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square test was used to determine the significance ...... Therefore, this study has the some problems of a self-answered questi- onnaire survey. ...... ILSI North America Monograph Series. Hydrati- ...... can be caused by any form of brain damage (9). Especially ...... defined size, position and form of the retinal deta- chment with ...
HealthMED

Volume 3 / Number 3 / 2009

Journal of Society for development of teaching and business processes in new net environment in B&H

EDITORIAL BOARD

Sadržaj / Table of Contents

Editor-in-chief Mensura Kudumovic

Editorial assistant Jasmin Musanovic

Our experience with evaluation of communication among

Secretaries Dzenana Jusupovic Azra Kudumovic

older patients and health workers .....................



Technical editor Eldin Huremovic

Lectors Mirnes Avdic Adisa Spahic Members Farah Mustafa (Pakistan) Yann Meunier (USA) Forouzan Bayat Nejad (Iran) Suresh Vatsyayann (New Zealand) Maizirwan Mel (Malaysia) Budimka Novakovic (Serbia) Bakir Mehic (Bosnia & Herzegovina) Diaa Eldin Abdel Hameed Mohamad (Egypt) Farid Ljuca (Bosnia & Herzegovina) Emina Nakas-Icindic (Bosnia & Herzegovina) Ago Omerbasic (Bosnia & Herzegovina) Slavica Ibrulj (Bosnia & Herzegovina) Fatima Jusupovic (Bosnia & Herzegovina) Aida Hasanovic (Bosnia & Herzegovina) Dijana Avdic (Bosnia & Herzegovina) Selma Alicelebic (Bosnia & Herzegovina) Bozo Banjanin (Bosnia & Herzegovina) Address of the Sarajevo, Bolnicka BB ditorial Board E Published by Volume 3 ISSN

phone/fax 00387 33 640 407 [email protected] http://www.healthmedjournal.com DRUNPP, Sarajevo Number 3, 2009 1840-2291

HealthMED is indexed in: - Thomson Reuters ISI web of Science - Science Citation Index-Expanded - EBSCO Academic Research Premier - Index Copernicus - getCITED, and etc.

ZmagoTurk, EvaTurk

195-203

*** Incidence of Depression and Its Demographic Correlates: Outcome of Descriptive Study at the Psychiatry OPD Penang, Malaysia ................................. 204-211 Tahir M. Khan, Syed A. Sulaiman, Mohamed A. Hassali, Syed W. Gillani, Mudassir Anwar, Khalid Hussain & Amer H. Khan

*** Ergonomic Analysis of Workload Diminution by the Use of Assistive Technical Equipment at Nursing Care . ........................................... 212-218

Jadranka Stricevic, Zvone Balantic, Zmago Turk, Dusan Celan

*** Physicians’ conceptions about various continuing medical education activities and the rol of pharmaceutical industry. Continuing medical education and pharmaceutical industry ............................. 219-224 Naim Nur, Sefa Levent Ozsahin

*** A systemic study on the protective effect of keratinocyte growth factor on type II alveolar epithelial cells against hyperoxia-induced injury in vitro ................. 225-234 Xiuxiang Liu, Changjun Lv, Xiuhong Jia, Yimin Sun, Shaodong Hua, Zhichun Feng

*** Medical nutrition prevention and medical nutrition therapy of lipid metabolism disorder Medicinska nutritivna prevencija i medicinska nutritivna terapija poremećaja metabolizma lipida . ......... 235-244 Budimka Novakovic, Jelena Jovicic, Fatima Jusupovic, Maja Grujicic, Ljiljana Trajkovic-Pavlovic, Sanja Bijelovic

*** Etiologic-epidemiologic characteristics of acute diarrheal diseases in pre-school children Etiološko-epidemiološke karakteristike akutnih dijarealnih oboljenja djece predškolskog uzrasta .............. 245-253 Sukrija Zvizdic, Mensura Kudumovic, Ines Rodinis-Pejic, Fadila Avdic-Kamberovic, Sabaheta Bektas, Lala Sokolovic, Mubera Tufekcic

HealthMED

Volume 3 / Number 3 / 2009

Journal of Society for development of teaching and business processes in new net environment in B&H

Sadržaj / Table of Contents

*** Quality of life after mastectomy of the breast cancer Kvalitet života nakon mastektomije zbog karcinoma dojke ............................................. 254-261 Samir Husic, Farid Ljuca, Sefik Hasukic, Deso Mesic

*** Clinical-genetic aspects of mental retardation of unknown etiology in selectively defined sample

Kliničko genetički aspekti mentalne retardacije kod nepoznate etiologije u selektivno definisanom uzorku . .................................... 262-266 Azra Metovic, Jasmin Musanovic, Marijana Filipovska-Musanovic, Avdo Sofradzija

*** Breast cancer patient`s quality of life compared to correctible risik factors of life style Kvalitet života pacijentica liječenih od karcinoma dojke u odnosu na korektibilne riziko faktore stila življenja ... 267-272 Sabina Saric

*** Metabolic syndrome in miners with hypertension Metabolicki sindrom u rudara sa hipertenzijom . .. 273-279 Munevera Becarevic, Fahir Barakovic, Farid Ljuca, Ajsa Tulumovic, Olivera Batic-Mujanovic

*** Skin changes and insulinemic curve changes, Conduction velocities of median and ulnar nerves: Preliminary study Kožne promjene, insulinska krivulja i kondukciona provodljivost medijalnog i ulnarnog nerva kod nedijabetičnih pacijenata; preliminarna studija ........................ 280-285 Edin Suljagic, Emir Tupkovic

*** Diabetes mellitus as a risk factor for stroke at the Neurology clinic of Clinical center of Sarajevo university Diabetes mellitus kao faktor rizika moždanog udara na neurološkoj klinici KCU Sarajevo ....................... 286-291 Salem Alajbegovic, Azra Alajbegovic, H.Resic

*** Fistula-in-ano - treatment and results in two year period Fistule anorektalne regije - tretman i rezultati u dvogodišnjem periodu ..................................... Adis Salihbegovic

292-295

*** Importance of physical activity in the patients with Diabetes Dellitus type 2 Značaj fizičke aktivnosti u oboljelih od Dijabetes Melitusa tip 2 .................................. 296-302 Edina Kuduzovic, Sabina Nuhbegovic, Farid Ljuca, Sanela Imamovic

*** Retinal detachment in the myopic eye Ablacija retine u miopnom oku ........................ Emina Alimanovic-Halilovic

303-306

*** Lung cancer risk from exposure to diagnostic x- rays Rizik za razvoj karcinoma pluća zbog izloženosti dijagnostičkom x-zračenju .............................. 307-313 Suvad Dedic, Nurka Pranjic

*** Reduction of cardiovascular risk-score in metabolic syndrome during an initial therapy with rosiglitazone Smanjenje kardiovaskularnog rizika-score kod metaboličkog sindroma tokom inicijalne terapije sa rosiglitazonom . ........................................... 314-321 Amra Macic-Dzankovic, Fuad Dzankovic, B. Pojskic, Z. Asimi

*** Results of treatment for children diagnosed with acute lymphoblastic leukemia with the bfm protocol Rezultati liječenja djece oboljele od akutne limfoblastne leukemije bfm protokolom . ............................. 322-326 Edo Hasanbegovic, Meliha Sakic, Adela Tunic, Senada Mehadzic

*** Ultrasound Assessment of Thyroid Volume in School Age Children Ultrazvučna procjena tireoidnog volumena u školske djece .................................................. 327-333 Amela Mornjakovic-Franca

*** Is chronic degenerative laryngitis in primary music teacher occupational disease - case report Hronični degenerativni laringitis kao profesionalna bolest kod učitelja muzike - prikaz slučaja ....... 334-338 Nurka Pranjic

***

Instructions for the autors ................................

