Artigos

Conteúdo (article):

Barriers and facilitators to medication adherence in chronic diseases: a scoping review

Ana Maria Rosa Freato Gonçalves1
E-mail: anafreato@hotmail.com; ORCID: http://orcid.org/0000-0002-9428-4539
Marília Silveira Almeida Campos¹
E-mail: mariliac@fcfrp.usp.br; ORCID: https://orcid.org/0000-0003-2420-4641
Lara Almeida de Menezes ²
E-mail: laramenezes07@usp.br; ORCID: https://orcid.org/0009-0005-4305-6180
Leonardo Régis Leira Pereira¹
E-mail: lpereira@fcfrp.usp.br; ORCID: https://orcid.org/0000-0002-8609-1390

1 Pharmaceutical Assistance and Clinical Pharmacy Research Center, Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (USP), Brazil.
* Corresponding author:
E mail: anafreato@hotmail.com

Abstract
To guide the interventions of health professionals, it is necessary to identify the reasons for non-adherence to treatment. This scoping review aims to identify and discuss barriers and facilitators for adherence to pharmacotherapy in chronic diseases. Of the 3482 eligible studies, it was observed that in the 114 studies that met the selection criteria, facilitators such as income, social support, older age, education, motivation to use pharmacotherapy, formation of a bond with the health professional, health education, believe in pharmacotherapy, realize the benefits of pharmacotherapy, motivation for self-care, and disease severity, were common to the various chronic health conditions. Regarding the common barriers, were: cost of the medication, complexity of pharmacotherapy; adverse drug reaction, greater number of prescribers and pharmacies used, greater number of visits to urgent and emergency services, believing that the medication is not necessary, and having depression. The analysis of these factors provides support for the health professional to identify the reasons that led to non-adherence and guide the interventions to be carried out, promoting adherence to treatment.
Keywords: Adherence to treatment; Revision; Cooperation and Adherence to Treatment; Knowledge, Attitudes and Practice in Health.

Introduction
The World Health Organization (WHO) estimates that 50 % of patients are not adherent to the treatment prescribed in developed countries1; in addition, there is evidence that non-adherence to therapy prescribed by a healthcare professional causes increased morbidity, mortality and higher costs, especially when dealing with chronic diseases2–5.
Furthermore, non-adherence to treatment has a major financial impact in terms of health expenses5; and in line with this fact, medication adherence in chronic diseases such as diabetes mellitus (DM), systemic arterial hypertension, and hypercholesterolemia, reduces the cost of hospitalizations and other related outcomes6.
In this universe, among the interventions to promote medication adherence, it is possible to mention: health education, pharmacotherapy management (using strategies to simplify therapy, for example), monitoring by the clinical pharmacist, cognitive-behavioral therapy, devices for remembering to use the medication, and incentives (financial, for example) for using the medication7. Within this context, in order to guide the intervention to be carried out, it is necessary to identify the reasons for non-adherence, and in this sense, the importance of identifying the barriers and facilitators for this behavior is highlighted7.
In this scenario, this review aims to identify and discuss the barriers and facilitators for adherence to pharmacotherapy in chronic diseases.

Methodology
The review was carried out according to the PRISMA-ScR protocol (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews Checklist)8, with the purpose of identifying relevant issues to measure adherence. This review was registered in PROSPERO (International Prospective Register of Systematic Reviews): 2020 CRD42020157637 and aimed to answer the following question: What factors influence patient/person medication adherence for chronic diseases?
The following Portuguese, English, and Spanish descriptors were used: Tratamento Farmacológico/Drug Therapy/Tratamiento Farmacológico; Educação de Pacientes como Assunto/Patient Education as Topic/Educación del Paciente como Assunto; Doença Crônica/Chronic Disease/Enfermedad Crónica; Adesão à Medicação/Medication Adherence/Cumplimiento de la Medicación; Patient Compliance; Treatment Adherence and Compliance.
The systematized search was carried out in June 2019 in the following databases: Scopus, Embase, PubMed, and the Virtual Health Library (VHL) and the search strategies used in each of these databases are described in Appendix A. The selection of studies was carried out using Ryyan QCRI® software.
The inclusion criteria for these articles were: written in English, Spanish or Portuguese; address factors associated with adherence to pharmacotherapy for chronic diseases; study with adults and/or elderly people; and patients with cognitive capacity. The exclusion criteria in this review were: editorials, narrative review, study protocol, cross-cultural adaptation, patients in palliative care, studies involving cancer patients, studies carried out with caregivers, and the prison population.
The search was carried out by two independent researchers (AMRFG and MSAC) to avoid bias in the inclusion and exclusion of studies, with disparities resolved by a consensus meeting.
Initially, the titles and/or abstracts were screened to identify the inclusion and exclusion criteria. Articles that did not contain sufficient data for selection based on title and abstract were read in full.
After selecting the studies, the following variables were collected: author and year of publication, location of the study, language, chronic disease/comorbidity, study design, sample number, factors associated with medication adherence evaluated, and whether there was statistical evidence of association. Furthermore, the factors associated with adherence were classified as barriers or facilitators and allocated to one of the following groups, as proposed by the WHO: Factors related to pharmacotherapy; Factors related to the person; Factors related to the health system and team; Socioeconomic factors; Factors related to pharmacotherapy; and Factors related to the disease1. An analysis of the methodological quality of the studies was not undertaken, since there was the possibility of including different research designs, which would make it difficult to compare the quality of such studies.

Data analysis
The data obtained were tabulated using the Microsoft Office Excel® program (Office 2013). For descriptive statistics, absolute and relative frequency (%) was used for the varying data.

Results
A search in the literature resulted in 4200 articles, of which 718 (17.09 %) were duplicates and 3368 articles (80.19 %) were excluded according to the established criteria. The factors that influenced adherence were extracted from 114 selected studies (Figure 1).
