Mobile medication manager application to improve adherence with immunosuppressive therapy in renal transplant recipients: A randomized controlled trial

English version

Autoři: Ahram Han ^aff001; Sang-il Min ^aff001; Sanghyun Ahn ^aff001; Seung-Kee Min ^aff001; Hye-jin Hong ^aff001; Nayoung Han ^aff002; Yon Su Kim ^aff003; Curie Ahn ^aff003; Jongwon Ha ^aff001
Působiště autorů: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea ^aff001; Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul, Korea ^aff002; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea ^aff003; Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Korea ^aff004
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0224595

Souhrn

Background

Nonadherence to immunosuppressive therapy after renal transplantation is associated with poor graft outcomes. We aimed to evaluate whether the use of the Adhere4U mobile medication manager application could improve adherence among renal transplant recipients ≥1 year posttransplantation. Adhere4U can provide medication reminders, monitor medication use, and provide information on immunosuppressants.

Methods

We conducted a prospective randomized controlled study to compare the rate of nonadherence to index immunosuppressant (tacrolimus or cyclosporine) in a group using the Adhere4U app (mobile group) and in another group receiving conventional care (control group). The primary outcome was the nonadherence rate, which was evaluated using an electronic medication event monitoring system during the 6-month intervention period. Our secondary outcome included self-reported adherence using the Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS) and the visual analog scale (VAS) based on a 4-week recall on days 28, 90, and 180. Longitudinal data of repeated measures of self-rated adherence were analyzed using generalized estimating equations (GEE) to compare the between-group difference in adherence change over time.

Results

Between November 2013 and May 2015, 138 renal transplant recipients were randomly allocated to the control (n = 67) or the mobile group (n = 71). The overall nonadherence rate over the 6-month study period by electronic monitoring was 63.6%, with no between-group difference [mobile group, 65.0% (n = 39/60); control group, 62.1% (n = 36/58); odds ratio 1.14; 95% confidence interval 0.53–2.40; p = 0.89]. Self-rated nonadherence assessed using the BAASIS and VAS at baseline was 53.7% and 51.5%, respectively. Although the self-rated nonadherence by BAASIS of the mobile group was lower than the control group throughout the study period, there was no between-group difference in the change of nonadherence over time (χ2 = 2.82, df = 3, p = 0.42 by logistic GEE). There also was no significant between-group difference in the nonadherence by VAS (χ2 = 1.71, df = 3, p = 0.63 by logistic GEE) over time. The main limitation of this study was the low rate of patient engagement with the app among the mobile group. The rate of app use was 47.6% (31/65) at 28 days, 33.9% (19/56) at 90 days, and 11.5% (6/52) at 180 days.

Conclusions

The Adhere4U application did not improve adherence to immunosuppressive therapy. Our evidence is limited by the high rate of attrition. Further studies on strategies to facilitate patient engagement with mobile interventions are warranted.

Klíčová slova:

Patients – Immunology – Schools – Renal transplantation – Immunosuppressives – Cell phones – Drug adherence – Apps

Zdroje

1. Wiebe C, Gibson IW, Blydt-Hansen TD, Pochinco D, Birk PE, Ho J, et al. Rates and determinants of progression to graft failure in kidney allograft recipients with de novo donor-specific antibody. Am J Transplant. 2015;15: 2921–2930. doi: 10.1111/ajt.13347 26096305

2. Denhaerynck K, Dobbels F, Cleemput I, Desmyttere A, Schafer-Keller P, Schaub S, et al. Prevalence, consequences, and determinants of nonadherence in adult renal transplant patients: a literature review. Transpl Int. 2005;18: 1121–1133. doi: 10.1111/j.1432-2277.2005.00176.x 16162098

3. Prihodova L, Nagyova I, Rosenberger J, Majernikova M, Roland R, Groothoff JW, et al. Adherence in patients in the first year after kidney transplantation and its impact on graft loss and mortality: a cross-sectional and prospective study. J Adv Nurs. 2014;70: 2871–2883. doi: 10.1111/jan.12447 24853863

