ORIGINAL RESEARCH
Assessing the Association Between Medication
Adherence and Glycemic Control
David M. Mosen, PhD, MPH; Harry Glauber, MB, BCh; Ashley B. Stoneburner, MPH;
and Adrianne C. Feldstein, MD, MS
ABSTRACT
Objectives: We studied the independent association of adher-
ence to oral hypoglycemic medications with poor glycemic con-
trol among a population of adults with type 2 diabetes (T2D),
adjusting for demographics, health behaviors, and clinical and
treatment characteristics.
Study Design: This was a retrospective cohort design.
Methods: We studied a population of Kaiser Permanente
Northwest (KPNW) members with T2D who either had: 1) good
glycemic control (glycated hemoglobin [A1C] <8.0%; n =
15,891) or 2) poor glycemic control (A1C >9.0%; n = 3709).
The primary independent variable was medication adherence
to 1 or more oral hypoglycemic medications. High medication
adherence was defined as at least 80% of days covered in
the 12 months prior to the A1C test date (yes vs no). Multiple
logistic regression was used to analyze the independent
association of medication adherence with poor glycemic
control, adjusting for demographics, health behaviors, medical
comorbidities, healthcare utilization, receipt of diabetes care
management services, and intensity of diabetes treatments. All
measures were constructed via KPNW’s electronic heath record.
Results: Increased adherence to oral hypoglycemic medica-
tions was associated with a lower likelihood (OR, 0.54; 95%
CI, 0.50-0.59; P <.0001) of having poor glycemic control, after
adjusting for demographics, health behaviors, comorbidities,
healthcare utilization, receipt of diabetes care management
services, and intensity of diabetes treatments.
Conclusions: Higher adherence to oral hypoglycemic medica-
tions is independently associated with a lower likelihood of
having poor glycemic control among an adult population with
T2D. Studies of the effects of measures to improve medication
adherence on population-level glycemic control are needed.
Am J Pharm Benefits. 2017;9(3):82-88
82 The American Journal of Pharmacy Benefits® | May/June 2017
ype 2 diabetes (T2D) is a chronic, progressive condition
T characterized by the failure of insulin secretion to
compensate for resistance to insulin’s actions, resulting
in hyperglycemia. The long-term complications of diabetes
contribute to its status as a leading cause of premature illness
and mortality.1 In 2012, 29.1 million individuals in the United
States had diabetes (approximately 90% of the patients had
T2D), and the prevalence appears to have increased in the past
2 decades.2 In 2012, diabetes resulted in $245 billion in costs,
including $176 billion in direct medical costs and $69 billion
in reduced productivity.3
The long-term control of hyperglycemia is essential in order
to improve health outcomes for populations with diabetes.
Poor glycemic control has been associated with microvascular
complications4-6 and mortality,7,8 whereas good control reduces
the development of microvascular and long-term cardiovascular
complications.9 Current clinical guidelines to manage glycemic
control utilize glycated hemoglobin (A1C) target levels, with
adjustment for age and length of illness10; however, A1C levels
greater than 75 mmol/mol (9.0%) are universally considered
to reflect poor control.11 Of particular concern, according to
data from a recent National Health and Nutrition Examination
Survey, the proportion of adults with diabetes with poor
glycemic control (A1C >9.0%) increased from 17.9% in the
2005-to-2008 period to 21.0% in the 2009-to-2012 period.12
Despite clinical evidence of the efficacy of several glucose-
lowering medications, adherence levels often remain sub-
optimal.13-17 Moreover, several studies have found that lower
medication adherence can be associated with poorer glycemic
control outcomes.14,18-23 However, these studies have several
limitations, including small sample sizes and analyses not
conducted on a population level.24,25
With this background, the primary objective of this study
was to analyze the independent association of adherence to
oral hypoglycemic medications with poor glycemic control
among adults with T2D on a population level. Such research
has significant clinical implications—given that medication
adherence is a potentially modifiable factor—that may be

influenced by quality improvement
initiatives. A secondary objective
was to identify demographics, health
behaviors, comorbidities, healthcare
utilization, diabetes care management
services, and treatment intensity mea-
sures associated with poor glycemic
control, with an emphasis on factors
that were modifiable.
METHODS
The institutional review board of Kaiser Permanente
Northwest (KPNW) in Portland, Oregon, approved the study
protocol and waived the need for patient consent for data
use, as is the protocol for data-only studies.
