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\begin{document}

\title{Impact of pharmacist-led medication therapy management in ambulatory
elderly patients with chronic diseases}



\author[1]{Xin WANG}%
\author[1]{Shihui Wang}%
\author[1]{Xiaojia Yu}%
\author[1]{Zhuo Ma}%
\author[1]{Huaguang Wang}%
\author[1]{Jing Yang}%
\author[1]{Lihong Liu}%
\affil[1]{Affiliation not available}%


\vspace{-1em}



  
  \date{May 19, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Aims: This study aimed to assess the impact of pharmacist-led medication
therapy management (MTM) for ambulatory elderly patients with chronic
diseases. Methods: Consecutive patients were enrolled from pharmacist
outpatient clinics from January 2016 to June 2018. Eligible subjects
were performed with MTM services by the pharmacists and had clinical
data for at least 2 clinic visits within a consecutive 12-month period
after the first MTM visit. The drug-related problems (DRPs) and
recommendations were evaluated using The Pharmaceutical Care Network
Europe (PCNE) Classification for Drug related problems V8.03. Results: A
total of 525 DRPs were identified during the study period. Treatment
effectiveness P1 (53.71\%) was the most common problems of DRPs. The
most frequently recommended intervention was changing the drug
(48.76\%). These interventions were accepted by the patients in 92.38\%
and were completely implemented in 90.48\%. The number of drugs taken
was the significant associated factor for DRPs. Post-intervention group
showed lower levels in systolic blood pressure (SBP) and diastolic blood
pressure (DBP) compared to the pre-intervention group. There were
statistically significant changes in total cholesterol (TC), low-density
lipoprotein cholesterol (LDL-C) and triglycerides (TG) between the pre-
and post-intervention group. The average cost of medications per patient
for every month decreased from 387.72 Ren Min Bi (RMB) to 355.17 RMB
(P=0.009). Conclusion: We confirmed that pharmacists has a valuable role
to perform MTM services for ambulatory elderly patients, not only in
identifying and solving the DRPs, but also in improving clinical
outcomes (BP and lipid level) and cost saving.%
\end{abstract}%



\sloppy


\textbf{What is already known about this subject}

\begin{itemize}
\tightlist
\item
  MTM services has been demonstrated positive effects on drug
  compliance, clinical effectiveness and safety.
\item
  Little is known about the incidence and characteristics of
  drug-related problems and the impact of pharmacist-led medication
  therapy management for ambulatory elderly patients with chronic
  diseases in China.
\end{itemize}

\textbf{What this study adds:}

\begin{itemize}
\tightlist
\item
  The proportion of patients with DRPs was high, with an average 2.15
  per patient.
\item
  Interventions by pharmacists significantly reduced the cost of
  medication and improved clinical outcomes (BP and lipids level).
\item
  It suggests that the pharmacist-led MTM services played an important
  role in improving health outcomes and saving medication cost.
\end{itemize}

\textbf{Main text}

\textbf{1 Introduction}

A drug-related problem (DRP) is defined as ``an event or circumstance
involving drug therapy that actually or potentially interferes with
desired health outcomes'' {[}1{]}. Strong evidence had shown that the
negative outcomes associated with DRPs are a major health issue {[}2{]}.
The majority of hospitalizations and emergency department visits caused
by DRPs were preventable, and an effective drug review for the
successful detection of DRPs remains an unmet clinical need.

Population aging is a global phenomenon {[}3{]}. Aging is accompanied
with decline of functional reserves and adaptability. Elderly patients
also often have concomitant medical conditions that require multiple
drugs. It is well known that polypharmacy is very common in elderly
patients and increases the risk of adverse drug events (ADEs), potential
drug--drug interactions and drug errors {[}4{]}, in addition it has
considerable impact on morbidity and mortality {[}5{]}.

\par\null

Health care providers must carefully investigate the use of drugs to
identify the DRPs, and try to solve these DRPs, especially the elderly
{[}6, 7{]}. Pharmacists are ideal medical team member to optimize drug
therapy, adjust drug doses, conduct medication reconciliation, improve
drug compliance, monitor laboratory indicators, conduct patient
education where appropriate {[}8{]}. By performing medication review or
medication therapy management (MTM), the pharmacist can identify and
resolve the DRPs {[}9{]}. MTM services has been demonstrated positive
effects on drug compliance, clinical effectiveness and safety
{[}10-12{]}. The core elements of MTM services include medication
therapy review (MTR), a personal medication record (PMR), a
medication-related action plan (MAP), intervention and referral, and
documentation and follow-up {[}13{]}.

