7505 Education, Ethics, Health, University of Tours, Tours, France
| | - Bruno Giraudeau
- Université de Tours, Université de Nantes, INSERM, SPHERE U1246, Tours, France.,INSERM CIC1415, CHRU de Tours, Tours, France
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12
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Tang J, Kerklaan J, Wong G, Howell M, Scholes-Robertson N, Guha C, Kelly A, Tong A. Perspectives of solid organ transplant recipients on medicine-taking: Systematic review of qualitative studies. Am J Transplant 2021; 21:3369-3387. [PMID: 33866675 DOI: 10.1111/ajt.16613] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 03/16/2021] [Accepted: 04/02/2021] [Indexed: 01/25/2023]
Abstract
Medicine-taking among transplant recipients is a complex and ubiquitous task with significant impacts on outcomes. This study aimed to describe the perspectives and experiences of medicine-taking in adult solid organ transplant recipients. Electronic databases were searched to July 2020, and thematic synthesis was used to analyze the data. From 119 studies (n = 2901), we identified six themes: threats to identity and ambitions (impaired self-image, restricting goals and roles, loss of financial independence); navigating through uncertainty and distrust (lacking tangible/perceptible benefits, unprepared for side effects, isolation in decision-making); alleviating treatment burdens (establishing and mastering routines, counteracting side effects, preparing for the unexpected); gaining and seeking confidence (clarity with knowledge, reassurance through collective experiences, focusing on the future outlook); recalibrating to a new normal posttransplant (adjusting to ongoing dependence on medications, in both states of illness and health, unfulfilled expectations); and preserving graft survival (maintaining the ability to participate in life, avoiding rejection, enacting a social responsibility of giving back). Transplant recipients take medications to preserve graft function, but dependence on medications jeopardizes their sense of normality. Interventions supporting the adaptation to medicine-taking and addressing treatment burdens may improve patient satisfaction and capacities to take medications for improved outcomes.
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Affiliation(s)
- James Tang
- Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia.,Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia
| | - Jasmijn Kerklaan
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia.,Department of Pediatric Nephrology, Academic Medical Center, Emma Children's Hospital, Amsterdam, the Netherlands
| | - Germaine Wong
- Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia.,Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia.,Centre for Transplant and Renal Research, Westmead Hospital, Westmead, NSW, Australia
| | - Martin Howell
- Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia.,Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia
| | - Nicole Scholes-Robertson
- Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia.,Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia
| | - Chandana Guha
- Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia.,Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia
| | - Ayano Kelly
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia
| | - Allison Tong
- Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia.,Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia
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13
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Mira FS, Figueiredo C, Rodrigues L, Romãozinho C, Galvão A, Figueiredo A, Alves R. Tacrolimus Trough Intravariability in Patients Treated With the Prolonged-Release Formulation Is a Risk Factor for Acute Graft Rejection. EXP CLIN TRANSPLANT 2021; 19:910-913. [PMID: 34545776 DOI: 10.6002/ect.2021.0231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Tacrolimus has a narrow therapeutic window, and lack of adherence to the therapeutic regimen is a main risk factor for acute graft rejection; hence, the prolonged-release formulation was created. A high intrapatient variability for tacrolimus trough levels has been associated with worse graft outcomes; therefore, we investigated the correlation between the tacrolimus variation coefficient and the development of biopsy-proven acute graft rejection in kidney transplant patients with typical maintenance immunosuppression versus the prolonged-release formulation. MATERIALS AND METHODS This was a single-center observational retrospective study that included all adult kidney transplants from deceased donors between January 2011 and December 2014 for which the transplant recipients were given maintenance therapy with tacrolimus prolonged-release formulation (Advagraf). The overall tacrolimus variation coefficient was calculated for the follow-up period from transplant until December 2019. Biopsy-proven acute graft rejection results were collected throughout follow-up. Statistical analysis was performed with SPSS software. RESULTS The study was composed of 147 patients with a mean follow-up time of 60.4 ± 15 months. The mean age of the patients was 47.5 ± 11.9 years and 67.3% were men. Of these 147 patients, 29 had at least 1 episode of acute graft rejection during follow-up. There was a significant correlation between patients with a higher tacrolimus variation coefficient and the presence of biopsy-proven acute graft rejection. Receiver operating characteristic curves were used to determine an intrapatient variability cutoff point of 28.3% for tacrolimus. Younger patients were also more likely than older patients to develop acute graft rejection in our sample. CONCLUSIONS High intrapatient variability of tacrolimus trough levels is a risk factor for acute graft rejection in kidney transplant patients.
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Affiliation(s)
- Filipe S Mira
- From the Nephrology Department, Coimbra University Hospital, and the Faculty of Medicine, Coimbra, Portugal
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14
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Ethical considerations in pediatric chronic illness: The relationship between psychological factors, treatment adherence, and health outcomes. Paediatr Respir Rev 2021; 39:48-53. [PMID: 34246544 PMCID: PMC8448946 DOI: 10.1016/j.prrv.2021.05.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Accepted: 05/25/2021] [Indexed: 11/23/2022]
Abstract
Children, adolescents, and young adults with chronic illnesses are often faced with complicated and burdensome treatments that not only require a great deal of time and energy to manage, but will also likely impact relationships with parents, siblings, and peers. Adolescents and young adults with chronic illness are often impacted by several unique and challenging factors that can ultimately impact health behaviors and treatment outcomes. Working with a psychologist can help to ameliorate these unique challenges, which will positively impact health behaviors and health outcomes. The present paper provides an overview of psychological interventions that were designed to target the unique challenges that are often associated with maladaptive health behaviors and ultimately poor health outcomes. As demonstrated in this commentary, when working with adolescents and young adults who have unique developmental challenges, it is important to deliver multi-faceted intervention approaches that utilize a number of different strategies and frameworks. These eclectic intervention approaches provide a unique opportunity to improve health behaviors during critical developmental periods, including the transition from childhood to adolescence to young adulthood.
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15
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Lichvar A, Chandran MM, Do V, Rendulic T, Szczepanik A, Pierce D, Park JM. Entrustable professional activities for pharmacy students: A primer for solid organ transplant preceptors. Am J Health Syst Pharm 2021; 78:zxab320. [PMID: 34350946 DOI: 10.1093/ajhp/zxab320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Indexed: 11/14/2022] Open
Abstract
DISCLAIMER In an effort to expedite the publication of articles , AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE The role of a solid organ transplant pharmacist is multifaceted and translates to diverse experiential and elective learning experiences that can be provided to pharmacy learners. Here we provide a guide to integrating pharmacy students into patient care and other pharmacist activities in solid organ transplantation. SUMMARY Thoughtful incorporation of learners into clinical practice and clinical research creates a positive learning environment for pharmacy students that can foster the development of core skills necessary for students to become "practice-ready" and "team-ready" pharmacy graduates and can equip them with valuable skills to incorporate into the specialty practice areas and careers they pursue. To help develop these educational experiences, attention to the list of core entrustable professional activities (EPAs) established by the American Association of Colleges of Pharmacy can help create a rich environment of learning with carefully cultivated tasks. Furthermore, learners can serve as transplant pharmacist extenders to assist in overall patient care and multidisciplinary involvement on the transplant team. This article serves as a "how-to" guide for applying the EPA framework to integrating pharmacy students in patient care and other pharmacist activities in solid organ transplantation and other specialty practice areas. CONCLUSION As pharmacy preceptors design and operationalize their teaching to incorporate EPAs, they can benefit from recommendations tailored to specialty practice areas such as solid organ transplantation. Students may start and finish these experiences at different EPA levels, but continuance of training will allow them to achieve the final EPA level across the 6 EPA domains.
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Affiliation(s)
- Alicia Lichvar
- Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL, and Department of Surgery, University of Illinois at Chicago, Chicago, IL, USA
| | | | - Vincent Do
- Department of Pharmacy, Yale New Haven Hospital, New Haven, CT, USA
| | - Trisann Rendulic
- Department of Pharmacy, University of Kentucky, Lexington, KY, USA
| | - Amanda Szczepanik
- Department of Pharmacy, University of Maryland Medical Center, Baltimore, MD, USA
| | - Dana Pierce
- Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL, USA
| | - Jeong M Park
- Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, MI, and Department of Pharmacy Services, Michigan Medicine, Ann Arbor, MI, USA
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16
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Melanson TA, Mersha K, Patzer RE, George RP. Loss to Follow-up in Adolescent and Young Adult Renal Transplant Recipients. Transplantation 2021; 105:1326-1336. [PMID: 32890129 PMCID: PMC7921205 DOI: 10.1097/tp.0000000000003445] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Patients' loss to follow-up (LFU) has significant impacts on outcomes and is a barrier to improving care, especially in adolescent and young adult (AYA) renal transplant recipients. There is limited information regarding the relationship between transfer of care from pediatric to adult transplant centers, age, and LFU among AYA renal transplant recipients. METHODS We studied 16 386 individuals aged 10-29 years who received kidney transplants between January 1, 2005 and December 31, 2015 using the Scientific Registry of Transplant Recipients. The primary outcome was LFU, which was defined as >1 year without follow-up in a transplant clinic/program. Death or graft failure within a year of the last follow-up was not classified as LFU. We performed a retrospective cohort study describing LFU using Pearson's chi-square tests. Multivariable logistic regression was used to estimate the change in likelihood of LFU associated with recipient characteristics and institution transfer. RESULTS In total, 22.26% (n = 3647) of our study population met criteria for LFU. About 11.17% (n = 1830) transferred institutions during the study period. LFU occurred in 50.18% of recipients who transferred institutions. LFU peaked at the age of 20 years, with 7.4% of 20-year-olds having LFU. The odds of LFU among renal transplant recipients who transferred institutions were 3.36 times greater (95% confidence interval, 3.1-3.6) than the odds of LFU among those who did not transfer institutions. CONCLUSIONS LFU is a critical problem faced by AYA renal transplant recipients, and institution transfer is a significant risk factor for LFU. Additional studies investigating the interplay between age, institution transfer, and LFU in the AYA population are still needed.
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Affiliation(s)
- Taylor A. Melanson
- Department of Surgery, Emory University School of Medicine, Atlanta, Georgia
| | - Karie Mersha
- Division of Pediatric Nephrology and Hypertension, Joe DiMaggio Children’s Hospital, Hollywood, Florida
| | - Rachel E. Patzer
- Department of Surgery, Emory University School of Medicine, Atlanta, Georgia
| | - Roshan P. George
- Department of Pediatric Nephrology, Emory University, Atlanta, Georgia
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17
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Taber DJ, Hirsch J, Keys A, Su Z, McGillicuddy JW. Etiologies and Outcomes Associated With Tacrolimus Levels Out of a Typical Range That Lead to High Variability in Kidney Transplant Recipients. Ther Drug Monit 2021; 43:401-407. [PMID: 33560095 PMCID: PMC8119313 DOI: 10.1097/ftd.0000000000000863] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Accepted: 12/27/2020] [Indexed: 11/25/2022]
Abstract
BACKGROUND High tacrolimus intrapatient variability (tac IPV) is associated with poor outcomes in kidney transplantation, including rejection, donor-specific antibodies, and graft loss. A common cause of high tac IPV is related to patient nonadherence, but this is yet to be conclusively demonstrated. METHODS This was a longitudinal cohort study comprising adult kidney recipients, who received transplants between 2015 and 2017, with follow-ups through February 2020. The goal of this study was to identify the most common etiologies of tac levels outside the typical range, which lead to high tac IPV, and assess the etiology-specific associations between high tac IPV and graft outcomes. Multivariate Cox regression was used to assess time-to-event analyses. RESULTS In total, 537 adult kidney recipients were included; 145 (27%) were identified as having a high tac IPV (>40%) 3-102 months post-transplant. Common etiologies of tac levels significantly outside the standard goal range (6-12 ng/mL) leading to high tac IPV included patient nonadherence (20%), infections (19%), tac-related toxicities (17%), and undocumented issues (27%). In multivariable Cox modeling, those with high tac IPV because of nonadherence had a 3.5 times higher risk of late acute rejection (P = 0.019) and 2.2 times higher risk of late graft loss (P = 0.044). No other etiologies in the typical tac level range were significantly associated with either acute rejection or graft loss. CONCLUSIONS Although high tac IPV has many causes, only high tac IPV caused by nonadherence is consistently associated with poor allograft outcomes.
