Fernandez-Lazaro et al.

BMC Family Practice (2019) 20:132

https://doi.org/10.1186/s12875-019-1019-3

RESEARCH ARTICLE Open Access

Adherence to treatment and related factors

among patients with chronic conditions in
primary care: a cross-sectional study
Cesar I. Fernandez-Lazaro1,2* , Juan M. García-González3, David P. Adams4, Diego Fernandez-Lazaro5,
Juan Mielgo-Ayuso6, Alberto Caballero-Garcia7, Francisca Moreno Racionero8, Alfredo Córdova6 and
Jose A. Miron-Canelo1

Abstract
Background: Adherence to treatment, a public health issue, is of particular importance in chronic disease therapies.
Primary care practices offer ideal venues for the effective care and management of these conditions. The aim of this
study is to assess adherence to treatment and related-factors among patients with chronic conditions in primary
care settings.
Methods: A cross-sectional study was conducted among 299 adult patients with ≥1 chronic condition(s) and
prescribed medication in primary healthcare centers of Spain. The Morisky-Green-Levine questionnaire was used to
assess medication adherence via face-to-face interviews. Crude and adjusted multivariable logistic regression models
were used to analyze factors associated with adherence using the Multidimensional Model proposed by the World
Health Organization — social and economic, healthcare team and system-related, condition-related, therapy-related,
and patient-related factors.
Results: The proportion of adherent patients to treatment was 55.5%. Older age (adjusted odds ratio 1.31 per 10-
year increment, 95% CI 1.01–1.70), lower number of pharmacies used for medication refills (0.65, 95% CI 0.47–
0.90), having received complete treatment information (3.89, 95% CI 2.09–7.21), having adequate knowledge
about medication regimen (4.17, 95% CI 2.23–7.80), and self-perception of a good quality of life (2.17, 95% CI
1.18–4.02) were independent factors associated with adherence.
Conclusions: Adherence to treatment for chronic conditions remained low in primary care. Optimal achievement
of appropriate levels of adherence through tailored multifaceted interventions will require attention to the
multidimensional factors found in this study, particularly those related to patients’ education and their information
needs.
Keywords: Treatment adherence, Medication adherence, Patient adherence, Patient education, Chronic conditions,
Multidimensional factors, WHO multidimensional framework, Primary care

* Correspondence: fernandezlazaro@usal.es
1
Department of Biomedical and Diagnostic Sciences, School of Medicine,
University of Salamanca, Calle Alfonso X el Sabio s/n, 37007 Salamanca, Spain
2
Department of Preventive Medicine and Public Health, School of Medicine,
IDISNA, University of Navarra, Pamplona, Spain
Full list of author information is available at the end of the article

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Fernandez-Lazaro et al. BMC Family Practice (2019) 20:132 Page 2 of 12

Background factors associated with medication adherence in primary

The increase in life expectancy and the aging of the care settings, venues that provide most of the care and
world population have been paralleled by an alarming management of chronic conditions [18–20]. Moreover,
growth in the global burden of chronic conditions [1]. some authors have also emphasized the need to develop
Chronic diseases are generally considered physical or studies in the context of primary care to better assess
mental conditions that last more than a year and require medication adherence, as these places offer more
ongoing care. They compromise the individuals’ physical accurate results and minimize selection bias [21]. Thus
and social function, the health-related quality of life, and we aim to use the WHO conceptual framework to evalu-
the economic sustainability of healthcare systems [2, 3]. ate adherence and related factors among chronic-disease
Their global prevalence has reached such unprecedented patients in these settings. Their assessments can guide
levels in many populations that chronic diseases cur- interventions that will reduce healthcare costs and im-
rently represent a public health concern. Roughly a prove patients’ health-related quality of life.
quarter of the European population suffers from at least
one chronic condition, and an estimated 50 million Methods
people suffer from multimorbidity [4], the co-occurrence Study design and settings
of two or more chronic diseases [5]. In the United A cross-sectional study was conducted in two primary
States, chronic conditions affect 60% of American adults, healthcare centers between August 2016 and March
and four in ten suffer from multimorbidity [6]. 2017 in Soria, an urban city of 39,000 inhabitants located
For people with chronic diseases, management of their in the autonomous community of Castile and Leon,
conditions is fundamental to minimize their impact, im- Spain. The Spanish National Health System (SNHS) pro-
prove health outcomes, prevent further disability, and re- vides universal health coverage to all Spanish citizens
duce healthcare costs [7, 8]. Adherence to treatment, the and foreign nationals and has two levels of care: Primary
extent to which patients are able to follow the agreed rec- Health Care and Specialist Care.
ommendations for prescribed treatments with healthcare Primary Health Care is distributed in health areas that
provider, is a key component of chronic disease manage- provide basic health care services through one or more
ment. Only half of patients with chronic conditions, how- healthcare centers. All centers operate strive to follow
ever, take their medications as prescribed, making the same principles to maximize healthcare accessibility
medication adherence improvement a priority of the pub- and equity within the country. Healthcare centers in
lic health agenda [9]. According to the World Health Spain offer services free of charge at the point of delivery
Organization (WHO), a series of factors, rather than a sin- such as consultations, health education, laboratory tests,
gle one, determine patients’ ability to follow treatment physical therapy, and radiographic exams [22]. Cur-
recommendations correctly. These factors interact and rently, the facilities of the study are the main healthcare
potentiate each other’s influence in a framework deter- centers of the Health Area of Soria and provide health-
mined by five dimensions — the social and economic, care services to the urban population of the city, one of
health-care team and system-related, condition-related, the 52 Spanish provincial capitals.
therapy-related, and patient-related [9].
Several attempts have been made in recent years to de- Population and sampling
termine the most influential factors of adherence. Most The sample population of the study was calculated based
research has focused on a single-dimension, usually pa- on the number of patients that attended the clinics and
tient-related factors [10] and have not taken into ac- an estimated prevalence of chronic conditions among
count the WHO framework. Other studies have focused primary care population of 70% [16]. We accepted an
on a single-disease, such as diabetes [11], coronary heart expected proportion of the participants not adhering to
disease [12], and asthma [13], or on a particular drug prescribed medications of 75% [23, 24], keeping a 95%
therapy [14], an approach which limits the utility of the confidence level, a 5% tolerated error level, and a design
findings to the condition under study. To identify facili- effect of 1. Taking into account a possible refusal rate of
tators of adherence among chronic-disease patients, it is 20%, the final sample size was calculated to be 344
necessary to consider more than a single chronic condi- patients.
tion and account for interaction of factors in a more The investigators screened potential candidates for
multi-dimensional approach. participation at each center. After candidates’ screening,
Spain has one of the highest prevalence of multimor- research assistants randomly approached potential par-
bidity [4, 15, 16] in Europe. Present demographic trends ticipants presenting at the centers for follow-up consul-
suggest its population will have the longest life expect- tations, confirmed their eligibility, and invited them to
ancy in the world by 2040 [17]. Nonetheless, no studies participate in the study. Patients aged 18 years or older
have used a multi-dimensional approach to evaluate who suffered from one or more chronic condition(s) and
Fernandez-Lazaro et al. BMC Family Practice (2019) 20:132 Page 3 of 12

had been prescribed medication for more than a year of Social and Economic Factors
treatment were considered eligible for inclusion in the
study. Individuals with cognitive impairment or mental Gender, age, immigration status (born in Spain vs. im-
conditions that prevented them from responding appro- migrated to Spain), household income (tertiles), living
priately, and those who declined to participate, were ex- status (living alone vs. living with someone), and highest
cluded from the study. A total of 23 health problems level of education (primary school or lower, secondary
were defined as chronic conditions in the study (Add- school, and university or higher) were included as social
itional file 1: Table S1). These conditions were selected economic factors.
because they are typically treated with prescribed medi-
cations and commonly occur in primary care settings. Healthcare Team and System-Related Factors

