A stewardship intervention program for safe medication management and use of antidiabetic drugs
Clinical Interventions in Aging
A stewardship intervention program for safe medication management and use of antidiabetic drugs
rui-yi Zhao 2
Xiao-wen he 2
Yan-min shan 2
ling-ling Zhu 1
Quan Zhou 0
0 Department of Pharmacy, s econd Affiliated h ospital, s chool of Medicine, Zhejiang University , hangzhou, Zhejiang Province, People's republic of China
1 geriatric VIP Care Ward, Division of n ursing
2 Clinical n urse specialist section, Division of n ursing
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Background: Diabetes patients are complex due to considerations of polypharmacy,
multimorbidities, medication adherence, dietary habits, health literacy, socioeconomic status,
and cultural factors. Meanwhile, insulin and oral hypoglycemic agents are high-alert
medications. Therefore it is necessary to require a multidisciplinary team’s integrated endeavors to
enhance safe medication management and use of antidiabetic drugs.
Methods: A 5-year stewardship intervention program, including organizational measures and
quality improvement activities in storage, prescription, dispensing, administration, and
monitoring, was performed in the Second Affiliated Hospital of Zhejiang University, People’s Republic
of China, a 3,200-bed hospital with 3.5 million outpatient visits annually.
Results: The Second Affiliated Hospital of Zhejiang University has obtained a 100%
implementation rate of standard storage of antidiabetic drugs in the Pharmacy and wards since August
2012. A zero occurrence of dispensing errors related to highly “look-alike” and “sound-alike”
NovoMix 30® (biphasic insulin aspart) and NovoRapid® (insulin aspart) has been achieved
since October 2011. Insulin injection accuracy among ward nurses significantly increased from
82% (first quarter 2011) to 96% (fourth quarter 2011) (P0.05). The number of medication
administration errors related to insulin continuously decreased from 20 (2011) to six (2014).
The occurrence rate of hypoglycemia in non–endocrinology ward diabetes inpatients during
2011–2013 was significantly less than that in 2010 (5.03%–5.53% versus 8.27%) (P0.01).
Percentage of correct management of hypoglycemia by nurses increased from 41.5% (April
2014) to 67.2% (August 2014) (P0.01). The percentage of outpatient diabetes patients receiving
standard insulin injection education increased from 80% (April 2012) to 95.2% (October 2012)
(P0.05). Insulin injection techniques among diabetes outpatients who started to receive insulin
were better than indicated in data from two questionnaire surveys in the literature, including the
percentage checking injection sites prior to injection (85.6%), priming before injection (98.1%),
rotation of injecting sites (98.1%), remixing before use (94.5%), keeping the pen needle under the
skin for 10 seconds (99.4%), and using the pen needle only once (88.7%). On-site inspection
indicated of great improvement in the percentage of drug-related problems in the antidiabetes
regimen between the first and second quarter of 2014 (1.08% versus 0.28%) (P0.05).
Conclusion: Quality improvements in safe medication management and use of antidiabetic
drugs can be achieved by multidisciplinary collaboration among pharmacists, nurses,
physicians, and information engineers.
Keywords: diabetes nursing specialists, injection technique, insulin, medication errors, oral
hypoglycemic agents, pharmacy, quality improvements
Introduction
Diabetes patients are usually complex due to consideration of polypharmacy,
multimorbidities, medication adherence, dietary habits, health literacy, socioeconomic
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status, and cultural factors.1 Meanwhile, insulin and oral
hypoglycemic agents are included in the Institute for Safe
Medication Practices (ISMP) list of high-alert medications
that bear a heightened risk of causing significant patient
harm when used in error.2 Therefore, safe medication use of
antidiabetic drugs should arouse a wide concern.