339-340

HealthMED - Volume 3 / Number 3 / 2009

Our experience with evaluation of communication among older patients and health workers ZmagoTurk1, EvaTurk2 1 2

University Clinical Centre Maribor, Slovenia Instituteof Public Health of the Republic of Slovenia (IPH-RS), Slovenia

Summary Background:Old age is identified by decreasing communication abilities. Objectives: To assess the communication between older patients and nurses and physicians at the primary and secondary health care level. Materials and Methods:A prospective study was carried out between September 2006 and August 2007 at the University Clinical Centre and Community Health Centre in Maribor, Slovenia. Two questionnaires with 7 and 8 questions were composed; one for physicians and nurses, and the other for older patients (groups: 65-75, 75+). Communication was assessed with direct (grade scale 1-5) and indirect parameters (time of treatment, duration of conversation, conversation about misc. subjects etc.). Old patients were interviewed at primary and secondary health care levels (Community Health Centre and private GP offices and in hospital: departments of internal medicine, traumathology and neurology). Data were analyzed by Chi-squared test (χ²), using SPSS for Windows 11. Results:There was a statistically significant difference of communication between health care providers working at the primary and secondary levels (p < 0.001). Furthermore, female physicians spend more time with their older patients compared to male physicians (p = 0.027). Conclusion: Most older patients and health care providers assessed their communication as good. However, there is still a need for improving communication, especially at the secondary health care level. Keywords: Communication, Older patients, Nurses, Physicians, Health Care.

Introduction According to the Green paper (1), the 25 EU countries have 18.2 million inhabitants aged 80 years and over, which represents 4 per cent of the total population. In 2014, the corresponding number will rise to 5.2 percent, i.e. to 24.1 million of the total population. Like other Member States of the EU, Slovenia is facing a growing percentage of older population. In the year 2006, 19.1% of the population was above 65, and 4.8% were already over 80 years of age (2). Old age is identified by multimorbidity; older people are more prone to injuries due to decreasing functional abilities and poorer daily living quality. Physical and sensory impairments increase with old age. This also includes a decrease in communication abilities. Communication is a complex process that involves passing a message between two or more people - intentionally or unintentionally. The process is often explained by using a simple model that suggests four essential features required for communication: the source of the message to be communicated, the message to be sent, the channel for communicating the message and the receiver of the message (3). Therapeutic communication is focused on the patient and on therapeutic and rehabilitation aims, but the primary aim still remains the same – to constitute a good communication relationship. Health care providers inform patients; they help them to express their feelings and mental reactions in fulfilling somatic, mental and social needs. Different causes of communication problems in the older population include sensory deficits, dementia, environmental changes and neurological damage (4).

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Better communication can improve the quality of health care. Evidence shows that good therapeutic communication improves patient self-management and patient satisfaction (5). The potential improvements for better quality of therapeutic conversation are as follows: health care providers should use simple (non-Latin) words and devote more time for conversation with elderly people, time conflicts should be resolved and overburdening of health care providers should be alleviated. Furthermore, continued medical education and additional education in general, as well as interpersonal communication culture are needed (6, 7). While the concept of a meaningful nurse-patient communication is important in every nursing specialty, it takes on particular relevance in elderly care for several reasons. Firstly, for many older patients, the nurses form the most regular, if not the only human contact (8). Secondly, without development of a nurse-patient relationship through communication, effective nursing care is impossible. As stated by Wells (9), effective and meaningful nursing care of the elderly depends on an effective and meaningful nurse-patient relationship. Thirdly, effective communication with older patients is essential and crucial for the provision of care, which is tailored to individual needs. Communication skills are therefore necessary in enabling nurses to gather relevant information about their patients. When detailed knowledge about the patients is not gained, they frequently have multiple nursing and medical problems, as well as an increased need for social and domestic support (10 – 15). Everyday consumer demand for health care providers to adopt higher standards of communication skills has become a “leitmotiv” within the framework of “patient - centeredness” (16, 17, 18). These patient - centered skills involve relationship, partnering, counseling, and communication (19, 20, 21). Recently, patient - centered communication has been recognized as an important part of effective health care (22). Patients visiting a healthcare facility may encounter a number of healthcare professionals who may influence the quality of their experience. Therefore, patients’ opinions regarding the quality of healthcare is a multidimensional subjective indicator that cannot be understood simply by observing care directly (23). 196

The aim of this study was to assess the communication between older patients and health care providers (nurses and physicians). Furthermore, we wanted to evaluate the differences in communication with older patients at the primary and secondary special health care levels, i.e. GP and special outpatient and inpatient health care. Based on the Health Care Climate Questionnaire (HCCQ) and other available communication questionnaires in literature and on the Internet, we developed two new questionnaires with 7 and 8 items. We evaluated their reliability and validity through confirmatory factor analysis (24). The objective of the study was to assess the communication of older patients with nurses and physicians and to assess whether there are differences in the communication with older patients at the primary and secondary health care levels. Methods Development of the questionnaire Two questionnaires were developed for the purpose of this particular study: one for the health providers (nurses and physicians) and the other for older patients. The questionnaire development followed three phases: a) identification of domains and items of relevance; b) pilot assessment of validity; c) pilot assessment of reliability of scales. Health care providers were involved in the creation and selection of items to be included or modified in the questionnaire, as they are an important source of information about factors that enable or hinder them to provide high quality health care. Older patients were involved in development of the questionnaire because of the interest in their particular point of view. We supposed that suggestions made by potential respondents might have helped to create a more effective questionnaire. Relevant issues for the communication suggested by the participants of discussions about the questionnaire were: respect, solving of problems, friendliness and nonverbal communication. Problem solving communication includes attempting to resolve patients’ problems, respec-

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ting the patients’ privacy, dealing with difficult situations and controlling emotions. Respect for patients is considered fundamental for understanding and considering how patients need to be treated (25). Two main aspects of interpersonal relationships in conceptualizing provider-patient communications are emphasized (26). These two aspects are control (from dominance to submission) and affiliation (from friendliness to hostility). Health care providers’ nonverbal immediacy has been found to be related to patients’ satisfaction with care (27). Concerning the basis of HCCQ format, we developed the new questionnaires with 7 and 8 questions and rated them on a 5-point Likert scale, ranging from 1 (not at all) to 5 (very much). This questionnaire was then piloted in reliability tests with a small group of older patients and health providers, men and women with different educational levels. This resulted in some minor revisions of used items. HCCQ was recognized by all the participants of the discussion as a very good questionnaire covering important communication domains and a good basis for the development of the new questionnaire. Two questionnaires were developed for the purposes of this particular study: one for health care providers (nurses and physicians), and the other for older patients. Quality of communication was assessed with the following parameters/questions: Health care providers – communication questionnaire: Q1: Do you think you are successful in your communication with older patients? (Primary health care level vs. Secondary health care level) (Scale 1-5; 1 = no; 2 = partly; 3 = don’t know; 4 = yes; 5 = very much) Q2: Do you think you are successful in your communication with older patients? (Physicians vs. Nurses) (Scale 1-5; 1 = no; 2 = partly; 3 = don’t know; 4 = yes; 5 = very much) Q3: Did you receive enough knowledge on communication during your undergraduate education? (Physicians vs. Nurses) (yes vs. no) Q4: Time spent for patient’s treatment and communication (Female Physicians vs.

Male Physicians) (Scale 1-5; 1 = up to 5 minutes; 2 = 6-10 minutes; 3 = 11-15 minutes; 4 = 16 – 20 minutes; 5 = more than 20 minutes) Q 5: Time spent for patient’s treatment (Primary level vs. Secondary level - Physicians) (Scale 1-5; 1 = up to 5 minutes; 2 = 6-10 minutes; 3 = 11-15 minutes; 4 = 16 – 20 minutes; 5 = more than 20 minutes) Q6: Time spend for patient’s treatment (Primary level vs. Secondary level - Nurses) (Scale 1-5; 1 = up to 5 minutes; 2 = 6-10 minutes; 3 = 11-15 minutes; 4 = 16 – 20 minutes; 5 = more than 20 minutes) Q7: Time spend for communication (Primary level vs. Secondary level – Physicians) (Scale 1 – 3; 1 = up to 5 minutes; 2 = 6-10 minutes; 3 = more than 10 minutes) Q8: Time spend for communication (Primary level vs. Secondary level – Nurses) (Scale 1 – 3; 1 = up to 5 minutes; 2 = 6-10 minutes; 3 = more than 10 minutes) Older patients - communication questionnaire: Q 1: Have you been given enough time by health care providers (physicians/nurses) to explain your problem to them? (Primary health care level vs. Secondary health care level) (Scale 1-5; 1 = never; 2 = mostly not; 3 = sometimes; 4 = mostly yes; 5 = yes, always) Q 2: Have your health care providers (physicians/nurses) given you enough information about the causes and symptoms of your disease? (Primary health care level vs. Secondary health care level) (yes vs. no) Q 3: Do your health care providers (physicians/ nurses) use simple (non-Latin) language? (Primary health care level vs. Secondary health care level) (yes vs. no) Q 4: Do you follow the advice given from health care providers? (Primary health care level vs. Secondary health care level) (Scale 1-5; 1 = never; 2 = mostly not; 3 = sometimes; 4 = mostly yes; 5 = yes, always)