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Affiliation(s)
- David J Taber
- Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, Charleston SC
| | - Jason Hirsch
- Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, Charleston SC
| | - Alison Keys
- College of Pharmacy, Medical University of South Carolina, Charleston SC
| | - Zemin Su
- Department of Medicine, Medical University of South Carolina, Charleston SC
| | - John W McGillicuddy
- Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, Charleston SC
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18
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Holderried M, Hoeper A, Holderried F, Heyne N, Nadalin S, Unger O, Ernst C, Guthoff M. Attitude and potential benefits of modern information and communication technology use and telemedicine in cross-sectoral solid organ transplant care. Sci Rep 2021; 11:9037. [PMID: 33907269 PMCID: PMC8079672 DOI: 10.1038/s41598-021-88447-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 04/06/2021] [Indexed: 12/20/2022] Open
Abstract
Situations like the COVID-19 pandemic urgently require the implementation of eHealth for vulnerable patient populations. Here we quantitatively evaluate use and potential of modern information and communication technology (ICT) in solid organ transplant (SOT) recipients. We conducted a structured, questionnaire-based, cross-sectional study that was addressed to patients after kidney, liver, pancreas, or combined transplantation. We focused on: sociodemographic data, present use of digital technologies in daily life and for health reasons, patients' eHealth literacy, and their overall attitude towards eHealth. A total of 234 patients completed the questionnaire. Most of the patients (90%) have a web-enabled computer, 78.2% have a smartphone, and 71.8% regularly search the internet for health-related information. Sixty-eight percent would like to receive discharge summaries online, and 54% would like to chat online with their physicians. Even though ICT use in daily life was age-related, no significant difference could be shown for health reasons or the type of transplanted organ. Modern ICT use is predominantly accepted for health reasons by SOT recipients. Regardless of the transplanted organ, a deeper integration of eHealth has potential for improving cross-sectoral care. To successfully implement eHealth technologies in cross-sectoral care future research should include online physician-patient communication, data security, data safety, and the aspects of quality and safety of care.
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Affiliation(s)
- Martin Holderried
- eHealth Research-Group, Department of Strategic Medical Development and Quality Management, University of Tuebingen, Hoppe-Seyler-Str. 6, 72076, Tuebingen, Germany
- Institute for Healthcare and Public Management, University of Hohenheim, Hohenheim, Stuttgart, Germany
| | - Ansgar Hoeper
- eHealth Research-Group, Department of Strategic Medical Development and Quality Management, University of Tuebingen, Hoppe-Seyler-Str. 6, 72076, Tuebingen, Germany
| | - Friederike Holderried
- eHealth Research-Group, Department of Strategic Medical Development and Quality Management, University of Tuebingen, Hoppe-Seyler-Str. 6, 72076, Tuebingen, Germany.
| | - Nils Heyne
- Department of Diabetology, Endocrinology, Nephrology, Section of Nephrology and Hypertension, University of Tuebingen, Tuebingen, Germany
| | - Silvio Nadalin
- Department of General-, Visceral- and Transplant Surgery, University of Tuebingen, Tuebingen, Germany
| | - Oliver Unger
- Faculty of Business Management and Economics, Julius-Maximilians-University, Wuerzburg, Germany
| | - Christian Ernst
- Institute for Healthcare and Public Management, University of Hohenheim, Hohenheim, Stuttgart, Germany
| | - Martina Guthoff
- Department of Diabetology, Endocrinology, Nephrology, Section of Nephrology and Hypertension, University of Tuebingen, Tuebingen, Germany
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19
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Association between medication adherence and intrapatient variability in tacrolimus concentration among stable kidney transplant recipients. Sci Rep 2021; 11:5397. [PMID: 33686160 PMCID: PMC7940492 DOI: 10.1038/s41598-021-84868-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 02/18/2021] [Indexed: 02/04/2023] Open
Abstract
This study analyzed the association between medication adherence and the intrapatient variability (IPV) of tacrolimus concentrations among kidney transplant recipients through a post hoc analysis of the dataset from a recently conducted randomized controlled trial. Among 138 patients enrolled in the original trial, 92 patients with ≥ 5 months of medication event monitoring system (MEMS) use and ≥ 4 tacrolimus trough values were included in this post hoc analysis. The variability of tacrolimus trough levels was calculated using coefficient variation (CV) and mean absolute deviation. Adherence was assessed using MEMS and self-report via the Basal Assessment of Adherence to Immunosuppressive Medication Scale. There were no statistically significant differences in the CV [median 16.5% [interquartile range 11.6–25.5%] and 16.0% [11.5–23.5%], respectively, P = .602] between the nonadherent (n = 59) and adherent groups (n = 33). There was also no significant correlation between the CV and adherence detected by MEMS (taking adherence, ρ = − 0.067, P = .527; dosing adherence, ρ = − 0.098, P = .352; timing adherence, ρ = − 0.113, P = .284). Similarly, adherence measured by self-report did not significantly affect the IPV (P = .452). In this post hoc analysis, nonadherent behavior, measured through electronic monitoring or self-report, did not affect the IPV.
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20
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Harrington CR, Yang GY, Levitsky J. Advances in Rejection Management: Prevention and Treatment. Clin Liver Dis 2021; 25:53-72. [PMID: 33978583 DOI: 10.1016/j.cld.2020.08.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Extended survival of liver transplant recipients has brought rejection management to the forefront of liver transplant research. This article discusses T-cell-mediated rejection, antibody-mediated rejection, and chronic rejection. We focus on the prevention and then discuss treatment options. Future directions of rejection management include biomarkers of rejection, which may allow for monitoring of patients who are considered high risk for rejection and detection of rejection before there is any clinical evidence to improve graft and patient survival. With improved graft life and survival of liver transplant recipients, the new frontier of rejection management focuses on immunosuppression minimization, withdrawal, and personalization.
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Affiliation(s)
- Claire R Harrington
- Department of Medicine, Northwestern University Feinberg School of Medicine, 676 North St. Clair Street, Suite 2330, Chicago, IL 60611, USA
| | - Guang-Yu Yang
- Department of Pathology, Northwestern University Feinberg School of Medicine, 251 E Huron St. Chicago, IL 60611, USA
| | - Josh Levitsky
- Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, 676 North St. Clair Street, Suite 1400, Chicago, IL 60611, USA; Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, 676 North St. Clair Street, Suite 1900, Chicago, IL 60611, USA.
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21
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Transplant regimen adherence for kidney recipients by engaging information technologies (TAKE IT): Rationale and methods for a randomized controlled trial of a strategy to promote medication adherence among transplant recipients. Contemp Clin Trials 2021; 103:106294. [PMID: 33515781 DOI: 10.1016/j.cct.2021.106294] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 01/19/2021] [Accepted: 01/22/2021] [Indexed: 01/08/2023]
Abstract
BACKGROUND Several studies report a high prevalence of non-adherence to prescribed immunosuppressive (IS) medications among kidney transplant recipients (KTRs), yet few interventions have been effective for helping patients sustain appropriate post-transplant adherence. We describe a multifaceted, evidence-based, medication adherence monitoring strategy ('TAKE IT') that leverages available transplant center resources to identify potential medication non-adherence and other concerns earlier to prevent complications that could result from inadequate IS adherence. METHODS The TAKE IT strategy includes: 1) medication adherence mobile application; 2) routine, online patient self-reported adherence assessments; 3) care alert notifications via the electronic health record (EHR) directed to transplant coordinators; 4) quarterly adherence reports to monitor IS values and summarize adherence trends; 5) deployment of adherence support tools tailored to specific adherence concerns. To test the TAKE IT intervention, we will conduct a two-arm, patient-randomized controlled trial at two large, diverse transplant centers (Northwestern University, Mayo Clinic, AZ) with planned recruitment of 450 KTRs (n = 225 per site) within 2 years of transplantation and 2 years of follow-up. Study assessments will take place at baseline, 6 weeks, 6, 12, 18 and 24 months. The primary effectiveness outcome is medication adherence via pill count, secondary outcomes include self-reported adherence and clinical outcomes. Process outcomes and cost-effectiveness will also be examined. CONCLUSION The TAKE IT trial presents an innovative approach to monitoring and optimizing medication adherence among a population taking complex medication regimens. This trial seeks to evaluate the effectiveness and feasibility of this strategy compared to usual care.
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22
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Sanders-Pinheiro H, Colugnati FAB, Denhaerynck K, Marsicano EO, Medina JOP, De Geest S. Multilevel Correlates of Immunosuppressive Nonadherence in Kidney Transplant Patients: The Multicenter ADHERE BRAZIL Study. Transplantation 2021; 105:255-266. [PMID: 32150041 DOI: 10.1097/tp.0000000000003214] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Immunosuppressive nonadherence is a risk factor for worse outcomes after kidney transplantation (KT). Brazil, having the world's largest public, fully covered transplantation system and the second-highest KT volume worldwide, provides a unique setting for studying multilevel correlates of nonadherence (patient, healthcare provider, transplant center, and healthcare system levels) independent of patients' financial burden. METHODS By applying a multistage sampling approach, we included 1105 patients from 20 KT centers. Nonadherence to immunosuppressives (implementation phase) was defined as any deviation in taking or timing adherence and dose reduction assessed by the Basel Assessment of Adherence to Immunosuppressive Medications Scale. Based on Bronfenbrenner's ecological model, we assessed multilevel factors using established instruments and measures specifically developed for this study and analyzed their independent contribution to nonadherence by performing sequential logistic regression analysis. RESULTS The nonadherence prevalence rate was 39.7%. The following factors were independently associated with nonadherence: Patient level-having a stable partner (odds ratio [OR]: 0.75; confidence interval [CI]: 0.58-0.97), nonadherence to appointments (OR: 2.98; CI: 2.03-4.39), and nonadherence to physical activity recommendations (OR: 1.84; CI: 1.38-2.46); and transplant center level-satisfaction with the waiting room structure (OR: 0.54; CI: 0.42-0.71), consultation >30 minutes (OR: 1.60; CI: 1.19-2.14), adequacy of the consultation frequency (OR: 0.62; CI: 0.43-0.90), and centers with >500 beds (OR: 0.58; CI: 0.46-0.73). CONCLUSIONS As the first multicenter study assessing multilevel correlates of nonadherence in KT, our findings point to the need for multilevel interventions beyond the patient level, targeting transplant center practice patterns as an approach to tackle nonadherence.