4. Nerini E, Bruno F, Citterio F, Schena FP. Nonadherence to immunosuppressive therapy in kidney transplant recipients: can technology help? J Nephrol. 2016;29: 627–636. doi: 10.1007/s40620-016-0273-x 26885659

5. Rebafka A. Medication adherence after renal transplantation-a review of the literature. J Ren Care. 2016;42: 239–256. doi: 10.1111/jorc.12181 27629770

6. Fine RN, Becker Y, De Geest S, Eisen H, Ettenger R, Evans R, et al. Nonadherence consensus conference summary report. Am J Transplant. 2009;9: 35–41. doi: 10.1111/j.1600-6143.2008.02495.x 19133930

7. Low JK, Williams A, Manias E, Crawford K. Interventions to improve medication adherence in adult kidney transplant recipients: a systematic review. Nephrol Dial Transplant. 2015;30: 752–761. doi: 10.1093/ndt/gfu204 24950938

8. Dayer L, Heldenbrand S, Anderson P, Gubbins PO, Martin BC. Smartphone medication adherence apps: potential benefits to patients and providers. J Am Pharm Assoc. 2013;53: 172–181.

9. Fishbein JN, Nisotel LE, MacDonald JJ, Pensak NA, Jacobs JM, Flanagan C, et al. Mobile application to promote adherence to oral chemotherapy and symptom management: a protocol for design and development. JMIR Res Protoc. 2017;6: e62. doi: 10.2196/resprot.6198 28428158

10. Kreyenbuhl J, Record EJ, Himelhoch S, Charlotte M, Palmer-Bacon J, Dixon LB, et al. Development and feasibility testing of a smartphone intervention to improve adherence to antipsychotic medications. Clin Schizophr Relat Psychoses. 2016; doi: 10.3371/csrp.krre.070816 27454213

11. Lakshminarayana R, Wang D, Burn D, Chaudhuri KR, Cummins G, Galtrey C, et al. Smartphone- and internet-assisted self-management and adherence tools to manage Parkinson's disease (SMART-PD): study protocol for a randomised controlled trial. Trials. 2014;15: 374. doi: 10.1186/1745-6215-15-374 25257518

12. Patel S, Jacobus-Kantor L, Marshall L, Ritchie C, Kaplinski M, Khurana PS, et al. Mobilizing your medications: an automated medication reminder application for mobile phones and hypertension medication adherence in a high-risk urban population. J Diabetes Sci Technol. 2013;7: 630–639. doi: 10.1177/193229681300700307 23759395

13. Ernst LL, Harden CL, Pennell PB, Llewellyn N, Lau C, Barnard S, et al. Medication adherence in women with epilepsy who are planning pregnancy. Epilepsia. 2016;57: 2039–2044. doi: 10.1111/epi.13586 27778312

14. Perera AI, Thomas MG, Moore JO, Faasse K, Petrie KJ. Effect of a smartphone application incorporating personalized health-related imagery on adherence to antiretroviral therapy: a randomized clinical trial. AIDS Patient Care STDS. 2014;28: 579–586. doi: 10.1089/apc.2014.0156 25290556

15. Israni A, Dean C, Kasel B, Berndt L, Wildebush W, Wang CJ. Why do patients forget to take immunosuppression medications and miss appointments: can a mobile phone app help? JMIR Public Health Surveill. 2016;2: e15. doi: 10.2196/publichealth.5285 27227150

16. Browning RB, McGillicuddy JW, Treiber FA, Taber DJ. Kidney transplant recipients' attitudes about using mobile health technology for managing and monitoring medication therapy. J Am Pharm Assoc. 2016;56: 450–454.

