In the Name of God the Compassionate the Merciful

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Archives of Iranian Medicine, Volume 15, Number 12, December 2012 iii Table of Contents

Table of Contents

736 • Original Articles Challenges and Success Factors in University Mergers and Academic Integrations A. Ahmadvand, K. Heidari, S. H. Hosseini, R. Majdzadeh 736

Six-fold Difference in the Stomach Cancer Mortality Rate between Northern and Southern Iran K. Zendehdel, M. Marzban, A. Nahvijou, N. Jafari 741

Correlation of Quality of Life with Gastroesophageal Reflux Disease amongst Qashqai Nomads in Iran S. J. Masoumi, F. Khademolhosseini, D. Mehrabani, F. Moradi, A. A. Mostaghni, N. Zare, A. Montazeri, M. Saberi-Firoozi 747

Sexual Dysfunction in Male Crystalline Heroin Dependents before and after MMT: A Pilot Study M. Babakhanian, Z. Alam Mehrjerd, Y. Shenaiy 751

Waiting Time for Specialist Consultation in Tehran A. Aeenparast, F. Farzadi, F. Maftoon 756

Identifying Causes of Laboratory Turnaround Time Delay in the Emergency Department M. Jalili, K. Shalileh, A. Mojtahed, M. Mojtahed, M. Moradi-Lakeh 759

Epidemiology of Four Main Nosocomial Infections in Iran during March 2007 – March 2008 based on the Findings of a Routine Sur- veillance System S. M. Zahraei, B. Eshrati, H. Masoumi Asl, Z. Pezeshki 764

A Qualitative Evaluation of Men Living with HIV: Views on Condom Use H. Fallahi, S. S. Tavafian, F. Yaghmaie, E. Hajizadeh, A. Rastegarpour, M. Fouroghi 767 772 • Review Article Current Status of Liver Transplantation R. F. Saidi 772 777 • Case Reports Osteoid Osteoma of the Trapezoid Bone D. Jafari, F. Najd Mazhar 777

Chorea-acanthocytosis: Report of Three Cases from Iran S. Karkheiran, B. Bader, M. Roohani, A. Danek, G. A. Shahidi 780 783 • Photoclinic M. T. Rajabi, S. S. Hosseini, F. Bazvand, S. Z. Tabatabaie, M. B. Rajabi 783

iv Archives of Iranian Medicine, Volume 15, Number 12, December 2012 Table of Contents

785 • History of Medicine in Iran Avicenna’s Canon of Medicine: A Look at Health, Public Health, and Environmental Sanitation M. Saffari, A. H. Pakpour 785 790 • Excerpts from Persian Medical Literature 792 • Letters to the Editor 795 • Subject Index to Volume 15 799 • Author Index to Volume 15

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 v Challenges and Success Factors in University Mergers and Academic Integrations

Original Article Challenges and Success Factors in University Mergers and Aca- demic Integrations

Alireza Ahmadvand MD•1, Kazem Heidari MD1, S. Hamed Hosseini MD1, Reza Majdzadeh DVM PhD1

Abstract Background: There are different reasons for mergers among higher education institutes. In October 2010 the Iran University of Medical Sciences (IUMS) merged with two other medical universities in Tehran. In this study, we aim to review the literature on academic integrations and university mergers to call the attention to challenges and reasons for the success or failure of university mergers. Methods: We searched for studies that pertained to university or college mergers, amalgamation, dissolution, or acquisition in the following databases: PubMed, Emerald, Web of Science, Scopus, and Ovid, without any limitations on country, language, or publication date. Two reviewers selected the search results in a joint meeting. We used content analysis methodology and held three sessions for consensus building on incompatibilities. Results: We reviewed a total of 32 documents. The “merger” phenomenon attracted considerable attention worldwide from the 1970s until the 1990s. The most important reasons for merging were to boost efficiency and effectiveness, deal with organizational fragmentation, broaden student access and implement equity strategies, increase government control on higher education systems, decentralization, and to establish larger organizations. Cultural incompatibility, different academic standards, and geographical distance may prevent a merger. In some countries, geographical distance has caused an increase in existing cultural, social, and academic tensions. Discussion: The decision and process of a merger is a broad, multi-dimensional change for an academic organization. Managers who are unaware of the fact that mergers are an evolutionary process with different stages may cause challenges and problems during organizational changes. Socio-cultural integration acts as an important stage in the post-merger process. It is possible for newly-formed schools, departments, and research centers to be evaluated as case studies in future research.