In relation to the characteristics of the studies (Appendix A), 13 (11.40 %) were carried out only with the population and one (0.88 %) was carried out with pregnant women, while the remainder (N: 100, 92.98 % ) were carried out only with adults or with adults and children. Most of the studies (59.65 %) evaluated the factors that influence the disease in only a chronic health condition; 38.42 % (78) measured the disease through subjective techniques, 28 studies (24.56 %) used objective techniques, while eight (7.02 %) used subjective and objective techniques (Table 1). In relation to the development of studies equipped to validate the factors that influence the success, only 4 (3.51 %) were clinical trials, being that the remainder present observational delineation and the majority (N: 48, 42.11 %) present cross-sectional delineation (Table 2).
From the 114 studies extracted, a total of 1080 factors were related to pharmacotherapy adherence, and of these, the majority (n:415; 38.42 %) were classified within the socioeconomic dimension, 241 (22.40 %) related to the patient, 172 (15.92) related to pharmacotherapy, 169 (15.64 %) related to training, and 82 (7.59 %) related to the team and the health system.
The factors that present evidence of association of medication adherence with the corresponding chronic disease are described in Chart 01; it is possible to observe that most of the factors are repeated in the most diverse chronic diseases.
With reference to the socioeconomic factors, among the facilitators for medication adherence are especially income, people under 80 years of age and not residing alone, or the female gender which appear both in the facilitators and in the barriers. Factors such as alcohol consumption, smoking, and illicit drugs appeared within the barriers, however, these factors were found only in studies in the context of hypothyroidism and HIV, respectively.
In relation to factors related to pharmacotherapy, we highlight better perceptions after using the medication, and difficulties in using the medication such as the appearance of Adverse Drug Reactions (ADR) and discomfort caused by the medication in the routine. The higher number of medications used was identified as a barrier and facilitator in the studies included in this review.
The factors related to training and the link with the health team stand out among the facilitators in the dimension of the health team system. In contrast, we found the lack of link (use of a greater number of doctors and pharmacies), together with greater number of visits to urgent and emergency services, among the barriers.
Among the facilitators related to people, it is worth highlighting motivation, or feeling capable of carrying out the treatment (self-efficacy) and health education. Among the barriers, we highlight not being motivated, feeling incapable and stopping using medication when clinical improvements are noticed. In relation to the factors related to the condition, it is observed that with the severity of the condition, the presence of comorbidities stands out, therefore they appear both in the facilitators and in the barriers.

Discussion
Several studies have shown that adherence to treatment is higher in the elderly (the age cut-off depended on the country in which the study was carried out) when compared to younger adults9–51; and when the comparison used elderly people over 80 years of age, the increase in medication adherence was no longer observed52,53, probably because in this age group unintentional adherence problems increase (forgetfulness, lack of psychomotor and cognitive skills, need for care)54,55. Furthermore, in relation to other dimensions, the factors that influence adherence are similar to other age groups; among the barriers it is possible to observe the number of medications used51,56; not believing in pharmacotherapy57; number of comorbidities56 and use of inappropriate medications for the elderly (risk of causing ADR)52. Among the facilitators are education52; subsidies for access to medication51; health education53 and quality of life58. In this way, such results contribute to the possibility of adopting similar behaviors among the elderly and non-elderly adults by the health professional in a scenario of possible non-adherence, since the barriers and facilitators are similar between these age groups.
Cross-sectional studies require low cost and can be carried out in shorter times compared to other observational studies; in contrast, it is not possible to carry out temporal correlations59. In this sense, considering that most of the studies in this review had a cross-sectional design, establishing the relationship between the cause and effect of the factors that influence medication adherence, especially the severity of the disease and the presence of comorbidities, was difficult, since such factors tend to appear in patients who do not adhere to treatment, this fact may have facilitated the appearance of these factors both in barriers14–16,18,24,29,33,35,37,41,48,51,60–64, as well as facilitators13,28,37,49,65–67. Therefore, despite issues related to the study design, and taking into account that these factors can motivate the patient to use the medication, it is noteworthy that the severity of symptoms and the presence of complications can motivate adherence since, according to the health belief model, perceived susceptibility motivates medication adherence68.
Still regarding the factors that influence adherence, divergences were found regarding alcohol consumption and smoking as barriers to adherence in the context of chronic pain12, hypothyroidism24, and smoking and use of illicit drugs in patients with HIV69. The habit of smoking is common in people with chronic pain70. Furthermore, differences between the populations used may explain such divergences, since these studies used younger people and there is evidence that the consumption of these substances is not associated with healthy aging71. Furthermore, a study carried out in the context of chronic respiratory diseases found evidence that medication adherence was lower in the group of people vaccinated against the influenza virus72. Moreover, a facilitator for adherence exclusively to DM was the habit of transporting insulin67, an important characteristic, since the person needs to transport and store insulin correctly when leaving home73; and finally, another facilitator found in the context of asthma was the diagnosis provided by basic health care46, the literature recommends that this chronic health condition be treated at the level of basic health care, with referral to a specialist being recommended in more severe cases74.
Gender was largely evaluated in the studies included in this review, however, some studies did not present evidence of an association between adherence and gender11–13,16–19,21,22,24,29,31–34,36,38, 42–47,49,57,63,67,69,75–96 and some studies found evidence that the female gender is a facilitator for adherence14,19,28,39,41,61,62,97,98, while others presented the female gender as a barrier to adherence15,26,35,37,50,52,99. These findings highlight a contradiction in the literature regarding gender as a factor that influences adherence.
Although most studies present polypharmacy as a barrier to adherence12,14,18,19,51,92,93,96, some studies presented evidence that the number of medications is a facilitator for adherence31–33,47, 49. This divergence can be explained mainly through factors linked to the healthcare team, that is, patients receiving several medications may have received better guidance on how to use them33. It is noteworthy that since the patient has access to the medication, polypharmacy in itself may not be an impediment to adherence and may denote a greater perception on the part of the patient of the susceptibility caused by the disease, thus motivating adherence32, but above all, believing in pharmacotherapy and accepting the disease may be facilitators for medication adherence that overlap with polypharmacy31,49.