Data collection Information about patients’ frequency of follow-up

A questionnaire, previously designed by an expert group care for chronic diseases (monthly or more fre-
in medication adherence, was used to obtain information quently, quarterly, and biannually or less frequently)
about patients’ socio-demographic characteristics and and the number of pharmacies used for medication
factors related to adherence. Prior to its implementation, refills were considered. Additionally, patient-provider
investigators piloted the survey on 30 subjects to ensure communication, perceived quality of healthcare de-
that it was easily understood, well-defined, and accur- livery, and level of treatment information received
ately addressed the goals of the study. were evaluated on a 5-point Likert scale: from “1″
Data collection took place in a clinic consultation room meaning very poor to “5″ meaning very good. Scores
after participants’ appointment with their healthcare pro- above “3″ were used to categorize respondents as
viders. Face-to-face, semi-structured interviews, were con- having good communication with provider, perceiving
ducted by a pharmacist with extensive experience in good quality of healthcare delivery, and receiving
adherence surveys. Each interviewer-patient session lasted complete treatment information for each item
between 20 and 30 minutes. Participation in the study was respectively.
voluntary and all the subjects received a detailed explan-
ation about the goals, objectives, methods, and purpose of Condition-Related Factors
the study. Patients, whose responses were coded to protect
their confidentiality, were also informed they could with- Data about condition-related factors included the
draw from the study at any time without penalty. number of chronic conditions, adjusted morbidity
The Ethics Committee of the Hospital Complex of So- group (AMG) based on the Clinical Risk Group clas-
ria approved this study. All participants provided written sification [27], and lifestyle behavior such as alcohol
informed consent to take part in the study. consumption, tobacco smoking use, and levels of
physical activity. The AMG is a new multi-morbidity
Measurement of exposure and covariates risk adjustment measure of disease severity, number
Self-reported adherence was determined using the Spanish of diseases, healthcare services utilization, and diffi-
validated version [25] of the four-item Morisky-Green-Levine culties associated with access to resources. This meas-
Medication Assessment Questionnaire [26]. This method is ure has been adapted to the Spanish Health System
simple, easy to implement, and has the ability to identify rea- and has been used by the Castile and Leon Health-
sons underlying the medication adherence behavior. Further- care Services since 2013 to manage patients with
more, it has been widely used in numerous studies and chronic conditions [28].
clinical settings. The questionnaire consists of 4 yes/no ques- Claim-based diagnoses were used to assign sub-
tions: (i) Do you ever forget to take your medicine? (ii) Are jects to a mutually exclusive, hierarchically ranked
you careless at times about taking your medicine? (iii) When risk, group burden of comorbid diseases: AMG1
you feel better, do you sometimes stop taking your medicine? (single minor chronic condition), AMG2 (multimor-
and (iv) If you feel worse when you take the medicine, do bidity with stable chronic conditions), and AMG3
you stop taking it? Each “yes” response received a score of (complex multimorbidity with severe chronic condi-
“1”, and each “no” response received a score of “0”. Patients’ tions). Regarding lifestyle, participants self-reported
overall medication adherence was categorized as follows: ≥3 their frequency of alcohol consumption (daily
score = low adherence; 1–2 score = medium adherence; and drinker, occasional drinker, and non-drinker), to-
0 score = high adherence. bacco smoking (smoker, ex-smoker, and non-
The following factors were considered for their pos- smoker), and physical activity during leisure time
sible association with medication adherence using the (active vs. non-active) according to the WHO rec-
WHO multidimensional framework [9]: ommendations [29].
Fernandez-Lazaro et al. BMC Family Practice (2019) 20:132 Page 4 of 12

Table 1 Social and Economic-, Healthcare Team and System-, and Condition-Related Factors of the Participants of the Study
according to their Self-Reported Measure of Medication Adherence, n = 299
Factors Total n (%) Adherent n (%) Poor Adherent n (%) Bivariate Analyses
n = 299 n = 166 n = 133 Crude OR 95% CI p-value
Social and Economic
Gender
Male 154 (51.5) 90 (54.2) 64 (48.1) Ref. Ref.
Female 145 (48.5) 76 (45.8) 69 (51.9) 0.78 (0.50 to 1.24) 0.295
Age, mean ± SD 65.79 ± 13.7 68.96 ± 12.8 61.83 ± 13.9 1.49 (1.24 to 1.78) < 0.001
Immigration Status
Born in Spain 251 (83.9) 156 (94.0) 95 (71.4) Ref. Ref.
Immigrated to Spain 48 (16.1) 10 (6.0) 38 (28.6) 0.160 (0.08 to 0.34) < 0.001
Household Income
1st Tertile (lowest income) 100 (33.44) 52 (31.33) 48 (36.09) Ref. Ref.
2nd Tertile 100 (33.44) 62 (37.35) 38 (28.57) 1.51 (0.86 to 2.65) 0.154
3er Tertile (highest income) 99 (33.11) 52 (31.33) 47 (35.34) 1.02 (0.59 to 1.78) 0.941
Living Status
Living alone 63 (21.1) 28 (16.9) 35 (26.3) Ref. Ref.
Living with someone 236 (78.9) 138 (83.1) 98 (73.7) 1.69 (1.01 to 3.08) 0.048
Education
Primary school or lower 176 (58.9) 98 (59.0) 78 (58.7) Ref. Ref.
Secondary school 88 (29.4) 51 (30.7) 37 (27.8) 1.10 (0.65 to 1.84) 0.726
University or higher 35 (11.7) 17 (10.2) 18 (13.5) 0.75 (0.36 to 1.55) 0.441
Healthcare Team and System-Related
Frequency of Follow-up Care
Monthly or more frequently 152 (50.8) 81 (48.8) 71 (53.4) Ref. Ref.
Quarterly 117 (39.1) 64 (38.6) 53 (39.8) 1.06 (0.65 to 1.72) 0.818
Biannually or less frequently 30 (10.0) 21 (12.7) 9 (6.8) 2.05 (0.88 to 4.75) 0.096
Number of Pharmacies Used for Refills, mean ± SD 1.64 ± 1.0 1.35 ± 0.8 2.00 ± 1.2 0.51 (0.40 to 0.66) < 0.001
Patient-provider Communication
Not having good communication 24 (8.0) 9 (5.4) 15 (11.3) Ref. Ref.
Having good communication 275 (92.0) 157 (94.6) 118 (88.7) 2.22 (1.03 to 6.11) 0.070
Quality of Healthcare Delivery
Not perceiving good quality of care 13 (4.3) 5 (3.0) 8 (6.0) Ref. Ref.
Perceiving good quality of care 286 (95.7) 161 (97.0) 125 (94.0) 2.06 (0.66 to 6.45) 0.214
Treatment Information Received
Not receiving complete information 161 (53.8) 60 (36.1) 101 (75.9) Ref. Ref.
Receiving complete information 138 (46.2) 106 (63.9) 32 (24.1) 5.58 (3.35 to 9.27) < 0.001
Condition-Related
Number of Chronic Conditions, mean ± SD 2.90 ± 1.5 3.08 ± 1.6 2.68 ± 1.5 1.19 (1.02 to 1.39) 0.027
Adjusted Morbidity Group
AMG1 62 (20.7) 29 (17.5) 33 (24.8) Ref. Ref.
AMG2 163 (54.5) 89 (53.6) 74 (55.6) 1.37 (0.76 to 2.46) 0.294
AMG3 74 (24.8) 48 (28.9) 26 (19.5) 2.10 (1.05 to 4.19) 0.035
Alcohol Consumption
Daily drinker 59 (19.7) 30 (18.1) 29 (21.8) Ref. Ref.
Fernandez-Lazaro et al. BMC Family Practice (2019) 20:132 Page 5 of 12