In order to determine the effectiveness of MTM services to identify DRPs
in elderly patients (age [?] 65) in outpatients, we evaluated the
incidence and characteristics of DRPs in outpatient patients conducted
by a group of pharmacists. This study also examined clinical outcomes
(blood pressure (BP), and lipids) pre- and post-intervention by
pharmacist. Thus, the purpose of this manuscript is to assess the impact
of pharmacist-led MTM for ambulatory patients.

\textbf{2 Methods}

\textbf{2.1 Ethics approval}

This study was approved by the institutional review boards of Beijing
Chao-Yang Hospital affiliated to Capital Medical University
(registration number: 2019-6-20-3).

\textbf{2.2 Study design and setting}

This was a retrospective cohort study conducted in a pharmacist
outpatient clinic in a general hospital in Beijing, China. Consecutive
patients were enrolled from January 2016 to June 2018. Four pharmacists
from the hospital interviewed patients at the pharmacist outpatient
clinic. The pharmacists conducted a comprehensive assessment of the
patient's medication. These three MTM pharmacists had completed training
program accredited by the American Pharmacists Association, with an
average of 10 years of hospital practice experience. The other
pharmacist had a physician certificate and was authorized to prescribe.

The inclusion criteria were patients aged [?] 65 years and with chronic
diseases, such as cardiovascular diseases (including hypertension,
hyperlipidemia, coronary artery disease and heart failure) or diabetes,
osteoporosis, gout. Eligible subjects were performed with MTM services
by the pharmacists and had clinical data for at least 2 clinic visits
within a consecutive 12-month period after the first MTM visit. These
patients were assigned into two groups (pre-intervention group and
post-intervention group) based on the date when they accepted the first
MTM services in the pharmacist outpatient clinic.

\textbf{2.3 Description of the intervention}

MTM was defined as analysis, education and monitoring services provided
by pharmacists to optimize patient outcomes {[}14{]}. For this study,
the MTM process included the following five steps: (1) collected
clinical information of patients and recorded a comprehensive list of
patients' medications, including previous and current medications and
whether there was any adverse drug reactions (ADR) during the
medication; (2) identified DRPs, such as unnecessary, suboptimal or
repeated medications, over- or under-dosing, toxicity or adverse
reaction; (3) identified patient's understanding of his/her medications
and diseases, and provided appropriate patient education based on the
knowledge deficits discovered; (4) provided treatment advices, including
those related to dosing and drug regimens based on the DRPs identified;
and (5) performed individual follow-up of the achievements of drug
treatment.

\textbf{2.4 Data collection}

The following information was documented: patients' demographic factors
(age, gender), diseases factors (active or currently under treatment),
therapeutic regimens (dosing, frequency, and treatment duration) of each
medication. Additionally, BP level, heart rate, laboratory findings
(such as lipid level, creatinine) and cost of medicines were collected.

\textbf{2.5 Outcome measures}

\textbf{2.5.1 Detection of DRPs}

The Detection of DRPs was the first outcome. The pharmacists were
required to work as usual, using their professional knowledge to
evaluate medication therapies. The DRPs were classified by the
pharmacists who performed the medication reviews. The DRPs were recorded
after evaluating the indication, dosage, adherence, adverse reactions,
and therapeutic effects of each medication. It was recommended to
optimize patients' drug therapy by the pharmacists. The DRPs and
recommendations were evaluated using The Pharmaceutical Care Network
Europe (PCNE) Classification for Drug related problems V8.03 regarding
problem, causes, planned interventions and intervention acceptance
{[}15{]}.

\textbf{2.5.2Clinical outcomes and cost-saving effect}

The clinical outcomes and cost-saving effect were the secondary
endpoints and compared on the first visit date (baseline) and the end of
follow-up. The outcomes of BP was mean diastolic blood pressure (DBP)/
systolic blood pressure (SBP) of hypertensive patients on every~visit.
The outcomes of lipids was concluded total~cholesterol (TC), low-density
lipoprotein cholesterol (LDL-C) and triglycerides (TG). The cost-saving
effect outcome was average costs of medications per patient for every
month. The drug costs were standardized over the study period.