Several studies presented ADR as a barrier to medication adherence21,33,60,64,67,81,97,100–102; furthermore, in this sense, the perception of the harm of pharmacotherapy16,23,28,48,60,64,78,81,97,99,103–105 was also found to be a barrier to adherence. In this way, the importance of carrying out interventions that aim to minimize the unwanted effects caused by the use of the medication is highlighted, with a view to promoting medication adherence. Despite the relevance of the multidisciplinary team for the prevention of ADR, the clinical pharmacist has a fundamental role in the prevention and reporting of ADR106. Finally, identifying the barrier that is motivating non-adherence instead of just identifying the presence of non-adherence, becomes essential in order to guide the interventions carried out by the health professional.
Bearing in mind that promoting medication adherence must be a mutual responsibility between the patient and the healthcare professional107, this review found evidence that corroborates this perspective on adherence, as among the facilitators for adherence there were the number and duration of medical consultations11,24,46,47,82,92,95, trust and satisfaction with the healthcare team22,24,33,66,80,104,108, access to the healthcare service35,62,99,109, and visit from the community health agent98. Corroborating the importance of forming a bond with the healthcare team, a greater number of prescribers and pharmacies, visits to urgent and emergency services are barriers to adherence14,18,47,110. In this context, contact with the healthcare team becomes essential for promoting adherence to pharmacotherapy.
In this universe, the perception of the severity of the disease and the benefits of pharmacotherapy9,13,21,23,30,62,66,75,78,80,81,97,103,111–113, together with health education11,13,24, 26–28,33,38,62,114–116, were identified as facilitators for adherence and corroborate the importance of the healthcare team in terms of promoting adherence to pharmacotherapy.
Another barrier to adherence found in the studies in this review was depression9,60,96,117,118, this is another trigger for health professionals to pay attention to when assessing adherence.
A limitation of this study was the inclusion of cross-sectional studies, making it impossible to determine the causal relationship between the factors that influence adherence and use of the medication, especially in factors related to the disease, however, the non-use of this study design would reduce the number of factors found, since most of the included studies had this design. Furthermore, it should be noted that the divergences found, possibly caused by the cross-sectional design, were widely discussed, providing the reader with a broad view of such situations.
In an Overview carried out by Gaste, Mathes119, the factors that influence adherence were presented in the most diverse chronic conditions, as well as being presented in the present review. However, the present review brought originality with regard to a greater number of factors and discussion especially about factors related to the health system and the person.
Clyne et al.120 found that health professionals tend to overestimate adherence to prescribed treatment in their patients. Thus, given the importance of understanding the peculiarities of the factors that lead patients to not adhere to pharmacotherapy, it should be routine in the clinical practice of health professionals121. The review carried out in this study provided a comprehensive view of the factors, especially with regard to the comparison between the various chronic health conditions, providing support for identifying the reasons that led to non-adherence to guide the interventions of health professionals.
This review included several chronic health conditions that go beyond chronic noncommunicable diseases, such as chronic pain and AIDS, considering the “umbrella” term chronic health problem in view of the need to use medications for a long period (greater than three months) common to all these health problems122. In this context, this review provided support for the comparison of these factors in the most diverse chronic health problems. The great similarity found in these factors is highlighted, that is, facilitators such as income, social support, older age, education, motivation to use pharmacotherapy, formation of a bond with the health professional, health education, believe in pharmacotherapy, realize the benefits of pharmacotherapy, motivation for self-care, and disease severity were common to the various chronic health conditions. Regarding the barriers were: cost of the medication, complexity of pharmacotherapy, adverse reaction to the medication, greater number of prescribers and pharmacies used, greater number of visits to urgent and emergency services, believing that the medication is not necessary, and having depression. This review contributed to highlighting the relevance of these factors, since chronic health conditions are common, and provided support to guide the interventions of health professionals from different areas, with a view to promoting medication adherence.

References
1. Sabaté Eduardo, World Health Organization. Adherence to Long-Term Therapies : Evidence for Action. World Health Organization; 2003.
2. Simpson SH, Eurich DT, Majumdar SR, et al. A meta-analysis of the association between adherence to drug therapy and mortality. BMJ. 2006;333(7557):15. doi:10.1136/bmj.38875.675486.55
3. Chisholm-Burns MA, Spivey CA. The “cost” of medication nonadherence: Consequences we cannot afford to accept. Journal of the American Pharmacists Association. 2012;52(6):823-826. doi:10.1331/JAPhA.2012.11088
4. Bargiacchi O, Brondolo R, Rizzo G, Garavelli PL. The Pharmacoeconomics of Antiretroviral Drugs and the Role of Adherence. Le Infezioniin Medicina, n.4,p. 245-250; 2012.
5. Gandjour A. Protocol-driven costs in trial-based pharmacoeconomic analyses. Expert Rev Pharmacoecon Outcomes Res. 2011;11(6):673-675. doi:10.1586/erp.11.75
6. Sokol MC, Mcguigan KA, Verbrugge RR, Epstein RS. Impact of Medication Adherence on Hospitalization Risk and Healthcare Cost. Vol 43.; 2005.
7. Kini V, Michael Ho P. Interventions to Improve Medication Adherence: A Review. JAMA - Journal of the American Medical Association. 2018;320(23):2461-2473. doi:10.1001/jama.2018.19271
8. Tricco AC, Lillie E, Zarin W, et al. PRISMA extension for scoping reviews (PRISMA-ScR): Checklist and explanation. Ann Intern Med. 2018;169(7):467-473. doi:10.7326/M18-0850
9. Gadkari AS, Mchorney CA. Unintentional Non-Adherence to Chronic Prescription Medications: How Unintentional Is It Really?; 2012. http://www.biomedcentral.com/1472-6963/12/98
10. Christensen AJ, Smith TW, Turner CW, Cundick KE. Patient Adherence and Adjustment in Renal Dialysis: A Person • Treatment Interactive Approach 1. Vol 17.; 1994.