Table 1 Social and Economic-, Healthcare Team and System-, and Condition-Related Factors of the Participants of the Study
according to their Self-Reported Measure of Medication Adherence, n = 299 (Continued)
Factors Total n (%) Adherent n (%) Poor Adherent n (%) Bivariate Analyses
n = 299 n = 166 n = 133 Crude OR 95% CI p-value
Occasional drinker 101 (33.8) 51 (30.7) 50 (37.6) 0.99 (0.52 to 1.87) 0.966
Non-drinker 139 (46.5) 85 (51.2) 54 (40.6) 1.52 (0.82 to 2.81) 0.824
Tobacco Smoking
Smoker 49 (16.4) 30 (18.1) 19 (14.3) Ref. Ref.
Ex-smoker 98 (32.8) 56 (33.7) 42 (31.6) 0.84 (0.42 to 1.70) 0.636
Non-smoker 152 (50.8) 80 (48.2) 72 (54.1) 0.70 (0.37 to 1.36) 0.294
Physical Activity
Non-active 128 (42.8) 64 (38.6) 64 (48.1) Ref. Ref.
Active 171 (57.2) 102 (61.4) 69 (51.9) 0.68 (0.43 to 1.07) 0.097
Abbreviations: CI, confidence interval; OR, odds ratio; SD, standard deviation; Ref., reference
Bold values are statistically significant at p-values ≤0.05

Therapy-Related Factors (questionnaire’s score ≥ 1/medium and low adherence).

Descriptive statistics included means and standard devia-
The number of prescriptions, pills, and use of medica- tions (SD) for quantitative variables and percentages for
tion by injections (use vs. non-use injections), and by in- categorical variables. We performed crude and adjusted
halers (use vs. non-use inhalers) included in the treatment multivariate logistic regression to evaluate factors associ-
of each participant were considered as therapy-related fac- ated with medication adherence. Covariates were in-
tors. Moreover, patients reported on a 5-point Likert scale cluded in the multivariate logistic regression model
the degree to which treatment interfered with their activ- based on the crude association with adherence (p-value
ities of daily living with “1” meaning not any interference ≤ 0.05). These variables were age, immigration status, liv-
to “5” meaning very much interference. Scores above “3” ing status, number of pharmacies used for medication
were used to categorize treatment respondents viewed as refills, treatment information received, number of
interfering with activities of daily living. chronic conditions, adjusted morbidity group, interfer-
ence of therapy on daily life activities, medication dosing
Patient-Related Factors reminders, patients’ knowledge about medication regi-
men, and self-perceived quality of life. Sensitivity ana-
Information collected about patient-related factors lyses were additionally performed to confirm the
reflected in participants’ functional independency of relationship between risk factors and adherence. No is-
activities of daily living evaluated using the Barthel Index: sues of multicollinearity were observed. These analyses
independent, slightly dependent, moderately dependent, se- were performed using Stata software, version 14.0 (Stata-
verely dependent, and totally dependent [30]; the use of aids Corp LP, College Station, TX) with a two-tailed level of
to remember medication-dosing schedules (no reminders, statistical significance set at p-value ≤ 0.05.
alarms/phones/pillboxes, and association of medication
with daily routines); knowledge of medication regimen, i.e., Results
specific amount, number, and frequency of doses (adequate Sample characteristics
vs. inadequate knowledge); and whether patients perceived Among the 344 eligible patients randomly invited to par-
overmedication in their treatment (perception vs. no- ticipate in the study, 41 (11.9%) refused to participate and
perception of overmedication). Individuals also reported 4 (1.2%) withdrew during the interview process. The char-
their self-perceived quality of life on a 5-point Likert scale acteristics of the excluded subjects were similar to those
with “1″ meaning very poor to “5″ meaning very good. of the overall group. The mean age of participants was
Scores above “3″ were used to categorize respondents as 65.8 ± 13.7 years; most were male (51.5%) and born in
having good quality of life. Spain (83.9%). Nearly half had at least graduated from sec-
ondary school (41.1%). Participants had a mean number of
Data management and statistical analysis 3.9 ± 2.2 prescriptions in their treatment and suffered an
For statistical analyses participants were categorized ac- average of 2.9 ± 1.5 chronic conditions (Table 1). The
cording to their responses of the Morisky-Green-Levine most common chronic conditions among participants
questionnaire into an “adherent group” (questionnaire’s were circulatory system diseases (71.2%), followed by
score = 0/high adherence) and a “poor-adherent group” endocrine and metabolic disorders (53.2%), and mental
Fernandez-Lazaro et al. BMC Family Practice (2019) 20:132 Page 6 of 12

