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Objective: Aim: Klebsiella pneumonia has emerged as an increasingly important cause of community-acquired nosocomial infections and many of these strains are highly virulent and exhibit a strong propensity to spread. Infections cause by K. pneumonia produces carbapen¬emase (KPC) enzyme and can be difficult to treat since only a few antibiotics are effective against them. Bacteriophage targeting this strain can be an alternative treatment. Characterisation of bacteriophage is utmost important in assisting the application of bacteriophage in phage therapy. Patients and methods: Materials and methods: In the present study, the lytic bacteriophage, k3w7, isolated by the host Klebsiella pneumoniae kP2 was characterised using transmission electron microscope (TEM), plaque assay, and restriction digestive enzyme to investigate mor¬phology, host spectrum, bacteriophage life cycle and stability accordingly. Results: Results and conclusions: As shown by TEM, k3w7 was observed to have the characteristic of icosahedral heads 100 nm and contractile sheaths 120 nm suggesting it belongs to the family of myoviridae.The Investigation has done on the phage growth cycle showed a short latent period of 20 min and a burst size of approximately 220 plaque forming units per infected cell. Stability test showed the phage was stable over a wide range of pH and temperatures. According to restriction analysis, k3w7 had 50 -kb double-stranded DNA genome as well as the heterogeneous nature of genetic material. These findings suggest that K3W7 has a potential use in therapy against infections caused by K. pneumonia produces carbapenemase.
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© ALUNA Publishing
Pol Merkur Lek, 2023; LI, 1: 4
Olena O. Khaustova, Vitaliy Y. Omelyanovich, Dmytro O. Assonov, Azize E. Asanova
Thomai Klimentidou, Anna Patsopoulou, Vasileios Tzenetidis, Pavlos Saras, Ioannis Apostolakis, Maria Malliarou
Iryna R. Vyshnevska, Olga V. Petyunina, Mykola P. Kopytsya, Anton O. Bilchenko, Larysa L. Peteneva
Daria M. Suprun, Maria K. Sheremet, Tetiana V. Hryhorenko, Mykola O. Suprun, Marja O. Nesterova, Ivan M. Okhrimenko, Alla L. Dushka
Abeer Ameen Baqer, Norefrina Shanaz Md Nor, Huda Salman Alagely, Mustafa Musa, Siti Noor Adnalizawati Adnan
Vladyslav A. Smiianov, Tetiana V. Ivakhniuk, Inna O. Plakhtiienko, Yevhen V. Smiianov, Polina O. Hornostaieva
Ivan М. Okhrimenko, Vadym D. Chornous, Oleksandr T. Nikolaiev, Victoria A. Shtykh, Stanislav O. Yuriev, Yaroslav S. Slivinskyi, Sergii M. Kotov
INTERVENTIONS Anna Olma, Witold Streb, Monika Lazar
Andrzej Witusik, Stella Kaczmarek, Marcin Kosmalski, Tadeusz Pietras
Viktor Vus, Kate Shipley, Tom Lühmann
Justyna Martyna Brzozowska, Joanna Gotlib
Waldemar Elikowski, Dariusz Angerer, Natalia Fertała, Magdalena Zawodna-Marszałek, Weronika Greberska, Teresa Ganowicz-Kaatz, Marek Słomczyński
Army Pambudi Suryo, Muhammad Arin Parenrengi
Alicja Skowronek, Marzena Kubat, Jadwiga Wolińska, Beata Łabuz-Roszak
© ALUNA Publishing House Pol Merkur Lek, 2023; LI, 1: 5-13
DOI: 10.36740/Merkur202301101
Olena O. Khaustova, Vitaliy Y. Omelyanovich, Dmytro O. Assonov, Azize E. Asanova
Aim: Evaluation of the eectiveness of the early 8-week monotherapy with escitalopram as a form of proactive psychosomatic
intervention for patients with post-COVID depression.
Materials and methods: 44 patients with post-COVID depression were involved in a proactive psychosomatic intervention in
the form of an 8-week intake of escitalopram (Medogram, Medochemiе Ltd) for 2–8 weeks in the case of a diagnosis of severe
depression. Hamilton Depression Scale (HAM-D), Somatic Symptom Scale (SSS-8), Quality of Life Scale (CQLS) were used to assess
symptoms and status dynamics.
Results: Patients with post-COVID depression after an 8-week course of escitalopram therapy showed a signicant reduction in
mental and somatic symptoms of depression and an improvement in quality of life. At the time of enrollment in the study, 12
(28.58%) individuals had mild depression, 15 (35.71%) had moderate depression, and 15 (35.71%) had severe depression. At the
end of the 8th weeks of taking the drug in 24 (57.14%) there were no signs of depression on the HAM-D scale, in 18 people there
were subclinical manifestations of depression. The eectiveness of escitalopram in reducing the symptoms of depression in this
study was 66%.
Conclusions: With the introduction of pharmacotherapy with escitalopram there was a signicant reduction in mental and so-
matic symptoms of depression and an improvement in quality of life. Escitalopram (Medochemie Ltd) may be an eective drug for
psychopharmacotherapy of depressive symptoms in patients who have had COVID-19. Further studies are promising its eective-
ness in the treatment of post-COVID depression.
KEY WORDS: proactive psychosomatic medicine, COVID-19, depression, escitalopram
Table 1. Consultative-liaison psychiatry: traditional and
proative models (modif. Sledge W.H., Lee H.B., 2015) [4]
Characteristic Traditional model Proactive model
Type of
psychiatrist, primary
care physician,
nurse, social worker
Case denition Consultation at
the request of
the attending
Screening based on
anamnesis, medical
records and report
of nursing sta
of intervention
for the attending
(entry in the
card / medical
Joint supervision
with close
of the
for treatment, risk
reduction =and
crisis management
Prevention of
behavioral barriers
to care, avoidance
of crises, synergy of
Outside the
team in the sta of
a multidisciplinary
In recent years, the world has been developing and
implementing a proactive approach to providing psychi-
atric care to patients of multidisciplinary hospitals, based
on the theoretical foundations of psychosomatic medi-
cine and its clinical embodiment – consultative-liaison
psychiatry [1]. Proactive psychosomatic medicine (PPM)
is a new way of providing psychological and psychiatric
services in general medical departments, based on the
principles of initiative, dedication, intensity and integra-
tion into general medical care [2].
The basis for the evolution of the system of psycholog-
ical and psychiatric care was the need to eectively man-
age the psychological and social aspects of any disease,
because it is these aspects that are partly an important
reason for the lack of eectiveness of therapy and the pa-
tient’s long stay in the hospital [3]. Recent baseline stud-
ies, meta-analyses and expert consensuses on proactive
psychiatric counseling in 2011–2018 [2–5] noted that 20
to 40% of patients in multidisciplinary hospitals also suer
with mental illness, which can signicantly complicate the
course, eectiveness of therapy and prognosis of somatic
pathology. Mental illness in patients of multidisciplinary
hospitals partly interferes with timely discharge from the
hospital, causes a greater number of additional consulta-
tions of related specialists and increases the overall cost
of medical care. Based on these studies, it was recognized
that psychiatric counseling is of great importance for the
Olena O. Khaustova et al.
supervision of patients of a somatic prole, and the main
features of the traditional and proactive models of con-
sultative and communicative psychiatry were identied
(Table 1.) [4].
Published in 2019 HOME studies [6] have made more
specic recommendations on how hospital psychiatric
services should be organized and what specic interven-
tions are needed for patients:
1. Early proactive biopsychosocial evaluation of newly
hospitalized patients using a biopsychosocial ap-
proach to identify all problems, including mental ill-
2. Creating a plan for comprehensive supervision and
systematic management of problems that create po-
tential obstacles to a quick discharge from the hospi-
3. Implementation of a comprehensive supervision
plan with daily examinations of the patient on the
progress of the psychosomatic state.
4. Integrated work with the sta of local departments
(doctors, nurses, other consultants and social as-
sistance specialists) and out-of-hospital services to
ensure the implementation of the comprehensive
supervision plan.
In 2019 The American Psychiatric Association’s Board
of Consultative and Communication Psychiatry initiated
the development of a resource document on proactive
counseling and communication psychiatry, which was
approved for publication on December 12, 2020. This
document notes the implementation of the model of
proactive consultative-liaison psychiatry which contents
four elements:
systematic screening for actual mental health prob-
lems in patients with a somatic prole (patients ad-
mitted to certain medical institutions are system-
atically checked for signs of active mental health
problems, especially those that may jeopardize the
provision of care);
early clinical intervention (proactive measures adapt-
ed to individual patients, with acombination of inter-
ventions for somatic and mental disorders);
providing care on the basis of a team multidiscipli-
nary approach (the mental
health team is part of the structure of the multidisci-
plinary hospital and provides comprehensive mental
health care directly in the general hospital);
integration of care with primary teams and services (a
proactive psychological and psychiatric team closely
coordinates work with primary services in real time,
often between clinicians of relevant experience: from
doctor to doctor, from nurse to doctor /nurse, from
social worker to social worker / rehabilitation special-
ist, and vice versa).
It is the proactive models of mental health care that
have been tested by the COVID-19 pandemic. Some hos-
pitals have decided to create separate departments spe-
cically designed to treat patients with acute psychiatric
needs and COVID-19 [7]. The rest have chosen to create
units of psychological-psychiatric or consultative-liaison
psychiatric care in the structure of multidisciplinary hospi-
tals [8, 9]. The latest scientic medical literature highlights
the potential of proactive psychological and psychiatric
care, to help reduce costs and length of hospital stay,
which are critical goals during this pandemic [10–13].
In addition to psychoeducation, increased motivation
and adherence to treatment and emotional support, the
authors note that clinically dened depression and other
mental disorders seen in patients requiring infectious iso-
lation in hospitals are also expected to be prevented and
treated. [11].
Indeed, infectious diseases, including respiratory viral
diseases, quite often lead to longterm negative medical,
biological and psychosocial consequences in sick per-
sons [14]. Novel coronavirus disease of 2019 (COVID-19),
a systemic infection that could potentially target various
organs and functions, is the most complex pandemic in
the twenty-rst century [15]. The death rate from COV-
ID-19 is approximately in the range of 3.4–5.5%, which
is signicantly higher than for seasonal inuenza caused
by the inuenza virus (1%) [16]. Moreover, despite the
fact that eective COVID-19 vaccines continue to be ap-
proved and distributed around the world, these injec-
tions are one step in a multi-step process to combat the
challenges posed by the pandemic. Even with millions
of people receiving COVID-19 vaccines, the virus will
continue to spread, and viral mutations will continue to
test the eectiveness of available vaccines. Many health
experts argue that identifying a medication that can pre-
vent people from developing severe COVID-19 illness is
also important, especially when it is an inexpensive and
widely available treatment [15].
COVID-19 has a signicant impact on people’s mental
health and quality of life. It is associated with numerous
psychological and societal eects, in particular with an
increase in the number of reports of an increase in the
number of mental disorders [17, 18]. Although recent evi-
dence suggests that in about 18% of patients who have
had SARS-CoV-2 infection, a psychiatric diagnosis is es-
tablished between 14 and 90 days after infection, long-
term data show that approximately 1 in 3 COVID-19 pa-
tients experiences neurological or psychiatric disorders 6
months after infection.
During the COVID-19 pandemic, the number of symp-
toms of depression reported by patients increased 3-fold
compared to the previous period [19, 20]. Already during
COVID-19, about 50% of patients report symptoms of
depression [20]. A signicant proportion of patients after
coronavirus report persistent fatigue, shortness of breath
and neuropsychological symptoms [21]. After over-
dressed depressive symptoms are also observed in most
people – up to 39% [22]. Persistent mental problems with
a critical level of depression are observed in COVID-19 sur-
vivors even 1 year after discharge from the hospital [23].
A number of researchers argue that due to depressive
manifestations, persons who survived COVID-19 can be
considered a risk group for suicide [24].
The mentally related eects of COVID-19 are likely to be
present for a long time and reach their peak later than the
pandemic itself [18, 25]. In addition to social phenomena,
for example, associated with lockdown, the cause of dis-
turbances may be that the coronavirus is able to stimulate
the development of psychological consequences through
direct infection of the central nervous system or indirectly
through the immune response [26]. Various mental dis-
orders, including those of the depressive spectrum, have
been linked to neuroinammatory processes [27].
Although mental health research currently focuses on
social anxiety and quarantine measures, mental disorders
caused by COVID-19 may become a problem to be ad-
dressed in the future [28]. Research is needed on how to
reduce the negative burden of post-COVID mental prob-
lems, in particular depressive disorders [18]. Thus, a num-
ber of therapy issues should be addressed, including the
question of eective psychopharmacological treatment
of post-COVID depression.
A recent meta-analysis [29] of studies conducted in
individuals with depressive disorder after antidepressant
treatment, predominantly including selective serotonin
severe reuptake inhibitors (SSRIs), conrms that in gen-
eral, antidepressants may be associated with a decrease
in plasma levels of 4 of the 16 inammations, including
IL-10, TNF-α and CCL-2, which are associated with the
severity of COVID-19 [30], as well as IL-6, which is highly
correlated with mortality from disease [31, 32]. These nd-
ings are consistent with a preliminary meta-analysis of 22
studies conducted by Hannestad et al. in 2011, where it
has been shown that treatment with SSRIs can reduce lev-
els of IL-1β, IL-6, and possibly TNF-α [33].
N. Hoertel et al. [34] reported the rst major observa-
tional study of antidepressant use in COVID-19. They con-
ducted a retrospective multicenter cohort study that ex-
amined the association between antidepressant use and
the risk of intubation or death in 7345 adults hospitalized
with COVID-19. 257 patients received SSRIs, 71 patients
received SSRIs, 59 patients received tricyclic antidepres-
sants, 94 – received tetracyclic antidepressants, 44 – an-
tidepressants of α2-antagonists, 6885 patients did not re-
ceive antidepressant treatment. The authors concluded
that the eects of escitalopram, uoxetine, paroxetine,
venlafaxine, or mirtazapine were largely associated with
reduced risk of intubation or death (all p<0.05).