17. Dobbels F, Berben L, De Geest S, Drent G, Lennerling A, Whittaker C, et al. The psychometric properties and practicability of self-report instruments to identify medication nonadherence in adult transplant patients: a systematic review. Transplantation. 2010;90: 205–219. doi: 10.1097/TP.0b013e3181e346cd 20531073

18. Weng FL, Israni AK, Joffe MM, Hoy T, Gaughan CA, Newman M, et al. Race and electronically measured adherence to immunosuppressive medications after deceased donor renal transplantation. J Am Soc Nephrol. 2005;16: 1839–48. doi: 10.1681/ASN.2004121059 15800121

19. Kuypers DR, Peeters PC, Sennesael JJ, Kianda MN, Vrijens B, Kristanto P, et al. Improved adherence to tacrolimus once-daily formulation in renal recipients: a randomized controlled trial using electronic monitoring. Transplantation. 2013;95: 333–40. doi: 10.1097/TP.0b013e3182725532 23263559

20. Barraclough KA, Isbel NM, Johnson DW, Campbell SB, Staatz CE. Once-versus twice-daily tacrolimus. Drugs. 2011;71: 1561–77. doi: 10.2165/11593890-000000000-00000 21861541

21. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67: 361–370. doi: 10.1111/j.1600-0447.1983.tb09716.x 6880820

22. Oh SM, Min KJ, Park DB. A study on the standardization of the hospital anxiety and depression scale for Koreans: a comparison of normal, depressed and anxious groups. J Korean Neuropsychiatr Assoc. 1999;38: 289–296.

23. Rammstedt B, John OP. Measuring personality in one minute or less: a 10-item short version of the big five inventory in English and German. J Res Pers. 2007;41: 203–212.

24. Kim SY, Kim JM, Yoo JA, Bae KY, Kim SW, Yang SJ, et al. Standardization and validation of big five inventory-Korean version(BFI-K) in elders. Korean J Biol Psychiatry. 2010;17: 15–25.

25. Schäfer-Keller P, Steiger J, Bock A, Denhaerynck K, De Geest S. Diagnostic accuracy of measurement methods to assess non-adherence to immunosuppressive drugs in kidney transplant recipients. Am J Transplant. 2008;8: 616–626. doi: 10.1111/j.1600-6143.2007.02127.x 18294158

26. Min SI, Ha J, Kang HG, Ahn S, Park T, Park DD, et al. Conversion of twice-daily tacrolimus to once-daily tacrolimus formulation in stable pediatric kidney transplant recipients: pharmacokinetics and efficacy. Am J Transplant. 2013;13(8): 2191–2197. doi: 10.1111/ajt.12274 23734831

27. Hulley SB, Cummings SR, Browner WS, Grady D, Newman TB. Designing clinical research: an epidemiologic approach. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2013. pp. 75.

28. Griva K, Davenport A, Harrison M, Newman SP. Non-adherence to immunosuppressive medications in kidney transplantation: intent vs. forgetfulness and clinical markers of medication intake. Ann Behav Med. 2012;44: 85–93. doi: 10.1007/s12160-012-9359-4 22454221

29. Muduma G, Shupo F, Dam S, Hawken N, Aballéa S, Odeyemi I, et al. Patient survey to identify reasons for non-adherence and elicitation of quality of life concepts associated with immunosuppressant therapy in kidney transplant recipients. Patient Prefer Adherence. 2016;10: 27–36. doi: 10.2147/PPA.S96086 26834463

30. Vervloet M, Linn AJ, van Weert JC, de Bakker DH, Bouvy ML, van Dijk L. The effectiveness of interventions using electronic reminders to improve adherence to chronic medication: a systematic review of the literature. J Am Med Inform Assoc. 2012;19: 696–704. doi: 10.1136/amiajnl-2011-000748 22534082

31. Anglada-Martinez H, Riu-Viladoms G, Martin-Conde M, Rovira-Illamola M, Sotoca-Momblona JM, Codina-Jane C. Does mHealth increase adherence to medication? Results of a systematic review. Int J Clin Pract. 2015;69: 9–32. doi: 10.1111/ijcp.12582 25472682