Physicians need to be aware of the pharmacological
mechanism of each class of drugs, contraindications,
precautions, drug–drug interactions (DDIs), and adverse
effects to formulate a safe and effective management plan
for diabetes patients.3 Several studies have described that
the situation in medication management and use (MMU) of
antidiabetic drugs was not optimistic. Classen et al reported
that 10.7% of patients exposed to insulin and hypoglycemic
agents experienced associated adverse drug events, from the
2004 Medicare Patient Safety Monitoring System sample’s
medical records.4 Geller et al estimated the insulin-related
hypoglycemia and errors leading to Emergency Department
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/w an reduced food intake and administration of the wrong
insu/
:s o
tthp rspe lin product. Severe neurologic sequelae and blood glucose
from roF levels of 50 mg/dL or less were documented in an estimated
ed 60.6% and 53.4%, respectively.5 Milligan et al analyzed
loda adverse drug events in older people with diabetes in the
now care home setting, via incident reports obtained from the
dgn National Reporting and Learning Service in the UK during
igA 2005–2009. They found 684 reports related to insulin and
isn 84 incidents related to oral hypoglycemic drugs. The most
itnon common error category with both types of drug therapy
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clinicians and patients to coordinate and participate in
rational use of antidiabetic drugs. Mitchell et al observed
that correct usage scores were significantly higher if initial
education on insulin pens was performed by a pharmacist
or nurse.7 Cohen discussed pharmacists’ role in ensuring
safe and effective hospital use of insulin in the inpatient
setting by minimizing the likelihood of medication errors
related to prescribing, transcription, dispensing,
administration, storage, and communication.8 However, there is little
literature on multidisciplinary teams’ integrated endeavors
to continuously enhance safe MMU of antidiabetic drugs in
large-scale hospitals.
The Second Affiliated Hospital of Zhejiang University
(SAHZU), a comprehensive academic medical center
hospital in the People’s Republic of China, successfully
1202
passed Joint Commission International (JCI) accreditation
on February 24 of 2013.9 SAHZU performed continuous
quality improvements in safe MMU of high-alert medications
during the journey to JCI accreditation and in the post–JCI
accreditation era. The aim of this article was to discuss the
effectiveness of stewardship intervention in MMU of
antidiabetic drugs and provide some reference for international
counterparts.
Methods
Data collection
A 5-year intervention program, covering the period from
2010 to 2014, focused on MMU of insulin/insulin analogs
and hypoglycemic drugs in SAHZU, a 3,200-bed hospital
with 3.5 million outpatient visits annually (data in 2013) in
Zhejiang Province, which has a population of approximately
54.4 million.
The implementation rate of standard storage of
antidiabetic drugs in the Pharmacy as well as in the wards was
calculated from on-site inspection results. The
appropriateness of antidiabetic regimens for inpatients was evaluated
by diabetes specialist nurses and auditing pharmacists. Data
on insulin injection accuracy among ward nurses,
coverage percentage of standard insulin injection education for
diabetes outpatients, and insulin injection techniques among
diabetes outpatients who started to receive insulin therapy
were obtained from on-site inspection, record forms, and
follow-up. Adverse drug reactions (ADRs) and medication
errors related to antidiabetic drugs were retrospectively
analyzed by retrieving data from an online no-fault reporting
system for all staff. All hypoglycemia events were derived
from a special online electronic platform for diabetes
nursing, and the occurrence rate of hypoglycemia in diabetes
patients was then calculated. The data presented in the study
is available in the archives of the Drug and Therapeutics
Committee of SAHZU. Access and use of these data need
permission from the SAHZU Drug and Therapeutics
Committee. The study was approved by The Ethics Committee
at SAHZU and it was in compliance with the Helsinki
Declaration.
Comprehensive intervention measures
Organizational measures
SAHZU established a team of diabetes nursing specialists
in September 2009. After 2-year endeavors, the team had
ten head nurses as core members, three full-time diabetes
specialist nurses, and 61 part-time diabetes specialist nurses,
on the basis of “one part-time diabetes specialist nurse per
ward”. A three-level diabetic nursing management system
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was thus formed: (
1
) primary nurses were responsible for
providing basic nursing and patient education (first level);
(
2
) part-time diabetes specialist ward nurses should further
strengthen diabetic patient education and contact full-time
diabetes specialist nurses for consultation, if necessary
(second level); and (
3
) full-time diabetes specialist nurses
provided consultation service and regular on-site inspection
(third level). Academic salons were held quarterly by a team
of diabetes nursing specialists. Physicians and diabetes nurses
worked together to treat outpatients in the Diabetes Center.
Key indicators of the diabetes specialist nursing service are
listed in Table 1.
According to JCI accreditation standards, a working
group, named “MMU”, was established in 2011 and played
a pivotal role in quality and patient safety associated with
medications. Information regarding ADRs, medication errors,
and hypoglycemia events were reported to the Division of
Medical Management, Division of Nursing, Pharmacy and
Office of Quality Management. Targeted quality
improvement activities were then carried out.