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Q5: Did you receive enough motivation for you treatment from health care providers? (Primary level health care vs. Secondary health care level) (yes vs. no) Q6: Do you think communication is crucial for health care among older patients? (Primary health care level vs. Secondary health care level) (yes vs. no) Q7: How do you assess the relationship between older patients and nurses? (Primary health care level vs. Secondary health care level) (Scale 1-5; 1 = very bad; 2 = bad; 3 = acceptable; 4 = good; 5 = excellent)

into those of primary and those of secondary health care levels as well as into a younger group (65-74 years) and an older group (75 years and older). 178 older people (91 women and 84 men) participated in the study. In addition, 112 nurses (6 men and 106 women; 63 at a primary health care level and 49 at a secondary health care level) and 76 physicians (42 men and 34 women; 38 at each health care level) participated in the study. The distribution of the participants in the study is presented in Table 1 and Table 2. Table 1: Distribution of older patients in the study Older patients  

Data collection

Male

Female

Total

86

92

178

65-74 years

50

35

85

> 75 years

36

57

93

Primary care level

51

50

101

Secondary care level

35

42

77

Traumatology

8

13

21

Internal medicine

16

20

36

Neurology

11

9

20

Number of patients

The study was carried out in the University Clinical Centre, Maribor, Slovenia (Department of Internal Medicine, Department of Neurology and Department of Traumathology), for research on the secondary health care level, and in the Community Health Centre, for research on the primary health care level. Patients were recruited by clinically trained staff. The sampling frame consisted of consecutive admissions of patients over 65 years of age on selected days during the period from September 2006 to August 2007, either to hospital or outpatient offices. The exclusion criteria were different disorders interfering with terminal illness or with heavy dementia. Prior to the study, written consent was obtained from all participants. Older patients were divided

Age distribution

Users on

Ethics approval for the study was obtained from the local (University Clinical Centre Maribor) Research Ethics Committee.

Table 2: Distribution of health care providers in the study Health care providers  Health care level

Physicians Male

Female

Primary (incl. 14 private GPs)

17

21

Secondary

25

Total N (%)

42 (55.3%)

198

N

Nurses

N

Total

Male

Female

38 (50%)

2

61

63 (56.2%)

101

13

38 (50%)

4

45

49 (43.8%)

85

34 (44.7%)

76 (100%)

6 -5.40%

106 (94.6%)

112 (100%)

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Measures

Results

Participants completed the newly developed questionnaires including general socio-demographic data such as age, gender and level of education. The questionnaires consisted of 7 and 8 items (with a 5 point Likert scale response format) to assess the communication of patients and health care providers. Statistical methods The Chi-square (χ²) test was used to test the proposed hypothesis of quality of communication under the sections health care providers and older patients. Statistical significance level was set at p-value < 0.05. All analyses were performed with SPSS for Windows, version 11.0.

Health care providers The results are presented in Table 3. The Chisquare (χ²) analysis indicated that health care providers at the primary health care level are more satisfied with their communication with patients, compared to health care providers at the secondary health care level. There was a statistically significant difference between physicians and nurses in terms of the self-assessed quality of their communication with their older patients, whereby physicians assessed their communication less successfully than nurses did. Furthermore, physicians in general, indicated that they did not receive enough knowledge regarding communication during undergraduate education, while nurses indicated the opposite.

Table 3. Quality of communication assessed by health care providers Questions

χ²

p-value

Q1: Do you think you are successful in your communication with older patients? (Primary level vs. Secondary level)

9.204

0.027*

Q2: Do you think you are successful in your communication with older patients? (Physicians vs. Nurses)

8.302

0.040*

Q3: Did you receive enough knowledge about communicating during your medical education? (Physicians vs. Nurses)

15.445

0.05

20 (11.5)

17 (12.7)

>0.05

Own experience

17 (8.3)

7 (6.8)

>0.05

6 (5.2)

18 (11.2)

0.001

* Chi-Square test, between age groups and between both genders Journal of Society for development of teaching and business processes in new net environment in B&H

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Up to half of participitants (n = 150, 48.7%) stated that relationship between pharmaceutical industry represantatives and physicians are important in their clinical practice. Role of relationship with pharmaceutical industry on opinions of physicians was shown in Table 4. While the reputation of the pharmaceutical company was foremost important (84.6%), advertisement or announcements and relations with sales representatives ranked lower and closer to each other. Table 4. Role of relation with pharmaceutical industry on opinions of doctors n =150

(%)

Reputation of the pharmaceutical firm

127

84.6

Advertisment or sponsored announcement

28

18.7

Pharmaceutical firm sales representative

16

10.7

Importance levels of reputation of the pharmaceutical company and relations with its representatives were significantly higher among young physicians than relatively older ones only (p =0.03). On the other hand there were no significant difference between GPs and non-GP group (data not shown).

Discussion CME activities for physicians serve several purposes. The ultimate goal is to improve the quality of health care. It aims at updating physicians’ professional knowledge and skills, and it has obvious implications on physicians’ attitudes and behaviour. CME activities are closely related to patient care, and the culture of continuing education has great importance for clinical (8-10). The main limitation of this study is that all results are based exclusively on the physicians ‘ self reporting and their self-assessed activities. Therefore, this study has the some problems of a self-answered questionnaire survey. Firstly, perceived importance and actual practice may be different, and our study does not address this. Secondly, because of the number of respondents was lower than anticipated and findings biased from those who were don’t willing to respond, our finding may be providing an incomplete picture of reality. We have shown that, while local and abroad congresses or CME courses and medical journals are regarded the most important CME activity for our physicians, majority of them prefer local conferences or CME courses to abroad ones. The preference for local conferences or CME courses, perhaps, should not be surprising, since it is being increasingly recognised that socio-geographical factors are highly relevant in the practice of medicine, and that scientific data gathered from one region are not universally applicable.

Table 5. Role of relation with pharmaceutical industry on opinions of doctors by gender and by age groups Gender

Age groups

Men n=102(%)

Women n=48 (%)

P Value*

0.05

72 (92.3)

54(75.0)

0.03

Advertisment or sponsored announcement

22 (25.0)

6 (12.5)

>0.05

12 (15.4)

16(22.2)

>0.05

Pharmaceutical firm sales representative

12 (11.8)

4 (8.3)

>0.05

9 (11.5)

7(9.7)

>0.05

* Chi-Square or Fisher exact test, between age groups and between both genders 222

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The preference for abroad conferences or CME courses for relatively younger and women physicians and own experients for relatively olders probably reflect the different experience of practice. The relatively younger physicians may find abroad conferences or CME courses more instructive for their postgraduate medical education to local ones, while relatively older physicians likely to favour the adequacy of their experience. Many physicians regard pharmaceutical firms as an important source of funding for clinical studies, congresses or CME courses and therefore interact with them in various ways (11,12). In this study we did not evaluate the quality, content, frequency or the outcome of the interaction of physicians with industry represantatives or attendence to industry-founded CME activities. Our study dealt only with self-reported opinions of physians on industry-related CME activities. In accordance with the study of Loh et al.(6), the reputation of pharmaceutical firm is of the foremost importance to the physicians (especially among young ones) and this is understandable from the perspective of industry’s contribution to establish research and development. However, it is still possible that firms with well established brands may have an unfair advantage over smaller unknown companies, and this may not encourage the sound practice of evidence-based medicine. Although our respondents did not highly rate the importance of sales personnel in conveying medical information, it is well known that such interaction can potentially influence clinical practice (6,13) and that more stringent regulation is necessary to minimise any conflict of interest potentially created by an unhealthy relationship between the physician and the industry.

