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\begin{document}

\title{KNOWLEDGE, ATTITUDE, AND PRACTICE CONCERNING INSULIN PENS IN VIETNAMESE
DIABETIC OUTPATIENTS: PREVALENCE AND IMPACT ON SAFETY AND DISEASE
CONTROL}



\author[1]{Ngo Thi Kim Cuc}%
\author[2]{Thi Vo}%
\author[1]{Chuyen Le}%
\affil[1]{Hue University of Medicine and Pharmacy}%
\affil[2]{Pham Ngoc Thach University of Medicine}%


\vspace{-1em}



  
  \date{May 27, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Rational, aims and objectives: This study aimed to assess knowledge,
attitude and practice (KAP) of using insulin pen in diabetes and
determine the related factors to the KAP, adverse drug reactions (ADRs)
and glycemic control status. Methods: In our descriptive study, 148
patients with diabetes were interviewed by 16-item questions on
knowledge and 8 questions on attitude, and were asked to present the
insulin pen injection technique with a sample insulin pen. Results:
Proportions of patient having a good knowledge, positive attitude, and
good practice were 45.9\%, 78.4\%, and 44.6\%, respectively. The three
most incorrect steps were skipping to prime pen needle (90.9\%), not
removing the used needle from the pen after using (87.8), and not
holding for specific count time before withdrawal of pen needle from
skin (50.7\%). Patients having duration of insulin one year or more had
better knowledge (p=0.025), more positive attitude (p=0.017), and better
practice of insulin (p=0.042). Patients using insulin combined with oral
diabetic medications or having history of using insulin vials had more
positive attitude of insulin role (0.038). Frequency of having good
knowledge was statistically significantly higher in participants who
received counseling from health professionals previously (p=0.001). The
study also found a positive correlation between good knowledge of
patients and good practical skills (p\textless{}0.001). Patients with
poor practice of insulin were more likely to have ADRs at the injection
sites (p = 0.013). The worse knowledge of patients was significant
related to the higher risk of hypoglycemia (p=0.001). KAP levels did not
correlate with glycemic control status. Conclusions: Positive attitude
in patients was recorded at a significant rate; however, knowledge and
practice needs improvement. This study was helpful to shape the patient
education and target specific patients for education.%
\end{abstract}%



\sloppy


\textbf{INTRODUCTION}

The number of people with diabetes has risen to 422 million in 2014.
Diabetes prevalence has been rising more rapidly in middle- and
low-income countries. WHO estimates that diabetes was the seventh
leading cause of death in 2016\textsuperscript{1}. Vietnam is situated
in the Southeast Asia region with a surface area of 365,000
km\textsuperscript{2}~and a population of approximately 97 million
(2018), ranking as the 15th most populous country in the
world\textsuperscript{2}.~Vietnam has both the highest and
fasted-growing rate of diabetes in Southeast Asia. In Vietnam, the
prevalence of diabetes has almost doubled within the past 10~years and
has consequently been recognized as a major public health burden. In
2012, the prevalence of diabetes was 5.4\%, with an additional 13.7\% of
individuals exhibiting impaired glucose tolerance\textsuperscript{3}.

Insulin is the main treatment for type 1 diabetes (T1DM) and in many
cases of uncontrolled type 2 diabetes (T2DM). According to the Institute
of Safe Pharmaceutical Practices of America\textsuperscript{4}, insulin
is classified as a high-alert medication and associated with medication
errors to use in the US. In 2004, a national report determined that 25\%
of all reports medication errors related to high-risk drugs and
insulin-related problems accounted for 16\%. Data published in 2010
indicated that the most common medication errors in the hospital
involved in administration insulin\textsuperscript{5}. The related
issues include lack of knowledge about insulin, a misconception of the
role of insulin therapy and errors in the practice of using insulin
techniques in diabetic patients\textsuperscript{6-9}. These are
important causes that lead to non-adherence to medicines, reduce the
effectiveness of treatment and increase the risk of adverse drug events
such as severe hypoglycemia, injection sites reactions, and diabetes
complications\textsuperscript{10,11}.