\textbf{2.6 Statistical analysis}

All data analyses were performed using SPSS version 23.0 software. A
descriptive analysis was conducted on patient's demographics, diseases
characteristics, types of DRPs, and recommendations. Comparisons between
the pre-intervention group and post-intervention group with regard to
clinical outcomes were given. Continuous data was computed with mean \selectlanguage{ngerman}±
standard deviation. Categorical variables were calculated with
frequencies and percentages. Groups were compared by Student's T test
for continuous variables, by the Mann-Whitney test for continuous
variables with non-parametric distribution, and by the chi-square test
or Fisher's exact tests for categorical data. Univariate analysis and
multiple linear regression were used to determine factors related to the
number of DRPs. A P value of \textless{}0.05 was considered to be
statistically significant.

\textbf{3 Results}

\textbf{3.1 Characteristics of study population}

A total of 288 eligible patients were invited by the pharmacists to
participate in the study during their daily outpatient visits, and 260
patients were recruited (participation rate 90.28\%). A total of 244
patients completed all required follow-up and were included in our study
(completion rate was 93.85\%). The patients had a mean of 8.76±4.35
ongoing medications during patients' routine clinic visits. The most
commonly seen comorbid conditions were hypertension (70.08 \%), heart
disease (56.56\%), and hyperlipidemia (29.92\%). The demographic and
clinical characteristics of these patients are described in Table 1.

\textbf{3.2 Detection of DRPs}

As shown in Table 2, a total of 525 DRPs were identified during the
study period. An average of 2.15 DRPs per patient was detected.
Treatment effectiveness P1 (53.71\%) was the most common problems of
DRPs followed by treatment safety (33.90\%). The main causes of DRPs
were related to drug selection (71.43\%) and dose selection (20.57\%).
These identified DRPs led to interventions proposed to prescribers in
96.19\% of the cases. The most frequently recommended intervention was
changing the drug (48.76\%), followed by changing the dosage (24.76\%)
and starting a drug (11.62\%). These interventions were accepted by the
patients in 92.38\% of the cases and were completely implemented in
90.48\%.

The univariate analysis showed that the ``number of drugs'' and ``number
of chronic conditions'' were the significant factors affecting the
number of DRPs. In the multivariate analysis, only ``number of drugs''
was associated with the number of DRPs (\emph{P} \selectlanguage{english}<0.0001), as described
in Table 3.

\selectlanguage{english}\textbf{3.3 Clinical outcomes and cost-saving effect}

There were 171 patients with hypertension in the study.
Post-intervention group showed lower levels in SBP and DBP compared to
the pre-intervention group (SBP: 134.56 +- 12.38 vs 149.08 +- 19.75, P =
0.000; DBP: 78.01 +- 9.78 vs 84.56 +- 11.34, P=0.000). There were 73
patients with hyperlipidemia in the study. There were statistically
significant changes in TC, LDL-C and TG between the pre-intervention
group and the post-intervention group (Table 4).

The average costs of medications per patient for every month were
387.72+-168.48 Ren Min Bi (RMB) in the pre-intervention group and
355.17+-180.03 RMB in the post-intervention group. The cost of
antihypertensive drugs was markedly declined (230.40+-138.14 vs
206.58+-112.74, P=0.001). However, the cost of lipid modifying agents was
increased (181.12+-106.14 vs 242.67+-175.56, P=0.006; Table 5).

\textbf{4 Discussion}

To the best of our knowledge, this study was the first to evaluate the
outcomes of pharmacist-led MTM services in ambulatory elderly patients
in mainland China. This study showed that the proportion of patients
with DRPs was high, with an average 2.15 per patient. Interventions by
pharmacists significantly reduced the cost of medication and improved
clinical outcomes (BP and lipids level). The average cost of medications
per patient for every month decreased from 387.72 to 355.17 RMB in our
study. It suggests that the pharmacist-led MTM services played an
important role in improving health outcomes and saving medication cost.

To be able to perform MTM services with high quality, the pharmacists
need to have full access to patient's medical and laboratory records.
Compared with many other outpatient clinics, in order to obtain more
comprehensive information, the pharmacists collected the medical records
of each patient for 30-40 minutes, including previous medical history,
previous medications, current medications, laboratory examination and
other information. This was important, for example, to understand why a
drug had been changed or to identify any adverse effect of earlier
drugs.