standardized storage
Standard storage of antidiabetic drugs focuses on the
following points: (
1
) Unopened bottles or pens of insulin should be
kept in the refrigerator until needed and may be used until the
expiry date on the label. Insulin that is currently in use should
be stored at room temperature for no more than 28 days and
then discarded. (
2
) Storing two insulin formulations with
similar-sounding names and similar-looking labels in close
proximity could easily lead to confusion, therefore insulin
must be stored in separate compartments corresponding to
each patient, and each product in use should be accurately
labeled with the patient name, identification number, start
date, and expiry date (Figure 1). (
3
) Organizational policy
defines how medications delivered by the patient are
identified and stored. Insulin formulations and oral hypoglycemic
drugs should not be stored at the patients bedside. (4) In
the Pharmacy, all antidiabetic drugs should be stored in a
special location with standard labels indicating high-alert
medications. In each ward, a standard label of high-alert
medication should be pasted to the place where insulin/
insulin analog are stored. (
5
) Strengthened management was
performed regarding look-alike and sound-alike (LASA)
antidiabetic drugs. The list and color photos of LASA
medications are available in the hospital local area network.
LASA medications are placed apart from one another on the
Pharmacy shelf, especially when LASAs don’t act alike, eg,
Tritace® (ramipril tablets; Sanofi S.A., Paris, France) and
Amary® (glimepiride tablets; Sanofi S.A.), and Monopril®
(fosinopril sodium tablets; Sino-American Shanghai Squibb
Pharmaceutical Co Ltd, Shanghai, People’s Republic of
China) and Glucophage® (metformin hydrochloride tablets;
Sino-American Shanghai Squibb Pharmaceutical Co Ltd).
standardized prescribing
Physicians are required to follow the current edition of
National Guideline for Prevention and Treatment of Type 2
Diabetes Mellitus published by Chinese Diabetes Society.10
When a physician prescribes a LASA medication via the
electronic medical record (EMR), the interface of EMR will
display a yellow background for this physician order. For
LASA insulin, a special warning will be seen during
prescription. For example, a warning (ie, “Please pay attention
to the distinction between NovoMix 30® [biphasic insulin
aspart] and NovoRapid® [insulin aspart]”) will display when
a physician prescribes NovoRapid® (Novo Nordisk A/S,
Hellerup, Denmark). Nonstandard abbreviation of medical
terminology (eg, “U” and “IU”) is prohibited from use in
physician orders of insulin. Insulin infusion speed and
measurable goals for blood glucose level must be specified when
the physician order is written. Sulfonylurea hypoglycemic
drugs (eg, tolbutamide, glipizide, gliclazide, glibenclamide,
glibornuride, gliquidone, glyclopyramide, and glimepiride)
are contraindicated in patients with history of allergy to
sulfonamide derivatives, such as antimicrobial sulfonamides,
diuretics (hydrochlorothiazide, amiloride, and indapamide),
COX-2 inhibitors (celecoxib and parecoxib), sulfonylureas,
and probenecid.11 If an insulin pen brought in by the patient
standardized dispensing
SAHZU improved the interface of the Pharmacy management
information system for prescription auditing in January 2013.
By this sophisticated software, pharmacists could see patient
information, including age, diagnosis, allergy history, body
weight, pregnancy status, clinical laboratory data (eg, blood
glucose levels), and drug information, such as approved drug
name, dose, administration route, dosing frequency, and the
list of all current medications, all such information visually
displays in the same interface.12
Pharmacists should be aware of “near misses” related to
inappropriate use of abbreviations, such as “U” and “IU”
instead of “units”. The potential consequence, clinical
relevance, and risk management of DDIs associated with oral
antidiabetic drugs are listed in Table 2.13–27 Auditing
pharmacists should check the appropriateness of drug combinations
and communicate with physicians if controversial physician
orders are identified. The inpatient Pharmacy started to
provide centralized intravenous admixture service for insulin
infusion preparation in November 2010.
The dosing time for oral hypoglycemic drugs should be
checked by pharmacists. Although most oral hypoglycemic
agents should be ingested 15–30 minutes before a meal,
some have specific requirements, for example, acarbose
1204
tablet should be taken at the start of main meals (taken
with first bite of meal). Diamicron® (gliclazide modified
release; Servier Laboratories, Neuilly-sur-Seine, France)
and Glucotrol XL® (glipizide extended release; Pfizer, Inc.,
New York, NY, USA) should be given once daily with
breakfast. Metformin should be taken with meals to help
reduce stomach or bowel side effects. SAHZU introduced
two unit-dose, automated dispensing machines in January
2011. An oral diabetic drug will be separately packaged into
a polymer bag on which special dosing requirement is printed
if it has special requirement of dosing time, which greatly
helps nurses administer oral diabetic drugs at the right time.