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Affiliation(s)
- Helady Sanders-Pinheiro
- Renal Transplantation Unit, University Hospital, Federal University of Juiz de Fora, Minas Gerais, Brazil and Núcleo Interdisciplinar de Estudos e Pesquisas em Nefrologia (NIEPEN), Juiz de Fora, Minas Gerais, Brazil
| | - Fernando A B Colugnati
- Renal Transplantation Unit, University Hospital, Federal University of Juiz de Fora, Minas Gerais, Brazil and Núcleo Interdisciplinar de Estudos e Pesquisas em Nefrologia (NIEPEN), Juiz de Fora, Minas Gerais, Brazil
| | - Kris Denhaerynck
- Department of Public Health, Institute of Nursing Science, University of Basel, Basel, Switzerland
| | - Elisa O Marsicano
- Renal Transplantation Unit, University Hospital, Federal University of Juiz de Fora, Minas Gerais, Brazil and Núcleo Interdisciplinar de Estudos e Pesquisas em Nefrologia (NIEPEN), Juiz de Fora, Minas Gerais, Brazil
| | - José O P Medina
- Hospital do Rim e Hipertensão, Oswaldo Ramos Foundation, Nephrology Discipline, Federal University of São Paulo, São Paulo, Brazil
| | - Sabina De Geest
- Department of Public Health, Institute of Nursing Science, University of Basel, Basel, Switzerland
- Department of Public Health and Primary Care, Academic Centre for Nursing and Midwifery, KU Leuven, Leuven, Belgium
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23
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Chu MC, Smith PJ, Reynolds JM, Palmer SM, Snyder LD, Gray AL, Blumenthal JA. Depression, Immunosuppressant Levels, and Clinical Outcomes in Postlung Transplant Recipients. Int J Psychiatry Med 2020; 55:421-436. [PMID: 32052665 DOI: 10.1177/0091217420906637] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Posttransplant depression has been linked to increased risk for adverse outcomes in lung transplant patients. Maintaining target serum immunosuppressant levels is also essential for optimal lung transplant clinical outcome and may be a crucial predictor of outcomes. Because depression could affect medication nonadherence, resulting in out-of-range immunosuppressant levels, we examined the relationship between posttransplant depression, immunosuppressant medication trough level variability, indexed by out-of-range values on clinical outcomes and coefficient of variability, and clinical outcomes. METHOD A consecutive series of 236 lung transplant recipients completed the Center for Epidemiological Studies-Depression two-month posttransplant. Immunosuppressant trough levels (i.e., tacrolimus or cyclosporine) within the range of individualized immunosuppressant targets were obtained at three-, six-, nine-month follow-up clinic visits. Clinical outcomes including hospitalizations and mortality were obtained from medical records. RESULTS Fourteen percent of patients were classified as depressed (Center for Epidemiological Studies-Depression ≥16), 144 (61%) of patients had at least 25% out-of-range immunosuppressant values, and the average coefficient of variability was 36%. Over a median of 2.6 years (interquartile range = 1.2), 32 participants died (14%) and 144 (61%) had at least one unplanned, transplant-related hospitalization. Both depression (hazard ratio = 1.45 (1.19, 1.76), p < . 01) and immunosuppressant variation (immunosuppressant out-of-range: hazard ratio = 1.41 (1.10, 1.81), p < .01) independently predicted more frequent hospitalizations and higher mortality. CONCLUSIONS Early posttransplant depression was associated with significantly worse clinical outcomes. While immunosuppressant level variability is also related to adverse outcomes, such variability does not account for increased risk observed with depression.
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Affiliation(s)
- Michael C Chu
- Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA
| | - Patrick J Smith
- Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA
| | - John M Reynolds
- Department of Medicine, Duke University Medical Center, Durham, NC, USA
| | - Scott M Palmer
- Department of Medicine, Duke University Medical Center, Durham, NC, USA
| | - Laurie D Snyder
- Department of Medicine, Duke University Medical Center, Durham, NC, USA
| | - Alice L Gray
- Department of Medicine, Duke University Medical Center, Durham, NC, USA
| | - James A Blumenthal
- Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA
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Ribaut J, Leppla L, Teynor A, Valenta S, Dobbels F, Zullig LL, De Geest S. Theory-driven development of a medication adherence intervention delivered by eHealth and transplant team in allogeneic stem cell transplantation: the SMILe implementation science project. BMC Health Serv Res 2020; 20:827. [PMID: 32878623 PMCID: PMC7465386 DOI: 10.1186/s12913-020-05636-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Accepted: 08/09/2020] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND Medication adherence to immunosuppressants in allogeneic stem cell transplantation (alloSCT) is essential to achieve favorable clinical outcomes (e.g. control of Graft-versus-Host Disease). Over 600 apps supporting medication adherence exist, yet they lack successful implementation and sustainable use likely because of lack of end-user involvement and theoretical underpinnings in their development and insufficient attention to implementation methods to support their use in real-life settings. Medication adherence has three phases: initiation, implementation and persistence. We report the theory-driven development of an intervention module to support medication adherence (implementation and persistence phase) in alloSCT outpatients as a first step for future digitization and implementation in clinical setting within the SMILe project (Development, implementation and testing of an integrated care model in allogeneic SteM cell transplantatIon faciLitated by eHealth). METHODS We applied Michie's Behavior Change Wheel (BCW) and the Capability-Opportunity-Motivation and Behavior (COM-B) model using three suggested stages followed by one stage added by our team regarding preparation for digitization of the intervention: (I) Defining the problem in behavioral terms; (II) Identifying intervention options; (III) Identifying content and implementation options; (IV) SMILe Care Model Prototype Development. Scientific evidence, data from a contextual analysis and patients'/caregivers' and clinical experts' inputs were compiled to work through these steps. RESULTS (I) Correct immunosuppressant taking and timing were defined as target behaviors. The intervention's focus was determined within the COM-B dimensions Capability (lack of knowledge, lack of routine), Opportunity (lack of cues, interruptions in daily routine) and Motivation (lack of problem solving, trivialization). (II) Five intervention functions were chosen, i.e. education, training, modelling, persuasion and enablement. (III) Twenty-four behavior change techniques were selected, e.g., goal setting, action planning and problem solving. (IV) Finally, seventeen user stories were developed to guide the SMILeApp's software development process. CONCLUSION Our example on the theory-driven development of an intervention module in alloSCT delivered by eHealth and transplant team using a rigorous 3 + 1-stage approach based on BCW, COM-B and agile software development techniques, can be used as methodological guidance for other eHealth intervention developers. Our approach has the potential to enhance successful implementation and sustained use of eHealth solutions in real-life settings.
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Affiliation(s)
- Janette Ribaut
- Department Public Health, Faculty of Medicine, Institute of Nursing Science, University of Basel, Bernoullistrasse 28, 4056, Basel, Switzerland.,Department of Hematology, University Hospital of Basel, 4031, Basel, Switzerland
| | - Lynn Leppla
- Department Public Health, Faculty of Medicine, Institute of Nursing Science, University of Basel, Bernoullistrasse 28, 4056, Basel, Switzerland.,Departments of Hematology, Oncology and Stem Cell Transplantation, University Medical Center Freiburg, 79110, Freiburg im Breisgau, Germany
| | - Alexandra Teynor
- Department of Computer Science, University of Applied Sciences, Augsburg, Germany
| | - Sabine Valenta
- Department Public Health, Faculty of Medicine, Institute of Nursing Science, University of Basel, Bernoullistrasse 28, 4056, Basel, Switzerland.,Department of Hematology, University Hospital of Basel, 4031, Basel, Switzerland
| | - Fabienne Dobbels
- Department Public Health, Faculty of Medicine, Institute of Nursing Science, University of Basel, Bernoullistrasse 28, 4056, Basel, Switzerland.,Academic Center for Nursing and Midwifery, Department of Public Health and Primary Care, University of Leuven, 3000, Leuven, Belgium
| | - Leah L Zullig
- Department of Population Health Science, Duke University, Durham, NC, USA.,Center of Innovation to Accelerate Discovery and Practice Transformation (ADAPT), Durham Veterans Affairs Health Care System, Durham, NC, USA
| | - Sabina De Geest
- Department Public Health, Faculty of Medicine, Institute of Nursing Science, University of Basel, Bernoullistrasse 28, 4056, Basel, Switzerland. .,Academic Center for Nursing and Midwifery, Department of Public Health and Primary Care, University of Leuven, 3000, Leuven, Belgium.
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25
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Beck DK, Tielen M, Rechards M, Timman R, Boonstra C, Versteegh J, van de Wetering J, Zietse R, van Gelder T, Weimar W, van Saase J, van Busschbach J, Massey EK. Comparison of a home-based (multi) systemic intervention to promoting Medication AdheRence and Self-management among kidney transplant recipients with care-as-usual: the MARS randomized controlled trial protocol. BMC Nephrol 2020; 21:374. [PMID: 32859157 PMCID: PMC7453377 DOI: 10.1186/s12882-020-02008-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Accepted: 08/03/2020] [Indexed: 11/10/2022] Open
Abstract
Background After kidney transplantation non-adherence and inadequate self-management undermine clinical outcomes and quality of life. Both have been demonstrated to be substantial in all age groups. However, interventions promoting adherence and self-management among kidney transplant recipients that have proven to be effective are scarce. In this study we aim to develop and test an intervention to optimize adherence and self-management. In this article we describe the background and design of the trial entitled ‘promoting Medication AdheRence and Self-management among kidney transplant recipients’ (MARS-trial)’. Methods/design This is a single-center, parallel arm randomized controlled trial. Nonadherent kidney transplant recipients aged 12 years or older are eligible for inclusion. Patients will be randomly assigned to either the experimental or a control group. The control group will receive care-as-usual. The experimental group will receive care-as-usual plus the MARS-intervention. The MARS-intervention is an outreaching intervention, based on the principles of (multi) systemic therapy which means involving the social network. A standardized intervention protocol is used for consistency but we will tailor the behavior change techniques used to the specific needs and determinants of each patient. The primary outcome of medication adherence will be measured using electronic monitoring. Secondary outcome measures regarding medication adherence and self-management are also assessed. Data is collected at baseline (T0), after a run-in period (T1), at six months post-baseline/end of treatment (T2) and after a six month follow-up period (T3). Discussion We combined elements of (multi) systemic therapy and evidence-based behavior change techniques to create an outreaching and highly individualized intervention. In this trial we will investigate the impact on medication adherence and self-management after kidney transplantation. Trial registration Netherlands Trial Register,trial number NTR7462. Registered 7th September 2018, https://www.trialregister.nl/trial/7264
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Affiliation(s)
- Denise Karin Beck
- Department of Internal Medicine - Section Nephrology & Transplantation, Erasmus Medical Center, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015, Rotterdam, GD, Netherlands.
