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1.  Adherence to Topical Glaucoma Medications in Ethiopian Patients 
Purpose:
Successful outcomes of medical treatment for glaucoma require proper and daily use of medication to prevent disease progression. The aim of this study was to determine the adherence to anti-glaucoma medications and factors associated with non-adherence among patients with ocular hypertension (OHT) or glaucoma at Jimma University Specialized Hospital, Ethiopia.
Materials and Methods:
A hospital based cross sectional study was conducted on 200 consecutive patients from July to November 2010 at Jimma University Hospital in Southwest Ethiopia. Patients with OHT or glaucoma who were taking topical anti-glaucoma medications for more than six months were included. The study subjects were interviewed and their medical records were reviewed. Non-adherence to glaucoma therapy (NAGT) was defined as self-reported on missed medications or missed appointments, or a physician noting poor adherence. A P < 0.05 was statistically significant.
Result:
Overall, 135 (67.5%) patients were non adherent to glaucoma therapy. Non adherence was associated with older age (P = 0.04), advanced stage of glaucoma (P = 0.01), longer frequency of follow up (P = 0.00) and financial problem (P = 0.000). Sex (P = 0.53), level of education (P = 0.09), and marital status (P = 0.77) were not statistically significantly associated with non-adherence to anti-glaucoma drug treatment.
Conclusion:
A relatively high proportion of patients were not adhering to the medications regimen for glaucoma. Older age, advanced glaucoma, lengthier frequency of follow-up and financial hardship were associated with non-adherence. Eye care providers should be aware of the problem of non-adherence to topical medications.
doi:10.4103/0974-9233.148350
PMCID: PMC4302478  PMID: 25624675
Glaucoma; Ocular Hypertension; Adherence; Topical Glaucoma Therapy; Ethiopia
2.  Evaluation of adherence to oral antiviral hepatitis B treatment using structured questionnaires 
World Journal of Hepatology  2012;4(2):43-49.
AIM: To assess adherence rates to nucleos(t)ide analogues (NUCs) therapy in patients with chronic hepatitis B virus infection and determine factors associated with adherence.
METHODS: The questionnaire study was conducted in the liver clinics at Concord Repatriation General Hospital. All patients who were currently taking one or more NUCs were asked to complete a structured, self-administered 32-item questionnaire. Adherence was measured using visual analogue scales. The patient’s treating clinician was also asked to assess their patient’s adherence via a structured questionnaire.
RESULTS: A total of 80 patients completed the questionnaire. Sixty six percent of the patients (n = 49) reported optimal adherence whilst 25 (33.8%) graded their adherence to NUCs as suboptimal. Thirty four (43%) patients reported to have omitted taking their NUCs sometime in the past. Recent non-adherence was uncommon. Amongst the patients who reported skipping medications, the most common reason cited was ”forgetfulness“ (n = 27, 56.25%). Other common reasons included: ran out of medications (n = 5, 10.42%), being too busy (n = 4, 8.33%) and due to a change in daily routine (n = 5, 10.42%). Patients who reported low adherence to other prescription pills were also more likely to miss taking NUCs (P = 0.04). Patients who were under the care of a language-discordant clinician were also more likely to report suboptimal adherence to NUCs (P = 0.04).
CONCLUSION: Adherence rates were much less than that expected by the physician and has potential adverse affect on long term outcome. Communication and education appear central and strategies need to be implemented to improve ongoing adherence.
doi:10.4254/wjh.v4.i2.43
PMCID: PMC3295851  PMID: 22400085
Patient compliance; Patient adherence; Antiviral agents; Hepatitis B; Chronic
3.  Drug adherence and multidisciplinary care in patients with multiple sclerosis: Protocol of a prospective, web-based, patient-centred, nation-wide, Dutch cohort study in glatiramer acetate treated patients (CAIR study) 
BMC Neurology  2011;11:40.
Background
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, for which no definitive treatment is available. Most patients start with a relapsing-remitting course (RRMS). Disease-modifying drugs (DMDs) reduce relapses and disability progression. First line DMDs include glatiramer acetate (GA), interferon-beta (INFb)-1a and INFb-1b, which are all administered via injections. Effectiveness of DMD treatment depends on adequate adherence, meaning year-long continuation of injections with a minimum of missed doses. In real-life practice DMD-treated patients miss 30% of doses. The 6-month discontinuation rate is up to 27% and most patients who discontinue do so in the first 12 months.
Treatment adherence is influenced by the socio-economic situation, health care and caregivers, disease, treatment and patient characteristics. Only a few studies have dealt with adherence-related factors in DMD-treated patients. Self-efficacy expectations were found to be related to GA adherence. Patient education and optimal support improve adherence in general. Knowledge of the aspects of care that significantly relate to adherence could lead to adherence-improving measures. Moreover, identification of patients at risk of inadequate adherence could lead to more efficient care.
In the near future new drugs will become available for RRMS. Detailed knowledge on factors prognostic of adherence and on care aspects that are associated with adequate adherence will improve the chances of these drugs becoming effective treatments. We investigate in RRMS patients the relationship between drug adherence and multidisciplinary care, as well as factors associated with adherence. Given the differences in the frequency of administration and in the side effects between the DMDs we decided to study patients treated with the same DMD, GA.
Methods/design
The Correlative analyses of Adherence In Relapsing remitting MS (CAIR) study is an investigator-initiated, prospective, web-based, patient-centred, nation-wide cohort study in the Netherlands.
The primary objective is to investigate whether GA adherence is associated with specific disciplines of care or quantities of specific care. The secondary objective is to investigate whether GA adherence is associated with specific aspects of the socio-economic situation, health care and caregivers, disease, treatment or patient characteristics.
All data are acquired on-line via a study website. All RRMS patients in the Netherlands starting GA treatment are eligible. Patients are informed by neurologists, nurses, and websites from national MS patient organisations. All data, except on disability, are obtained by patient self-reports on pre-defined and random time points. The number of missed doses and the number of patients having discontinued GA treatment at 6 and 12 months are measures of adherence. Per care discipline the number of sessions and the total duration of care are measures of received care. The full spectrum of non-experimental care that is available in the Netherlands is assessed. Care includes 'physical' contacts, contacts by telephone or internet, health-promoting activities and community care activities. Care received over the preceding 14 days is assessed by patients at baseline and every other week thereafter up to month 12. Every 3 months neurologists and nurses record care disciplines to which patients have been referred.
The Dutch Adherence Questionnaire-90 (DAQ-90) is a 90-item questionnaire based on the World Health Organisation (WHO) 2003 report on adherence and comprehensively assesses five domains of evidence-based determinants of adherence: socio-economic, health care and caregivers, disease, treatment, and patient-related factors. In addition, self-efficacy is assessed by the MS Self-Efficacy Scale (MSSES), and mood and health-related quality of life (HRQoL) by the Multiple Sclerosis Quality of Life-54 questionnaire (MSQoL-54). Relapses and adverse events probably or definitively related to GA are also reported.
Discussion
In this study data is mainly acquired by patients' self-reporting via the internet. On-line data acquisition by patients does not require study visits to the hospital and can easily be integrated into daily life. The web-based nature of the study is believed to prevent missing data and study drop-outs. Moreover, the automated process of filling in questionnaires ensures completeness and consistency, thus improving data quality. The combination of patient-reported outcomes, fully web-based data capture and nation-wide information to all eligible patients are distinguishing features of the study and contribute to its scientific potential.
Trial registration
Netherlands Trial Register (NTR): NTR2432
doi:10.1186/1471-2377-11-40
PMCID: PMC3080802  PMID: 21450086
4.  Self-management skills in adolescents with chronic rheumatic disease: A cross-sectional survey 
Background
For adolescents with a diagnosis of lifelong chronic illness, mastery of self-management skills is a critical component of the transition to adult care. This study aims to examine self-reported medication adherence and self-care skills among adolescents with chronic rheumatic disease.
Methods
Cross-sectional survey of 52 adolescent patients in the Pediatric Rheumatology Clinic at UCSF. Outcome measures were self-reported medication adherence, medication regimen knowledge and independence in health care tasks. Predictors of self-management included age, disease perception, self-care agency, demographics and self-reported health status. Bivariate associations were assessed using the Student's t-test, Wilcoxon rank sum test and Fisher exact test as appropriate. Independence in self-management tasks were compared between subjects age 13-16 and 17-20 using the chi-squared test.