LASA insulin/insulin analogs should be dispensed with
obvious distinction. Considering that antidiabetic drugs are fall
risk–increasing medications due to potential hypoglycemic
events,28 SAHZU required that all insulins/insulin analogs
and oral hypoglycemic drugs dispensed by the Pharmacy
be labeled with increased fall risk warnings beside the
identification of high-alert medications. If outpatients and
inpatients receive antidiabetic therapy at discharge, they will
get special written patent education from the Pharmacy, such
as requirements for medication storage, dosing time, DDIs,
and awareness of increasing fall risk.
Administration
All kinds of insulin/insulin analog should be administered
according to the Chinese edition of “Injection
Recommendation for Patients with Diabetes”29 published by the Chinese
Diabetes Society in 2011. In April 2012, diabetes specialist
nurses initiated a plan-do-check-act (PDCA) cycle to improve
the coverage percentage of standard insulin injection
education for outpatients with diabetes. The process is as follows:
(
1
) The attending endocrinology physician assures that there
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is an indication for using insulin and the patient has not ever
received insulin therapy. A special seal, reading “please
start insulin therapy only after receiving standard injection
technique education”, is then affixed on the outpatient’s
medical record. The patient will be instructed to go to the
Diabetes Center for special education. Only after receiving
injection education can the patient be permitted to get insulin
syringe needles from the Diabetes Center. (
2
) A diabetes
specialist nurse (ie, teaching staff) prepares two copies of
the insulin injection training record sheet and education card
for each patient. By repeated teaching and mock injection
on the model, patients or authorized family gradually master
injection skills. After signature by both teaching staff and
the patient, a copy of the training record sheet and
education card is given to the patient. (
3
) The teaching staff signs
on the outpatient medical record so as to let the attending
physician know that the patient has completed the process of
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:ttsph rsope Spot checks on insulin injection accuracy among ward
from roF nurses are conducted quarterly. Fifty nurses’ activities are
examined using mock injections on the model every quarter.
Specialized training was then given. Furthermore, SAHZU
has required that two licensed health care professionals must
perform a “double check” prior to administering intravenous
infusions of insulin, by implementing a standardized
independent double-check process, since January 2013.
Monitoring
Physicians and nurses should document ADRs following
antidiabetes therapy. Diabetic nurse specialists should
investigate the occurrence rate and cause of hypoglycemia among
diabetes inpatients. Furthermore, the process of diagnosis and
treatment of hypoglycemia was standardized hospital-wide
in April 2014.
Outcome measures
The outcome measures of the intervention program included
implementation rate of standard storage in the Pharmacy as
well as in wards, occurrence of dispensing errors related to
antidiabetic drugs, insulin injection accuracy among ward
nurses, the number of actual medication administration errors
(MAEs) related to insulin/insulin analogs and oral
hypoglycemic agents, occurrence rates of hypoglycemia in diabetes
inpatients who were not hospitalized in the endocrinology
ward, occurrence rate of hypoglycemia in diabetes patients
1206
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in neurology wards, percentage of correctly managed
hypoglycemia, the coverage percentage of standardized insulin
injection education for diabetes outpatients, insulin injection
techniques among diabetes outpatients who start to receive
insulin therapy, and percentage of drug-related problems in
the antidiabetes regimen.
statistical analysis
A descriptive analysis was performed. Pearson’s chi-square
test was used for testing percentage differences between two
groups. A P-value 0.05 was considered to be statistically
significant. A P-value 0.01 was considered to be highly
significant.
Results and discussion
Implementation rate of standard storage
SAHZU has achieved a 100% implementation rate of
standard storage of antidiabetic drugs in the Pharmacy and
wards since August 2012. Meanwhile, the phenomenon that
a vial of regular insulin was used for multiple inpatients was
abolished from then on.
Medication errors
In August 2011, there were six medication errors related to
NovoMix 30® and NovoRapid®, which were two products
that looked very similar (Figure 2), including four near
misses (one prescribing error and three dispensing errors)
and two actual MAEs. The inpatient Pharmacy
immediately performed quality improvements, emphasizing that
NovoMix 30® must be marked with an additional label
specifying “Novomix30®” and colored “blue”, which was
distinctive from the background color of NovoRapid®
(ie, “orange”). Since October 2011, SAHZU has achieved
zero occurrence of dispensing errors related to NovoMix
30® and NovoRapid®.
The number of actual MAEs related to insulin/insulin
analogs exhibited continuous decrease in number, from 20
(data in 2011) to six (data in 2014) (Figure 3), and the
relative percentage of MAE subtype is presented in Figure 4.