| | - Mirjam Tielen
- Department of Internal Medicine - Section Nephrology & Transplantation, Erasmus Medical Center, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015, Rotterdam, GD, Netherlands
| | - Marloes Rechards
- Department of Internal Medicine - Section Nephrology & Transplantation, Erasmus Medical Center, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015, Rotterdam, GD, Netherlands
| | - Reinier Timman
- Department of Medical Psychology and Psychotherapy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
| | - Charlotte Boonstra
- Department of Medical Psychology and Psychotherapy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
| | - Josette Versteegh
- Department of Pediatric Nephrology, Erasmus MC - Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, Netherlands
| | - Jacqueline van de Wetering
- Department of Internal Medicine - Section Nephrology & Transplantation, Erasmus Medical Center, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015, Rotterdam, GD, Netherlands
| | - Robert Zietse
- Department of Internal Medicine - Section Nephrology & Transplantation, Erasmus Medical Center, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015, Rotterdam, GD, Netherlands
| | - Teun van Gelder
- Department of Internal Medicine - Section Nephrology & Transplantation, Erasmus Medical Center, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015, Rotterdam, GD, Netherlands
| | - Willem Weimar
- Department of Internal Medicine - Section Nephrology & Transplantation, Erasmus Medical Center, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015, Rotterdam, GD, Netherlands
| | - Jan van Saase
- Department of Internal Medicine - Section Nephrology & Transplantation, Erasmus Medical Center, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015, Rotterdam, GD, Netherlands
| | - Jan van Busschbach
- Department of Medical Psychology and Psychotherapy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
| | - Emma Kay Massey
- Department of Internal Medicine - Section Nephrology & Transplantation, Erasmus Medical Center, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015, Rotterdam, GD, Netherlands
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26
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Belaiche S, Décaudin B, Caron A, Depas N, Vignaux C, Vigouroux S, Coiteux V, Magro L, Sirvent A, Huynh A, Turlure P, Farge D, Lioure B, Bruno B, De Berranger E, Maillard N, Bourhis JH, Bay JO, Bulabois CE, Ceballos P, Fegueux N, Hicheri Y, Vincent L, Rialland F, Gandemer V, Taque S, Cornillon J, Contentin N, Galambrun C, Plantaz D, Odou P, Yakoub-Agha I. Medication non-adherence after allogeneic hematopoietic cell transplantation in adult and pediatric recipients: a cross sectional study conducted by the Francophone Society of Bone Marrow Transplantation and Cellular Therapy. Fundam Clin Pharmacol 2020; 35:435-445. [PMID: 32740936 DOI: 10.1111/fcp.12593] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 06/09/2020] [Accepted: 07/27/2020] [Indexed: 12/14/2022]
Abstract
Medication non-adherence (NA) after allogeneic hematopoietic cell transplantation (allo-HCT) can lead to serious complications. This study assesses NA in French adult and pediatric recipients and identifies factors associated with NA. In accordance with the EMERGE and STROBE guidelines, a cross sectional multicentric survey was conducted. We used a self-reported questionnaire that was adapted to adults and pediatrics and that could provide a picture of all three phases of medication adherence: initiation, implementation, persistence. We enrolled 242 patients, 203 adults (mean age: 51 years old, 50.7% male) and 39 children (mean age: 9 years old, 56.4% female). Reported NA was estimated at about 75% in both populations, adults and pediatrics. In adults, the univariate analysis showed that patients less than 50 years old (P = 0.041), (i) treated with cyclosporine (P = 0.02), (ii) treated with valacyclovir/acyclovir (P = 0.016), and (iii) experiencing side effects (P = 0.009), were significantly more non-adherent. In multivariate analysis, only recipient age was significantly associated to NA (P = 0.05). The limited size of the pediatric population did not allow us to draw any statistical conclusion about this population. To the best of our knowledge, this is the first study in France on NA in allo-HCT recipients. Our results highlight the age factor as the only factor related to NA. Further studies are needed to confirm our observations and refine results in pediatric populations, currently most at risk of medication NA.
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Affiliation(s)
| | | | - Alexandre Caron
- EA 2694 - Santé publique: épidémiologie et qualité des soins, CHU Lille, Univ. Lille, Lille, F-59000, France
| | - Nicolas Depas
- EA 2694 - Santé publique: épidémiologie et qualité des soins, CHU Lille, Univ. Lille, Lille, F-59000, France
| | - Claire Vignaux
- Service Hématologie Adulte, CHU Bordeaux, Bordeaux Cedex, F-33076, France
| | - Stephane Vigouroux
- Service Hématologie Adulte, CHU Bordeaux, Bordeaux Cedex, F-33076, France
| | | | | | - Anne Sirvent
- Service Hématologie Pédiatrique, CHU Montpellier, Montpellier, F-34090, France
| | - Anne Huynh
- Institut Universitaire du Cancer Toulouse - Oncopole, Toulouse Cedex 9, F-31059, France
| | - Pascal Turlure
- Service Hématologie Adulte, CHU Dupuytren, Limoges Cedex, F-87042, France
| | - Dominique Farge
- Service Hématologie Adulte, APHP- Hopital Saint Louis, Paris, F-75010, France
| | - Bruno Lioure
- Service Hématologie Adulte, Hopital de Hautepierre, CHU de Strasbourg, Strasbourg, F-67200, France
| | - Bénédicte Bruno
- Service Hématologie Pédiatrique, CHU Lille, Lille, F-59000, France
| | - Eva De Berranger
- Service Hématologie Pédiatrique, CHU Lille, Lille, F-59000, France
| | - Natacha Maillard
- Service Hématologie Adulte, CHU Poitier, Poitier, F-86000, France
| | - Jean-Henri Bourhis
- Service Hématologie Adulte, Institut Gustave Roussy, Villejuif Cedex, F-94805, France
| | | | | | - Patrice Ceballos
- Service Hématologie Adulte, CHU Montpellier, Montpellier, F-34090, France
| | - Nathalie Fegueux
- Service Hématologie Adulte, CHU Montpellier, Montpellier, F-34090, France
| | - Yosr Hicheri
- Service Hématologie Adulte, CHU Montpellier, Montpellier, F-34090, France
| | - Laure Vincent
- Service Hématologie Adulte, CHU Montpellier, Montpellier, F-34090, France
| | - Fanny Rialland
- Service Hématologie Pédiatrique, CHU Nantes, Nantes, F-44000, France
| | - Virginie Gandemer
- Service Hématologie Pédiatrique, CHU Rennes, Rennes Cedex 9, F-35033, France
| | - Sophie Taque
- Service Hématologie Pédiatrique, CHU Rennes, Rennes Cedex 9, F-35033, France
| | - Jérôme Cornillon
- Service Hématologie Adulte, Institut de Cancérologie Lucien Neuwirth, Saint Etienne, F-42000, France
| | - Nathalie Contentin
- Service Hématologie Adulte, Centre Henri Becquerel, Rouen Cedex, F 76038, France
| | - Claire Galambrun
- Service Hématologie Pédiatrique, APHM Hopital La Timone, Marseille, F-13005, France
| | - Dominique Plantaz
- Service Hématologie Pédiatrique, CHU Grenoble, La Tronche, F-38700, France
| | - Pascal Odou
- Institut de Pharmacie, CHU Lille, Lille, F-59000, France
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Pankhurst T, Evison F, Mytton J, Williamson S, Kerecuk L, Lipkin G. Young adults have worse kidney transplant outcomes than other age groups. Nephrol Dial Transplant 2020; 35:1043-1051. [PMID: 32459843 DOI: 10.1093/ndt/gfaa059] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Accepted: 02/21/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The objective of this study was to establish if renal transplant outcomes (graft and patient survival) for young adults in England were worse than for other age groups. METHODS Outcomes for all renal transplant recipients in England (n = 26 874) were collected from Hospital Episode Statistics and the Office for National Statistics databases over 12 years. Graft and patient outcomes, follow-up and admissions were studied for all patients, stratified by age bands. RESULTS Young adults (14-23 years) had substantially greater likelihood [hazard ratio (HR) = 1.26, 95% confidence interval (CI) 1.10-1.19; P < 0.001] of kidney transplant failure than any other age band. They had a higher non-attendance rate for clinic appointments (1.6 versus 1.2/year; P < 0.001) and more emergency admissions post-transplantation (25% of young adults on average are admitted each year, compared with 15-20% of 34- to 43-year olds). Taking into account deprivation, ethnicity, transplant type and transplant centre, in the 14- to 23-year group, return to dialysis remained significantly worse than all other age bands (HR = 1.41, 95% CI 1.26-1.57). For the whole cohort, increasing deprivation related to poorer outcomes and black ethnicity was associated with poorer outcomes. However, neither ethnicity nor deprivation was over-represented in the young adult cohort. CONCLUSIONS Young adults who receive a kidney transplant have a significant increased likelihood of a return to dialysis in the first 10 years post-transplant when compared with those aged 34-43 years in multivariable analysis.
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Affiliation(s)
- Tanya Pankhurst
- Department of Nephrology, University Hospitals Birmingham, Birmingham, UK
| | - Felicity Evison
- Department of Nephrology, University Hospitals Birmingham, Birmingham, UK
| | - Jemma Mytton
- Department of Nephrology, University Hospitals Birmingham, Birmingham, UK
| | | | - Larissa Kerecuk
- Department of Nephrology, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
| | - Graham Lipkin
- Department of Nephrology, University Hospitals Birmingham, Birmingham, UK
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Taber DJ, Posadas‐Salas A, Su Z, Rao V, Rohan V, Nadig S, McGillicuddy JW, Dubay D, Fleming JN. Preliminary assessment of safety and adherence to a once‐daily immunosuppression regimen in kidney transplantation: Results of a randomized controlled pilot study. Clin Transplant 2020; 34:e13844. [DOI: 10.1111/ctr.13844] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 02/13/2020] [Accepted: 02/21/2020] [Indexed: 11/28/2022]
Affiliation(s)
- David J. Taber
- Division of Transplant Surgery College of Medicine Medical University of South Carolina Charleston SC USA
| | - Aurora Posadas‐Salas
- Division of Transplant Nephrology College of Medicine Medical University of South Carolina Charleston SC USA
| | - Zemin Su
- Division of General Internal Medicine College of Medicine Medical University of South Carolina Charleston SC USA
| | - Vinaya Rao
- Division of Transplant Nephrology College of Medicine Medical University of South Carolina Charleston SC USA
| | - Vinayak Rohan
- Division of Transplant Surgery College of Medicine Medical University of South Carolina Charleston SC USA
| | - Satish Nadig
- Division of Transplant Surgery College of Medicine Medical University of South Carolina Charleston SC USA
| | - John W. McGillicuddy
- Division of Transplant Surgery College of Medicine Medical University of South Carolina Charleston SC USA
| | - Derek Dubay
- Division of Transplant Surgery College of Medicine Medical University of South Carolina Charleston SC USA
| | - James N. Fleming
- Department of Pharmacy Services Medical University of South Carolina Charleston SC USA
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29
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Manzia TM, Angelico R, Gazia C, Lenci I, Milana M, Ademoyero OT, Pedini D, Toti L, Spada M, Tisone G, Baiocchi L. De novo malignancies after liver transplantation: The effect of immunosuppression-personal data and review of literature. World J Gastroenterol 2019; 25:5356-5375. [PMID: 31558879 PMCID: PMC6761240 DOI: 10.3748/wjg.v25.i35.5356] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Revised: 08/08/2019] [Accepted: 08/24/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Immunosuppression has undoubtedly raised the overall positive outcomes in the post-operative management of solid organ transplantation. However, long-term exposure to immunosuppression is associated with critical systemic morbidities. De novo malignancies following orthotopic liver transplants (OLTs) are a serious threat in pediatric and adult transplant individuals. Data from different experiences were reported and compared to assess the connection between immunosuppression and de novo malignancies in liver transplant patients. AIM To study the role of immunosuppression on the incidence of de novo malignancies in liver transplant recipients. METHODS A systematic literature examination about de novo malignancies and immunosuppression weaning in adult and pediatric OLT recipients was described in the present review. Worldwide data were collected from highly qualified institutions performing OLTs. Patient follow-up, immunosuppression discontinuation and incidence of de novo malignancies were reported. Likewise, the review assesses the differences in adult and pediatric recipients by describing the adopted immunosuppression regimens and the different type of diagnosed solid and blood malignancy. RESULTS Emerging evidence suggests that the liver is an immunologically privileged organ able to support immunosuppression discontinuation in carefully selected recipients. Malignancies are often detected in liver transplant patients undergoing daily immunosuppression regimens. Post-transplant lymphoproliferative diseases and skin tumors are the most detected de novo malignancies in the pediatric and adult OLT population, respectively. To date, immunosuppression withdrawal has been achieved in up to 40% and 60% of well-selected adult and pediatric recipients, respectively. In both populations, a clear benefit of immunosuppression weaning protocols on de novo malignancies is difficult to ascertain because data have not been specified in most of the clinical experiences. CONCLUSION The selected populations of tolerant pediatric and adult liver transplant recipients greatly benefit from immunosuppression weaning. There is still no strong clinical evidence on the usefulness of immunosuppression withdrawal in OLT recipients on malignancies. An interesting focus is represented by the complete reconstitution of the immunological pathways that could help in decreasing the incidence of de novo malignancies and may also help in treating liver transplant patients suffering from cancer.