Conclusion Our survey provides an important knowledge at this severely under-explored area of perceived importance of CME activities for physicians. Our findings reiterate that clinical practice is not merely an issue of practising evidence-based medicine, but is influenced by other factors, such as the perceptions at various forms of information dissemination and the acceptance of pharmaceutical industry involvement. Acknowledgements: The authors wish to thank all the physicians who gave up their time to participate in the study

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Literature 1. Candy PC (2000) Preventing “information overdose”: developing informationliterate practitioners. J Contin Educ Health Prof 20:228-237. 2. McColl A, Smith H, White P, Field J (1998) General practitioner’s perceptions of the route to evidence based medicine: a questionnaire survey. BMJ 316: 361-365. 3. Freeman AC, Sweeney K (2001) Why general practitioners do not implement evidence: qualitative study. BMJ 323:1100-1102. 4. Lam WW, Fielding R, Johnston JM, Tin KYK, Leung GM (2004) Identifying barriers to the adoption of evidence-based medicine practice in clinical clerks: a longitudinal focus group study. Med Educ 38:987-997.

13. Brennan TA, Rothman DJ, Blank L, Blumenthal D, Chimonas SC, Cohen JJ, Goldman J, Kassirer JP, Kimball H, Naughton J, Smelser N (2006) Health industry practices that create conflicts of interest: a policy proposal for academic medical centers. JAMA 295:429-433.

Corresponding author: Naim NUR, MD Department of Public Health, School of Medicine, Cumhuriyet University, 58140-Sivas / Turkey e-mail: [email protected]

5. Lesmes-Anel J, Robinson G, Moody S (2001) Learning preferences and learning styles: a study of Wessex general practice registrars. Br J Gen Pract 51: 559– 564. 6. Loh LC, Ong HT, Quah SH (2007) Impact of various continuing medical education activities on clinical practice-A survey of Malaysian doctors on its perceived importance. Ann Acad Med Singapore 36:281-284. 7. http://www.die.gov.tr/TURKISH/ISTATIS/ Esg2/58SIVAS/saglik1.htm. Accessed 16 December, 2007. 8. Shannon S (2003) Educational objectives for CME programmes. Lancet 361:1308. 9. Zeiger RF (2004) Towards continuous medical education. J Gen Intern Med 20:91–94. 10. Towle A (1998) Continuing medical education: Changes in health care and continuing medical education fort he 21st century. BMJ 316:301-304. 11. Lexchin J (1993) Interactions between physicians and the pharmaceutical industry: What does the literature say? Can Med Assoc J 149(10):14011407. 12. Collier J, Iheanacho I (2002) The pharmaceutical industry as informant. Lancet 360:1405-1409.

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A systemic study on the protective effect of keratinocyte growth factor on type II alveolar epithelial cells against hyperoxia-induced injury in vitro Xiuxiang Liu1, Changjun Lv1, Xiuhong Jia1, Yimin Sun2, Shaodong Hua3, Zhichun Feng3,* 1 2 3

The hospital affilicated Binzhou Medical University, Binzhou, Shandong Province, China Wudi hospital affilicated Binzhou Medical University, Binzhou, Shandong Province, China Military general hospital of Beijing PLA, Beijing, China

Summary The proliferation and trans-differentiation of type II alveolar epithelial cells (AEC2) are critical for the alveolar epithelial repair. However, AEC2 themselves can be damaged by severe or sustained lung injury as well. Although many research groups have reported the inhibitive effect of hyperoxia on AEC2 hyperplasia, there is a lack of systemic study on the damages imposed by hyperoxia to AE2 cells. In this work, the toxic effects of 95% oxygen on AEC2 and the protective roles of keratinocyte growth factor (KGF) were systemically investigated in vitro. Our results revealed that 95% oxygen severely suppressed AEC2 proliferation, decreased cell viability and increase the cell proportion at G2 and S phases. Simultaneously, it promoted the apoptosis and necrosis of AEC2 and reduced the expression of SP-C, AQP5 and TTF-1 remarkably. In all these aspects, KGF antagonized with hyperoxia and substantially recovered the viability and behavior of AEC2. These findings helped to achieve an thorough insight to the toxic effect of oxygen on AEC2 and settled some argues about the mechanism of high oxygen in alveolar epithelial cell injury. Additionally, we reconfirmed the general idea that keratinocyte growth factor (KGF) is a promising agent for the treatment of acute hyperoxic lung injury. Key words: Keratinocyte Growth Factor; Type II Alveolar Epithelial Cells; Oxygen-Induced Lung Injury; Cell Proliferation; Cell Cycle; Apoptosis

Introduction Type II alveolar epithelial cell (AEC2) proliferates and transdifferentiates into type I alveolar epithelial cell (AEC1) after many forms of lung injury and is thought to exert a critical role in alveolar epithelial repair (1, 2). On the other hand, however, these defenders of the alveolus themselves could also be damaged under severe or sustained lung injuries induced by for example toxin (3-5), radiation (6, 7) and hyperoxia (8, 9). As high concentration of oxygen is frequently needed in the treatment of patients with pulmonary insufficiency such as premature newborns or adults suffering from severe respiratory illness, the toxic effect of hyperoxia on alveolar epithelial cells is an intensive research point in acute lung injury studies (10-13). Unfortunately, most researchers focused their attention on the oxygen-induced injuries in AEC1, the remolding roles of AEC2 in alveolar epithelial repair and the promotive actions of keratinocyte growth factor (KGF) in alveolar repair process while the damages imposed by hyperoxia to AEC2 themselves was ignored more or less. Although many reports have documented the inhibitive effect of hyperoxia on the proliferation and differentiation of AEC2 (8, 14-18), there is a lack of systemic study concerning the damages imposed by hyperoxia to AE2 cells as well as the counteracting roles of KGF against oxygen. Keratinocyte growth factor (KGF), a heparin-binding fibroblast growth factor also known

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as FGF-7, is a potent mitogen highly specific for epithelial cells (19, 20). Although the exact mechanism of the action of KGF is largely unknown, it has been shown to promote the proliferation and differentiation of type II alveolar epithelial cells in vitro and in vivo (16, 21-23). In addition, many other effects of KGF on the airway epithelium have been uncovered in recent years including cell migration, survival, DNA repair and induction of surfactant apoproteins and enzymes involved in the detoxification of reactive oxygen species (20, 24-26). Moreover, KGF administration was also found to be protective when given before several forms of lung injury including bleomycin, hydrochloric acid, radiation and hyperoxia (15, 27-30). Despite all this, more knowledge is needed to comprehend the precise roles of KGF in protecting AEC2 against each form of lung injury especially hyperoxia-induced lung injury. In present work, we conducted a specific and systemic investigation over the toxic effects of hyperoxia on type II alveolar epithelial cells (AEC2). The adverse actions of oxygen on the proliferation, viability, cell cycle, apoptosis and necrosis, ultra-structures of AEC2 as well as the expression of SP-C, AQP5 and TTF-1 in AEC2 were thoroughly investigated. At the same time, the protective roles of KGF for AEC2 against hyperoxia were also tested. Our results provide a systemic and overall insight into the hyperoxia-imposed damages in AEC2 and reconfirmed the general idea that keratinocyte growth factor (KGF) is a promising agent for the treatment of acute hyperoxic lung injury. Materials and Methods Reagents and antibodies MEM medium and fetal bovine serum (FBS) were purchased from Hyclone (USA). Trypan blue, DMSO, hochest 33342, rat IgG and keratinocyte growth factor (KGF) were obtained from Sigma. Rabbit anti-goat IgG-FITC antibody and texas-red conjugated goat anti-rabbit antibody were purchased from Sigma while antibodies against surfactant protein C (SP-C), aquaporin 5 (AQP5) and thyroid transcription factor (TTF-1) were purchased from Santa Cruz Biotechnology 226