11. Miura T, Kojima R, Sugiura Y, Mizutani M, Takatsu F, Suzuki Y. Incidence of Noncompliance and Its Influencing Factors in Patients Receiving Digoxin. Vol 19.; 2000.
12. Broekmans S, Dobbels F, Milisen K, Morlion B, Vanderschueren S. Pharmacologic Pain Treatment in a Multidisciplinary Pain Center Do Patients Adhere to the Prescription of the Physician?; 2010. www.clinicalpain.com
13. Nicklas LB, Dunbar M, Wild M. Adherence to pharmacological treatment of non-malignant chronic pain: The role of illness perceptions and medication beliefs. Psychol Health. 2010;25(5):601-615. doi:10.1080/08870440902783610
14. Choudhry NK, Fischer MA, Avorn J, et al. The implications of therapeutic complexity on adherence to cardiovascular medications. Arch Intern Med. 2011;171(9):814-822. doi:10.1001/archinternmed.2010.495
15. Khanna R, Pace PF, Mahabaleshwarkar R, Basak RS, Datar M, Banahan BF. Medication adherence among recipients with chronic diseases enrolled in a state medicaid program. Popul Health Manag. 2012;15(5):253-260. doi:10.1089/pop.2011.0069
16. Krauskopf K, Federman AD, Kale MS, et al. Chronic obstructive pulmonary disease illness and medication beliefs are associated with medication adherence. COPD: Journal of Chronic Obstructive Pulmonary Disease. 2015;12(2):151-164. doi:10.3109/15412555.2014.922067
17. Hatah E, Lim KP, Ali AM, Shah NM, Islahudin F. The influence of cultural and religious orientations on social support and its potential impact on medication adherence. Patient Prefer Adherence. 2015;9:589-596. doi:10.2147/PPA.S79477
18. Tavares NUL, Bertoldi AD, Mengue SS, et al. Factors associated with low adherence to medicine treatment for chronic diseases in brazil. Rev Saude Publica. 2016;50. doi:10.1590/S1518-8787.2016050006150
19. Dabaghian F, Maryam R, Sadighi J, Ghods R. Adherence to prescribed medications of Iranian traditional medicine in a group of patients with chronic disease. J Res Pharm Pract. 2016;5(1):52. doi:10.4103/2279-042x.176563
20. Calabria S, Cinconze E, Rossini M, et al. Adherence to alendronic or risedronic acid treatment, combined or not to calcium and vitamin D, and related determinants in Italian patients with osteoporosis. Patient Prefer Adherence. 2016;10:523-530. doi:10.2147/PPA.S95634
21. Shruthi R, Jyothi R, Pundarikaksha HP, Nagesh GN, Tushar TJ. A study of medication compliance in geriatric patients with chronic illnesses at a tertiary care hospital. Journal of Clinical and Diagnostic Research. 2016;10(12):FC40-FC43. doi:10.7860/JCDR/2016/21908.9088
22. Fortuna RJ, Nagel AK, Rocco TA, Legette-Sobers S, Quigley DD. Patient Experience With Care and Its Association With Adherence to Hypertension Medications. Am J Hypertens. 2018;31(3):340-345. doi:10.1093/ajh/hpx200
23. Ding W, Li T, Su Q, Yuan M, Lin A. Integrating factors associated with hypertensive patients’ self-management using structural equation modeling: A cross-sectional study in Guangdong, China. Patient Prefer Adherence. 2018;12:2169-2178. doi:10.2147/PPA.S180314
24. el Helou S, Hallit S, Awada S, et al. Adherence to levothyroxine among patients with hypothyroidism in lebanon. Eastern Mediterranean Health Journal. 2019;25(3):149-159. doi:10.26719/emhj.18.022
25. Lauffenburger JC, Gagne JJ, Song Z, Brill G, Choudhry NK. Potentially disruptive life events: what are the immediate impacts on chronic disease management? A case-crossover analysis. BMJ Open. 2016;6:10958. doi:10.1136/bmjopen-2015
26. Quisel T, Foschini L, Zbikowski SM, Juusola JL. The association between medication adherence for chronic conditions and digital health activity tracking: Retrospective analysis. J Med Internet Res. 2019;21(3). doi:10.2196/11486
27. Teshome DF, Bekele KB, Habitu YA, Gelagay AA. Medication adherence and its associated factors among hypertensive patients attending the Debre Tabor General Hospital, Northwest Ethiopia. Integr Blood Press Control. 2017;10:1-7. doi:10.2147/IBPC.S128914
28. Kolios AGA, Hueber AJ, Michetti P, et al. ALIGNed on adherence: subanalysis of adherence in immune-mediated inflammatory diseases in the DACH region of the global ALIGN study. Journal of the European Academy of Dermatology and Venereology. 2019;33(1):234-241. doi:10.1111/jdv.15179
29. Akdogan N, Incel-Uysal P, Oktem A, Hayran Y, Yalcin B. Educational level and job status are the most important factors affecting compliance with oral antihistamine therapy for patients with chronic urticaria. Journal of Dermatological Treatment. 2019;30(2):183-188. doi:10.1080/09546634.2018.1476651
30. Horne R, Weinman J. PATIENTS’ BELIEFS ABOUT PRESCRIBED MEDICINES AND THEIR ROLE IN ADHERENCE TO TREATMENT IN CHRONIC PHYSICAL ILLNESS. Vol 47.; 1999.