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Affiliation(s)
- Tommaso Maria Manzia
- HPB and Transplant Unit, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
| | - Roberta Angelico
- Division of Abdominal Transplantation and HPB Surgery, Bambino Gesù Children's Hospital IRCCS, Rome 00165, Italy
| | - Carlo Gazia
- HPB and Transplant Unit, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
- Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC 27101, United States
| | - Ilaria Lenci
- Hepatology and Liver Transplant Unit, University of Tor Vergata, Rome 00133, Italy
| | - Martina Milana
- Hepatology and Liver Transplant Unit, University of Tor Vergata, Rome 00133, Italy
| | | | - Domiziana Pedini
- Division of Abdominal Transplantation and HPB Surgery, Bambino Gesù Children's Hospital IRCCS, Rome 00165, Italy
| | - Luca Toti
- HPB and Transplant Unit, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
| | - Marco Spada
- Division of Abdominal Transplantation and HPB Surgery, Bambino Gesù Children's Hospital IRCCS, Rome 00165, Italy
| | - Giuseppe Tisone
- HPB and Transplant Unit, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
| | - Leonardo Baiocchi
- Hepatology and Liver Transplant Unit, University of Tor Vergata, Rome 00133, Italy
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30
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Gokoel SRM, Gombert-Handoko KB, Zwart TC, van der Boog PJM, Moes DJAR, de Fijter JW. Medication non-adherence after kidney transplantation: A critical appraisal and systematic review. Transplant Rev (Orlando) 2019; 34:100511. [PMID: 31627978 DOI: 10.1016/j.trre.2019.100511] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2019] [Revised: 08/27/2019] [Accepted: 08/28/2019] [Indexed: 10/26/2022]
Abstract
Medication non-adherence is one of the most important causes for shortened graft survival subsequently leading to a reduction in kidney graft survival results. Our aim was to provide an overview of its prevalence, risk factors, diagnostic methods and interventions to improve adherence in kidney transplant recipients. Therefore, we systematically searched the databases PubMed, COCHRANE Library, Web of Science and EMBASE for studies addressing "medication adherence", "compliance", "adherence", "kidney transplantation" and "life style factors". We identified 96 studies that satisfied our inclusion criteria. A problematic lack of a uniformly accepted definition for non-adherence was found, consequently leading to a wide range in non-adherence prevalence (36-55%). Using one uniformly accepted non-adherence definition should therefore be encouraged. A wide range in diagnostic methods makes it difficult to accurately detect non-adherence. Heterogeneous results of intervention studies make it difficult to select the best adherence enhancing method, challenging the battle against medication non-adherence. Literature suggests a combination of personalized interventions, based on patient-specific non-adherent behavior, to be most successful in improvement of adherence. High quality diagnostic methods and multidisciplinary, personalized interventions with focus on relevant clinical outcome are essential in overcoming medication non-adherence in kidney transplant recipients.
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Affiliation(s)
- Sumit R M Gokoel
- Division of Nephrology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands.
| | - Kim B Gombert-Handoko
- Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, the Netherlands
| | - Tom C Zwart
- Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, the Netherlands
| | - Paul J M van der Boog
- Division of Nephrology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands
| | - Dirk Jan A R Moes
- Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, the Netherlands
| | - Johan W de Fijter
- Division of Nephrology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands
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31
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Dumortier J, Duvoux C, Dubel L, Bazin F, Houssel-Debry P. A Multicenter, Prospective, Observational Study of Conversion from Twice-Daily Immediate-Release to Once-Daily Prolonged-Release Tacrolimus in Liver Transplant Recipients in France: The COBALT Study. Ann Transplant 2019; 24:506-516. [PMID: 31451681 PMCID: PMC6728630 DOI: 10.12659/aot.916041] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Background In adult liver transplant patients, the use of prolonged-release tacrolimus may have treatment adherence benefits over the immediate-release formulation. The aim of this study was to characterise real-world practice data on conversion of liver transplant recipients from immediate- to prolonged-release tacrolimus in France. Material/Methods A prospective, observational study (NCT02143479) was conducted in 18 transplant centers in France between June 2014 and March 2016. Liver transplant recipients (n=398) included patients who changed from immediate-release to prolonged-release tacrolimus within the first three months (early conversion group) (n=205) or between three and 12 months after transplantation (late conversion group) (n=184). Clinical data were collected at an initial baseline outpatient visit and six-month and 12-month follow-up visits. Endpoints included the dose conversion ratio from immediate-release to prolonged-release tacrolimus, number of and reasons for additional visits due to conversion, safety, and tolerability. Results Baseline clinical and demographic characteristics were similar between the two cohorts. The mean ±SD ratio of conversion of tacrolimus dose was 1.04±0.28; 1.01±0.28 (early) and 1.08±0.28 (late) (p=0.0247). The mean ±SD time from conversion to the first tacrolimus trough blood concentration was 30.8±42.8 days; 24.8±45.4 days (early) and 37.5±38.7 days (late). Only one patient required an additional visit due to conversion. Reasons for conversion included the physician’s preference (56.3%), center practice (38.6%), and the dosing frequency (36.0%). Conversion was associated with a low rate of graft rejection, and no new safety issues were reported. Conclusions Conversion of liver transplant recipients from immediate-release to prolonged-release tacrolimus within three to 12 months of transplantation was easy to manage and associated with favorable clinical outcomes and safety profiles.
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Affiliation(s)
- Jérôme Dumortier
- Departement of Hepatology, Edouard Herriot Hospital, Lyon, France
| | - Christophe Duvoux
- Department of Hepatology, Henri Mondor Hospital APHP, Paris Est University UPEC, Créteil, France
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32
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Manickavasagar R, Wong G, Alexander SI, Francis A, Prestidge C, Larkins NG, Le Page A, Lim WH. Allograft outcome following repeat transplantation of patients with non-adherence-related first kidney allograft failure: a population cohort study. Transpl Int 2019; 32:1247-1258. [PMID: 31408545 DOI: 10.1111/tri.13492] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 03/11/2019] [Accepted: 08/08/2019] [Indexed: 11/30/2022]
Abstract
Nonadherence is an important risk factor for premature allograft failure after kidney transplantation, but outcomes after re-transplantation remain uncertain. Using data from the Australian and New Zealand Dialysis and Transplant registry, the associations between causes of first allograft failure and acute rejection-related and non-adherence-related allograft failure following re-transplantation were examined using competing risk analyses, treating the respective alternative causes of allograft failure and death with functioning graft as competing events. Fifty-nine of 2450 patients (2%) lost their first allografts from nonadherence. Patients who lost their first kidney allograft from nonadherence were younger at the time of first kidney allograft failure but waited longer for a second allograft (>5 years: 54% vs. 20%, P < 0.001) compared with other causes. Compared with patients who lost their first allograft from causes other than nonadherence, the adjusted subdistribution hazard ratio (HR and 95% CI) for acute rejection-related second allograft failure was 0.58 (0.08, 4.07; P = 0.582) for patients with allograft failure attributed to nonadherence and was 6.30 (1.34, 29.67; P = 0.020) for non-adherence-related second allograft failure. In this cohort of transplant recipients who have received second allografts, first allograft failure secondary to nonadherence was associated with a marginally greater risk of allograft failure attributed to nonadherence in subsequent transplantation.
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Affiliation(s)
| | - Germaine Wong
- Centre for Transplant and Renal Research, Westmead Hospital, Sydney, NSW, Australia.,Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, NSW, Australia.,University of Sydney, Sydney, NSW, Australia
| | - Stephen I Alexander
- Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, NSW, Australia.,University of Sydney, Sydney, NSW, Australia
| | - Anna Francis
- Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, NSW, Australia.,University of Sydney, Sydney, NSW, Australia
| | | | - Nicholas G Larkins
- Perth Children's Hospital, Perth, WA, Australia.,School of Paediatrics and Child Health, Telethon Kids Institute, University of Western Australia, Perth, WA, Australia
| | - Amelia Le Page
- Department of Nephrology, Monash Children's Hospital, Melbourne, Vic., Australia.,Department of Paediatrics, School of Clinical Sciences, Monash University, Melbourne, Vic., Australia
| | - Wai H Lim
- Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia.,School of Medicine, University of Western Australia, Perth, WA, Australia
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Abstract
Advancement in kidney transplantation has led to prolonged survival in our population with kidney disease. Newer agents of immunosuppression have made this possible with less rejections and lesser opportunistic infections and transplant related deaths. Preventative care like timely vaccines, cancer screenings, aggressive blood pressure, blood sugar, lipid control, timely referral to consultants is required in these patient population to provide quality care and to prolong their survival. Primary care physicians are the best advocate for our transplant populations. To care for these complex transplant patients, it is vital for primary care physicians to be familiar with the overall approach on our patients.
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Affiliation(s)
- Kavitha Ramaswamy
- Thomas Jefferson University Hospital, Division of Nephrology, 833 Chestnut St, Suite 700, Philadelphia, PA 19107, USA.
| | - Hector M Madariaga
- Good Samaritan Medical Center, Department of Medicine, 235N Pearl St, Brockton, MA 02301, USA
| | - Beje S Thomas
- Georgetown University Medical Center, MedStar Georgetown Transplant Institute, 3800 Reservoir Road, Washington, DC 20007 USA
| | - Edgar V Lerma
- University of Illinois at Chicago College of Medicine/ Advocate Christ Medical Center, Oak Lawn, IL, USA
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34
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Chen G, Bell CS, Loughhead P, Ibeche B, Bynon JS, Hall DR, De Golovine A, Edwards A, Dar WA. Exploration of the Stanford Integrated Psychosocial Assessment for Transplantation With Psychosocial and Medical Outcomes in Kidney and Kidney–Pancreas Transplant Recipients. Prog Transplant 2019; 29:230-238. [DOI: 10.1177/1526924819854480] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Introduction: The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a psychometric instrument designed to assess patient risk for transplant. We investigated the association between SIPAT scores and demographic data with psychosocial and medical outcomes within a diverse kidney/kidney–pancreas transplant population. Design: The SIPAT was administered to all pretransplant candidates. A retrospective review of transplanted patients who had at least 6 months of follow-up was completed. Results: The sample included 136 patients: male (n = 77 [57%]) with a mean age of 47 years old. Thirty-eight percent were black (n = 51), 55% had less than a high school education (n = 74), and 65% had low socioeconomic status (n = 89). Statistical difference was found among SIPAT scores and substance use and support system instability ( P = .035, P = .012). Females ( P = .012) and patients with a history of psychopathology ( P = .002) developed or had a relapse of psychopathology following transplant. Patients with more than a high school education ( P = .025) and who were less than 30 years ( P = .026) had higher rejection incidence rates. Risk factors for rehospitalizations included Hispanic race, diabetes, and low socioeconomic status ( P = .036, P = .038, P = .014). African American/Black and male patients had higher incidence of infection events ( P = .032, P = .049). Mortality and treatment nonadherence were not significantly associated with SIPAT scores or demographic variables. Conclusion: The SIPAT was associated with posttransplant substance use and support system instability, while demographic variables were associated with the development and/or relapse of psychopathology, graft loss, rejection, infection events, and medical rehospitalizations. Revision of the SIPAT to include additional demographic components may lend to improved prediction of transplant outcomes.