Results
Subjects were age 13-20 years (mean 15.9); 79% were female. Diagnoses included juvenile idiopathic arthritis (44%), lupus (35%), and other rheumatic conditions (21%). Mean disease duration was 5.3 years (SD 4.0). Fifty four percent reported perfect adherence to medications, 40% reported 1-2 missed doses per week, and 6% reported missing 3 or more doses. The most common reason for missing medications was forgetfulness. Among health care tasks, there was an age-related increase in ability to fill prescriptions, schedule appointments, arrange transportation, ask questions of doctors, manage insurance, and recognize symptoms of illness. Ability to take medications as directed, keep a calendar of appointments, and maintain a personal medical file did not improve with age.
Conclusions
This study suggests that adolescents with chronic rheumatic disease may need additional support to achieve independence in self-management.
doi:10.1186/1546-0096-9-35
PMCID: PMC3254592  PMID: 22145642
Self-management; transition; pediatric rheumatology
5.  Predictors of adherence to antiretroviral therapy among people living with HIV/AIDS in resource-limited setting of southwest ethiopia 
Background
Good adherence to antiretroviral therapy is necessary to achieve the best virological response, lower the risk that drug resistance will develop, and reduce morbidity and mortality. Little is known about the rate and predictors of adherence in Ethiopia. Therefore this study determines the magnitude and predictors of adherence to antiretroviral therapy among people living with HIV/AIDS in Southwest Ethiopia.
Methods
A cross sectional study was carried out from January 1, 2009 to March 3, 2009 among 319 adult PLWHA (≥ 18 years) attending ART clinic at Jimma university Specialized Hospital (JUSH). Multiple Logistic regression models were constructed with adherence and independent variables to identify the predictors.
Results
About 303(95%) of the study subjects were adherent based on self report of missed doses (dose adherence) in a one-week recall before the actual interview. The rate of self reported adherence in the study based on the combined indicator of the dose, time and food adherence measurement was 72.4%. Patients who got family support were 2 times [2.12(1.25-3.59)] more likely to adhere than those who didn't get family support as an independent predictor of overall adherence (dose, time and food). The reasons given for missing drugs were 9(27.3%) running out of medication/drug, 7(21.2%) being away from home and 7(21.2%) being busy with other things.
Conclusion
The adherence rate found in this study is similar to other resource limited setting and higher than the developed country. This study highlights emphasis should be given for income generating activities and social supports that helps to remember the patients for medication taking and management of opportunistic infections during the course of treatment.
doi:10.1186/1742-6405-7-39
PMCID: PMC2988692  PMID: 21034506
6.  Medication Adherence Among Community-Dwelling Patients With Heart Failure 
Mayo Clinic Proceedings  2011;86(4):273-281.
OBJECTIVE: To determine medication use and adherence among community-dwelling patients with heart failure (HF).
PATIENTS AND METHODS: Residents of Olmsted County, Minnesota, with HF were recruited from October 10, 2007, through February 25, 2009. Pharmacy records were obtained for the 6 months after enrollment. Medication adherence was measured by the proportion of days covered (PDC). A PDC of less than 80% was classified as poor adherence. Factors associated with medication adherence were investigated.
RESULTS: Among the 209 study patients with HF, 123 (59%) were male, and the mean ± SD age was 73.7±13.5 years. The median (interquartile range) number of unique medications filled during the 6-month study period was 11 (8-17). Patients with a documented medication allergy were excluded from eligibility for medication use within that medication class. Most patients received conventional HF therapy: 70% (147/209) were treated with β-blockers and 75% (149/200) with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Most patients (62%; 127/205) also took statins. After exclusion of patients with missing dosage information, the proportion of those with poor adherence was 19% (27/140), 19% (28/144), and 13% (16/121) for β-blockers, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and statins, respectively. Self-reported data indicated that those with poor adherence experienced more cost-related medication issues. For example, those who adhered poorly to statin therapy more frequently reported stopping a prescription because of cost than those with good adherence (46% vs 6%; P<.001), skipping doses to save money (23% vs 3%; P=.03), and not filling a new prescription because of cost (46% vs 6%; P<.001).
CONCLUSION: Community-dwelling patients with HF take a large number of medications. Medication adherence was suboptimal in many patients, often because of cost.
Community-dwelling patients with heart failure take a substantial number of medications; the authors of this study of 209 patients found that medication adherence is suboptimal, primarily because of the cost of treatment.
doi:10.4065/mcp.2010.0732
PMCID: PMC3068886  PMID: 21389248
7.  A Randomized Controlled Trial Comparing the Effects of Counseling and Alarm Device on HAART Adherence and Virologic Outcomes 
PLoS Medicine  2011;8(3):e1000422.
Michael Chung and colleagues show that intensive early adherence counseling at HAART initiation resulted in sustained, significant impact on adherence and virologic treatment failure, whereas use of an alarm device had no effect.
Background
Behavioral interventions that promote adherence to antiretroviral medications may decrease HIV treatment failure. Antiretroviral treatment programs in sub-Saharan Africa confront increasing financial constraints to provide comprehensive HIV care, which include adherence interventions. This study compared the impact of counseling and use of an alarm device on adherence and biological outcomes in a resource-limited setting.
Methods and Findings
A randomized controlled, factorial designed trial was conducted in Nairobi, Kenya. Antiretroviral-naïve individuals initiating free highly active antiretroviral therapy (HAART) in the form of fixed-dose combination pills (d4T, 3TC, and nevirapine) were randomized to one of four arms: counseling (three counseling sessions around HAART initiation), alarm (pocket electronic pill reminder carried for 6 months), counseling plus alarm, and neither counseling nor alarm. Participants were followed for 18 months after HAART initiation. Primary study endpoints included plasma HIV-1 RNA and CD4 count every 6 months, mortality, and adherence measured by monthly pill count. Between May 2006 and September 2008, 400 individuals were enrolled, 362 initiated HAART, and 310 completed follow-up. Participants who received counseling were 29% less likely to have monthly adherence <80% (hazard ratio [HR] = 0.71; 95% confidence interval [CI] 0.49–1.01; p = 0.055) and 59% less likely to experience viral failure (HIV-1 RNA ≥5,000 copies/ml) (HR 0.41; 95% CI 0.21–0.81; p = 0.01) compared to those who received no counseling. There was no significant impact of using an alarm on poor adherence (HR 0.93; 95% CI 0.65–1.32; p = 0.7) or viral failure (HR 0.99; 95% CI 0.53–1.84; p = 1.0) compared to those who did not use an alarm. Neither counseling nor alarm was significantly associated with mortality or rate of immune reconstitution.
Conclusions
Intensive early adherence counseling at HAART initiation resulted in sustained, significant impact on adherence and virologic treatment failure during 18-month follow-up, while use of an alarm device had no effect. As antiretroviral treatment clinics expand to meet an increasing demand for HIV care in sub-Saharan Africa, adherence counseling should be implemented to decrease the development of treatment failure and spread of resistant HIV.
Trial registration
ClinicalTrials gov NCT00273780
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Adherence to HIV treatment programs in poor countries has long been cited as an important public health concern, especially as poor adherence can lead to drug resistance and inadequate treatment of HIV. However, two factors have recently cast doubt on the poor adherence problem: (1) recent studies have shown that adherence is high in African HIV treatment programs and often better than in Western HIV clinics. For example, in a meta-analysis of 27 cohorts from 12 African countries, adequate adherence was noted in 77% of subjects compared to only 55% among 31 North America cohorts; (2) choice of antiretroviral regimens may impact on the development of antiretroviral resistance. In poor countries, most antiretroviral regimens contain non-nucleoside reverse transcriptase inhibitors (NNRTIs), such as nevirapine or efavirenz, which remain in the patient's circulation for weeks after single-dose administration. This situation means that such patients may not experience antiretroviral resistance unless they drop below 80% adherence—contrary to the more stringent 95% plus adherence levels needed to prevent resistance in regimens based on unboosted protease inhibitors—ultimately, off-setting some treatment lapses in resource-limited settings where NNRTI-based regimens are widely used.
Why Was This Study Done?