31. Shalansky SJ, Levy AR. Effect of Number of Medications on Cardiovascular Therapy Adherence Cardiology. Vol 36.; 2002. www.theannals.com
32. Grant RW, O’leary KM, Weilburg JB, Singer DE, Meigs JB. Impact of Concurrent Medication Use on Statin Adherence and Refill Persistence. http://archinte.jamanetwork.com/
33. Burge, S. et al. Correlates of Medication Knowledge and Adherence: Findings From the Residency Research Network of South Texas. Fam Med, n. 7, v. 10, p.712-718, 2005.
34. Axelsson M, Brink E, Lundgren J, Lötvall J. The influence of personality traits on reported adherence to medication in individuals with chronic disease: An Epidemiological study in West Sweden. PLoS One. 2011;6(3). doi:10.1371/journal.pone.0018241
35. Muzina DJ, Malone DA, Bhandari I, Lulic R, Baudisch R, Keene M. Rate of non-adherence prior to upward dose titration in previously stable antidepressant users. J Affect Disord. 2011;130(1-2):46-52. doi:10.1016/j.jad.2010.09.018
36. Laliberté F, Nelson WW, Lefebvre P, Schein JR, Rondeau-Leclaire J, Duh MS. Impact of daily dosing frequency on adherence to chronic medications among nonvalvular atrial fibrillation patients. Adv Ther. 2012;29(8):675-690. doi:10.1007/s12325-012-0040-x
37. Desai PR, Adeyemi AO, Richards KM, Lawson KA. Adherence to oral diabetes medications among users and nonusers of antipsychotic medication. Psychiatric Services. 2014;65(2):215-220. doi:10.1176/appi.ps.201300118
38. Sufiza Ahmad N, Ramli A, Islahudin F, Paraidathathu T. Medication adherence in patients with type 2 diabetes mellitus treated at primary health clinics in Malaysia. Patient Prefer Adherence. 2013;7:525-530. doi:10.2147/PPA.S44698
39. Langley CA, Bush J. The Aston Medication Adherence Study: Mapping the adherence patterns of an inner-city population. Int J Clin Pharm. 2014;36(1):202-211. doi:10.1007/s11096-013-9896-3
40. Cheung MMY, Lemay K, Saini B, Smith L. Does personality influence how people with asthma manage their condition? Journal of Asthma. 2014;51(7):729-736. doi:10.3109/02770903.2014.910220
41. Gupte-Singh K, Kim G, Barner JC. Impact of comorbid depression on medication adherence and asthma-related healthcare costs in Texas Medicaid patients with asthma. Journal of Pharmaceutical Health Services Research. 2015;6(4):197-205. doi:10.1111/jphs.12111
42. Smalls BL, Gregory CM, Zoller JS, Egede LE. Assessing the relationship between neighborhood factors and diabetes related health outcomes and self-care behaviors. BMC Health Serv Res. 2015;15(1). doi:10.1186/s12913-015-1086-7
43. Serna MC, Real J, Cruz I, Galván L, Martin E. Monitoring patients on chronic treatment with antidepressants between 2003 and 2011: Analysis of factors associated with compliance. BMC Public Health. 2015;15(1). doi:10.1186/s12889-015-2493-8
44. Li YT, Wang HHX, Liu KQL, et al. Medication Adherence and Blood Pressure Control Among Hypertensive Patients With Coexisting Long-Term Conditions in Primary Care Settings. Medicine (United States). 2016;95(20). doi:10.1097/MD.0000000000003572
45. Tan CSL, Teng GG, Chong KJ, et al. Utility of the morisky medication adherence scale in gout: A prospective study. Patient Prefer Adherence. 2016;10:2449-2457. doi:10.2147/PPA.S119719
46. Bidwal M, Lor K, Yu J, Ip E. Evaluation of asthma medication adherence rates and strategies to improve adherence in the underserved population at a Federally Qualified Health Center. Research in Social and Administrative Pharmacy. 2017;13(4):759-766. doi:10.1016/j.sapharm.2016.07.007
47. Surbhi S, Graetz I, Wan JY, Gatwood J, Bailey JE. The effect of opioid use and mental illness on chronic disease medication adherence in superutilizers. J Manag Care Spec Pharm. 2018;24(3):198-207. doi:10.18553/jmcp.2018.24.3.198
48. Lemay J, Waheedi M, Al-Sharqawi S, Bayoud T. Medication adherence in chronic illness: Do beliefs about medications play a role? Patient Prefer Adherence. 2018;12:1687-1698. doi:10.2147/PPA.S169236
49. Shani M, Lustman A, Vinker S. Adherence to oral antihypertensive medications, are all medications equal? J Clin Hypertens. 2019;21(2):243-248. doi:10.1111/jch.13475
50. Bhuyan SS, Shiyanbola O, Deka P, et al. The role of gender in cost-related medication nonadherence among patients with diabetes. Journal of the American Board of Family Medicine. 2018;31(5):743-751. doi:10.3122/jabfm.2018.05.180039
51. Lefort M, Neufcourt L, Pannier B, et al. Sex differences in adherence to antihypertensive treatment in patients aged above 55: The French League Against Hypertension Survey (FLAHS). J Clin Hypertens. 2018;20(10):1496-1503. doi:10.1111/jch.13387
52. Pradhan S, Panda A. Effect of potentially inappropriate medication on treatment adherence in elderly with chronic illness. Biomedical and Pharmacology Journal. 2018;11(2):935-943. doi:10.13005/bpj/1451
53. Lai X, Zhu H, Huo X, Li Z. Polypharmacy in the oldest old (≥80 years of age) patients in China: A cross-sectional study. BMC Geriatr. 2018;18(1). doi:10.1186/s12877-018-0754-y
54. Smaje A, Weston-Clark M, Raj R, Orlu M, Davis D, Rawle M. Factors associated with medication adherence in older patients: A systematic review. Aging Medicine. 2018;1(3):254-266. doi:10.1002/agm2.12045
