journal of health science 2014.7

Journal of Health

Science

Volume 2, Number 7, July 2014 (Serial Number 8)

David

David Publishing Company

www.davidpublishing.com

PublishingDavid

Publication Information Journal of Health Science is published monthly in hard copy (ISSN 2328-7136) by David Publishing Company located at 240 Nagle Avenue #15C, New York, NY 10034, USA. Aims and Scope Journal of Health Science, a monthly professional academic journal, covers all sorts of researches on Nutrition and Dietetics, Epidemiology and Public Health, Disaster Management, Physiology and Counseling, Health Psychology and Behavior, Health and Rehabilitation, Exercise and Nutrition Sciences, Nursing Practice and Health Care, Health Policies and Administrations, Health Informatics, Environmental and Occupational Health, Community Health, Public Health, Health Education and Research, as well as other issues related to Health Science. Editorial Board Members Bernhard Schlag (Germany), Masatsugu Tsuji (Japan), Panagiota Florou-Paneri (Greece), Khanferyan Roman (Russian), Subbiah Elango (India), Bruce C.M. Wang (USA), María del Carmen Solano Ruiz (Sweden), Viacheslav Kravtsov (Russia), Rajendra Prasad (India), Martinez Lanz Patricia (México), Marjan Malešič (The Republic of Slovenia), Beena Elizabeth Thomas (India), Metin Picakciefe (Turkey), Radostina Ivaylova Aleksandrova (Bangladesh), Jakir Hossain Bhuiyan Masud (Bangladesh), Kashef N. Zayed (Oman), Seyed Mohammad Jazayeri (Iran), Miguel Rego Costa Soares-Oliveira (Portugue), Mustafa Yildiz (Turkey), Trevor Cornelius Stuart Archer (Sweden). Editorial Office 240 Nagle Avenue #15C, New York, NY 10034, USA Tel: 1-323-984-7526, 323-410-1082; Fax: 1-323-984-7374, 323-908-0457 E-mail: [email protected], [email protected] Copyright©2014 by David Publishing Company and individual contributors. All rights reserved. David Publishing Company holds the exclusive copyright of all the contents of this journal. In accordance with the international convention, no part of this journal may be reproduced or transmitted by any media or publishing organs (including various websites) without the written permission of the copyright holder. Otherwise, any conduct would be considered as the violation of the copyright. The contents of this journal are available for any citation. However, all the citations should be clearly indicated with the title of this journal, serial number and the name of the author. Abstracted / Indexed in Database of EBSCO, Massachusetts, USA Universe Digital Library S/B, ProQuest Summon Serials Solutions, USA Google Scholar (scholar.google.com) American Federal Computer Library Center (OCLC), USA Universe Digital Library Sdn Bhd (UDLSB), Malaysia China National Knowledge Infrastructure (CNKI), China Subscription Information Price (per year): Print $520, Online $320, Print and Online $600. David Publishing Company 240 Nagle Avenue #15C, New York, NY 10034, USA Tel: 1-323-984-7526, 323-410-1082; Fax: 1-323-984-7374, 323-908-0457 E-mail: [email protected]

David Publishing Company

www.davidpublishing.com

DAVID PUBLISHING

D

Journal of Health Science

Volume 2, Number 7, July 2014 (Serial Number 8)

Contents Health Informatics

307 The Effective Activation of Apoptosis by AO-95 from the Aerial Part of Alpiniae officinarum in

A549 Cell Line

Xiaobin Zeng, Hongbo Chen, Jun Tian, Yang Wang, Liao Cui and Xueyan Wang

318 Changes of Immunoreactivity Status in Patients with Osteosarcoma on the Background of

Chemotherapy

Djamilya Sh. Polatova, Margarita S. Gildieva and Khurshid G. Abdikarimov

325 From Awareness to Action Using the Survey Feedback Method

Ann Fridner, Birgit Pingel, Lise Tevik Løvseth, Marie Gustafsson Sendén and Karin Schenck-Gustafsson

Disaster Management

330 Nurse Documentation in Deteriorating Patients Prior to In-hospital Cardiac Arrest—A Pilot

Study in A Swedish University Hospital

Lars Aas, Maria Ouchterlony and Therese Djärv

338 Relation of Nausea and Vomiting in Acute Myocardial Infarction to Location of Infarct

Kooli Sami, Laamouri Noura, Raddaoui Abdelhafidh, El Heni Najla, Ghazali Hanene and Souissi Sami

340 Mental Health Predictor of the Sixth Batch Indonesian Nurse and Certified Care Worker

Candidates Migrate to Japan under the Japan–Indonesia Economic Partnership Agreement in

Pre-migration Stage

Susiana Nugraha and Yuko Ohara-Hirano

Journal of Health Science 2 (2014) 307-317

The Effective Activation of Apoptosis by AO-95 from the

Aerial Part of Alpiniae officinarum in A549 Cell Line

Xiaobin Zeng1, 5, Hongbo Chen2, Jun Tian3, Yang Wang4, Liao Cui1 and Xueyan Wang5

1. Guangdong Key Laboratory for Research and Development of Natural Drugs, Department of Pharmacology, Guangdong Medical

College, Zhanjiang 524023, Guangdong, China

2. The Shenzhen Key Lab of Gene and Antibody Therapy, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055,

Guangdong, China

3. College of Life Science, Jiangsu Normal University, Xuzhou 221116, Jiangsu Province, China

4. Shenzhen Xinpeng Shengwu Gongcheng Co. LTD, Shenzhen 518055, Guangdong, China

5. Key Lab for New Drug Research of TCM and Shenzhen Branch, State R & D Centre for Viro-Biotech, Research Institute of

Tsinghua University in Shenzhen, Shenzhen 518057, Guangdong, China

Received: May 19, 2014 / Accepted: June 25, 2014 / Published: July 30, 2014. Abstract: The study was designed to examine the apoptosis inducing activity of the AO-95 from the aerial part of Alpiniae officinarum. The AO-95 treatment to three human lung cancer cell lines (A549, NCI-H460 and NCI-H23) resulted in a dose-dependent inhibition of cell growth. The authors selected A549 cell line as a test model system. The AO-95 induced apoptosis of A549 obviously, as shown by the results of cell cycle distribution analysis and cell apoptosis assay. Treatment of A549 with AO-95 markedly decreased the mitochondrial transmembrane potential (ΔΨm) suggesting AO-95-induced apoptosis may involve a mitochondrial-related pathway. Two compounds were isolated from AO-95 and their structures were identified as 3-phenylpropanal and 4-phenylbutan-2-one. Meanwhile, ten different components accounting for 98.38% of the total AO-95 composition were identified by gas chromatography-mass spectrometry. The major components were 3-phenylpropanal (33.09%) and 4-phenylbutan-2-one (51.16%). And these two compounds showed notable cytotoxic activity with IC50 values of 14.90-78.46 µg/mL. In summary, the AO-95, dominated by phenylpropanoid constituents, shows effective apoptosis inducing activity by mitochondrial-related pathway and may be developed as an agent against human lung cancer. Key words: Alpiniae officinarum, apoptosis, lung cancer, mitochondrial-related pathway.

1. Introduction

Alpiniae officinarum is a plant in the ginger family,

cultivated in Southeast Asia. It originated in China,

where its name ultimately derives. It can grow several

feet high, with long leaves and reddish-white flowers.

The rhizomes, known as galangal, are valued for their

spicy flavor and aromatic scent. These are used

throughout Asia in curries and perfumes, and were

previously used widely in Europe. They are also used

Corresponding author: Xiaobin Zeng, doctor, assistant

researcher, research field: Chinese medicine. E-mail: [email protected]. Jun Tian, doctor, lecturer, research field: Chinese medicine. E-mail: [email protected].

as a traditional Chinese medicine for their

anti-inflammatory, antioxidant, anti-proliferative,

anticancer, and antiemetic effects [1-5]. Previous

phytochemical studies on their rhizomes resulted in the

isolation of monoterpenes, diarylheptanoids, flavonoids

and phenylpropanoids [6-10]. However, to the best of

our knowledge, there has been remarkably little

research on the chemistry and bioactivity of the aerial

part of A. officinarum. The annual production of the

aerial part of A. officinarum now exceeds 1,000,000 t,

but the utilisation is still low. Every year, a large

number of the aerial parts of A. officinarum have been

thrown away as a waste from A. officinarum production.

DAVID PUBLISHING

D

The Effective Activation of Apoptosis by AO-95 from the Aerial Part of Alpiniae officinarum in A549 Cell Line

308

Lung cancer is one of the most common cancers with

annually increasing occurrence worldwide. Lung

cancer is the most common cause of cancer-related

death in men and women, and is responsible for 1.38

million deaths annually, as of 2008 [11]. Apoptosis is a

form of programmed cell death. It is also necessary for

the destruction of cells considered a threat such as cells

infected with viruses, cells with DNA damage, and

cancerous cells. During apoptosis, cellular contents are

not released and inflammation does not occur.

Impaired regulation of apoptosis leads to a variety of

diseases [12]. Cells undergoing apoptosis show

characteristic morphological and biochemical features.

These features include chromatin aggregation, nuclear

and cytoplasmic condensation, partition of cytoplasm

and nucleus into apoptotic bodies which contain

ribosomes, morphologically intact mitochondria and

nuclear material [13]. In vivo, these apoptotic bodies

are rapidly recognized and phagocytized by either

macrophages or adjacent epithelial cells. Due to this

efficient mechanism for the removal of apoptotic cells

in vivo no inflammatory response is elicited. In vitro,

the apoptotic bodies as well as the remaining cell

fragments ultimately swell and finally lyse. This

terminal phase of in vitro cell death has been termed

“secondary necrosis” [14]. Apoptosis inducer can

prevent tumor formation, and side effects are rare.

The aim of the present study was to investigate

components with the apoptosis inducing activity from

the aerial part of A. Officinarum, and the chemical

composition of AO-95 was also investigated.

2. Materials and Methods

2.1 Plant Materials

The aerial part of A. officinarum was collected in

Xuwen County, Guangdong province, China

(September 2012) and identified by Dr. Xiaobin Zeng

(Guangdong Key Laboratory for Research and

Development of Natural Drugs, Guangdong Medical

College, China). Voucher specimens (No. 120915)

were deposited at the herbarium of Guangdong Key

Laboratory for Research and Development of Natural

Drugs, Guangdong Medical College, China.

2.2 Chemicals and Reagents

Diaion D-101 macroporus resin was the product of

Xi’an Lanxiao Resin Corporation Ltd. (Xi’an, China).

RPMI-1640 medium, fetal bovine serum (FBS) and

trypsin-EDTA solution (1 ×) were obtained from

Hyclone (Logan, UT). Mitotracker green was

purchased from Invitrogen (Carlsbad, CA, USA).

Annexin-V/PI Apoptosis Detection Kit and JC-1 were

purchased from Beyotime Institute of Biotechnology

(Jiangsu, China), PI (Propidium iodide) was purchased

from Sigma (St. Louis, MO, USA). All other chemicals

were analytical or HPLC grade and obtained from

Shanghai Chemical Reagents Co., Ltd (Shanghai,

China).

2.3 Extraction and Fractionation of Plant Material

The herb (5.0 kg) was minced and extracted three

times with 95% ethanol. The solvent was removed

under vacuum to yield the crude extract (600 g). A

suspension of the extract in H2O was centrifuged and

then applied to a D-101 macroresin column (80 mm ×

1300 mm) and eluted with H2O (10 L), 10% ethanol

(10 L), 30% ethanol (10 L), 50% ethanol (10 L), 70%

ethanol (10 L), and 95% ethanol (10 L) successively.

Each eluent was concentrated and dried to yield 250.5

g, 110.0 g, 59.0 g, 130.0 g, 25.7 g, 12.6 g of dried

elutes, respectively. The 95% ethanol eluent (12.6 g)

was fractionated over a silica gel column (300 g, 70 ×

3 cm) by eluting with cyclohexane-ethyl acetate

(100:1, 5 L), (33:1, 4 L), (20:1, 5 L), (15:1, 5 L), (10:1,

3 L), (2:1, 4 L), (1:1, 5 L). This process yielded 10

fractions (AO-95-1-AO-95-10). AO-95-3 (1.35 g)

was separated on a silica gel column (50 g, 45 × 2 cm),

using cyclohexane-ethyl acetate (100:1, 1.5 L), (50:1,

3 L), (25:1, 1.5 L), (15:1, 1.2 L), (10:1, 1.3 L) to yield

compound 1 (368 mg). AO-95-6 (1.06 g) was further

purified by a silica gel column (30 g, 38 × 2 cm) and

eluted with cyclohexane-ethyl acetate (100:1, 1 L),


309

(25:1, 0.8 L), (15:1, 1 L), (10:1, 1.2 L), (5:1, 1.5 L) to

obtain compound 2 (550 mg).

2.4 Analysis the Chemical Component of AO-95

The chemical composition of the AO-95 was

analyzed using GC/MS. The AO-95 (10 μg) was

dissolved in cyclohexane (1 mL) and 1 μL of the

solution was injected into a GC/MS (QP-2010

Shimadzu Co., Kyoto, Japan). The capillary column

was HP-Innowax (length = 30 m, i.d = 0.25 mm,

thickness = 0.25 μM). Helium was used as the carrier

gas at a flow rate of 1 mL/min. The column inlet

pressure was 55.8 kPa. The GC column oven

temperature was increased from 50 to 280 °C at a rate

of 10 °C/min, with a final hold time of 10 min. Injector

and detector temperatures were maintained at 280 °C.

EI mode was at 70 eV, while mass spectra were

recorded in the 30-450 amu range and ion

source-temperature was 200 °C. The AO-95

components were identified by comparison of their

mass spectra with those in the NIST08s GC/MS library

and those in the literature [15].

2.5 Cell Culture

Human lung cancer cell lines (A549, NCI-H460 and

NCI-H23) were obtained from the American Type

Culture Collection and cultured in RPMI 1640 medium

containing 10% FBS, 100 U/mL penicillin and 100

μg/mL streptomycin. Cells were cultured at 37 °C in a

humidified 5% CO2 incubator. The extract (AO), the

0% ethanol elute (AO-0), the 10% ethanol elute

(AO-10), the 30% ethanol elute (AO-30), the 50%

ethanol elute (AO-50), the 70% ethanol elute (AO-70),

the 95% ethanol elute (AO-95), 4-phenylbutan-2-one,

3-phenylpropanal and cisplatin were dissolved in

dimethyl sulfoxide (DMSO) (final DMSO concentration

≤ 0.5%). In all experiments, the cells in RPMI 1640

medium plus DMSO only were used as the control.

2.6 Cell Viability Assay

Cells were seeded in a 96-well plate at a density of 5

× 103 cells/well. The total volume was adjusted to 200

μL with growth medium. At 24 h after the seeding, the

cells were exposed to AO, AO-0, AO-10, AO-30,

AO-50, AO-70, AO-95, 4-phenylbutan-2-one,

3-phenylpropanal and cisplatin. Cell viability was

examined after 24, 48 or 72 h using a standard MTT

method [16]. Drug effect was expressed as percentage

relative to the controls.

2.7 DNA Cell Cycle Analysis

A549 cells were seeded at a density of 1 × 105

cells/well in a six-well plate. 24 h after the seeding, the

cells were treated with AO-95 (0-50 μg/mL) for 48 h at

37 °C. Cells were fixed overnight with 95% ethanol at

-20 °C and stained with PI solution (100 μg/mL). Cell

cycle distribution analysis [17] was performed using a

flow cytometer (Beckman-Coulter, Inc., Indianapolis,

IN).

2.8 Cell Apoptosis Assay

Apoptotic cells were detected by flow cytometry

with Annexin V-FITC/PI dual staining [18]. After

AO-95 treatment, the cells were harvested by

trypsinization, rinsed twice with PBS, and suspended

in 500 µL of binding buffer. The suspended cells were

incubated for 15 min at 4 °C with 5 µL Annexin

V-FITC solution, and incubated for another 5 min at

4 °C after adding 10 µL of PI solution. Flow cytometric

analysis of apoptotic cells was performed with a flow

cytometer (Beckman-Coulter, Inc., Indianapolis, IN).

The emitted green fluorescence of annexin V (FL1) and

red fluorescence of PI (FL2) were detected by a flow

cytometer. For each sample, 10,000 events were

recorded. The amount of early apoptosis, late apoptosis,

and necrosis was determined as the percentage of

annexin-V+/PI-; annexin-V+/PI+; and annexin-V-/PI+

cells, respectively.

2.9 Detection of Mitochondrial Membrane Potential (ΔΨm)

JC-1 easily penetrates cells and healthy

mitochondria. A green fluorescent JC-1 probe exists as

a monomer at low membrane potentials. However, at


310

higher potentials, JC-1 forms red-fluorescent

“J-aggregates”. The ratio of red/green JC-1

fluorescence is dependent only on the mitochondrial

membrane potential [19]. Briefly, after treatment, the

cells were incubated at 37 °C for 1 h with 5 mg/L JC-1

(Beyotime Biotech, Nantong, China), then washed

twice with PBS and placed in fresh medium without

serum. Lastly, images were viewed and scanned by

flow cytometry (Beckman-Coulter, Inc., Indianapolis,

IN) at 490 excitation and 530 emissions for green, and

at 540 excitation and 590 emissions for red. The ratios

of red/green fluorescent densities were calculated.

2.10 Statistical Analysis

All data were expressed as mean ± SD. from at least

three independent experiments, each performed in

quintuplicate.

3. Results and Analysis

3.1 Chemical Composition of AO-95

Comparing their GC-MS and NMR data with the

literature, the compounds isolated from AO-95 were

identified as 3-phenylpropanal (1) [15] and

4-phenylbutan-2-one (2) [15].