There were nine MAEs related to oral hypoglycemic agents
during 2011–2013, including two case in 2011 (omission
[two]), three cases in 2012 (omission [one], duplicate dosing
[one], and improper handling of physician orders [one]), and
four cases in 2013 (dosing time error [two] and omission
[two]). Inspiringly, there was only one MAE related to oral
hypoglycemic drug in 2014 (omission [one]).
With the aid of the new interface with the
prescription auditing software, auditing pharmacists prospectively
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identified and intercepted 13 potential adverse DDIs,
including clarithromycin–repaglinide (n=6), fluvastatin–
sulfonylurea (n=3), fluvoxamine–gliclazide (n=1), and
metformin–contrast agents (n=3), in 2013. Alternative
metabolizing enzyme inhibitors (clarithromycin,
fluvastatin, and fluvoxamine) and cessation of metformin before
contrast-enhanced examination were suggested by
pharmacists, and these suggestions were accepted by physicians.
Zero occurrence of abbreviations such as “IU” and “U”
and of physician orders without noting infusion rate has
been achieved since October 2012. From the beginning
of February 2011, physician orders with inappropriate
dosing time of oral hypoglycemic agents were abolished.
Moreover, the appropriateness of insulin-glucose
combination in total parenteral nutrition (TPN) admixture aroused
pharmacist’s special concern. The amount of regular insulin
given (added directly to the TPN solution) depends on the
plasma glucose level; if the level is normal and the final
solution contains 25% dextrose, the usual starting dose is
5 to 10 units of regular insulin/L of TPN fluid. Anecdotally,
in October 2013, a diabetic patient who just had thoracic
surgery was prescribed with TPN therapy. Insulin, 28 units,
was included in this TPN order; however, his physician
mistakenly prescribed 5% glucose injection instead of 50%
glucose injection as the type of carbohydrate. An auditing
pharmacist successfully intercepted this prescribing-related
near miss with potential severe hypoglycemia.
On-site inspection by diabetes nurse specialists in the first
and second quarter of 2014 indicated of great improvement
in the appropriateness of antidiabetic drug use in diabetes
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h pe inpatients (Table S1). In the first quarter, antidiabetes
from roF regimens for 1,200 diabetes patients were checked, and
ded 13 cases (1.08%) were identified as having drug-related
lona problems, including inappropriate choice of insulin (n=2),
odw inappropriate drug combination (n=1), inappropriate
dosign ing frequency (n=3), inappropriate dosing route (n=1), and
ingA poor awareness of medication reconciliation (n=6). Targeted
sno lectures were then provided by a senior endocrinology
physiitne cian, a diabetes nurse specialist, and a clinical pharmacist. In
trve the second quarter, antidiabetes regimens for 1,400 diabetes
lIna patients were checked, and only four cases (0.28%) were
iilcn observed with drug-related problems, ie, inappropriate choice
C of insulin (n=4). There was statistically significant difference
in the percentage of drug-related problems in antidiabetes
regimen between the two quarters (1.08% versus 0.28%)
(P0.05 [chi-square test]). Medication reconciliation was
effectively strengthened in the second quarter of 2014.
Insulin injection technique
The coverage percentage of standard insulin injection
education for outpatients with diabetes successfully increased
from 80% (April 2012) to 95.2% (October 2012) (P0.05
[chi-square test]). After interventions, in October 2012
insulin injection techniques were improved among diabetic
outpatients who started to receive insulin therapy, including
the percentage of checking injection sites prior to injection
(85.6%), percentage of priming before injection (98.1%),
percentage of rotation of injecting sites (98.1%), percentage
of remixing before use (94.5%), percentage of keeping the
pen needle under the skin for 10 seconds (99.4%), and
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percentage of using the pen needle only once (88.7%). The
corresponding data seemed more optimistic than those from
an insulin injection technique questionnaire survey in 16
countries and 20 centers in mainland People’s Republic of
China (Table 3).30,31 Insulin injection accuracy among ward
nurses significantly increased from 82% (first quarter 2011)
to 96% (fourth quarter 2011) (P0.05 [chi-square test]).
ADrs
The ADRs reporting system showed that there were
seventeen cases of ADRs induced by antidiabetic drugs
during 2011–2014. Oral hypoglycemic agents accounted for
ten ADRs (metformin [four], acarbose [three], gliclazide
sustained release [two], and glimepiride [one]). Insulin and
insulin analogs accounted for seven ADRs. The clinical
manifestation of ADRs included hypoglycemia (n=7), diarrhea
(n=4), rash (n=4), abdominal distension (n=2), chills (n=1),
vomiting (n=1), increased anal aerofluxus (n=1), itchiness
(n=1), and dizziness (n=1). All 17 ADRs were mild and
cured with supportive treatment.
hypoglycemia
Table 4 lists the occurrence rates of hypoglycemia in
hospitalized diabetes patients who were not from the
endocrinology ward, during 2010–2013. The situation during
2011–2013 was significantly more optimistic than that in
2010 (5.03%–5.53% versus 8.27%) (P0.01 [chi-square
test]). The Department of Neurology was observed to have
a high occurrence rate of hypoglycemia in diabetes patients
in 2010 (30.5%). Therefore, this department was selected
as a place for performing quality improvements.