Escitalopram is a selective serotonin reuptake inhibi-
tor used to treat depressive disorders and generalized
anxiety disorder [35, 36]. The results of a number of stud-
ies indicate that escitalopram is a fairly eective antide-
pressant and causes a small number of side eects when
taken [37]. No less interesting is the recent information
about the antiviral eect of escitalopram (in particular
on SARS-CoV-2 through inhibition of sphingomyelinase),
which makes the study of the eectiveness of this drug
in the treatment of depression in patients with COVID-19
who have recently had it and have post-COVID depres-
sive manifestations especially interesting. However, at
the start of this study, most of the information found in
the scientic medical literature about studies conducted
or planned mainly concerned the safe and/or potentially
benecial qualities of escitalopram, rather than its eec-
tiveness in reducing depressive symptoms in patients
who have had COVID-19 [33, 34, 38].
The aim of the work was to evaluate the eectiveness
of proactive psychosomatic intervention in the form of
8-week monotherapy with escitalopram in patients with
post-COVID depression.
According to the proactive model of consultative-
liaison and communication psychiatry, all patients ad-
mitted to the hospital with a diagnosis of coronavirus
disease were screened for signs of active mental health
problems, especially those that could jeopardize the
provision of care.
After screening and obtaining informed consent,
44 patients with post-COVID depression were involved
in the study. 2 patients withdrew from the study prema-
turely; their data were not taken into account in the nal
processing of the results.
Inclusion criteria: The study included men and non-
pregnant non-breastfeeding women between the ages
Table 2. Study design.
Screening assessment for eligibility n=67)
Not included due to non-inclusion criteria (n=25)
Signing of informed consent and involvement in the study
T1: status rating by scales
HAM-D, HADS-D, SSS-8, CQLS Before starting the medication
Early withdrawal from the study (n=2)
T2: HAM-D score 2 weeks after taking the drug
T3: HAM-D rating 4 weeks after taking the drug
T4: HAM-D status rating 6 weeks after taking the drug
T5: HAM-D status rating 8 weeks after taking the drug
Analysis and statistical processing of the data (n=44)
Table 3. Dynamics of results on scales on the rst and last day
of the study.
Scale T1 (week 0 ) T5 (Week
8 )
t p
HADS-D 15.00±3.09 7.09±2.36 –14.09 <0.001
HAM-D 21.26±3.59 7.04±2.45 –24.85 <0.001
SSS-8 6.90±3.46 4.52±2.72 5.37 <0.001
CQLS 58.23±14.61 69.54±10.61 4.58 <0.001
Olena O. Khaustova et al.
of 18 and 75 who had had COVID-19 less than 1 month
ago and had ≥11 points on the Depression subscale of the
Hospital Anxiety and Depression scale.
Exclusion criteria: Patients who participated in another
study for 1 month prior to or during screening who had
undergone surgery in the previous 6 months were not
included in the study. Patients who abused psychoactive
substances at the time of screening, had uncontrolled
or unstable cardiovascular, pulmonary, gastrointestinal,
urogenital, endocrine, neurological or psychiatric disor-
ders were not enrolled in the study. Patients who used ac-
counting drugs or opiate analgesics for >5 days during the
month before screening were not included in the study.
The primary endpoints were the depression severity
level on the Depression subscale of the Hospital Anxiety
and Depression Scale (HADS-D) and the Depression Se-
verity Level on the Hamilton Depression Scale (HAM-D)
for assessing depression. Secondary endpoints were so-
matic symptoms on the Somatic Symptom Scale (SSS-8)
and Quality of Life Scale by A.S. Chaban (CQLS) were used.
To assess the symptoms, the 17-factor Hamilton De-
pression Rating Scale, Hospital Anxiety and Depression
Scale (Depression subscale), Somatic Symptoms Scale
and Chaban A.S. Quality of Life Scale were used.
The 17-item Hamilton Depression Rating Scale (HAM-
D) consists of 17 items (9 of which are rated from 0 to
4points, and 8 from 0 to 2 points) lled out by a specialist
during a structured clinical interview [39]. Interpretation
of the nal score was carried out according to the up-
dated in 2019 NICE recommendations for the treatment
and management of depression in adults: 0–7 – absence
of depression, 8–13 – subclinical manifestations, 14–18 –
moderate manifestations, 19–22 – moderate manifesta-
tions, 23+ – severe manifestations of depression [40].
The Hospital Scale of Anxiety and Depression (HADS-
D) is a self-esteem scale often used to assess anxiety and
depression. Developed by Zigmond & Snaith in 1983, it
includes two subscales – anxiety and depression [41]. The
depression subscale contains 7 statements, estimated
from 0 (absence of a sign) to 3 (maximum severity of a
sign). The maximum score for the depression subscale is
from 0 to 21. The interpretation is as follows: 0–7 – nor-
mal, 8–10 – risk zone, 11 or more – clinically pronounced
depression [42].
The Somatic Symptom Scale (SSS-8) is a brief self-
questionnaire of the somatic manifestations of depres-
sion developed by Gierk B. et al. [43]. The scale consists
of 8 questions, each of which is rated from 0 to 4 points,
where 0 is “Not at all bothered”, 4 is “Very disturbing”. The
assessment of somatic symptoms occurs by calculating
the total score, which can vary from 0 to 32 points. The re-
sults are interpreted as follows: 0–3 points – the minimum
degree of intensity of manifestations, 4–7 – low, 8-11 – av-
erage, 12–15 – high, 16–32 – a very high degree of inten-
sity of manifestation of somatic symptoms [44].
Chaban A.S. Quality of Life Scale (CQLS) is a question-
naire designed to assess the quality of life, containing 10
questions on dierent aspects of the life of the subject. It
is necessary to indicate the number of points that is most
suitable, from 0 (“Not at all satised” to 10 (“Extremely
satised”). Assessment of the quality of life occurs by cal-
culating the total score, which can vary from 0 to 100. A
score of up to 56 points corresponds to an extremely low
level of quality of life, from 57 to 66 – low, 67–75 points
correspond to an average level, 76–82 points – high, from
83 points – a very high level of quality of life [42].
The study was conducted on the clinical basis of
the Department of Medical Psychology, Psychosomatic
Medicine and Psychotherapy of the Bogomolets National
Medical University. After obtaining informed consent and
conducting a screening procedure, if the inclusion cri-
teria were met, the participants lled out the CQLS and
SSS-8 questionnaires and a structured clinical interview
was conducted with them to assess depression (HAM-D),
which corresponds to the time point T1. The study design
is presented in Table 2.
A structured clinical interview (HAM-D) was conduct-
ed with participants every 2 weeks after 2 weeks (T2), 4
weeks (T3), 6 weeks (T4), and 8 weeks (T5). After the 8th
week, a second assessment was carried out on the CQLS,
SSS-8 and HADS-D scales. Pharmacological intervention
consisted of taking escitalopram (Medoprom, Medoche-
mie Ltd) 5 mg per day for the rst week and 10 mg per day
for 2–8 weeks for the initial level of mild to moderate de-
pression and taking escitalopram (Medoprom, Medoche-
Table 4. Changes in average values on the rst and last day of
the study.
Scale Changes in averages
T1 and T5
95% CI
HADS-D –7.90 –9.03; –6.77
HAM-D –14.21 –15.36; –13.05
SSS-8 –2.38 –3.27; –1.48
CQLS +11.31 6.32; 16.28
Table 5. HAM-D scores for 8 weeks.
HAM-D indicators at dierent time points, M±SD
T1 T2 T3 T4 T5
±3.593,4, 5
±3.483, 4,5
±2,501, 2, 4, 5
±2.431, 2, 3, 5
±2.451, 2, 3, 4
1 dierence from T1 indicators is statistically signicant, p<0.05;
2 the dierence from T2 indicators is statistically signicant, p<0.05;
3 the dierence from the T3 indicators is statistically signicant, p<0.05;
4 the dierence from the T4 indicators is statistically signicant, p<0.05;
5 the dierence from the T5 indicators is statistically signicant, p<0.05.
mie Ltd) 10 mg per day for the rst week and 20 mg per
day for 2–8 weeks for severe initial levels of depression.
To assess the normality of the distribution, the Shapiro
Wilk criterion was used. Quantitative data are presented
by mean value and standard deviation [M±SD]. Qualita-
tive data are presented through n and %. To compare
treatment outcomes at time points T1 and T5 Students’-
t Test was used for related samples; to compare HAM-D
results at points T1–T5 the Repeated Measures Analysis of
Variance (rANOVA) (rANOVA) was applied. The Bonferroni
Correction Method was used for the post-hoc evaluation.
Correlation analysis was performed using the Pearson cri-
terion. To statistically process the results, Microsoft Excel
and Python were used with packages NumPy, Pandas,
scipy, statsmodels. The data visualization was done using
Python with the Seaborn package. The statistical signi-
cance was set to p<0.05.
According to the proactive model of consultative-
liaison and communication psychiatry, 67 patients hos-
pitalized with a diagnosis of coronavirus disease were
screened for signs of active mental health problems,
namely depressive manifestations. 44 people (65.7%)
were conrmed to have clinically signicant symptoms of
depression (≥11 on the depression subscale of the hospi-
tal anxiety and depression scale).
42 (95.5%) patients with post-COVID depression com-
pleted the study; 2 (4.5%) patients left the study early,
their data were not taken into account in the nal process-
ing of the results. Among the persons studied, there were
31 (73.80%) women and 11 (26.19%) men. The average
age of the participants was 38.02±9.50 years. All quantita-
tive indicators obeyed the normal law of distribution.
At the time of enrollment in the study, 12 (28.58%)
individuals had mild depression, 15 (35.71%) had moder-
ate depression, 15 (35.71%) had severe depression (Fig. 1).
Fig. 1. Distribution of examined persons by severity of depression (by HAM-D) and the severity of somatic symptoms (SSS-8).
Fig. 2. Distribution of the studied persons by the level of quality of life at the time of T1 and T5.
HAM-D (T1) SSS-8(T1)
Number of participants
Olena O. Khaustova et al.
The average value on the HAM-D scale was 21.26±3.59, on
the HADS-D scale – 15.00±3.09.
The minimum level of manifestations of somatic symp-
toms had 7 (16.66%) subjects, low – 19 (45.23%), medium
– 12 (28.58%), high – 4 (9.52%). The average score on the
SSS-8 scale was 6.90±3.46.
22 (52.38%) participants at the time of enrollment in
the study rated their level of quality of life as very low, 8
(19.04%) as low, 6 (14.28%) as average, 3 (7.14%) as high
and 3 (7.14%) as very high. The average value on the CQLS
scale at the time of attraction (T1) was 58.23±14.61.
After 8 weeks (T5), there was a statistically signicant de-
crease in HADS-D, HAM-D and SSS-8 and a statistically sig-
nicant increase in CQLS (Table 3.).
At the end of the 8th week of taking the drug, 18
(42.86%) subjects remained subclinical manifestations of
Fig. 3. Dynamics of HAM-D indicators during 8 weeks.
Fig. 4. Correlation matrix of scale and age characteristics.
depression on the HAM-D scale, the rest of the study con-
tingent had no signs of depression at all. The number of
subjects with a minimum level of somatic symptoms in-
creased – at the end of the 8th week, 17 subjects (40.47%)
had such a result. Thus, a low level of somatic symptoms
was in 21 (50%) subjects, average – in 3 (7.14%) subject,
high – only in 1 person (2.38%). Changes in average indi-
cators on the rst and last day of the study are presented
in Table 4.
We noted an improvement in the quality of life –
within 8 weeks, a signicant shift to the left decreased, to-
wards a low quality of life. Thus, at the time point T5, only
3 (7.14%) subjects had a very low level of quality of life, a
low 13 (30.95%) subjects, an average 14 (33.3%) sub-
jects, a high – 6 (14.28%) subjects, a very high – 6 (14.28%)
subjects (Fig. 2).
The dynamics of the overall score on the Hamilton
Depression Scale over 8 weeks was statistically signicant
(F=225.32, p<0.000). Post-hoc tests showed a statistically
signicant dierence between the averages of the Hamil-
ton Scale at individual time points (Table 5), with the ex-
ception of T1 and T2.
The graph of the dynamics of depressive symptoms
(Fig. 3) allows us to visually assess that a signicant de-
crease could be observed after 4 weeks (T3) of taking esci-
Correlation analysis revealed that at the beginning of
the study the total score on the HAM-D scale (T1) had a
moderate directly proportional correlation with the total
scores on the HADS-D scale (r=0.419, p<0.01) and the SSS-
8 scale (r=0.393, p<0.01), and there was also a moderate
inversely proportional relationship with the CQLS quality
of life shower (r=–0.385, p<0.012).
The overall HADS-D score at the beginning of the
study had a moderate, directly proportional relationship
with the result of the HADS-D scale at the end of the study
(point T5, r=0.419, p<0.01), with the shower of the HAM-
D scale at point T5 (r=0.488, p<0.001), with indicators of
the SSS-8 scale at point T1 (r=0.489, p<0.001) and point T5
(r=0.307, p<0.05).
The CQLS score at the start of the study had a moder-
ate inversely proportional relationship also to the SSS-8
score at the same time point (r=–0.403, p<0.008). The pa-
tients’ age had a moderate, directly proportional relation-
ship with the CQLS score at 8 weeks (r=0.311, p<0.05). The
thermal correlation matrix is shown in Fig. 4.
Post-COVID depressive manifestations are a serious
challenge for the mental health system, so the introduc-
tion of a proactive model of consultative-liaison and com-
munication psychiatry to provide patients with depressive
disorders with specialized care within the department of a
multidisciplinary hospital was timely and appropriate [44].
At the time of involvement in this study, most patients
had moderate manifestations of depression. These results
are consistent with data obtained by Raman et al. in 2021:
2–3 months after the onset of the disease, patients with
COVID-19 were more likely to report symptoms of moder-
ate and severe depression compared to the control group
[45]. High rates of depression make it relevant to develop
a number of actions aimed at rehabilitating and re-adap-
tation of the persons who have had COVID-19 [46].
The eectiveness of escitalopram in reducing symp-
toms of depression in this study was 66%. A systematic
review and meta-analysis by Cipriani et al. (2018) shows
that escitalopram is signicantly more eective than most
other antidepressants and easier to tolerate in patients
[37]. Another meta-analysis is 2020 also showed that esci-
talopram is associated with a rapid reduction in the sever-
ity of symptoms of depression after critical somatic condi-
tions (using the example of a stroke) [47].