In previous studies, the average number of DRPs per person was lower
than the result in our study {[}16, 17{]}. A study from Australia
reported that 130 DRPs were found in 73 patients (mean 1.8 DRPs per
patient) {[}16{]}. Rhalimi et al revealed an average of 1.37 DRPs per
patient in French community pharmacies {[}17{]}. There might be several
explanations for why the number of DRPs in this study was higher than in
other studies. First, our study was conducted in a tertiary hospital
rather than a community pharmacy. Most of the patients who come to the
pharmacist clinic had medication problems, so there were more DRPs than
other studies. Second, there were several available tools to evaluate
DRPs. We chose to use the PCNE V8.03 classification system, but other
available assessment tools may differ slightly in some aspects, and
therefore, other tools may observe different results.

Adverse drug event (possibly) occurring was quite common problems of
DRPs in our study. This was also the most common pharmaceutical care
problem in the Kwint's study {[}18{]}. This finding could give support
to the hypothesis that pharmacists have adequately addressed patients'
problems in the pharmacist outpatient services. For example, it was well
known that elderly people were at high risk of side effects from
non-steroidal anti-inflammatory drugs (NSAIDs), such as gastrointestinal
bleeding and renal toxicity, and that NSAIDs also increase the risk of
hypertension and heart failure {[}19, 20{]}. High doses of
dihydropyridines calcium-channel blockers often caused ankle edema,
headache, flushing and tachycardia {[}21{]}. In order to reduce the
occurrence of adverse reactions, the pharmacists may reduce the dose of
the drug or switch it to another medicine according to the symptoms.

In our study, no or incomplete drug treatment in spite of existing
indication was the main causes subtype of DRPs. For example, some
patients did not receive the standard ''ABCDE'' method for secondary
prevention of coronary artery disease: antiplatelet therapy, blood
pressure management, cholesterol management, diabetes treatment, and
exercise; it was recommended that it was often used to reduce the
cardiovascular risk {[}22{]}. Although cardiac rehabilitation following
a cardiovascular event is a Class I recommendation of the European
Society of Cardiology, the American Heart Association and the American
College of Cardiology, it remains vastly underutilized, accounting for
15\% to 50\% of the targeted population participating in such services
{[}23-27{]}. Lack of awareness on the importance of those drugs and fear
of ADRs were possible causes. The high incidence of incomplete drug
treatment in our study highlights the need for pharmacists to conduct a
MTM services in elderly patients to optimize drug treatment.

The overall acceptance rate of pharmacist interventions was relatively
high (90.48\%), which was higher than what has been reported in other
studies {[}28, 29{]}. This is probably due to the fact that adequate
training and experience in clinical pharmacy are important factors for
meeting the specific challenges of MTM service.

Multivariate analysis showed that the number of drugs taken was
associated independent risk factor for the number of DRPs, which was
consistent with most previous studies {[}30-32{]}. Patients taking large
amounts drugs tend to experience adverse drug reactions, potential
drug--drug interactions, decreased compliance and drug selection
problems {[}33-35{]}. It was recommended that patients could visit
pharmacist clinic to conduct medication reorganization and reduce
unnecessary drugs. Pharmacists can review medication history and
identify medication issues in these patients. Pharmacists were familiar
with not only medication but also the interaction between the drug and
the disease. Therefore, it was recommended that pharmacists could
provide MTM services for ambulatory patients who receiving long-term
pharmacotherapy {[}36{]}.

After one year MTM service, the improvements in several clinical
outcomes among the patients were significant. Hypertension and
hyperlipidemia increase the risk of fatal or non-fatal cardiovascular
events {[}24-26{]}. Like other studies, our study also found that the
MTM service improved BP and lipid level among patients {[}37-39{]}.
Regarding cost-saving effect, the post-intervention group experienced a
significant reduction in total costs of medications per patient for
every month. This decrease in medication expenditures was similar to
those reported in other MTM services studies {[}37, 40{]}.

Some limitations of this study have to be taken into account. First, it
was a retrospective study and the patient population in this study was
small. This could lead to non-significant results. Second, all involved
pharmacists performed comprehensive medication reviews as described in
the methods section. Still, limitations in the inter-rater reliability
cannot be ruled out. Finally, the lack of usual care group was a
limitation of the present study, therefore, in terms of clinical
outcomes and cost-saving effect, the self-comparison study of patients
pre- and post- intervention were conducted.