Two-thirds of patients with T2DM in Vietnam had poor glycemic and
metabolic control\textsuperscript{12}. In many counties in the world,
pharmacists play a key role in diabetes management and improvement of
patient health\textsuperscript{13}. However, Vietnamese pharmacists'
clinical role is still limited. The basic concepts of clinical pharmacy
were introduced in Vietnam in 1990\textsuperscript{14}, and until 2012,
the Ministry of Health released the Guidelines on Clinical Pharmacy
Practice in Hospitals to encourage and develop clinical pharmacy
activities\textsuperscript{15}. Recently, Ministry of Health published
Guidelines on Clinical Pharmacy Practice for non-communicable diseases
(NCDs) in 2019\textsuperscript{16} and diabetes is one of targeted NCDs
for national programs. Medication errors involving insulin are common,
particularly during the administration stage, and may cause severe harm.
Little is known about the prevalence of insulin administration errors in
hospitals, especially in resource-restricted settings in Vietnam.
According to our knowledge, until now only one study of Nguyen et
al\textsuperscript{17}determined that the error rate in preparation and
administration of insulin for \emph{inpatients} was 28.8\%, all with
potentially moderate/severe outcome. They suggested that interventions
suitable for resource-restricted settings need to be developed and
tested to improve insulin preparation and administration, probably
starting with education and providing information. Most diabetic
patients are treated at home. Therefore, this study aimed to assess
knowledge, attitude, and practice regarding insulin pen use among
diabetic \emph{outpatients} in a teaching hospital and determined
related factors to the KAP, adverse drug reactions (ADRs) and glycemic
control status. The study's findings will help the hospital's clinical
pharmacy team to establish the next educational interventions for
patients.

\textbf{METHODS}

\textbf{Study design and participants}

A descriptive study was conducted in the Department of Endocrinology and
Metabolism out-patient clinic in a training hospital (Hue University
Hospital) between March 2018 and May 2019 in Hue, Vietnam.

The eligibility criteria for the patient were: (1) being 18 years of age
or older; (2) being diagnosed with type 1 and/or 2 diabetes and not
pregnant; (2) being prescribed one or more of the disposable insulin
pens for a minimum of 8 weeks; (3) self - administering insulin pens,
(4) having information about a glycated hemoglobin (HbA1c) test and
fasting plasma~glucose (FPG) test, and (5) being willing to participate
in the research. The criterion of eight weeks insulin pen use was chosen
to observe the alteration in HbA1c levels.

The exclusion criteria were: (1) being not physically or mentally able
to carry out the interview, (2) already surveyed. Consequently, 148
patients who fulfilled the research criteria and were willing to
participate were enrolled in this study.

\textbf{Measurement instruments}

The patient information was collected through a direct interview. The
questionnaire consisted of socio-demographic and medical backgrounds of
patients, and three domains namely, knowledge, attitude and practice
(KAP) of insulin pen using techniques.

\textbf{Socio-demographic and clinical characteristics form}

The socio-demographic data comprised of age, gender, location, level of
education, occupation. Clinical profile of patients consisted of
diabetes-related data (For example: type, duration of diabetes, duration
of insulin therapy, family history, comorbidity), diabetic treatment and
outcomes, and adverse drug reactions (ADRs). The HbA1c and other
parameters were collected from the patients' medical records that
existed for last 3 months. Injection sites on patient's body were
checked with observation and palpation for (1) lipodystrophy
(lipohypertrophy, lipoatrophy), (2) pain, (3) bleeding, (4) bruise, (5)
insulin leakage, and/or (6) broken needle. The presence of at least one
of them was accepted as a complication.

\textbf{Development of KAP questionnaire and data collection}

The questionnaire used for the survey related to KAP were recognized
after review of similar questionnaires used in other
studies\textsuperscript{6,10}and was modified by the authors and
underwent content validation by a peer group comprising two senior
clinical pharmacists and one endocrinologist. It was pre-tested on a
group of 30 diabetic outpatients to ensure that the questionnaire was
unambiguous. The final questionnaire had a total of 16 questions related
to knowledge, 8 questions pertained to attitude, and 10-step checklists
of practice steps.

Knowledge was measured using 16 questions related to hypoglycemia and
insulin use. Example of questions covering knowledge was ``What are
causes of hypoglycemia?'' Answers were provided with multiple choices
and ``Don't know'' followed by correct and incorrect responses to
further evaluate the responses. One point was offered for each correct
response and the total score was calculated. Score ranges of 0--8, 9-16
were considered as poor and good knowledge, respectively.

An attitude was assessed using eight 5-point Likert scale related to
patient's opinion on insulin role. For example, ``Insulin use helps to
prevent complications of diabetes.'' Responses to above questions were
assessed with 5 categorical responses:~ (1) Strongly disagree, (2)
Disagree, (3) Neither agree nor disagree, (4) Agree, (5) Strongly agree.
The average scores of the attitude of each patient ranged above 3 point
were categorized as having positive attitudes.