32. Reese PP, Bloom RD, Trofe-Clark J, Mussell A, Leidy D, Levsky S, et al. Automated reminders and physician notification to promote immunosuppression adherence among kidney transplant recipients: a randomized trial. Am J Kidney Dis. 2017;69: 400–409. doi: 10.1053/j.ajkd.2016.10.017 27940063

33. Becker S, Kribben A, Meister S, Diamantidis CJ, Unger N, Mitchell A. User profiles of a smartphone application to support drug adherence—experiences from the iNephro project. PLoS One. 2013;8: e78547. doi: 10.1371/journal.pone.0078547 24194946

34. Eysenbach G. The law of attrition. J Med Internet Res. 2005;7: e11. doi: 10.2196/jmir.7.1.e11 15829473

35. Geramita EM, Dabbs AJD, DiMartini AF, Pilewski JM, Switzer GE, Posluszny DM, et al. Impact of a mobile health intervention on long-term nonadherence after lung transplantation: follow-up after a randomized controlled trial. Transplantation. 2019. [Epub ahead of print]

36. Rosenberger EM, DeVito Dabbs AJ, DiMartini AF, Landsittel DP, Pilewski JM, Dew MA. Long-term follow-up of a randomized controlled trial evaluating a mobile health intervention for self-management in lung transplant recipients. Am J Transplant. 2017;17(5): 1286–1293. doi: 10.1111/ajt.14062 27664940

37. Kelders SM, Kok RN, Ossebaard HC, van Gemert-Pijnen JE. Persuasive system design does matter: a systematic review of adherence to web-based interventions. J Med Internet Res. 2012;14: e152. doi: 10.2196/jmir.2104 23151820

38. Looyestyn J, Kernot J, Boshoff K, Ryan J, Edney S, Maher C. Does gamification increase engagement with online programs? a systematic review. PLoS One. 2017;12: e0173403. doi: 10.1371/journal.pone.0173403 28362821

39. Schmid-Mohler G, Thut MP, Wuthrich RP, Denhaerynck K, De Geest S. Non-adherence to immunosuppressive medication in renal transplant recipients within the scope of the integrative model of behavioral prediction: a cross-sectional study. Clin Transplant. 2010;24: 213–222. doi: 10.1111/j.1399-0012.2009.01056.x 19674014

40. Adams AS, Soumerai SB, Lomas J, Ross-Degnan D. Evidence of self-report bias in assessing adherence to guidelines. Int J Qual Health Care. 1999;11: 187–192. doi: 10.1093/intqhc/11.3.187 10435838

41. Gorevski E, Succop P, Sachdeva J, Cavanaugh TM, Volek P, Heaton P, et al. Is there an association between immunosuppressant therapy medication adherence and depression, quality of life, and personality traits in the kidney and liver transplant population? Patient Prefer Adherence. 2013;7: 301–307. doi: 10.2147/PPA.S34945 23620661

42. Dobbels F, Vanhaecke J, Dupont L, Nevens F, Verleden G, Pirenne J, et al. Pretransplant predictors of posttransplant adherence and clinical outcome: an evidence base for pretransplant psychosocial screening. Transplantation. 2009;87: 1497–1504. doi: 10.1097/TP.0b013e3181a440ae 19461486

43. Molloy GJ, O'Carroll RE, Ferguson E. Conscientiousness and medication adherence: a meta-analysis. Ann Behav Med. 2014;47: 92–101. doi: 10.1007/s12160-013-9524-4 23783830

44. Kakihara M. Mobile Apps in APAC: 2016 report; 2016 [cited 2017 June 28]. Database: thinkwithgoogle [Internet]. Available from: http://apac.thinkwithgoogle.com/intl/en/articles/mobile-apps-in-apac-2016-report.html

45. Haberer J. Medication event monitoring systems. In: Gellman MD, Turner JR, editors. Encyclopedia of behavioral medicine. New York, USA: Springer; 2013. pp. 1215–1219.

46. Park LG, Howie-Esquivel J, Dracup K. Electronic measurement of medication adherence. West J Nurs Res. 2015;37(1): 28–49. doi: 10.1177/0193945914524492 24577868