Study Setting and Data Sources
The study was conducted at KPNW, a nonprofit, group-model
healthcare system in northwest Oregon and southwest
Washington. The system consists of 15 medical clinics and
2 hospitals that serve more than 500,000 members. KPNW
membership demographics (age, sex, race/ethnicity) are
similar to the larger population in the geographic area.
We used the electronic health record (EHR) (Epic Systems
Corporation; Madison, Wisconsin) and administrative data
systems to ascertain information on patient membership;
demographics; clinical data, including height and weight;
laboratory results; and medical healthcare utilization.
Population Selection
We conducted a retrospective cohort of KPNW members
who met all the following inclusion
criteria: 1) had an A1C test between
Figure. Population Process Flow
July 1, 2014, and June 30, 2015; 2) were
18 years or older on the A1C test date;
3) were on the KPNW diabetes registry
with a T2D indication at the time of the
A1C test; and 4) had continuous health
plan enrollment for 12 or more months
prior to the A1C test date, which was
defined as the index date. If the results
of multiple A1C tests were available
between July 1, 2014, and June 30, 2015,
A1C >9.0% (n = 4750)
the latest value was used in the analysis.
KPNW members enter the diabetes
registry through any of 3 ways: 1)
A1C >9.0% and receipt of
receipt of treatment with oral hypo- ≥1 hypoglycemic meds
glycemic medications, 2) 2 or more (n = 3709)
abnormal fasting or nonfasting glucose
test results in the previous 3 years (eg, A1C indicates glycated hemoglobin.
www.ajpb.com
Medication Adherence and Glycemic Control
PRACTICAL IMPLICATIONS
Among a population of adult patients with type 2 diabetes, higher adherence to oral hypoglycemic
medications was independently associated with a lower likelihood of having poor glycemic control.
■■ These findings have clinical significance, given that medication adherence is a potentially
modifiable factor.
■■ More research is needed to understand: 1) which interventions are most successful in improv-
ing medication adherence, and 2) whether subsequent improvements in medication adher-
ence result in an improvement in glycemic control.
fasting glucose >125 mg/dL, nonfasting glucose >200 mg/
dL), or 3) 1 or more elevated A1C test results (>6.5%). In
addition, those with T2D had an International Classification
of Diseases, Ninth Revision (ICD-9)-related encounter (in
any medical setting) as far back as membership existed. T2D
ICD-9 codes include any of the following: 250.00, 250.02,
250.12, 250.20, 250.22, 250.30, 250.32, 250.40, 250.42,
250.52, 250.60, 250.62, 250.70, 250.72, 250.80, 250.82,
250.90, and 250.02.
Uncontrolled and Good Glycemic Control Groups
The process flow describing the study population is shown
in the FIGURE. We identified 37,514 members who met the
initial inclusion criteria. Of this population, 4759 members
had an A1C value greater than 9.0% and formed the poor
glycemic control group, while 27,514 had an A1C value less
than 8.0% and made up the good glycemic control group.
Another 5250 members with A1C values between 8.0% and
9.0% were not included in the analysis. The final analytic
population (n = 19,600) included poor (3709) and good
(15,891) glycemic control populations that received 1 or
SELECTION CRITERIA
1) A1C test between July 1, 2014, and June 30, 2015
2) At least 18 years at time of A1C test
3) Entered in diabetes registry prior to test date (type 2 diagnosis)
4) ≥12 months of continuous health plan enrollment prior to A1C test
N = 37,514
A1C between 8.0% and 9.0%
A1C <8.0%
(n = 5250);
(n = 27,514)
not included in analysis
A1C <8.0% and receipt of
≥1 hypoglycemic meds
(n = 15,891)
Vol. 9, No. 3 | The American Journal of Pharmacy Benefits® 83
Mosen et al
more oral hypoglycemic medications in the 12 months prior
to the A1C test. Generally, adherence to oral hypoglycemic
medications and other study covariates was measured in the
year prior to the A1C test date, for a complete study period
between July 1, 2013, and June 30, 2015.
Study Variables
Dependent variable. The primary dependent variable was
poor glycemic control (A1C >9.0%) versus good glycemic
control (A1C <8.0%).