Practice was assessed by using a 10-step checklist when demanding
patients to demonstrate how to inject with similar sample pens.
Pharmacists observed patients and each step was assessed in order to
evaluate the correct and incorrect practice. One point was offered for
each correct step and the total score was calculated. Score ranges of
0--5, 6-10 were considered as poor and good practice, respectively.

According to American Diabetes Association Guidelines
2019\textsuperscript{18}, FPG target belongs to 80 - 130 mg/dL (4.4 --
7.2 mmol/L) and a HbA1C is \textless{}7\% (53 mmol/mol) for nonpregnant
adult patients. Less stringent HbA1C (\textless{}8\%) and FPG (90 - 150
mg/dL) are appropriate for patients with more complicated disease
features or the elderly.

\textbf{Data collection}

On each day of survey, the first five consecutive adult patients were
selected, explained about the survey and if willing, interviewed in a
separate space. Surveys were carried out once or two a week.

\textbf{Ethical considerations}

The study was approved by the local university ethical review board
(Document Number: H2018/060). The study was conducted in a spirit of
respecting the private information and patients had oral informed
consent before data collection. After data collection, the patients who
were incorrectly implementing the steps of insulin injection were
trained by the researchers until the erroneous implementation is
corrected.

\textbf{Statistical Analysis}

All data was analyzed by using SPSS software version 20.0. Data was
expressed in frequency, percentage, mean \selectlanguage{ngerman}± SD. Chi-squared test was used
for intergroup comparison of categorical variables and assessment the
correlation between the variables. All analyses were two-tailed. The p
value of \textless{}0.05 was considered to be statistically significant.

\textbf{RESULTS}

\textbf{Patient characteristics and clinical profile of participants}

A total of 148 patients were included in the study of which the majority
(62.2\%) were female and 60 years and older (63.5\%). Regarding the
educational level, only 14.8\% had higher educational level than high
school. Much more than a half of the patient (55.4\%) lived in urban
areas. The retired people or unemployed (66.2\%) were of the highest
proportion and 20.3\% of them had family history of diabetes (Table 1)

Table 1 is inserted here

The majority were diagnosed as type 2 diabetes mellitus (96.6\%), had
duration of diabetic diagnosis of five years and more (70.3\%) and the
duration of insulin treatment of one year and more (70.3\%), and
comorbidities (89.2\%). The mean FPG result and HbA1C levels were 10.6 ±
4.1 mmol/L and 8.4 ± 1.6 mg/dL, respectively. There were 35.9\% and
24.4\% of patients achieved treatment goals.

There were only two type insulin used: insulin aspart (70/30) and
insulin glargine. The majority of patients were only prescribed one type
of pen, of which the proportion of patients using insulin aspart (70/30)
pen accounted for 79.7\%. A large of patients (87\%) admitted that they
had been treated with insulin vial previously. Eighty-night patients
(60.1\%) reported that they had received counseling for insulin pen from
health professionals previously. The majority (73.6\%) of patients was
indicated oral diabetes medication combined with insulin.

Regarding the ADRs of the respondents, 77.7\% of them suffered at least
a problem at injection sites such as bruise (65.5\%), pain (60.1\%),
bleeding (31.1\%), insulin leakage (20.9\%), lipodystrophy (14.9\%),
distortion, bending of needle (4.7\%). The data reveals nearly half of
participants (45.3\%) suffered from hypoglycemia recently.

\textbf{Knowledge regarding hypoglycemia and insulin}

Of 16 questions related to knowledge, the mean number of right answers
was 8.2 ± 2.3 compared to the maximum score of 16 and 45.9\% had good
knowledge. Frequency distributions of true responses regarding knowledge
were presented in \textbf{Table 2} .

Table 2 is inserted here

\textbf{Attitude regarding insulin therapy}

Of the 148 participants, 78.4\% of study group had a positive attitude
about using of insulin with mean score of 3.4 ± 0.5 compared to the
maximum score of 5. Frequency distributions of patients' responses
regarding attitudes were presented in \textbf{Fig. 1} .

Fig. 1 is inserted here

\textbf{Practice skill regarding using of the insulin pen}

There were 66 patients (44.6\%) had a good practice of insulin pens with
a mean score of 5.2 ± 1.4 compared to the maximum score of 10. Frequency
distributions of correct steps regarding insulin pen injection were
reported in \textbf{Table 3} .