\textbf{5 Conclusions}

This study described the number and type of DRPs in ambulatory patients
and clinical and economic outcomes pre- and post-intervention by
pharmacist-led MTM services. DRPs were commonly observed among
ambulatory patients. We confirmed that pharmacists has a valuable role
to perform MTM services for ambulatory elderly patients, not only in
identifying and solving the DRPs, but also in improving clinical
outcomes (BP and lipid level) and cost saving.

\par\null

\textbf{Acknowledgments}

We thank all the original authors of the included studies for their
wonderful work.

\textbf{Authors' contributions}

XW and LHL designed the experiments. XW, XJY, HGW, JY and LHL carried
out the experiments. XW, SHW and ZM collected and analyzed the data. XW
wrote the article. All authors reviewed the article.

\textbf{Conflict of interest statement}

The authors have no relevant affiliations or financial involvement with
any organization or entity with a financial interest in or financial
conflict with the subject matter or materials discussed in the
manuscript.

\textbf{Funding}

This manuscript has been produced without funding.

\textbf{Data availability statement:}

Data available on request from the authors.

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  Cheema E, Sutcliffe P, Singer DR. The impact of interventions by
  pharmacists in community pharmacies on control of hypertension: a
  systematic review and meta-analysis of randomized controlled
  trials.~Br J Clin Pharmacol. 2014; 78 (6):1238--1247.
\item
  Lin HW, Lin CH, Chang CK, et al. Economic outcomes of
  pharmacist-physician medication therapy management for polypharmacy
  elderly: A prospective, randomized, controlled trial.~J Formos Med
  Assoc. 2018; 117 (3):235--243.
\end{enumerate}

\textbf{Table 1 The demographic and clinical characteristics of 244
patients}\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
\textbf{Characteristics} & \textbf{Total(N=244)}\tabularnewline
\midrule
\endhead
Demographics (n = number of patients) &\tabularnewline
Age, year, mean \selectlanguage{ngerman}± SD & 72.54\selectlanguage{ngerman}±9.96\tabularnewline
65--79 years, n (\%) & 204(83.61\%)\tabularnewline
[?]80 years, n (\%) & 40(16.39\%)\tabularnewline
Female, n (\%) & 143(58.61\%)\tabularnewline
Number of medications taken, mean \selectlanguage{ngerman}± SD & 8.76\selectlanguage{ngerman}±4.35\tabularnewline
Active chronic conditions\selectlanguage{english},n\selectlanguage{english}(\%\selectlanguage{english}) &\tabularnewline
Hypertension & 171(70.08\%)\tabularnewline
Heart disease & 138(56.56\%)\tabularnewline
Hyperlipidemia & 73(29.92\%)\tabularnewline
Diabetes mellitus & 70(28.69\%)\tabularnewline
Osteoporosis & 42(17.21\%)\tabularnewline
Gout & 36(14.75\%)\tabularnewline
Constipation & 20(8.20\%)\tabularnewline
Chronic obstructive pulmonary disease & 18(7.38\%)\tabularnewline
Gastric ulcer/gastritis & 14(5.74\%)\tabularnewline
Gastroesophageal reflux disease & 12(4.92\%)\tabularnewline
Insomnia & 10(4.10\%)\tabularnewline
Kidney disease & 8(3.28\%)\tabularnewline
Others & 33(13.52\%)\tabularnewline
Anatomical therapeutic chemical classification,n(\%) &\tabularnewline
A: Alimentary tract and metabolism &\tabularnewline
A02 Drugs for acid related disorders & 82\tabularnewline
A06 Drugs for constipation & 69\tabularnewline
A10 Drugs used in diabetes & 122\tabularnewline
A11 Vitamins & 24\tabularnewline
B: Blood and blood-forming organs &\tabularnewline
B01 Anti-thrombotic agents & 266\tabularnewline
C: Cardiovascular system &\tabularnewline
C01 Cardiac therapy & 102\tabularnewline
C02 Antihypertensives & 684\tabularnewline
C03 Diuretics & 45\tabularnewline
C04 Peripheral vasodilators & 52\tabularnewline
C05 Vasoprotectives & 33\tabularnewline
C07 Beta blocking agents & 207\tabularnewline
C08 Calcium channel blockers & 143\tabularnewline
C09 Agents acting on the renin-angiotensin system & 245\tabularnewline
C10 Lipid modifying agents & 134\tabularnewline
G: Genital urinary and sex hormones &\tabularnewline
G04 Urologicals & 15\tabularnewline
M: Musculoskeletal system & 36\tabularnewline
N: Nervous system &\tabularnewline
N05 Psycholeptics & 45\tabularnewline
(Anxiolytics, hypnotics, anti-psychotics i.e. neuroleptics)
&\tabularnewline
N06 Antidepressants & 12\tabularnewline
No ATC code & 32\tabularnewline
\bottomrule
\end{longtable}