A total of ten different components of the AO-95,

accounting for 98.4% of the total AO-95 composition,

were identified by GC-MS analysis. The identified

chemical composition, retention time, and percentage

composition are given in Fig. 1a and Fig. 1b. The most

abundant components of the AO-95 were 4-phenylbutan

-2-one (51.16%), 3-phenylpropanal (33.09%), and

2-benzyl-4,5-dihydro-1H-imidazole (6.99%). Seven

(a)

Number Retention time (min)

Compounds Composition (%)

1 12.25 3-phenylpropanal 33.09

2 14.69 4-phenylbutan-2-one 51.16

3 19.13 hexadecane 0.59

4 23.32 1-(4-hydroxy-3-methoxyphenyl)propan-2-one 1.87

5 25.25 Cubenol 0.41

6 29.59 butyl octyl phthalate 0.95

7 31.45 butyl 2-ethylhexyl phthalate 0.98

8 32.31 3β-chlorocholest-5-ene 0.59

9 36.56 N-(2-bromophenyl)-2-oxo-2H-chromene-3-carboxamie 1.75

10 37.48 2-benzyl-4,5-dihydro-1H-imidazole 6.99

(b)

Fig. 1 GC/MS total ion chromatogram of AO-95. (a)： GC chromatogram of AO-95; (b)： Chromatographic and

spectroscopic properties of AO-95 chemical constituents.


311

other components such as hexadecane (0.59%),

1-(4-hydroxy-3-methoxyphenyl) propan-2-one

(1.87%), Cubenol (0.41%), butyl octyl phthalate

(0.95%), butyl 2-ethylhexyl phthalate (0.98%),

3β-chlorocholest-5-ene (0.59%), and

N-(2-bromophenyl)-2-oxo-2H-chromene-3-carboxami

e (1.75%) were in less amounts. However, oxygenated

sesquiterpenes, sesquiterpene hydrocarbons, and others

were also found as trace or minor components.

3.2 Cell Viability Analysis

To evaluate the effect of the samples on the cell

viability of lung cancer cell lines, the MTT assay was

used. The AO, AO-0, AO-10, AO-30, AO-50, AO-70,

AO-95, 3-phenylpropanal and 4-phenylbutan-2-one

were treated to three lung cell lines (A549, NCI-H460

and NCI-H23) and the authors found the samples

(AO-95, 3-phenylpropanal and 4-phenylbutan-2-one)

showed effectively cytotoxic activity. AO-95 showed a

remarkable dose-dependent inhibition of cell growth

(Fig. 2a-2c). Human lung cell line A549 was more

sensitive to AO-95 than the other two cell lines

(NCI-H460 and NCI-H23). Very few of the

compounds found in AO-95 have been tested for

(a)

(b)


312

(c)

Sample IC50 (µg/mL)

A549 NCI-H460 NCI-H23

AO-95 4.70 ± 0.54 11.64 ± 1.26 18.46 ± 1.78

4-phenylbutan-2-one 30.23 ± 3.04 61.32 ± 7.05 78.46 ± 6.98

3-phenylpropanal 14.90 ± 1.66 21.64 ± 2.03 28.46 ± 3.05

Cisplatin 10.6 ± 1.29 18.7 ± 1.83 26.54 ± 2.66

(d)

Fig. 2 Cytotoxicity of AO-95, 4-phenylbutan-2-one and 3-phenylpropanal in NCI-H460, A549 and NCI-H23 cells. The percentage of viability of treated cells was determined by MTT assay. (a): NCI-H460 cell line was treated with various concentrations of AO-95 (0-50 µg/mL) for 24 h, 48 h, and 72 h; (b): A549 cell line was treated with various concentrations of AO-95 (0-50 µg/mL) for 24 h, 48 h, and 72 h; (c): NCI-H23 was treated with various concentrations of AO-95 (0-50 µg/mL) for 24 h, 48 h, and 72 h; (d): IC50 values for the inhibition of human lung tumor cell line NCI-H460, A549 and NCI-H23 of AO-95, 4-phenylbutan-2-one, 3-phenylpropanal and Cisplatin 48 h after treatment.

anticancer properties. However, it has been reported in

literature that 3-phenylpropanal (33.09%) shows

selective toxicity against human NHIK 3025 cells [20].

Moreover, the authors found that 3-phenylpropanal

and 4-phenylbutan-2-one is active against A-549,

NCI-H460 and NCI-H23 cell lines with IC50 values

shown in Fig. 2d. However, no such cytotoxicity assays

have been performed for the other major components

of AO-95 (1-(4-hydroxy-3-methoxy phenyl)

propan-2-one,

N-(2-bromophenyl)-2-oxo-2H-chromene-3-carboxami

de and 2-benzyl-4,5-dihydro-1H-imidazole. Therefore,

the cytotoxicity of the AO-95 may be due to abundant

phenylpropanoid compounds in the AO-95.

3.3 Effect of AO-95 on Cell Cycle Distribution

To explain the mechanism of cell growth inhibition

by AO-95 concerning cell cycle change. The cell cycle

distributions of A549 cells were investigated by flow

cytometry after treatment with AO-95. Several studies

have shown that the induction of apoptosis might be

due to cell cycle arrest [21, 22]. Therefore, inhibition of

the cell cycle has been appreciated as a target for the

management of cancer. As shown in Fig. 3a and Fig. 3b,

AO-95 could cause G0/G1 phase cell cycle arrest in

A549 cells. G0/G1 is one of the reliable biochemical


313

AO-95 (0 µg/mL) AO-95 (3.125 µg/mL) AO-95 (6.25 µg/mL)

AO-95 (12.5 µg/mL) AO-95 (25 µg/mL) AO-95 (50 µg/mL)

(a)

Cell cycle Percentage (%)

0.5% DMSO

50 (µg/mL)

25 (µg/mL)

12.5 (µg/mL)

6.25 (µg/mL)

3.125 (µg/mL)

Apoptosis 0 9.507 0 0 0 1.976

Go/G1 55.871 64.323 62.753 61.218 55.037 54.685

s 35.575 24.534 32.548 32.703 32.962 34.963

G2/M 8.554 11.143 4.699 6.079 12.001 10.352

(b)

Fig. 3 Cell cycle analysis of A549 cells treated with AO-95 for 24 h by flow cytometry. (a): Cell cycle profile was examined by flow cytometry with PI staining. Cell number was counted according to DNA content of G0/G1, S, and G2/M phases. (b): Statistics of cell number of G0/G1, S, and G2/M phases in cell cycle, and the results are means of three independent experiments.

markers of apoptosis. A549 cells were exposed to

3.125, 6.25, 12.5, 25 and 50 µg/mL of AO-95 for 48 h.

The data show that the AO-95-induced apoptosis of

A549 was dose-dependent, with around 64.32 % of the

G0/G1 cells at concentration of 50 µg/mL of the AO-95.

It was suggested that AO-95 induced A549 cell death

involved in a mechanism of apoptosis.

3.4 Apoptosis Induced by AO-95

In order to determine whether AO-95 can cause


314

apoptosis of A549, the effect of AO-95 on the

apoptosis of the cells was examined by Annexin V and

PI double staining. As shown in Fig. 4, apoptotic cells

were increased in a dose-dependent manner following

AO-95 treatments for 24 h, when compared to that in

the control group that was treated with vehicle only.

The data showed that the AO-95-induced apoptosis of

A549 was dose-dependent, with around 61.0% of the

cells in early apoptosis at concentration of 50 µg/mL of

the AO-95. The result suggests that AO-95 could

damage A549 by inducing apoptosis of the cells.

3.5 Mitochondrial Membrane Potential (ΔΨm) of A549 Decreased AO-95

Mitochondria are not only a major contributor of

ATP to the cells, but also play a crucial role in the

regulation of cell apoptosis. The maintenance of

mitochondrial membrane potential is essential for cell

survival and function. This experiment was to test

whether AO-95 treatment could decrease ΔΨm of the

cells. Fig. 5 shows that AO-95 treatment increase the

number of the cells with collapsed ΔΨm (the cells

in B2). There is also a growing body of evidence

AO-95 (0 µg/mL) AO-95 (3.125 µg/mL)

AO-95 (12.5 µg/mL) AO-95 (50 µg/mL)

Fig. 4 AO-95 induces the apopptosis of A549 cells. The cells were treated with different concentrations of AO-95 (as indicated) for 24 h. The control cells were treated with vehicle only. The percentages of viable, apoptotic and necrotic cells were determined by flow cytometry using staining of Annexin V-FITC and PI. 1: Cells in necrosis; 2: Cells in later apoptotic; 3: Viable cells; 4: Cells in early apoptosis.


315

AO-95 (0 µg/mL) AO-95 (3.125 µg/mL)

AO-95 (6.25 µg/mL) AO-95 (12.5 µg/mL)

Fig. 5 The cells were treated with different concentrations of AO-95 (as indicated). The control cells were treated with vehicle only. The effect of mitochondria was examined. AO-95 decreases mitochondrial membrane potential ΔΨm of A549. ΔΨm of A549 was detected by flow cytometry with the fluorescent dye JC-1 staining as described in “Materials and Methods”. The percentage of the cells with collapsed ΔΨm is in B2.

indicating that AO-95 is able to induce apoptosis by

helping to dissipate the membrane potential of

mitochondria and therefore make it more permeable.

The loss of mitochondrial transmembrane potential

is a hallmark for apoptosis. Mitochondria undergo

major changes in membrane integrity before classical

signs of apoptosis become manifest. These changes

concern both the inner and the outer mitochondrial

membranes, leading to a disruption of the inner

transmembrane potential (ΔΨm) and the release of

intermembrane proteins through the outer membrane.

In this experiment, mitochondrial transmembrane

potential (ΔΨm) was assessed using JC-1, a specific

fluorescent probe for the analysis of mitochondrial

transmembrane potential. The mitochondrial

transmembrane potential decreased in a

concentration-dependent manner, with the major

decrease occurring at 48 h, suggesting that AO-95

induced A549 cell apoptosis through the mitochondrial

pathway.


316

4. Conclusions

In the present study, the AO-95 could effectively

inhibit tumor growth in vitro. The results also indicate

that AO-95-induced apoptosis of A549 cells may

involve a mitochondrial-related pathway. Furthermore,

other pathways regulating apoptosis should be further

investigated. Also, AO-95 from the aerial part of A.

officinarum contains high phenylpropanoids (including

4-phenylbutan-2-one and 3-phenylpropanal).

Therefore, consumption of the aerial part of A.

officinarum may be an effective strategy for cancer

protection.

Acknowledgements

This research was partly supported by the Start Fund

of Guangdong Medical College (XB1302), National

Natural Science Foundation of China (31301585),

Science & Technology Innovation Fund of Guangdong

Medical College (STIF 201104), and Shenzhen basic

research project (JCYJ20120616142424467).

References

[1] Kiuchi, F., Shibuya, M., and Sankawa, U. 1982.

“Inhibitors of Prostaglandin Biosynthesis from Ginger.”

Chem. Pharm. Bull 30: 754-757.

[2] Shen, J., Zhang, H. Y., Xu, B., and Pan, J. X. 1998. “The

Antioxidative Constituents of Rhizomes of Alpinia

Offocinarum.” Nat. Prod. Res. Dev. 10: 33-36.

[3] Ali, M. S., Tezuka, Y., Banskota, A. H., and Kadota, S.

2001. “Blepharocalyxins C-E, Three New Dimeric

Diarylheptanoids, and Related Compounds from the Seeds

of Alpinia Blepharocalyx.” J. Nat. Prod. 64: 491-496.

[4] Heo, M. Y., Sohn, S. J., and Au, W. W. 2001.

“Anti-genotoxicity of Galangin as a Cancer

Chemopreventive Agent Candidate.” Mut. Res. 488:

135-150.

[5] Zhu, M., Lew, K. T., and Leung, P. 2002. “Protective

Effects of Plant Formula on Ethanol-Induced Gastric

Lesions in Rats.” Phytother. Res. 16: 276-280.

[6] Lu, W., and Jiang, L. H. 2006. “Chemical Constituents

and Pharmacological Activities of Alpinia Offcinarum

Hance.” Chin. Pharm 15: 19-21.

[7] Zhao, L., Qu, W., Fu, J. Q., and Liang, J. Y. 2010. “A New

Diarylheptanoid from the Rhizomes of Alpinia

Officinarum.” Chin. J. Nat. Med. 8: 241-243.

[8] An, N., Zhang, H. W., Xu, L. Z., Yang, S. L., and Zou, Z.

M. 2010. “New Diarylheptanoids from the Rhizome of

Alpinia officinarum Hance.” Food. Chem 119: 513-517.

[9] Liu, D., Qu, W., Zhao, L., and Liang, J. Y. 2012. “A Novel

Dimeric Diaryheptanoid from the Rhizomes of Alpinia

officinarum.” Chin. Chem. Lett 23: 189-192.

[10] Xu, S. M., Huang, X. J., Wang, Y., and Ye, W. C. 2012.

“A New Cadinane Sesequiterpene from the Rhizomes of

Alpinia officinarum.” Chin. J. Nat. Med. 10: 374-377.

[11] Ferlay, J., Shin, H. R., Bray, F., Forman, D., Mathers, C.,

and Parkin, D. M. 2010. “Estimates of Worldwide Burden

of Cancer in 2008: GLOBOCAN 2008.” Inter. J. Canc.

127: 2893-2917.

[12] He, X. J., Wang, Y. H., Hu, H., and Zhang, Z. X. 2012. “In

Vitro and In Vivo Antimammary Tumor Activities and

Mechanisms of the Apple Total Triterpenoids.” J. Agric.

Food Chem. 60: 9430-9436.

[13] Mancini, M., Anderson, B. O., Caldwell, E., Sedghinasab,

M., Paty, P. B., and Hockenbery, D. M. 1997.

“Mitochondrial Proliferation and Paradoxical Membrane

Depolarization During Terminal Differentiation and

Apoptosis in a Human Colon Carcinoma Cell Line.” J.

Cell. Biol. 138: 449-469.

[14] Eastman, A. 1993. “Apoptosis: A Product of Programmed

and Unprogrammed Cell Death.” Toxicol. Appl. Pharm.

121: 160-164.

[15] Adams, R. P. 2001. Identification of Essential Oils

Components by Gas Chromatography/Mass Spectroscopy.

Carol Stream, IL, USA: Allured Publishing Corporation.

[16] He, X. J., and Liu, R. H. 2007. “Triterpenoids Isolated

From Apple Peels Maybe Responsible for Their

Anticancer Activity.” J. Agric. Food. Chem. 55:

4366-4370.

[17] Yun, J. M., Afaq, F., Khan, N., and Mukhtar, H. 2009.

“Delphinidin, an Anthocyanidin in Pigmented Fruits and

Vegetables, Induces Apoptosis and Cell Cycle Arrest in

Human Colon Cancer Hct116 Cells.” Mol. Carcinog 48:

260-270.

[18] Chen, N. Y., Lai, H. H., Hsu, T. H., Lin, F. Y., Chen, J. Z.,

and Lo, H. C. 2008. “Induction of Apoptosis in Human

Lung Carcinoma A549 Epithelial Cells with an Ethanol

Extract of Tremella Mesenterica.” Biosci. Biotechnol.

Biochem. 72: 1283-1289.

[19] Reers, M., Smith, T. W., and Chen, L. B. 1991.

“J-aggregate Formation of a Carbocyanine as a

Quantitative Fluorescent Indicator of Membrane

Potential.” Biochem 30: 4480-4486.


317

[20] Dornish, J. M., Pettersen, E. O., and Oftebro, R. 1989.

“Modifying Effect of Cinnamaldehyde and

Cinnamaldehyde Derivatives on Cell Inactivation and

Cellular Uptake of Cis-Diamminedichloroplatinum (П) in

Human NHIK 3025 Cells.” Canc. Res. 49: 3917-3921.

[21] Hartwell, L. H., and Kastan, M. B. 1994. “Cell Cycle

Control and Cancer.” Sci. 266: 1821-1828.

[22] Vermeulen, K., Berneman, Z. N., and Van Bockstaele, D.

R. 2003. “Cell Cycle and Apoptosis.” Cell. Prolif. 36:

165-175.


Changes of Immunoreactivity Status in Patients with

Osteosarcoma on the Background of Chemotherapy

Djamilya Sh. Polatova, Margarita S. Gildieva and Khurshid G. Abdikarimov Republican Oncology Research Center of the Ministry of Health of Uzbekistan, Tashkent, 100179, Uzbekistan Received: May 05, 2014 / Accepted: July 23, 2014 / Published: July 30, 2014. Abstract: Background: To study the features of cellular and humoral parameters of immune system in patients with osteosarcoma before and after chemotherapy. Methods: Clinical, laboratory, instrumental, immunological (immunofluorescence method, immunoassay analysis). Presented approved chemotherapy protocol for patients with osteosarcoma. Results: In all patients with osteosarcoma identified cell immunodeficiency and activation of humoral immunity factors before chemotherapy and significant increase of IgA and circulating immune complexes after chemotherapy. Conclusions: Imbalance in the immune system can serve as diagnostic and prognostic criterion of the disease on the background of chemotherapy. Key words: Cellular immunity, humoral immunity, osteosarcoma, immunoglobulins lymphocytes.