Given that adherence may not be as crucial an issue as previously thought, antiretroviral treatment programs in sub-Saharan Africa may be spending scarce resources to promote adherence to the detriment of some potentially more effective elements of HIV treatment and management programs. Although many treatment programs currently include adherence interventions, there is limited quality evidence that any of these methods improve long-term adherence to HIV treatment. Therefore, it is necessary to identify adherence interventions that are inexpensive and proven to be effective in resource-limited settings. As adherence counseling is already widely implemented in African HIV treatment programs and inexpensive alarm devices are thought to also improve compliance, the researchers compared the impact of adherence counseling and the use of an alarm device on adherence and biological outcomes in patients enrolled in HIV programs in rural Kenya.
What Did the Researchers Do and Find?
The researchers enrolled 400 eligible patients (newly diagnosed with HIV, never before taken antiretroviral therapy, aged over 18 years) to four arms: (1) adherence counseling alone; (2) alarm device alone; (3) both adherence counseling and alarm device together; and (4) a control group that received neither adherence counseling nor alarm device. The patients had blood taken to record baseline CD4 count and HIV-1 RNA and after starting HIV treatment, returned to the study clinic every month with their pill bottles for the study pharmacist to count and recorded the number of pills remaining in the bottle, and to receive another prescription. Patients were followed up for 18 months and had their CD4 count and HIV-1 RNA measured at 6, 12, and 18 months.
Patients receiving adherence counseling were 29% less likely to experience poor adherence compared to those who received no counseling. Furthermore, those receiving intensive early adherence counseling were 59% less likely to experience viral failure. However, there was no significant difference in mortality or significant differences in CD4 counts at 18 months follow-up between those who received counseling and those who did not. There were no significant differences in adherence, time to viral failure, mortality, or CD4 counts in patients who received alarm devices compared to those who did not.
What Do These Findings Mean?
The results of this study suggest that intensive adherence counseling around the time of HIV treatment initiation significantly reduces poor adherence and virologic treatment failure, while using an alarm device has no effect. Therefore, investment in careful counseling based on individual needs at the onset of HIV treatment initiation, appears to have sustained benefit, possibly through strengthening the relationship between the health care provider and patient through communication, education, and trust. Interactive adherence counseling supports the bond between the clinic and the patient and may result in fewer patients needing to switch to expensive second-line medications and, possibly, may help to decrease the spread of resistant HIV. These findings define an adherence counseling protocol that is effective and are highly relevant to other HIV clinics caring for large numbers of patients in sub-Saharan Africa.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000422.
UNAIDS provides information about HIV treatment strategies
The American Public Health Association has information about adherence to HIV treatment regimens
The US Department of Health and Human Services has information for patients about adherence to HIV treatment
The World Health Organization provides information about HIV treatment pharmacovigilance
doi:10.1371/journal.pmed.1000422
PMCID: PMC3046986  PMID: 21390262
8.  Predictors of non-adherence among individuals with bipolar disorder receiving treatment in a community mental health clinic 
Comprehensive psychiatry  2008;50(2):100-107.
Background
Subjective experience of illness is a critical component of treatment adherence in populations with bipolar disorder (BPD). This cross-sectional analysis examined clinical and subjective variables in relation to adherence in 140 individuals with BPD receiving treatment with mood stabilizing medication.
Methods
Non-adherence was defined as missing 30% or more of medication on the Tablets Routine Questionnaire (TRQ), a self-reported measure of medication treatment adherence. Adherent and non-adherent groups were compared on measures of attitudes towards illness and treatment including the Attitudes towards Mood Stabilizers Questionnaire (AMSQ), the Insight and Treatment Attitudes Questionnaire (ITAQ), The Rating of Medication Influences (ROMI), and the Multidimensional Health Locus of Control Scale (MHLC).
Results
Except for substance abuse comorbidity, adherent individuals (N=113, 80.7%) did not differ from non-adherent individuals (N=27, 19.3%) on clinical variables. However, non-adherent individuals had reduced insight into illness, more negative attitudes towards medications, fewer reasons for adherence, and more perceived reasons for non-adherence compared to adherent individuals. The strongest attitudinal predictors for non-adherence were difficulties with medication routines (OR 2.2) and negative attitudes towards drugs in general (OR 2.3).
Limitations
Results interpretation is limited by cross-sectional design, self-report methodology and sample size.
Conclusions
Comorbid substance abuse, negative attitudes towards mood stabilizing medication, and difficulty managing to take medication in the context of one's daily schedule are primary determinants of medication treatment adherence. A patient-centered, collaborative model of care that addresses negative attitudes towards medication and difficulty coping with medication routines use may be ideally suited to address individual adherence challenges.
doi:10.1016/j.comppsych.2008.06.008
PMCID: PMC2746444  PMID: 19216885
Bipolar disorder; treatment adherence; compliance; subjective experience; attitudes towards treatment; mood stabilizers
9.  Compliance with Pharmacotherapy and Direct Healthcare Costs in Patients with Parkinson’s Disease: A Retrospective Claims Database Analysis 
Background
Parkinson’s disease (PD) is a progressive neurological disorder for which, at present, there is no cure. Current therapy is largely based on the use of dopamine agonists and dopamine replacement therapy, designed to control the signs and symptoms of the disease. The majority of current treatments are administered in tablet form and can involve multiple daily doses, which may contribute to sub-optimal compliance. Previous studies with small groups of patients suggest that non-compliance with treatment can result in poor response to therapy and may ultimately increase direct and indirect healthcare costs.
Objective
To determine the extent of non-compliance within the general PD population in the USA as well as the patient characteristics and healthcare costs associated with compliance and non-compliance.
Methods
A retrospective analysis from a managed care perspective was conducted using data from the USA PharMetrics patient-centric claims database. PharMetrics claims data were complete from 31 December 2005 to 31 December 2009. Patients were included if they had at least two diagnoses for PD between 31 December 2005 and 31 December 2008, were older than 18 years of age, were continuously enrolled for at least 12 months after the date of the most recent PD diagnosis, and had no missing or invalid data. The follow-up period was the most recent 12-month block of continuous enrollment that occurred between 2006 and 2009. Patients were required to have at least one PD-related prescription within the follow-up period. The medication possession ratio (MPR) was used to categorise patients as compliant or non-compliant. Direct all-cause annual healthcare costs for patients with PD were estimated for each patient, and regression analyses were conducted to determine predictors for non-compliance.
Results
A total of 15,846 patients were included, of whom 46 % were considered to be non-compliant with their prescribed medication (MPR <0.8). Predictors of non-compliance included prescription of a medication administered in multiple daily doses (p < 0.0001), a period of <2 years since the initial PD diagnosis (p = 0.0002), a diagnosis of gastrointestinal disorder (p < 0.0001), and a diagnosis of depression (p < 0.0001). Non-compliance was also found to be related to age, with a lower odds of non-compliance in patients aged 41–80 years than in patients aged ≥81 years (p < 0.05). Although total drug mean costs were higher for compliant patients than non-compliant patients (driven mainly by the cost of PD-related medications), the mean costs associated with emergency room and inpatient visits were higher for patients non-compliant with their prescribed medication. Overall, the total all-cause annual healthcare mean cost was lower for compliant ($77,499) than for non-compliant patients ($84,949; p < 0.0001).
Conclusion
Non-compliance is prevalent within the general USA PD population and is associated with a recent PD diagnosis, certain comorbidities, and multiple daily treatment dosing. Non-compliance may increase the burden on the healthcare system because of greater resource usage compared with the compliant population. Treatments that require fewer daily doses may have the potential to improve compliance, which in turn could reduce the economic burden associated with PD.
doi:10.1007/s40258-013-0033-1
PMCID: PMC3717155  PMID: 23649891
10.  Medication adherence behaviors of Medicare beneficiaries 
Background
Medication adherence is crucial for positive outcomes in the management of chronic conditions. Comprehensive medication consultation can improve medication adherence by addressing intentional and unintentional nonadherence. The Medicare Part D prescription drug benefit has eliminated some cost barriers. We sought to examine variables that impact self-reported medication adherence behaviors in an ambulatory Medicare-beneficiary population and to identify the factors that influence what information is provided during a pharmacist consultation.
Methods
Medicare beneficiaries who attended health fairs in northern California were offered medication therapy management (MTM) services during which demographic, social, and health information, and responses to survey questions regarding adherence were collected. Beneficiaries were also asked which critical elements of a consultation were typically provided by their community pharmacist. Survey responses were examined as a function of demographic, socioeconomic, and health-related factors.