Significant improvements in the occurrence rate of hypoglycemia
were achieved with diabetes patients in three wards of
Department of Neurology during 2010–2013 (30.5% versus
11.3%–13.9%) (P0.01 [chi-square test]) (Figure 5).
Furthermore, the process of diagnosis and treatment of
hypoglycemia was standardized hospital-wide, and continuous
quality improvement was achieved regarding the percentage
of correctly managed hypoglycemia during April–August
2014 (Figure 6).
limitations
Although our program may be of interest to health care
professionals elsewhere, it has several limitations. Firstly,
the paper is largely descriptive. Ideally, it would have been
even better if we had controls (another hospital without the
program). Nevertheless, it includes a longitudinal follow-up,
and one can appreciate the gradual improvement in outcome
year by year. Secondly, the program seems simplistic, and it
is obvious that if we undertake “strong measures”, we may
expect “strong results”. We did not evaluate the
pharmacoeconomic issue (ie, the cost/benefit ratio, the “human cost”,
antidiabetes efficacy, and satisfaction from patients and
medical staff) or the applicability of these measures over time.
Thirdly, the number of ADRs seemed too few, indicating
further opportunity of improvements in ADR surveillance.
Conclusion
In this article, we introduced a 5-year continuous intervention
program focusing on safe MMU of “high-alert” antidiabetic
drugs, and summarized related risk-management measures
and quality improvement activities in medication storage,
prescribing, dispensing, administration, and monitoring
that were implemented at SAHZU during the journey to JCI
accreditation and post-JCI accreditation. The goal of
intervention program has been achieved through multidisciplinary
collaboration among pharmacists, nurses, physicians, and
information engineers.
Acknowledgments
This work was supported by Zhejiang Provincial Bureau of
Education (grant numbers 201225325 and N20140209), the
National Natural Science Foundation of China (grant number
81373488), the National Major Projects of China (grant
number 2012ZX09506001–004), and the National Health
and Family Planning Commission of the People’s Republic
of China (National Key Clinical Discipline Construction:
Clinical Nursing Specialist).
Disclosure
The authors report no conflicts of interest in this work.
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Supplementary material
2. repaglinide 1 mg three times daily plus lantus ® Qn still resulted in
high blood sugar. The regimen was replaced by humulin ® r three
times daily; however, the physician forgot to stop repaglinide use
3. repaglinide 1mg three times daily plus lantus ® Qn still resulted in high
blood sugar. The regimen was replaced by novorapid ® three times
daily; however, the physician forgot to stop repaglinide use
4. The patient received Diamicron® MR (gliclazide modified release
tablets) 30 mg once daily, then the hypoglycemic regimen was switched
to humulin ® r three times daily plus lantus Qn during the stay in
hospital; however, the physician forgot to stop Diamicron® Mr use
5. Diamicron® Mr 60 mg once daily was initially used. later, the
hypoglycemic regimen was switched to humulin ® r three times daily
plus lantus ® Qn; however, the physician forgot to stop Diamicron ®
Mr use. A hypoglycemic event occurred at bedtime
6. The patient received novoMix 30 ® 16 units before breakfast, 8 units
before supper plus lantus ® 10 units Qn. This regimen was the same
with that before admission and was used for 5 days after admission
Action
novorapid ® was replaced by novoMix 30 ®
(biphasic insulin aspart) twice daily
Physician was advised to replace novolin 30r
by novorapid ®. glycosylated hemoglobin was
checked, and endocrinology consultation was
requested
Physician order of lantus ® Qn at discharge
was canceled. novoMix ® 30 twice daily was
prescribed, and referral to the Department of
endocrinology was required 1 week later
novoMix ® 30 dose at lunch was canceled, and
doses in morning and evening were adjusted
Once daily use of glucotrol Xl ® was suggested,
and endocrinology physician was consulted
The diabetes nurse contacted the patient family
and requested patient to see local endocrinology
physician
The inappropriate physician order was identified
1 day after admission glipizide sustained release
was canceled
Physician was advised to stop insulin the same
day and prescribe insulin when postoperative diet
recovered. Postoperative follow-up indicated use
of novorapid ® plus lantus ®
repaglinide use was canceled
The inappropriate physician order was identified
1 day after admission; repaglinide was canceled
thereafter
The diabetes nurse contacted the physician.