Keywords: Health Facility Merger, Health Facility Acquisition, Multi Institutional Systems, Systems Integration, Academic Medical Centers

Cite the article as: Ahmadvand A, Heidari K, Hosseini SH, Majdzadeh R. Challenges and Success Factors in University Mergers and Academic Integrations. Arch Iran Med. 2012; 15(12): 736 – 740.

Introduction education. One could readily track the movement from smaller, single-site, and specialized campuses towards larger, multi-site, n higher education, combining organizations in the form of a more comprehensive organizations.7 merger has occurred with both general and specific defini- A merger is still a viable policy option in Iran, as the merger of I tions.1 In the broad sense, a merger is defined as “any form of two universities (K. N. Toosi University of Technology and Ab- organizational combination” and more specifically, it is “a distin- baspour University of Technology) has recently been proposed by guishing type of inter-institutional cooperation, characterized by the Ministry of Science, Research, and Technology.8 irreparable entirety”.2–4 In Iran, one recent experience of a university merger happened In the specific definition, one or both entities will formally fade in October 2010 in which the Iran University of Medical Sciences away and re-emerge as a new body. The transfer of ownership (IUMS) was merged into two other major medical universities occurs with general and common possession of the properties of based in Tehran, Tehran University of Medical Sciences (TUMS) the former organizations. Goedegebuure and Yuzhuo describe the and Shahid Beheshti Medical University (SBMU).9 This merger merger as follows: “the combination of two or more separate in- raised numerous questions in the minds of decision-makers, high- stitutions into a single new organizational entity, in which control and middle-level managers, academic staff, and the general pub- rests with a single governing body and a single chief executive lic. Has this type of merger occurred in other parts of the world? body, and whereby all assets, liabilities, and responsibilities of the If yes, what were the managerial experiences of those mergers? former institutions are transferred to the single new institution”.5,6 In this paper we attempt to answer as many of these questions as As a policy option, merging received plenty of attention in the possible by reviewing the pertinent literature on academic integra- 1970’s primarily because it was one of the popular means by tions and university mergers. We sought to determine answers to which governments initiated systematic restructuring of higher the following questions. What were the experiences with university mergers in other countries? What were the reasons for these Authors’ affiliation: 1Knowledge Utilization Research Center, Tehran Univer- sity of Medical Sciences, Tehran, Iran. mergers? What types of university and academic mergers have •Corresponding author and reprints: Alireza Ahmadvand MD, Knowledge been described? How many phases have been considered in the Utilization Research Center, Tehran University of Medical Sciences, Tehran, merger process? What are the elements of success in university Iran. Tel: +98-217-727-5549, E-mail: [email protected] Accepted for publication: 4 July 2012 mergers? Which methods and/or tools have been used to evaluate the effects on organizational outcomes?

736 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 A. Ahmadvand, K. Heidari, S. H. Hosseini, et al.