1. Introduction

Osteosarcoma-one of the most aggressive malignant

human tumors occurs mainly in adolescents, and

usually affects bones that form knee joint, and is

characterized by early hematogenous dissemination

[1-6]. Today one of the most promising directions of

modern oncology is to study the role of immune system

in the pathogenesis of malignant tumors. Over the last

20 years period of studying the role of immunology in

carcinogenesis obtained data supporting the role of

immune system in anticancer protection of organism,

there are studies on mechanisms leading to the

destruction of tumor cells and mechanisms of

phenomenon of immunological tolerance of tumor

cells [6, 7-11]. Thus, according to the literature, the

immune system of the body is essential in the

pathogenesis of malignant tumors, including

osteosarcoma [4, 5]. Nowadays, malignant bone

tumors present complicated and insufficient explored

problem. This is explained by rarity of their origin,

Corresponding author: Djamilya Sh. Polatova, Ph.D.,

research fields: skin, soft tissue, bone oncology. E-mail: [email protected].

biological features of this group of tumors and

connected with their pattern of clinical course,

approaches to diagnostics and therapy. It is known, that

bone malignant tumors are heterogeneous group of

nosological form of tumors. Mainly they were

presented by sarcomas with aggressive course, inclined

to early hematogenous metastasis and frequent

recurrence. In recent years, modern medicine has

achieved significant progress in the combined

treatment of bone tumors. At the same time, in spite of

dilation the complex treatment possibilities of applying

the new generation of chemotherapy remain unsolved

problem. Probably in most cases, it is associated with

the initial state of the immune system and tumor cell

resistance to drugs. It should be noted that, works on

the treatment of osteosarcomas are rare in the country

as well as abroad [2, 4, 11-15].

The purpose of research was to investigate the

characteristics of cellular and humoral immune system

parameters in patients with osteosarcoma before and

after chemotherapy.


The authors examined 42 patients with histological

DAVID PUBLISHING

D

Changes of Immunoreactivity Status in Patients with Osteosarcoma on the Background of Chemotherapy

319

verified osteosarcoma who were treated at the National

Cancer Center of Uzbekistan. Male patients

predominated, they were 28, and female patients are 14.

Average age of patients was 19.5 ± 0.6 years. In

majority of patients tumor was located on bones,

forming knee joint (77%). For the accurate definition

of prevalence of tumor process there was used

radiography or CT of thoracic organs and skeletal

scintigraphy. In National Cancer Center of Uzbekistan

there were confirmed different protocols of

preoperative chemotherapy up to 4 cycles by CAP

regimen (Cyclophosphamide 400-600 mg/m2,

Doxorubicin 50-60 mg/m2 and Cisplatin 100-120

mg/m2 intravenously during one day) or Doxorubicin

30 mg/m2 in 1-3 d, and also to the protocol inserted 72

hourly intra-arterial infusion of Doxorubicin 90 mg/m2

and Cisplatin 100-120 mg/m2 during the next 6 h.

Besides, according to the protocol patients were

inserted 72 hourly intra-arterial infusions of

Doxorubicin 90 mg/m2 and Cisplatin 100-120 mg/m2

during the next 6 h. Then local radiotherapy of total

focal dose (TFD) 36-40 Gy was performed. The next

stage was surgical removal of tumor-patients were

conducted organ conservative plastic-reconstructive

operations with replacement of defect with

endoprosthesis. There were provided from 6 to 9 cycles

of adjuvant chemotherapy after operation. At disease

progression patients underwent chemotherapy with

Iphosphamide 3 g/m2 in combination with Etoposide

150 mg/m2 during 3 d. Patient’s selection was carried

out according the tumor stage, spread, morphology and

age of examined patients.

Immunological investigations included study of

cellular and humoral parameter of patients’ immune

system with osteosarcoma before treatment and after

conduction of the first cycle of chemotherapy.

Immunological investigations were performed at the

Immunological Institute in the laboratory of

Immunocytokines. Determination of cellular immunity

(CD3+, CD4+, CD8+, CD16+, CD20+), and also

identification of activated markers of lymphocytes

(CD25+, CD38+ and CD95+) was carried out with

using of monoclonal antibodies with counting by

fluorescent microscope [16]. Humoral group of

immunity was assessed by definition of main serum of

immunoglobulins IgG, IgA and IgM in the serum of

peripheral blood with IFA method. Circulating

Immune Complexes (CIC) various measures defined

with spectrophotometer method [16]. Results of the

study were subjected to statistical analysis using the

Student-Fisher’s test, the data processed on PC using

soft Statistica-6. For clarity of obtained results all the

studied parameters of immune system were transferred

to percentage with respect to 100% for the norm.

3. Results and Discussion

Content of leukocytes insignificantly increased

before treatment in patients with osteosarcoma in

comparison control group. It should be noted that

reliable difference was observed in the group of

patients after the first cycle of chemotherapy with the

data of control group. General contents of leucocytes

was decreased up to 51% by attitude to 100% of control

group in the patients group with osteosacoma, that

conformed to 3275.8 ± 236.5 kL/mkL, at that time as

this index was equal to 6500 ± 295.0 kL/mkL (P < 0.05)

in control group (Diagram 1). It is known that leading

importance in antitumor protection of organism is

belonged to the cellular group of immunity, where the

T-lymphocytes play the key role. The authors also

analyzed the data by condition of lymphocytes of

peripheral blood. Investigation showed that authentic

repression of general number of lymphocytes was not

detected in patients with osteosarcoma before

treatment. As it can be seen from the table, percentage

of lymphocytes before chemotherapy compiled 91%.

Whereas after the first cycle of chemotherapy is

observed authentic increase of general number of

lymphocytes by compare with the data of control group

and groups of before treatment, which compiled 120%

regarding to control. So, comparative and absolute

content of lymphocytes were reliably increased after the


320

Diagram 1 Cellular link state of patients’ immunity with osteosarcoma on the background of treatment.

course of chemotherapy in comparison with the data of

control group (P < 0.05).

It is known, that CD3+, CD4+, CD8+ receptors are

related to phenotypic markers of T-lymphocytes. It was

shown that starting and regulation of efficacy of

immune response is determined in many of them with

specific antigen of T-lymphocytes. The authors know

that degree of superficial expression of CD3+ receptors

on membrane of T-lymphocytes reflects its

transmissible function and allows identifying general

quantity of T-lymphocytes [9. 10, 13, 17-20]. Analysis

of T-cell immunity showed that the relative content of

CD3+ T-lymphocytes in patients with osteosarcoma

was lower than control group. Thus, comparative

number CD3+ Т-lymphocytes in patients group was

87% before treatment regarding to 100% control group

(P < 0.05). Absolute values of CD3+ T-lymphocytes of

patients and healthy persons group differed

significantly (P < 0.05), wherein the absolute content

of T-lymphocytes in patients was inhibited by 2.6 times

compared to control. Obtained results were presented

as diagram 1. It should be noted that after

chemotherapy content of T-lymphocytes decreased up

to 81% and was significantly suppressed in comparison

with the control group before treatment.

In analyses of T-cellular group of immunity,

including characteristics of subpopulation of CD4+

Т-helpers/inductors and CD8+ Т-cytotoxic

lymphocytes, in patients with osteosarcoma was

detected suppression of subpopulation of CD4+

Т-helpers/inductors regarding to control group. Thus,

comparative and absolute contents of CD4+

Т-helpers/inductors in patients was authentically

suppressed by compare with the data of control group

(P < 0.001) before and after treatment. The relative

number of CD4+ T-helpers/inductors in patients before

and after treatment was inhibited by 1.8 times

compared to the values of control group.

Absolute number of CD4+ Т-helpers/inductors was

suppressed in 2.7 times in comparison with the data of

control group. In percentage deficit of CD4+

Т-helpers/inductors before chemotherapy compiled

80% regarding to control and after chemotherapy-64%.

It is clear that the lack of T-cells population in

osteosarcoma due to predominantly suppression of

CD4+ T-helpers/inductors, which are the necessary and

important part in the formation of cells-killers, carrying

immediate elimination of tumour cells [21, 22]. In


321

examining group of patient with osteosarcoma was

observed considerably increased expression of CD8+

in comparison with control group (P < 0.001) before

and after conducting of chemotherapy. Thus, relative

number of CD8+ Т-cytotoxic lymphocytes was

increased in 1.8 times before treatment but in the group

in 2.4 after chemotherapy in compare with control

group correspondingly. It is known that cytotoxic

CD8+ Т-lymphocytes play the important role in

pathogeneses of oncological diseases [23-25]. It was

established that the main function of cytotoxic

lymphocytes is their sharing in ensuring of antitumor

protection, which shows taken results [21, 25]. This

implies that correlation of CD4+/CD8+ (IRI) were

significantly differed from the data of control group

with significant suppression in the group of patients

before and after conducting of chemotherapy.

Individual amplitude of importance of IRI in patients

with osteosarcoma fluctuated from 0.4 to 1.14, but in

most part of patients IRI was lower than 1.0. In

percentage terms, it is obviously, that in the patients

before chemotherapy IRI was suppressed to 75%, but

in the group of after chemotherapy-64% regarding the

control group. Clearly, reducing the IRI observed due

to the suppression of the relative number of CD4+

T-lymphocytes and increase of relative content of

CD8+ T-lymphocytes. Consequently, in osteosarcoma

it is detected Т-cellular immune deficit, which was

connected with disbalance of the main immune

regulator subpopulation of Т-lymphocytes (CD4+

Т-helpers/inductors and CD8+ Т-cytotoxic

lymphocytes). It is known that CD16+ is membrane

low-affinity IgG-receptor of third type. At the stage of

activation of killer cells appear additional cofactors, in

presence of natural killers comes into cytolysis.

Apparently, in oncological process, in particularly in

osteosarcoma immunological surveillance at all stages

of development and functioning of the cells are

disturbed. Thus, analysis showed the presence of

significant changes were not detected in the group of

patients with control group before and after the

chemotherapy. It should be noted, that insignificant

increase the number of CD16+ is observed in the group

of patients in comparison with the data of control

before and after the treatment, although reliable

differences were not detected. By the data, some

energy is observed by killer cells concerning to

malignant cells (Diagram 1).

Also the authors studied activation markers of

peripheral blood lymphocytes in patients with

osteosarcoma. These markers began to be studied

relatively recently, so in the literature highlight a few

papers devoted to the study of their functional activity,

particularly in malignant processes, and this due to

their study in the research. Analysis of activated

markers of lymphocytes allows to study the processes

of activation, proliferations, differentiation and

apoptosis of immune competent cells [22, 24, 25].

Expression of CD25+, CD95+ and CD38+ were

studied from lymphocytes activation markers. It is

known, that receptor CD25+ presented with -chain,

which is expressed on activated Т-lymphocytes. In

activation of Т-lymphocytes, cytokine interleukin-2

plays the important role in development, maturation

and regulation of immune response, which supports the

proliferation of activated Т-lymphocytes and

B-lymphocytes [1]. Analysis of CD25+ expression on

lymphocytes did not detect the presence of authentic

differences between investigated groups. Thus,

expression of CD25+ in patients was differed in 1.2

times from the value of control group (Diagram. 1).

Expression of CD95+ on activated lymphocytes was

authentically increased in patients with osteosarcoma

after chemotherapy by compare with control group

correspondingly (P < 0.05), the contents of CD95+

before and after chemotherapy was increased to 103%

and 120%, correspondingly in comparison with control

group. It is obviously, that it was connected with the

process of apoptosis in immune competent cells, that is

explained appearing the immune deficit state.

Expression of CD38+ in lymphocytes of patients group

before and after chemotherapy composed 120% and


322

94%, correspondingly. It is known, that CD38+ is

precursor of Т- and В-lymphocytes [22, 25].

Humoral group of immunity was studied by

expression of markers CD20+ and B-lymphocytes and

by serum concentration of the main classes of

immunoglobulin IgA, IgG и IgM. Received data

showed that expression of CD20+ was insignificant

suppressed in the group of patients with osteosarcoma

after performing the first cycle of chemotherapy. The

authors detected, that the contents of CD20+ compiled

105% and 94%, correspondingly in comparison with

the control group before and after chemotherapy.

Immunoglobulins play an important intermediary

function in the cascade development of the immune

response and partially can condition the effectiveness

of final, effector responses of cellular immunity on the

inactivation and elimination of mutant cells [8, 10, 20].

It is known, that circulating antibody is one of their

effector factors of immunity, rendering antispecific

protection [24, 25]. Studying the concentration of

serum immunoglobulin allowed detecting disbalance

in the contents of main immunoglobulin after the

chemotherapy. The authors detected the reliable

increasing of IgА and prevalence of IgМ after

conducting chemotherapy. Content of IgА compiled

106% and 154%, in the group of patients before and

after chemotherapy, correspondingly in compare with

control group. IgМ level had not reliable differences in

control group before chemotherapy but after

chemotherapy its contents compiled 110% regarding

the control group.

Consequently humoral immune link was

characterized by reliable increasing the serum

construction of IgA and IgМ in peripheral blood of

patients with osteosarcoma after chemotherapy

(Diagram 2).

The authors also studied the quantitative characteristic

of Circulating Immune Complexes (CIC) in the serum

of peripheral blood of patients with osteosarcoma.

Investigation showed the reliable increasing of large

and small magnitude CIC before and after performing

chemotherapy in compare with the data of control

group. It is known that small CIC has pathogenic effect

to the vessels and tissues of organism. Thus, 3% of CIC

and 4% of CIC were increased correspondingly in 2.4

and 2.8 times in patients group before treatment in

compare with the results of control group (Diagram 2).

Conducting chemotherapy showed the suppression of

CIC in 3% and 4% regarding the patients group before

chemotherapy. CIC 3% in patients group before and

Diagram 2 Humoral state of immune link of patients with osteosarcoma on the background of treatment.


323

after chemotherapy made up 212% and 331%,

according to relatively control group. But CIC 4%

made up 227% and 407%, correspondingly.

Consequently the authors detected activation of

humoral immune link (immunoglobulin A and

circulating immune complexes) independently from

performing chemotherapy, the greatest activation was

observed in patients group after conducting

chemotherapy.

4. Findings

(1) In patients with osteosarcoma was detected

T-cellular immune deficit, which is appeared by deficit

of CD4+ Т-helpers/inductors on the background of

increased number of CD8+ Т-lymphocytes.

(2) In the result of disbalance of subpopulation

T-lymphocytes it is marked significant decrease of

immune regulator index, which is the index of

inadequacy of immune response.

(3) Detected disbalance of humoral immune link

was intensified significant increase of immunoglobulin

A before the conducting of chemotherapy and CIC after

chemotherapy.

(4) From the side of activated markers are observed

suppression of functional activation of lymphocytes

after chemotherapy, except CD95+ marker of apoptosis,

which is increased and appeared forming of cellular

immune deficit after chemotherapy.

5. Conclusions

So, the authors have analyzed cellular and humoral

parameters of immune reactivity of patients with

osteosarcoma before and after chemotherapy. There has

been detected disbalance in the state of cellular and

humoral component of immunity before the starting of

chemotherapy in investigation. Increase the humoral

factors activity, in particularly immunoglobulin-A and

circulating immune complexes of great and small

magnitude was observed after conducting of

chemotherapy, practically in all patients with

osteosarcoma. Received data characterizes the

immunoreactivity state of patients with osteosarcoma

before and after treatment and can serve as diagnostic

and prognostic criteria of this disease on the

background of chemotherapy.

References

[1] Solovyev, Yu. N. 1993. “Bone Tumors.” In Pathologic

Anatomic Diagnostics of Human Tumor Guideline in 2

Books under Red, edited by Kraevskiy, N. A. Medicine.

[2] Trapeznikov, N. N., Erenina, L. A., Kutateladze, T. O.,

and co-authors, 1984. “Survival and Prognoses in the

Condition of Adjuvant Chemotherapy in Patients with

Osteogenic Sarcoma.” Questions of Oncology 30 (7):

33-40.

[3] Trapeznikov, N. N., Dolgushin, B. I., and Ishankhodjaev,

U. U. 1993. “Intraarterial Infusion and the Level of Blood

Circulation of Tumor in Osteogenic Sarcoma.” Reporter

ОSC RАМS 1: 40-42.

[4] Trapeznikov, N. N., Solovyev, Yu. N., and Yeremina, L.

A. 1993. “Progress in the Treatment of Osteogenic

Sarcoma.” Reporter ОSC RАМS 1: 3-9.

[5] Trapeznikov, N. N., Aliev, М .D., and Solovyev, Yu. N.

2001. “Osteosarcoma of Extremities Treatment During

The Century (Semi-Centennial Experience).” Reporter

RАМS 9: 46-49.

[6] Seshkovskiy, M. S. 1978. Primary Malignant Tumor of

Bones (Clinical-Rengeno-Morphological Investigation).

Moscow: Diss. M.D.

[7] Anichkov, N. M. 2005. “Pathogenesis of Cachexia in

Malignant Tumors.” Archive of pathology 67 (5): 51-56.

[8] Bogatirev, V. N. 1991. Value of Quantitative Methods of

Investigation (Morphometry, Flow Cytometry,

Microdencytometry) in Clinical Oncocytology. Moscow:

Dissert. Doct. Med. Sciences.

[9] Kadagidze, Z. G. 1994. “Subpopulation of Lymphocytes

in Malignant Growth.” Questions on Oncology 30 (1):

28-29.

[10] Ketlinskiy, S. A. 2002. “The Role of T-helpers Types 1

and 2 in Regulation Cellular and Humoral Immunity.”

Immunology 23 (2): 77-79.

[11] Trapeznikov, N. N., Erenina, L. A., and Kondratyev, V. G.

1981. “Combined Methods of Osteogenic Sarcoma

Treatment: Past Experience and Perspectives for The

Future.” Reporter АМS USSR 7: 65-69.

[12] Moisenko, V. M. 2002. “Pecularities Monoclonal

Antibodies in the Treatment of Malignant Tumors.”

Practical Oncology 3 (4): 253-261.

[13] Sinyukov, P. A. 1993. Up to Date Approaches to

Chemotherapy of Osteogenic Sarcoma, Abstract Dis.

M.D., Moscow.


324

[14] Abe, S., Higaki, S., Ogawa, К. 1997. “Long Term Intensive Chemotherapy For Osteosarcoma Around The Knee–Can We Minimize the Surgical Margins and Preserve the Joint?” In Proceedings of. ISOLS meeting, New York, 179-180.