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Affiliation(s)
- Gloria Chen
- Transplant Center, Memorial Hermann Hospital, Houston, TX, USA
| | - Cynthia S. Bell
- Department of Pediatric Nephrology and Hypertension, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
| | | | - Bashar Ibeche
- Department of Surgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - John S. Bynon
- Department of Surgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - David R. Hall
- Department of Surgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Aleksandra De Golovine
- Department of Internal Medicine, Renal Diseases and Hypertension, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Angelina Edwards
- Department of Internal Medicine, Renal Diseases and Hypertension, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Wasim A. Dar
- Department of Surgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
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35
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von Moos S, Schalk G, Mueller TF, Laube G. Age-associated decrease in de novo donor-specific antibodies in renal transplant recipients reflects changing humoral immunity. IMMUNITY & AGEING 2019; 16:9. [PMID: 31168309 PMCID: PMC6509825 DOI: 10.1186/s12979-019-0149-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2018] [Accepted: 04/25/2019] [Indexed: 01/09/2023]
Abstract
Background Older age at organ transplantation is associated with increased risk of infection and malignancy but reduced risk of cellular rejection. De novo donor-specific anti-HLA antibodies (dnDSA), are key biomarkers associated with reduced long-term allograft survival, yet there is a lack of data focusing on age-associated changes. Methods Development of dnDSA was restrospectively analyzed in all subjects who received a kidney transplant at the University Hospital Zurich between 01/2006 and 02/2015. Follow up continued until 03/2016. The incidence of dnDSA in different age categories was compared with special focus on the extremes of age: children < 10 years (n = 19) and adults ≥60 years of age (n = 110). Results Incidence of dnDSA gradually decreased with age, with older recipients having a significantly lower risk (HR 0.21, p = 0.0224) compared to pediatric recipients. Cumulative incidence of dnDSA at 2, 5 and 10 years was 6.2, 9.1 and 36% in the older recipients versus 5.3, 29.5 and 47.1% in pediatric recipients. Median time to development of dnDSA was similar (older 720 days, min 356, max 3646 days; children 1086 days, min 42, max 2474 days). Annual incidence was highest within the first two years after transplantation in the older recipients and peaked in years two to four in pediatric recipients. DnDSA were predominantly class II. More dnDSA were observed with cyclosporine as compared to tacrolimus. Conclusion Older kidney transplant recipients have a lower risk of developing dnDSA than pediatric recipients, pointing towards reduced humoral immune reactivity with increasing age. This observation raises the question of adjustment in immunosuppression.
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Affiliation(s)
- Seraina von Moos
- 1Department of Nephrology, University of Zurich and University Hospital Zurich, Rämistrasse 100, 8091 Zürich, Switzerland
| | - Gesa Schalk
- 2Department of Nephrology, University of Zurich and University Children's Hospital, Steinwiesstrasse 75, 8032 Zurich, Switzerland
| | - Thomas F Mueller
- 1Department of Nephrology, University of Zurich and University Hospital Zurich, Rämistrasse 100, 8091 Zürich, Switzerland
| | - Guido Laube
- 2Department of Nephrology, University of Zurich and University Children's Hospital, Steinwiesstrasse 75, 8032 Zurich, Switzerland
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36
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Mac QD, Mathews DV, Kahla JA, Stoffers CM, Delmas OM, Holt BA, Adams AB, Kwong GA. Non-invasive early detection of acute transplant rejection via nanosensors of granzyme B activity. Nat Biomed Eng 2019; 3:281-291. [PMID: 30952979 PMCID: PMC6452901 DOI: 10.1038/s41551-019-0358-7] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Accepted: 01/16/2019] [Indexed: 12/14/2022]
Abstract
The early detection of the onset of transplant rejection is critical for the long-term survival of patients. The diagnostic gold standard for detecting transplant rejection involves a core biopsy, which is invasive, has limited predictive power and carries a morbidity risk. Here, we show that nanoparticles conjugated with a peptide substrate specific for the serine protease granzyme B, which is produced by recipient T cells during the onset of acute cellular rejection, can serve as a non-invasive biomarker of early rejection. When administered systemically in mouse models of skin graft rejection, these nanosensors preferentially accumulate in allograft tissue, where they are cleaved by granzyme B, releasing a fluorescent reporter that filters into the recipient's urine. Urinalysis then discriminates the onset of rejection with high sensitivity and specificity before features of rejection are apparent in grafted tissues. Moreover, in mice treated with subtherapeutic levels of immunosuppressive drugs, the reporter signals in urine can be detected before graft failure. This method may enable routine monitoring of allograft status without the need for biopsies.
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Affiliation(s)
- Quoc D Mac
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech College of Engineering and Emory School of Medicine, Atlanta, GA, USA
| | - Dave V Mathews
- Emory Transplant Center, Emory University, Atlanta, GA, USA
| | - Justin A Kahla
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech College of Engineering and Emory School of Medicine, Atlanta, GA, USA
| | - Claire M Stoffers
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech College of Engineering and Emory School of Medicine, Atlanta, GA, USA
| | - Olivia M Delmas
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech College of Engineering and Emory School of Medicine, Atlanta, GA, USA
| | - Brandon Alexander Holt
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech College of Engineering and Emory School of Medicine, Atlanta, GA, USA
| | - Andrew B Adams
- Emory Transplant Center, Emory University, Atlanta, GA, USA.
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.
| | - Gabriel A Kwong
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech College of Engineering and Emory School of Medicine, Atlanta, GA, USA.
- Parker H. Petit Institute of Bioengineering and Bioscience, Atlanta, GA, USA.
- Institute for Electronics and Nanotechnology, Georgia Tech, Atlanta, GA, USA.
- Integrated Cancer Research Center, Georgia Tech, Atlanta, GA, USA.
- The Georgia Immunoengineering Consortium, Emory University and Georgia Tech, Atlanta, GA, USA.
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37
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Seibert SR, Schladt DP, Wu B, Guan W, Dorr C, Remmel RP, Matas AJ, Mannon RB, Israni AK, Oetting WS, Jacobson PA. Tacrolimus trough and dose intra-patient variability and CYP3A5 genotype: Effects on acute rejection and graft failure in European American and African American kidney transplant recipients. Clin Transplant 2018; 32:e13424. [PMID: 30318646 PMCID: PMC6317347 DOI: 10.1111/ctr.13424] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Revised: 09/18/2018] [Accepted: 10/08/2018] [Indexed: 02/01/2023]
Abstract
BACKGROUND Suboptimal immunosuppression after kidney transplantation contributes to toxicity and loss of efficacy. Little is known regarding the impact of intra-patient variability of tacrolimus (TAC) doses and troughs in the early post-transplant period or the influence of genetic variants on variability. METHODS Coefficients of variation (CV) of TAC troughs and doses of 1226 European American (EA) and 246 African American (AA) adult recipients enrolled in DeKAF Genomics were compared for association with acute rejection and graft failure. Additionally, the influence of recipients' number of CYP3A5 loss-of-function alleles was assessed. RESULTS Acute rejection was associated with greater CV of dose in AA (P < 0.001) and EA recipients (P = 0.012). Graft failure was associated with a greater CV of dose (P = 0.022) and trough (P < 0.001) in AA, and higher CV of trough (P = 0.024) in EA recipients. In EA, CYP3A5 loss-of-function alleles were associated with decreased CV of trough (P = 0.0042) and increased CV of dose (P < 0.0001). CONCLUSION CYP3A5 loss-of-function alleles influence intra-patient TAC trough and dose variability. High variability of TAC dose increases risk of acute rejection. High variability of TAC trough increases risk of graft failure. Early clinical recognition of TAC dose and trough variability may improve patient management and outcomes.
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Affiliation(s)
- Stephan R Seibert
- Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota
| | - David P Schladt
- Chronic Disease Research Group, Minneapolis Medical Research Foundation, Hennepin County Medical Center, Minneapolis, Minnesota
| | - Baolin Wu
- Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota
| | - Weihua Guan
- Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota
| | - Casey Dorr
- Minneapolis Medical Research Foundation, Hennepin County Medical Center, Minneapolis, Minnesota
| | - Rory P Remmel
- Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota
| | - Arthur J Matas
- Department of Surgery, University of Minnesota, Minneapolis, Minnesota
| | - Roslyn B Mannon
- Department of Nephrology, University of Alabama, Birmingham, Alabama
| | - Ajay K Israni
- Division of Nephrology, Hennepin County Medical Center, Epidemiology & Community Health, University of Minnesota, Minneapolis, Minnesota
| | - William S Oetting
- Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota
| | - Pamala A Jacobson
- Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota
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38
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Vanhoof JMM, Vandenberghe B, Geerts D, Philippaerts P, De Mazière P, DeVito Dabbs A, De Geest S, Dobbels F. Shedding light on an unknown reality in solid organ transplant patients' self-management: A contextual inquiry study. Clin Transplant 2018; 32:e13314. [PMID: 29897621 DOI: 10.1111/ctr.13314] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/29/2018] [Indexed: 01/28/2023]
Abstract
Traditional quantitative and qualitative research methods inadequately capture the complexity of patients' daily self-management. Contextual inquiry methodology, using home visits, allows a more in-depth understanding of how patients integrate immunosuppressive medication intake, physical activity, and healthy eating in their daily lives, and which difficulties they experience when doing so. This mixed-method study comprised 2 home visits in 19 purposively selected adult heart, lung, liver, and kidney transplant patients, asking them to demonstrate how they implement the aforementioned health behaviors. Meanwhile, conversations were audio-taped and photographs were taken. Audio-visual materials were coded using directed content analysis. Difficulties and supportive strategies were identified via inductive thematic analysis. We learned that few patients understood what "sufficiently active" means. Physical discomforts and poor motivation created variation across activity levels observed. Health benefits of dietary guidelines were insufficiently understood, and their implementation into everyday life considered difficult. Many underestimated the strictness of immunosuppressive medication intake, and instructions on handling late doses were unclear. Interruptions in routine and busyness contributed to nonadherence. We also learned that professionals often recommend supportive strategies, which patients not always like or need. This contextual inquiry study revealed unique insights, providing a basis for patient-tailored self-management interventions.
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Affiliation(s)
- Jasper M M Vanhoof
- Department of Public Health and Primary Care, Academic Centre for Nursing and Midwifery, KU Leuven, Leuven, Belgium
| | - Bert Vandenberghe
- Meaningful Interactions Lab (Mintlab), imec, KU Leuven, Leuven, Belgium
| | - David Geerts
- Meaningful Interactions Lab (Mintlab), imec, KU Leuven, Leuven, Belgium
| | | | | | - Annette DeVito Dabbs
- Department of Acute and Tertiary Care, School of Nursing, University of Pittsburgh, Pittsburgh, PA, USA
| | - Sabina De Geest
- Department of Public Health and Primary Care, Academic Centre for Nursing and Midwifery, KU Leuven, Leuven, Belgium.,Department Public Health, Institute of Nursing Science, University of Basel, Basel, Switzerland
| | - Fabienne Dobbels
- Department of Public Health and Primary Care, Academic Centre for Nursing and Midwifery, KU Leuven, Leuven, Belgium.,Department Public Health, Institute of Nursing Science, University of Basel, Basel, Switzerland
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39
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Sitruk L, Couchoud C, Hourmant M, Tuppin P, Macher MA, Legeai C. [Description of immunosuppressive maintenance treatments post kidney transplant through the National System of Health Insurance]. Nephrol Ther 2018; 14:523-530. [PMID: 29887268 DOI: 10.1016/j.nephro.2018.03.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Revised: 03/02/2018] [Accepted: 03/18/2018] [Indexed: 01/08/2023]
Abstract
The aim of this study was to describe the drug dispensing of maintenance immunosuppression treatment in 2014 for patients who received a kidney transplant in 2012, based on the data of the French national health insurance and to compare those results with the information collected in the national database for kidney recipients. For each patient, are considered all drugs dispensing with their dates of issue, the molecules and their presentations (number of pills and dosage). Among 2463 transplanted adults in 2012, 73% have received tacrolimus monohydrate, 59% mycophenolate mofetil, 54% prednisone and 20% cyclosporin in 2014. The daily doses but not the number of tablets per day declined with age. The most frequent association was tacrolimus monohydrate-mycophenolate mofetil-steroids in 34% of the cases. The use of mTOR inhibitors, rare generally (7%), is more common in patients aged 66-85 years. Associations did not differ significantly according to diabetic status, for patients with a kidney from an elderly donor or according to the number of mismatch. The daily doses estimated from the deliverance in pharmacy are respectively similar, understated and over-estimate for tacrolimus, mycophenolate mofetil and cyclosporin compared to the national database. This study confirms the difficulty of apprehending drug consumption based only on dispensing in pharmacies or punctual recording even if it allows a fairly comprehensive view of French practices.