ATC, anatomical therapeutic chemical.

\textbf{Table 2 Classification of DRPs identified according to PCNE
V8.03 (N=525)}\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
\textbf{Code} & \textbf{Detailed classification} & \textbf{N
(\%)}\tabularnewline
\midrule
\endhead
\textbf{Problems} & \textbf{Problems} &\tabularnewline
P1 & Treatment effectiveness & 282(53.71\%)\tabularnewline
P1.1 & No effect of drug treatment & 51(9.71\%)\tabularnewline
P1.2 & Effect of drug treatment not optimal &
158(30.10\%)\tabularnewline
P1.3 & Untreated symptoms or indication & 73(13.90\%)\tabularnewline
P2 & Treatment safety & 178(33.90\%)\tabularnewline
P2.1 & Adverse drug event (possibly) occurring &
178(33.90\%)\tabularnewline
P3 & Other & 65(12.38\%)\tabularnewline
P3.1 & Problem with cost-effectiveness of the treatment &
14(2.67\%)\tabularnewline
P3.2 & Unnecessary drug-treatment & 51(9.71\%)\tabularnewline
\textbf{Causes} & \textbf{Causes} &\tabularnewline
C1 & Drug selection & 375(71.43\%)\tabularnewline
C1.1 & Inappropriate drug according to guidelines/formulary &
34(6.48\%)\tabularnewline
C1.2 & Inappropriate drug (within guidelines but otherwise
contra-indicated) & 106(20.19\%)\tabularnewline
C1.3 & No indication for drug & 26(4.95\%)\tabularnewline
C1.4 & Inappropriate combination of drugs, or drugs and herbal
medications, or drugs and dietary supplements &
30(5.71\%)\tabularnewline
C1.5 & Inappropriate duplication of therapeutic group or active
ingredient & 34(6.48\%)\tabularnewline
C1.6 & No or incomplete drug treatment in spite of existing indication &
145(27.62\%)\tabularnewline
C2 & Drug form & 23(4.38\%)\tabularnewline
C2.1 & Inappropriate drug form (for this patient) &
23(4.38\%)\tabularnewline
C3 & Dose selection & 108(20.57\%)\tabularnewline
C3.1 & Drug dose too low & 38(7.24\%)\tabularnewline
C3.2 & Drug dose too high & 29(5.52\%)\tabularnewline
C3.3 & Dosage regimen not frequent enough & 17(3.24\%)\tabularnewline
C3.4 & Dosage regimen too frequent & 13(2.48\%)\tabularnewline
C3.5 & Dose timing instructions wrong, unclear or missing &
11(2.10\%)\tabularnewline
C4 & Treatment duration & 19(3.62\%)\tabularnewline
C4.2 & Duration of treatment too long & 19(3.62\%)\tabularnewline
\textbf{Planned interventions} & \textbf{Planned interventions}
&\tabularnewline
I1 & At prescriber level & 525\tabularnewline
I1.2 & Prescriber asked for information & 6(1.14\%)\tabularnewline
I1.3 & Intervention proposed to prescriber &
505(96.19\%)\tabularnewline
I1.4 & Intervention discussed with prescriber &
14(2.67)\tabularnewline
I3 & At drug level & 525\tabularnewline
I3.1 & Drug changed to & 256(48.76\%)\tabularnewline
I3.2 & Dosage changed to & 130(24.76\%)\tabularnewline
I3.3 & Formulation changed to & 8(1.52\%)\tabularnewline
I3.4 & Instructions for use changed to & 12(2.29\%)\tabularnewline
I3.5 & Drug paused or stopped & 58(11.05\%)\tabularnewline
I3.6 & Drug started & 61(11.62\%)\tabularnewline
\textbf{Intervention Acceptance} & \textbf{Intervention Acceptance}
&\tabularnewline
A1 & Intervention accepted & 485(92.38\%)\tabularnewline
A1.1 & Intervention accepted and fully implemented &
475(90.48\%)\tabularnewline
A1.3 & Intervention accepted but not implemented &
10(1.90\%)\tabularnewline
A2 & Intervention not accepted & 40(7.62\%)\tabularnewline
A2.2 & Intervention not accepted: no agreement &
26(4.95\%)\tabularnewline
A2.3 & Intervention not accepted: other reason (specify) &
14(2.67\%)\tabularnewline
\bottomrule
\end{longtable}