Medication adherence. Adherence to oral hypoglycemic
medications was the primary independent variable in the
analysis. We used the proportion of days covered (PDC) to
construct medication adherence—a measure well described
in the literature26 and considered to be more consistent than
another adherence measure commonly used with electronic
pharmacy information, such as the medication possession
ratio.27 The denominator included the total number of days
between the first hypoglycemic medication fill and the end
of the 365-day observation period, prior to the A1C test date.
The numerator included total days covered by prescription
fills during the denominator period. High medication adher-
ence was defined as 80% or more days covered during the
denominator period. If multiple medications were prescribed,
a measure of total average days covered was constructed. No
insulin use was included in the adherence measure.
Covariate measures. We identified 6 groups of covariate
measures: demographics, health behaviors, comorbidities,
healthcare utilization, use of diabetes care management
services, and diabetes treatment-intensity measures. The
rationale for selecting these measures was 2-fold. First,
they are important factors previously associated with poor
glycemic control in the literature. Second, adjusting for
these measures on a population level increased the ability
to better assess the independent association of medication
adherence with poor glycemic control.
Demographics. Using KPNW’s EHR, we measured age
(continuous: assessed upon A1C test date), sex (female
vs male), race/ethnicity, and primary language status
(non–English speaker: yes vs no).
Health behaviors. Two health behavior measures
were included. The first, current tobacco use (yes vs no),
was assessed at the time closest to the A1C test, with a
1-year look-back period. Second, current physical activity
status—whether an individual exercised 4 or more times
per week (yes vs no)—was the most recent measurement
assessed closest to the A1C test date. This information,
systematically assessed at routine KPNW office visits and
asked in person by clinic staff, was the most recent update
in the member’s EHR.
84 The American Journal of Pharmacy Benefits® | May/June 2017
Comorbidities. Four comorbidity measures were
analyzed. The first was obesity, as reflected by a body mass
index (BMI) of 30 or higher (yes vs no) if height and weight
were available, using the most recent assessment with a
look-back period of 60 months (5 years). The Charlson
Comorbidity Index (CCI) score was used to assess patient-
level comorbidities. CCI score (continuous), an established
risk of mortality score in the medical literature,28,29 was
constructed using utilization of inpatient and outpatient
services in the year prior to the A1C test date. The duration of
diabetes was assessed by measuring months on the diabetes
registry (continuous) as far back as membership existed.
Healthcare utilization. Four dichotomous (yes vs no)
variables assessed healthcare utilization in the year prior to
the A1C assessment date: 1) primary care visits (1 or more
visits vs none), 2) specialty care visits (excluding visits to
internal medicine, family practices or pediatrics; 1 or more
visits vs none), 3) hospital admission (1 or more admissions
vs none), and 4) emergency department (ED) utilization (1
or more visits vs none).
Diabetes care management services. Enrollment in
diabetes care management services was assessed by any
contact with a diabetes care management program (yes vs
no) in the year prior to the A1C assessment date.
Diabetes treatment intensity measures. Two diabetes
treatment measures were assessed in the year prior to the
A1C test date: 1) use of oral hypoglycemic medications (1
medication vs 2 or more medications) and 2) use of insulin
(any use vs no use).