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Affiliation(s)
- Lola Sitruk
- Agence de la biomédecine, 1, avenue du Stade-de-France, 93212 Saint-Denis-La-Plaine cedex, France
| | - Cécile Couchoud
- Agence de la biomédecine, 1, avenue du Stade-de-France, 93212 Saint-Denis-La-Plaine cedex, France
| | - Maryvonne Hourmant
- Service de néphrologie et d'immunologie clinique, CHU, 30, boulevard Jean-Monnet, immeuble Jean-Monnet, 44093 Nantes cedex 1, France
| | - Philippe Tuppin
- Caisse nationale de l'Assurance maladie des travailleurs salariés, Direction de la stratégie des études et des statistiques, 26-50, avenue du Professeur-André-Lemierre, 75986 Paris cedex 20, France
| | - Marie-Alice Macher
- Agence de la biomédecine, 1, avenue du Stade-de-France, 93212 Saint-Denis-La-Plaine cedex, France
| | - Camille Legeai
- Agence de la biomédecine, 1, avenue du Stade-de-France, 93212 Saint-Denis-La-Plaine cedex, France.
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40
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Stapleton SM, Bababekov YJ, Perez NP, Fong ZV, Hashimoto DA, Lillemoe KD, Watkins MT, Chang DC. Variation in Amputation Risk for Black Patients: Uncovering Potential Sources of Bias and Opportunities for Intervention. J Am Coll Surg 2018; 226:641-649.e1. [DOI: 10.1016/j.jamcollsurg.2017.12.038] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Accepted: 12/19/2017] [Indexed: 10/18/2022]
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41
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Hartono JL, Koh T, Lee GH, Tan PS, Muthiah M, Aw MM, Madhavan K, Kow A, Lim KB. Predictors of Non-adherence to Immunosuppressive Therapy in Asian Liver Transplant Recipients. Transplant Proc 2018; 49:1419-1424. [PMID: 28736016 DOI: 10.1016/j.transproceed.2017.02.049] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Accepted: 02/23/2017] [Indexed: 10/19/2022]
Abstract
BACKGROUND Adherence to immunosuppressive medications has been shown to affect post-transplant outcomes. We aimed to determine the level of adherence to immunosuppressive therapy in liver transplant (LT) recipients and to elucidate factors associated with it, as well as patient preferences on the dosing schedule. METHODS LT recipients were recruited during transplant clinic follow-up. A validated Morisky 8-item questionnaire was completed by patients to assess their adherence to immunosuppressive therapy. Adherence was determined by the sum of the responses to the questionnaire. Low, medium, and high adherence were defined by a Morisky score of >2, 1 to 2, and 0, respectively. Data on the patient's socio-economic and clinical background, dosing schedule of immunosuppressant medications, and patient preferences were included in the questionnaire. RESULTS A total of 107 LT recipients were approached and 75 completed the questionnaire. The majority of patients (48/74, 64.9%) preferred a once-daily medication regimen. The proportion of high adherence was 24/75 (32.0%), medium adherence was 51/75 (42.7%), and low adherence was 19/75 (25.3%). Multivariate analysis showed younger age and post-transplant duration >5 years as independent predictors for low adherence. Among low-adherence patients, 16/19 (84.2%) patients were on a twice-daily regimen, and, of these, 14/16 (87.5%) preferred their medications to be reduced to once daily. CONCLUSIONS A significant proportion (68%) of LT recipients had low to moderate adherence to medications, with younger age and longer post-transplant duration of >5 years as independent predictors. Early identification of at-risk patients is essential to allow implementation of measures to improve adherence. Simplifying medication regimens to once daily is a potential way to improve adherence.
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Affiliation(s)
- J L Hartono
- Yong Yoo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, National University Health System, Singapore
| | - T Koh
- Department of Pharmacy, National University Health System, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - G H Lee
- Yong Yoo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, National University Health System, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - P S Tan
- Yong Yoo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, National University Health System, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - M Muthiah
- Yong Yoo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, National University Health System, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - M M Aw
- Yong Yoo Lin School of Medicine, National University of Singapore, Singapore; Department of Pediatrics, Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore
| | - K Madhavan
- Yong Yoo Lin School of Medicine, National University of Singapore, Singapore; Division of Hepatobiliary and Pancreatic Surgery, National University Health System, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - A Kow
- Yong Yoo Lin School of Medicine, National University of Singapore, Singapore; Division of Hepatobiliary and Pancreatic Surgery, National University Health System, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - K B Lim
- Yong Yoo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, National University Health System, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore.
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42
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Steinberg EA, Moss M, Buchanan CL, Goebel J. Adherence in pediatric kidney transplant recipients: solutions for the system. Pediatr Nephrol 2018; 33:361-372. [PMID: 28349215 DOI: 10.1007/s00467-017-3637-0] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Revised: 02/24/2017] [Accepted: 02/27/2017] [Indexed: 12/13/2022]
Abstract
Non-adherence remains a significant problem among pediatric (and adult) renal transplant recipients. Non-adherence among solid organ transplant recipients results in US$15-100 million annual costs. Estimates of non-adherence range from 30 to 70% among pediatric patients. Research demonstrates that a 10% decrement in adherence is associated with 8% higher hazard of graft failure and mortality. Focus has begun to shift from patient factors that impact adherence to the contributing healthcare and systems factors. The purpose of this review is to describe problems within the systems implicated in non-adherence and potential solutions that may be related to positive adherence outcomes. Systems issues include insurance and legal regulations, provider and care team barriers to optimal care, and difficulties with transitioning to adult care. Potential solutions include recognition of how systems can work together to improve patient outcomes through improvements in insurance programs, a multi-disciplinary care team approach, evidence-based medical management, pharmacy-based applications and interventions to simplify medication regimens, improved transition protocols, and telehealth/technology-based multi-component interventions. However, there remains a significant lack of reliability in the application of these potential solutions to systems issues that impact patient adherence. Future efforts should accordingly focus on these efforts, likely by leveraging quality improvement and related principles, and on the investigation of the efficacy of these interventions to improve adherence and graft outcomes.
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Affiliation(s)
- Elizabeth A Steinberg
- Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO, USA.
| | - Mary Moss
- Department of Pharmacy, Children's Hospital Colorado, Aurora, CO, USA
| | - Cindy L Buchanan
- Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO, USA.,Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA
| | - Jens Goebel
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA
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Sanders-Pinheiro H, Colugnati FAB, Marsicano EO, De Geest S, Medina JOP. Prevalence and correlates of non-adherence to immunosuppressants and to health behaviours in patients after kidney transplantation in Brazil - the ADHERE BRAZIL multicentre study: a cross-sectional study protocol. BMC Nephrol 2018; 19:41. [PMID: 29463231 PMCID: PMC5819659 DOI: 10.1186/s12882-018-0840-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Accepted: 02/08/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Non-adherence to immunosuppressive therapy is a prevalent risk factor for poor clinical and after kidney transplantation (KT), and has contributed to the lack of improvement in long-term graft survival over the past decade. Understanding the multilevel correlates and risk factors of non-adherence is crucial to determine the optimal level for planning interventions, namely at the patient, health care provider, KT centre, and health care system level. Brazil, having the largest public transplantation program in the world and with regional differences regarding access to health services and service implementation, is in a unique position to study this multilevel approach. Therefore, the Adhere Brazil Study (ADHERE BRAZIL) was designed to assess the prevalence and variability of non-adherence to immunosuppressants and to health behaviours among adult KT recipients in Brazil, and to assess the multilevel correlates of non-adherence to immunosuppressive medication. We describe the rationale, design, and methodology of the ADHERE BRAZIL study. METHODS/DESIGN This is an observational, cross-sectional, multicentre study that includes 20 Brazilian KT centres. A stratified sampling approach is used, based on strata, with the following characteristics considered: geographical region and transplant activity (number of KTs per year). A random sample of patients (proportional to the size of the centre within each stratum) is selected from each centre. The prevalence of different health behaviours is assessed through self-report. The assessment of multilevel correlates of non-adherence is guided by the ecological model that considers factors at the level of the patient, health-care professional, and transplant centre, using established instruments or instruments developed for this study. Data will be collected over an 18-month period, with information obtained during the regular follow-up visits to the transplant outpatient clinic and directly entered into the Research Electronic Data Capture (RedCap) system. Data entry is performed by a trained professional who is part of the transplant team. The data collection began in December 2015. DISCUSSION This multicentre study is the first to evaluate multilevel correlates of non-adherence in KT patients and will provide a reliable estimate of non-adherence in Brazilian KT patients. TRIAL REGISTRATION ClinicalTrials.gov on 10/10/2013, NCT02066935 .
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Affiliation(s)
- Helady Sanders-Pinheiro
- Renal Transplantation Unit, University Hospital, Federal University of Juiz de Fora, Rua Benjamin Constant, 1044/1001, Juiz de Fora, MG 36015-400 Brazil
- Núcleo Interdisciplinar de Estudos e Pesquisas em Nefrologia [NIEPEN], Rua Benjamin Constant, 1044/1001, Juiz de Fora, MG 36015-400 Brazil
| | - Fernando Antonio Basile Colugnati
- Renal Transplantation Unit, University Hospital, Federal University of Juiz de Fora, Rua Benjamin Constant, 1044/1001, Juiz de Fora, MG 36015-400 Brazil
- Núcleo Interdisciplinar de Estudos e Pesquisas em Nefrologia [NIEPEN], Rua Benjamin Constant, 1044/1001, Juiz de Fora, MG 36015-400 Brazil
| | - Elisa Oliveira Marsicano
- Renal Transplantation Unit, University Hospital, Federal University of Juiz de Fora, Rua Benjamin Constant, 1044/1001, Juiz de Fora, MG 36015-400 Brazil
- Núcleo Interdisciplinar de Estudos e Pesquisas em Nefrologia [NIEPEN], Rua Benjamin Constant, 1044/1001, Juiz de Fora, MG 36015-400 Brazil
| | - Sabina De Geest
- Institute of Nursing Science, Department of Public Health, Faculty of Medicine, University of Basel, Basel, Switzerland
- Academic Centre for Nursing and Midwifery, Department of Public Health and Primary Care, Faculty of Medicine, KU-Leuven, Leuven, Belgium
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44
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Arms MA, Fleming J, Sangani DB, Nadig SN, McGillicuddy JW, Taber DJ. Incidence and impact of adverse drug events contributing to hospital readmissions in kidney transplant recipients. Surgery 2017; 163:430-435. [PMID: 29174434 DOI: 10.1016/j.surg.2017.09.027] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Revised: 09/07/2017] [Accepted: 09/26/2017] [Indexed: 11/26/2022]
Abstract
BACKGROUND The incidence and impact of adverse drug events (ADEs) leading to hospitalization and as a predominant risk factor for late graft loss has not been studied in transplantation. METHODS This was a longitudinal cohort study of adult kidney recipients transplanted between 2005 and 2010 and followed through 2013. There were 3 cohorts: no readmissions, readmissions not due to an adverse drug event, and adverse drug events contributing to readmissions. The rationale of the adverse drug events contribution to the readmission was categorized in terms of probability, preventability, and severity. RESULTS A total of 837 patients with 963 hospital readmissions were included; 47.9% had at least one hospital readmission and 65.0% of readmissions were deemed as having an ADE contribute. The predominant causes of readmissions related to ADEs included non-opportunistic infections (39.6%), opportunistic infections (10.5%), rejection (18.1%), and acute kidney injury (11.8%). Over time, readmissions due to under-immunosuppression (rejection) significantly decreased (-1.6% per year), while those due to over-immunosuppression (infection, cancer, or cytopenias) significantly increased (2.1% increase per year [difference 3.7%, P = .026]). Delayed graft function, rejection, creatinine, graft loss, and death were all significantly greater in those with an ADE that contributed to a readmission compared the other two cohorts (P < .05). CONCLUSION These results demonstrate that ADEs may be associated with a significant increase in the risk of hospital readmission after kidney transplant and subsequent graft loss.