[15] Ayala, A. G., Ro Jy, and Raymond, A. K. 1996. “Chemotherapy Induced Tumor Necrosis in Conventional Osteosarcoma of Bone: An Important Prognostic Factor.” In Proceedings of 2 Osteosarcoma Research Conference, Bologna, 91.

[16] Zalyalieva, M. V., and Prokhorova, P. S. 2001. Determination methods of subpopulation of lymphocytes. №1 DP 20000774 D/P МКП 6601 №33/48 26.02.2001.

[17] Afonina, G. B., and Bordonos, V. G. 1990. “Change of Membranes Structures and Function of Lymphocytes and Neutrophilic Granulocytes in Norm and Pathology.” Immunology and Allergology 24: 103-105.

[18] Ilina, N. I., Latisheva, T. B., Pinegin, B. V., and Setdikova, N. Kh. 2000. “Secondary Immune Deficiency Syndrome (Protocols of Diagnostics and Treatment).” Immunology 5: 8-9.

[19] Imelbaeva, E. A., Khayrulina, R. M., Medvedev, Y. A., Aznabaeva, L. F., and Gilmanov, A. J. 2004. “Methodical Indications to the Lessons in Immunology and Serology:

Educational-methodical Manual for Specialists in Clinical Laboratory Diagnostics.” Ufa: BSMU.

[20] Pinegin, B. V., and Khaitov, R. M. 1997. “Immundiagnostics of Disease, Connected with Immune Disorders.” Hemotology and Transfusiology 42 (2): 40-44.

[21] Cheredeyev, A. N., Gorlina, N. K., and Kozlov, I. G. 1999. “CD-markers in Practice of Clinical-Diagnostic Laboratory.” Clinical Laboratory of Diagnostics 6: 25-31.

[22] Chukhlovin, A. B. 1999. “Increase the Apoptosis of Leucocytes in Peripheral Blood Due to the Development of Leucopenia after Intensive Chemotherapy.” Questions of Oncology 45 (4): 384-387.

[23] Solovyev, Yu .A. 2000. “Cytokin Production in Patients VID in Dynamics of Immunocorrelating Therapy.” Allergology and Immunology 1 (2): 34.

[24] Filchenkov, A. A., Stepanov, Y. M., Lipkin, V. M., and Kushlinskiy, N. E. 2002. “Participation of Systems FAS/FAS-ligand in Regulation of Homeostases and Functioning of Immune System Cells.” Allergology and Immunology 3 (1): 24-35.

[25] Freidlin, I. S., Kuznetsova, S. A. 1999. Immune Complexes and Cytokines, Medical Immunology 1 (1-2): 27-36.


From Awareness to Action Using the Survey Feedback

Method

Ann Fridner1, 2, Birgit Pingel1, Lise Tevik Løvseth3, Marie Gustafsson Sendén1, 2 and Karin Schenck-Gustafsson2

1. Department of Psychology, Centre of Gender Medicine, Karolinska Institutet, Stockholm University, Stockholm, SE-10691,

Sweden

2. Centre of Gender Medicine, Karolinska Institutet, and Cardiac Unit, Department of Medicine, Karolinska University Hospital,

Stockholm, SE-10691, Sweden

3. Department of Research and Development Trondheim, St. Olavs University Hospital, Norway

Received: June 17, 2014 / Accepted: July 18, 2014 / Published: July 30, 2014. Abstract: Reports from European university hospitals show an increase in work-related mental strain. Four European university hospitals started a comprehensive research program called Health and Organisation among University hospitals Physicians in Europe—the HOUPE Study in the year 2003. Based on the results from the HOUPE study, the authors conducted an intervention project together with HR-consultants at one of the participating hospitals. A collected cross-sectional survey in 2005 among permanently employed academic physicians (N = 1800, response rate 60%) at Karolinska University Hospital in Sweden. Results from the study were used in survey feedback seminars (N = 250). This method is a way of systematic collection of data to process and give feedback to the organisation’s members in order to initiate organisational change. By providing results based on the total sample, on each division, and unpublished data from each clinic the authors aimed to improve physicians’ health and work satisfaction and thereby enhance the health of the physicians. Feedback seminars can arouse many emotions and might make people defensive. The role of resistance in the process of change is a paradox in that resistance slows down change. However, without resistance there will be no change at all. The authors conducted 20 feedback seminars of three hours duration where results were discussed relating mainly to the psychosocial work environment, psychological distress, and career paths, i.e., job demands, control at work, social interactions, leadership, commitment to the organisation, harassment at work, burnout, depression and suicide ideation. Altogether, 250 physicians participated in these meetings. To achieve acceptance for organisational change, data about relevant conditions in the organisation have to be processed in a systematic way in collaboration with all those who will benefit from changes, in concrete work units as divisions and clinics. Key words: Work interventions, HR-consultants, physician health.

I. Introduction

Reports from European university hospitals show an

increase in work-related mental strain, and increased

turnover rates among university hospitals physicians [1,

2]. Physicians face a heavy burden of work stressors,

whose contribution to psychological distress is

increasingly [3]. Physicians are at risk of burnout,

depression, and suicide [4, 5]. Physicians who are

mentally distressed are more likely to report making

Corresponding author: Ann Fridner, Ph.D., associated

professor, research fields: public health, work and organizational psychology, clinical psychology, gender medicine. E-mail: [email protected].

recent medical errors, to score lower in assessments

measuring empathy, to plan to retire early, and to have

higher job dissatisfaction, which have been associated

with reduced patient satisfaction [6-8]. Physicians seek

help to a lesser degree and later in the course of disease

than do other groups, and they appear to be especially

reluctant to seek help for mental health problems due to

concerns about confidentiality [9, 10].

Academic medicine is responsible for several

important tasks associated with improving the health of

the public, such as education, patient care, and clinical

research. Recent research has shown an increased

attrition from positions in academic medicine [11]. In

DAVID PUBLISHING

D

From Awareness to Action Using the Survey Feedback Method

326

2003, four university hospitals started a comprehensive

research program called Health and Organisation

among University hospitals Physicians Europe—The

HOUPE study. This project aims to provide a

systematic investigation of how research activity, work

conditions, gender equality, and career advancement,

affect the health and wellbeing of physicians. Based on

the results from the HOUPE study the authors

conducted an intervention project with academic

physicians at Karolinska University Hospital in

Sweden. By presenting data from different

organisational levels within one hospital, the authors

aimed to ameliorate working conditions and thereby

enhance the health of physicians. When data are seen as

objective and specific, new social facts about one’s

own organisational situation become a more significant

force for change than general principles about human

behaviour used in psychology theory. For participants,

the more meaningful, relevant and understandable the

material is, the greater the likelihood of change [12].

Past literature on survey feedback often deals with

how to change opinions and attitudes of individuals in

different organisations in a top-down fashion. The

employee is expected to experience the organisation

and the working environment in a new way [13], and

thereby be able to create and implement changes in the

workplace. The current project primarily used a

bottom-up design in which the authors obtained a

record of the physicians’ experiences of their work

environment and their suggestions for changes as

outcome. The study was interactive and the researchers

sought knowledge together with those concerned.

Assessment of wellbeing using valid instruments

creates a common language that can help physicians

and their organisation to address well-being issues.

2. Case Description

The authors used a cross-sectional survey among

academic physicians permanently employed at a

governmental university hospital in Sweden (N = 1800,

response rate 60 %). Assessment instruments:

Physician Career Path Questionnaire, General Health

Questionnaire-12, Mini Oldenburg Burnout Inventory,

Question About Suicidal Ideation and Attempted

Suicide, and selected scales from the Questionnaire

about Psychological and Social Factors at Work

[14-18]. All scales are presented in Fridner, et al. [4, 5,

9]. The results of the survey were presented (Fig. 1)

during meetings with: the management of the hospital

(level 1), management of eight divisions (level 2), the

local medical association, and the HR departments

(level 1 and 2). Written reports were distributed to

levels one and two [19]. The third level included clinics

with at least 50 physicians before data were presented.

If fewer physicians were working in the clinic, clinics

were merged. Clinical data were only presented during

the feedback meetings.

The survey feedback method means making a

systematic collection of data, which is then processed

and fed back to the organisation’s members. A

distinction is made between a top-down and a

bottom-up method. In the project, the authors used both

top-down and bottom-up methods, i.e., the authors

started by giving back compiled data to the

management of the hospital, management of the eight

divisions, the local physician’s association and the

central HR-department. Then physicians working in all

clinics were invited to participate in a survey feedback

seminar with the aim of suggesting changes in their

own work places as well as in the organisation.

Seminar proceedings were as follows:

Introduction by the head of clinic and

HR-consultant

Presentation of results (researcher)

Group discussions

- How the physicians think and feel regarding the

responses they have studied today.

- What are the physicians good at, and what can

they do better?

All groups presented their discussions

A researcher from HOUPE documented the

seminars and wrote a report on each


327

Fig. 1 HOUPE survey feedback model.

3. Discussion and Evaluation

Feedback seminars can arouse many emotions and

might make people defensive but resistance might

precede deeper awareness [20]. This was quite obvious

during feedback seminars. The most common criticism

was about the questionnaire used, i.e., the items were

wrong, and the researchers were responsible for the

response rate not being even higher (60%). Gender

equality was not an issue considered worth discussing.

Male physicians could not believe the answers

concerning the frightening conditions that female

physicians had described. Comments like “Physicians

are selected people. You do not need to be Einstein to

grasp it, therefore I will not explain it to you” indicated

a great amount of stress. The role of resistance in the

process of change is paradoxical. The paradox is that

resistance slows down change, but without resistance

there is no change at all [21]. If change has no roots

among those concerned, there is a risk of increased

frustration with malfunctioning structures. Through

feedback seminars the physicians were given an

opportunity to show their spontaneously aroused stress,

and during the group discussions they gained a deeper

awareness about the truth of the results and were able

to suggest constructive changes in working conditions.

A regular iterative process of enquiry and feedback

from physicians could identify barriers to improvement

and issues that negatively affect wellbeing. The written

reports from the feedback seminars, distributed only to

each clinic, represent the technical foundation for

change.

All employed physicians, the hospital management

and HR-consultants received a written report in which

the results from the overall survey were presented, as

well as the results from each division. In this way, the

physicians were able to compare their results with the

rest of the hospital. For instance, comparing data on

burnout showed that the laboratory division had low

percentages of burnout, while the thorax division and


328

oncology division had higher rates. In all, 250

physicians participated in a three-hour survey feedback

seminar.

The HOUPE project manager, the head of clinic, and

the HR-consultant were responsible for the feedback

process at each clinic. Feedback meetings were held to

discuss results related mainly to the psychosocial work

environment, psychological distress and career paths,

i.e., job demands, control at work, social interactions,

leadership, commitment to the organization,

harassment at work, burnout, depression and suicide

ideation. Out of 27 invited clinics/merged clinics, 20

were participating in feedback meetings at the hospital.

It was recommended that feedback seminars should

lead to a written action plan specifying concrete

specific activities, which should be integrated in the

different clinics’ action plans. An action plan with

concrete activities enhances the improvements regarding

factors in the work organisation [22]. Researchers

documented the seminars and wrote written reports for

each of them. A composite report presented the

feedback processes during all meetings [23].

What this paper adds

It demonstrates how the feedback process is original

by:

(1) Showing the resistance, anger and stress about

the survey results.

(2) Addressing results in a constructive way.

(3) Showing that written reports and informative

meetings with HR-consultants, head of clinics and

research team together with the physicians provide a

basis for joint efforts towards change.

4. Funding

AF: Vinnova (Dnr 2002-01943, 2005-00749,

2008-02262) and KSG: Centre of Gender Medicine,

Karolinska Institutet and Erica Lederhausen foundation.

5. Competing Interests

There is no competing interest for any of the

authors (neither financial nor other).

6. Authors’ contribution

AF designed the study. AF, KSG and LTL were

responsible for data collection and are guarantors of the

study. AF and LTL prepared the data sets. AF, BP and

MGS reviewed the literature. AF and BP conducted the

interventions, and wrote the drafts of the manuscripts.

All authors read and approved the final manuscript.

Acknowledgement

The authors are grateful to the physicians who

participated in this study. The authors thank the entire

HOUPE Study Research Group.

References

[1] Misra-Hebert, A. D., Kay, R., and Stoller, J. K. 2004. “A Review of Physician Turnover: Rates, Causes, and Consequences.” Am J Med Qual 19: 56-66.

[2] Wallace, J. E., Lemaire, J. B., and Ghali, W. A. 2009. “Physician Wellness: A Missing Quality Indicator.” Lancet 374: 1714-1721.

[3] Tyssen, R. 2007. “Health Problems and the Use of Health Services among Physicians: A Review Article with Particular Emphasis on Norwegian Studies. [Review].” Ind Health 45: 599-610.

[4] Fridner, A., Belkic, K., Marini, M., Minucci, D., Pavan, L., and Schenck-Gustafsson, K. 2009. “Survey on Recent Suicidal Ideation among Female University Hospital Physicians in Sweden and Italy (The Houpe Study): Associations with Work Stressors.” Gender Medicine 6: 314-328.

[5] Fridner, A., Belkic, K., Minucci, D., Marini, M., Putoto, G., Simonato, P., and Schenck-Gustafsson, K. 2011. “Work Environment and Recent Suicidal Thoughts among Male University Hospital Physicians in Europe (HOUPE) Study.” Gender Medicine 8: 269-279.

[6] Taylor, C., Graham, J., Potts, H., Candy, J., Richards, M., and Ramirez, A. 2007. “Impact of Hospital Consultants´Poor Mental Health on Patient Care.” BMJ 190: 268-269.

[7] Leiter, M. P., Frank, E., and Marheson, T. J. 2009. “Demands, Values, and Burnout. Relevance for Physicians.” Can Fam Physician 55:1224-5.e1-6.

[8] Orton, P., Orton, C., and Gray, D. P. 2012. “Depersonalised Doctors: a Cross-Sectional Study of 564 doctors, 760 Consultations and 1876 Patient Reports in Uk General Practice.” BMJ Open 2: e000274.

[9] Fridner, A., Belkić, K., Marini, M., Gustafsson Sendén, M., and Schenck-Gustafsson, K. 2012. “Why Don´t


329

Physicians Seek Needed Professional Help for Mental Distress?” Swiss Med Wkly 142: w13626.

[10] Løvseth, L. T., Aasland, O. G., Fridner, A., Schenck-Gustafsson, K., Jónsdóttir, L. S., Einarsdóttir, T., Marini, M., Minucci, M., Pavan, L., Götestam, K. G., and Linaker, O. M. 2013. “Psychosocial Work Factors as Moderators of Confidentiality as a Barrier to Seeking Social Support. A Cross-Sectional Study of University Hospital Physicians in Four European Cities [the HOUPE Study].” Work 09/2013; doi:10.3233/WOR-131725.

[11] Pololi, L., Krupat, E., and Brennan. R. 2012. “Why Are A Quarter of Faculty Considering Leaving Academic Medicine? A Study of Their Perceptions of Institutional Culture And Intenion to Leave at 26 Representative U.S. Medical schools.” Academic Medicine 87: 858-869.

[12] Mann, C., F. 1961 Studying and Creating Change. In the planning of change, edited by Bennis, W. G., Benne, K. D., and Chin. R. New York: Holt, Rinehart, and Winston.

[13] Elo, A-L., Leppänen, A., and Sillanpä, P. 1998. “Applicability of Survey Feedback for an Occupational Health Method in Stress Management.” Occupational Medicine 48: 181-188.

[14] Fridner, A. 2004. “Career Paths and Career Patterns among Physicians with a Ph.D.” Ph.D. thesis, Uppsala University, Department of Psychology.

[15] Goldberg, D., and Williams, P. 1991. A user’s Guide to the General Health Questionnaire. London: Nfer-Nelson.

[16] Demerouti, E., Bakker, A. B., Vardakou, I., and Kantas, A. 2003. “The Convergent Validity of Two Burnout

Instruments: A Multitrait-Multimethod Analysis.” Eur J Psychol Assess 19: 12-23.

[17] Meehan, P. J., Lamb, J. A., and Saltzman, L. E. 1992. “O’Carroll PW. Attempted Suicide among Young Adults: Progress Toward a Meaningful Estimate of Prevalence.” Am J Psychiatry 149: 41-44.

[18] Lindström, K. 2002. User’s Guide for the QPS Nordic General Nordic Questionnaire for Psychological and Social Factors at Work. Copenhagen, Denmark: Nordic Council of Ministers.

[19] Fridner, A., Pingel, B., and Hansen, N. 2006. Läkares hälsa och arbetsvillkor vid Karolinska Universitetssjukhuset (Physicians’ Health and Working Conditions at Karolinska University Hospital). Stockholm: Karolinska University Hospital.

[20] Peiro, J., Gonzalez-Roma, V., and Canero, J. 1999. “Survey Feedback as a Tool for Changing Managerial Culture: Focusing on Users Interpretations—A Case Study.” European Journal of Work and Organizational Psychology 8: 537-550.

[21] Arhenfelt, B. 2001. Förändring som tillstånd [Changes as a state]. Lund: Studentlitteratur.

[22] Björklund, C., Grahn, A., Jensen, I., and Bergström, G. 2007. “Does Survey Feedback Enhance the Psychological Work Environment and Decrease Sick Leave?” European Journal of Work and Organizational Psychology 16: 76-93.

[23] Pingel, B., Schenck-Gustafsson, K., and Fridner, A. 2009. On Gender Inequality among Physicians—the HOUPE Study. Stockholm: Stockholm City Council.