Table 3 is inserted here

\textbf{Factors associated with KAP results}

Analysis of factors associated with KAP results was summarized
in\textbf{Table 4} . Patients having duration of insulin one year or
more had better knowledge (p=0.025), more positive attitude (p=0.017),
and better practice of insulin (p=0.042). Patients using insulin
combined with oral diabetic medications or having history of using
insulin vials had more positive attitude of insulin role (0.038).
Frequency of having~good knowledge~was statistically significantly
higher in participants who received counseling from health professionals
previously (p=0.001). The study also found a positive correlation
between good knowledge of patients and good practical skills
(p\textless{}0.001). Other independent variables such as age, sex,
location, occupation, level of education, duration of diabetes, family
history, and comorbidity did not affect significantly statistically with
KAP results.

Table 4 is inserted here

\textbf{KAP results associated with ADRs and glycemic control status}

Patients with poor practice of insulin were more likely to have ADRs at
the injection sites (p = 0.013). The worse knowledge of patients was
significant related to the higher risk of hypoglycemia (p=0.001).
However, KAP levels did not correlate with both FPG and HbA1c control
status (\textbf{Table 5} ).

Table 5 is inserted here

\textbf{DISCUSSIONS}

\textbf{Knowledge regarding hypoglycemia and insulin}

Hypoglycemia is one of the most common acute complications of diabetes
mellitus. The knowledge of patients associated with hypoglycemia will
help in the prevention and management of the problem.~ The study
revealed that that the majority of patients were familiar with symptoms
and remedial measures for hypoglycemia, but much fewer patients knew the
level of glycaemia considered as hypoglycemia, precipitating factors of
hypoglycemia or using glucometer to check blood glucose at home. The
poor knowledge maybe is reasons why the rate of hypoglycemia during
previous month of patients was quite high (57.5\%). This hypothesis was
confirmed by statistical analysis when patients having good knowledge
were less likely to get hypoglycemic (p=0.001) (Table 5). These findings
are consistent with the prior study in India\textsuperscript{19}. They
found that only 66.1\% diabetic patients had good knowledge on
hypoglycemia. Other study of Kahsay et al. found that~self/family blood
glucose monitoring at home could not guarantee to minimize the
occurrence of hypoglycemia events\textsuperscript{20}.

Regarding the knowledge of the insulin pen use, the majority of the
patients knew various types of insulin, injection sites, requirement of
rotation of the injection sites, injection site complications, and the
right time to inject insulin regard to meals, and storage condition of
spare insulin pens. However, the survey revealed that many patients did
not have good knowledge on insulin needle and expiration date after
opening the pen. For example, only 9 patients (6.1\%) knew to have to
use a new pen needle for each injection while the others (93.9\%) reused
needles many times for savings. If the needle is not removed from the
pen between two injections, air may leak into the injector causing wrong
dose insulin injection\textsuperscript{10}. Reusing the needle may
result in distortion, bending of needle encountered in 7 patients and
can cause painful injections in 60.1\%. Other studies reported that pen
needle reuse was quite high in their study with a range of
50\%-80\%\textsuperscript{9,10}and this problem increased the risk of
lipohypertrophy\textsuperscript{7,8,10}. Compared to other studies, this
very disappointing result in our study requires special attention on
this point at patient education.

Many patients misunderstood that the in-use insulin pens had to be kept
in the refrigerator at 2-8\textsuperscript{0}C. Mitchell et
al.\textsuperscript{9} reported that three-fourths of users did not
follow the manufacturer's instructions for storage of the in-use insulin
pens. All patients knew the location of abdominal injection, but only
62.8\% of patients knew more than one injection site on the body. A
survey in China reported that more than 80\% of patients only limited
changes in the abdominal area\textsuperscript{8}. The repetition of the
same injection site increased the risk of
lipohypertrophy\textsuperscript{7}. In our study, 14.9\% patients
reported lipodystrophy while this rate was 29.0\% in other
study\textsuperscript{7}.

\textbf{Attitude regarding insulin therapy}

Majority of the respondents had a positive attitude regarding insulin
role to prevent complication, to improve health and to better control
blood glucose, and found insulin injection techniques easy and not-time
consuming. However, patients were uncertain or their attitudes were
clustered at the high and low extremes on insulin role compared to diet,
exercise, and oral anti-hyperglycemic~agents' role, and dependence on
physician because of insulin use. Cosson et al.\textsuperscript{21}
evaluated perceptions of insulin therapy in patients with type 2
diabetes and found that two-thirds of adults reported that transitioning
to insulin therapy was less difficult than expected and 21\% of adults
considered injections to be a major patient fear.