DRPs, drug-related problems.

\textbf{Table 3 Statistical analysis of factors associated with the
number of DRPs}\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
Variables & Univariate analysis & Univariate analysis & Univariate
analysis & Multivariate analysis & Multivariate analysis & Multivariate
analysis\tabularnewline
\midrule
\endhead
& Unstandardized & 95\% Confidence & P value & Unstandardized & 95\%
Confidence & P value\tabularnewline
& coefficients \selectlanguage{greek}β & interval for \selectlanguage{greek}β & & coefficients \selectlanguage{greek}β & interval for \selectlanguage{greek}β
&\tabularnewline
Age & 0.044 & 0.036-0.138 & 0.273 & & &\tabularnewline
Gender & -0.191 & -0.053 to 0.445 & 0.669 & & &\tabularnewline
Number of drugs & 0.24 & 0.036-0.637 & <0.0001 & 0.24 & 0.036-0.637 &
<0.0001\tabularnewline
Number of chronic conditions & 0.286 & 0.094-0.344 & 0.005 & 0.177 &
0.145-0.893 & 0.15\tabularnewline
\bottomrule
\end{longtable}

DRPs, drug-related problems.

\textbf{Table 4 Blood pressure and lipids outcomes of two groups}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
& Pre-intervention & Post-intervention & P\tabularnewline
\midrule
\endhead
Hypertensive patients (n=171) & & &\tabularnewline
SBP mean (mm Hg) & 149.08\selectlanguage{ngerman}±19.75 & 134.56\selectlanguage{ngerman}±12.38 & 0.000\tabularnewline
DBP mean (mm Hg) & 84.56\selectlanguage{ngerman}±11.34 & 78.01\selectlanguage{ngerman}±9.78 & 0.000\tabularnewline
Hyperlipidemia patients (n=73) & & &\tabularnewline
TC (mmol L\textsuperscript{-1}) & 6.17\selectlanguage{ngerman}±1.34 & 4.51\selectlanguage{ngerman}±0.80 &
0.027\tabularnewline
LDL-C (mmol L\textsuperscript{-1}) & 3.26\selectlanguage{ngerman}±1.08 & 2.54\selectlanguage{ngerman}±0.57 &
0.000\tabularnewline
TG (mmol L\textsuperscript{-1}) & 2.47\selectlanguage{ngerman}±0.93 & 1.69\selectlanguage{ngerman}±0.90 &
0.000\tabularnewline
\bottomrule
\end{longtable}

SBP, systolic blood pressure; DBP, diastolic blood pressure; TC,
total~cholesterol; LDL-C, low-density lipoprotein cholesterol; TG,
triglycerides.

\textbf{Table 5 Average cost of medications per patient for every month}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
& Pre-intervention & Post-intervention & P\tabularnewline
\midrule
\endhead
Average drug cost per patient for every month (RMB) & 387.72\selectlanguage{ngerman}±168.48 &
355.17\selectlanguage{ngerman}±180.03 & 0.009\tabularnewline
Cost of antihypertensive drugs(RMB) & 230.40\selectlanguage{ngerman}±138.14 & 206.58\selectlanguage{ngerman}±112.74 &
0.001\tabularnewline
Cost of lipid modifying agents(RMB) & 181.12\selectlanguage{ngerman}±106.14 & 242.67\selectlanguage{ngerman}±175.56 &
0.006\tabularnewline
\bottomrule
\end{longtable}

RMB, Ren Min Bi.

\selectlanguage{english}
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