Materials and Methods tion,7 and the establishment of larger organizations.13 In an analysis by Bates et al., an increase in actual tuition rates Due to the more general nature of this recent merger, for this and faculty salaries in addition to lower numbers of students were study we considered a broad research scope with an exploratory factors that increased the private four-year college merger rates.18 perspective on reviewing the merger process. However, financial profits have not been the primary incentive We sought to contain our research to university or college merg- for mergers in many countries. Because of their “non-profit sta- ers, amalgamation, dissolutions, or acquisitions. The following tus” perspective, university leaders, administrators, and boards of keywords were selected separately and in combination: (univer- trustees may not seek merger partners19 contrary to the fact that sity OR college OR academic staff) AND (merger OR amalgama- other businesses usually merge to gain additional profits through tion OR acquisition OR integration OR dissolution). We searched increased market power and economies of scale or scope.20 for studies in these databases: PubMed, Emerald, Web of Science, Scopus, and Ovid, without limitations on country, language, and What types of university and academic mergers have been de- publication date. scribed? After the preliminary search we included a wide range of study The most frequent types of mergers are twin-partner vs. multi- designs (e.g., case studies, descriptive studies, or literature re- partner; horizontal vs. vertical (e.g., organizations with similar or views). We attempted to include as many organizational reports, different academic profiles); voluntary vs. involuntary; single- books, theses, dissertations, and other related grey literature sector vs. cross-sectoral; and consolidation vs. take-over.7 In as possible, by sensitive searching in both Google and Google many cases, it is not possible to clearly categorize the merger as Scholar. This research also included supplementary studies from belonging to just one type of merger process. exploratory examination of the bibliographies of the latest studies. Two reviewers in a joint meeting chose search results based on What are the challenges, elements of success and causes of failure title, abstract, and the overall quality of the published evidence. in university mergers? We used content analysis methodology to develop our questions, We divided the answer to this question into three parts: cultural extract answers, and then refine these questions. This was fol- aspects of the merger, geographical distance, and successes and lowed by a narrative answer of the questions. We held three ses- failures. sions for consensus building on incompatibilities. Cultural aspects of the merger Results When studying challenges in “historically and symbolically un-complimentary” organizations, the human aspect of mergers A total of 38 documents were selected for appraisal, of which we and the resultant culture conflicts that have been encountered by 21 chose 32 for the extraction and synthesis phase, relied for the most leaders and upper management are the topics of research. Cul- part on original researches. Questions and related answers follow. tural incompatibility may cause institutions to become reluctant to merge. A dissimilarity in academic missions or cultures may 18 What were the experiences of university mergers in other countries? block an otherwise valuable merger. What were the reasons for these mergers? Examples of cultural conflict, both organizational and academic, Published literature on university mergers date from 1968. Two and the subsequent forces that act as a barrier to a merger, should articles by Jessop10 and O’Malley11 in the former Journal of Irish caution high-level decision-makers to employ expert leadership Medical Association explored the relation of a university merger to keep these damaging conflicts to a minimum. Decision-makers with medical education and services. However, there was a lack of should attempt to develop new relationships and establish high 7,21 original publications on university mergers from 1968 until 1996. morale within the newly formed academic organization. In 1996, Draper described the prospects, problems, and promises Cultural differences are frequently seen as the cause of and rea- in the merger of the United Kingdom colleges of nursing with sons for organizational problems after mergers. By using a sense- departments of nursing in universities to support the formation of making perspective and evaluating ethnographic data from eight a unified educational system.12 Finnish-Swedish mergers, Vaara has specified three concomitant In 2002, Harman et al. debated that the merger phenomenon had cultural sensemaking processes: “search for rational understand- attracted considerable worldwide attention from the 1970s to the ing of cultural characteristics and differences”, “suppressed emo- 1990s, and has since reappeared on the policy agenda.7 Hundreds tional identification with either of the merging sides”, and “pur- of universities and colleges in different countries have recently poseful manipulation of the cultural conceptions for more or less undergone merger processes. We specifically located merger ex- legitimate purposes”. It has been stated that leaders and high-level periences in China,6 the United States of America,13 Norway,14 managers involved in post-merger procedures should understand South Africa,15 Germany,16 and Hong Kong.17 and implement cultural conceptions through these three process- As a model and mechanism of restructuring and increasing levels es. These processes emphasize concerns such as the underlying of institutional collaboration in higher education systems, many structures behind cultural differences that cause them to maintain drivers and pressures in different countries have been proposed “acculturation/acculturative” processes that play a central role in to be the reasons behind the merger of academic organizations. a post-merger, in addition to the incompatibility of values and be- 22 The most important is a boost of efficiency and effectiveness with liefs amongst individuals. regards to substantial growth in student admissions, solving the problems of organizational fragmentation, broaden student access Geographical distance in merger and implement equity strategies, to increase government control It is believed that mergers are often associated with problems, of the overall direction of higher education systems, decentraliza- stress, and concern among managers and staff. Norwegian Tele-