Results
Of the 586 beneficiaries who were provided MTM services, 575 (98%) completed the adherence questions. Of responders, 406 (70%) reported taking medications “all of the time”. Of the remaining 169 (30%), the following reasons for nonadherence were provided: 123 (73%) forgetfulness; 18 (11%) side effects; and 17 (10%) the medication was not needed. Lower adherence rates were associated with difficulty paying for medication, presence of a medication-related problem, and certain symptomatic chronic conditions. Of the 532 who completed survey questions regarding the content of a typical pharmacist consultation, the topics included: 378 (71%) medication name and indication; 361 (68%) administration instructions; 307 (58%) side effects; 257 (48%) missed-dose instructions; and 245 (46%) interactions. Subsidy recipients and non-English speakers were significantly less likely to be counseled on drug name, indication, and side effects. The presence of certain health conditions was also associated with missing consultation elements.
Conclusion
While Medicare beneficiaries are generally adherent to medication therapy, adherence barriers must be identified and addressed during comprehensive medication consultation.
doi:10.2147/PPA.S64825
PMCID: PMC4172241  PMID: 25258521
pharmacist consultation; adherence behaviors
11.  Understanding barriers to medication adherence in the hypertensive population by evaluating responses to a telephone survey 
Background:
Although hypertension is a major risk factor for cardiovascular disease, adherence to hypertensive medications is low. Previous research identifying factors influencing adherence has focused primarily on broad, population-based approaches. Identifying specific barriers for an individual is more useful in designing meaningful targeted interventions. Using customized telephonic outreach, we examined specific patient-reported barriers influencing hypertensive patients’ nonadherence to medication in order to identify targeted interventions.
Methods:
A telephone survey of 8692 nonadherent hypertensive patients was conducted. The patient sample comprised health plan members with at least two prescriptions for antihypertensive medications in 2008. The telephone script was based on the “target” drug associated with greatest nonadherence (medication possession ratio [MPR] <80%) during the four-month period preceding the survey.
Results:
The response rate was 28.2% of the total sample, representing 63.8% of commercial members and 37.2% of Medicare members. Mean age was 63.4 years. Mean MPR was 61.0% for the target drug. Only 58.2% of Medicare respondents and 60.4% of commercial respondents reported “missing a dose of medication”. The primary reason given was “forgetfulness” (61.8% Medicare, 60.8% commercial), followed by “being too busy” (2.7% Medicare, 18.5% commercial) and “other reasons” (21.9% Medicare, 8.1% commercial) including travel, hospitalization/sickness, disruption of daily events, and inability to get to the pharmacy. Prescription copay was a barrier for less than 5% of surveyed patients.
Conclusion:
Our findings indicate that events interfering with daily routine had a significant impact on adherence. Medication adherence appears to be a patterned behavior established through the creation of a routine and a reminder system for taking the medication. Providers should assess patients’ daily schedules and medication-taking competency to develop and promote a medication routine.
doi:10.2147/PPA.S18481
PMCID: PMC3090381  PMID: 21573051
adherence; hypertension; antihypertensive therapy
12.  Self-Reported Adherence to Medications in a Pediatric Renal Clinic: Psychological Aspects 
PLoS ONE  2013;8(7):e69060.
Background
Chronically ill children and adolescents comprise a vulnerable population that requires specific considerations in order to positively impact their treatment outcome. Pediatric renal patients can be non-compliant and also forgetful in taking their medications.
Objective
The objectives of the study were to (a) assess medication adherence and (b) to identify emotionality and variables that influence non-adherence by use of “The Child & Adolescent Adherence to Medication Questionnaire” (CAAMQ), which was constructed at Texas Tech University Health Sciences Center.
Methods
Pediatric renal patients from 10 to 21 years-of-age, taking three or more medications, for longer than a three-month period, were eligible to complete the CAAMQ.
Results
Thirty-four patients participated in the study. Many of the respondents had problems remembering to take their medications on weekends (P = 0.021). The majority of the patients stated that they were not bothered about having to take their medications (70.6%); and that taking pills did not interfere with their daily activities (85.3%). Open-ended questions in the CAAMQ identified patients’ feelings of sadness, distress, and the importance of strong family support systems. The study participants reported that they preferred to take their medications at school, in the nurses’ office or in a place where privacy was assured. The results indicated that Prednisone was the most disliked of all of the medications. Female patients were more reactive and secretive than males regarding peers knowing about their disease and medication schedules (P<0.017).
Conclusions
Non-adherence in pediatric patients is a complex and serious problem, which ultimately affects the patients’ health. Privacy and daily routine were found to impact the patients’ adherence to medications. Creative and individualized reminders for teenagers need to be developed and validated. Further studies that take into consideration developmental and motivational factors may help researchers identify modifiable psychosocial predictors that will lead to improved medication adherence.
doi:10.1371/journal.pone.0069060
PMCID: PMC3715481  PMID: 23874868
13.  A Spanish Pillbox App for Elderly Patients Taking Multiple Medications: Randomized Controlled Trial 
Background
Nonadherence and medication errors are common among patients with complex drug regimens. Apps for smartphones and tablets are effective for improving adherence, but they have not been tested in elderly patients with complex chronic conditions and who typically have less experience with this type of technology.
Objective
The objective of this study was to design, implement, and evaluate a medication self-management app (called ALICE) for elderly patients taking multiple medications with the intention of improving adherence and safe medication use.
Methods
A single-blind randomized controlled trial was conducted with a control and an experimental group (N=99) in Spain in 2013. The characteristics of ALICE were specified based on the suggestions of 3 nominal groups with a total of 23 patients and a focus group with 7 professionals. ALICE was designed for Android and iOS to allow for the personalization of prescriptions and medical advice, showing images of each of the medications (the packaging and the medication itself) together with alerts and multiple reminders for each alert. The randomly assigned patients in the control group received oral and written information on the safe use of their medications and the patients in the experimental group used ALICE for 3 months. Pre and post measures included rate of missed doses and medication errors reported by patients, scores from the 4-item Morisky Medication Adherence Scale (MMAS-4), level of independence, self-perceived health status, and biochemical test results. In the experimental group, data were collected on their previous experience with information and communication technologies, their rating of ALICE, and their perception of the level of independence they had achieved. The intergroup intervention effects were calculated by univariate linear models and ANOVA, with the pre to post intervention differences as the dependent variables.
Results
Data were obtained from 99 patients (48 and 51 in the control and experimental groups, respectively). Patients in the experimental group obtained better MMAS-4 scores (P<.001) and reported fewer missed doses of medication (P=.02). ALICE only helped to significantly reduce medication errors in patients with an initially higher rate of errors (P<.001). Patients with no experience with information and communication technologies reported better adherence (P<.001), fewer missed doses (P<.001), and fewer medication errors (P=.02). The mean satisfaction score for ALICE was 8.5 out of 10. In all, 45 of 51 patients (88%) felt that ALICE improved their independence in managing their medications.
Conclusions
The ALICE app improves adherence, helps reduce rates of forgetting and of medication errors, and increases perceived independence in managing medication. Elderly patients with no previous experience with information and communication technologies are capable of effectively using an app designed to help them take their medicine more safely.
Trial Registration
Clinicaltrials.gov NCT02071498; http://clinicaltrials.gov/ct2/show/NCT02071498 (Archived by WebCite at http://www.webcitation.org/6OJjdHVhD).
doi:10.2196/jmir.3269
PMCID: PMC4004137  PMID: 24705022
medication; patient nonadherence; mobile apps; patient safety; elderly
14.  Factors influencing adherence to the food by prescription program among adult HIV positive patients in Addis Ababa, Ethiopia: a facility-based, cross-sectional study 
Background
One way of addressing malnutrition among HIV/AIDS patients is through the Food by Prescription program (FBP) and many studies have explained the treatment outcomes after therapeutic food supplementation, though available evidences on adherence levels and factors associated with these sorts of programs are limited. The findings of this study would therefore contribute to the existing knowledge on adherence to Ready-to-Use Therapeutic/Supplementary Food (RUF) in Ethiopia.
Methods
A facility-based, cross-sectional study supplemented with qualitative methods was conducted among 630 adult HIV + patients. Their level of adherence to RUF was measured using the Morisky 8-item Medication Adherence Scale (MMAS-8). The total score on the MMAS-8 ranges from 0 to 8, with scores of <6, 6 to <8, and 8 reflecting low, medium, and high adherence, respectively. Patients who had a low or a moderate rate of adherence were considered non-adherent.