A study by Pastoor D., Gobburu J. (2013) indicates that
with 8 weeks of use of escitalopram, there is a decrease
in symptoms of depression compared to the initial level
by at least 50%, uctuating in various studies from 44 to
55% [48]. In a recent study by Si T., Wang et al. (2018), a
68% reduction in symptoms of depression was reported
(from 29.7 to 9.4 on the Hamilton scale) for 8 weeks at a
dosage of 10 mg per day [30]. Thus, it can be assumed that
the eectiveness of escitalopram in reducing depressive
symptoms after suering COVID-19 is not lower than the
eectiveness of the drug in other populations.
Starting escitalopram as early as possible with de-
pressive symptoms due to COVID-19 has the potential
to reduce the mental eects of coronavirus illness and
stop the further development of post-COVID depression.
Given that taking escitalopram along with antiviral drugs
is considered safe [49], it is promising to take already dur-
ing COVID-19 therapy, that is, within the proactive model
of psychosomatic medicine. Further studies on this topic
could clarify which format of therapy is most eective.
An interesting nding was a stronger association of
quality of life with somatic symptoms than with a depres-
sive state as such. In our opinion, this can be explained by
a signicant somatization of depressive symptoms in pa-
tients with post-COVID depression, that is, manifestations
of somatized (masked, larval) depression. Such depression
is characterized by the same biochemical changes in the
brain as depression with typical symptoms, but a variety of,
partly non-specic, somatic symptoms come to the fore.
Therefore, in patients with post-COVID depression,
aective symptoms, exacerbated by a state of loneliness
and isolation, can be hidden or poorly dierentiated may
be hidden. for numerous complaints of a somatic nature.
However, the reduction of somatized depressive manifes-
tations under the inuence of escitalopram aected the
improvement of the quality of life. Improving the quality
of life and simultaneously reducing the degree of mani-
festation of somatic symptoms after 8 weeks of taking
escitalopram may be serve as an argument in favor of
this hypothesis. In a study of the eectiveness of escit-
alopram in the treatment of somatoform disorders, Mul-
ler et al. found that the drug signicantly reduces symp-
toms and improves the functioning of such patients [50].
Somatization of symptoms of anxiety and depression in
the era of COVID-19 has become common [51,52] and is
a promising topic for further research. Given the inversely
proportional relationship of somatization with resilience
and resilience with depressive manifestations [51, 53], it is
no less interesting to study the eectiveness of psychop-
harmacotherapy in improving the resilience of patients
with post-COVID depression. Especially since, according
to the World Happiness Report 2021 on the eects of the
COVID-19 pandemic [54], as well as last year’s Xinli Chi et
al. study [55,56], nearly 2/3 of the people showed post-
traumatic growth after suering PTSD, anxiety, or depres-
sive disorder.
The introduction of a proactive model of consultative-
liaison psychiatry within the COVID department of a multi-
Olena O. Khaustova et al.
disciplinary hospital for patients with depressive disorders
was timely and appropriate, as it ensured early screening
for depression and early initiation of escitalopram for the
onset of depressive symptoms due to COVID-19.
Based on current knowledge of SARS-CoV-2, drugs
combining anti-inammatory and antiviral eects and a
favorable adverse eect prole should be the most prom-
ising therapeutic strategies to combat this viral infection.
In this context, SSRIs are not only inexpensive and widely
available drugs with a safe tolerability prole (even in el-
derly patients), but also t signicantly into this eects
Patients with post-COVID depression who underwent
an 8-week course of escitalopram therapy (Medopram,
Medochemiе Ltd) had a signicant reduction in the men-
tal and somatic symptoms of depression and an improve-
ment in quality of life. Thus, escitalopram may be a prom-
ising drug for psychopharmacotherapy of depressive
symptoms in patients who have had COVID-19. Further
study of its eectiveness in randomized controlled trials
is needed to obtain a promising drug for psychopharma-
cotherapy of depressive symptoms in patients who have
had COVID-19.
Further research is also needed on the eectiveness
of the implementation of the proactive model of consul-
tative-liaison and communication psychiatry in multidis-
ciplinary hospitals for patients with comorbid psychoso-
matic pathology.
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* Contribution: A – Work concept and design, B – Data collection and analysis, C – Responsibility for statistical analysis, D – Writing the article, E – Critical review, F – Final approval.
The work is a fragment of the research project “A dynamic biopsy-
chosocial model of medical and psychological care for patients of
multidisciplinary hospitals in a rapidly changing associative crisis
society (diagnosis, treatment, rehabilitation, prevention)”, state reg-
istration No. 0119U103910.
Olena O. Khaustova – 0000-0002-8262-5252 A, B, F
Vitaliy Y. Omelyanovich – 0000-0001-8587-1312 D, E
Dmytro O. Assonov – 0000-0002-6803-6961 B, C, D
Azize E. Asanova – 0000-0001-9326-0618 B, D
The Authors declare no conict of interest.
Olena O. Khaustova
Bogomolets National Medical University
13 T. Shevchenko blvd., 01601Kyiv Ukraine
tel: +38093-9503403
© ALUNA Publishing House
Pol Merkur Lek, 2023; LI, 1: 14-20
DOI: 10.36740/Merkur202301102.
Aim: Of this study was to investigate the level of Military Nursing Ocers’(MNOS) compassion competence and their personal level
of compassion at work and their correlation with the professional quality of life.
Materials and methods This is a cross-sectional study carried out from December 2019 to May 2020 using the method of convenience
sampling. The study involved 235 MNOs serving in Greek Military Hospitals. A single questionnaire containing Compassion at
Work index, Compassion competence scale and ProQOL 5 was used for data collection. A total of 400 questionnaires were distrib-
uted with a response rate of 58.75%. Data analysis was performed using the statistical package SPSS 22.0.
Results: The research showed that there was a signicant positive correlation of the Compassion Satisfaction score with the com-
passion at work and compassion competence scales. So, the more compassion participants had, the more satisfaction they re-
ceived from the care they put into their work. Conversely, the more compassion participants had, the less burnout they felt.
Regarding secondary traumatic stress, it was found that the higher the participants’ score on the dimensions of compassion in the
dimension “Being non-judgmental”, “Being tolerant to personal distress” and “Being empathic”, the lower the secondary traumatic
stress they felt. The position at hospital, the score on the compassion dimension in the dimension “Experiencing the suering of
others” were found to be independently related to the Compassion Satisfaction score. Specically, Head Nurses had a 3.86 points
lower score compared to Nurse managers. Higher values in the “Experiencing the suering of others” dimension were related
to a higher Compassion Satisfaction score. Nursing Ocers who scored higher in compassion dimensions such as “Being non-
judgmental”, “Being tolerant to personal distress” and “Being empathic”, they felt lower secondary traumatic stress.
Conclusions: It is really important for Military nursing Ocers to be compassionate in order to get more satisfaction from caring
about their work and feel less burnout.
KEY WORDS: Compassion at work, Compassion competence, Military Nurse, Professional Quality of Life
displays of empathic emotions (eg, warmth, aection,
sensitivity) are part of supervisors’ behavior in daily ac-
tivities [3].
Compassion at work has been shown to be particu-
larly benecial for emotionally exhausted employees
and it is argued that its consolidation will bring benets
to all involved, customers and employees [4]. In recent
years, an orientation towards actions aimed at customer
satisfaction has been strongly observed. Compassion in
the workplace is consistent with treating customers with
sensitivity and responding with understanding, while it
also appears to have a positive eect on increasing em-
ployee productivity [3]. There are organizations, such as
hospitals, where compassion is a core emotion for the
services provided by employees. Research has proven
that most patients wish during nursing care to have
more personal relationships with the nurses who care for
Military Nursing Ocers (MNOs), in their dual capac-
ity as nurses and military ocers, regularly face the obli-
gation to lead a team that is usually tasked with patient
health improvement. Military Nursing managers in mili-
tary hospitals need to maintain institution’s administra-
tive mission not only routine in nursing tasks but also
in military missions. [1]. Kelly (2010) has stated that the
military nurses’ obligation to follow orders and partici-
pate in battleeld operations “may contradict to the val-
ues and beliefs of civilian health care professionals”[2].
Particular interest was shown in the value of compassion
at work and specically in public organizations, arguing
that compassion in the workplace can be activated ei-
ther when the employee and the supervisor share a chal-
lenging situation or stressful experience. in relation to a
client or on a routine and ongoing basis when displays
Thomai Klimentidou1, Anna Patsopoulou2, Vasileios Tzenetidis2, Pavlos Saras3, Ioannis Apostolakis4,
Maria Malliarou2
them, while compassion seems to lead to a reduction in
stress, better management of chronic diseases, faster re-
covery and greater satisfaction of both patients and em-
ployees [5]. Also, a longitudinal study showed that su-
pervisors’ compassion and support towards employees
had positive eects on both organizational and employ-
ees’ compassionate behavior towards others. Based on
this assumption, the Compassionate Workplace Model
was created, which is based on compassionate feelings
(such as love, generosity, sensitivity, etc.) that employees
receive from their superiors [6].
The indulgence of employees’ emotional state, and
thus the satisfaction oered by acts of compassion, are
related to job satisfaction. However, excessive compas-
sion in combination with the frequent care of sick peo-
ple can have negative eects on the mental health of
health professionals with the appearance of emotional
disorders, such as secondary post-traumatic stress, fa-
tigue from the provision of empathetic care, etc [ 7].
The present study seeks to investigate MNOs level of
compassion at work, compassion competence. and their
correlation with professional quality of life.
This is a cross-sectional study conducted from De-
cember 2019 to May 2020 in the 5 Hellenic Armed Forc-
es General Military Hospitals. The present study seeks to
investigate MNOs level of compassion at work, compas-
sion competence. and their correlation with professional
quality of life.
The research hypotheses were that Compassion
competence and level of compassion at work are re-
lated to their professional quality of life Accordingly re-
search questions were if compassion competence and
level of compassion at work are related to their profes-
sional quality of life The study was fully compliant with
STROBE reporting guidelines for observational research
[8] The study population consisted of MNOs of the Hel-
lenic Armed Forces using the method of convenience
sampling. Criteria for participation has been set for the
MNOs to be working for one of the ve Hellenic Armed
Forces General Military Hospitals; 401 Athens General
Military Hospital (401 AGMH), 404 General Military Hos-
pital (404 GMH), 424 General Military Training Hospital
(424 GMTH), Athens Naval Hospital (ANH) and 251 Air
Force General Hospital (251 AFGH). An exclusion crite-
rion has been dened as less than 2 years of work expe-
rience. A total of 400 questionnaires were distributed to
a population of about 600 people and 235 were com-
pleted (response rate 58.75%) with average completion
time about 20 minutes.
The study tool consisted of four dierent parts: Socio-
demographic and professional data using 11 questions,
Compassion at Work index, Compassion Competence
Scale and ProQOL-5. Compassion at Work index is a reli-
able and valid tool which contains 24 questions record-
ing the frequency of specic feelings or behaviors in the
workplace, answered in 5-point Likert scales (1=almost
never to 5=almost always) with 5 subscales: “Experienc-
ing the suering of others”, “Being non-judgmental”, “Be-
ing tolerant to personal distress”, “Being empathic” and
“Takes appropriate action”. The tool has been developed
by Roey Park and it measures the level of compassion
at work and identies the areas that may need to en-
hance in order to become a more compassionate person
[9]. The validity and reliability of the questionnaire in the
Greek population was also tested. Cronbach Alpha was
found to be 0.87.
Compassion Competence Scale is a questionnaire
with 17 questions answered in 5-point Likert scales
(1=Strongly Agree to 5=Strongly Disagree). It has 3 sub-
scales: “Communication”, “Sensitivit y” and “Insight” and it
was created by Lee and Seomun in 2016 [10]. The validity
and reliability of the questionnaire in the Greek popula-
tion was also tested. Cronbach Alpha was found to be
0.91. Dimension scores can be obtained by calculating
the means of the item-scores in each dimension. The
Professional Quality of Life Scale is a self-report measure
with 30 items which reects the positive and negative
eects of working with people who have experienced
extremely stressful events. The ProQol 5 is divided in
three subscales: Secondary Traumatic Stress, Burnout
and Compassion Satisfaction. Compassion Satisfaction
measures positive aspect of a helper’s professional qual-
ity of life. Burnout and Secondary Traumatic Stress sub-
scales measure the negative aspects. The terms “com-
passion fatigue” and Secondary Traumatic Stress are
used interchangeably. ProQOL 5 questionnaire Greek
version is available free by ProQol organization. The term
“professional quality of life” or ProQOL with three com-
ponents of compassion satisfaction, secondary traumat-
ic stress and burnout, refers to the positive and negative
emotions that a person describes in his/her job as a con-
tributor and a rescuer [11].
The Kolmogorov-Smirnov test was used to test the
null hypothesis that the data set comes from a Nor-
mal distribution. P-value of the Kolmogorov-Smirnov
test ranged from, from 0.101 to 0.541 for dimensions
of Compassion at work index and from 0.093 to 0.356
for dimensions of Compassion Competence Scale, in-
dicating no deviation from normality. Mean values and
standard deviations (SD) were used to describe quanti-
tative variables. Pearson’s correlation was used to deter-
mine the correlation between compassion at work scale
and compassion competence scale It was calculated
that with the sample size of 200 participants or more
the study would have >95% power to detect signicant
associations via regression models, for an eect size of
0.15 or more and at a signicance level of 0.05. Signi-
cance levels were two-tailed and the statistical signi-
Thomai Klimentidou et al.
cance was set at 0.05. The statistical program SPSS 22.0
was used for the analysis.
For the conduct of the research, permission to distrib-
ute the questionnaires was granted by the 401 AGMH,
424 GMTH, AHN and 251 AFGH Ethics Committee. Use
of the Compassion at Work, Compassion Competence
and MLQ-5X Scale questionnaires was licensed by the
original researchers. The participants were informed
about the purpose of the study the preservation of their
anonymity, the voluntary nature of their participation
and the right to refuse to continue. The questionnaire in-
cluded a form of condentiality and inform consent. The
authors state that there are no conicting interests that
could potentially inuence the evaluation of the work.