(USA). All other chemicals were standard commercial products of analytical grade. Isolation and culture of AEC2 AEC2 were isolated from pathogen-free male Sprague-Dawley rats (200-250 g) as previously described by Bhaskaran M. et al (31).The purity of AEC2 was 97.3 ± 2.7% as determined by modified Papanicolaou staining and the viability was 97.2% ± 1.8%. AEC2 were cultured in 24-well plates (4×105 / well) in 0.5 ml MEM medium supplemented with 10% FBS plus 100 IU/ml penicillin and 100 μg/ml streptomycin and maintained at 37ºC under specific atmosphere for 1-8 days. The control group was maintained under a humidified atmosphere of 5% CO2 plus 95% air while other two groups, high oxygen group and KGF group, were exposed to a humidified atmosphere of 5% CO2 plus 95% oxygen. Simultaneously, the KGF group was supplemented with 10 ng/ml KGF. The media were changed every 24 h. Cell growth observation AEC2 were cultured in 24-well plates (4×105 / well) in 0.5 ml MEM medium supplemented with 10% FBS plus 100 IU/ml penicillin and 100 μg/ml streptomycin and maintained at 37ºC under specific atmosphere for 1-8 days. Three wells were selected from each group every 48 hours to record the cell growth states. Each well was digested with 0.25% trypsin and gently pipetted to obtain a homogeneous cell suspension. Then the cells were observed and photographed by TE2000 digital inverted microscope (Nikon, Japan). Cell viability assay AEC2 were digested into cell suspension with 0.25% trypsin then nine drops of cell suspension were transferred into a small test tube and mixed with a drop of 0.4% trypan blue staining solution. The numbers of viable cells (unstained cells) and dead cells (stained cells) were counted within 3

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min in a hemocytometer. Each sample was tested for 6 times and 5 samples were selected from each group for cell viability assay. Cell viability (%) = numbers of viable cells/total cell numbers × 100%. Cell cycle and apoptosis assay Triple samples of 1×105 cells were collected from each group and subjected to cell cycle with FACScan flow cytometer system (Becton Dickinson, USA) according to the instruction provided by manufacturer. The apoptosis assay was conducted with annexin V-FITC apoptosis kit provided by Beijing Biosea Biotechnology Corporation (Beijing, China). In the graphs generated by Cellquest software, viable cells (Annexin-V-/PI-) were located in III quadrant (bottom left), early apoptosis cells (Annexin-V+/PI-) were located in IV quadrant (bottom right), while late apoptosis cells (Annexin-V+/PI+) were located in I quadrant (top right). Ultra-structure observation AEC2 were digested by 0.25% trypsin, dispersed and centrifuged at 2000 rpm for 5 min. The cell pellet was fixed in 2.5% glutaraldehyde for more than 24 h, post-fixed in 1.0% aqueous OsO4 for 2 h. After stepwise dehydration in 50%, 70%, 90% and 100% acetone, cell pellet was cleared in propylene oxide, embedded in epon-816 and polymerized at 60 oC for 3 days. The 50 nm slices were examined by transmission electron microscope (TEM) (JEM-1230, Japan) Laser scanning confocal microscopy (LSCM) AE2 cells were cultured in specific vials for LSCM under respective conditions for different periods then fixed in 4% paraformaldehyde for 10 min, and washed 5 times by 0.01M PBS. Two aliquots were prepared from one vial. One aliquot was added with goat antibody against SP-C (1:500) and rabbit antibody against AQP5 (1:500), the other was added with goat antibody against

TTF-1 (1:500). After incubated in wet box at 4oC for 24h and washed in 0.01M PBS for three times, the former aliquot was added with rabbit anti-goat IgG-FITC antibody and texas-red conjugated goat anti-rabbit antibody while the later was added with rabbit anti-goat IgG-FITC antibody alone. After another 2 hours of incubation at 37oC and washes in 0.01M PBS, hoechst 33342 was added to a final concentration of 10ng/ml and the samples were incubated at room temperature for 20 min. Afterwards, cells were washed by 0.01M PBS and mounted by VECTASHIELD® Mounting Medium (Vector Laboratories, USA), then the samples were observed under C1-SHS laser scanning confocal microscope (Nikon, Japan). Excitation wavelength for each fluorescent substance was as follows: hochest 33342, 408 nm; FITC, 488 nm; and Texas Red, 514 nm. Simultaneously, a negative control was prepared for each sample which was treated the same as its counterpart except for addition with diluent instead of the primary antibody. Real-time RT-PCR AE2 cells were collected and total RNA was prepared using Trizol (Invitrogen). For the detection and quantification of individual mRNA, the following PCR primer sequences were used: SP-C (Forward: 5′-TGGTAGTCCTTGTCGTCGTG-3′, Reverse: 5′-CACCTTTGCTCCACAGGTTT-3′); AQP5 (Forward: 5′-AATGCGCTGAACAACAACAC-3′, Reverse: 5′-TTATGGGCTTCTGCTCCTGT -3′); TTF-1 (Forward: 5′-CGGCGACAGGTACTTCTGCT-3′, Reverse: 5′-TGCCACCTTACCAGGACACC-3′) and β-actin (Forward: 5′-TCACCCACACTGTGCCCATCTATGA-3′, Reverse: 5′-CATCGGAACCGCTCATTGCCGATAG-3′). The real-time PCR analysis was performed on a real-time PCR instrument (BioRad) and the amount of specific mRNA expression was normalized to β-actin gene. Statistical analysis All values in the text and figures are expressed as the mean ± SEM. Statistical significance was determined by a Student’s t-test using the software

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package SPSS (http://SPSS.com, Chicago, USA) for Windows 11.5. A value of p 4 years

1

12.5

1

12.5

2

25.0

Overall:

3

37.5

5

62.5

8

100.0

were registered in 50.0% of infected individuals, with average duration of 3 days. Mild dehydration degree was registered in 6 (75.0%) patients. Concerning the type of nutrition of infected individuals, salmonelloses occurred in older age groups consuming combined food. Therapy for the infected individuals was in accordance with recommendations of the WHO and assessment of general condition of a patient. In the group of protozoa, Entamoeba histolytica was registered in 13 (5.5%) infected individuals, as etiologic agent of diarrheal diseases. As monomicrobial infection, amoebas were confirmed in 12 (92.3%) individuals, while adenovirus antigens were also confirmed in one patient. Concerning the age and gender of the infected individuals, infections with Entamoeba histolytica were confirmed in the group aged 3 to 4 or over 4, in both genders, occurring more frequently in males (Table 4). Concerning the season of occurrence of amoebiasis, infections occurred in the third and fourth trimester of the year. Diarrhea was dominant in

the clinical features of amoebiasis in all individuals. It was manifested by the occurrence of 2-3 or numerous liquid and yellow stools with mucous traces, while blood traces were registered in feces of only one patient. Diarrhea lasted for 3 to 5 days in average. The second significant clinical symptom, vomiting, was registered in 5 or 45.4% of infected individuals, with 2-3 daily vomits and lasting for 2-3 days. Febrile condition (temperature of 380C) was registered in 45.4% of infected individuals. Febrile condition lasted for 2 days in average. Stomach pain was registered in 54.5% of infected individuals, lasting for 3 days in average. Respiratory difficulties (coughing, otalgy, sneezing and rhinitis) occurred in 2 individuals, which is important to highlight in terms of their frequent occurrence in the case of gastroenteritis of virus etiology. Mild and moderate dehydration degrees were registered in 5 (45.4%) infected individuals. Therapy of amoebiasis implied compensation for water, electrolytes and diet nutrition. Certain number of patients was treated with antibiotics and antipyretics.