however, when discharged the patient was still
receiving Diamicron® Mr 30 mg once daily,
novorapid ® three times daily and lantus Qn
The physician was advised to stop Diamicron®
use
Physician was advised to switch to novorapid ®
three times daily plus lantus ® Qn
(Continued)
from roF
Inspection time
received before admission did not change after hospitalization. The
inappropriateness was found the day after admission
4. The patient received novoMix 30 ® 8 units before breakfast, 8 units
before lunch, 8 units before supper plus lantus ® 10 units Qn
Action
consultation
consultation. After surgery, the regimen was
replaced by novorapid ® three times daily plus
The physician order was canceled, and the
patient was transferred to the Department
of endocrinology
Abbreviation: Qn, Quaque nocte, every night.
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1. Morello CM , Hirsch JD , Lee KC . Navigating complex patients using an innovative tool: the MTM Spider Web . J Am Pharm Assoc ( 2003 ). 2013 ; 53 ( 5 ): 530 - 538 .
2. ismp.org [homepage on the Internet]. ISMP High-alert medications . Institute for Safe Medication Practices; 2015 [cited October 10 , 2014 ]. Available from: http://www.ismp.org/Tools/highAlertMedicationLists. asp. Accessed June 27 , 2015 .
3. Kopecky C . Use of noninsulin antidiabetic medications in hospitalized patients . Crit Care Nurs Clin North Am . 2013 ; 25 ( 1 ): 39 - 53 .
4. Classen DC , Jaser L , Budnitz DS . Adverse drug events among hospitalized Medicare patients: epidemiology and national estimates from a new approach to surveillance . Jt Comm J Qual Patient Saf . 2010 ; 36 ( 1 ): 12 - 21 .
5. Geller AI , Shehab N , Lovegrove MC , et al. National estimates of insulin-related hypoglycemia and errors leading to emergency department visits and hospitalizations . JAMA Intern Med . 2014 ; 174 ( 5 ): 678 - 686 .
6. Milligan FJ , Krentz AJ , Sinclair AJ . Diabetes medication patient safety incident reports to the National Reporting and Learning Service: the care home setting . Diabet Med . 2011 ; 28 ( 12 ): 1537 - 1540 .
7. Mitchell VD , Porter K , Beatty SJ . Administration technique and storage of disposable insulin pens reported by patients with diabetes . Diabetes Educ . 2012 ; 38 ( 5 ): 651 - 658 .
8. Cohen MR . Pharmacists' role in ensuring safe and effective hospital use of insulin . Am J Health Syst Pharm . 2010 ; 67 ( 16 Suppl 8 ): S17 - S21 .
9. Joint Commission International [homepage on the Internet] . JCI-Accredited Organizations . Available from: http://www.jointcommissioninternational. org/about-jci/jci-accredited-organizations/?c= China&a=Academic%20 Medical%20Center%20Hospital%20Program. Accessed July 10 , 2015 .
10. Chinese Diabetes Society. [homepage on the Internet] . Available from: http://www.diab. net.cn/guideline.jsp 1210
11. Li W , Zhu LL , Zhou Q. Safe medication use based on knowledge of information about contraindications concerning cross allergy and comprehensive clinical intervention . Ther Clin Risk Manag . 2013 ; 9 : 65 - 72 .
12. Zhu LL , Zhou Q . Intervention for improving the appropriateness of physician orders for oral medications in geriatric VIP patients during the journey to JCI accreditation . Ther Clin Risk Manag . 2013 ; 9 : 273 - 275 .
13. Tornio A , Niemi M , Neuvonen PJ , Backman JT . Drug interactions with oral antidiabetic agents: pharmacokinetic mechanisms and clinical implications . Trends Pharmacol Sci . 2012 ; 33 ( 6 ): 312 - 322 .
14. Niemi M , Backman JT , Neuvonen M , Laitila J , Neuvonen PJ , Kivistö KT . Effects of fluconazole and fluvoxamine on the pharmacokinetics and pharmacodynamics of glimepiride . Clin Pharmacol Ther . 2001 ; 69 ( 4 ): 194 - 200 .
15. Shobha JC , Muppidi MR . Interaction between voriconazole and glimepiride . J Postgrad Med . 2010 ; 56 ( 1 ): 44 - 45 .