All subjects gave their informed consent for inclusion
before they participated in the study. The study was con-
ducted in accordance with the Declaration of Helsinki,
and the protocol was approved by the Ethics Committee
of 401 AGMH, 424 GMTH, AHN and 251 AFGH.
The research involved 235 MNOs with an average
age of 38.0 years (SD = 8.8). Of all participants, 80.9%
were women and 19.1% were men. The majority of par-
ticipants were married (65.8%) and 37.1% having no chil-
dren. Regarding their academic background 41.8% held
a postgraduate or doctoral degree, 54.0% had a nursing
specialty and 4.8% a nursing specialization. Most of the
participants (57%) were working in the Army and 57.8%
were senior-ranked Ocers, while 77.0% of the partici-
pants were Head Nurses of Departments. Their mean
years of service was 15.1 years (SD = 8.6). Regarding
their working conditions, 81.1% of the participants were
working shifts (Table 1).
Table 2 returns the scores of the participants on the
dimensions of compassion at work (scores can range
from 1 to 5 points with higher values indicate greater
compassion) and compassion competence scale (scores
can range from 1 to 5 points with higher values indicat-
ing greater compassion competence). The mean score
in the dimension “Being alive to the suering of others”
was 3.85 points (SD= .73 points), in the dimension “Be-
ing non-judgmental” it was 3.85 points (SD= .64 points),
in the dimension “Being tolerant to personal distress” it
was 3.92 points (SD= .75 points), in the dimension “Be-
ing empathic” it was 3.19 points (SD= .60 points) and
in the dimension “ Takes appropriate action’ was 3.56
points (SD= .89 points). The mean score on the dimen-
sion “Communication” was 3.87 points (SD=.55 points),
on the dimension “Sensitivity” it was 3.97 points (SD=.63
points) and on the dimension “Insight” it was 3.75 units
(SD=.65 points). The mean score on the dimension “Com-
passion Satisfaction” was 35.71 points (SD=7.26 points),
on the dimension “Burnout” it was 23.97 points (SD=6.00
points) and on the dimension “Secondary Traumatic
Stress” it was 20.67 points (SD=5.57 points).
Table 1. Demographics of participants.
N %
Gender Male 45 19.1
Female 190 80.9
Age, mean (SD) 38.0 (8.8)
or doctoral
No 110 58.2
Yes 79 41.8
Nursing spe-
No 87 46.0
Yes 102 54.0
No 180 95.2
Yes 9 4.8
Medical Corps
Army 134 57
Navy 31 13.2
Air Force 70 29.8
Rank Junior Ocer 98 42.2
Senior Ocer 134 57.8
Department Nursing
Ocer 181 77.0
Hospital Nursing
Hospital Nursing
3 1.3
Department Head Nurse 42 17.9
Other 9 3.8
Years of service.
mean (SD) 15.1 (8.6)
Years of service
in current
mean (SD)
11.3 (8.4)
Medical Departments 56 24.7
Surgical Departments 72 31.7
Mixed Departments 4 1.8
Closed Departments
(in direct contact with
61 26.9
Closed Departments
(without direct contact
with patients)
8 3.5
Outpatient Departments 14 6.2
Administrative 12 5.3
Individual decision 69 30.3
Hierarchy Decision 103 45.2
Common decision 56 24.6
shift work No 42 18.9
Yes 180 81.1
number of shifts per month Mean (SD)
Evening shift 3.3 (2.3) 3 (2–5)
Night shift 2.7 (2.1) 2 (1–4)
24-hour shift 3.1 (0.8) 3 (2–4)
Table 2. Scores of participants in the Compassion competence
scale and Compassion at work index and ProQOL 5.
Min Max mean SD
Compassion at work
the suering of others
1.40 5.00 3.85 .73
Being non-judgmental 1.40 5.00 3.85 .64
Being tolerant to personal
1.33 5.00 3.92 .75
Being empathic 1.33 4.67 3.19 .60
Takes appropriate action 1.00 5.00 3.56 .89
Compassion Competence
Communication 1.57 5.00 3.87 .55
Sensitivity 1.60 5.00 3.97 .63
Insight 1.25 5.00 3.75 .65
ProQOL 5
Compassion Satisfaction 13.00 50.00 35.71 7.26
Burnout 13.00 41.00 23.97 6.00
Secondary Traumatic
10.00 43.00 20.67 5.57
Table 3. Pearson correlation between the dimensions of pro-
fessional quality of life with the scales of com passion at work
index and compassion competence scale.
at work index
the suering
of others
r 0.37 -0.28 0.01
P <0.001 <0.001 0.851
non-judgmental r 0.04 -0.15 -0.17
P 0.527 0.024 0.011
Being tolerant to
personal distress r 0.18 -0.34 -0.57
P 0.005 <0.001 <0.001
Being empathic r 0.38 -0.20 -0.25
P <0.001 0.002 <0.001
r 0.35 -0.23 0.03
P <0.001 <0.001 0.611
communication r 0.55 -0.40 -0.07
P <0.001 <0.001 0.287
sensitivity r 0.34 -0.31 -0.07
P <0.001 <0.001 0.271
insight r 0.44 -0.33 0.03
P <0.001 <0.001 0.653
Table 3 gives the Pearson correlation coecients
of the dimensions of professional quality of life with
the scales of compassion at work index and compas-
sion competence scale. There was a signicant positive
correlation of the Compassion Satisfaction score with
the compassion at work and compassion competence
scales. So, the more compassion participants had, the
more satisfaction they received from the care they put
into their work. Conversely, the more compassion par-
ticipants had, the less burnout they felt. Regarding sec-
ondary traumatic stress, it was found that the higher the
participants’ score on the dimensions of compassion in
the dimension “Being non-judgmental”, “Being tolerant
to personal distress” and “Being empathic”, the lower the
secondary traumatic stress they felt.
In order to test the predictions, a hierarchical multi-
ple regression was conducted, with two blocks of vari-
ables. The rst block included the position at the hos-
pital (0 = head of the department, 1 = Nurse director)
as the predictors, with Compassion Satisfaction score
as the dependent variable (R2=0.20, p<0.001). In block
two, levels of compassion scales were also included as
the predictor variable, with diculties in Compassion
Satisfaction score as the dependent variable (R2=0.41,
p<0.001). When the dimensions of compassion scales
were entered it also had signicant explanatory power
(R2=0.41, p<0.001), with the increase in R2 being signi-
cant (p<0.001), suggesting that compassion contributed
signicantly to the interpretation of that particular di-
The position at hospital, the score on the compas-
sion dimension in the dimension “Experiencing the
suering of others” were found to be independently re-
lated to the Compassion Satisfaction score. Specically,
Head Nurses had a 3.86 points lower score compared to
Nurse managers. Higher values in the “Experiencing the
suering of others” dimension were related to a higher
Compassion Satisfaction score.
Having the Burnout score as a dependent variable,
the model containing only the demographic and work
data of the participants had no signicant explana-
tory power (R2=0.20, p<0.697). When the dimensions
of compassion scales were entered it also had signi-
cant explanatory power (R2=0.47, p<0.001), with the
increase in R2 being signicant (p<0.001), suggesting
that compassion contributed signicantly to the inter-
pretation of that particular dimension. Higher values in
the “Being tolerant to personal distress” dimension was
related to a lower Burnout score (gure 1).
Having the Secondary Traumatic Stress score as the
dependent variable, the model containing only the
demographic and work data of the participants had
no signicant explanatory power (R2=0.01, p=0.598).
When the dimensions of compassion scales were en-
tered it gained signicant explanatory power (R2=0.29,
p<0.001), with the increase in R2 being signicant
(p<0.001), contributed signicantly to the interpreta-
tion of that particular dimension. suggesting that com-
Thomai Klimentidou et al.
Fig. 1. Correlation of the Burnout score with the “Being tolerant to personal distress dimension.
Fig. 2. Correlation of the Secondary Traumatic Stress score with the “Being tolerant to personal distress dimension.
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12. Lee Y. Seomun G: Development and validation of an instrument to measure nurses’ compassion competence. Applied nursing research 2016;30:76–82. doi:10.1016/j.
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Challenges Journal 2019; 2(1):30. doi: 10.32437/mhgcj.v2i1.47
passion higher values in the “Being tolerant to personal
distress” dimension were related to a lower Secondary
Traumatic Stress score (gure 2).
In the the present study, 235 Nurse Ocers took part,
the majority being women with a percentage of 80.9%
and 19.1% men. The largest percentage of participants
were married (65.8%) with 2 children (30.6%). Most par-
ticipants served in the Army (57%). 57.8% were Senior
Ocers and 77.0% were Department Managers, with a
nursing specialty title in 54% or a master’s or doctorate in
41.8%. This study aimed to assess MNOs level of compas-
sion at work, compassion competence. and their correla-
tion with professional quality of life. Results veried that
Nursing Ocers at a higher leadership role in hospital
(nurse managers) had a greater level of compassion at
work and compassion competence than those who were
at a lower leadership role in hospital (head nurses). This
nding could be explained because Nursing managers’
role is to support of compassionate practices for sta
and improvement of the work environment and sta
well-being [12; 13]. Also, Lee and Seomun agree that
compassion competence is related to work-related char-
acteristics such as position at work.
This study’s nding was a signicant positive corre-
lation of the Compassion Satisfaction score with com-
passion at work and compassion competence. The re-
sults of the present research agree with the study of.
Lee and Seomun whose study have concluded that
compassion competence was a predictive variable for
compassion satisfaction and burnout [12].
The more compassionate nursing ocers were, the
more satisfaction they received from caring about their
work and the less burnout they felt. Also, the higher
the participants’ score on the compassion dimensions
“Being non-judgmental”, “Being tolerant to personal
distress” and “Being empathic”, the lower the second-
ary post-traumatic stress they felt. The Burnout score
was lower when the values in the dimension of com-
passion in the “Being tolerant to personal distress” task
Finally, higher values in the dimension of compas-
sion in the “Being tolerant to personal distress” task were
related to a lower Secondary Traumatic Stress score.
Lee and Semoun’s study results were that the perceived
compassion competence of clinical nurses was noted to
be a predictive factor for compassion satisfaction and
burnout in the professional quality of life. Lee and Seo-
mun also agreed that compassion competence is a fac-
tor inuencing professional quality of life [12].
The limitations of the study concerned: a) the re-
quirement for MNOs to exhibit more than two years of
work experience in a military hospital. b) the COVID-19
pandemic. c) the nature and mission of the Armed
Forces Health Service. which are related to national se-
curity and territorial integrity plans d) cross-sectional
nature of the study e) the use of self-reported meas-
ures; f) the low participation of male nurse; g) the en-
rolment method for possible bias.
This study aimed to evaluate Military Nursing Ocers’
level of compassion at work, compassion competence.
and their correlation with professional quality of life.
A positive correlation was found between Compas-
sion Satisfaction and compassion at work and compas-
sion competence scales. Nursing Ocers who scored
higher in compassion dimensions such as “Being non-
judgmental”, “Being tolerant to personal distress” and
“Being empathic”, they felt lower secondary traumatic
stress. It is really important for Military nursing Ocers
to be compassionate in order to get more satisfaction
from caring about their work and feel less burnout.
Thomai Klimentidou et al.
* Contribution: A – Work concept and design, B – Data collection and analysis, C – Responsibility for statistical analysis, D – Writing the article, E – Critical review, F – Final approval.
Maria Malliarou – 0000-0002-6619-1028 A, C, D, E, F
Thomai Klimentidou B, C,D
Vasileios Tzenetidis – 0000-0002-5714-6567 E
Anna Patsopoulou – 0000-0002-6281-6633 E
Ioannis Apostolakis – 0000-0002-2108-8852E,F
Pavlos Saras – 0000-0001-9967-5152 E, F,
The Authors declare no conict of interest.
Maria Malliarou
Laboratory of Education and Research of Trauma Care
and Patient Safety, Nursing Faculty,
University of Thessaly, Greece
tel: +306944796499
e-mail: malliarou
© ALUNA Publishing House Pol Merkur Lek, 2023; LI, 1: 21-29
DOI: 10.36740/Merkur202301103
Iryna R. Vyshnevska, Olga V. Petyunina, Mykola P. Kopytsya, Anton O. Bilchenko, Larysa L. Peteneva
Aim of our study was to determine the role of the clinical and biochemical markers in predicting the outcomes at one year in
patients with STEMI who have undergone primary PCI.
Materials and methods: The study included 165 patients admitted with STEMI within 12 hours of the onset of symptoms be-
tween January 2020 and August 2021. All patients underwent primary PCI according to the guidelines, followed by standard
examination and treatment at the hospital. Blood samples for biomarker analysis (MMP-9, cTnI) and other routine tests were taken
on admission. At six months after the event, all patients underwent clinical follow-up. Patients were contacted either by phone,
through family members or their physicians 1 year after the event.
Results: The composite endpoint reached 9% of patients at one-year follow-up. ROC analysis of MMP-9 with the one-year com-
posite endpoint showed an AUC=0.711, with 91.7% sensitivity, and 47.4% specicity, 95% CI – 0.604 to 0.802, p=0.0037. ROC
analysis of EQ-5D questionnaire with the one-year composite endpoint showed AUC = 0.73, the 95% CI – 0.624 to 0.820, p<
0.0195, with sensitivity 54.5% and specicity 94.7%. A logistic regression model showed a statistical association with the com-
posite endpoint at one year after STEMI in both EQ-5D (OR=0.89, 95% CI: 0.8313- 0.9725, p=0.0079) and MMP-9 (OR=1.0151, 95%
CI:1.0001-1.0304, p=0.0481).
Conclusions: The level of MMP-9 more than 194 ng/ml and <55 points in EQ-5D predicts major adverse cardiovascular events, in-
cluding cardiovascular mortality and progressive heart failure, as well as other elements of composite endpoints, during a 1-year
follow-up in patients with STEMI after primary PCI. Future studies are needed to clarify this result.