Results
The level of adherence was found to be 36.3% with a 95.0% response rate. With the exception of the educational status, other socio-demographic variables had no significant effect on adherence. Those who knew the benefits of the FBP program were 1.78 times more likely to adhere to the therapy than the referent groups. On the other hand, patients who were not informed on the duration of the treatment, those prescribed with more than 2 sachets/day and had been taking RUF for more than 4 month were less likely to adhere. The main reasons for non-adherence were not liking the way the food tasted and missing follow-up appointments. Stigma and sharing and selling food were the other reasons, as deduced from the focus group discussion (FGD) findings.
Conclusion
The observed level of adherence to the FBP program among respondents enrolled in the intervention program was low. The major factors identified with a low adherence were a low level of education, poor knowledge on the benefits of RUF, the longer duration of the program, consuming more than two prescribed sachets of RUF per day, and not being informed about the duration of the treatment. Therefore, counseling patients on the program’s benefits, including the treatment plans, would likely contribute to improved adherence.
doi:10.1186/2049-9957-3-20
PMCID: PMC4101708  PMID: 25035809
Factors; Adherence; Food by prescription program; HIV positive; Addis Ababa; Ethiopia
15.  Adherence to Antiretroviral Prophylaxis for HIV Prevention: A Substudy Cohort within a Clinical Trial of Serodiscordant Couples in East Africa 
PLoS Medicine  2013;10(9):e1001511.
Jessica Haberer and colleagues investigate the association between high adherence to antiretroviral pre-exposure prophylaxis and HIV transmission in a substudy of serodiscordant couples participating in a clinical trial.
Please see later in the article for the Editors' Summary
Background
Randomized clinical trials of oral antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention have widely divergent efficacy estimates, ranging from 0% to 75%. These discrepancies are likely due to differences in adherence. To our knowledge, no studies to date have examined the impact of improving adherence through monitoring and/or intervention, which may increase PrEP efficacy, or reported on objective behavioral measures of adherence, which can inform PrEP effectiveness and implementation.
Methods and Findings
Within the Partners PrEP Study (a randomized placebo-controlled trial of oral tenofovir and emtricitabine/tenofovir among HIV-uninfected members of serodiscordant couples in Kenya and Uganda), we collected objective measures of PrEP adherence using unannounced home-based pill counts and electronic pill bottle monitoring. Participants received individual and couples-based adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell to <80%. Participants were followed monthly to provide study medication, adherence counseling, and HIV testing. A total of 1,147 HIV-uninfected participants were enrolled: 53% were male, median age was 34 years, and median partnership duration was 8.5 years. Fourteen HIV infections occurred among adherence study participants—all of whom were assigned to placebo (PrEP efficacy = 100%, 95% confidence interval 83.7%–100%, p<0.001). Median adherence was 99.1% (interquartile range [IQR] 96.9%–100%) by unannounced pill counts and 97.2% (90.6%–100%) by electronic monitoring over 807 person-years. Report of no sex or sex with another person besides the study partner, younger age, and heavy alcohol use were associated with <80% adherence; the first 6 months of PrEP use and polygamous marriage were associated with >80% adherence. Study limitations include potential shortcomings of the adherence measures and use of a convenience sample within the substudy cohort.
Conclusions
The high PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high degree of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. Low PrEP adherence was associated with sexual behavior, alcohol use, younger age, and length of PrEP use.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, about 2.5 million people (mostly living in sub-Saharan Africa) become infected with HIV, the virus that causes AIDS. HIV, which is usually transmitted through unprotected sex with an HIV-infected partner, destroys immune system cells, leaving infected individuals susceptible to other infections. There is no cure for AIDS, although antiretroviral drugs can hold HIV in check, and there is no vaccine against HIV infection. Individuals can reduce their risk of HIV infection by abstaining from sex, by having only one or a few low risk sexual partners, and by always using a condom. In addition, antiretroviral drugs can potentially be used in two ways to reduce HIV transmission. First, these drugs could be given to HIV-positive individuals to reduce their infectiousness. Second, antiretroviral drugs could be given to HIV-uninfected people to reduce acquisition of the virus. This approach—pre-exposure prophylaxis (PrEP)—has provided varying levels of protection against HIV infection in randomized controlled trials (RCT; studies that monitor the outcomes of groups of patients randomly assigned to receive different test drugs or a placebo/dummy drug).
Why Was This Study Done?
One hypothesis for the varying efficacy of PrEP in RCTs is differential adherence—differences in whether trial participants took the antiretroviral drugs correctly. Antiretroviral drugs only control HIV infections effectively when they are taken regularly and adherence to antiretroviral PrEP is probably also important for HIV prevention. Here, the researchers investigate adherence to antiretroviral prophylaxis in a substudy within the Partners PrEP Study, a placebo-controlled RCT of oral antiretroviral drugs among nearly 5,000 HIV-uninfected members of serodiscordant couples in East Africa. In serodiscordant couples, only one partner is HIV-positive; 20% of couples in Africa who know their HIV status are serodiscordant. In the Partner PrEP Study, the efficacy of HIV protection with oral antiretroviral drugs was 67%–75%.
What Did the Researchers Do and Find?
The researchers selected a “convenience” sample—a sample is taken non-randomly from a population that is close at hand—of 1,147 HIV-uninfected partners enrolled in Uganda. They used unannounced home-based pill counts (an approach that reduced the chance of participants dumping unused pills to appear more adherent than they actually were) and electronic pill bottle monitoring (a microchip in the medication bottle cap recorded whenever the bottle was opened) to measure PrEP adherence in this cohort. All the participants received adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell below 80%. Fourteen participants, all of whom had been assigned to placebo, became HIV-positive during the adherence substudy. The average adherence to PrEP was 99.1% and 97.2% as measured by unannounced pill counts and by electronic monitoring, respectively. About 7% and 26% of participants had less than 80% adherence as measured by unannounced pill count and electronic monitoring, respectively, during at least one 3-month period of the substudy. Greater than 80% adherence was associated with the first 6 months of PrEP use and polygamous marriage. Adherence less than 80% was associated with report of no sex or sex with another person besides the study partner, younger age, and heavy alcohol use. Finally, the adherence intervention (intensified counseling) was well received and in the first unannounced pill count after the intervention, adherence increased to above 80% in 92% of participants.
What Do These Findings Mean?
These findings indicate that the high level of PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high level of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. The findings also suggest that low PrEP adherence is associated with sexual behavior, alcohol use, younger age, and length of PrEP use. Several aspects of the study design may limit the accuracy of these findings. For example, although the adherence measures used here are probably more accurate than participant reports of missed doses and clinic-based pill counts (adherence measures that are often used in RCTs), they are not perfect. Nevertheless, these findings provide further support for the ability of PrEP to prevent HIV acquisition when taken regularly; they suggest that adherence interventions in the implementation setting should address sexual behavior, risk perception, and heavy alcohol use; and they provide data to guide ethical decisions about resource allocation for prevention and treatment of HIV infection.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001511.
The 2012 UNAIDS World AIDS Day Report provides up-to-date information about the AIDS epidemic and efforts to halt it
Information is available from the US National Institute of Allergy and infectious diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and information on HIV transmission and prevention and on PrEP
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on HIV and AIDS in Uganda, on HIV prevention, and on PrEP (in English and Spanish)
PrEP Watch provides detailed information about PrEP and links to other resources; it includes personal stories from people who have chosen to use PrEP
More information about the Partners PrEP Study is available
Personal stories about living with HIV/AIDS are available through Avert, through Nam/aidsmap, and through the charity website Healthtalkonline
doi:10.1371/journal.pmed.1001511
PMCID: PMC3769210  PMID: 24058300
16.  Adherence to Antiretroviral Therapy and associated factors among HIV infected children in Ethiopia: unannounced home-based pill count versus caregivers’ report 
BMC Pediatrics  2013;13:132.
Background
The introduction of Antiretroviral Therapy (ART) has brought a remarkable reduction in HIV-related mortality and morbidity both in adults and children living with HIV/AIDS. Adherence to ART is the key to the successful treatment of patients as well as containment of drug resistance. Studies based on caregivers’ report have shown that adherence to ART among children is generally good. However, subjective methods such as caregivers’ report are known to overestimate the level of adherence. This study determined the rate of adherence and its predictors using unannounced home-based pill count and compared the result with caregivers’ report in a tertiary referral hospital in Ethiopia.