55. Richard J, Botelho J, Dudrak R, York E. Home Assessment o f Adherence to Long-Term Medication in the Elderly.; 1992.
56. Zuckerman IH, Sato M, Rattinger GB, Zacker C, Stuart B. Does an increase in non-antihypertensive pill burden reduce adherence with antihypertensive drug therapy? Journal of Pharmaceutical Health Services Research. 2012;3(3):135-139. doi:10.1111/j.1759-8893.2012.00092.x
57. Park HY, Seo SA, Yoo H, Lee K. Medication adherence and beliefs about medication in elderly patients living alone with chronic diseases. Patient Prefer Adherence. 2018;12:175-181. doi:10.2147/PPA.S151263
58. Holt EW, Muntner P, Joyce CJ, Webber L, Krousel-Wood MA. Health-related quality of life and antihypertensive medication adherence among older adults. Age Ageing. 2010;39(4):481-487. doi:10.1093/ageing/afq040
59. Wang X, Cheng Z. Cross-Sectional Studies: Strengths, Weaknesses, and Recommendations. Chest. 2020;158(1):S65-S71. doi:10.1016/j.chest.2020.03.012
60. Mann DM, Ponieman D, Leventhal H, Halm EA. Predictors of adherence to diabetes medications: The role of disease and medication beliefs. J Behav Med. 2009;32(3):278-284. doi:10.1007/s10865-009-9202-y
61. Chen HF, Tsai YF, Lin YP, Shih MS, Chen JC. The relationships among medicine symptom distress, self-efficacy, patient-provider relationship, and medication compliance in patients with epilepsy. Epilepsy and Behavior. 2010;19(1):43-49. doi:10.1016/j.yebeh.2010.06.007
62. Ambaw AD, Alemie GA, Wyohannes SM, Mengesha ZB. Adherence to antihypertensive treatment and associated factors among patients on follow up at University of Gondar Hospital, Northwest Ethiopia. BMC Public Health. 2012;12(1). doi:10.1186/1471-2458-12-282
63. Frech S, Kreft D, Guthoff RF, Doblhammer G. Pharmacoepidemiological assessment of adherence and influencing co-factors among primary open-angle glaucoma patients—An observational cohort study. PLoS One. 2018;13(1). doi:10.1371/journal.pone.0191185
64. Russell J, Kazantzis N. THE NEW ZEALAND MEDICAL JOURNAL Medication Beliefs and Adherence to Antidepressants in Primary Care. Vol 121.; 2008.
65. Ibrahim OM, Jirjees F, Al-Obaidi H, Mohamed Ibrahim OH, Jirjees J, Mahdi HJ. Barriers Affecting Compliance of Patients with Chronic Diseases: A Preliminary Study in United Arab Emirates (UAE) Population. Barriers Affecting Compliance Of Patients With Chronic Diseases : A Preliminary Study In United Arab Emirates (Uae) Population.; 2011. https://www.researchgate.net/publication/236700105
66. Mekonnen HS, Gebrie MH, Eyasu KH, Gelagay AA. Drug adherence for antihypertensive medications and its determinants among adult hypertensive patients attending in chronic clinics of referral hospitals in Northwest Ethiopia. BMC Pharmacol Toxicol. 2017;18(1). doi:10.1186/s40360-017-0134-9
67. Gerada Y, Mengistu Z, Demessie A, Fantahun A, Gebrekirstos K. Adherence to insulin self administration and associated factors among diabetes mellitus patients at Tikur Anbessa specialized hospital. J Diabetes Metab Disord. 2017;16(1). doi:10.1186/s40200-017-0309-3
68. Clark, M. N. et al, Self-Management of Cronic Disease by Older Adults. Journal of Aging and health, v. 3, n. 1, p. 3-27, 1991.
69. Degroote S, Vogelaers D, Vermeir P, et al. Determinants of adherence in a cohort of Belgian HIV patients: A pilot study. Acta Clin Belg. 2014;69(2):111-115. doi:10.1179/0001551214Z.00000000035
70. Fishbain DA, Lewis JE, Cole B, Cutler RB, Rosomoff HL, Rosomoff RS. Variables associated with current smoking status in chronic pain patients. Pain Medicine. 2007;8(4):301-311. doi:10.1111/j.1526-4637.2007.00317.x
71. Daskalopoulou C, Stubbs B, Kralj C, Koukounari A, Prince M, Prina AM. Associations of smoking and alcohol consumption with healthy ageing: A systematic review and meta-analysis of longitudinal studies. BMJ Open. 2018;8(4). doi:10.1136/bmjopen-2017-019540
72. Dhamane AD, Schwab P, Hopson S, et al. Association between adherence to medications for COPD and medications for other chronic conditions in COPD patients. International Journal of COPD. 2016;12:115-122. doi:10.2147/COPD.S114802
73. Bahendeka Ramaiya Kaushik Andrew Babu Swai Fredrick Otieno Sarita Bajaj Sanjay Kalra Charlotte Bavuma Claudine Karigire SM, Bahendeka S, Kaushik R, et al. EADSG Guidelines: Insulin Storage and Optimisation of Injection Technique in Diabetes Management. doi:10.6084/m9.figshare.7594157
74. Wu TD, Brigham EP, McCormack MC. Asthma in the Primary Care Setting. Medical Clinics of North America. 2019;103(3):435-452. doi:10.1016/j.mcna.2018.12.004
75. Nelson, E. C., et al. Impact os pacientes perceptions on compliance with treatment for hypertension. Medical Care, v. XVI, n. 11, p. 893-906, 1978.