KEY WORDS: STEMI, myocardial infarction, EQ-5D, MMP-9
Ukraine takes rst place among European countries
in cardiovascular morbidity and mortality. The Public
Health Center of the Ministry of Health of Ukraine re-
ports that according to the data of the ranking com-
piled based on the number of deaths of the population
in Ukraine, the most frequent cause is cardiovascular
diseases (CVD), which accounted for 64.3% of the total
structure. Coronary artery disease is the most common
form of CVD and the leading cause of loss of health and
life for both men and women all over the world [1]. Acute
myocardial infarction remains signicant in the structure
of mortality, which is associated not so much with prob-
lems in treatment approaches but with the complexity
of early prediction of complications. Therefore, it is es-
sential to perform risk assessments in ST-elevation myo-
cardial infarction (STEMI) patients to improve long-term
survival. Biomarkers play a benecial conrmatory role
in diagnosis and prognostic utility [2].
Matrix metalloproteinases (MMPs) are a component
of the extracellular matrix and are closely associated
with the instability of atherosclerotic plaque. Histologi-
cal studies have indicated that atheroma lesions express
MMP-9 in unstable plaques. [3, 4, 5]. The presence of
MMP-9 protein in coronary atherosclerotic lesions was
rst found by Brown et al. in 1997 [6]. The results of these
studies showed that MMP-9 was mainly distributed in
the shoulder regions, necrotic core, and the brous cap
of the atherosclerotic plaques and that MMP-9 levels
and activity were higher in unstable plaques than in
stable plaques [7]. Moreover, MMP-9 plays a pivotal role
in tissue and extracellular matrix remodeling in both
standard and pathological processes. [8]. MMP-9, one of
the endopeptidases responsible for the degradation of
the extracellular matrix, can cleave collagen as the lat-
ter’s main component, thereby contributing to favorable
remodeling and preservation of the systolic function of
the left ventricle. MMP-9 is present in the human body
Iryna R. Vyshnevska et al.
even during embryonic laying and involves the forma-
tion of heart tissues from the 16th day of embryogenesis.
[9]. Established that cardiac broblasts are rich in MMP-
9, which contributes to a decrease in collagen synthesis.
MMP-9 is involved in the migration of cardiac broblasts
to myobroblasts, which in turn play a role in scar tissue
formation in patients with STEMI [10]. Several investiga-
tors indicated that increasing evidence suggests that
MMP-9 can serve as a biomarker to evaluate the severity
of coronary artery lesions and to predict the long-time
poor outcomes and mortality of STEMI on the long term.
However, data on the specic impact of baseline plasma
MMP-9 levels and its utility as a prognostic marker after
STEMI are still limited and conicting [8]. In the last dec-
ade, quality of life (QoL) has become an important meas-
ure related to short- and long-term prognosis. The Euro-
Qol 5 Dimension (EQ-5D) is the preferred instrument for
patient-reported outcomes (PRO) [11]. We tried to estab-
lish routine risk factors, PRO, and modern biomarkers to
estimate their role in STEMI prognosis.
The study’s aim was to determine the role of clinical
and biochemical markers in predicting one-year out-
comes in STEMI patients who underwent primary percu-
taneous coronary intervention (PCI).
The study was approved by local ethics committee
(protocol № 4, 10.04.2019). All patients signed informed
consent under the Helsinki Declaration.
165 STEMI patients admitted within 12 hours after
the onset of the rst symptoms with STEMI diagnosis
were included in this study. STEMI was diagnosed ac-
cording to the last European guidelines [12]. The inclu-
sion criteria were STEMI and successfully performed pri-
mary PCI with epicardial blood ow TIMI III, ≥ 18 years,
signed informed consent, and the patient’s physical,
mental, and territorial possibilities to participate in the
trial. Exclusion criteria: decompensated valvular heart
disease, active bleeding, hemoglobin level below 90 g/l,
severe liver disease, kidney failure (glomerular ltration
rate (GFR) < 60 ml/min), mental disorders, drug abuse,
alcohol addiction, surgical interventions within two
months prior enrollment to the study, planned coronary
revascularization three months after the event, myocar-
dial infarction in anamnesis, Killip class III-IV, permanent
atrial brillation, active malignancy.
The minimum number of patients needed for an ef-
fect size of 0.5 and 80% power was 164 [13].
At the end of six months after the event, all patients
came to the site for an additional investigation, clinical
assessment, ECG, echocardiography with strain, deter-
mination of biomarkers, and treatment compliance.
1-year after the event, the patients were contacted by
phone, by their family members, or by their physicians.
PRO was assessed using EQ-5D at admission and
6-months after the event. The mean value was calculat-
ed for each group of patients.
The primary composite endpoint was:
the composition of all-cause death, new incident of
myocardial infarction; ischemic stroke or transient
ischemic attack, heart failure decompensation with
or without hospitalization, hospitalization due to
any cardiovascular disease deterioration.
Secondary endpoint:
mean change in EQ-5D questionnaire between
baseline and 6 months.
Table 1. Baseline characteristics of the study population.
Characteristics MMP-9≤ 201.7 ng/ml MMP-9>201.7 ng/ml р
Age, years 61.00±10.32 60.68±9.02 0,878
Gender, мale-1; female-2 34/10 (77.3/22.7) 32/12 0,623
Current smoking, n (%) 23/52.3 20/45,5 0,522
Type 2 diabetes mellitus, n (%) 9/20.5 13/29,5 0,460
Hypertension, n (%) 38/86.4 39/88,6 0,522
CAD family anamnesis, n (%) 13/29,5 14/31,8 0,817
MI anterior localization, n (%) 24/54,5 23/52,3 0,831
Killip class >1, n (%) 1 1 1.0
SBP, mm Hg 130.95±31.40 138.52±27.20 0.232
DPB, mm Hg 82.91±14.53 84.25±13.13 0.652
HR, beats per minutes 76.15±10.67 76.50±13.31 0.893
Time from pain started to revascularization beginning, hours 6,11±5,21 4.73±4.44 0.215
Notes: CAD – coronary artery disease, SBP – systolic blood pressure, DBP – diastolic blood pressure, HR – heart rate, MI – myocardial infarction
9% of study patients reached the primary composite
The presence of hypertension diagnosed following
the European guidelines [14]. Diagnosis of hypercho-
lesterolemia determined according to the European
guidelines [15]. Diagnosis of type 2 diabetes mellitus
conrmed according to the current ADA statement
(2022) [16].
Percutaneous coronary intervention was performed
on an “Integris Allura” (Philips Healthcare, Best, The Neth-
erlands). A team used a radial approach by the Seldinger
technique and recorded several projections of coronary
arteries. The “Ultravist-370” (Bayer Pharma GmbH, Ger-
many) and automatic injector for contrast enhancement
were used. The amount of the injected contrast is 8 – 10
mL for the left coronary artery and 6 mL for the right
coronary artery. The radiation exposure shifted from 20
to 35 mGy cm. Two independent specialists analyzed
images visually and quantitatively. Unclear angiograms
were excluded from analysis.
Within two to twelve hours after the rst symptom
onset for all signicant stenosis, more than 75% PCI was
performed. Integrity bare-metal stent (Boston Scientic,
USA) implanted in 67 patients, and Resolute Integrity
drug-eluting stent (Medtronic, USA) used in 23 patients.
All investigated patients received standard treatment
according to current ESC protocols. For every patient we
determined Killip class of acute heart failure.
The eective intervention was dened as a reduction
of stenosis in infarct-related arteries by up to 30% with
TIMI 3 after the restoration of coronary blood ow. Low-
molecular heparin was not prescribed after PCI.
The pharmaco-invasive strategy has been provided
to patients that could not be delivered in catheter labo-
ratory in proper time-window. Tenecteplase has been
chosen as a thrombolytic agent. Twenty two percent of
investigated patients received this type of treatment.
The dose is calculated according to body weight, the
maximum dose did not exceed 10.000 units (50 mg of
Transthoracic echocardiography and Doppler were
performed in all STEMI patients in the rst 24 hours after
admission to the intensive cardiac care unit. The exami-
nation was conducted on Toshiba TUS-A500 (Aplio 500,
Japan) on days 3-5 after the event and six months after
the discharge by the only operator to minimize bias. Left
ventricular end-diastolic volume (LVEDV), LV end-systol-
ic volume (LVESV), LV mass (LVM), and LV ejection frac-
tion (LVEF) according to Simpson’s biplane method were
measured automatically. Early to late diastolic transmi-
tral ow velocity (E/A) and the ratio between early mitral
inow velocity and mitral annular early diastolic velocity
(E/e’) were used to assess diastolic function by impulse
transmitral Doppler regime. Global longitudinal strain
(GLS) was performed with speckle tracking and analyzed
by post-processing of apical images of the LV. GLS less
than 16% is abnormal, GLS more than 18% is normal, and
GLS from 16% to 18% is borderline [17, 18].
Blood samples for biomarker analysis and other
routine tests were collected at admission (MMP-9, car-
diac troponin I). The blood samples were carefully centri-
fuged and isolated within 30 minutes of sample collec-
tion and then stored in plastic tubes and frozen at -70°C
until transport to the laboratory. The determination of
biomarkers was carried out on an enzyme immunoassay
analyzer-photometer Immunochem-2100 by enzyme
Table 2. Baseline laboratory ndings of the study population.
Characteristics MMP-9≤ 201.7 ng/ml MMP-9>201.7 ng/ml р
GFR, ml/minute 74.41±26.66 76.07±29.11 0.783
Triglycerides, mml/l 2.12±1.28 1.80±0.85 0.186
HDL-C, mmol/l 0.99±0.19 1.06±0.37 0.317
LDL-C, mmol/l 2.42±1.12 2.69±1.03 0.291
Total cholesterol, mmol/l 4.58±1.35 4.69±1.14 0.699
Glucose, mmol/l 7.26±3.15 7.72±4.36 0.576
WBC*109/L 8.87±2.78 9.44±2.58 0.331
Hemoglobin, g/l 140.84±20.04 134.88±17.51 0.149
Troponin I 5.17±1.8 6.27±1.9 0.32
Notes: GFR – glomerular ltration rate, HDL-C – high-density lipoprotein cholesterol, LDL-C – low-density lipoprotein cholesterol,
WBC – white blood cells.
Iryna R. Vyshnevska et al.
Table 3. Echocardiography at admission.
Characteristics MMP-9≤ 201.7 ng/ml MMP-9>201.7 ng/ml р
LV EDV, ml 125.01±23.70 122.22±25.14 0.606
LV EDV index 63.69±12.72 64.02±11.82 0.902
LV EDV, ml 62.33±19.89 63.41±15,38 0,783
LV EDV index 31.70±10.34 32,99±7,35 0,517
LA volume 36.09±8.06 35,20±10,34 0,668
LA volume index 19.12±6,.15 18,25±4,89 0,484
LV EF, % 46.63±6.33 47,09±5,54 0,724
Е/А 0.95±0.35 1,11±0,38 0,086
LV myocardial mass, г 211.00±46.10 209,80±44,29 0,905
LV myocardial mass index 112.25±19.87 118,01±27,33 0,283
Е/е median 14.51±5.31 12,99±4,42 0,239
TAPSE RV 21.42±2.65 21,98±2,87 0,428
Global longitudinal strain, % -10.23±2.46 -10,72±1,93 0,488
Notes: LA – left atrium, LV – left ventricle, EDV – end-diastolic volume, ESV – end-systolic volume, IVS – interventricular septum,
EF – ejection fraction, TAPSE – Tricuspid annular plane systolic excursion, RV – right ventricle
Table 4. Angiographic and procedural characteristics and medical therapy in the study population.
Characteristics MMP-9≤ 201.7 ng/ml MMP-9>201.7 ng/ml р
Right coronary artery 24/54.5 30/68.2 0.189
Left coronary artery main 7/15.9 10/22.7 0.418
Left anterior descending artery 31/70.5 33/75.0 0.632
Circumex 15/34.1 15/34.1 1.0
Coronary artery with stenosis more than 75%
1 vessel 15/34.1 8/18.2 0.0895
2 vessels 13/25.0 14/31.8 0.478
3 and more vessels 16/36.4 22/50.0 0.197
Type of stent
Bare-metal stent 30/65.9 28/63.6 0.823
Drug-eluting stent 14/25.0 16/29.5 0.632
Medical therapy
Acetylsalicylic acid 44/100 44/100 1,0
Clopidogrel 16/36 14/31.8 0.8
Ticagrelor 28/63 30/68 0.9
Β-adrenoblockers 40/90 41/93 0.87
ACEi /ARAII 44/100 44/100 1.0
Statins 44/100 44/100 1.0
Notes: ACEi – Angiotensin-converting enzyme inhibitors; ARAII – angiotensin receptors II antagonists; MMP-9 – matrix matalloproteinase-9
immunoassay using commercial kits. MMP-9 levels were
measured using the Human MMP-ELISA KIT Invitrogen,
Austria (Ref. BMS2016-2), and the standard concentra-
tion range is from 0 to 15.0 ng/ml. Troponin I (TnI) levels
were determined using the Troponin I-ELISA kit (Xema,
Russia), with the standard concentration range of 0-10.0
ng/ml. The study group was divided into two groups,
high and low MMP-9 (n=44 each), based on individual
plasma MMP-9 concentrations, using 201.7 ng/mL (low-
er quartile 159.8 and upper quartile 230.6 ng/mL) as the
cuto value, which was the cuto point with the highest
combination of sensitivity and specicity calculated us-
ing receiver performance analysis (ROC). Total cholester-
ol (TC), low-density lipoprotein cholesterol (LDL), high-
density lipoprotein cholesterol (HDL), and triglycerides
(TG) were measured by an enzymatic method (biochem-
ical automatic analyzer “Humastar 200”). The fasting glu-
cose level was measured by the glucose oxidase method
(automatic biochemical analyzer “Humastar 200”, Ger-
many). The coecients of variation within and between
analyzes were < 5%.
Statistical Package for the Social Sciences was used
to perform analysis. Measures of central tendency in-
clude the mean, median, and mode, and measures of
variability including standard deviation, variance, mini-
mum, and maximum variables have been done with
the help of descriptive statistics. Analysis of normally
distributed continuous variables was done by t-test.
ROC curves were built to show the association of dif-
ferent parameters to have predictive power in relation
to adverse outcomes. Youden’s index was used to de-
termine an optimal cut-o value for the MMP-9 plasma
level and the score of the EQ-5D questionnaire. Patients
were divided into two groups based on the median:
high and low MMP-9. The Kaplan-Meier curve esti-
mates the survival function, with dierences assessed
by log-rank tests. To predict a binary outcome logistic
regression analysis was used.