Table 2 Therapy- and Patient-Related Factors of the Participants of the Study according to their Self-Reported Measure of
Medication Adherence, n = 299
Factors Total n (%) Adherent n (%) Poor Adherent n (%) Bivariate Analyses
n = 299 n = 166 n = 133 Crude OR 95% CI p-value
Therapy-Related
Number of prescriptions, mean ± SD 3.90 ± 2.2 3.94 ± 2.2 3.85 ± 2.3 1.02 (0.92 to 1.13) 0.725
Number of pills, mean ± SD 4.36 ± 2.9 4.26 ± 2.9 4.50 ± 3.0 0.97 (0.90 to 1.05) 0.482
Medication through injections
Using injections 33 (11.0) 18 (10.8) 15 (11.3) Ref. Ref.
Not using injections 266 (89.0) 148 (89.2) 118 (88.7) 1.05 (0.51 to 2.16) 0.905
Therapy through inhalers
Using inhalers 28 (9.4) 14 (8.4) 14 (10.5) Ref. Ref.
Not using inhalers 271 (90.6) 152 (91.6) 119 (89.5) 1.28 (0.59 to 2.78) 0.538
Interfering with Activities of Daily Living
Interfering 27 (9.03) 10 (6.0) 17 (12.8) Ref. Ref.
Not-interfering 272 (91.0) 156 (94.0) 116 (87.2) 2.29 (1.01 to 5.18) 0.047
Patient-Related
Functional Independency of Daily Living Activities
Independent 234 (78.3) 127 (76.5) 107 (80.5) Ref. Ref.
Slightly dependent 49 (16.4) 29 (17.5) 20 (15.0) 1.22 (0.65 to 2.28) 0.530
Moderately dependent 16 (5.4) 10 (6.0) 6 (4.5) 1.40 (049 to 3.99) 0.524
Severely dependent 0 (0) 0 (0) 0 (0) – – –
Totally dependent 0 (0) 0 (0) 0 (0) – – –
Medication Dosing Reminders
Not using any reminder 85 (28.4) 27 (16.3) 58 (43.6) Ref. Ref.
Use of alarms/phones/pillboxes 80 (26.8) 50 (30.1) 30 (22.6) 3.58 (1.88 to 6.81) < 0.001
Association of medication with daily routines 134 (44.8) 89 (53.6) 45 (33.8) 4.25 (2.38 to 7.59) < 0.001
Patient’s Knowledge about Medication Regimen
Not having an adequate knowledge 173 (57.9) 75 (45.2) 98 (73.7) Ref. Ref.
Having an adequate knowledge 126 (42.1) 91 (54.8) 35 (26.3) 3.40 (2.08 to 5.56) < 0.001
Perceived Overmedication in the Treatment
Perception of overmedication 26 (8.7) 12 (7.2) 14 (10.5) Ref. Ref.
Not-perception of overmedication 273 (91.3) 154 (92.8) 119 (89.5) 1.51 (0.67 to 3.39) 0.317
Self-Perceived Quality of Life
Not having good quality of life 153 (51.2) 76 (45.8) 77 (57.9) Ref. Ref.
Having good quality of life 146 (48.8) 90 (54.2) 56 (42.1) 1.63 (1.03 to 2.58) 0.038
Abbreviations: CI, confidence interval; OR, odds ratio; SD, standard deviation; Ref., reference
Bold values are statistically significant at p-values ≤0.05

and nervous system diseases (37.8%) (Additional file 1: forgetting to take medications (79.0%), being careless at
Table S1). times about taking medications (29.3%), discontinuing
medications when feeling better (21.1%), and discontinu-
Adherence to treatment ing medications when feeling worse (24.1%) (Additional
The proportion of adherent patients to treatment ac- file 1: Table S2).
cording to the Morisky-Green-Levine questionnaire was
55.5%. Medium and low adherence rates were 39.8% and
4.7% respectively and comprised the “poor-adherent Factors associated with adherence
group” (44.5%). The likely causes for non-adherence Bivariate logistic analyses revealed several factors associ-
among the poor-adherent group were occasionally ated with medication adherence in all the WHO
Fernandez-Lazaro et al. BMC Family Practice (2019) 20:132 Page 7 of 12

Table 3 Multivariable Logistic Regression Models between Factors in the WHO’s Domains and Medication Adherence as Measured
by the Four-Item Morisky-Green-Levine Self-Reported Questionnaire, n = 299
Multivariate Logistic Regression
Factors Adjusted OR 95% CI p-value
Social and Economic
Age (per 10-year increment) 1.31 (1.01–1.70) 0.039
Immigration Status
Born in Spain Ref. Ref.
Immigrated to Spain 0.64 (0.25 to 1.65) 0.352
Living Status
Living alone Ref. Ref.
Living with someone 1.81 (0.89 to 3.68) 0.099
Healthcare Team and System-Related
Number of Pharmacies Used for Refills 0.65 (0.47 to 0.90) 0.008
Treatment Information Received
Not receiving complete information Ref. Ref.
Receiving complete information 3.89 (2.09 to 7.21) < 0.001
Condition-Related Factors
Number of Chronic Conditions 1.31 (0.99 to 1.73) 0.061
Adjusted Morbidity Group
AMG1 Ref. Ref.
AMG2 0.68 (0.28 to 1.69) 0.410
AMG3 0.84 (0.28 to 2.79) 0.836
Therapy-Related
Interfering with Activities of Daily Living
Interfering Ref. Ref.
Not-interfering 1.52 (0.53 to 4.34) 0.432
Patient-Related
Medication Dosing Reminders
Not using any reminder Ref. Ref.
Use of alarms/phones/pillboxes 1.56 (0.69 to 3.52) 0.281
Association of medication with daily routines 1.55 (0.74 to 3.28) 0.244
Patient’s Knowledge about Medication Regimen
Not having an adequate knowledge Ref. Ref.
Having an adequate knowledge 4.17 (2.23 to 7.80) < 0.001
Self-Perceived Quality of Life
Not having good quality of life Ref. Ref.
Having good quality of life 2.17 (1.18 to 4.02) 0.013
Abbreviations: CI, confidence interval; OR, odds ratio; Ref., reference
Bold values are statistically significant at p-values ≤0.05

dimensions (Table 1 and Table 2). Variables signifi- 1.70), refilled prescriptions in lower number of pharma-
cantly associated with adherence (p-value ≤ 0.05) were cies (0.65, 95% CI 0.47–0.90), received complete infor-
included in the multivariable logistic regression ana- mation about treatment (3.89, 95% CI 2.09–7.21), had
lyses. After multivariable adjustment, five factors were adequate knowledge about medication regimen (4.17,
independently associated with adherence (Table 3). Par- 95% CI 2.23–7.80), and self-perceived of having good
ticipants who were older (adjusted odds ratio 1.31 per quality of life (2.17, 95% CI 1.18–4.02) were more likely
10-year increment, 95% confidence interval [CI] 1.01– to adhere to treatment schedule regimens (Fig. 1).
Fernandez-Lazaro et al. BMC Family Practice (2019) 20:132 Page 8 of 12

Fig. 1 Multivariate Logistic Regression Analysis. The forest plot displays the Adjusted Odds Ratio (OR) and 95% Confidence Interval (CI) for factors associated
with medication adherence — older age, lower number of pharmacies used for medication refills, having received complete treatment information, having
adequate knowledge about medication regimen, and self-perception of a good quality of life — among patients with chronic conditions in Primary Care. The
model was further adjusted for immigration status, living status, number of chronic conditions, adjusted morbidity group, interference of therapy on daily life
activities, and use of medication dosing reminders. Abbreviations: OR, odds ratio; CI, confidence interval