Nurse Documentation in Deteriorating Patients Prior to

In-hospital Cardiac Arrest—A Pilot Study in A Swedish

University Hospital

Lars Aas1, Maria Ouchterlony1 and Therese Djärv1, 2

1. Department of Emergency Medicine, Karolinska University Hospital, Solna, Stockholm, SE-171 76, Sweden

2. Department of Medicine in Solna, Karolinska Institutet, Stockholm, Sweden

Received: May 23, 2014 / Accepted: July 25, 2014 / Published: July 30, 2014. Abstract: Presence of abnormal vital signs prior to IHCA and consequently higher mortality has been found in numerous studies. It is unknown whether abnormal vital signs are acted upon or not and how this affects the outcome of the IHCA. Aim: Compare differences in journal notes regarding abnormal vital signs or worry by nurses up until 24 h between survivors and non-survivors after an in-hospital cardiac arrest (IHCA). Design: Pragmatic retrospective case-control study in a Swedish university hospital. Methods: All IHCA during 2007-2011 was reviewed (n = 720). Out of them, 20 (3%) fulfilled the inclusion criteria; survived 30 d, had their IHCA at a general ward, were aged > 18 years and had documented abnormal vital signs or nurse worries. Out of the non-survivors, two controls were after matching for age, sex and number of diseases randomly drawn for each case. Pearson's chi test was used to assess significance on the level of 0.05 in differences between survivors and non-survivors. Results: Of 20 survivors with preceding abnormal vital signs prior to IHCA, 15 patients (75%) had documented worries or action taken by a nurse compared to 23 patients (58%) among non-survivors (p-value: 0.258). Conclusion: The journal documentation 24 h prior to a IHCA was fairly equal in numbers between patients surviving at least 30 d afterwards compared to those not surviving, but the content of the journal notes had a slightly higher, but not statistical significant, frequency of worry or action taken by attending nurses in survivors. Keywords: In-hospital cardiac arrest, abnormal vital signs, nurse management, survival rate.

1. Introduction

Observations are a key factor when working with ill

patients at a hospital and a cornerstone in a nursing job

[1]. Unexpected patient deterioration is a normal

clinical problem at a hospital and nurses are

continuously exposed to problems such as time

pressure, not enough time spent with the patient, the

level of their clinical experience, less autonomous

manner of working, being able to communicate with

correct medical language to convey the seriousness of

the situation, proper documentation and recognizing a

worry or an issue that needs to be dealt with straight

Corresponding author: Lars Aas, master, research fileds:

nursing science, emergency medicine. E-mail: [email protected].

away [2-5]. It has been shown that with early

identification and timely patient management, patient

outcomes can be improved [5] but during an 8 h shift a

single nurse can face up to 50 significant clinical

judgments in a medical admissions unit in where

abnormal vital signs might only be one [6]. However,

since it has been found that patients expressing

abnormal vital signs have higher mortality it is

important with high nurse awareness despite many

difficult clinical judgments [7, 8]. By detecting these

abnormal vital signs timely treatment can be

administered leading to less organ dysfunction and

therefore a reduced risk of in-hospital cardiac arrest

(IHCA) [9]. One systematic approach aiming to reduce

adverse events is through the identification of early

DAVID PUBLISHING

D

Nurse Documentation in Deteriorating Patients Prior to In-hospital Cardiac Arrest —A pilot Study in A Swedish University Hospital

331

warning signals (EWS) [10, 11]. The basis of the EWS

is the constant monitoring of patients’ basic vital signs

such as respiratory rate, pulse, blood pressure and

conscious level [5, 12]. If the patient triggers any of

these EWS, appropriate actions must be taken by the

nurse and the nurse needs to decide whether an

appropriate nursing action is suitable or if more

advanced medical support is needed since these EWS

often precede cardiac arrest or death [6, 12]. In order to

increase patient safety and early identification of

deteriorating patients, effective observation and

documentation of concern regarding patients and

abnormal vital signs can be done with a standard

structure in journal entries [13, 14]. Even if it is known

that nurses tend to lack documentation in deteriorating

patients and that patients demonstrate abnormal vital

signs many hours prior to IHCA [6, 11, 15], it remains

unknown, whether these abnormal vital signs were

acted upon, i.e., noted and given appropriate attention

within the regular clinic work among all other tasks

performed simultaneously, and if this is related to the

survival of an IHCA.


2.1 Aim

To compare differences in journal notes regarding

abnormal vital signs or worry by nurses up until 24 h

between 30-days survivors and non-survivors after an

in-hospital cardiac arrest.

2.2 Design

The study design was a pragmatic retrospective

case-control study in a university hospital. The data

source used was the national cardiac arrest register

(NCAR) in Sweden as previously described in detail by

[16].

2.3 Setting

The Karolinska University Hospital (Karolinska) is

one of Europe’s biggest university hospitals. In its

region, Karolinska is especially responsible for

providing highly specialized medical care and serves as

the trauma referral center of its area. Karolinska has

about 1680 hospital beds, about 109 000 care instances

are produced every year and the hospital receives more

than 162 000 acute visits per year [17].

2.4 Participants

All IHCA at Karolinska reported to the NCAR

during 2007-2011 were reviewed (n = 720). The case

definitions (inclusion criteria’s) were age above 18

years, IHCA, survival ≥ 30 d, general ward as place of

IHCA (medical-, surgical-, geriatric-, oncology-,

neurological-, orthopedic-, ear-nose-throat-, infection-,

gynecology-, rheumatic wards and radiology

department) and one or more in journal text

documented abnormal vital sign(s) by the attending

nurse in charge according to local medical emergency

team (MET) criteria as advocated by Bell et al.[17]

(Table 1). The time frame of 30 d was chosen as

previous study done by Bell et al. [17] showed that

patients with abnormal vital signs had almost a ten-fold

increased mortality rate during the first 30 d. Exclusion

criteria’s were patients with normal or missing

information on vital signs, designated “do not attempt

Table 1 Local Medical Emergency Team criteria at Karolinska University Hospital as developed by Bell et al. (2005).

The Medical Emergency Team criteria

Acute change in respiratory rate to < 8 or > 30 breaths/min

Acute change in pulse oximetry saturation to < 90%

Acute change in heart rate to < 40 or > 130/min (beats/min)

Acute change in systolic blood pressure to < 90 mm/Hg

Acute change in conscious state

Staff member is worried about the patient.


332

resuscitation”, patients < 18 years and patients at the

various intensive care units, emergency room and

surgical theaters since these patients per definition

often had abnormal vital signs and medical teams were

working on these patients continuously. Also, a nurse

often only had one or very few patients to attend during

the shift and thus was not representative for the nurses

working at general wards.

Of all 720 patients experiencing IHCA during

2007-2011, only 20 (3%) patients met the inclusion

criteria and were identified as cases. For each case, two

controls were matched regarding sex, age group (< 30

years, 30-64 years, 65-80 years, > 80 years) and

number of diseases documented in the medical record

when admitted to the hospital (none, one, at least two).

When matching cases with controls, if there were more

than two possible controls, the control closest in age

was chosen. An acute change in consciousness was not

found in any journal notes made by the attending nurse

24 h prior to IHCA and thusly not presented any further

in this study.

2.5. Data Collection and Classification

All survivors and non-survivors were identified

through NCAR and data were drawn from the ordinary

medical record by the personal security numbers. All

medical records were reviewed by a study specific

protocol developed by experienced clinicians on the

basis of Harrisson [18] protocol and local MET

criterion (Table 1). The protocol gathered data such as

sex, age, medical history (yes or no regarding the

following conditions; cardiovascular disease, diabetes

mellitus, lung disease, kidney disease, joint disease,

psychiatric illness, cancer and other, number of

diseases at point of admission and vital signs (yes or no

according to local MET criterion, normal or missing

vital signs as illustrated in Table 1: respiratory rate,

pulse oximetry saturation, heart rate and systolic blood

pressure) in journal notes. All journal notes were

printed, given a unique number and anonymized

regarding survival status so reviewers were unaware of

dealing with a case or a control while gathering data

from the journal files to the database.

After gathering all data, medical history as grouped

into three categories (none, one, at least two) and

categorization of the vital signs and documented

actions taken according to journal notes by the nurse

was made into five categories. 1) Not noted meant that

no abnormal vital signs or nurse worry regarding

deterioration of the patient were noted in the text of the

journal notes, but numbers mentioning abnormal vital

signs was found somewhere in the journal. 2) Noted,

not acted meant that abnormal vital signs or nurse

worry for the patient was noted but no action was taken

according to the journal notes. 3) Noted, unclear acted

meant that the journal notes did not provide a clear

answer to whether action was taken in regards to the

abnormal vital signs. 4) Noted, acted upon meant that

abnormal vital signs or nurse worry for the

deteriorating patient were noted and some form of

action was taken, i.e., nursing action including

notifying the doctor in charge. Results will be

presented in these categories but since it might be of

clinical interest to know which vital sign stood out as

missed, even if numbers will be small and test for

statistical significance will not be done, data will be

presented in hypothesis generating purposes for future

studies. All matters where confusion regarding how to

classify journal notes occurred was discussed until

consensus and doubled checked for accuracy by two

independent researchers.

2.6. Ethical Consideration

The study was reviewed by the regional ethics

committee in Stockholm, Sweden.

2.7. Data Analysis

Descriptive statistics were used for survivors and

non-survivors (median and range for age, length of stay,

time of journal note prior to IHCA and number of

journal notes and frequency for gender, number of

diseases at time of admission, time of IHCA, journal


333

notes showing worry and vital signs). Also, comparative

statistics (Pearson Chi-square) were used to analyze

differences between survivors and non-survivors

regarding the number of diseases at admission and

hours before IHCA showing worry by the attending

nurse in journal notes. All analysis was performed

using the statistical computer software, SPSS, version

17.0.

3. Result

3.1 Participants

The survivors had a median age of 68 and consisted

of 11 men (55%) (Table 2). There was one survivor

with no diseases, eight with one disease and 11 with

two or more diseases at time of admission (Table 2).

Regarding type of medical history, the most common

was cardiovascular disease in both survivors as well as

non-survivors (85% and 60%, respectively) as well as

the second most common disease was cancer for

survivors as well as non-survivors (30% and 40%,

respectively). The frequency of diabetic and lung

disease was slightly higher in non-survivors than

survivors. The reason for admission into hospital was

mainly linked to heart problems for survivors (5

patients, 25%) but even abdominal problems (4

patients, 20%) and planned operations/visits (4 patients,

20%) were reason for admission. Among the

non-survivors, respiratory problems (9 patients, 23%)

and infection (8 patients, 20%) were the two main

reason for admission (data not shown). The median

length of hospitalization prior to IHCA was 13 d (range

2 to 58 d) in for survivors but shorter in non-survivors

(4 d, range 1 to 70 d). Time of cardiac arrest was

distributed fairly equally over the 24 h period with

slightly more cardiac arrest during daytime in

non-survivors than survivors (Table 2). Table 2 Description of adult patients suffering an in-hospital cardiac arrest (ihca) in a general ward at Karolinska University Hospital between the years 2007 to 2011 and surviving at least 30 d afterwards (survivors) compared to matched* controls not surviving at least 30 d.

Characteristics Survivors Number (%) 20 (100)

Non-survivors Number (%) 40 (100)

P-value

Age (years) NA

Median (range) 68 (48-90) 67 (43-90)

Gender NA

Male 11 (55) 22 (55)

Female 9 (45) 18 (45)

Number of diseases at admission

0 1 (5) 2 (5) NA

1 8 (40) 16 (40) NA

2+ 11 (55) 22 (55) NA

Length of stay in days

Median (range) 13 (2-58) 4 (1-70) 0.108**

Time of IHCA 0.287**

Daytime 4 (20) 18 (45)

Evening 6 (30) 9 (23)

Nighttime 5 (25) 12 (30)

Hours before IHCA showing worry by the nurse in journal notes

Median (range) 11 (1-24) h 12 (1-24) h 0.788**

Journal notes showing worry 15 (75) 23 (58) 0.258**

*Each case was matched to two controls according to sex, age group (< 30, 31-64, 65-79, > 80) and number of disease(s) (0, 1 or at least 2) ** Pearson Chi-Square


334

3.2 Documentation Prior to Cardiac Arrest

3.2.1 Frequency of Journal Notes and Nurse Worry

In both survivors and non-survivors, the frequency

of journal notes written were high (95% and 90% had

at least 1 note, respectively) 24 h prior to IHCA as well

as the median number of notes per patient were similar

between survivors and non-survivors (4 and 3

respectively during the 24 h period prior to IHCA).

These notes could concern anything from signs of

deterioration, the nurse meeting with next-of-kin,

planning for future care outside the hospital or the

general condition of the patient. When looking at the

time interval from the journal note to the IHCA, results

were similar between survivors and non-survivors in

time range (1-24 h in both groups) and median time (11

h and 12 h, respectively) (Table 2).Out of all journal

notes, the survivors had a higher frequency of notes

containing a nurse worry and a nursing action than the

control group (75% and 58% of all notes contained

nurse worry or nursing action, respectively).

3.2.2 Documentation of and Actions Taken Against

Abnormal Vital Signs

Looking at journal notes documenting abnormal

vital signs regardless of the number of journal notes

made in each case or control, it was found that 7

survivors (35%) versus 9 non-survivors (29%) in total

were classified as Not noted (Table 3) due to one or

more in the medical file registered abnormal vital signs

not mentioned as text in the journal notes.

Noted, not acted journal notes was found in 5

survivors (25%) compared to among 4 non-survivors

(10%) with abnormal vital sign(s) noted in journal

notes but not acted upon. The Noted, unclear acted

classification was not found in any patient.

Noted, acted upon was the classification with the

most frequent journal notes made regarding notification

of abnormal vital sign(s) and actions taken to remedy

the abnormal vital sign(s). 12 patients among the

survivors (60%) as well as 21 patients (53%) among

the non-survivors had one or more documentations of

Table 3 Number of abnormal vital signs (respiratory rate, saturation, heart rate and blood pressure) presented in the classifications; Not noted, Noted, not acted and Noted, unclear acted, based on the journal entries from the study group at Karolinska University Hospital between the years 2007-2011 among adult patients suffering an in-hospital cardiac arrest at a general ward and surviving at least 30 d afterwards compared to matched* controls not surviving at least 30 d.

Classification Survivors Number (%) 20 (100)


P-value

Not noted 7 (35) 9 (23) 0.359**

Noted, not acted 5 (25) 4 (10) 0.144**

Noted, unclear acted 0 (NA) 0 (NA)

Noted, acted upon 12 (60) 21 (53) 0.783**

*Each case was matched to two controls according to sex, age group (< 30, 31-64, 65-79, > 80) and number of disease(s) (0, 1 or at least 2) ** Pearson Chi-Square

Table 4 Number of missing recorded vital signs in journal notes at Karolinska University Hospital between the years 2007-2011 among adult patients suffering an in-hospital cardiac arrest at a general ward and surviving at least 30 d afterwards (cases) compared to matched* controls not surviving at least 30 d.

Missed Vital sign

Survivors Number (%) 20 (100)


Respiratory rate 15 (75) 32 (80)

Saturation 1 (5) 6 (15)

Heart rate 0 (0) 10 (25)

Blood pressure 2 (10) 10 (25)


335

abnormal vital sign(s) in their journal notes.

4. Discussion

This pragmatic retrospective case-control study in a

university hospital demonstrated that journal

documentation 24 h prior to a IHCA was fairly equal in

numbers between patients surviving at least 30 d

afterwards compared to those not surviving, but the

content of the journal notes had a slightly higher, but

not statistical significant, frequency of worry or action

taken by attending nurses in survivors. The equal

frequency of journal notes in the 24 h interval prior to

IHCA might indicate a frequent contact with the patient

during. Respiratory rate was found to be missing in a

majority of journal notes whilst heart rate was noted in

all survivors. Weakness of the study include the small

numbers of cases identified, due to narrow selected

inclusion criteria to assess the hypothesis of a

difference in nurse documentation as a proxy for nurse

awareness prior to a IHCA in survivors compared to

non-survivors. Initially it was thought that the study,

with its 720 patients with IHCA, would give more than

20 cases. The researchers chose not to prolong the time

period to gather more cases since clinical practice and

awareness of vital signs likely have improved over the

years. Another limitation was the lack of possibility of

measuring what actions, worries or thoughts were not

noted in the journal notes. A prospective study could

remedy this, however the author believe there exists no

difference between case and control groups since it is

unknown for the attending nurse that the patient will

suffer IHCA within 24 h when the journal notes were

documented.

Strengthens of the study include the matched

case-control design, access to the NCAR, the range of

the study enveloped four years and included initially all

IHCA reported at the hospital. The pre-determined

protocol provided transferability along with audit

ability and data was as far as possible anonymized for

cases and controls which increased reliability. Another

strength is the use of established well-known objective

MET criteria as well as priori decided study protocol

based on Harrisson et al.´s study from 2005. The

finding of a median time of journal notes of 11 h prior

to IHCA in survivors might mask a deterioration of the

patients the hours closest to the IHCA since Hillman et

al. [15] found that the presence of antecedents prior to

IHCA were slightly higher 0-8 h prior to IHCA than

8-48 h prior to IHCA. Looking at the number of

patients with documented worry or action taken by the

nurse, the number varied from over two-thirds in the

survivors compared to just over half in the

non-survivors. The portion with notes is in line with

previous studies demonstrating notes in about half to

two thirds of the patients [15, 19, 20, 22]. On possible

reason for journal notes classified into the categories

not noted and noted, not acted might be due to

multitasking, in a study by Berg et al. [21],

multitasking information exchange was found in

almost half of the total number of observed activities.

This high number of activities made when multitasking

the very important activity, information exchange,

could be a reason result in easily get lost or forgotten

information. The lack of action taken noted in these

journal notes is something which should prompt a

reaction seeing that studies shows an increase in

abnormal vital signs prior to IHCA [7, 8, 15, 19, 22].

The findings of this study is of importance as it

shows that attending nurses often missed to note

respiratory rate in journal notes, if this would be

repeated in larger future studies, it could prompt efforts

to educate staff in the importance of discovering EWS

in regards to the missing respiratory rates and

documenting of general vital signs on a regular basis,

encouraging staff to keep acting on their worry. The

findings of this pilot study showed that the both

survivors as well as non-survivors had a high number

of journal notes in the 24 h interval prior IHCA.