Statistical Analysis
We first examined the association of adherence to oral
hypoglycemic medications and other covariate measures
with poor glycemic control using χ2 analysis. Variables
that were significant in the bivariate analysis (P <.05) were
included in a final logistic regression model. The model
examined the independent association of adherence to oral
hypoglycemic medications and other covariate measures
with poor glycemic control. Odds ratios (ORs) and 95%
confidence intervals (CIs) were constructed for medication
adherence and each covariate measure. The final logistic
regression model included all covariate measures with the
exception of: 1) ED utilization, which was not significant in
the bivariate analysis, and 2) proteinuria. The proteinuria
measure, although significant in the bivariate analysis, was
dropped from the final logistic regression model because of a
high level of missing information. The final model included
the following variables: age (continuous), sex (female vs male
[reference group]), and race/ethnicity (Hispanic, African
American, Asian American/Pacific Islander, other race
 Medication Adherence and Glycemic Control

[Native American/Aleutian/Eskimo] Table 1. Population Characteristics: Poor Glycemic Control Versus Good Glycemic Control
vs white [reference group]). Poor Glycemic Control: Good Glycemic Control:
Characteristic A1C >9.0% (n = 3709) A1C <8.0% (n = 15,891) P

RESULTS Medication adherence

Bivariate results are presented in TABLE 1 High adherence (≥80% days covered) 1275 (34.4%) 8448 (53.2%) <.0001
and multivariate results are in TABLE 2. Demographics
Significant multivariate results are Age, years: mean ± SD 57.5 ± 12.5 64.5 +/– 12.0 <.0001
presented below. Female, n (%) 1734 (46.8%) 7740 (48.7%) <.05
Race ethnicity, n (%) <.0001
Adherence to Oral Hypoglycemic White 2601 (70.1%) 12,872 (81.0%)
Medications Hispanic 471 (12.7%) 970 (6.1%)
Those with high adherence to oral hypo- African American 204 (5.5%) 564 (3.6%)
glycemic medications were less likely Asian American/Pacific Islander 267 (7.2%) 1005 (6.3%)
to have poor glycemic control (OR, Other race
166 (4.5%) 480 (3.0%)
0.54; 95% CI, 0.50-0.59) compared with (Native American/Aleutian/Eskimo)
those with low medication adherence, Non-English speaker, n (%) 148 (4.0%) 447 (2.8%) <.001
adjusting for other study covariates. Health behaviors
Tobacco user, n (%) 380 (10.3%) 1367 (8.7%) .001
Association of Covariate Measures Exercise ≥4 times/week, n (%) 862 (23.6%) 4537 (28.8%) <.0001
With Poor Glycemic Control Comorbidities
Demographics. Of the demographic BMI ≥30, n (%) 2766 (74.6%) 10,437 (65.8%) <.0001
factors, age, sex, and race/ethnicity CCI score, mean ± SD 2.04 +/– 1.7 2.32 +/– 1.9 <.0001
were significantly associated with poor Months on KPNW diabetes registry,
102.8 +/– 71.9 93.4 +/– 70.5 <.0001
glycemic control. Specifically, younger mean ± SD
age (OR, 0.96; 95% CI, 0.95-0.96) was Proteinuria, n (%)a 821 (36.7%) 2463 (26.9%) <.0001
associated with poorer glycemic con- Healthcare utilization
trol, while women (OR, 0.88; 95% CI, ≥1 primary care visits, n (%) 3407 (91.9%) 15,038 (94.6%) <.0001
0.81-0.96) were less likely to have poor ≥1 specialty care visits, n (%) 3198 (86.2%) 14,496 (91.2%) <.0001
glycemic control than men. Lastly, ≥1 hospital admissions, n (%) 370 (10.0%) 2089 (13.2%) <.0001
African Americans (OR, 1.40; 95% CI, ≥1 ED visits, n (%) 990 (26.7%) 4125 (26.0%) 0.36
1.16-1.69), Hispanics (OR, 1.62; 95% Diabetes care management
CI, 1.40-1.87), Asian Americans/Pacific ≥1 contacts with diabetes care
1729 (46.6%) 2761 (17.4%) <.0001
Islanders (OR, 1.31; 95% CI, 1.11-1.55), management services
and those of other race (OR, 1.44; 95% Diabetes Treatment
CI, 1.17-1.77) were more likely to have Number of hypoglycemic meds <.0001
poor glycemic control compared with 1 1824 (49.2%) 10,894 (68.6%)
non-Hispanic whites. ≥2 1885 (50.8%) 4997 (31.5%)
Health behaviors. One of 2 health Any insulin use 1493 (40.3%) 2865 (18.0%) <.0001
behaviors, exercise status was signifi- A1C indicates glycated hemoglobin; BMI, body mass index; CCI, Charlson Comorbidity Index; ED, emergency department;
cantly associated with glycemic control KPNW, Kaiser Permanente Northwest; SD, standard deviation.
a
Sample limited to those with proteinuria tests (N = 11,389; 2240 uncontrolled, 9149 controlled)
in the multivariate analysis. Those who
exercised 4 or more times per week
were less likely to have poor glycemic control (OR, 0.75; care registry (OR, 1.06; 95% CI, 1.05-1.07) was associated
95% CI, 0.68-0.82) compared with those who exercised 3 with increased likelihood of having poor glycemic control.