Table 4 – Gender and age distribution of individuals infected with amoebas Age of infected individuals

Male

%

Female

%

Overall:

%

0-6 months

0

0.0

0

0.0

0

0.0

7-24 months

1

8.3

0

0.0

1

8.3

3-4 years

3

25.0

2

16.6

5

41.6

> 4 years

4

33.3

2

16.6

6

50.0

Overall:

8

66.6

4

33.3

12

100.0

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5. Discussion Analysis of etiology of infective gastroenteritises in pre-school children is aimed at discovering and observing enteropathogenic microorganisms, as well as undertaking certain preventive and therapeutic measures with the purpose of putting them under control. This form of examination provides not only an insight into the types of circulating microorganisms in a narrow area, but also an insight into their basic characteristics, diversity and occurrence, as well as their antimicrobial susceptibility. This is important from the aspect of possible necessity of antimicrobial treatment of certain etiologic agent and disease, or undertaking adequate empiric therapy. It is necessary to have these indications in order to undertake certain preventive measures as well. It is well-known today that acute infective diarrheas are the second most frequent in terms of the occurrence in younger children, following respiratory diseases. Reports from the world centers, as well as the studies conducted based on samples of the patients treated in hospitals in this country, suggest that viruses represent significant and leading etiologic agents causing these diseases (4,6,10,15,16). Our study did not discover any case of the infection with E. coli or Schigella spp., unlike other studies, where these bacteria are discovered as well in fecal samples of infected children (17). Etiologic correlation of intestinal diseases was confirmed in 61 or 25.9% of infected individuals, out of 235 examined patients. Out of 61 microbiologically positive patients, one etiologic agent of the disease was confirmed in 58 or 95.0% of individuals, and two etiologic agents in 3 or 5.0%. In the group of pathogenic or potentially pathogenic microorganisms, rota-, adeno- and coronaviruses, Entamoeba histolytica, yeasts of the genus Candida, Giardia lamblia, Salmonella enteritidis and Salmonella spp. of group D and Pseudomonas spp. were isolated and/or confirmed. Microscopic examination of native and colored specimen of feces of infected individuals confirmed in a certain number of patients coproleucocytes, rare erythrocytes, fat drops, epithelial cell aggregations, rare blastospores of Candida spp., reduced or absent bacterial flora within the normal flora of gastro-

intestinal system and mucous. These microscopic findings were greatly significant, since they were indicating a corresponding infective disease. As we know from the bibliography available, viruses are the most frequent etiologic agents of the diseases. In our sample, rotaviruses were confirmed in 36 or 15.3% of treated individuals, adenoviruses in 5 or 2.1% of infected individuals, and Coronaviruses in 1 or 0.4% of individuals. Entamoeba histolytica takes the second place in terms of frequency of the occurrence, being confirmed in 13 or 5.5% of infected individuals, and Giardia intestinalis in 1 or 0.4% of individuals. Bacteria of the genus Salmonella, Salmonella enteritidis (group D), takes the third place in terms of the frequency of causing the diseases, being confirmed in 8 or 13.1% of patients. This is a significant finding in terms of analysis of etiology of the diseases. Rotaviruses as etiologic agents of diarrheal diseases occur in both genders of all age groups and throughout the year. Their occurrence does not vary in terms of the seasons. They occur as monomicrobial infection in most of the infected individuals. Diarrhea, vomiting, occurrence of moderate to high body temperature and characteristic respiratory difficulties are dominant in the clinical features of rotaviroses. Stools are frequent, pulpy, being green-colored and with mucous traces in a certain number of infected individuals. Blood finding in feces is not characteristic of rotaviroses. Mild or moderate dehydration degree occurs in most of the infected individuals. Severe forms of dehydration were not registered. These findings are important with the purpose of undertaking adequate therapeutic measures, compensation for water and electrolytes, diet nutrition and home treatment. Antibiotic therapy is not indicated for this kind of infective agents. Gastroenteritises of amoebic etiology were confirmed based on their finding in the native and Lugol-colored specimens of feces, prepared out of their liquid part. Cysts and/or vegetative forms of Entamoeba histolytica, with or without ingested erythrocytes, were found in feces. They were the only discovered pathogen in most of the patients infected with amoebas, with reduced number of bacteria within the normal intestinal microflora. These infections are more frequent in older children (aged 3-4 or older). This is explained by a

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kind of consumed food and possible consumption of contaminated food and water. Amoebiasis was registered in both genders, during the warm months of the year. Diarrhea is dominant in the clinical features, with the average of 2-3 daily stools and duration of 3-5 days. Febrile condition occurred in a half of individuals, with the average duration of 2 days. Unlike rotaviroses, respiratory difficulties and other accompanying clinical symptoms are not significantly present in amoebic infections. These indications represent an answer to reduced number of registered dehydrations, which were registered in less than a half infected individuals. Social status of infected individuals, as well as the place of their residence, had no significance in terms of the occurrence of this disease. Therapy for the patients implies compensation for the loss of fluids and electrolytes, with both antibiotic and antipyretic therapy being introduced in more severe forms of the disease. Bacteria of the genus Salmonella were confirmed as the third significantly isolated etiologic agent of diarrheal diseases in pre-school children. They belonged to the serologic group D, i.e. Salmonellae enteritidis were identified by serotyping. As etiologic agents, salmonellas were confirmed in 8 or 3.4% of infected individuals over the age of 7 months. The disease occurred during the warm months of the year, which explains that increased temperature is favorable for their persistence and spreading. Diarrhea was present in all patients, lasted for 3 to 7 days, 3 to 5 times a day. Stools are yellow- or green-colored, mucous is present in feces and blood is absent in most of the patients. Vomiting was not registered in any of the infected individuals. Increased body temperature was registered in 2/3 of infected individuals, usually at 380C. Respiratory difficulties and other reasons for fluid loss were registered in most of the patients. Mild dehydration was registered in a certain number of individuals. Salmonella infection was registered in children of middle social status, from urban areas, consuming combined food. Treatment was carried out in ambulance and implied compensation for the loss of fluids and electrolytes and diet nutrition. There were no death cases.

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6. Conclusion Based on the study conducted in this group of individuals infected during one year, it can be concluded that infective agents were found and confirmed in 25.9% of individuals. Monomicrobial infection was found in 95.0% of infected individuals with confirmed infective agent, while two pathogenic microorganisms caused the infection in a small number of patients. Out of the overall number of positive findings, rotaviruses were the most frequently confirmed; Entamoeba histolytica takes the second place in terms of the frequency, while bacteria of the genus Salmonella take the third place. Findings of other etiologic agents of the disease can be individually significant in causing infective diseases, but their incidence and frequency of occurrence, with isolation of some other potentially pathogenic etiologic agents, is not always sufficient and this requires a more extensive analysis. This certainly does not mean that their findings in infected individuals do not represent a significant health problem, which should be approached with equal consciousness. The clinical features described have their own specificities, as well as common characteristics. It is important to highlight that ecological features of the circulation and incidence of individual pathogenic microorganisms in the region of Sarajevo Canton have not been significantly changed, as well as that ecology of microorganisms must be continuously observed with the purpose of understanding and discovering its changes, which can have an influence on therapeutic regimes, prevention or introduction of certain sanitary and protective measures.

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Literature 1. Ahiadeke C. Breast-feeding, diarrhea and sanitation as components of infant and child health: a study of large scale survey dana from Ghana and Nigeria. J Biosoc Sci 2000; 32:47-61. 2. Perera BJ, Ganesan S, Jayarasa J, Ranaweera S. The inpact of breastfeeding practices on respiratory and diarrheal disease in infancy: a study from Sri Lanka. J Trop Pediatr 1999; 45:115-8. 3. Parashar UD, Bresse JS, Gentsch JR, Glass RI. Rotavirus. Emerg Infect Dis 1998; 4:561-70. 4. Al-Gallas N, Bahri O, Bouratbeen A, el al. Etiology of Acute Diarrhea in Children and Adult in Tunis, Tunisia, with Emphasis on Diarrheagenic Escherichia coli: Prevalence, Phenotyping and Molecular Epidemiology. Am J Trop Med Hyg 2007; 77(3):571-82. 5. Reither K, Ignatius R, Weitzel T, et al. Acute childhood diarrhoea in northern Ghana: epidemiological, clinical and microbiological characteristics. Infect Dis 2007; 7(1):104. 6. Gomes TA, Rassi V, MacDonald KL, et al. Enteropathogens associated with acute diarrheal disease in urban infants in Sao Paulo, Brasil. J Infect Dis 1991; 164:561-70. 7. Parachar UD, Bresee JS, Glass RI. The global burden of diarrhoeal disease in children. Bull World Health Organ 2003; 81:236.