Sensitivity analyses are consistent with prior research in Spain performed in

To test the robustness of our results and the validity and chronic patients [33], but significantly different in terms
reliability of the methods used for assessing adherence, of the adherence rate of 18% reported in tertiary-care
we conducted multiple linear regression analysis using settings [23].
patient’s overall medication score (0–4 score) as con- Patient’s knowledge about medication regimen pro-
tinuous dependent variable. Age, the number of pharma- vided the strongest predictor of adherence. A large pro-
cies used to refill prescriptions, treatment information portion of participants found it difficult to explain the
received, and knowledge about treatment were consist- amount, number, and frequency of doses associated with
ently associated with medication adherence (Table 4). their medications, negatively affecting their adherence.
For patients with chronic conditions, understanding of
Discussion their own diseases and the complex regimens may repre-
To our knowledge, this is the first attempt to determine sent a challenge [34]. For example, Friis et al. [35] found
factors associated with adherence under the WHO that individuals with long-term diseases had more diffi-
multidimensional framework in patients with chronic culties in comprehending provider health information.
conditions in primary care settings in Spain. The results Similarly, Fredericksen et al. [36] and Kvarnström et al.
showed that slightly more than half of the subjects of [37] reported frequent misconceptions and lack of un-
the cohort remained adherent to long-term therapies for derstanding of the purpose of medications among the
chronic conditions, which points to substantial room for chronically ill.
improvement at the primary-care level. Forgetfulness Our analyses also proved that treatment information
was the main likely cause of non-adherence among the was an important predictor of adherence. Clear, un-
poor adherence group. After adjustment for several vari- biased, and proper information improves patients’ un-
ables, we found age, the number of pharmacies used for derstanding of their treatment, increases awareness of
medication refills, the treatment information received, benefits and risks of medication, and sets realistic expec-
patients’ knowledge about medication regimen, and self- tations, which improves adherence [38]. Nonetheless,
perceived quality of life as independent factors of patients frequently receive little information about treat-
adherence. ment during clinical consultations [39] and have needs
The adherence rate found in our study was consistent and concerns that are not addressed [40].
with the WHO report that states “in developed coun- General practitioners (GPs), responsible for much of
tries, adherence among patients suffering chronic dis- the prescribing medication and counseling for chronic
eases averages only 50%” [9]. Compared with previous conditions [18–20], have reported time pressure as a fre-
international studies, the adherence rate assessed in this quent barrier for informing and educating patients in
study was similar to the 53% found in Chinese primary- primary care settings [38]. Moreover, physicians have
care centers [31], the 48% reported in uninsured Ameri- acquired strategies to manage consultation times by
can patients who attended community health centers interrupting patients before giving them the opportunity
[32], but slightly higher than the 39% observed in Italian to explain their concerns completely [41]. Such circum-
outpatient adults [24]. At the national level, our findings stances may lead patients to experience greater
Fernandez-Lazaro et al. BMC Family Practice (2019) 20:132 Page 9 of 12

Table 4 Multiple Linear Regression Analysis of Factors of Adherence using the Morisky-Green-Levine’s Scale Score, n = 299
Multivariate Linear Regression Model
Factors Correlation Coeficient SE 95% CI p-value
Social and Economic
Age (per 10-year increment) −0.15 0.04 (−0.23 to −0.07) 0.001
Immigration Status
Born in Spain Ref. Ref.
Immigrated to Spain 0.27 0.15 (−0.02 to 0.56) 0.070
Living Status
Living alone Ref. Ref.
Living with someone − 0.18 0.11 (− 0.40 to 0.04) 0.107
Healthcare Team and System-Related
Number of Pharmacies Used for Refills 0.14 0.05 (0.04 to 0.24) 0.005
1
Treatment Information Received −0.20 0.05 (− 0.30 to − 0.10) < 0.001
Condition-Related Factors
Number of Chronic Conditions −0.07 0.04 (−0.16 to 0.01) 0.077
Adjusted Morbidity Group
AMG1 Ref. Ref.
AMG2 0.11 0.14 (−0.16 to 0.39) 0.427
AMG3 0.15 0.18 (−0.21 to 0.51) 0.412
Therapy-Related
Interfering with Activities of Daily Living
Interfering Ref. Ref.
Not-interfering 0.06 0.16 (−0.27 to 0.38) 0.736
Patient-Related
Medication Dosing Reminders
Not using any reminder Ref. Ref.
Use of alarms/phones/pillboxes 0.02 0.14 (−0.25 to 0.29) 0.878
Association of medication with daily routines −0.17 0.13 (−0.42 to 0.09) 0.200
1
Knowledge about Medication Regimen −0.17 0.05 (−0.26 to − 0.08) < 0.001
1
Self-Perceived Quality of Life −0.05 0.04 (−0.14 to 0.04) 0.264
Abbreviations: SE, standard error; CI, confidence interval; Ref., reference
Bold values are statistically significant at p-values ≤0.05
1
Introduced as Likert scale score (1–5)

frustration, and to wish that their provider had more lifestyles [43, 44]. Likewise, pharmacists have enhanced
time to spend talking to them addressing their concerns medication adherence by using motivational interview-
[42]. ing skills, reviewing patients’ regimens, supervising
To improve patients’ education and to tackle the non- treatment efficacy and security, and discussing the man-
adherence concern, GPs have enlisted more cooperation agement of missed doses. [45]. These factors suggest the
from other allied health professionals such as nurses and importance of strengthening collaboration between GPs,
pharmacists [37]. They can play an important role in pa- nurses, and pharmacists to improve patients’ care. Pa-
tients’ education and counseling. Nurses can educate pa- tients also believe that interprofessional collaborations
tients by providing information on diseases and patients’ are needed to provide the best care possible [46].
diagnosis [43, 44]. Additionally, they can promote self- We found that, as the number of pharmacies used for
management of chronic conditions and support medica- refilling prescriptions increased, treatment adherence de-
tion adherence. Similarly, pharmacists may enrich pa- creased. This is consistent with previous studies that
tient’s education by providing information regarding have found patients who made more visits to more phar-
medication such as proper use of drugs, potential side macies and those with less refill consolidation were sub-
effects and interactions, dosing schedules, and healthy stantially less adherent to their therapies [47, 48]. This
Fernandez-Lazaro et al. BMC Family Practice (2019) 20:132 Page 10 of 12