16. Schelleman H , Bilker WB , Brensinger CM , Wan F , Hennessy S. Antiinfectives and the risk of severe hypoglycemia in users of glipizide or glyburide . Clin Pharmacol Ther . 2010 ; 88 ( 2 ): 214 - 222 .
17. Park JY , Kim KA , Park PW , Park CW , Shin JG . Effect of rifampin on the pharmacokinetics and pharmacodynamics of gliclazide . Clin Pharmacol Ther . 2003 ; 74 ( 4 ): 334 - 340 .
18. Xu H , Williams KM , Liauw WS , Murray M , Day RO , McLachlan AJ . Effects of St John's wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide . Br J Pharmacol . 2008 ; 153 ( 7 ): 1579 - 1586 .
19. Fichtenbaum CJ , Gerber JG . Interactions between antiretroviral drugs and drugs used for the therapy of the metabolic complications encountered during HIV infection . Clin Pharmacokinet . 2002 ; 41 ( 14 ): 1195 - 1211 .
20. Baerlocher MO , Asch M , Myers A . Five things to know about... metformin and intravenous contrast . CMAJ . 2013 ; 185 ( 1 ): E78 .
21. Niemi M , Neuvonen M , Juntti-Patinen L , Backman JT , Neuvonen PJ . Effect of fluconazole on the pharmacokinetics and pharmacodynamics of nateglinide . Clin Pharmacol Ther . 2003 ; 74 ( 1 ): 25 - 31 .
22. Niemi M , Neuvonen PJ , Kivistö KT . The cytochrome P4503A4 inhibitor clarithromycin increases the plasma concentrations and effects of repaglinide . Clin Pharmacol Ther . 2001 ; 70 ( 1 ): 58 - 65 .
23. Kajosaari LI , Niemi M , Neuvonen M , Laitila J , Neuvonen PJ , Backman JT . Cyclosporine markedly raises the plasma concentrations of repaglinide . Clin Pharmacol Ther . 2005 ; 78 ( 4 ): 388 - 399 .
24. Honkalammi J , Niemi M , Neuvonen PJ , Backman JT . Dose-dependent interaction between gemfibrozil and repaglinide in humans: strong inhibition of CYP2C8 with subtherapeutic gemfibrozil doses . Drug Metab Dispos . 2011 ; 39 ( 10 ): 1977 - 1986 .
25. Kajosaari LI , Backman JT , Neuvonen M , Laitila J , Neuvonen PJ . Lack of effect of bezafibrate and fenofibrate on the pharmacokinetics and pharmacodynamics of repaglinide . Br J Clin Pharmacol . 2004 ; 58 ( 4 ): 390 - 396 .
26. Niemi M , Backman JT , Juntti-Patinen L , Neuvonen M , Neuvonen PJ . Coadministration of gemfibrozil and itraconazole has only a minor effect on the pharmacokinetics of the CYP2C9 and CYP3A4 substrate nateglinide . Br J Clin Pharmacol . 2005 ; 60 ( 2 ): 208 - 217 .
27. Aquilante CL , Kosmiski LA , Bourne DW , et al. Impact of the CYP2C8 *3 polymorphism on the drug-drug interaction between gemfibrozil and pioglitazone . Br J Clin Pharmacol . 2013 ; 75 ( 1 ): 217 - 226 .
28. Chen Y , Zhu LL , Zhou Q. Effects of drug pharmacokinetic/ pharmacodynamic properties, characteristics of medication use, and relevant pharmacological interventions on fall risk in elderly patients . Ther Clin Risk Manag . 2014 ; 10 : 437 - 448 .
29. Chinese Diabetes Society. [homepage on the Internet] . Available from: http://diab.net.cn/uploadfile/zhusheguideline.pdf
30. De Coninck C , Frid A , Gaspar R , et al. Results and analysis of the 2008-2009 Insulin Injection Technique Questionnaire survey . J Diabetes . 2010 ; 2 ( 3 ): 168 - 179 .
31. Ji J , Lou Q. Insulin pen injection technique survey in patients with type 2 diabetes in mainland China in 2010 . Curr Med Res Opin . 2014 ; 30 ( 6 ): 1087 - 1093 .
1. The patient received humalog ® 25 16 units before breakfast, 8 units Diabetes nurse suggested physician ask for
2. The patient received novoMix 30 ® 6 units before breakfast, 8 units novoMix 30 ® was replaced by novorapid ®
3. The patient received novoMix 30 ® 14 units before breakfast, 14 units Diabetes nurse suggested physician ask for