Journal notes did not necessarily show abnormal vital

signs or nurse worry, but showed that the attending

nurse had contact with the patient frequently the last 24

h thus increasing patient safety and increasing the


336

chances of detecting deterioration in vital signs of the

patient. This finding, of an equal frequent

documentation in both cases and controls together with

the high amount of notes containing information

regarding worry or vital signs might indicate high nurse

awareness.

In conclusion, this pragmatic case-control study has

demonstrated that nurse worry was more frequently,

not statistical significant, noted in journal notes prior to

an IHCA in 30 d survivors compared to non-survivors.

References

[1] Pinsky, M. R. 2007. “Hemodynamic Evaluation and

Monitoring in the ICU.” Chest 133: 1-17.

[2] Kenward, G., and Hodgetts, T. 2002. “Nurse Concern: A

Predictor of Patient Deterioration.” Nursing Times 98 (22):

38-39.

[3] Andrews, T., and Waterman, H. 2005. “Packaging: A

Grounded Theory of How to Report Physiological

Deterioration Effectively.” Journal of Advanced Nursing

52 (5): 473-481.

[4] Thompson, C., Bucknall, T., Estabrookes, C. A.,

Hutchinson, A., Fraser, K., de Vos, R., Binnecade, J.,

Barrat, G., and Saunders, J. 2007. “Nurses’ Critical Event

Risk Assessments: A Judgment Analysis.” Journal of

Clinical Nursing 18: 601-612.

[5] Endacott, R., Scholes, J., Cooper, S., McConnell-Henry,

T., Porter, J., Missen, K., Kinsman, L., and Champion, R.

2012. “Identifying Patient Deterioration: Using

Simulation and Reflective Interviewing to Examine

Decision Making Skills in a Rural Hospital.” International

Journal of Nursing Studies 29: 710-717.

[6] Cooper, S., McConnell-Henry, T., Cant, R., Porter, J.,

Missen, K., Kinsman, L., Endacott, R., and Scholes, J.

2011. “Managing Deteriorating Patients: Registered

Nurses´ Performance in A Simulated Setting.” The Open

Nursing Journal 5: 120-126.

[7] Lighthall, G. K., Markar, S., and Hsiung, R. 2009.

“Abnormal Vital Signs are Associated with An Increased

Risk for Critical Events in US Veteran Inpatients.”

Resuscitation 80: 1264-1269.

[8] Bleyer, A. J., Vidya, S., Russel, G. B., Jones, C. M., Sujata,

L., Daeihagh, P., and Hire, D. 2011. “Longitudinal

Analysis of One Million Vital Signs in Patients in An

Academic Medical Center.” Resuscitation 82: 1387-1392.

[9] Rivers, E., Nguyen, B., Havstad, S., Ressler, J., Muzzin,

A., Knoblich, B., Peterson, E., and Tomlanovich, M. 2007.

“Early Goal Directed Therapy in the Treatment of Severe

Sepsis and Septic Shock.” New England Journal of

Medicine 345: 1368-77.

[10] Hodgetts, T. J., Kenward, G., Vlackonikolis, I., Payne, S.,

Castle, N., Crouch, R., Ineson, N., and Shaikh, L. 2002.

“Incidence, Location and Reasons for Avoidable

In-hospital Cardiac Arrest in A District General Hospital.”

Resuscitation 54: 115-123.

[11] Furhman, L., Lippert, A., Perner, A., and Östergaard, D. 2008. Incidence, “Staff Awareness and Mortality of Patients at Risk on General Wards.” Resuscitation 7: 325-330.

[12] Hogan, J. 2006. “Why don’t Nurses Monitor Respiratory Rates of Patients?” British Journal of Nursing 15 (9): 489-492.

[13] Odell, M., Victor, C., and Oliver, D. 2009. “Nurses’ Role in Detecting Deterioration in Ward Patients: Systematic Literature Review.” Journal of Advanced Nursing 65 (10): 1992-2006.

[14] Stevenson, J. E., and Nilsson, G. 2012. “Nurses’ Perception of An Electronic Patient Record from A Patient Safety Perspective: A Qualitative Study. Journal of Advanced Nursing 68 (3): 667-676.

[15] Hillman, K. M., Bristow, P. J., Chey, T., Daffurn, K., Jacques, T., Norman, S. L., Bishop, G. F., and Simmons, G. 2002. “Duration of Life-threatening Antecedents Prior to Intensive Care Admission.” Intensive Care Medicine 28: 1629-1634.

[16] Källestedt, M. L., Berglund, A., Enlund, M., and Herlitz, J. 2012. ”In-hospital Cardiac Arrest Characteristics and Outcome after Defibrillator Implementation and Education: from 1 Single Hospital in Sweden.” American Journal of Emergency Medicine 30 (9): 1712-1718.

[17] Bell, M. B., Konrad, D., Granath, F., Ekbom, A., and Martling, C-R. 2006. “Prevalence and Sensitivity of MET-criteria in a Scandinavian University Hospital.” Resuscitation 70: 66-73.

[18] Harrisson, G. A., Jaques, T. C., Kilborn, G., and McLaws, M-L. 2005. “The Prevalence of Recordings of the Signs of Critical Conditions and Emergency Responses in Hospital Wards—the SOCCER Study.” Resuscitation 65: 149-157.

[19] Schein, R., Hazday, N., Pena, M., Ruben, B. H., and

Sprung, C. L. 1990. “Clinical Antecedents to In-hospital

Cardiopulmonary Arrest.” Critical care medicine 96 (6):

1388-1392.

[20] Stokke, T., and Kahlfoss, C. 1999. “Structure and Content

in Norwegian Nursing Care Documentation.”

Scandinavian Journal of Caring Sciences 13: 18-25.

[21] Berg, L. M., Ehrenberg, A., Florin, J., Östergren, J., and


337

Göransson, K. E. 2012. ”An Observational Study of

Activities and Multitasking Performed by Clinicians in

Two Swedish Emergency Departments.” European

Journal of Medicine 19: 246-251.

[22] Franklin, C., and Mathew, J. 1994. “Developing Strategies

to Prevent In-hospital Cardiac Arrest: Analyzing

Responses of Physicians and Nurses in the Hours Before

the Event.” Critical Care Medicine 22 (2): 244-248.


Relation of Nausea and Vomiting in Acute Myocardial

Infarction to Location of Infarct

Kooli Sami, Laamouri Noura, Raddaoui Abdelhafidh, El Heni Najla, Ghazali Hanene and Souissi Sami

Emergency Department, Regional Hospital Ben Arous, Tunis, 1089, Tunisia

Received: May 23, 2014 / Accepted: July 23, 2014 / Published: July 30, 2014. Abstract: Nausea and vomiting occur frequently in patients with acute myocardial infarction (AMI). To determine whether the incidence of nausea and vomiting in patients with AMI varies with infarct location, the authors studied 80 patients who had been admitted to the hospital for ST-segment elevation AMI. Data were prospectively collected from patients with AMI and nausea or vomiting for one year. Patients were enrolled if the diagnosis of AMI with nausea or vomiting is retained. The infarct location (i.e., inferior vs. anterior) in the patients with STEMI was determined using the established World Health Organization electrocardiographic criteria. Of the 80 patients included, nausea was reported in 44 patients (55%) and vomiting in 36 patients (45%). The mean age was 58, 1 ± 11, 8 years old, and males comprised 62 patients (77.5%). Inferior AMI was present in 47 patients (58.8%) and anterior AMI in 33 patients (41.2%). The peak serum troponin I concentrations was significantly greater in those with anterior AMI than in those with inferior AMI respectively 0.52 ± 0.28 ng/mL and 0.50 ± 0.34 ng/mL. In conclusion, nausea and vomiting are common presenting symptoms in patients with either inferior or anterior wall AMI, but their frequency is unrelated to the infarct location. Key words: Acute myocardial infarction, location, nausea, vomiting.

1. Introduction

Nausea and vomiting are common presentation of

acute myocardial infarction (AMI). The

pathophysiology of this atypical presentation remains

uncertain. Few studies have reported that nausea and

vomiting as symptoms of AMI and its location [1, 2].

To try to determine the relation between this two

symptoms and the location of AMI, the authors

performed a cohort study of 80 patients admitted to the

emergency department of the hospital for AMI.

2. Methods

Data were prospectively collected from patients with

AMI and nausea or vomiting for one year: October

2010 to September 2011. Subjects were enrolled if the

diagnosis of AMI with nausea or vomiting is retained.

The infarct location (i.e., inferior vs. anterior) in the

patients with STEMI was determined using the

Corresponding author: Kooli Sami, doctor, research field:

practioner. E-mail: [email protected].

established World Health Organization

electrocardiographic criteria and was confirmed by an

experienced cardiologist. The anterolateral, lateral and

the anteroseptal infarcts were classified as anterior. The

inferoposterior and inferolateral infarcts were

classified as inferior.

Data were collected and treated using SPSS 18.0.

3. Results

Of the 80 patients with AMI, 47 (58%) were

diagnosed with inferior wall AMI and 33 (42%) with

anterior wall AMI. The baseline characteristics of the

patients with inferior and anterior wall AMI were

similar (Table 1). The peak serum Troponin I

concentration was significantly higher greater in

patients with anterior AMI than in those inferior AMI.

The vast majority of patients in each infarct group were

treated using thrombolytic agents 70 patients (87.5%)

with success in 62.4% of patients.

Nausea was reported at clinical presentation in 51%

of patients with inferior AMI and 60% of patients with

DAVID PUBLISHING

D

Relation of Nausea and Vomiting in Acute Myocardial Infarction to Location of Infarct

339

Table 1 Baseline characteristics.

Characteristic Inferior AMI N = 47

Anterior AMI N = 33

P value

Age (years) 58.1 ± 11.8 57.6 ± 9.4 0.62

Men 33 29 0.73

Smokers 30 28 0.28

BMI (kg/m2) 26.97 ± 2.46 26.8 ± 2.84 0.42

History of hypertension 18 12 0.27

History of diabetes 15 8 0.54

Troponin I ng/mL 0.50 ± 0.34 0.52 ± 0.28 0.02

Table 2 Nausea vomiting on presentation stratified by AMI location.

Symptom Inferior AMI N = 47

Anterior AMI N = 33

P value

Nausea 24 20 0.12

Vomiting 19 17 0.39

anterior AMI. Vomiting was reported at presentation

40% of the patients with inferior AMI and 51% of

patients with anterior AMI. These two differences were

not statistically significant (Table 2).

4. Discussion

Few studies evaluated the relation of nausea and

vomiting with both STEMI and non STEMI [3]. In

those studies, these two symptoms seems to occur

much more in STEMI leading to the hypothesis that the

stimulus might be located in the epicardial portion of

the left ventricle [4, 5].

Nausea and vomiting can be prominent symptoms in

patients experiencing AMI without precordial pain [6].

In the authors’ study, almost all patients have chest

pain or epigastric pain associated with these two

symptoms. Nausea was reported in 55% of their

patients and vomiting in 45%. Although, a slightly

greater numeric incidence of nausea and vomiting was

recorded for the inferior than for the anterior AMI

group (respectively 43 vs. 37), the differences were not

statistically significant and were probably of little

clinical relevance.

5. Conclusions

Nausea and vomiting are common presenting

symptoms in patients with either inferior or anterior

wall AMI, but their frequency is unrelated to the infarct

location. Other studies with a greater number of

patients will be helpful to confirm this hypothesis.

References

[1] C̆ulić, V. 2012. “Nausea and Vomiting in Acute

Myocardial Infarction.” The American Journal of

Cardiology 109 (7): 1081.

[2] Herlihy, T., Mc Ivor, M., Cummings, C. C., Ciu, C. O.,

and Alikahn, M. 1987. “Nausea and Vomiting during

Acute Myocardial Infarction and Its Relation to Infarct

Size and Location.” Am j Cardiol 60: 20-22.

[3] Kirchberger, I., Meisinger, C., Heier, M., Kling, B.,

Wende, R., Greschik, G., Von Scheidt, W., and Kuch, B.

2011. “Patients-reported Symptoms in Acute Myocardial

Infarction: Differences related to ST-segment elevation.” J

Intern Med 270: 58-64.

[4] Gnecchi, T., Ruscone, S., Guzzetti, F., and Lombardi, R.

1986. “Lack of Association Between Prodromes Nausea

and Vomiting, and Specific Electrocardiographic Patterns

of Acute Myocardial Infarction.” International Journal of

Cardiology 11 (1): 17-23.

[5] Shakoor, M. T., Sher, F., and Shah, S. F. 2008. “Incidence

of Atypical Presentation of Myocardial Infarction.”

Pakistan Heart Journal 48 (1-2): 15-20.

[6] Park, C. B., Hwanq, H. G., Jo, B. H., and Kim, C. J. 2013.

“Acute Myocardial Infarction Patient with Recurrent

Vomiting: What is the Best Treatment.” International

Journal of Cardiology 162 (3): 56-57.


Mental Health Predictor of the Sixth Batch Indonesian

Nurse and Certified Care Worker Candidates Migrate to

Japan under the Japan–Indonesia Economic

Partnership Agreement in Pre-migration Stage

Susiana Nugraha and Yuko Ohara-Hirano

Nagasaki University, Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, 852-8520, Japan

Received: May 12, 2014 / Accepted: June 23, 2014 / Published: July 30, 2014. Abstract: Under the JI-EPA (Japan-Indonesia Economic Partnership Agreement), approximately one thousand nurse and certified care worker candidates have been migrated to Japan since 2008. Migration has been known as a risk factor of mental well-being. Little is known about how the in pre-migration stage may affect the migrant’s mental health. The study examines the mental health predictor in pre-migration stage using cross sectional design. Gender, Age, EPA course, educational degree, working background, language proficiency, motivation for migration and knowledge about destination country selected as mental health predictor. The results showed

that the variable knowledge about living environment is the only independent variable which is correlate with GHQ in the model, =

-0.20, P < 0.05. The finding may assume that the knowledge as part of cognitive preparation plays important role in explaining the mental health of the EPA candidates in pre-migration stage. Key words: Nurse, certified care worker, pre-migration, mental health.

1. Introduction

International migration has been becoming a fact of

current modern life and increasing by the year. Boosted

by the forces of globalization, uneven development and

demographic changes, migration has become a

defining feature of economic, social and political life in

a mobile world [1]. People migrate to improve their

well-being, through economic expansion and social

opportunity [2]. Migration of the high skilled-worker

such as health certified care workers has been linked

with globalization and closely followed by general

trend in international migration. With an estimated

worldwide shortage of 4.3 million health care

professionals, international migration and recruitment

of health certified care worker from developing

Corresponding author: Yuko Ohara-Hirano, Ph.D.,

professor, research field: study on EPA nurse and care worker. E-mail: [email protected]/[email protected].

country to developed countries has become

pre-eminent issue in global health [3]. Nurse and

physicians have sought employment abroad for many

reasons, including high unemployment in the

health-care labor market in their home country [4]. On

the other side, there are a lot of shortage of professional

health certified care worker in some developed country

due to increasing the ageing population and technology

advancement in medical field. According to Kingma

(2008), nurse migration has become social

phenomenon which occurs in a context of increasing

global mobility and a growing competition for scarce

skills, including skills needed in the healthcare sector.

Japan is a developed country with the third world’s

highest longevity of life expectancy (84.19 years)

combined with low fertility rate (1.21/couple) [5], and

elderly population was more than 23.30% in 2011

census [6]. By 2035, predicted 33.40% of the total

DAVID PUBLISHING

D

Mental Health Predictor of the Sixth Batch Indonesian Nurse and Certified Care Worker Candidates Migrate to Japan under the Japan–Indonesia Economic Partnership Agreement in Pre-migration Stage

341

population, corresponding to one in three people, will

be elderly [7]. The increasing number of the elderly has

required several changes in policy and strategy such as

health system. Japan tried to reduce the demand for

medical services by improving social services for the

elderly and their families and providing long-term care

services [8]. Implementation of long term care

insurance encourages shifting the place for treating and

rehabilitating patients in chronic illness from hospital

to facilities for long term care, in care facilities, and

home visiting nursing. This program implementation

might also increase demand in care workforce such as

nurse and certified care worker to support the

operational of long term care facilities. The demand of

care worker personnel estimated in range 2,320,000 to

2,440,000 by the year of 2025 [9]. On the other hand,

the demand of nurse workforce also sharply have been

increasing, in line with the growing aged population,

revision of the standard ratio of nurses per patient for

quality care (from 1:10 to 1:7), the revision of medical

treatment fees, and the high turnover of nursing

personnel [10]. Although the number of nurse license

holders has been increasing, as Japanese Government

optimistically calculate [11] geographic imbalanced of

nurse workforce has been increasing. Hirano pointed

out that most of the nurse especially fresh graduate

nurses tend to work in highly-equipped hospital instead

of working in midsize or small hospital in rural area

[12]. Eventually, as shown in scenarios presented by

Fushimi and Kobayashi (2013) on the long term

perspectives of the demand of practice nursing

personnel, in 2025, the demand of the nurses are out of

supply.

Considering the above condition, in 2008, Japan

started to globalize their health human resources by

opening labor market for foreign nurses and certified

care worker under Economic Partnership Agreement

with some South East Asian countries including

Indonesia, Japan–JI-EPA (Indonesia Economic

Partnership Agreement) is a bilateral trade agreement

between Indonesia and Japan outlining certain term to

facilitate trade relation and favorable trading term. On

the other hand this agreement also contains a unique

chapter named “movement of the natural person”. This

program was developed to facilitate Indonesian health

care professional to work in Japan under prescribed

condition [13]. According to the agreement,

“movement of the natural person” under JI-EPA

contains two health care professions, namely, nurse

and certified care worker. To be qualified for EPA

nurse candidate, one have to be a qualified registered

nurse under the laws and regulation of Indonesia,

having obtained Diploma III (three years professional

education) from an academy of nursing in Indonesia or

having graduated from a faculty of nursing of

university in Indonesia, with total experience as nurse

for at least two years. Whereas for the certified care

worker candidates, ones should have graduated from a

faculty of nursing or obtained Diploma III from an

academy of nursing in Indonesia without any working

experience qualification [14]. Health care migration

under JI-EPA is the first system which involves

government to government cooperation. Unlike other

migration, the program under JI-EPA is a special case

in term of policy and system. This program governed

by a bilateral agreement and underpinned by the

intention to promote free trade [13].