finding underlies the importance of the role of pharma- problem, the interviewer was not affiliated with the
cist in the context of medication adherence. study sites and had no contact with participants prior to
The use of a single pharmacy allows patients to have a the interview. Another limitation reflects the nature of
long-term relationship with pharmacists that fosters the study itself. The cross-sectional design may limit
pharmacist-patient communication and counseling. Use evaluation of cause-effect relationships. Longitudinal
of only one pharmacy to refill prescriptions also facilitates studies should explore the temporal validity of the asso-
the pharmacist’s ability to track patients’ medication, im- ciations found here. Lastly, the reference proportion of
proves patients’ follow up, and establishes a consistent participants not adhering to prescribed medications pro-
medication record. Having a pharmacy-based computer posed to calculate the sample size of the study differs
system connecting all pharmacies may be one possible ap- from the final findings, which may have somewhat
proach; however, it may lead patient to confusion in man- underpowered our results. Nonetheless, study’s strengths
aging medications and hinder communication between rest in the assessment of overall adherence in patients
patient, physicians, nurses, and pharmacists. Moreover, with chronic diseases rather than adherence to one sin-
pharmacists have reported a lack of confidence in having gle condition or particular drug therapy. We have con-
a complete idea of medication lists when patients use mul- sidered a number of common chronic conditions and
tiple pharmacies and may be less likely to optimize drug evaluated several factors using the WHO conceptual
utilization and safety [49]. Use of a single pharmacy, com- framework. Furthermore, since multimorbidity has be-
monly called a “pharmacy home”, has been proposed as a come the rule rather the exception in primary care set-
helpful way to foster patient-pharmacist communication tings [20], our research provides a more realistic and
and maintain a better control of medication [47, 48, 50]. accurate assessment of the non-adherence problem.
However, a pharmacy home may be impractical for many
patients and increase out of pocket costs [51]. As such, in-
tegrating pharmacists into primary care, as previously dis- Conclusions
cussed, may represent the most evidence-based and Adherence to long-term treatments for chronic condi-
feasible approach. Such an example occurs in North Caro- tions remains a challenging issue in primary care. A low
lina, where clinical pharmacist practitioners are integrated proportion of patients followed the recommendations
into primary care in team-based models of care having from healthcare providers which underlines the need of
positive impact on clinical and cost outcomes [52, 53]. reinforcing medication adherence in primary care. Our
Self-perception of a good quality of life and older age results should help to design new interventions aimed to
were also associated with adherence. Nonetheless, a lack enhance adherence. Considerable attention should be
of consensus exists about their precise effect. While given to the multidimensional factors potentially amen-
some studies corroborate our findings suggesting a rela- able to intervention found in this study such as patient’s
tionship between quality of life and adherence attributed knowledge and information. Health professionals should
to the influence of some psycho-social characteristics re- emphasize on meeting patients’ information needs and
lated to the ability of manage chronic diseases [54], reinforcing their education on treatment and diseases.
others have not found such association [55]. Similarly, Our results also provide firm evidence of the positive
the effect of age has been inconsistent across adherence impact of pharmacists on patients’ adherence when hav-
studies. An increase in age is generally associated with a ing a consolidated relationship. Due to current and fu-
greater adherence as younger people may perceive less ture challenges in primary care, future research is
severity of disease. This association continues until the needed to evaluate the extent of integrating pharmacists
onset of some aging processes, such as cognitive impair- into new team-based models of primary care.
ments, which usually occurs around the 70 years of age,
in which adherence starts to decline [56].
Our results should be interpreted in light of several Additional file
limitations. Self-reported questionnaires use for measur-
ing adherence may be susceptible to recall bias and may Additional file 1: Table S1. Proportion of Study Participants with
Chronic Conditions. Table S2. Level of Adherence and Likely Causes of
underestimate the true extent of non-adherence [57]. Non-Adherence according the Morisky-Green-Levine Questionnaire.
Nonetheless, the Morisky-Green-Levine questionnaire (DOCX 16 kb)
has yielded fair psychometric properties (sensitivity =
0.81, specificity = 0.44), and provided a useful tool to
evaluate medication adherence in numerous chronic dis- Abbreviations
ease studies. Furthermore, patients may want to please AMG: Adjusted morbidity group; CI: Confidence interval; GPs: General
practitioners; OR: Odds ratio; Ref: Reference; SD: Standard deviation;
their healthcare providers with their responses and may SE: Standard error; SNHS: Spanish National Health System; WHO: World
incur in social desirability bias. To minimize this Health Organization
Fernandez-Lazaro et al. BMC Family Practice (2019) 20:132 Page 11 of 12