76. Dompeling Petrus Van Grunsven EM, van Schayck Hans Folgering CP, Molema J, van Weel C. Treatment with Inhaled Steroids in Asthma and Chronic Bronchitis: Long-Term Compliance and Inhaler Technique. Vol 9.; 1992. http://fampra.oxfordjournals.org/
77. Billups SJ, Malone DC, Carter BL. The relationship between drug therapy noncompliance and patient characteristics, health-related quality of life, and health care costs. Pharmacotherapy. 2000;20(8I):941-949. doi:10.1592/phco.20.11.941.35266
78. Park HY, Seo SA, Yoo H, Lee K. Medication adherence and beliefs about medication in elderly patients living alone with chronic diseases. Patient Prefer Adherence. 2018;12:175-181. doi:10.2147/PPA.S151263
79. de Lourdes Souza Dewulf N, Aparecida Monteiro R, Dinis Costa Passos A, Meloni Vieira E, Ernesto de Almeida Troncon L. Adesão Ao Tratamento Medicamentoso Em Pacientes Com Doenças Gastrintestinais Crônicas Acompanhados No Ambulatório de Um Hospital Universitario. Vol 42.; 2006.
80. Gauchet A, Tarquinio C, Fischer G. Psychosocial Predictors of Medication Adherence among Persons Living with HIV. Vol 14. Lawrence Erlbaum Associates, Inc; 2007.
81. Clifford S, Barber N, Horne R. Understanding different beliefs held by adherers, unintentional nonadherers, and intentional nonadherers: Application of the Necessity-Concerns Framework. J Psychosom Res. 2008;64(1):41-46. doi:10.1016/j.jpsychores.2007.05.004
82. Weiss GA, Bartov E. Article in The Israel Medical Association Journal: IMAJ ·. Vol 13.; 2011. https://www.researchgate.net/publication/221830612
83. Farley, J. F., et al. Antiphsycotic Adhrence and its correlation to health outcomes for chronic comorbid conditions. Prim Care Companion CNS Disord, n. 14, v. 13, 2012.
84. Park YH, Kim H, Jang SN, Koh CK. Predictors of adherence to medication in older Korean patients with hypertension. European Journal of Cardiovascular Nursing. 2013;12(1):17-24. doi:10.1016/j.ejcnurse.2011.05.006
85. Marcum ZA, Zheng Y, Perera S, et al. Prevalence and correlates of self-reported medication non-adherence among older adults with coronary heart disease, diabetes mellitus, and/or hypertension. Research in Social and Administrative Pharmacy. 2013;9(6):817-827. doi:10.1016/j.sapharm.2012.12.002
86. Banik, S.; Ray, D.; Kumar. S. Analyzing the Pattern of Prescription Noncompliance in Patients of Cardiac and Diabetic Clinic of a Terceary Care Hospital. American Journal of Drug Discovery and Development, n. 3, v. 2, p. 106-112, 2013
87. Cantudo-Cuenca MR, Jiménez-Galán R, Almeida-González C v., Morillo-Verdugo R. Concurrent use of comedications reduces adherence to antiretroviral therapy among HIV-infected patients. Journal of Managed Care Pharmacy. 2014;20(8):844-850. doi:10.18553/jmcp.2014.20.8.844
88. Asefzadeh B, Rett D, Pogoda TK, Selvin G, Cavallerano A. Glaucoma medication adherence in veterans and influence of coexisting chronic disease. J Glaucoma. 2014;23(4):240-245. doi:10.1097/IJG.0000000000000044
89. Huertas-Vieco MP, Pérez-García R, Albalate M, et al. Psychosocial factors and adherence to drug treatment in patients on chronic haemodialysis. Nefrologia. 2014;34(6):737-742. doi:10.3265/Nefrologia.pre2014.Jul.12477
90. Xia Z, Xiao Z, Ma E, Xu F. Impact of mood disorder on medication adherence in patients with chronic diseases at a shanghai rural hospital. International Journal of Pharmacology. 2015;11(5):518-522. doi:10.3923/ijp.2015.518.522
91. Kearney SM, Aldridge AP, Castle NG, Peterson J, Pringle JL. The association of job strain with medication adherence is your job affecting your compliance with a prescribed medication regimen? J Occup Environ Med. 2016;58(7):707-711. doi:10.1097/JOM.0000000000000733
92. Evans C, Marrie RA, Zhu F, et al. Adherence and persistence to drug therapies for multiple sclerosis: A population-based study. Mult Scler Relat Disord. 2016;8:78-85. doi:10.1016/j.msard.2016.05.006
93. Napolitano F, Napolitano P, Angelillo IF. Medication adherence among patients with chronic conditions in Italy. Eur J Public Health. 2016;26(1):48-52. doi:10.1093/eurpub/ckv147
94. Etebari F, Pezeshki MZ, Fakour S. Factors related to the non-adherence of medication and nonpharmacological recommendations in high blood pressure patients. J Cardiovasc Thorac Res. 2019;11(1):28-34. doi:10.15171/jcvtr.2019.05
95. Kellici S, Miraci M, Fida M. Medication Adherence among Albanian Patients with Rheumatoid Arthritis Pregnancy and Dermatologic Pathologies View Project Biologic Treatment in Psoriasis View Project. https://www.researchgate.net/publication/331559670
96. Idiáquez, J. F., et al. Adhesión al tratamiento farmacológico y descripción de sus factores asociados en pacientes con miastenia grave. Rev Neurol, v. 66, n. 1, p. 15-20, 2018.
97. Yoel U, Hammad-Abu T, Cohen A, Aizenberg A, Vardy D, Shvartzman P. Population Minority a in Adherence of Scenes the Behind. IMAJ. 2013;15:17-22.