The median of MMP-9 was equal to 201.7 ng/ml.
There were no signicant dierences between both
MMP-9 groups in age, medical history and clinical as-
sessment. Baseline characteristics and hemodynamic
parameters presented in Table 1.
Laboratory values (Table 2), and echocardiography
data (Table 3) also were similar between investigated
Coronary angiogram data did not show any signi-
cant statistical dierences between the study groups
(Table 4). Moreover, standard medical therapy after dis-
charge was prescribed in 100% of both groups and did
not dier signicantly.
The indicators of the EQ-5D quality of life question-
naire signicantly improved six months after the event
in both groups (p=0.001 and p=0.0006, relatively), but
there was no signicant statistical dierence between
the median groups (Table 5).
In our study, the composite endpoint reached 9% of
patients at one-year follow-up. Although the one-year
outcome was higher in the high MMP-9 group than the
low MMP-9 group, this was not statistically signicant
(p<0.05), the same tendency was after 6-months follow-
up (p=0.09), table VI.
We used Receiver operating characteristic (ROC)
analysis to identify the level of MMP-9 that might be as-
sociated with the one-year composite primary endpoint.
In ROC analysis, the cut-o for MMP-9 was equal to
≥194,6 ng/ml, the area under the curve (AUC) was 0.711,
with 91.7% sensitivity, and 47.4% specicity, 95% con-
dence interval (CI) of 0.604 to 0.802, p=0.0037 (Figure 1).
We tested the results of the EQ-5D questionnaire in re-
lation to the eect of the latter on the combined endpoint,
using ROC analysis. The associated criterion was equal to
≤ 55 points, the CI – 0.624 to 0.820, AUC is 0.73, p< 0.0195,
with sensitivity 54.5% and specicity 94.7% (Figure 2).
The Kaplan-Meier survival plot for patient who had a
good prognosis and for those who reached the endpoint
based on calculated cut-o is presented in Figure 3.
Table 5. Comparison of mean changes of EQ-5D questionnaire.
Characteristics MMP-9≤ 201.7 ng/ml MMP-9>201.7 ng/ml р
EQ-5D at admission 72.16±7.81 68.95±11.00 0.120
EQ-5D 6 months 77.67±7.89 76.50±8.71 0.521
p 0.001 0.0006
Table 6. Comparison of reached endpoints among groups with dierent MMP-9 levels.
MMP-9≤ 201.7 ng/ml MMP-9>201.7 ng/ml р
Composite endpoint 6-month after the event, % 2.3% 4.5% 0.500
Composite endpoint 1-year after the event, % 2.3%
Iryna R. Vyshnevska et al.
A logistic regression model was built with a pur-
poseful selection of covariates (Table 6) which showed
that EQ-5D and MMP-9 were statistically associated
with the composite endpoint at one year after STEMI.
This model has a p = 0.3582 (X2=8.8149) in the Hosmer-
Lemeshow test which allows us to state that the data
was adjusted appropriately to the model. In addition
to assessing the discriminative ability of the model, we
found that it had an AUC of 0.86, which is considered
a normal discriminative ability, and CI is from 0.766 to
0.927 (Table 7).
In the presented study, we received data concerning
the clinical implication of MMP-9 in the prognostication
of adverse outcomes after STEMI. ROC analyses revealed
the cut-o level of MMP-9 of more than 194, 6 pg/ml
might be useful in prognosis. After that, we used Kaplan-
Meier analysis and found that patients from a group
with higher MMP-9 levels had more often cardiovascular
composite endpoint during one-year follow-up. Moreo-
ver, the level of MMP-9 with EQ-5D were independent
predictors of the one-year composite primary endpoint
Fig. 1. ROC curve showing the MMP-9 level to predict a one-
year composite endpoint.
Fig. 2. ROC curve showing the association of EQ-5D question-
naire with the one-year composite endpoint prediction.
Fig. 3. Kaplan-Meier analysis showing one-year composite endpoint according to MMP-9 level. Matrix metalloproteinase-9 cut-
o: 194.6 ng/ml. Cox’s F-Test, p = 0.04487.
(OR 1, 04 and 0.9039; 95% CI 0.9990-1.0293 and 0.8345-
0.9790) relatively.
Many studies have shown that MMP-9 is involved in
the process of atherosclerosis development [3, 7, 4] Wang
et al. determined that MMP-9 is a critical factor in the de-
velopment of atherothrombosis in patients with AMI (haz-
ard ratio: 2.72; 95% CI: 1.24-5.98; p=0.026) [19]. The latter
studied MMP levels in post-AMI patients and found that
increased plasma MMP-9 levels predicted future coronary
revascularization after an 18-month follow-up.
Although many studies have shown that MMP-9 can
serve as a biomarker of vulnerable plaques, its predictive
value for adverse cardiovascular outcomes is controver-
sial. Some studies didn’t show statistically signicant re-
sults, which is why the results we have provided have a
high actuality [20, 8, 21].
Increased MMP-9 levels are associated with the de-
terioration of LV dysfunction [22], while some MMP-9
substrates participate in the cardiac remodeling pro-
cess [23]. Also, Sakata, et al. [24], demonstrated that the
remodeling process is stimulated mainly by the simul-
taneous activation of a few MMPs, such as MMP-2 and
MMP-9. In our result, we did not nd any changes in
echocardiography parameters dependent on the MMP
levels at admission. We did not estimate any dynamic
changes in echocardiography, so, we cannot give any
conclusion about early or late cardiac remodeling and
their connection with the biomarker.
We also used PRO as a measurement tool as an equiva-
lent for routine outcomes and compared it with biomark-
er MMP-9. PROs are outcomes that patients report based
on an assessment of their condition without interpreta-
tion by the clinician. Today, PROs are actively included in
all clinical trials and sometimes even replace established
endpoints such as MACE. The purpose of the active im-
plementation of PRO is to assess the patient’s state of
health at the stage of recovery after an adverse event, and
to assess the quality of life against the background of the
therapy used since it’s a crucial variable. [25].
Shufelt C, et al. 2019, were conducted a study that
investigated the relationship between PRO and cardiac
biomarkers in stable ischemic heart disease that may
develop MACE. They concluded that patient-reported
physical health in stable ischemic heart disease is sig-
nicantly and inversely related to NT-pro BNP [26].
Health-related quality of life (HRQoL) assessment is
very important in modern health care. One signicant
study was conducted in England with the participation
of 9566 AMI patients. Investigators found that reduced
HRQoL was associated with female sex (−4.07, 95% CI
−4.88 to −3.25), type II diabetes mellitus (−2.87, 95% CI
−3.87 to −1.88), previous AMI (−1.60, 95% CI −2.72 to
−0.48), previous angina (−1.72, 95% CI −2.77 to −0.67),
chronic renal failure (−2.96, 95% CI −5.08 to −0.84;
−3.10, 95% CI −5.72 to −0.49), chronic obstructive pul-
monary disease (−3.89, 95% CI −5.07 to −2.72) and cer-
ebrovascular disease (−2.60, 95% CI −4.24 to −0.96).
Researchers have shown that assessing HRQoL both in
the hospital and following the patient’s discharge may
be important in determining who could benet from
well-tailored interventions [27].
In the prospective, observational study TIGRIS, 9126
patients that experienced MI for 3 years at most were
enrolled. A total of 8978 patients have completed the
EQ-5D questionnaire. The determined results showed
that a poorer quality of life is clearly linked to the risk of
hospitalization and MACE [28].
Henriksson C, et al. 2014, demonstrated in their
study that EQ-VAS of less than 50 points was correlated
to delay in hospital admission from symptoms onset. It
was independent of other factors. The authors suggest
that depression could be a reason for the poor quality
of life status.
In the EPICOR trial among known predictors of mor-
tality after an acute coronary syndrome, the EQ-5D
questionnaire took third place after age and low ejec-
tion fraction. In predictive power, EQ-59 quality of life
was superior to the elevated creatinine level, in-hospi-
Table 7. Multivariate logistic regression analysis for potential predictors of one-year composite endpoint.
Dependent constituent: ММР-9
Univariate analysis (χ2=16,06; P = 0,0067) Multivariate analysis (χ2=13,80; P < 0,0032)
β-coecient Odd ratio 95% CI Р β-coecient Odd ratio 95% CI Р
MMP-9, ng/ml 0.0139 1.0140 0.9990-
1.0293 0.068 0.015024 1.0151 1.0001-
1.0304 0.0481
Age, years 0.045670 1.0467 0.9274-
1.1814 0.4597
Hypertension -1.77352 0.1697 0.0160-
1.8035 0.1413 -1.93520 0.1444 0.0153-
1.3634 0.0911
DM 2T 1.28472 3.6136 0.6940-
18.8175 0.1270 1.44638 4.2477 0.8373-
21.5489 0.0809
EF % 0.040264 1.0411 0.9080-
1.1937 0.5640
EQ-5D, points -0.10107 0.9039 0.8345-
0.9790 0.0131 -0.10632 0.89 0.8313-
0.9725 0.0079
Notes: EF – ejection fraction; MMP-9 – matrix matalloproteinase-9; DM 2T – diabetes mellitus type 2.
Iryna R. Vyshnevska et al.
tal cardiac complications and male gender, and even
prescription of diuretics at discharge [29].
Shah P., et al. 2009, investigated the inuence of life
quality on survival after STEMI in patients older than 85
years. They have found that aggressive treatment was
associated with reasonable long-term survival and ex-
cellent quality of life [30].
In the study, we proved by ROC analysis that the EQ-
5D questionnaire had an association with a composite
one-year endpoint (sensitivity 54.5% and specicity 94,
7%, p< 0.0195). This questionnaire had low sensitivity,
and the MMP-9 biomarker had low specicity. When
conducting a logistic regression analysis both factors
showed their predictive power, and we managed to in-
crease the area under the curve up to 0.860. This indi-
cates the signicance of the results obtained. Thus, for
the rst time, we combined this biomarker with the pa-
tient-reported outcomes and showed that both tools
eectively complement each other.
There was considered a broad spectrum of CAD types
in the above-mentioned investigations. The fact that the
patients’ group consisted of only STEMI was of great ben-
et to our research. This made the use of a simple survey
a dependable method that allowed us to identify one of
the most vulnerable patients and possibly, correct their
quality of life to improve their prognosis.
There are some limitations to our study. First, the
fact that this was a single-centered study might lead
to enrollment bias. Second, in order to establish a di-
rect relationship between MMP-9, EQ-5D, and clinical
outcomes, a greater number of patients should be in-
cluded. Furthermore, no dynamic measurement was
done for MMP-9. However, this study may be a door
to future improvements in the tactics of managing pa-
tients after STEMI. Third, comparing our results with
other studies is dicult due to dierences in the medi-
cal therapy, storage techniques, follow-up period, and
ELISA kits. Fourth, we investigated the predictive val-
ue of MMP-9 using a cut-o of 194,6 ng/ml from ROC
analysis. Therefore, the reached results can be applied
only to our cohort, and this cut-o may dier from
previous studies. This issue needs validation in other
larger populations.
In conclusion, we found that an MMP-9 level of
more than 194 ng/ml and < 55 points in EQ-5D predicts
a composite primary endpoint during a 1-year follow-
up in STEMI. Determining the levels of MMP-9 in STE-
MI patients might be used in routine clinical practice.
Moreover, frequent monitoring may be considered in
patients with high MMP-9 levels in order to receive ad-
ditional information about the prognosis. EQ-5D is an
eective tool that should be used in combination with
routine MACE. Future studies are needed to clarify ob-
tained result.
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* Contribution: A – Work concept and design, B – Data collection and analysis, C – Responsibility for statistical analysis, D – Writing the article, E – Critical review, F – Final approval.
Iryna R. Vyshnevska B, C, D
Olga V. Petyunina B, C, D
Mykola P. Kopytsya A-F
Anton O. Bilchenko E
Larysa L. Peteneva C
The Authors declare no conict of interest.
Iryna R. Vyshnevska
L. Malaya Avenue, 2a, Kharkiv , 61039, Ukraine
tel: +380959359759
© ALUNA Publishing House
Pol Merkur Lek, 2023; LI, 1: 30-34
DOI: 10.36740/Merkur202301104
Aim: The aim is to study and to improve the motivation of mental health preservation of specialists in the eld of special and
inclusive education according to European experiences.
Materials and methods: The experimental part of the research involved the use of the valid psychodiagnostic methods and tech-
niques: direct and indirect observation, standardized questionnaire survey, semi-standardized individual interviews, psychodiag-
nostic methods. The research was attended by 131 Master’s degree students (aged 25-27), specialty 053 Psychology, Educational
program – special, clinical psychology.
Results: The program “European practices of motivation development of mental health preservation” expands perception of ca-
pabilities, which encourages the disclosure of the creative potential of the individual; anxiety symptoms disappear (or decrease);
a system of value orientations is formed; the desire to strengthen spiritual and physical strength.
Conclusions: Program contributes to the formation of an image of mentally healthy person, stimulation to adhere to a mentally
healthy lifestyle and the motivation development of mental health preservation.
KEY WORDS: mental health, motivation, special education, social inclusion
Daria M. Suprun1, Maria K. Sheremet1, Tetiana V. Hryhorenko1, Mykola O. Suprun1,
Marja O. Nesterova1, Ivan M. Okhrimenko2, Alla L. Dushka3
of mental health preservation of mentioned special-
ists, who not only perform important and complex pro-
fessional functions, but at the same time are the role
model and example of behaviour [3, 4]. This motivation
development is the basis of ensuring the quality and
eectiveness of their professional activity, creation of
prerequisites for acceptance and providing European
values and ideas of social cohesion. In conditions of
wartime specialists in the eld of special and inclusive
education must increase the social responsibility of
universities based on the best European practices of
social innovations, social cohesion and social commu-
nity. And at the same time they must present and pro-
vide an eective role of universities as drivers of civil
protection, support for civilians from aected areas of
humanitarian disaster after the army conicts. Thus, in
the conditions of the changes in the system of social
and spiritual values, the economic crisis in the country,
the task of maintaining and strengthening the mental
health seems very relevant [4,5, 6]. On the basis of the
analysis and generalization of European experience,
scientic and theoretical practice and sources on the
research problem, the main con ceptual approaches to
the research of the motivation of mental health preser-
vation of specialists in the eld of special and inclusive
education have been determined.