Acknowledgments 3. Bernell S, Howard SW. Use Your Words Carefully: What Is a Chronic Disease.
We would like to thank all the primary care physicians and the staff of the Front Public Health. 2016;4:159 doi.org/10.3389/fpubh.2016.00159.
centers for their cooperation with the study. Special thanks to Juan Gastelu- 4. van der Heide I, Snoeijs S, Melchiorre MG, Quattrini S, Boerma W, Schellevis
Iturri Bilbao, Francisco Javier Iglesias Gomez, and Valentín del Villar Sordo to F, et al. Innovating care for people with multiple chronic conditions in
facilitate the coordination of this study. Many thanks to all the patients for Europe. Brussels: ICARE4EU; 2015.
their willingness to participate. 5. Boyd CM, Martin Fortin MD. Future of multimorbidity research: how should
understanding of multimorbidity inform health system design? Public
Authors’ contributions Health Rev. 2010;32:1.
C. F-L., the primary author, was involved in design of the study, conducted 6. Centers for Disease Control and Prevention, National Center for Chronic
the research, performed the data analysis and interpretation, and drafted the Disease Prevention and Health Promotion (NCCDPHP). Chronic Diseases in
manuscript. J. G-G. assisted in data analysis and drafting the manuscript and America. 2019. https://www.cdc.gov/chronicdisease ,Accessed 17 Jan 2019.
provided critical edits to the manuscript. D. A. was involved with study con- 7. Lorig KR, Ritter P, Stewart AL, Sobel DS, Brown BW Jr, Bandura A, et al.
ception, study oversight, and provided critical edits to the manuscript. D. F-L. Chronic disease self-management program: 2-year health status and health
was involved with data interpretation and provided critical edits to the care utilization outcomes. Med Care. 2001;39:1217–23.
manuscript. J.M-A. assisted in data analyses and interpretation of the data. 8. Bodenheimer T, Lorig K, Holman H, Grumbach K. Patient self-management
A.C-G., was involved in the conception and design of the design. F.M.R. was of chronic disease in primary care. Jama. 2002;288:2469–75. https://doi.org/
involved in the conception of the study and data acquisition. A.C. assisted in 10.1001/jama.288.19.2469.
interpretation of the data and provided critical edits to the manuscript. J. M- 9. Sabaté E. Adherence to long-term therapies: evidence for action.
C. was the senior author involved with study conception and design, study Switzerland: World Health Organization; 2003.
oversight, and provided critical edits to the manuscript. All authors have ap- 10. Molimard M, Le Gros V. Impact of patient-related factors on asthma control.
proved the final version of the manuscript. J Asthma. 2008;45:109–13. https://doi.org/10.1080/02770900701815727.
11. Venditti EM, Tan K, Chang N, Laffel L, McGinley G, Miranda N, et al. Barriers
Funding and strategies for oral medication adherence among children and
This research did not receive any specific grant from funding agencies in the adolescents with Type 2 diabetes. Diabetes Res Clin Pract. 2018;139:24–31.
public, commercial, or not-for-profit sectors. https://doi.org/10.1016/j.diabres.2018.02.001.
12. Kripalani S, Gatti ME, Jacobson TA. Association of age, health literacy, and
Availability of data and materials medication management strategies with cardiovascular medication
Data will be available upon reasonable request from the corresponding adherence. Patient Educ Couns. 2010;81:177–81. https://doi.org/10.1016/J.
author. PEC.2010.04.030.
13. Bidwal M, Lor K, Yu J, Ip E. Evaluation of asthma medication adherence rates
Ethics approval and consent to participate and strategies to improve adherence in the underserved population at a
Participation in the study was entirely voluntary. All participants provided Federally Qualified Health Center. Res Soc Adm Pharm. 2017;13:759–66.
written informed consent to take part in the study. Before patients https://doi.org/10.1177/2040622317714966.
consented to participate in the interview, all the subjects received a detailed 14. Casebeer L, Huber C, Bennett N, Shillman R, Abdolrasulnia M, Salinas GD,
both written and oral information about the study. Patients were also et al. Improving the physician-patient cardiovascular risk dialogue to
informed that they could withdraw from the study at any time without improve statin adherence. BMC Fam Pract. 2009;10:48. https://doi.org/10.
penalty. Patients’ information was coded and stored safely, and only the 1186/1471-2296-10-48.
researcher had access to it. This study was conducted in accordance with 15. Palladino R, Tayu Lee J, Ashworth M, Triassi M, Millett C. Associations
the Declaration of Helsinki and was approved by the Ethics Committee of between multimorbidity, healthcare utilisation and health status: evidence
the Hospital Complex of Soria. from 16 European countries. Age Ageing. 2016;45:431–5. https://doi.org/10.
1093/ageing/afw044.
Consent for publication 16. Prados-Torres A, Poblador-Plou B, Calderón-Larrañaga A, Gimeno-Feliu LA,
Written consent was received from all participants to publicly share the González-Rubio F, Poncel-Falcó A, et al. Multimorbidity Patterns in Primary
results of the study. Care: Interactions among Chronic Diseases Using Factor Analysis. PLoS One.
2012;7:e32190. https://doi.org/10.1371/journal.pone.0032190.
Competing interests 17. Foreman KJ, Marquez N, Dolgert A, Fukutaki K, Fullman N, McGaughey M,
The authors declare that they have no competing interests. et al. Forecasting life expectancy, years of life lost, and all-cause and cause-
specific mortality for 250 causes of death: reference and alternative
Author details scenarios for 2016–40 for 195 countries and territories. Lancet. 2018;392:
1 2052–90. https://doi.org/10.1016/S0140-6736(18)31694-5.
Department of Biomedical and Diagnostic Sciences, School of Medicine,
University of Salamanca, Calle Alfonso X el Sabio s/n, 37007 Salamanca, 18. Van Oostrom SH, Picavet HSJ, De Bruin SR, Stirbu I, Korevaar JC, Schellevis
Spain. 2Department of Preventive Medicine and Public Health, School of FG, et al. Multimorbidity of chronic diseases and health care utilization in
Medicine, IDISNA, University of Navarra, Pamplona, Spain. 3Department of general practice. BMC Fam Pract. 2014;15:61. https://doi.org/10.1186/1471-
Sociology, Pablo de Olavide University, Seville, Spain. 4Dual Enrollment 2296-15-61.
Program, Point University-Savannah Campus, Savannah, GA, USA. 19. Glynn LG, Valderas JM, Healy P, Burke E, Newell J, Gillespie P, et al. The prevalence
5
Department of Cell Biology, Histology and Pharmacology, University of of multimorbidity in primary care and its effect on health care utilization and
Valladolid, Soria, Spain. 6Department of Biochemistry, Molecular Biology and cost. Fam Pract. 2011;28:516–23. https://doi.org/10.1093/fampra/cmr013.
Physiology, Faculty of Physical Therapy, University of Valladolid, Soria, Spain. 20. Fortin M, Lapointe L, Hudon C, Vanasse A. Multimorbidity is common to family
7
Department of Anatomy and Radiology, University of Valladolid, Soria, Spain. practice: is it commonly researched? Can Fam Physician. 2005;51:244–5.
8
Castile and Leon Healthcare Services, Valladolid, Spain. 21. Prado JC, Mion D. Adherence to Medication: The Importance of Research in
Primary Care. Am J Hypertens. 2010;23:109–9. https://doi.org/10.1038/ajh.2009.205.
Received: 17 April 2019 Accepted: 30 August 2019 22. Ministry of Health and Social Policy. Health Information Institute. National
Health System of Spain. Madrid; 2012. http://www.msps.es/en/organizacion/
sns/libroSNS.htm ,Accessed 29 Jun 2019
References 23. Jansa M, Hernandez C, Vidal M, Nunez M, Bertran MJ, Sanz S, et al.
1. Christensen K, Doblhammer G, Rau R, Vaupel JW. Ageing populations: the Multidimensional analysis of treatment adherence in patients with multiple
challenges ahead. Lancet. 2009;374:1196–208 doi.org/10.1016/S0140-6736 chronic conditions. A cross-sectional study in a tertiary hospital. Patient
(09)61460-4. Educ Couns. 2010;81:161–8. https://doi.org/10.1016/j.pec.2009.12.012.
2. Bloom DE, Cafiero E, Jané-Llopis E. Abrahams-Gessel S. Fathima S, et al. The 24. Napolitano F, Napolitano P, Angelillo IF, Group CW. Medication adherence
global economic burden of noncommunicable diseases. Program on the among patients with chronic conditions in Italy. Eur J Pub Health. 2015;26:
Global Demography of Aging: Bloom LR; 2012. 48–52. https://doi.org/10.1093/eurpub/ckv147.
Fernandez-Lazaro et al. BMC Family Practice (2019) 20:132 Page 12 of 12