Under the agreement, the nurse and certified care

workers arriving under EPA are designated as

“candidate” until they pass the national board

examination for registered nurse and certified care

worker [15] despite of that they formerly have already

been as registered nurses in their home country. Under

the program, the candidates are allowed to work as

trainee at medical institution and or long term care

facilities in Japan for a maximum of three years for the

nurses and maximum of four years for the certified care

worker candidates, while learning Japanese language

and preparing for national board examination. If they

pass national board examination within the duration,

they will be licensed as registered nurse or certified

care worker, and allowed to stay in Japan as long as


342

they work as a nurse/certified care worker with three

years visa renewal, but if they fail in the examination,

they have to return to their home country [14]. National

board examination which is conducted in Japanese

language has been being noticed as a hurdle for the

candidates, as the low passing rate among foreign

examinees proved that condition [1].

Migration is the process of social change whereby an

individual moves from one cultural setting to another

for the purposes of settling down either permanently or

for a prolonged period. A basic underlying theme in the

existing literature linking migration and mental health

is that the disruptions of moving to a new environment

can negatively affect health, including mental

well-being and reducing the net benefit of the

migration [2, 16]. The migration process was

influenced by diverse psychological and social factors,

whose complex interaction affected well-being/health

[17]. The process of migration itself is not just a phase,

but a series of event, which are influenced by number

of factors prolonged period of time and these phases in

return are influenced by other factors at social and

individuals level [16]. Stillman et al. (2006) suggested

that to truly understand the effect of migration on

mental health, one must compare the mental health of

migrants to what their mental health would have been

had when they stayed in their home country. In the

context of migration, pre-departure phase can be

considered as the beginning of the migration process as

such affects the rest of migratory journey [18].

The preparation of migration undertakes their

acceptance by the new host community and the process

of migration itself are some of the macro-factors in the

origin of mental disorders [19]. The pre-migration

experiences, interpretations, and actions considerably

influenced immigration and establishing experiences.

Bughra, et al. (2011), identified the pre-migration

process that predispose individual to mental well-being

such as reason for migration, preparations, group or

singly migration, degree of control to the migration.

Socio-demographic background was also identified as

risk factor for mental health such as gender, age,

socioeconomic status, social support, and occupational

status [20].

Several studies related to the mental health of the

EPA nurse and certified care worker candidates have

been performed both qualitatively and quantitatively.

However, no studies that specifically examined mental

health condition in the pre-migration stage. Few of

them are qualitative studies conducted by Alam and

Wulansari, (2010), and Setyowati, et al. (2010), which

revealed numereus socio cultural issues faced by the

EPA candidates that may lead their job and cultural

stress in their working field namely communication

barrier, salary and rewards issues, being treated as

assistance nurse, feeling loneliness, different in

working culture, facing national board examination,

and lack of information provided during pre-departure

program. A quantitative study has been conducted by

Hirano (2012), to figure out the mental health status of

Indonesian EPA candidates leaving for Japan after the

Great East Japan Earthquake, revelaed that knowledge

about actual living and working condition in Japan is a

major indicator of the mental health of the candidates,

but not their worry concerning the earthquake.

Considering the research finding toward EPA

candidates, mental health predictor in pre-migration

stage and common mental health risk factors, this study

aimed to figure out the best model for mental health

predictors in determining mental health of the sixth

batch Indonesian EPA nurse and certified care worker

candidates in pre-migration stage.

2. Methods

2.1 Participants and Data Collection

The participants of this study were the sixth batch

Indonesian EPA nurses and certified care worker

candidates departed in 2013, with total of 156

candidates. The data collection was conducted in June

23th to 24th 2013. Before departure to Japan, the

candidates must finish 6 month Japanese language

training. The pre-departure orientation program


343

conducted few days before the departure. The

questionnaires were distributed to all candidates who

attended the pre-departure orientation which was held

in June 22nd to 24th 2013, at Depok, West Java,

Indonesia, in cooperation with the National Agency for

Placement and Protection of Indonesian Migrant

Workers (BNP2TKI). A total 148 of the candidates

have agreed to participate in the baseline study and

signed the information consent, whilst another 8

candidates did not participate in the survey.

Seven pages of questionnaire were prepared for this

study; consist of socio-demographic status, motivation

to work in Japan, preparation for going to Japan,

self-reported social support, 12 items from the GHQ

(General Health Questionnaire) in Indonesian version,

degree of knowledge on information about Japan,

Indonesian version SCAS-R (Sociocultural Adaptation

Scale-Revision), and self-rated Japanese language

proficiency. All questions were conveyed in

Indonesian language. Using computer-based statistic

software SPSS 16, the descriptive statistics analysis

conducted for describing the demographic

characteristic of the participants. Person’s correlation

coefficient and independent sample t-test analysis are

conducted for bivariate analysis and multiple linear

regression models have been selected to figure out the

correlation between mental health and its predictors.

This research has been approved by the ethical

committee of Nagasaki University.

2.2 Term and Measurement

2.2.1 Mental Health

This study selects mental health as outcome variable.

Mental health is a vital component of people

well-being. The WHO (World Health Organization)

defines mental health as a state of well-being in which

the individual realizes his or her own abilities, can cope

with the normal stresses of life, can work productively

and fruitfully, and is able to make a contribution to his

or her community (WHO, 2007). The health and

mental well-being of migrant populations is influenced

by complex and interrelated factors. According to

Ornstein (2002), the social determinants of health,

which are the socio-economic conditions that influence

the health of individuals, communities and

jurisdictions, affect both physical health and mental

health. GHQ, a self-administered instrument designed

to identify nonpsychotic psychiatric disturbance in the

community, is selected to be dependent variable. The

GHQ-12 is a measure of current mental health, which is

focus on two major areas–the inability to carry out

normal function and appearance of new and distressing

experiences [21]. GHQ has been used worldwide with

versions available in a large number of languages

including Indonesian language. The GHQ-12 is used in

this research to identify the overarching mental health

condition and coded as 1-2-3-4.

2.2.2 Socio-demographic Data

The demographic data such as Age, Gender, Final

degree, Economic status, Working background, and

Occupation they classified under the EPA program

(nurse or certified care worker) have been selected as

control variables. Basic nursing educational background

in Indonesia, divided into two basic nursing educational

pathways, namely vocational nurse and professional

nurse. The three years nursing school also called D3 is

basic nursing educational for vocational nurse.

Professional education for nursing school conducted in

two phases, whereas the academic level performed in

four years and one year for professional level. The

economic status divided into two self-reported

economic condition, i.e., “Very difficult/Difficult to

survive” and “Not so difficult to survive”. Working

background in this study was defined as “Previous

working status before applying EPA program” which is

categorize into “Working” and “Not working”. This

study categorized EPA course in nurse course and

certified care worker course.

2.2.3 Motivation for Migration

To assess motivation for migration, 16 questions

about the reason for applying to work in Japan under

EPA program were asked, which was used in previous


344

study (Hirano, 2010). From that list, 10 questions being

selected as the pull factor from the destination country

that motivated the candidates to migrate. Pull factor in

this study is defined as an attractiveness of Japan as the

destination country to encourage the candidate to

perform the migration. Ward, et al. (2001) proposed

that voluntary immigrant are pulled or attracted toward

new country in pursuit of personal familial, social,

financial and political goals and voluntarily choose to

resettle in a new country. Therefore pull factors in this

study include “I have some family/relatives who have

already lived in Japan”, “I wish to develop my

professional carrier”, “I can have chance to work in

Japan sooner than work in other country”, “I am

interested in Japanese culture such as Cartoon and

Comic”, “I wish to support my family economically”,

“I can earn a higher salary in Japan than in other

country”, “I wish to learn advanced Japanese technology

in nursing”, “I want to utilize my experience in Japan

for my future work at the hospital/elderly home in other

country”,” I want to marry Japanese partner” and “I am

not required to pay commission fees for overseas

placement”. Yes and No answers were provided and

being scored with 1 and 0.

2.2.4 Preparation for Migration

Three questions regarding with the preparation for

migration were asked with Yes and No answers as “I

contacted some of early batches of Indonesian

nurses/certified care worker who went to Japan”, “I

have started to collect information about Japanese

society and culture”, and “I have met my future

Japanese employer in Indonesia”.

2.2.5 Knowledge about Destination Country

To assess the degree of knowledge about destination

country, twenty questions were asked about Japan in

term of security, climate, working condition, the

amount of income to be earned, and how to get in touch

with Indonesian community, and etc. These questions

have been used in previous study by Hirano (2012),

with slight modification to adjust to the current

condition of the candidates.

To select the most appropriate indicators in term of

knowledge about destination country, factor analysis

using principal component analysis with Varimax

rotation in three step factor analysis was conducted.

Using confirmatory factor analysis and considering

the logic theory and previous study, the reliability and

validity of the factors and item in selected model were

assessed. The knowledge about destination country

into two factors was divided. The first factor was

labeled as “Knowledge about working condition”, and

contains of “Salary I can actually receive after

deducted with tax, insurance housing etc.”, “Kind of

nursing intervention that I can perform while I am

candidate”, “Job description of nurse/certified care

worker candidates in Japan”, and “Responsibility I

have to take/shoulder at my work place in Japan”. This

factor has been confirmed by reliability analysis with

Cronbach’s alpha = 0.70. The second factor was

labeled as Knowledge about living environment,

contains of “Security of the residential area Where I

will stay in Japan”, “whether I will welcomed by

Japanese people”, “Climate where I will stay in

Japan”, “experience of work and lives of EPA

program earlier batch from Indonesia”, and “Working

culture of Japanese such as their custom to work 2-3

hours longer than the written in the contract”. The

questions were confirmed by Cronbach’s alpha = 0.78.

2.2.6 Self-reported Japanese Language Proficiency

All of the candidates have had minimum 6 m

language training program prior the departure to Japan.

Self-reported language proficiency was used to

measure the candidate’s level of language proficiency

by providing multiple choice questions i.e. “How is

your Japanese language proficiency at this moment?”

The choices are “Advance”, “Intermediate”

“Elementary” and “Beginner”.

2.2.7 Social Support

In this study, social support is considered as the

factor that affects mental health. Moral support given

by family or relative to go to Japan is measured by

Likert scale “Very much”, “Much”, “Not so much”,


345

and “Not at all”.

2.2.8 Socio-cultural Adaptation

Socio-cultural adaptation is defined in term of

behavioral skills, as an ability to “fit in” or effectively

interact with member of the host country [22]. To

assess the socio-cultural adaptation scale, Ward and

Kennedy (1996) revealed the SCAS (socio-cultural

adaptation scale). This scale measures the amount of

behavioral and cognitive difficulties experienced by

individual when adjusting to a new culture and society.

In this research, SCAS is used to assess the level of

socio-cultural adaptation especially in pre-migration

stage. Before asking the question, an introductory

statement is used i.e., “Living in a different culture

often involves learning new skills and behavior.

Thinking about living in Japan, please rate your

competence at each the following behaviors (from 1 =

Not at all competent; to 5 = Extremely competent)”.

The score shows the level of competency in adjusting

with socio-cultural different. This scale measures the

amount of behavioral and cognitive difficulties

experienced by the candidates when adjusting to the

new culture or society [23].

3. Results

3.1 Socio-demographic Characteristics

Table 1 shows the distribution of the socio

demographic status of the study participants. The

average age is 24.61 years, with age range 21-35 years

old with 63.5% female. Percentage number of certified

care worker candidates is 71.60% while nurse

candidates are only 28.40%. All of candidates hold

nursing educational background where 68.90% are

graduated from three years diploma of nursing school

and 31.10% are graduated from the bachelor of nursing.

The current economic condition of the candidates

shows that 1.40% of the candidates are in “very

difficult to survive” condition, 42.60% in “difficult but

able to survive” condition, and 56.00% in “not so

difficult to survive” condition. The previous working

status of the candidates, before applying EPA program,

shows that 60.80% of the candidates are being

employed and 38.5% are being unemployed.

Self-rated language proficiency was administered to

identify the level of language proficiency. The results

showed that 2% of the candidates rate themselves in

“Advance level” of language proficiency, 29.70% in

“Intermediate level”, 59.50% in “Elementary level”,

and 8.80% in “Basic level”.

3.2 Bivariate Analysis

The association between each predictor variables

with GHQ as outcome variable is estimated using

bivariate analysis. Independent sample t-test and

Pearson’s correlation has been conducted to find direct

correlation between each independent variable and

GHQ. The result from t-test analysis shows that there is

significant difference of GHQ score in term of

educational background (P < 0.05) the candidates who

graduated from three years diploma nursing school

tend to have healthier mental health compare with the

ones who graduated from bachelor nursing school. In

terms of working status when applying EPA program,

the candidates who were not worked tend to have

healthier mental health compare with those who were

worked (P < 0.05). There is no significant different in

Gender, EPA course, Economic status, Motivation for

migration, and Preparation for migration with GHQ.

Pearson’s correlation coefficient test shows that the

strongest correlation with GHQ-12 score are found in

knowledge about living environment in destination

country (r = -0.38, P < 0.01), followed by knowledge

about working condition (r = -0.32, P < 0.01), Age (r =

0.24, P < 0.01), Japanese language proficiency (r =

0.24, P < 0.05), Socio cultural adaptation (SCAS) (r =

-0.22, P < 0.05), Pull factor for migration (r = -0.21, P

< 0.05) and Moral support from family/relatives to go

to Japan (r = -0.19, P < 0.05).

3.3 Multivariate Analysis

The independent variables are selected and

evaluated by multiple linear regression analysis models


346

Table 1 The distribution of the socio-demographic characteristic.

Socio-demographic characteristics n = 148

Age 24.61 (SD = 2.36) Min: 21 max: 35

Gender

Male 54 (36.50%)

Female 94 (63.50%)

EPA course

Nurse 42 (28.40%)

Certified care worker 106 (71.60%)

Education degree

Vocational level (3 years diploma) 102 (68.90%)

Professional level (4 year bachelor + 1 year) 46 (31.10%)

Current economic condition

Very difficult to survive/Difficult but able to survive 65 (44.00%)

Not so difficult to survive 83 (56.00%)

Job status when applying EPA program

Working 90 (60.80%)

Not working 57 (38.50%)

Missing 1 (0.70%)

Japanese language proficiency

Advance 3 (2.00%)

Intermediate 44 (29.70)

Elementary 88 (59.50%)

Beginner 13 (8.80%)

Average of pull factor motivation 6.95 (SD = 1.40) Range 1-10

Average moral support from family/relatives 3.53 (SD = 0.55) Range 1-4

Average socio cultural adaptation scale (SCAS) 3.50 (SD = 0.43) Range 2-105

Average knowledge about working condition 10.03 (SD = 2.08) Range 4-16

Average knowledge about living environment 12.70 (SD = 2.16) Range 4-20

Average GHQ-12 24.84 (SD = 4.46) Range 12-48

using GHQ as outcome variable. Multiple regressions

identify the best combination of predictors of the

dependent variables. Therefore, careful selection of the

predictor variable is needed. The selection variable is

based on its direct correlation with GHQ. Age, Gender

and EPA course are selected as control variables even

though there is no direct correlation with GHQ. Final

degree, working status when applying EPA program,

Japanese language proficiency, SCAS-R, pull factor

that motivate the candidate for migration, moral

support from family/relatives to go to Japan and

knowledge about working condition and knowledge

about living environment are included.

The results in multivariate analysis are as shown in

Table 2. Mental health condition of the sixth batch of

Indonesian EPA candidates are explained by the

selected predictors with R2 = 0.25, P < 0.01.

Significant correlation only found in variable

knowledge about living environment ( = -0.20).

4. Discussion

The finding in bivariate analysis revealed that

“working status when applying EPA program” and

“educational background” have significantly difference

in explaining mental health. The candidates who did

not work when applying EPA program have healthier

mental health than that of candidate who has been

working when applying EPA program. It may be


347

Table 2 Multiple regression analysis results for pre-departure mental health.

Predictor variables Beta

Age 0.15

Gender 0.07

EPA course 0.01

Educational degree 0.03

Moral support from family/relatives to go to Japan -0.11

Socio cultural adaptation scale -0.09

Knowledge about working condition -0.15

Knowledge about living environment -0.20*

Job status when applying EPA program 0.01

Japanese language proficiency 0.08

Pull factor motivation 0.07

R square 0.25

Significant 0.00

F 4.04

Number of study participant 148

*: P < 0.05

assumed that the candidates who have been working as

registered nurse when applying EPA program, faced

difficult situation because they have to quit from their

stable job. Joining the EPA program put them on the

uncertain condition whether they will be passed the

national board examination to be a registered nurse in

Japan. On the other hand, the candidates who have not

been working when applying EPA program, tend to be

more enthusiastic because this program will give them

a new job and make them exited entering new working

environment. The candidates who graduate from 3

years diploma nursing school have healthier mental

health compare with the bachelor degree. This finding

might be assumed that to join with the EPA program,

regardless their basic nursing educational degree, the

candidate will start the same level of job in Japan. This

system is adjusted to the current existing system in

Japan, whereas the national board examination has

become the main factor in determining career path [24].