The main mission of European education is to
contribute to the knowledge development of society
through research, excellence, quality education and
international cooperation. Its concept requires a new
purposes’ orientation, principles, content, methods,
obtained knowledge according to incarnation in life
of personaloriented paradigm of education [1, 2]. So,
our research provides new requirements for training
in high educational institutions in the context of social
cohesion, social support, social inclusion. Therefore
there is a necessity of forming a new generation of spe-
cialists which can provide expert help by implementing
and increasing the innovative experience of the Euro-
pean standard, which should be carried out in rational
combination with innovative experience of Ukrainian
scientists. The course of building the European demo-
cratic legal state, which Ukraine has taken, requires
from specialists in the eld of special and inclusive ed-
ucation to increase the eciency of their professional
activities to ensure the processes of social cohesion,
which depends on the mental health of personnel. It is
within this paradigm that great importance is attached
to the mental health of an individual capable of self-
improvement and self-actualization. Thus, of particular
importance is the problem of motivation development
The aim is to study and to improve the motivation of
mental health preservation of specialists in the eld of
special and inclusive education according to European
The research was conducted during 2020-2022,
which involved future specialists of Department of Spe-
cial Psychology and Medicine, Faculty of Special and
Inclusive Education, National Pedagogical Dragomanov
University, Kyiv, Ukraine.
The development of the motivation was carried out
in two stages: at the rst, a psychodiagnostic examina-
tion of the sample was provided, aimed at determining
the formation of the motivation of mental health preser-
vation of specialists in the eld of special and inclusive
education, at the second, the psychological eective-
ness of the program for the development of such moti-
vation was investigated. The training program “European
practices of motivation development of mental health
preservation” was provided, based on the experience
of scientic cooperation between the Faculty of Special
and Inclusive Education of National Pedagogical Drago-
manov University and relevant faculties of European
countries: Sapienza University, Rome, Italy, Masaryk Uni-
versity, Brno and Tomas Bata University, Zlin, Czech Re-
public, The John Paul II Catholic University, Lubin, Poland
etc. The Program was built taking into account the pecu-
liarities of the best European practice of mental health
preservation. It was provided within the framework of
ERASMUS Jean Monnet LS project “European Studies of
Social Innovation in Education (ESSIE)” [7].
The research was attended by 131 Master’s degree
students (aged 25-27), specialty 053 Psychology, educa-
tional program – special, clinical psychology. 72 partici-
pants made up the control group (CG) and 59 – the ex-
perimental group (EG). The EG included specialists who
demonstrate low (n=30) and satisfactory (n=29) indica-
tors of motivation of mental health preservation. During
the training course, the EG participated in all procedures
of the cycle of formative psychological inuences, and
the CG (which included 32 persons with the low level
of developed motivation of mental health preservation
and 40 with the satisfactory level) acted as a reference
point comparing with the developing and formative ef-
fects were evaluated.
For achievement the aim, the set of complementary
methods was applied: theoretical methods: (analysis,
synthesis, comparison, generalization) were used to nd
out the state of the problem of the motivation devel-
opment in the psychological theory and practice and
to determine the essence and structure of mentioned
motivation; empirical (direct and indirect observation,
standardized questionnaire survey, semi-standardized
individual interviews), psychodiagnostic methods – “Per-
sonal Orientation Inventory”, (POI, Everett L. Shostrom)
[8, 9], “Level of Subjective Control” (RSK, J. Rotter) [10],
“Rokeach Value Survey” (values scales) (M. Rokich), “Bass
Orientation Inventory”, “Individual Typological Ques-
tionnaire” (ITQ) [12], “Attitude to Health” [13], made it
possible determination of criteria and factors of mental
health preservation and allowed to carry out a practical
test and to determine the psychological eectiveness
of the program of motivation development of mental
health preservation of specialists; the statistic methods
were applied to process research results, to establish
quantitative relationships between the investigated in-
dicators, to ensure qualitative analysis and verication of
empirical data.
According to aim, the criteria were developed, which
make it possible to provide diagnostic of the state of
formation of the researched motivation. The criteria for
evaluating the level of motivation development includ-
ed: the criterion of needs (indicators of self-actualization
and generalization of expectations), the value criterion
(indicators of value and personal orientations), the per-
sonal criterion (indicators of leading trends) and the be-
havioral criterion (an indicator contains the set of skills
and practical solutions of tasks related to the mental
health preservation). On the basis of the dened crite-
ria, the four levels of formation of researched motivation
were determined: the high (innovative); the sucient
(productive); the middle (reconstructive); the low (repro-
ductive) [14, 15, 16].
This study was performed according to the require-
ments of the Regulations on Academic Honesty of Na-
tional Pedagogical Dragomanov University. The prelimi-
nary consent to participate in the research was obtained
from all respondents.
At the rst stage of research, in order to study the
state of formation of motivation of mental health pres-
ervation of specialists in the eld of special and inclusive
education and to determine its levels according to the
developed criteria, the algorithm of psychodiagnostic
examination was improved by providing European diag-
nostic standards.
The results of the research showed that some future
specialists (22.9%) have the low level of motivation to
mental health preservation. The insucient part (24.4%)
of specialists was characterized by the high level of mo-
tivation of mental health preservation. It was established
that lack of motivation (or its low level) and negative
(indierence) attitude of individuals towards their men-
tal health have a persistent and systemic nature, which
negatively aects their work capacity and professional
Thus, the state of motivation development of the
mental health preservation of specialists in the eld of
inclusive education is at the insucient level of its de-
velopment. This conclusion led to the determination of
ways of psychocorrective work of the motivation devel-
opment among future specialists: the training program
“European practices of motivation development of men-
Daria M. Suprun et al.
Table 1. Comparison of orientation types in EG (n=59) and CG
(n=72) before and after the research according to the indica-
tors of Bass Orientation Inventory (%).
of the
Self-orientation Interaction-
cut 25.4 26.4 50.9 48.6 23.7 25.0
Final cut 37.3 26.4 30.5 47.2 32.2 26.4
Table 2. Comparison of the scales’ indicators of the averaged
prole in EG (n=59) and CG (n=72) before and after the re-
search according to the Individual Typological Questionnaire .
Previous cut Final cut
1 3.1 3.5 3.4 3.7
2 3.0 3.4 3. 0 3.6
3 4.3 4.4 4.5 4.2
4 6.3 5.8 6.0 5.7
5 6.1 6.0 4.5 6.0
6 5.9 5.5 4.7 5.3
7 5.0 5.5 5.5 5.4
8 6.2 5.0 5.0 5.5
9 5.7 5.4 4.4 5.2
10 5.7 4.0 4.9 4.5
1 – falsity; 2 – aggravation; 3 – extraversion; 4 – spontaneity; 5 – ag-
gressiveness; 6 – rigidity; 7 – introversion; 8 – sensitivity; 9 – anxiety;
10 – lability (emotionality)
tal health preservation” was provided, which was built
taking into account the peculiarities of professional ac-
tivity of indicated specialists and the peculiarities of their
attitude to mental health preservation.
This program of training sessions made it possible
to improve the indicators of the motivation develop-
ment in the EG signicantly. According to the criterion of
needs, the motivation development was conrmed: the
indicators of self-actualization according to Personal Ori-
entation Inventory showed that the indicator of general
self-actualization increased (from 65.50 to 82.30 points),
the indicators revealed according to the scales of auto-
sympathy (from 7.30 to 7 .78 points), the need for knowl-
edge (7.55 before the training and 8.50 after), autonomy
(6.00 and 7.30, respectively), self-understanding (7.00
and 8.70). In all cases the dierences are signicant (p ≤
0.05). The level of subjective control in the EG increased
on such scales as internality in the eld of failure (from 4
to 6) and internality in relation to mental health and ill-
ness (from 5 to 8), and general internality also increased
(from 4 to 6). Consequently, the quantity of specialists
who considered themselves responsible for their mental
health has been increased. The quantity of interview-
ees with the high level of subjective control increased
signicantly (from 32.2% to 52.5%), which indicated the
development of emotional stability, determination, and
a high level of self-control.
According to the value criterion, the quantity of re-
spondents of the EG increased from 55.9 to 66.1%, who
considered the following terminal values of individual
self-realization to be the most signicant: mental health,
self-condence, beauty of nature and art, productive life,
active professional activity. The increase in the individu-
ally signicant direction of value orientations has been
established, which is an indicator of increase of the level
of motivational readiness of an individual for changes,
awareness of own role in the organization of life ac-
tivities. The analysis according to the indicators of Bass
Orientation Inventory showed a signicant motivation
development of mental health preservation, which was
reected in the quantity increase of participants of the
EG with the type of orientation towards the task (from
23.7% to 32.2%), towards oneself (from 25.4% to 37.3%)
and in the quantity decrease of interviewees with the fo-
cus on interaction and communication (from 50.9% to
30.5%) (dierences are signicant at p ≤ 0.05) (Table 1).
The personal criterion: according to the scales of the
Individual Typological Questionnaire aggressiveness
indices decreased from 6.1 to 4.5 points. There is also a
signicant decrease in diagnostically important rigidity
indicators from 5.9 to 4.7 points. Positive changes were
also observed in the spontaneity indicators (6.3 and 6.0
points). It is indisputable that the high points on the scales
of sensitivity (from 6.2 to 5.0), anxiety (from 5.7 to 4.4) and
lability (from 5.7 to 4.9) also decreased in the EG (Table 2.).
The behavioral criterion: according to the Attitude to
Health Questionnaire recognition of the impact of quit-
ting smoking on health in EG increased from 18.6% to
37.3%; refusal to drink alcohol – from 10.2% to 30.5%;
regular exercise – from 20.3% to 49.2%; regular relaxa-
tion training – from 5.1% to 40.7%; providing the re-
gime and rationalization of work and rest – from 8.5%
to 20.3%; adherence to a healthy diet – from 10.2% to
23.7%; involvement in health and rehabilitation activi-
ties – from 16.9% to 32.2%.
As a result of the systematic analysis of the researched
problem [17, 18, 19, 20], the essence and structure of the
motivation of mental health preservation was revealed.
It has been established that the motive of mental health
preservation can be formed if the specialist in the eld of
special and inclusive education person has the necessary
set of values at his disposal, which meets the socially de-
termined individual needs. It is worth noting that on the
basis of the empirical research it was found that the mo-
tivation of mental health preservation is closely related
to such personal characteristics as adequate self-esteem,
self-awareness, self-analysis, social values, focus on busi-
ness, creativity, social adaptability, self-regulation.
Therefore, the motivation for mental health preser-
vation of specialists in the eld of special and inclusive
education is a system of value orientations, internal
incentives to preserve, restore and strengthen men-
tal health, it is a desire to preserve and to improve the
potential given by nature by providing the norms of a
mentally healthy lifestyle, which modern psychological
science considers as an optimally balanced style of hu-
man behavior aimed at preserving and improving men-
tal health. The purpose of which is to satisfy the psycho-
logical, social and biological needs and aspirations of the
individual [21-25].
The obtained results convincingly indicate that the
psychotraining program contributes to psychological
correction and formation of self-image as a mentally
healthy person, stimulation of adherence to a healthy
lifestyle and development of motivation to preserve all
components of mental health. This is conrmed by the
growing desire of specialists in the eld of special and
inclusive education for self-development, self-improve-
ment, self-actualization and awareness of own choices,
focus on the goal, overcoming diculties, developing
emotional stability, forming proper self-esteem, posi-
tive self-perception and value orientations, objectifying
actual needs in order to determine life plans for main-
taining mental health. Therefore, the proposed program
contributed to the development of the participants’ mo-
tivation of mental health preservation.
The program “European practices of motivation devel-
opment of mental health preservation” expands percep-
tion of capabilities, which encourages the disclosure of
the creative potential of the individual; anxiety symp-
toms disappear (or decrease); a system of value orien-
tations is formed; the desire to strengthen spiritual and
physical strength.
Therefore, we have the opportunity to implement
and increase the innovative experience of the motiva-
tion development of mental health preservation accord-
ing to the best European standards, which should be
carried out in a rational combination with the innovative
experience of Ukrainian scientists-organizers of higher
education in the eld of modern education in social in-
clusion and social cohesion.
As a result of the systematic analysis of the speci-
ed problem, the essence of the motivation of mental
health preservation of specialists in the eld of special
and inclusive education was revealed. The criteria base
was developed, which makes it possible to diagnose the
state of formation of the motivation of mental health of
specialists in the eld of special and inclusive education
included. The criteria for evaluating the level of motiva-
tion: the criterion of needs (indicators of self-actualiza-
tion and generalization of expectations), the value crite-
rion (indicators of value and personal orientations), the
personal criterion (indicators of leading trends) and the
behavioral criterion (an indicator contains set of skills
and practical solutions of tasks related to the mental
health preservation.
The training program “European practices of motiva-
tion development of mental health preservation” was
provided. In general, the eectiveness of the approved
training program has been proven by means of analysis
of the data of the experimental research.
The issue of studying the psychological mechanisms
of maintaining the abilities and skills of a mentally
healthy lifestyle, as well as the development of appro-
priate teaching and training psychological methods for
providing mentioned processes requires further devel-
opment, in order to maximise their impact.
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* Contribution: A – Work concept and design, B – Data collection and analysis, C – Responsibility for statistical analysis, D – Writing the article, E – Critical review, F – Final approval.
Daria M. Suprun – 0000-0003-4725-094X A, C
Maria K. Sheremet – 0000-0003-1437-3820 A, E
Tetiana V. Hryhorenko – 0000-0002-2002-6668 C
Mykola O. Suprun – 0000-0002-4198-9527 B, D
Marja O. Nesterova – 0000-0001-6703-7797 A
Ivan M. Okhrimenko – 0000-0002-8813-5107 B, F
Alla L. Dushka – 0000-0003-0805-7813 E, F
The Authors declare no conict of interest.
Ivan M. Okhrimenko
National Academy of Internal Aairs, Kyiv, Ukraine
Abeer Amen Baqer1, Norefrina Shanaz Md Nor2, Huda Salman Alagely3, Mustafa Musa4,5,
Siti Noor Adnalizawati Adnan6
Abeer Ameen Baqer et al.