25. Val Jiménez A, Amorós Ballestero G, Martínez Visa P, Fernández Ferré ML, 45. Mino-León D, Reyes-Morales H, Flores-Hernández S. Effectiveness of
León SM. Descriptive study of patient compliance in pharmacologic involving pharmacists in the process of ambulatory health care to improve
antihypertensive treatment and validation of the Morisky and Green test. drug treatment adherence and disease control. J Eval Clin Pract. 2015;21:
Aten Primaria. 1992;10:767–70. 7–12. https://doi.org/10.1111/jep.12207.
26. Morisky DE, Green LW, Levine DM. Concurrent and predictive validity of a 46. Kelly DV, Young S, Phillips L, Clark D. Patient attitudes regarding the role of
self-reported measure of medication adherence. Med Care. 1986;24:67–74. the pharmacist and interest in expanded pharmacist services. Can Pharm J
27. Hughes JS, Averill RF, Eisenhandler J, Goldfield NI, Muldoon J, Neff JM, et al. (Ott). 2014;147:239–47. https://doi.org/10.1177/1715163514535731.
Clinical Risk Groups (CRGs): a classification system for risk-adjusted 47. Choudhry NK, Fischer MA, Avorn J, Liberman JN, Schneeweiss S, Pakes J,
capitation-based payment and health care management. Med Care. 2004; et al. The implications of therapeutic complexity on adherence to
42:81–90. https://doi.org/10.1097/01.mlr.0000102367.93252.70. cardiovascular medications. Arch Intern Med. 2011;171:814–22. https://doi.
28. Gerencia Regional de Castilla y León. Estrategia de Atención al Paciente org/10.1001/archinternmed.2010.495.
Crónico en Castilla y León [Integrated Healthcare Model for Chronic 48. Marcum ZA, Driessen J, Thorpe CT, Gellad WF, Donohue JM. Effect of
Patients in the Regional Health Services of Castile and Leon]. Valladolid: multiple pharmacy use on medication adherence and drug–drug
Junta de Castilla y León; 2015. interactions in older adults with Medicare Part D. J Am Geriatr Soc. 2014;62:
29. World Health Organization. Global recommendations on physical activity for 244–52. https://doi.org/10.1111/jgs.12645.
health. World Health Organization. Geneva; 2010. http://apps.who.int/iris/ 49. Fleming M, Nemlekar P, Brown CM, Cantu R. Exploratory study of
handle/10665/44399 ,Accessed 9 Sept 2018 community pharmacists’ perceptions about new or transferred prescription
30. Mahoney FI, Barthel DW. Functional evaluation: the Barthel index. Md State incentives. J Am Pharm Assoc. 2012;52:e53–8. https://doi.org/10.1331/
Med J. 1965;14:61–5. JAPHA.2012.11096.
31. Li YT, Wang HHX, Liu KQL, Lee GKY, Chan WM, Griffiths SM, et al. Medication 50. Salanitro AH, Kripalani S. Prescription refill management and its effect on
Adherence and Blood Pressure Control Among Hypertensive Patients With adherence. Arch Intern Med. 2011;171:822–3. https://doi.org/10.1001/
Coexisting Long-Term Conditions in Primary Care Settings. Medicine archinternmed.2010.481.
(Baltimore). 2016;95:e3572. https://doi.org/10.1097/MD.0000000000003572. 51. Zhang Y, Gellad WF, Zhou L, Lin Y-J, Lave JR. Access to and use of $4
32. Fernandez-Lazaro CI, Adams DP, Fernandez-Lazaro D, Garcia-González JM, generic programs in Medicare. J Gen Intern Med. 2012;27:1251–7. Epub
Caballero-Garcia A, Miron-Canelo JA. Medication adherence and barriers 2012 Feb 7. https://doi.org/10.1007/s11606-012-1993-9.
among low-income, uninsured patients with multiple chronic conditions. 52. Scott MA, Heck JE, Wilson CG. The Integral Role of the Clinical Pharmacist
Res Social Adm Pharm. 2019;15:744–53. https://doi.org/10.1016/j.sapharm. Practitioner in Primary Care. N C Med J. 2017;78:181–5. https://doi.org/10.
2018.09.006. 18043/ncm.78.3.181.
33. Pagès-Puigdemont N, Tuneu L, Masip M, Valls P, Puig T, Mangues MA. 53. Hawes EM, Misita C, Burkhart JI, McKnight L, Deyo ZM, Lee R-A, et al.
Determinants of medication adherence among chronic patients from an Prescribing pharmacists in the ambulatory care setting: experience at the
urban area: a cross-sectional study. Eur J Pub Health. 2019;29:419–24. University of North Carolina Medical Center. Am J Heal Pharm. 2016;73:
https://doi.org/10.1093/eurpub/cky259. 1425–33. https://doi.org/10.2146/ajhp150771.
34. Wens J, Vermeire E, Van Royen P, Sabbe B, Denekens J. GPs’ perspectives of 54. Holt EW, Muntner P, Joyce CJ, Webber L, Krousel-Wood MA. Health-related
type 2 diabetes patients’ adherence to treatment: A qualitative analysis of quality of life and antihypertensive medication adherence among older
barriers and solutions. BMC Fam Pract. 2005;6:20. https://doi.org/10.1186/ adults. Age Ageing. 2010;39:481–7. https://doi.org/10.1093/ageing/afq040.
1471-2296-6-20. 55. Côté I, Farris K, Feeny D. Is adherence to drug treatment correlated with
35. Friis K, Lasgaard M, Osborne RH, Maindal HT. Gaps in understanding health health-related quality of life? Qual Life Res. 2003;12:621–33. https://doi.org/
and engagement with healthcare providers across common long-term 10.1023/A:1025180524614.
conditions: a population survey of health literacy in 29 473 Danish citizens. 56. Krueger KP, Berger BA, Felkey B. Medication adherence and persistence: a
BMJ Open. 2016;6:e009627. https://doi.org/10.1136/bmjopen-2015-009627. comprehensive review. Adv Ther. 22:313–56. https://doi.org/10.1007/
36. Fredericksen RJ, Gibbons L, Brown S, Edwards TC, Yang FM, Fitzsimmons E, BF02850081.
et al. Medication understanding among patients living with multiple 57. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353:
chronic conditions: Implications for patient-reported measures of 487–97. https://doi.org/10.1056/NEJMra050100.
adherence. Res Soc Adm Pharm. 2018;14:540–4. https://doi.org/10.1016/j.
sapharm.2017.06.009. Publisher’s Note
37. Kvarnström K, Airaksinen M, Liira H. Barriers and facilitators to medication Springer Nature remains neutral with regard to jurisdictional claims in
adherence: a qualitative study with general practitioners. BMJ Open. 2018;8: published maps and institutional affiliations.
e015332. https://doi.org/10.1136/bmjopen-2016-015332.
38. Say RE, Thomson R. The importance of patient preferences in treatment
decisions--challenges for doctors. BMJ. 2003;327:542–5. https://doi.org/10.
1136/bmj.327.7414.542.
39. Barry CA, Bradley CP, Britten N, Stevenson FA, Barber N. Patients’ unvoiced
agendas in general practice consultations: qualitative study. BMJ. 2000;320:
1246–50. https://doi.org/10.1136/bmj.320.7244.1246.
40. Barber N, Parsons J, Clifford S, Darracott R, Horne R. Patients’ problems with
new medication for chronic conditions. Qual Saf Health Care. 2004;13:172–5.
https://doi.org/10.1136/qhc.13.3.172.
41. Marvel MK, Epstein RM, Flowers K, Beckman HB. Soliciting the Patient’s
Agenda. JAMA. 1999;281:283. https://doi.org/10.1001/jama.281.3.283.
42. Smith ML, Bergeron CD, Adler CH, Patel A, Ahn S, Towne SD, et al. Factors
associated with healthcare-related frustrations among adults with chronic
conditions. Patient Educ Couns. 2017;100:1185–93. https://doi.org/10.1016/J.
PEC.2016.12.033.
43. Celio J, Ninane F, Bugnon O, Schneider MP. Pharmacist-nurse collaborations
in medication adherence-enhancing interventions: A review. Patient Educ
Couns. 2018;101:1175–92. https://doi.org/10.1016/J.PEC.2018.01.022.
44. Matthys E, Remmen R, Van Bogaert P. An overview of systematic reviews on
the collaboration between physicians and nurses and the impact on patient
outcomes: what can we learn in primary care? BMC Fam Pract. 2017;18:110.
https://doi.org/10.1186/s12875-017-0698-x.