or fewer times per week. Healthcare utilization. Three of 4 utilization variables
Comorbidities. Two comorbidity measures were associ- were significantly associated with glycemic control. Having
ated with poor glycemic control. Specifically, those with a BMI a primary care visit (OR, 0.95; 95% CI, 0.94-0.97) or specialty
of 30 or greater (OR, 1.18; 95% CI, 1.07-1.30) were more likely care visit (OR, 0.98; 95% CI, 0.98-0.99) was associated with
to have poor glycemic control compared with those with a a lower likelihood of poor glycemic control compared
BMI of less than 30. Moreover, longer duration on the diabetes with no primary or specialty care utilization. Interestingly,

Vol. 9, No. 3 | The American Journal of Pharmacy Benefits® 85

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Mosen et al

Table 2. Logistic Regression Results: Characteristics Associated With were more likely to have poor glycemic control compared
Poor Glycemic Control with those using 1 oral hypoglycemic medication and no
Characteristic OR 95% CI P insulin, respectively.
Medication adherence
High adherence (≥80% days covered) (vs
0.54 0.50-0.59 <.0001 DISCUSSION
low adherence [<80% days covered])
Improving glycemic control is a central goal of contemporary
Demographics
diabetes management. Nevertheless, many patients with
Age 0.96 0.95-0.96 <.0001 diabetes do not succeed in reaching goal A1C levels. This
Female (vs male) 0.88 0.81-0.96 <.01 can be a source of significant frustration for patients and
Race ethnicity <.0001 clinicians and portends a greater disease burden upon health
White 1.00 N/A systems. Although a range of demographic, behavioral, and
Hispanic 1.62 1.40-1.87 <.0001 clinical factors were associated with poorer glycemic control,
African American 1.40 1.16-1.69 <.0001 we found that medication adherence, as reflected by PDC of
Asian American/Pacific Islander 1.31 1.11-1.55 <.0001 at least 80%, was the most significant factor associated with
Other race satisfactory glycemic control. In our study, we found that
1.44 1.17-1.77 <.0001
(Native American/Aleutian/Eskimo) those with high adherence to oral hypoglycemic medications
Non-English speaker (n, %) 1.01 0.81-1.27 .91 were 46% less likely to have poor glycemic control compared
Health behaviors with those with low adherence. Our study results are unique,
Tobacco user (vs nonuser) 0.99 0.86-1.13 .87 given that we found this relationship among a population
Exercise ≥4 times/week (vs <4 times) 0.75 0.68-0.82 <.0001 of adults with T2D receiving care in an integrated system
Comorbidities (serving more than 500,000 individuals) after adjusting for
BMI ≥30 (vs BMI <30) 1.18 1.07-1.30 <.001 a comprehensive set of patient-level covariate measures.
CCI score 1.00 0.97-1.03 .93 Surprisingly, receipt of diabetes care management services
Months on diabetes registry 1.06 1.05-1.07 <.0001 was associated with poor glycemic control. Rather than
Healthcare utilization showing the potential ineffectiveness of care management
≥1 primary care visits (vs none) 0.95 0.94-0.97 <.0001 services, the receipt of these services is likely a marker for
≥1 specialty care visits (vs none) 0.98 0.98-0.99 <.0001 higher disease severity. Similar results were found for insulin
≥1 hospital admissions (vs none) 0.85 0.79-0.92 <.0001 use and higher use of oral hypoglycemic medications.
Diabetes care management Our findings are consistent with other recent research
≥1 contacts diabetes care findings that examined medication adherence and glycemic
2.80 2.55-3.07 <.0001
management services (vs none) control. A study by Feldman and colleagues30 of the EHRs
Diabetes treatment of more than 200,000 adults with diabetes in Israel found
Number of hypoglycemic meds that lower medication adherence was associated with a
1 1.00 N/A greater likelihood of having poor glycemic control (A1C
≥2 2.09 1.93-2.27 <.0001 >9%). Similarly, a retrospective cohort study by Farmer and
Any insulin use (vs none) 2.31 2.09-2.55 <.0001 colleagues31 using the Clinical Practice Research Datalink
BMI indicates body mass index; CCI, Charlson Comorbidity Index; CI, confidence interval;
found that reduced medication adherence was associated
N/A, not applicable; OR, odds ratio. with smaller reductions in A1C values compared with greater
medication adherence.