Regardless the final degree in Indonesia, as long as

hold the nursing license or certified care worker license,

they can start the same level of job in nursing or

certified care worker job. On the other hand, final

degree of nursing education has the very important

role in nursing carrier development in their home

country. According to Indonesian nursing standard of

competency, the authority and competency in

performing nursing practice is based on nursing

educational background [25]. Consequently, for the

three years diploma nursing graduate, to work as EPA

candidates could be a distinct “advantage” because

they obtain the same position with BSN (Bachelor of

Nursing).

Moral support from family and relatives,

significantly correlate with GHQ. Social support is

assumed to become critically important in the

pre-migration phase because in this phase the

candidates faced fairly unstable conditions, to leave

their family and friends. The candidates who have

better social support tend to have less stress facing

pre-migration stage. Research conducted by Ryan, et al.

(2006) suggested that adequate social support may

protect those who were poorly prepared for their

migration from being depressed. In line with the

reseach conducted by Chou (2009), that perceived

social support not only significantly related to

depressive symptom reversely but also moderating the

harmful effect of poor migration planning on

depressive symptomatology in post migration.

Compare with the one who have lesser support, the


348

candidate who have better social support tend to be

mentally healthier, and they are sorrounded by the

people who support them to deal with such stressfull

event in pre-migration stage.

SCAS in pre migration stage measures the

competency level of expectation in socio cultural

adaptation after migration. The result of bivariate

analysis shows that SCAS significantly correlate with

GHQ. The candidates who have higher competency

expectation show healthier mental health.

Pre-migration socio cultural adaptation expectation

research conducted by Jasinskaja-Lahti and Yijala

(2011) revealed that the expected difficulties in

socio-cultural adapatation were directly related to

increase pre-acculturative stress. Acculturative define

as the psychological, somatic, and social difficulties

that may accompany acculturation processes, often

manifesting in anxiety, depression and other forms of

mental and physical maladaptation [26]. In other words

the competency level of sociocultural adaptation in

pre-migration stage will help the candidates dealing

with the stressful event before migration and help to

enhance their confidentiality in cultural adjustment in

the new society.

The bivariate analysis also proved that the language

proficiency significantly correlate with GHQ, whereas

the better proficiency shows healthier mental health.

Japanese language proficiency plays important role for

successful interaction with the host country’s

community. It has been noticed that Japanese language

becomes a hurdle for those who did not get accustomed

with Chinese character such as Indonesian. Mastering

Japanese language might improve and potentially

facilitate psycho-social adjustment to a host society.

Study conducted among Japanese Brazilian migrant,

found that with moderate fluency in Japanese to be

psychologically less distress [27]. Another study of

migration also cited that, communication competence

in the language of the host country language is

positively related with cultural adjustment [23, 28]. In

other words we can say in that, those who have higher

language proficiency in pre-migration stage tend to be

more confidence to migrate to Japan and keep healthier

mental health.

The study also found the significant correlation

between pull factors that motivated the candidate to

migrate to Japan. The candidates who were more

motivated by pull factors likely to have healthier

mental health. Pull factor defined as something

concerning the country to which a person migrates.

People will migrate generally because the new place

has “pull” factors that motivated their movement.

Study among Japanese Brazilian who migrate to Japan

showed that those who motivated by pull factors to

improve their quality of life in Japan, were better

equipped to tolerate with living condition in Japan [27].

Knipscheer, et al. (2000), on his study among Ghanaian

migrants in the Netherland showed that those who

motivated by pull factor in the host country were more

adapted to the host country. It may assume that the

candidate who more motivated by pull factor from the

host country tend to have better preparartion for

adjustment towards destination country.

The knowledge about destination country which

devided into knowledge about working condition and

living environment has stronger correlation with

mental health, compare with other variables.

Particularly, variable “Knowledge about living

environment” in Japan was also consistently correlates

with GHQ in multiple regression models. Whereas,

other predictor variables such as Age, Gender, EPA

course, moral support and knowledge about working

condition showed non-significant correlation with

GHQ, although the entire model have statistically

significant in explaining mental health of the sixth

batch Indonesian nurse and certified care worker

candidates in pre-migration stage. This study showed

that the knowledge about living environment become

substantial factor in determining mental health in

pre-migration stage. Bughra (2004), revealed that the

preparation for the act of migration is a significant

factor in the outcome on pre-migration stress.


349

This finding also accordance with former research

conducted by Hirano (2012) toward the fourth batch

EPA candidates who depart to Japan few months after

the East Great Earthquake (2011). The result showed

that knowledge about the actual living and working

conditions in Japan is a major indicator of the mental

health of the Indonesian nurse and certified care worker

candidates, instead of their worry concerning the

earthquake. Previous study toward the first batch also

conducted by Setyowati, et al. (2010) identified that

one of the stress predictor among the EPA candidates is

lack of information about the condition of the

destination country such as working and living

condition provided during pre-departure program. This

study finding is consistent with previous studies,

although each study subject (EPA batch) was exposed

with information about Japan in different time range.

The sixth batch exposed with six month Japanese

language training prior to migration, whereas the fourth

batch with three months language training and the first

batch have no pre-departure language training program.

This finding may assume that although the candidates

have been exposed with pre-departure language

training program in different time range, the

knowledge about living environment still becoming

their concern to be aware. Another assumption is that

the disseminated knowledge in pre-departure program

is general knowledge about Japanese society and

environment when in the fact is that the candidates will

be assigned in various working place with different

living environment. Therefore, the knowledge about

living environment still becomes a concern for the

candidates prior to migration. Degree of knowledge

about the condition of in destination country shows the

level of cognitive preparedness for migration.

Successful preparation in term of knowledge

acquisition of the new societies may lessen

psychological maladjustment prior to migration [17].

Several limitation of the present study should be

addressed where this study is based on cross sectional

data. Consequently, any findings in mental health

predictor cannot show the causal sense. Longitudinal

data are needed to figure out the causal and temporal

relation between pre-migration and post-migration.

Any finding in this research should encourage further

investigation on examining how pre-migration factors

affected mental health of new migrant in post migration

stage. Some variables measured the self-reported of

current condition; therefore the results could not be

generalized for clinical mental health condition.

However, as being noticed that mental health

measurements are measured the perceived feeling, this

study contributes to resolving the predictors of

the mental health of EPA candidate in pre-migration

stage.

5. Conclusions

In this study, the concepts of mental health were

used overarching concept, not referring to any specific

type of illness or disorder. Pre-migration defined as an

early step of migration, whereas the potential migrant

such as EPA candidates may involve in pre-migratory

activities organized by the receiving society as well as

collecting information about destination country.

Knowledge about living environment such as security

of residential area, whether they will be welcomed by

Japanese people, climate in their residence in Japan,

experience of work and life of EPA earlier batch and

working culture of Japanese, such as their custom to

work 2-3 hour longer than the written in contract

become a very important factor in determining the

candidate’s mental health. In this study, the knowledge

about living environment refers the living environment

in the future assigned working place.

Health care worker migration under JI-EPA involves

government to government cooperation. Unlike other

migration, the migration program under JI-EPA is a

special case in term of policy and system, this program

governed by a bilateral agreement under the Economic

Partnership Agreement. Some pre-migration condition

may not emerge in this study as being revealed in other

voluntary migration. Data collecting instrument


350

(questionnaire) modification might be necessary for

further study to find the most appropriate mental health

predictor in nurse and care worker migration EPA

program in pre-migration stage. However, this study

finding may become an input for both countries in

improvement for pre-departure preparation. These

finding suggests an improvement in knowledge

dissemination about the destination country.

Improvement in disseminating knowledge about

working condition and living environment, during

pre-departure orientation might become an effective

aid in dealing with pre-migration stress and assist the

candidates preparing the better adaptation with the new

living condition in destination country. Mental health

condition in pre-migration stage may affect the mental

health condition in post migration stage.

Acknowledgements

This article is part of “Study on mental health

condition of the 6th batch nurse and care worker

candidates’ under JI-EPA agreement, in pre and post

migration stage”.

This research was supported by the president's

discretionary fund of Nagasaki University, Japan

(Principal Investigator: Yuko Ohara-HIRANO).

References

[1] International Organization for Migration 2006. “Migration and Human Resouces for Health : From Awareness to Action.” Geneva: International Organization for Migration.

[2] Stillman, S., McKenzie, D., and Gibson, J. 2006. Migration and Mental Health: Evidence from Natural Experiement. Bureau for Research and Economic Analysis of Development.

[3] Taylor, A., Hwenda, L., Larsen, B., and Daulaire, N. 2011. “Stemming the Braindarin—A WHO Global Code of Practice on International Recruitent of Health Personnel.” The New England Journal of Medicine 365: 2348-2351.

[4] Bach, S. 2003. International Migration of Health Workers: Labor and Social Isues. Sectoral Activities Program

[5] WHO 2010. “World Life Expectancy.” Geneva: World

Health Organization. [6] Cabinet Office, Government of Japan. 2012. “Policies on

Cohesive Society, Cabinet Office, Government of Japan.” Accessed October 28, 2013. http://www8.cao.go.jp/kourei/whitepaper/w-2012/zenbun/s1_1_1_02.html.

[7] National Institute of Population and Social Security Research 2012. “Population Projections for Japan (January 2012): 2011 to 2060.” Tokyo: National Institute of Population and Social Security Research.

[8] Horlacher, D. E., and MacKellar, L. 2003. “Population Ageing in Japan: Policy Lessons for South East Asia.” Asia Pacific Development Journal 3: 97-122.

[9] Ministry of Health and Welfare 2012. “The Future Vision of the Integrated Reform of Social Security Service and Taxation.” Ministry of Health and Welfare.

[10] Matsuno, A. 2009. “Nurse Migration: The Asian Perspectives.” ILO Regional Office for Asia and the Pacific.

[11] MHLW 2014. “Ministry of Health Labour and Welfare, Japan.” Accessed May 5, 2014. http://www.mhlw.go.jp/file/05-Shingikai-11601000-Shokugyouanteikyoku-Soumuka/0000037613.pdf.

[12] Hirano-Ohara, Y. 2014. “Beyond the Myth of the JPEPA: Realities and Suggestion.” in Migration of Filiupino Nurses under the Japan-Philippine Economic Partnership Agreemnet—Trend and Challange, edited by Hirano-Ohara, Y., and Yonneno-Reyes, M. Manila: Nagasaki University.

[13] Ogawa, R. 2012. Globalization of Care and the Context of Reception of SouthEast Asian Care Worker in Japan. International Migration of South East Asian Care Worker to Japan under Economic Partnership Agreement.

[14] IJ-EPA Agreement. “Annex 10 referred to chapter 7-Specific Commitment for The Movement of Natural Person.” Accessed December 11, 2007. http://www.ditjenkpi.kemendag.go.id/website_kpi/Umum/IJEPA/Annex10(ID).pdf.

[15] Ohno, S. 2012. “South East Asian Nurses and Cregiving

Workers Transending the National Boundaries: An

Overview of Indonesian and Filipino Workers in Japan

and Abroad.” International Migration of South East Asian

Nurses and Care worker to Japan under Econonomic

Partnership Agreement: 541-569.

[16] Bughra, D. 2004. “Migration and Mental Health” Acta

Psychiatrica Scandinavica 109: 243-258.

[17] Burgelt, P. T., Morgan, M., and Pernice, R. 2008.

“Staying or Returning: Pre-Migration Influences on the

Migration Process of German Migrant in New Zaeland."

Journal of Community & Applied Social Psychology 18:

280-298.

[18] Gushulak, B., and MacPherson, D. 2011. “Health Aspect


351

of the Pre-departure Phase of Migration.” PLoS Medicines

8 (5): 1-7.

[19] Bughra, D., Ghupta, S., Bhui, K., Craig, T., Nisha, D.,

INGLEBY, J., Kikbride J., and Moussaoui, D. 2011.

“WPA Guidance on Mental Health and Mental Health

Care in Migrants." Official Journal of The World

Psychiatry Association 10 (1): 2-10.

[20] Tinghog, P., Hemmingsson, T., and Lundberg, I. 2007.

“To What Extent May the Association Between Immigrant

Status and Mental Illness be Explained by Socioeconomic

Factor?” Soc Psychiatry sychiatr Epidemiol 42:

990-996.

[21] Goldberg, D., and William, P. 1988. “General Health

Questionnaire (GHQ-12)." Accessed February 12, 2014.

http://shop.gl-assessment.co.uk/home.php?cat=416.

[22] Ward, C., and Kennedy, A. 1994. “Acculturation Strategy

and Psychological Adjustment and Sociocultural

Competence During Cross-cultural Transition.”

International Journal of Psychology 18 (3): 329-343.

[23] Ward, C., and Kennedy, A. 1999. “The Measurement of

Socio-cultural Adaptation.” Intrenational Journal of

Intercultural Relation 23 (4): 659-657.

[24] Japan Nursing Association 2011. “Nursing in Japan.”

Shibuya-Tokyo: Departement of International Afair Japan

Nursing Association.

[25] Indonesian Health Profession Educational Quality 2012. Accessed March 24, 2014. http://hpeq.dikti.go.id/v2/images/Produk/18.3-Draf-STANDAR-KOMPETENSI-PERAWAT.pdf.

[26] Berry, J. 2006. “Stress Perspective on Acculturation.” In The Cambridge Handbook of Acculturation Psychology, edited by Sam, L. D., and Berry, W. J. Cambridge: Cambridge University Prss.

[27] Asakura, T., and Murata, A. K. 2006. “Demography, Immigration Background, Difficulties with Living in Japan and Psychological Distress Among Japanese Brazilians i Japan." Journal Immigration Health 8 (4): 325-328.

[28] Yang, R., Noels, K., and Saumure, K. 2006. “Multiple Routes to Cross-cultural Adaptation for International Students; Mapping the Path Between Self-construals, English Language Confidence and Adjustment.” International Journal of Intercultural Relation 30 (4): 487-505.

[29] Cabinet Secretariat. 2012. “The Future Vision of the Integrated Reform of social security service and taxation.” Accessed December 24, 2013. http://www.cas.go.jp/jp/ seisaku/syakaihosyou/seihu_yotou/kourou.pdf.

[30] Yagi, N., Mackey, T. K., Liang, B. A., and Gerlt, L. 2013. “Japan-Phiulipines Economic Partnesrhip Agreement (JPEPA)-Analysis of a Failed Nurse Migration Policy.” International Journal of Nursing Studies 51 (2): 243-250.

[31] World Health Organization 2010. “World Life Expectancy.” World Health Organization.

[32] Kingma, M. 2008. “Nurses on the Move: Historical Perspective and Current Issues.” JIN: The Online Journal of Issues in Nursing 13.

[33] Hirano-Ohara, Y. 2012. “The Mental Health Status of Indonesian Candidates Leaving for Japan under the Japan–Indonesia Economic Partnership Agreement: After the Great East Japan Earthquake.” International Journal of Japanese Sociology 21.

[34] Setyowati, Susanti, H., Yetti, K., Hirano Y., and Kawaguchi, Y. 2010. “Indonesian Nurse in Japan Who Face Job and Cultural Stress in Major Problems Faced by the Nurse Candidates Working in Japan Under IJ-EPA Agreement.” Bulletin of Kyushu University Asia Center 5.

[35] Alam, B., and Wulansari, S. A. 2010. “Creative Friction :Some preliminary Consideration on the Socio-cultural Issues Encountered by Indonesian Nurses in Japan.” Bulletin of Kyushu University 5: 183-193.

[36] Setyowati, Susanti, H., Yetti, K., Hirano, Y., and Kawaguchi, Y. 2010. “The Experience of Indonesian Nurses in Japan who Face the Job and Cultural Stress in Their Work: Qualitative study.” Bulletine of Kyushu University 5:109-209

[37] Zimet, G., Dahlem, N., Zimet, S., and Farley, G. 1988. “The multidimensional scale of perceived social support.” J. Pers Assess 52: 30-41.

[38] Chou, K.-L. 2009. “Pre-migration Planning and Depression among New Migrants to Hong Kong: The Moderationg Role of Social Support.” Journal of Affective Disorder 114: 85-93.

[39] Ryan, L., Leavey, G., Golden, A., Blizard, R., and King, M. 2006. “Depression in Irish Immigrant living in London: Case-control Study.” British Journal of Psychiatry 188: 560-566.

[40] Update, J. “Indonesia Today.” Accessed October 12,

2010. http://www.jakartaupdates.com/.

[41] Jasinskaja-Lahti and Yijala, A. 2011. “The Model of

Pre-acculturative Stress—A Pre-migration Study of

Potential Migrant from Rusia to Finland.” International

Journal of Intercultural Relations 35: 499-510.

[42] Ward, C., Furnham, A., and Bochner, S. 2001. The

Psychology of Culture Shock. Philadelphia: Routledge.

[43] Knipscheer, Jong, E., De, Klebber, R., and Lamptey, E.

2000. “Ghanaian Migrants in The Netherlands: General

Health, Acculturative Stress and Utilization of Mental

Health Care.” Journal of Community Psychology 28 (4):

459-476.

[44] Ministry of Health Labour and Welfare. “Ministry of

Health Labour and Welfare.” Accessed March 25, 2014.

www.mhlw.go.jp/file/04-Houdohapyou-10805000-Iseiky


352

oku-Kangoka/0002.pdf.

[45] Ministry of Health, Labour and Welfare. “Dai 26 Kai Kaigofukushishi EPA ni Motodzuku Kokka Shiken no Kekka (The Breakdown of the 26th Care Worker National Examination Results).” Accessed March 27, 2014. Available: www.mhlw.go.jp.

[46] Fushimi and Kobayashi, M. 2013. “Chōki-teki Kango Shokuin Jukyū Mitōshi no Suikei (Estimation of the Long Term Manpower Demands and Supplies of Nursing Personnel).” Accessed May 12, 2014. http://www.mhlw.go.jp/stf2/shingi2/2r9852000000eydo-att/2r9852000000eyf5.pdf.

journal of health science 2014.7

Documents