To isolate phage that is active against carbapen-
emase producing K. pneumoniae and to characterise
isolated bacteriophage with respect to morphology,
killing curve and stability under physical and chemical
conditions. Evaluation of bacteriophage characteristic
will assist in revealing its potential as therapeutic agent
against infections caused by KPC.
Carbapenem resistances K. pneumoniae (KP2) was ob-
tained from the Culture Collection Centre at Department
of Biological Sciences and Biotechnology, Faculty of Sci-
ence and Technology, Universiti Kebangsaan Malaysia
(UKM). Culture was maintained in the laboratory by using
nutrient agar slants at 4 °C. For liquid preparations, bacte-
rial culture was grown in Luria Bertani broth (LB; Oxoid)
at 37°C with agitation at 200 rpm. Bacterial cell concen-
trations was measured by culture-based counting for
colony-forming unit (CFU). LB agar, Nutrient agar, and LB-
soft agar contains bacteriological agar (0.75 %) and bac-
teriophage broth (20 mL) comprised of pepton (100 g/L),
beef extract (30 g/L), yeast extract (50 g/L), NaCl (25 g/L),
potassium dihydrogen phosphate (80 g/L) were used for
phage6 propagation and plaque count analyses.
Klebsiella pneumonia (KP2) specic bacteriophage
was isolated from sewage water by enrichment tech-
nique and p6hage activity was detected by spot assay
[8] and plaque assay using double-layer agar overlay
technique [9]; the titer was expressed as Plaque-forming
unit/milliliter (PFU/mL). Bacteriophage plaques were
harvested from the agar plate and single bacteriophage
plaque was puried three times on host strain by the
standard procedure [10]. Bacteriophages were further
concentrated by polyethylene glycol (PEG) precipitation.
The puried bacteriophages were stored in SM buer
(50 mmol/L Tris-HCl, pH 7.5; 0.1 mol/L NaCl; 8 mmol/L
MgSO4) with 0.01 % gelatin (pH 7.2) at 4 °C.
The host range of the isolated bacteriophage desig-
nated k3w7 was assessed on a range of Gram-positive
and Gram-negative strains of (E. coli, Pseudomonas spe-
cies, S. aureus, etc.) clinically isolated bacteria beside 14
MDR-K.pneumoniae isolates that were obtained from
Culture Collection Centre at Department of Biologi-
cal Sciences and Biotechnology, Faculty of Science and
Technology, Universiti Kebangsaan Malaysia (UKM) and
listed in (Table 1). Spot test was used to test the suscep-
tibility of bacterial isolates [8].
Phage morphology was visualised using 100-kV Trans-
mission electron microscope (Thermo sher Talos L120 C/
Fig. 1. Plaques (uniform clear, diameter of ≈3 mm) formed by
newly isolated K3w7 bacteriophage on the double layer agar
plate with a lawn of K. pneumonia kP2.
Table 1. Bacterial strains used in host rang and their suscepti-
bility to the phages.
Bacteria K3w7 Bacteria K3w7
K.pneumoniae 1 -MRSA 2908 -
K.pneumoniae 2
(KP2) +MRSA 2192 -
K.pneumoniae 3 -E. coli 11035 -
K.pneumoniae 4 -E. coli 1 -
K.pneumoniae 5 -E. coli ATCC -
K.pneumoniae 6 -E. coli 4 -
K.pneumoniae 7 -E. coli 2891 -
K.pneumoniae 8 +Pseudomonas aeruginosa
R1707903 -
K.pneumoniae 9 +Pseudomonas aeruginosa
B 7546 -
K.pneumoniae 10 -Pseudomonas aeruginosa
P6171 -
K.pneumoniae 11 -Bacillus subtillis -
K.pneumoniae 12 +Serratia marcescens -
K.pneumoniae 13 -Enterococcus faecalis -
K.pneumoniae 14 -Shigella -
K.pneumoniae 15 -Pseudomonas aeruginosa
B 7546 -
S. aureus 99 -Pseudomonas aeruginosa
S. aureus 4 -Pseudomonas aeruginosa
P6168 -
MRSA/pa -Salmonella typhi -
MRSA 3 -Salmonella typhi 2356 -
USA) with the following protocol: Five microliters of (1010)
pfu/ml PEG precipitated phage lysate was used as starting
material according to Taha et al.[11] using negative stain-
ing at Electron Microscope Unit, UKM. The isolated phage
was classied in accordance with The International Com-
mittee on Taxonomy of Viruses (ICTV) recommendation
[12]. Furthermore, Positive staining (ultrathin section) was
used to monitor the eect of the phage on the bacterial
membrane, bacteria- phage combination was prepared
by adding the bacterial culture in MOI 1 following the pro-
tocol adapted by Broskey et al. [13].
A one-step growth curve of k3w7 was performed ac-
cording to the method of Kropinski [14]. The density of a
mid-exponential bacterial culture (LBB) was adjusted to
2×108 CFU/mL. 0.1 mL of the phage lysate was added to
0.9 mL of the bacterial suspension to achieve 0.01 MOI.
Phages were allowed to adsorb for 10 min at 37°C. The
obtained pellets were resuspended in SM buer (1 mL)
to eliminate non-adsorbed phages, This suspension was
diluted in 10 mL of LB medium (1:10,000) and incubated
at 37°C in shaking incubator. At specic time intervals
(5, 10, 20, 25, 30, 40, 50, 60,70 and 80 min), aliquots of
0.1 mL were withdrawn and bacteriophage titers was
determined using kP2 as the host on the double-layer
agar. Experiment was performed on three dierent occa-
sions, and values depict the mean of three observations
± standard deviation.
For pH-stability testing, 100 L of bacteriophage sam-
ple (108 PFU/mL) was mixed in a tube containing SM bu-
er with pH ranging from 2 to 14 (adjusted using NaOH or
HCl) and incubated for 1 h at 37°C. For thermal-stability
testing, 100 L bacteriophage lysate (108 PFU/mL) was
mixed with 900 L SM buer. Samples were maintained
in a water bath ranging from 30°C to 80°C for 60 min. The
sensitivity of each phage to chloroform was tested us-
ing 10% chloroform concentration. Chloroform was in-
troduced to 1 × 109 PFU/mL phage concentration in SM
buer to nal chloroform content of 10 % (v/v). The phage
was shaking to dislodge in the chloroform and allowed for
1 hour at room temperature. All Samples were withdrawn
after one hour of incubation and checked for phage titers
using KP2 as the host on the double-layer agar [10].
Bacteriophage DNA was extracted and puried
from phage lysate (1010–1011 PFU/mL) by proteinase
K method, followed by resuspension in Tris–EDTA buer
after ethanol precipitation [10]. Puried bacteriophage
DNA samples was subjected to digestion with restriction
enzymes (EcoRI, smaI, xbaI, NdeI, XhoI and PstI) (Thermo
Fisher Scientic, USA) according to the procedure rec-
ommended by manufacturer.
Ethical approval was not necessary to pursue this re-
search work.
This study characterised a newly isolated bacterio-
phage k3w7 specically infecting carbapenem produc-
ing K. pneumoniae designated as KP2 and described
the biological features of the isolated bacteriophage.
Bacteriophage k3w7 was isolated from sewage sample
and exhibited potent lytic activity with clear plaques (3
mm in diameter). Plaques of k3w7 was surrounded by a
large halo (Fig. 1). This result similar to result obtain by
our team in previous study where most of the isolated
phages plaque surrounded with large halo [15]. That in-
dicating the production of large amounts of depolymer-
ase activity. Previously, studies have shown that some
tail bre and tail spike proteins often display polysaccha-
ride-depolymerase activity [16]. A study has found that
in several bacteriophages, the depolymerase domain
protein was a part of phage structural proteins (mostly
on tail bres) which permits phage adsorption, invasion,
and disintegration of host bacterial cell [17].
Fig. 2. (A) Transmission electron micrographs of the puried k3w7 using scale bars of 100 nm. (B) Representative TEM images
of 50 nm sections of untreated control and (C) k3w7-treated K. pneumoniae (KP2), TEM images show an evident Weakened and
disruption of the cell wall after exposure to k3w7 MOI 1 for 1 h..
Abeer Ameen Baqer et al.
Bacteriophage with a broad host range is considered
suitable candidates for phage therapy trials because the
bacteriophage can be utilised against a broad range of
species strains [18].
K3w7 phage was found to be specic towards K.
pneumoniae by infecting KP2 isolate beside another
three isolates of K. pneumoniae exhibiting extended
spectrum beta-lactamaes (ESBL) (data is not published).
ESBL is known to cause hospital acquired catheter asso-
ciated urinary tract infection (UTI), none of the Escheri-
chia coli, Pseudomonas species, Staphylococcus aureus
and others bacteria showed susceptibility to this bacte-
riophage (Table 1).
The use of such bacteriophages in situations where
multiple drug resistant bacteria are encountered can
be an alternative for clinicians in combating infection.
However, before applying any bacteriophage for any
therapeutic purpose, determination of its characters is
essential. One of the criteria for classication of bacte-
riophages to a particular group is their morphological
and genetic characteristics. TEM showed that k3w7 be-
longs to the Myoviridae family with the characteristic of
icosahedral heads 100 nm and contractile sheaths 120
nm (Fig. 2a). As has been reported earlier, head and tail
size of k3w7 matched with the size range of the T4-like
phages [19], suggesting a close resemblance of the iso-
lated phage with T4 phages. As shown in (Fig. 2b), the
exposure of KP2 to phage k3W7 in MOI 1 after 1h incu-
bation (37 ºC) led to the drastic changes in intracellular
density, disintegration of the cell wall and the cell mem-
brane. Furthermore, the bacterial cells were Enlarged
and a protuberance suspected to be a bacteriophage.
These changes suggesting that k3w7 can eectively ad-
sorb and penetrated to the outer membrane without
prior destabilisation and there with reach the pepti-
doglycan substrate. Maciejewska et al. [20] reported that
endolysins were responsible for peptidoglycan degrada-
tion and conrmed on outer membrane permeabilised
bacteria prepared from dierent Gram-negative species
and strains.
Results of burst-size experiments, reported in
(Fig.3a), showed that k3w7 has relatively short laten-
cy period (approximately 20 minutes) which is a good
characteristic for phage therapy. The computed burst-
size was of ≈220 bacteriophage particles per infected
cell. The burst sizes of the isolated phage in this current
study are considered large when compared to other K.
pneumoniae phages in which the average burst size was
as small as 50 PFU/cell [21]. Dierences in burst size and
the latent period of dierent phages depend on the na-
ture of the phage, the physiological state of the host, the
composition of the growth medium, pH and the temper-
ature of incubation [22]. K3w7 stability was investigated
at dierent pHs and temperatures. The results showed
that no apparent eect on k3w7 was observed after 1
hour of incubation at pH values ranging from 6 to 10.
However, the phage dramatically lost its activity at pHs
lower than 3 and higher than 11 (Fig. 3b). Recent study
has noted that the tailed phage is stable at pH 5.0 to 9.0
[23]. The thermal stability test shown in (Fig.3c) indicate
that phage k3w7 was relatively heat stable, with high vi-
ability range of active phages from 80%-98% that were
detected after 1 hour of incubation at 30 ºC to 60 ºC.
This stability of k3w7 considered high compare with
previously isolated Klebsiella that was sensitive to high
temperature, with a 100- fold decline in titre observed
after only 10 min at 60°C [21]. However, no phage were
detected when tested at 70 ºC and 80 ºC. The Eect of
chloroform on bacteriophages was conducted to distin-
guish the sensitivity of the bacteriophage to chloroform,
an eect that is usually because of the damage of the
lipid components of the cell membrane. Chloroform ex-
posure did not have an adverse eect on phage titres.
(Fig. 3d). They remained unaected by 10% chloroform
treatment after incubation for 1 h. However, Venturini et
al. [24] reported the stability of K. pneumoniae phages
after exposure to chloroform varied between no eect
and a decrease of stability by 2-3 logs of phages concen-
An MOI of 0.1 produced the maximum bacterio-
phage titre for k3w7 phage, signifying that 0.1 was the
optimal MOI for the phage titre production. This MOI
produced lysates of about more than 4 × 1010 PFU/mL
(Fig. 3e). The high adsorption rate of phages in the cur-
rent study is higher than what was reported in a recent
study targeting the Klebsiella phage [25]. The phages
could dier in their rates of adsorption because of ei-
ther the absence or presence of extra side tail bres or
an improved tail bre. For example, a high mutation
rate of the phage stf gene would ensure the presence
of side tail bre polymorphism, therefore, contributing
to rapid adaptation of the phage populatio between
diametrically dierent habitats of benthic biolm and
planktonic liquid culture [26]. To detect genomic ma-
terial of the isolated phage, the bacteriophage DNA
was extracted and digested by dierent restriction en-
zymes of type II. Taking the size of each fragment base,
the size of the phage DNA was calculated. The size of
phage DNA was found to be 48.0 kb (Fig. 4). The action
of type-II restriction enzymes revealed that genome
of k3w7 was sensitive to pstI ,NdeI and xbaI, smaI and
resist for digestion by EcoRI and XhoI enzymes. Many
phages possess other anti-restriction mechanisms that
make their DNA resistance to host restriction endonu-
cleases. These mechanisms include the inhibition of
restriction enzymes by phage-encoded proteins, the
modication of DNA via self- methylation or activa-
tion of host methylase, or the lack of recognition sites
for particular restriction enzymes [27]. The restrictions
exhibited dierent restriction endonuclease patterns.
These dierent conrmed the presence of many restric-
tions sites (Fig. 4). Nevertheless, this evidence shows
the closeness of k3w7 to Mu-like viruses based on its
genome size. The genome size of k3w7 was found to be
approximately 50 kb with pstI digestion which is close
to the genome size of 43 kb of Mu-like viruses.
Fig. 3. (A) One-step growth experiments. Latent phase from 0 to 20 min; Rise phase from 20 to 70 min, and Plateau phase from
70 to 80 min. (B) pH stability tests of phage k3w7 that held at dierent pH for 60 min . (C) Eect of temperature on bacterio-
phage activity that held at dierent temperatures for 60 min.(D) The eect of chloroform (10%) on bacteriophage consentration.