98. Remondi FA, Cabrera MAS, de Souza RKT. Não adesão ao tratamento medicamentoso contínuo: Prevalência e determinantes em adultos de 40 anos e mais. Cad Saude Publica. 2014;30(1):126-136. doi:10.1590/0102-311X00092613
98. Denhaerynck K, Berben L, Dobbels F, et al. Multilevel factors are associated with immunosuppressant nonadherence in heart transplant recipients: The international BRIGHT study. American Journal of Transplantation. 2018;18(6):1447-1460. doi:10.1111/ajt.14611
100. Awad A, Osman N, Altayib S. Medication adherence among cardiac patients in Khartoum State, Sudan: A cross-sectional study. Cardiovasc J Afr. 2017;28(6):350-355. doi:10.5830/CVJA-2017-016
101. Wei L, Champman S, Li X, et al. Beliefs about medicines and non-adherence in patients with stroke, diabetes mellitus and rheumatoid arthritis: A cross-sectional study in China. BMJ Open. 2017;7(10). doi:10.1136/bmjopen-2017-017293
102. Tedla YG, Bautista LE. Drug Side Effect Symptoms and Adherence to Antihypertensive Medication. Am J Hypertens. 2016;29(6):772-779. doi:10.1093/ajh/hpv185
103. Márquez, C. H., et al. Influencia de las creencias hacia los medicamentos en la adherencia al tratamiento concomitante en pacientes VIH+. Farm Hosp, v. 39, n. 1, p. 23-28, 2015.
104. Lee S, Jiang L, Dowdy D, Alicia Hong Y, Ory MG. Attitudes, beliefs, and cost-related medication nonadherence among adults aged 65 or older with chronic diseases. Prev Chronic Dis. 2018;15(12). doi:10.5888/pcd15.180190
105. Zidan A, Awisu A, El-Hajj MS, Al-Abdulla SA, Figueroa DCR, Kheir N. Medication-Related Burden among Patients with Chronic Disease Conditions: Perspectives of Patients Attending Non-Communicable Disease Clinics in a Primary Healthcare Setting in Qatar. Pharmacy. 2018;6(3):85. doi:10.3390/pharmacy6030085
106. van Grootheest K, Olsson S, Couper M, de Jong-van den Berg L. Pharmacists’ role in reporting adverse drug reactions in an international perspective. Pharmacoepidemiol Drug Saf. 2004;13(7):457-464. doi:10.1002/pds.897
107. Vrijens B, de Geest S, Hughes DA, et al. A new taxonomy for describing and defining adherence to medications. Br J Clin Pharmacol. 2012;73(5):691-705. doi:10.1111/j.1365-2125.2012.04167.x
108. Nagy, V. T.; Wolf, G. R. Cognitive Predictors of compliance in chronic disease patients. Medical Care, v. 22, n. 8, p. 912-921, 1984
109. Sherman BW, Glave Frazee S, Fabius RJ, Broome RA, Manfred JR, Davis JC. Impact of Workplace Health Services on Adherence to Chronic Medications. www.ajmc.com
110. Lauffenburger JC, Khan NF, Brill G, Choudhry NK. Quantifying Social Reinforcement Among Family Members on Adherence to Medications for Chronic Conditions: a US-Based Retrospective Cohort Study. J Gen Intern Med. 2019;34(6):855-861. doi:10.1007/s11606-018-4654-9
111. Hsiao CY, Chang C, Chen CD. An investigation on illness perception and adherence among hypertensive patients. Kaohsiung Journal of Medical Sciences. 2012;28(8):442-447. doi:10.1016/j.kjms.2012.02.015
112. Unni E, Shiyanbola OO. Clustering medication adherence behavior based on beliefs in medicines and illness perceptions in patients taking asthma maintenance medications. In: Current Medical Research and Opinion. Vol 32. Taylor and Francis Ltd; 2016:113-121. doi:10.1185/03007995.2015.1105204
113. Turrise S. Illness representations, treatment beliefs, medication adherence, and 30-day hospital readmission in adults with chronic heart failure a prospective correlational study. Journal of Cardiovascular Nursing. 2016;31(3):245-254. doi:10.1097/JCN.0000000000000249
114. Kelly, G. R.; Scott, J. E. Medication compliance and health education among outpatients with cronic mental disorders. Medical Care, v. 28, n. 12, 1990.
115. Hernandez-Tejada MA, Campbell JA, Walker RJ, Smalls BL, Davis KS, Egede LE. Diabetes empowerment, medication adherence and self-care behaviors in adults with type 2 diabetes. Diabetes Technol Ther. 2012;14(7):630-634. doi:10.1089/dia.2011.0287
116. Awwad O, Akour A, Al-Muhaissen S, Morisky D. The influence of patients’ knowledge on adherence to their chronic medications: a cross-sectional study in Jordan. Int J Clin Pharm. 2015;37(3):504-510. doi:10.1007/s11096-015-0086-3
117. Sheth SS, Coleman J, Cannon T, et al. Association between depression and nonadherence to antiretroviral therapy in pregnant women with perinatally acquired HIV. AIDS Care - Psychological and Socio-Medical Aspects of AIDS/HIV. 2015;27(3):350-354. doi:10.1080/09540121.2014.998610
118. Daniali SS, Darani FM, Tavassoli E, Afshari A, Forouzande F, Eslami AA. The prevalence of depression and its association with self-management behaviors in chronic disease patients. Iran J Psychiatry Behav Sci. 2019;13(1). doi:10.5812/ijpbs.10161
119. Gast A, Mathes T. Medication adherence influencing factors - An (updated) overview of systematic reviews. Syst Rev. 2019;8(1). doi:10.1186/s13643-019-1014-8
120. Clyne W, McLachlan S, Mshelia C, et al. “My patients are better than yours”: Optimistic bias about patients’ medication adherence by Eeuropean health care professionals. Patient Prefer Adherence. 2016;10:1937-1944. doi:10.2147/PPA.S108827
121. Meddings J, Kerr EA, Heisler M, Hofer TP. Physician assessments of medication adherence and decisions to intensify medications for patients with uncontrolled blood pressure: Still no better than a coin toss. BMC Health Serv Res. 2012;12(1). doi:10.1186/1472-6963-12-270.
122. Bernell S, Howard SW. Use Your Words Carefully: What Is a Chronic Disease? Front Public Health. 2016;4. doi:10.3389/fpubh.2016.00159