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Affiliation(s)
- Michelle A Arms
- College of Medicine, Medical University of South Carolina, Charleston, SC
| | - James Fleming
- Department of Surgery, Division of Transplant Surgery, College of Medicine, Medical University of South Carolina, Charleston, SC
| | - Deep B Sangani
- College of Medicine, Medical University of South Carolina, Charleston, SC
| | - Satish N Nadig
- Department of Surgery, Division of Transplant Surgery, College of Medicine, Medical University of South Carolina, Charleston, SC; Department of Pharmacy Services, Ralph H. Johnson VAMC, Charleston, SC
| | - John W McGillicuddy
- Department of Surgery, Division of Transplant Surgery, College of Medicine, Medical University of South Carolina, Charleston, SC; Department of Pharmacy Services, Ralph H. Johnson VAMC, Charleston, SC
| | - David J Taber
- Department of Surgery, Division of Transplant Surgery, College of Medicine, Medical University of South Carolina, Charleston, SC; Department of Pharmacy Services, Ralph H. Johnson VAMC, Charleston, SC.
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Rozen-Zvi B, Schneider S, Lichtenberg S, Green H, Cohen O, Gafter U, Chagnac A, Mor E, Rahamimov R. Association of the combination of time-weighted variability of tacrolimus blood level and exposure to low drug levels with graft survival after kidney transplantation. Nephrol Dial Transplant 2017; 32:393-399. [PMID: 28025383 DOI: 10.1093/ndt/gfw394] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2016] [Accepted: 10/01/2016] [Indexed: 12/19/2022] Open
Abstract
Background The variability of tacrolimus blood levels has been shown to be associated with inferior graft survival. However, the effect of variability during the early post-transplantation period has not been evaluated. We sought to evaluate the association between time-weighted variability in the early post-transplantation period and graft survival. We also explored the interaction between drug level variability and exposure to inadequate drug levels. Methods This retrospective cohort study included all patients who underwent kidney transplantation in the Rabin Medical Center and were treated with tacrolimus. Time-weighted coefficient of variability (TWCV) was defined as time-weighted standard deviation divided by the mean drug level. Univariate and multivariate Cox proportional hazard model was used with the primary outcome of patients and graft survival. Results The study population included 803 patients who underwent kidney transplantation between 1 January 2000 and 29 September 2013. The high tertile of TWCV of tacrolimus blood levels was associated with reduced graft survival by univariate and multivariate analyses [hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.14-2.53, P = 0.01 and HR 1.74, 95% CI 1.14-2.63, P = 0.01, respectively]. The interaction between high TWCV and exposure to inadequately low drug levels was significantly associated with reduced survival (P = 0.004), while the interaction between TWCV and high drug blood levels was not. One hundred and thirty patients (16.2%) had the combination of high TWCV and exposure to low drug values (<5 ng/mL). These patients had reduced graft survival by univariate and multivariate analyses (HR 2.42, 95% CI 1.57-3.74, P < 0.001 and HR 2.6, 95% CI 1.65-4.11, P < 0.001, respectively). Conclusions The combination of high TWCV and exposure to low drug levels might identify high-risk patients in the early post-transplantation period.
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Affiliation(s)
- Benaya Rozen-Zvi
- Department of Nephrology, Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel.,Sacker School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Shira Schneider
- Department of Nephrology, Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel.,Sacker School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Shelly Lichtenberg
- Department of Nephrology, Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel.,Sacker School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Hefziba Green
- Sacker School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Internal Medicine B, Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel
| | - Ori Cohen
- Sacker School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Internal Medicine D, Rabin Medical Center-Hasharon Hospital, Petach Tikva, Israel
| | - Uzi Gafter
- Sacker School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Avry Chagnac
- Department of Nephrology, Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel.,Sacker School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Eytan Mor
- Sacker School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Transplantation, Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel
| | - Ruth Rahamimov
- Department of Nephrology, Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel.,Sacker School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Transplantation, Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel
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46
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Bia MJ. Slow Rise in Serum Creatinine Level in a Kidney Transplant Recipient 3 Years Post-Transplant. Clin J Am Soc Nephrol 2017; 12:1692-1694. [PMID: 28336817 PMCID: PMC5628727 DOI: 10.2215/cjn.12691216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Affiliation(s)
- Margaret J Bia
- Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut
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47
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Depression in Kidney Transplant Recipients: Prevalence, Risk Factors, and Association With Functional Disabilities. J Nerv Ment Dis 2017; 205:788-792. [PMID: 28763404 DOI: 10.1097/nmd.0000000000000722] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
This study examined the prevalence, risk factors, and disability associated with depression. We conducted a cross-sectional, observational study in 217 consecutive kidney transplant (KT) recipients routinely followed-up at a Kidney Transplantation Clinic in Northern Thailand. Participants were assessed using the Charlson Comorbidity Index (CCI), the nine-item Patient Health Questionnaire (PHQ-9), and the 12-item self-report of World Health Organization Disability Assessment Scale, Version 2.0 (WHODAS). Twenty-eight (12.9%) patients had depression (PHQ-9 score, ≥10). A binary logistic regression analysis found that the CCI score was significantly higher in KT recipients with depression (β = 0.54, p < 0.01). After the adjustment of education and glomerular filter rates, an ordinal logistic regression analysis revealed that the PHQ-9 scores were positively correlated with the WHODAS scores (β = 0.39, p < 0.01). In KT recipients, physical comorbidity is associated with depression, and depression is correlated with functional disability.
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48
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Shemesh Y, Peles-Bortz A, Peled Y, HarZahav Y, Lavee J, Freimark D, Melnikov S. Feelings of indebtedness and guilt toward donor and immunosuppressive medication adherence among heart transplant (HTx) patients, as assessed in a cross-sectional study with the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS). Clin Transplant 2017; 31. [PMID: 28696505 DOI: 10.1111/ctr.13053] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/06/2017] [Indexed: 01/28/2023]
Abstract
BACKGROUND Nonadherence (NA) to immunosuppressive (IS) medications after organ transplant is a major risk factor for transplant failure, morbidity, and treatment costs. This study examined the association between feelings of indebtedness and guilt toward the donor, and IS medication adherence among HTx patients. METHODS In this cross-sectional, descriptive, correlational study, a convenience sample of 102 HTx patients, from the outpatient facility of a tertiary medical center in Israel, completed the BAASIS, a validated instrument for assessing adherence, and reported their feelings of indebtedness and guilt toward the donor. RESULTS Missing a dose or skipping two or more doses, taking medication >2 hours before or after the recommended dosing time, altering the prescribed amount, or completely stopping the IS treatment in the last 4 weeks, characterized 64 patients (64%). The highest score received the item "timing nonadherence," characterizing 58 patients (56.9%). Age, waiting time, and time since transplant, guilt feelings, and indebtedness to donor explained 17% (R2 =.17) of the variance in adherence (χ2(5) =13.22, P=.021), with age, time since transplant, and guilt feelings significantly explaining adherence. CONCLUSION Physicians and nurses should inquire about the presence of guilt feelings, as they might be associated with NA to medications after HTx.
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Affiliation(s)
- Yedida Shemesh
- Heart Institute, Sheba Medical Center, Tel Hashomer, Israel
| | | | - Yael Peled
- Heart Failure Service and Heart Institute, Sheba Medical Center, Tel Hashomer, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel
| | - Yedael HarZahav
- Heart Institute, Sheba Medical Center, Tel Hashomer, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel
| | - Jacob Lavee
- Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel.,Heart Transplantation Unit, Department of Cardiac Surgery, Sheba Medical Center, Tel Hashomer, Israel
| | - Dov Freimark
- Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel.,Department of Cardiac Surgery, Sheba Medical Center, Tel Hashomer, Israel
| | - Semyon Melnikov
- Sackler Faculty of Medicine, Stanley Steyer School of Health Professions, Nursing Department, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel
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49
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Vallejos X, Wu C. Digital Medicine: Innovative Drug-Device Combination as New Measure of Medication Adherence. J Pharm Technol 2017; 33:137-139. [PMID: 34860983 DOI: 10.1177/8755122517704212] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
In September 2015, the Food and Drug Administration accepted the first digital medicine new drug application for a drug-device combination of Otsuka's Abilify® (aripiprazole) and an ingestible sensor embedded in the tablet that digitally records ingestion. When this digital medicine is taken, it sends a signal to a patch worn by the patient. The information is recorded, time-stamped, and relayed to any Bluetooth-enabled device and, with patients' consent, to their physicians and/or their caregivers. An encapsulation model in which a tablet is co-encapsulated with the ingestible sensor has been successfully used in the setting of renal transplant, diabetes, hypertension, and hypercholesterolemia.
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50
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Nevins TE, Nickerson PW, Dew MA. Understanding Medication Nonadherence after Kidney Transplant. J Am Soc Nephrol 2017; 28:2290-2301. [PMID: 28630231 PMCID: PMC5533244 DOI: 10.1681/asn.2017020216] [Citation(s) in RCA: 100] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Alloimmunity remains a barrier to long-term graft survival that necessitates lifelong immunosuppressive therapy after renal transplant. Medication nonadherence has been increasingly recognized as a major impediment to achieving effective immunosuppression. Electronic medication monitoring further reveals that nonadherence manifests early after transplant, although the effect is delayed. The etiology of nonadherence is multifactorial, with the strongest risk factors including past nonadherence and being an adolescent or young adult. Other risk factors with smaller but consistently important effects include minority race/ethnicity, poor social supports, and poor perceived health. In children, risk factors related to parental and child psychologic and behavioral functioning and parental distress and burden are also important. Qualitative systematic reviews highlight the need to tailor interventions to each transplant recipient's unique needs, motivations, and barriers rather than offer a one size fits all approach. To date, relatively few interventions have been studied, and most studies conducted were underpowered to allow definitive conclusions. If the kidney transplant community's goal of "one transplant for life" is to become a reality, then solutions for medication nonadherence must be found and implemented.
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Affiliation(s)
- Thomas E. Nevins
- Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota
| | - Peter W. Nickerson
- Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; and
| | - Mary Amanda Dew
- Department of Psychiatry, University of Pittsburgh School of Medicine and Medical Center, Pittsburgh, Pennsylvania
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