\textbf{Practice skill regarding using of the insulin pen}

The three most incorrect steps were skipping to prime pen needle
(90.9\%), not removing the used needle from the pen after using (87.8),
and not holding for specific count time before withdrawal of pen needle
from skin (50.7\%). Particularly, 44 of 118 (37.3\%) patients using
mixed insulin did not mix them before injection. Medication errors
related to insulin pen practice were reported commonly in many
studies\textsuperscript{9}. Mitchell et al, revealed that three-fourths
of users did not follow the manufacturer's instructions for proper
administration and storage of insulin pens\textsuperscript{9}.

\textbf{Factors associated with KAP results, ADRs and glycemic control
status}

We found a significant relationship between the patient's better
knowledge and the patient's longer duration of insulin therapy (\selectlanguage{english}[?] one
year) (p = 0.025) and receiving consultation from health professionals
(p = 0.001). Several recent studies have shown the importance of
hospital pharmacists performing patient education for diabetes
mellitus\textsuperscript{9,13,22}.

Patients with longer insulin treatment are likely to have a more
positive attitude (p = 0.017). This result is similar to the study of
Cosson E.\textsuperscript{21} conducted in France in 2019 patients after
using insulin reported fewer negative feelings and more positive
feelings.

Our study also found that patients improved their attitude after changed
from vials to the use of a pen (p \textless{} 0.001). This is consistent
with Ramadan et al.'s study\textsuperscript{23} in which 85.7\% of pen
users found it more convenient shifting to pen and the insulin pen was
significantly less painful than the conventional vial/syringe.

Patients using insulin combined with oral anti-diabetic drugs (OAD) had
better attitude on insulin role (p=0.038). A similar KAP survey in
India\textsuperscript{6} found that patient using insulin with longer
duration of OAD use (\selectlanguage{english}[?] 3 years) was associated with better perception on
benefits of insulin use (p~\textless{} 0.001), awareness that insulin is
not habit forming in nature (\emph{P} ~= 0.001), need for continuity in
insulin use (p~= 0.002), and the confidence for self-administration of
insulin (p~= 0.042).

Duration on insulin therapy (\selectlanguage{english}[?]1 year) and patient's good knowledge
significantly improved the patient's practical skills (p = 0.042 and
\textless{}0.001, respectively). Then, patients with good injection
technique were less likely to get ADRs in injection sites (p=0.013).
Mitchell et al. reported that correct usage scores of insulin pens were
significantly higher if initial education on insulin pens was performed
by a pharmacist or nurse\textsuperscript{9}.

Our study found that KAP levels did not correlate with both FPG and
HbA1c control status. However, the study of Solanki et al. in
2017\textsuperscript{24} recorded that there was positive correlation
between KAP score and glycemic control, with significance for only
glycosylated hemoglobin and not fasting blood sugar, postprandial blood
sugar. One of the reasons maybe that our KAP questionnaire only focused
on hypoglycemia and insulin pens but not cover broad diabetic
management.

\textbf{Strengths and limitations}

One of the major advantages of this study is to determine which
knowledge patients lacked and the erroneous steps of insulin injection,
as well as related factors in order to shape the patient education and
target specific patients for education. However, some limitations should
be considered when interpreting the results. Firstly, KAP questionnaire
was focused only on insulin pen use, but not covered a broader domain in
treatment of diabetes. Secondly, patients in our study used only two
types of insulin pens (Insulin Aspart 70/30 and Insulin Glargine)
because of the hospital's limited resources.

\textbf{CONCLUSION}

Positive attitude in patients was recorded at a significant rate;
however, knowledge and practice need improvement. Our findings suggest
that the initial patient education on insulin pen use given by
healthcare professionals is important for new patients, which can reduce
significantly the risk of ADRs at injection sites and hypoglycemia.

\section*{Acknowledgments}

{\label{acknowledgments}}

The authors wish to thank hospital clinical pharmacists in Hue
University Hospitals for helping us to conduct the research and patients
for participating in evaluation the tool in this research.

\textbf{Funding}

This study was funded by Hue University of Medicine and Pharmacy.

\textbf{Conflict of interest}

TKCN, THV, and CL declare that they have no conflicts of interest in
relation to this work.

\textbf{Ethics approval:} Hue University of Medicine and Pharmacy.

\textbf{Author Contributions:} TKCN, THV, anh CL designed the study.
TKCN, THV collected and analyzed the data of the study. All authors are
major contributors in writing the manuscript. All authors read and
approved the final manuscript.

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\verb`Table 1-5.docx`  available at \url{https://authorea.com/users/297340/articles/426451-knowledge-attitude-and-practice-concerning-insulin-pens-in-vietnamese-diabetic-outpatients-prevalence-and-impact-on-safety-and-disease-control}

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