those with 1 or more hospital admissions were less likely Our results have direct applicability to clinical practice,
to have poor glycemic control (OR, 0.85; 95% CI, 0.79-0.92) given that medication adherence is a modifiable factor that
compared with those with no hospital admissions, adjusting could improve. A recent study by de Vries McClintock and
for patient-level covariates. colleagues32 found that a brief in-person and telephone-based
Diabetes care management services and treatment. intervention program improved adherence to diabetes medi-
Perhaps serving as a proxy for disease severity, those with 1 cations, which was associated with a subsequent improve-
or more diabetes care management visits (OR, 2.80; 95% CI, ment in glycemic control. Our results, coupled with previous
2.55-3.07) were more likely to have poor glycemic control research findings, provide a focus for quality improvement
compared with those with no contact. Similarly, those using opportunities to improve medication adherence.
more than 1 oral hypoglycemic medication (OR, 2.09; 95% We also found interesting relationships between several
CI, 1.93-2.27) and any insulin (OR, 2.31; 95% CI, 2.09-2.55) covariate measures and glycemic control that have direct

86 The American Journal of Pharmacy Benefits® | May/June 2017


applicability to clinical care. First, we found that African
Americans and other ethnic minorities were more likely to
have poor glycemic control compared with non-Hispanic
whites, even after adjusting for medication adherence and
other patient-level covariates. These results are similar to
research findings from Lafata and colleagues33 that found
that African American–Caucasian differences in glycemic
control could not be explained by medication adherence.
These results give the larger KPNW delivery system an
opportunity to develop quality improvement interventions
to further address racial disparities in glycemic control.
In addition, 2 potentially modifiable factors were found
to be associated with glycemic control. First, we found
that increased exercise (4 or more times per week vs 3 or
fewer times) was independently associated with a lower
likelihood of having poor glycemic control after adjusting for
medication adherence and other study covariates. Second,
a BMI of 30 or higher (vs BMI <30) was associated with a
greater likelihood of poor glycemic control. These results
reinforce the importance of lifestyle interventions to improve
glycemic control and identify another important quality
improvement opportunity, specifically, interventions that
target weight loss and improvement in medication adherence
for adults with T2D.
Limitations
Our study has some important limitations. First, the T2D
population was identified using electronic databases; thus,
they may not be completely accurate and may misclassify
some patients. Similarly, medication adherence was
constructed from pharmacy dispensing information and may
not reflect the medications that were actually taken by the
patients observed in the study. Third, given that the study
occurred in a group-model health maintenance organization
(HMO) setting in the Pacific Northwest, the results cannot
be generalized beyond this setting.
CONCLUSIONS
Future research should examine which system-level interven-
tions are most successful in improving medication adherence
and whether such improvement is associated with subsequent
improvements in glycemic control. Such interventions should
be pragmatic clinical trials or rigorous observational studies
that can be implemented in real-world delivery systems with
high levels of generalizability to clinical practice.
Among a population of patients with T2D in a group-
model HMO care delivery system, we found that higher
adherence to oral hypoglycemic medications was indepen-
dently associated with a lower likelihood of having poor
glycemic control. This finding remained significant, even after
www.ajpb.com
Medication Adherence and Glycemic Control
adjusting for patient-level demographics, health behaviors,
comorbidities, healthcare utilization, use of diabetes care
management services, and diabetes treatment measures.
Author Affiliations: Center for Health Research, Kaiser Permanente
Northwest (DMM, ABS, HC), Portland, OR; Kaiser Permanente Northwest
Quality Management and Systems (HG, ACF), Portland, OR.
Source of Funding: None.
Author Disclosures: The authors report no relationship or financial
interest with any entity that would pose a conflict of interest with the
subject matter of this article.
Authorship Information: Concept and design (DMM, HC, ACF, HG);
acquisition of data (ABS, ACF); analysis and interpretation of data
(ABS, DMM); drafting of the manuscript (DMM, HC, ACF, HG); critical
revision of the manuscript for important intellectual content (DMM, HC,
ABS, ACF, HG); statistical analysis (ABS); provision of patients or study
materials (ABS).
Address Correspondence to: David M. Mosen, PhD, MPH, Kaiser
Permanente Northwest, Center for Health Research, 3800 N Interstate
Ave, Portland, OR 97227. E-mail: david.m.mosen@kpchr.org.
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