Methods
A cross-sectional study was conducted between December 1, 2011 and January 30, 2012. The study participants were 210 children on ART and their caregivers attending pediatric ART clinic of Tikur Anbessa Hospital (TAH), Addis Ababa University. Caregivers were interviewed at the ART clinic using a structured questionnaire. Then, unannounced home-based pill count was done 7 days after the interview.
Results
Caregiver-reported adherence in the past 7 days prior to interview was 93.3%. Estimated adherence using unannounced home-based pill count was found, however, to be 34.8%. On multivariate logistic regression model, children with married [aOR = 7.85 (95% CI: 2.11,29.13)] and widowed/divorced [aOR = 7.14 (95% CI: 2.00,25.46)] caregivers, those who were not aware of their HIV sero-status [aOR = 2.35 (95% CI:1.09, 5.06)], and those with baseline WHO clinical stage III/IV [OR = 3.18 (95% CI: 1.21, 8.40] were more likely to adhere to their ART treatment. On the other hand, children on d4T/3Tc/EFV combination [OR = 0.10 (95% CI: 0.02, 0.53)] were less likely to adhere to their treatment. Caregivers’ forgetfulness and child refusal to take medication were reported as the major reasons for missing doses.
Conclusion
The level of adherence based on unannounced home-based pill count was unacceptably low. Interventions are urgently needed to improve adherence to ART among children at TAH. Besides, a longitudinal study measuring adherence combined with clinical parameters (viral load and CD4 count) is needed to identify a simple and reliable measure of adherence in the study area.
doi:10.1186/1471-2431-13-132
PMCID: PMC3766076  PMID: 24229394
Children; HAART; Adherence; Home-based unannounced pill count; Ethiopia
17.  The effect of reminder systems on patients’ adherence to treatment 
Background
Patient adherence is an important component of the treatment of chronic disease. An understanding of patient adherence and its modulating factors is necessary to correctly interpret treatment efficacy and barriers to therapeutic success.
Purpose
This meta-analysis aims to systematically review published randomized controlled trials of reminder interventions to assist patient adherence to prescribed medications.
Methods
A Medline search was performed for randomized controlled trials published between 1968 and June 2011, which studied the effect of reminder-based interventions on adherence to self-administered daily medications.
Results
Eleven published randomized controlled trials were found between 1999 and 2009 which measured adherence to a daily medication in a group receiving reminder interventions compared to controls receiving no reminders. Medication adherence was measured as the number of doses taken compared to the number prescribed within a set period of time. Meta- analysis showed a statistically significant increase in adherence in groups receiving a reminder intervention compared to controls (66.61% versus 54.71%, 95% CI for mean: 0.8% to 22.4%). Self-reported and electronically monitored adherence rates did not significantly differ (68.04% versus 63.67%, P = 1.0). Eight of eleven studies showed a statistically significant increase in adherence for at least one of the reminder group arms compared to the control groups receiving no reminder intervention.
Limitations
The data are limited by imperfect measures of adherence due to variability in data collection methods. It is also likely that concomitant educational efforts in the study populations, such as instructions regarding proper administration and importance of correct dosing schedules, contributed to improved patient adherence, both in reminder and control arms. The search strategy could have missed relevant studies which were categorized by disease rather than adherence.
Conclusions
Reminder-based interventions may improve adherence to daily medications. However, the interventions used in these studies, which included reminder phone calls, text messages, pagers, interactive voice response systems, videotelephone calls, and programmed electronic audiovisual reminder devices, are impractical for widespread implementation, and their efficacy may be optimized when combined with alternative adherence-modifying strategies. More practical reminder-based interventions should be assessed to determine their value in improving patient adherence and treatment outcomes.
doi:10.2147/PPA.S26314
PMCID: PMC3287416  PMID: 22379363
patient adherence; medication reminders; treatment compliance
18.  Predictors of adherence to antiretroviral therapy among HIV-infected persons: a prospective study in Southwest Ethiopia 
BMC Public Health  2008;8:265.
Background
The devastating impact of AIDS in the world especially in sub-Saharan Africa has led to an unprecedented global effort to ensure access to antiretroviral (ARV) drugs. Given that medication-taking behavior can immensely affect an individual's response; ART adherence is now widely recognized as an 'Achilles heel' for the successful outcome. The present study was undertaken to investigate the rate and predictors of adherence to antiretroviral therapy among HIV-infected persons in southwest Ethiopia.
Methods
The study was conducted in the antiretroviral therapy unit of Jimma University Specialized Hospital. A prospective study was undertaken on a total of 400 HIV infected person. Data were collected using a pre-tested interviewer-administered structured questionnaire at first month (M0) and third month (M3) follow up visits.
Results
A total of 400 and 383 patients at baseline (M0) and at follow up visit (M3) respectively were interviewed. Self-reported dose adherence in the study area was 94.3%. The rate considering the combined indicator (dose, time and food) was 75.7%. Within a three month follow up period, dose adherence decreased by 2% and overall adherence rate decreased by more than 3%. Adherence was common in those patients who have a social support (OR, 1.82, 95%CI, 1.04, 3.21). Patients who were not depressed were two times more likely to be adherent than those who were depressed (OR, 2.13, 95%CI, 1.18, 3.81). However, at the follow up visit, social support (OR, 2.42, 95%CI, 1.29, 4.55) and the use of memory aids (OR, 3.29, 95%CI, 1.44, 7.51) were found to be independent predictors of adherence. The principal reasons reported for skipping doses in this study were simply forgetting, feeling sick or ill, being busy and running out of medication in more than 75% of the cases.
Conclusion
The self reported adherence rate was high in the study area. The study showed that adherence is a dynamic process which changes overtime and cannot reliably be predicted by a few patient characteristics that are assumed to vary with time. Adherence is a process, not a single event, and adherence support should be integrated into regular clinical follow up.
doi:10.1186/1471-2458-8-265
PMCID: PMC2518153  PMID: 18667066
19.  Association between adherence to calcium-channel blocker and statin medications and likelihood of cardiovascular events among US managed care enrollees 
Background
Prior studies have found that patients taking single-pill amlodipine/atorvastatin (SPAA) have greater likelihood of adherence at 6 months than those taking 2-pill calcium-channel blocker and statin combinations (CCB/statin). This study examines whether this adherence benefit results in fewer cardiovascular (CV) events.
Methods
A retrospective cohort study was conducted using administrative claims data from the IMS LifeLink: US Health Plan Claims database, identifying adults already taking CCB or statin (but not both) who had an index event of either initiating treatment with SPAA or adding CCB to statin (or vice versa) between April 1, 2004 to August 31, 2005. Inclusion criteria included age 18+ years, continuously enrolled for minimum of 6 months prior and 18 months following treatment initiation, >1 diagnosis of hypertension, and no prescription claims for SPAA or added CCB or statin for 6 months prior. Exclusion criteria included >1 claim with missing or invalid days supplied, age 65+ years and not enrolled in Medicare Advantage, or history of prior CV events, cancer diagnosis, or chronic renal failure. The primary outcome measure was the rate of CV events (myocardial infarction, heart failure, angina, other ischemic heart disease, stroke, peripheral vascular disease, or revascularization procedure) from 6 to 18 months following index date, analyzed at three levels: 1) all adherent vs. non-adherent patients, 2) SPAA vs. dual-pill patients (regardless of adherence level), and 3) adherent SPAA, adherent dual-pill, and non-adherent SPAA patients vs. non-adherent dual-pill patients.
Results
Of 1,537 SPAA patients, 56.5% were adherent at 6 months, compared with 21.4% of the 17,910 CCB/statin patients (p < 0.001). Logistic regression found SPAA patients more likely to be adherent (OR = 4.7, p < 0.001) than CCB/statin patients. In Cox proportional hazards models, being adherent to either regimen was associated with significantly lower risk of CV event (HR = 0.77, p = 0.003). A similar effect was seen for SPAA vs. CCB/statin patients (HR = 0.68, p = 0.02). In a combined model, the risk of CV events was significantly lower for adherent CCB/statin patients (HR = 0.79, p = 0.01) and adherent SPAA patients (HR = 0.61, p = 0.03) compared to non-adherent CCB/statin patients.