12. Vandepitte J, Engbaek K, Piot P, Heuck CC. Basic laboratory procedures in clinical bacteriology. WHO Geneva 1991. 13. Zvizdić Š, Bešlagić E. Medicinska mikrobiologija s parazitologijom. Visoka zdravstvena škola Sarajevo, 2007. 14. Bottone EJ. Schneiersons atlas of diagnostic microbiology. Seventh Edition, Abbott Laboratories, North Chicago, Illinois 1982. 15. Zvizdić Š. Uloga serotipova rotavirusa u etiologiji akutnih dijarealnih oboljenja u djece predškolskog uzrasta. Doktorska disertacija, Sarajevo; Medicinski fakultet Univerziteta u Sarajevu, 1991. 16. Ahmetagić S, Jusufović E, Jasminka Petrović, Vildana Stojić, Zineta Delibegović. Acute infectious diarrhea in children. Med Arh 2003; 57(2):87-92. 17. Nguyen TV, Van PL, Gia KN, et al. Detection and characterization of diarrheagenic E. coli from children under 5 years of age in Hanoi, Vietnam. J Clin Microbiol 2005; 43:755-60.

Corresponding author: Sukrija Zvizdic, Department of microbiology, Medical Faculty of the University of Sarajevo, Bosnia and Herzegovina, e-mail: [email protected]

8. Black RE. Morris SS, Bryce J. Whede and why are 20 million children dying every year? Lancet 2003; 361:2226-34. 9. Durepaire N, Pradie MP, Ploy MC, et al. Les adenovirus dans les prelevements de selles ieu hospitalier. Comparaison avec les principaux agents de gastroenterites (rotavirus, campylobacter, salmonella). Pathol Biol 1995; 43:601-10. 10. Alain S, Denis F. Epidemiologie des diarrhees aigues infectieuses en France et en Europe. Archives de pediatrie 2007; 14(Supll 3):132-44. 11. Doern GV, Herrmann JE, Henderson P, et al. Detection of rotavirus with a new polyclonal antibody enzyme immunoassay (Rotazyme II) and a commercial latex agglutination test (Rotalex): comparison with monoclonal antibody enzym immunoassay. J Clin Microbiol 1986; 23:226-9. Journal of Society for development of teaching and business processes in new net environment in B&H

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Quality of life after mastectomy of the breast cancer Kvalitet života nakon mastektomije zbog karcinoma dojke Samir Husic1, Farid Ljuca2, Sefik Hasukic3, Deso Mesic3 1 2 3

Center of Palliative care – Hospice UCC Tuzla, Bosnia and Herzegovina, Department of Physiolgy, Medical faculty Univesity in Tuzla, Bosnia and Herzegovina, Surgical Department UCC Tuzla, Bosnia and Herzegovina

Summary Introduction: The measure of the quality of patients’ lives that have cancer makes a possibility for the most adequate therapy procedure. Brest cancer which causes damage of the body image is often connected with psychological morbidity. Aim of the research: This survey was to measure patients’ quality of life after the mastectomy of the breast cancer, before and after three months treatment in Daily hospice. Questioners and methods: The survey was held of the department of palliative care–Hospice, University-clinical centre Tuzla. The questioners group consisted of 35 patients, who have finished with the oncology treatment, and who have been visiting Daily hospice for about two weeks. Control group was also consisted 35 patients but they unless the fact that they haven’t been visiting Daily hospice. The testing was based on the use of SF-36 scale. Results: The quality of life in both groups, during the first testing was quite similar 0,35 ± 0,10 in questioners group and 0,39 (from 0,25 to 0,78) in control group. According to the second testing, the whole quality of life for the questioners group becomes much better, with the medium value of 0,59 ± 0,11 which is statistically significant concerning the first testing (p=0,0001) the second testing done with patients of control group, shows results of the medium value of 0,34 (from 0,25 to 0,70) which is slightly worse from the first test (p=0,02). 254

Conclusion: Treatment of multidisciplinary team of Daily hospice has a favorable effect of the quality of life patients who had mastectomy. Key words: quality of lives, mastectomy, Daily hospice. Sažetak Uvod. Mjerenje kvalitete života pacijenata sa malignim tumorima omogućava izbor najadekvatnijeg terapijskog postupka. Karcinom dojke ošećuje tjelesni imidž i uzrokuje psihološki morbiditet. Promjena izgleda tijela zbog tretmana karcinoma dojke (mastektomija, kemoterapija) je potencijalan i aktuelan izvor distresa i psiho-socijalnih teškoća. Gledajući se u ogledalo žene zaključuju da su ružne, manje žestvene, nepoželjne, vide sebe kroz operacijski ožiljak, gubitak kose. Sve to može ponekad praviti veću bol nego činjenica da boluju od karcinoma. Postoji često osjećaj lične izgubljenosti zbog gubitka dijela tijela, inferiornost. Kosa je vidljiv i emotivno važan dio tijela, tako da njen gubitak u toku kemoterapije predstavlja veliki problem posebno za socijalni, psihički i emocionalni aspekt kvalitete života. Mnoge žene alopeciju opisuju kao najstrašniji događaj u njihovoj bolesti i dešavalo se da odbiju nastaviti primanje kemoterapije. Bolesnicima valja pomoći u traganju za značenjem njihova života, steći njihovo puno povjerenje te otvoriti prostore komunikacije u nekad posve izoliranih i povučenih bolesnika. Dnevni hospicij

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posjeduje redovit i strukturiran program aktivnosti te ga bolesnici mogu posjećivati u dane koji njima najbolje odgovaraju. To potiče pacijentovu mobilnost i neovisnost, olakšava komunikaciju, podiže dobro raspoloženje, smanjuje uznemirenost i stres i poboljšava fizičku kondiciju. Kreativne aktivnosti radne terapije nemaju samo namjeru odvratiti bolesnika od neugodnih misli već ga i stimulirati, obogatiti mu život, vratiti osjećaj vlastite vrijednosti, ispunjenja i uspjeha. Cilj: Izmjeriti kvalitet života kod pacijentica nakon mastektomije zbog tumora dojke, prije i poslije tromjesečnog tretmana u dnevnom hospisu. Ispitanici i metode. Studija je rađena na odjelu palijativne njege, Univerzitetsko–kliničkog centra Tuzla. Ispitivanu grupu činilo je 35 pacijentica sa završenim specifičan onkološki tretman nakon mastektomije zbog tumora dojke koje su posjećivale dnevni hospis a kontrolnu 35 pacijentica koje nisu posjećivale dnevni hispis. Primjenjena je SF- 36 skala za procenu kvaliteta života, u dva testa u razmaku od 12 nedelja. Rezultati. Ukupan kvalitet života u ispitivanoj i kontrolnoj grupi pri prvom testiranju je bilo sličan tj. 0,35 ± 0,10 u ispitivanoj i 0,39 (od 0,25 do 0,78) u kontrolnoj grupi. Pri drugom testiranju kvalitet života u ispitivanoj grupi je bolji sa srednjom vrijednosti od 0,59 ± 0,11 što je statistički značajno bolje u odnosu na prvi test (p= 0,0001), nasuprot kontrolne grupe gdje srednja vrijednost kvaliteta života pri drugom testiranju nakon tri mjeseca pokaže rezultat od 0,34 (od 0,25 do 0,70) što predstavlja pogoršanje u odnosu na prvi test (p=0,02). Fizičko kao i mentalno zdaravlje, kao subskale ukupnog kvaliteta života, u ispitivanoj grupi su u poboljšanju, dok su u kontrolnoj grupi rezultati lošji prilikom drugog testiranja. Zaključak. Tretman multidisciplinarnog tima dnevnog hospisa poboljšava kvalitet života pacijentica nakon mastektomije, poboljšava se fizičko zdravlje, a napredak u mentalnom zdravlju je vezan za okupacionu terapiju, aktivnosti psihoterapeuta i socijalnog radnika.. Većina pacijentica je smatrala kako su sadržaji u dnevnom hospisu (okupaciona terapija, aktivnosti psihoterapeuta sa grupnim i individualnim tretmanima, otvorenost komunikacije među samim pacijentima, te sigurnost u redovnom praćenju, kontrolisanju i savjetovanju od strane ljekara i medicinske sestre, kao članova multidiscipli-