Conclusions
Patients receiving SPAA rather than a 2-pill CCB/statin regimen are more likely to be adherent. In turn, adherence to CCB and statin medications is associated with lower risk of CV events in primary prevention patients.
doi:10.1186/1471-2261-10-29
PMCID: PMC2897772  PMID: 20565779
20.  Evaluation of multiple measures of antiretroviral adherence in the Eastern European country of Georgia 
Introduction
There is little information on adherence to antiretroviral therapy (ART) in the Eastern European region. This prospective study evaluated multiple measures of adherence and their association with viral suppression among HIV patients in Georgia.
Methods
A prospective cohort study enrolled 100 consecutive antiretroviral-naïve adult (age ≥18 years) patients, who were followed for three months. Adherence was assessed by medication refill and three self-report measures (an AIDS Clinical Trial Group [ACTG] tool for four-day adherence, a visual analogue scale [VAS] and a rating task for 30-day adherence). The VAS represented a line anchored by 0 and 100% corresponding to the percentage of prescribed doses taken. The rating task asked patients to rate their ability to take all medications as prescribed, with responses categorized into six levels of adherence: very poor (0%), poor (20%), fair (40%), good (60%), very good (80%) and excellent (100%). Patients with adherence of ≥95% by medication refill, ACTG and VAS, and ≥80% by rating task, were defined as adherent.
Results
Of 100 patients enrolled, eight had missing data and were excluded from analysis. Among the remaining 92 patients, the median age was 39 years, and 70% were men. Major modes of HIV acquisition were injection drug use (IDU; 47.3%) and heterosexual contact (44.1%). The proportions of adherent patients were as follows: 68% by medication refill, 90% by ACTG questionnaire, 38% by VAS and 42% by rating task. On average, four months after commencing ART, 52 (56.5%) patients had a viral load <400 copies/ml and 26 (28.3%) patients had a viral load <50 copies/ml. Of 43 persons with a history of IDU, 22 (51.2%) reached a viral load of <400 copies/ml. In multivariate analysis, only refill adherence was a statistically significant predictor of viral suppression of <400 copies/ml: the risk ratio was 1.7 (95% CI: 1.1–2.8). Refill adherence, VAS and rating task were associated with viral suppression of <50 copies/ml. Non-IDUs were twice as likely to achieve viral load <50 copies/ml compared to IDUs. Refill adherence had the largest area under the receiver-operating characteristic curve for predicting viral suppression.
Conclusions
Medication refill adherence was the strongest predictor of viral suppression. IDUs can achieve optimal virologic outcomes, but may require additional adherence support.
doi:10.7448/IAS.17.1.18885
PMCID: PMC3983475  PMID: 24721464
antiretroviral therapy; adherence; Eastern Europe; injection drug use; viral suppression
21.  Use of antipsychotic and antidepressant within the Psychiatric Disease Centre, Regional Health Service of Ferrara 
Background
This study aimed at describing the type and dosage of psychopharmaceuticals dispensed to patients with psychiatric disorders and to assess the percentage of patients treated with antipsychotics and antidepressants, the associated therapies, treatment adherence, and dosages used in individuals registered at the Psychiatric Disease Center (PDC), Regional Health Service of Ferrara.
Methods
The analysis focused on therapeutic programmes presented to the Department of Pharmacy of the University Hospital of Ferrara of 892 patients treated by the PDC (catchment area of 134605 inhabitants). All diagnoses were made according to International Classification of Diseases (ICD-9). The analysis focused on prescriptions from September 2007 to June 2009. Data on adherence to prescribed therapy have were processed by analysis of variance.
Results
Among the patients 63% were treated with antipsychotics and 40% with antidepressants. Among patients receiving antipsychotics 92% used second-generation antipsychotics (SGAs) whereas the remaining 8% used first generation antipsychotics (FGAs). Antipsychotic doses were lower than Daily Defined Dose (DDDs), and SGAs were often given with anticholinergics to decrease side effects. Mean adherence to antipsychotic therapy was 64%. Among antidepressants, selective serotonin reuptake inhibitors (SSRIs) were the most often prescribed, 55%. Dosages of these were within the limits indicated by the technical datasheet but higher than DDDs. Only 26% of patients underwent monotherapy. In antidepressants polytherapy, medication was associated with another antidepressant, 6% or with an antipsychotic, 51%. Mean adherence to the antidepressant therapy was 64%.
Conclusions
Patients treated with antipsychotics tend to use doses lower than DDDs. The opposite tendency was noted in patients treated with antidepressants. Only a small percentage of patients (14%) modified their neuroleptic therapy by increasing the dosage. On the contrary, patients treated with antidepressants mainly tended to reduce the doses of their drugs. This study highlights the tendency to follow combination therapies, prescribing SGAs together with anticholinergics in order to minimize extrapyramidal side effects or by combining two antidepressants. The study showed low adherence for both pharmaceutical therapies, which is typical in the setting of the analyzed diseases.
doi:10.1186/1472-6904-11-21
PMCID: PMC3293025  PMID: 22185397
22.  Patient Adherence to Tuberculosis Treatment: A Systematic Review of Qualitative Research 
PLoS Medicine  2007;4(7):e238.
Background
Tuberculosis (TB) is a major contributor to the global burden of disease and has received considerable attention in recent years, particularly in low- and middle-income countries where it is closely associated with HIV/AIDS. Poor adherence to treatment is common despite various interventions aimed at improving treatment completion. Lack of a comprehensive and holistic understanding of barriers to and facilitators of, treatment adherence is currently a major obstacle to finding effective solutions. The aim of this systematic review of qualitative studies was to understand the factors considered important by patients, caregivers and health care providers in contributing to TB medication adherence.
Methods and Findings
We searched 19 electronic databases (1966–February 2005) for qualitative studies on patients', caregivers', or health care providers' perceptions of adherence to preventive or curative TB treatment with the free text terms “Tuberculosis AND (adherence OR compliance OR concordance)”. We supplemented our search with citation searches and by consulting experts. For included studies, study quality was assessed using a predetermined checklist and data were extracted independently onto a standard form. We then followed Noblit and Hare's method of meta-ethnography to synthesize the findings, using both reciprocal translation and line-of-argument synthesis. We screened 7,814 citations and selected 44 articles that met the prespecified inclusion criteria. The synthesis offers an overview of qualitative evidence derived from these multiple international studies. We identified eight major themes across the studies: organisation of treatment and care; interpretations of illness and wellness; the financial burden of treatment; knowledge, attitudes, and beliefs about treatment; law and immigration; personal characteristics and adherence behaviour; side effects; and family, community, and household support. Our interpretation of the themes across all studies produced a line-of-argument synthesis describing how four major factors interact to affect adherence to TB treatment: structural factors, including poverty and gender discrimination; the social context; health service factors; and personal factors. The findings of this study are limited by the quality and foci of the included studies.
Conclusions
Adherence to the long course of TB treatment is a complex, dynamic phenomenon with a wide range of factors impacting on treatment-taking behaviour. Patients' adherence to their medication regimens was influenced by the interaction of a number of these factors. The findings of our review could help inform the development of patient-centred interventions and of interventions to address structural barriers to treatment adherence.
From a systematic review of qualitative research, Munro and coauthors found that a range of interacting factors can lead to patients deciding not to complete their course of tuberculosis treatment.
Editors' Summary
Background.
Every year nearly nine million people develop tuberculosis—a contagious infection, usually of the lungs—and about two million people die from the disease. Tuberculosis is caused by Mycobacterium tuberculosis, bacteria that are spread in airborne droplets when people with active tuberculosis sneeze or cough. Tuberculosis can be cured by taking several strong antibiotics daily for at least six months but many patients fail to complete this treatment because the drugs have unpleasant side-effects and the treatment is complicated. In addition, people often feel better soon after starting treatment so they stop taking their tablets before all the bacteria in their body are dead. Poor treatment adherence (poor compliance) means that people remain infectious for longer and are more likely to relapse and die. It also contributes to the emergence of drug-resistant tuberculosis. To help people complete their treatment, the World Health Organization recommends a strategy known as DOTS (directly observed treatment, short course). As part of this strategy, a health worker or a tuberculosis treatment supporter—a person nominated by the health worker and the patient—watches the patient take his/her antibiotics.
Why Was This Study Done?