narnog tima dnevnog hospisa) bili osobito korisni u menadžmentu stresa, relaksaciji i opuštenosti, boljoj komunikaciji i povjerenju, razvijanju samonjege i samopomoći, rješavanju komplikacija bolesti kao što je limfostaza i sl. Ključne riječi: kvalitet života, mastektomija, dnevni hospis 1. Introduction The first decade of 21st century has led us into global crisis of moral, spiritual and intellectual scales. Materialistic approach to life, system of life subordinated to realization of the term ‘have’, dominates over trying to implement the term ‘be’. The patients are facing emotional and psychical pain, have doubts about the treatment’s outcome, and often with appliance of aggressive diagnostic and therapy procedures. All listed above disturb basic characteristics of quality of life and dignity of the patients. Subtle approach of medical staff to a patient, full of high ethic and moral values, relieves the sense of loneliness, and contributes to better outcome of the treatment and improvement of quality of life. The quality of life is used today to describe the seriousness of the illness, to monitor the treatment, evaluate the effect of new therapy procedures.1 The quality of life is complex pleasure about our own lives, subjective experience of each individual. The quality of working life is also important.2 About 32% of population during the lifetime suffers from some kind of malignancy, and almost 50% of the patients demand medical, social, financial support of the health system, their family and society.3 Inquiry about the quality of life of healthy people has shown that healthy people feel mentally or physically ill six days per month, 10 % of healthy people don’t feel healthy fourteen days per month. Four basic aspects of quality of life relate to4,5: - Physical welfare: energy, force, functionality, sleep, peace, relaxation - Mental welfare: concentration, depression, dejection, fear, sadness, sorrow. - Social welfare: parenthood, family, love, finance, home, home budget. - Spiritual welfare: hope, desperation, religion, piety.

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Breast cancer is a malignancy which develops in late stage of painless tumor, without subjective discomfort. Often the patients and the surrounding experience this tumor like a punishment for something they didn’t deserve. According to the different number of new cases of breast cancer, there are: - High risk countries (countries of North Europe and North America) - Mild risk countries ( countries of South Europe and South America) - Low risk countries (Asian and African countries) 6. The descendants of migrants from low risk countries, in three generations get multiply high risk of suffering from breast cancer, which tells us about the importance of environment factors and lifestyle for occurrence of breast cancer7. According to data from Oncology department of UCC Tuzla, for the period between 2002 and 2006, total number of breast cancer patients was 531.

Figure 1. Ca mammae in Tuzla canton in period between 2002. and 2006. Psychological morbidity, along with breast cancer, became the subject of the research back in 80s8. It was said that 20-30 % of women who had manifestations of mental or psychosocial disorders were related to diagnosis and treatment. The 90s studies9 suggest that those disorders are temporary, and that frequency of these symptoms related to a small number of women. It is emphasized that the time for adaptation and avoiding psychological disorders is estimated to first four to six weeks.10 It is of great importance to estimate the 256

risk and demand patient to seek specialist’s opinion, after making a diagnosis and before starting with a treatment. ‘Mutilation’ caused by mastectomy makes women feel great emotional distress. Chemotherapy leads to depression and anxiety, bad reaction about losing their hair and gaining weight. All mentioned change body image of the patient and cause psychological distress11. The change of body image due to breast cancer treatments (mastectomy, chemotherapy) is the source of distress and psycho-social difficulties12. Looking themselves in the mirror, patients come to think they are ugly, undesirable, and the only thing they can see is the operational scar and hair loss. Sometimes all this can cause greater pain than the fact they are suffering from cancer. Patients often speak about their emotional problems when the treatment is completed, and dominating problems are: inadequate and insecure about making decisions in life, feeling of low self-esteem, anxiety and depression. The biggest obstacle for efficient identification of patient’s psychological problems is time and space limit, and limited number of professional consultants13. That is why it is important for patients to work in support groups, with other patients. Patients who attend group counseling can help other patients and help significantly to medical professionals. Support groups will not extend their lives but they will certainly improve the quality of life for these women. Daily hospice: St. Christopher Hospice (London) set the improvement of the quality of life of the patients as the primary aim by adding new dimensions to care package that is already established for the patient and her family14. They help women to get out of their homes, to get some rest from their illness, to associate with others and feel support, along with the set of various activities. Light exercises in the Physiotherapy ward with relaxing music are the part of regular program. That stimulates mobility, improves mood, and reduces anxiety and stress. Work therapy has intention to stimulate the patient, enrich her life, and restore self-esteem. Friendships made in groups help restoring self-respect and self-confidence which makes family relationship better15. It is necessary to gain patients’ trust and help some isolated and unsociable patients with communication. “Some

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patients stuck on the surface level of their experience and they need help to go to some deeper level during their treatment” 16. 2. Aims 1. Define the quality of life of patients after mastectomy caused by breast cancer, and after completed treatment, during the first visit and after three months’ treatment given by the team of daily hospice 2. Using the same test, define the quality of life of patients after mastectomy caused by breast cancer, who were not involved in the treatment program in daily hospice 3. Examined patients and methods 3.1. Examined patients There has been a study conducted in the ward of palliative care of UCC Tuzla. Examined group consisted of thirty-five patients who had mastectomy due to breast cancer, and who visited the daily hospice of palliative care in twelve weeks’ time. Control group consisted of thirty-five patients who also had mastectomy due to breast cancer but who didn’t visit the daily hospice.

The basic criteria to enter the examined group were: examinees should have some kind of confirmed pathohistological diagnosis of breast cancer, and after the diagnosis examinees had mastectomy, and that they have completed specific oncologic treatment (chemotherapy or radiotherapy) according to their oncologist. 3.2. Methods Evaluation of the quality of life by using SF 36 scale is actually expression of total quality of life which is a sum of values from two components: total physical health and total mental health, which consists of four subscales. The values up to 0,25 points imply bad quality of life, between 0,26 and 0,50 is medium quality of life; between 0,51 and 0,75 is good quality of life, and values above 0,76 imply excellent quality of life. Therefore, SF 36 scale has three levels: thirty-six items (level 1), grouped in eight scales (level 2), and third level consists of two summed evaluations based on evaluation of total psychical and mental health. SF 36 test is valid based on project of International Quality of Life Assessment (IQOLA) for evaluation of health, and many examinations show reliability17 and validity18.

Table 1. Demographic characteristics of interviewees Subjects’characteristics

Inside the hospice (n=35)

Outside the hospice (n =35)

In total (n =70)

Age at the time of test Age at the time of op. Living Alone Family with: Low Financial Middle status: High

59,85 ± 10,37 53,37 ± 10,44 8 27 20 14 1

58,77 ± 9,01 53,00 ± 8, 77 6 29 29 12 4

59,31±9, 67 53,18 ± 9,67 14 56 56 26 5

Table 2. Clinical characteristics of the specimen Subjects’characteristics

Inside the hospice (n=35)

Outside the hospice (n =35)

In total (n =70)

Mastectomy: total / partial

35 / 0

33 / 2

68 / 2

Metastasis: Yes / no

9 / 26

10 / 25

19 / 51

Ca type: ductale / lobulare

33 / 2

32 / 3

65 / 5

Localization: R*/ L**/ B***

19 / 13 / 3

14 / 20 / 1

33 / 33 / 4

* R = right; ** L = left; ***B = Both Journal of Society for development of teaching and business processes in new net environment in B&H

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4. Statistical data processing The research was conducted in a form of data analysis gathered through a patients’ survey in the daily hospice of palliative care in JZU UKC Tuzla (Public health centre Tuzla). The information gathered was introduced into a specially created data base on a PC. Statistical processing was conducted by biomedical application software called ‘MedCalc for Widows version 9.4.2.0.’ For graphical processing and presentation following applications were used: SmartDraw 2008 and Office package applications ‘Microsoft Power Point 2007. The complete work was done in a Microsoft Word for Windows and later converted into pdf. format and sent to print. The comparison was made between two groups of test subjects, groups of patients who visited the daily hospice and control groups of patients who were not treated at the hospice. Numerical data are displayed through measurements of central tendency and suitable dispersion measurements. For testing the hypothesis of independent sample concept, between two groups, the T-test and Mann-Whitney test were used, if a discrepancy in distribution was spotted or if a variable was measured by an ordinal scale. For testing the hypothesis of the difference of frequency of parameters of dichotomous scale, the Hi squaretest 2 by 2 was used. For testing the repeated measurements of dependent samples, Parni T-test and Wilcoxon’s tests were used, and results were comprehensively displayed through charts and appropriate graphs. For statistical significance of ‘p’ value the usual level of significance was used, namely ‘p