Although DOTS has contributed to improved tuberculosis control, better patient compliance is needed to halt the global tuberculosis epidemic. Treatment adherence is a complex behavioral issue and improving treatment outcomes for tuberculosis (and for other diseases) requires a full understanding of the factors that prevent people taking medicines correctly and those that help them complete their treatment. In this study, the researchers have done a systematic review (a study in which the medical literature is surveyed and appraised using defined methods to reach a consensus view on a specific question) of qualitative studies that asked patients, carers, and health workers which factors contributed to adherence to tuberculosis treatment. Qualitative studies collect non-quantitative data so, for example, a qualitative study on tuberculosis treatment might ask people how the treatment made them feel whereas a quantitative study might count bacteria in patient samples.
What Did the Researchers Do and Find?
The researchers searched electronic databases and reference lists for qualitative studies on adherence to tuberculosis treatments and also consulted experts on tuberculosis treatment. They carefully read the 44 published papers that met their predefined inclusion criteria and then used a method called “meta-ethnography” to compare the factors (themes) associated with good or bad adherence in the different studies and to synthesize (reach) a consensus view of which factors influence adherence to tuberculosis treatment. The researchers identified eight major factors associated with adherence to treatment. These included: health service factors such as the organization of treatment and care; social context (family, community and household influences); and the financial burden of treatment. Finally, the researchers interpreted the themes that emerged from the studies to build a simple model that proposes that adherence to tuberculosis treatment is influenced by four interacting sets of factors—structural factors (including poverty and gender discrimination), social context factors, health service factors, and personal factors (including attitudes towards treatment and illness).
What Do These Findings Mean?
The findings of this systematic review of qualitative research on patient adherence to tuberculosis treatment are inevitably limited by the quality and scope of the original research. Consequently, further studies into patients' understanding of tuberculosis and its treatment are needed. Nevertheless, the findings and the model proposed by the researchers indicate that patients often take their tuberculosis medications under very difficult conditions and that they cannot control many of the factors that prevent them taking their drugs. So, although current efforts to improve adherence to tuberculosis treatments emphasize instilling a willingness to take their medications into patients, this systematic review suggests that more must be done to address how factors such as poverty and gender affect treatment adherence and to tailor support systems to patients' needs. Most importantly, it indicates that future interventions should involve patients more in the decisions made about their treatment.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040238.
MedlinePlus has an encyclopedia page on tuberculosis (in English and Spanish)
See the US National Institute of Allergy and Infectious Disease fact sheet on tuberculosis
US Centers for Disease Control and Prevention provide a variety of fact sheets and other information resources on tuberculosis
World Health Organization has produced the 2007 Global Tuberculosis Control report (in English with key findings in French and Spanish), information on DOTS (in English, Spanish, French, Russian, Arabic and Chinese), and A Guide for Tuberculosis Treatment Supporters
See the brief guide to systematic reviews, published by the British Medical Journal
doi:10.1371/journal.pmed.0040238
PMCID: PMC1925126  PMID: 17676945
23.  Effects of and satisfaction with short message service reminders for patient medication adherence: a randomized controlled study 
Background
Medication adherence is critical for patient treatment. This study involved evaluating how implementing Short Message Service (SMS) reminders affected patient medication adherence and related factors.
Methods
We used a structured questionnaire to survey outpatients at three medical centers. Patients aged 20 years and older who were prescribed more than 7 days of a prescription medication were randomized into SMS intervention or control groups. The intervention group received daily messages reminding them of aspects regarding taking their medication; the control group received no messages. A phone follow-up was performed to assess outcomes after 8 days. Data were collected from 763 participants in the intervention group and 435 participants in the control group.
Results
After participants in the intervention group received SMS reminders to take medication or those in the control group received no messages, incidences of delayed doses were decreased by 46.4 and 78.8% for those in the control and intervention groups, respectively. The rate of missed doses was decreased by 90.1% for participants in the intervention group and 61.1% for those in the control group. We applied logistic regression analysis and determined that participants in the intervention group had a 3.2-fold higher probability of having a decrease in delayed doses compared with participants in the control group. Participants in the intervention group also showed a 2.2-fold higher probability of having a decrease in missed doses compared with participants in the control group.
Conclusions
Use of SMS significantly affected the rates of taking medicine on schedule. Therefore, daily SMS could be useful for reminding patients to take their medicine on schedule.
doi:10.1186/1472-6947-13-127
PMCID: PMC4225681  PMID: 24238397
Short message service (SMS); Medication reminders; Personal medication platform; Patient compliance
24.  Mobile phone text message reminders of antipsychotic medication: is it time and who should receive them? A cross-sectional trust-wide survey of psychiatric inpatients 
BMC Psychiatry  2014;14:15.
Background
Poor adherence to antipsychotic medication is a widespread problem, and the largest predictor of relapse in patients with psychosis. Electronic reminders are increasingly used to improve medication adherence for a variety of medical conditions, but have received little attention in the context of psychotic disorders. We aimed to explore the feasibility and acceptability of including short message service (SMS) medication reminders in the aftercare plan of service users discharged from inpatient care on maintenance antipsychotic medication.
Methods
We conducted a cross-sectional, trust-wide survey in the inpatient units of the Oxleas National Health Service (NHS) Foundation Trust in the UK between June 29 and August 3, 2012. Using a self-report questionnaire and the Drug Attitude Inventory, we examined inpatient attitudes towards antipsychotic drugs, past adherence to antipsychotic medication, frequency of mobile phone ownership, and interest in receiving SMS medication reminders upon discharge from the ward. Predictors of a patient’s interest in receiving electronic reminders were examined using simple logistic regression models.
Results
Of 273 inpatients, 85 met eligibility criteria for the survey, showed decisional capacity, and agreed to participate. Of the 85 respondents, over a third (31-35%) admitted to have forgotten to take/collect their antipsychotic medication in the past, and approximately half (49%) to have intentionally skipped their antipsychotics or taken a smaller dose than prescribed. Male patients (55%), those with negative attitudes towards antipsychotics (40%), and those unsatisfied with the information they received on medication (35%) were approximately 3 to 4 times more likely to report past intentional poor adherence. The large majority of respondents (80-82%) reported having a mobile phone and knowing how to use SMS, and a smaller majority (59%) expressed an interest in receiving SMS medication reminders after discharge. No variable predicted a patient’s interest in receiving electronic reminders of antipsychotics.
Conclusions
Automatic SMS reminders of antipsychotic medication were acceptable to the majority of the survey respondents as an optional service offered upon discharge from inpatient care. Automatic electronic reminders deserve further investigation as a flexible, minimally invasive, cost-effective and broadly applicable tool that can potentially improve antipsychotic adherence and clinical outcomes.
doi:10.1186/1471-244X-14-15
PMCID: PMC3922751  PMID: 24447428
Antipsychotics; Medication adherence; Electronic reminders; SMS; Mobile phone; Inpatients
25.  Factors associated with medication adherence among heart failure patients and their caregivers 
Background
Reducing the rate of rehospitalization among heart failure patients is a major public health challenge; medication non-adherence is a crucial factor shown to trigger rehospitalizations. Objective: To collect pilot data to inform the design of educational interventions targeted to heart failure patients and their caregivers to improve medication adherence.
Methods
Heart failure patients with an implantable cardioverter defibrillator and their family caregivers were recruited from an outpatient electrophysiology clinic at an urban university medical center (N = 10 caregiver and patient dyads, 70% race/ethnic minority, mean patient age = 63 years). Quantitative and qualitative research methods were utilized. Semi-structured individual interviews were conducted to assess patients’ and caregivers’ individual interest in, and access to, new medication adherence technologies. Patient adherence to medications, medication self-efficacy, and depression were assessed by validated questionnaires. Medication adherence and hospitalization rates were assessed among patients at 30-days post-clinic visit by mailed survey.
Results
At baseline, 60% of patients reported sometimes forgetting to take their medications. The most common factors associated with non-adherence included forgetfulness (50%), having other medications to take (20%), and being symptom-free (20%). At 30-day follow-up, half of patients reported non-adherence to their medications, and 1 in 10 reported being hospitalized within the past month. Dyads reported widespread access to technology, with the majority of dyads showing interest in mobile applications and text messaging. There was less acceptance of medication-dispensing technologies; caregivers and patients were concerned about added burden.
Conclusions
The majority of etiologies of medication non-adherence were subject to intervention. Enthusiasm from patients and caregivers in new technologies to aid in adherence was tempered by potential burden, and should be considered when designing interventions to promote adherence.
doi:10.5430/jnep.v5n3p22
PMCID: PMC4307014  PMID: 25635204
Heart failure; Caregiving; Adherence; Nursing education

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