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 737 Challenges and Success Factors in University Mergers and Academic Integrations mark College, a multi-campus institution of five campuses locat- Later, in the consummation phase, the two merging organizations ed at large distances apart was integrated in 1994. This merger join, speeding up the process of combining the organizations. In was expected to result in academic and administrative economies this phase of the merger, the new organization gains a more uni- of scale. One challenge, both during and after this merger, was fied operational identity. In the consummation phase, ignoring is- the relatively large distance between the campuses that ranged sues on organizational compatibility is more difficult. The new from 20 to 180 kilometers. This distance was a major obstacle organization’s full integration and realization of the benefits of its to attaining their goals. To eliminate this barrier, this institution merger does not occur until the post-merger phase. According to developed technological infrastructures such as internet, email, some authors, it may take four to five years for a merger to attain telephone, and videoconferencing. The results of their study have its full potential.25 revealed that even if information technology overcomes some Shrivastava defines three levels for integration following a shortcomings, other important aspects remain that should not be merger: procedural, physical and socio-cultural, all of which lead overlooked. For example, the fact that good technology can not to the defining of procedures and policies, sharing of office space directly, nor satisfactorily replace personal contact. Geographical and a common ideology in terms of regulations and culture.26 In distances have impacted the expectations of this merger such as the context of higher education in China, three categories have lowering administrative costs or academic gains in the form of been described in terms of levels of integration by Wang: superfi- cross-disciplinary courses and programs, and increased co-oper- cial, deep and kernel.27 Superficial integration happens early in the ation in teaching and research. Possibly, geographical distance initial stages of the merger process and is focused on combining increased the existing cultural, social, and academic tensions.14,23 administrations. Institutions and their leadership, financial, regu- latory, and planning arrangements become more united with the Successes and failures intent to assist in building a departure point for a merger of deeper In the United States, Cohen et al. reviewed the initial failures and levels. However, the restructuring and specialization of different analyzed factors responsible for the relative success of a merger disciplines that involves the integration of departments and insti- between two large tertiary academic hospital systems in 1997. tutes sustains a new organization through its deep merger. When They explained the tactics in developing a set of principles for ap- the concepts and cultures within the organization go through re- propriate continued guidance of the merger and discussed the fu- definition and integration, the kernel phase or cultural aspect is ture strategy for the merged organization. In 2000, three years af- completed, of which this phase is considered to be the most vital ter this merger they surveyed the two merged centers to determine component of integration for academic staff.21,23 the integration of their 19 clinical departments across five broad areas: 1) conferences, 2) residency programs, 3) common faculty Which methods and/or tools can be used to evaluate the effects of a and support staff, 4) finances, and 5) research. The researchers merger on organizational outcomes? noted that the overall clinical integration was 42%, which was We have attempted to locate a set of standardized tools for evalu- most frequent with regards to conferences (50%) and least fre- ating effects of a merger on academic organizational outcomes. quent with finances (25%), with a range of 20%–72%. There were However since evaluation methodology is more common for six departments that had more than 50% clinical integration after businesses and economic organizations,28 it is difficult to adapt three years. Surprisingly, they discovered that the single-chairper- these tools to academic organizations. son model for department leadership was the most successful in achieving major clinical integration of the previously detached Discussion departments. According to Cohen et al., the skills of leaders to act as a team and lead the change process was the most vital factor for This review of the literature revealed that the decision and pro- the attainment of a sensible level of clinical integration.24 cess of a merger is a broad, multi-dimensional change for an aca- Successful staff integration of pre-merger organizations with demic organization that consists of an extensive range from the the intent to achieve synergy was a common, major challenge not actual physical joining to deep socio-cultural mission-focused only for the management of individual institutions, but also for mergers. entire higher education systems.6 We have located numerous reports and case studies of estab- However, Cohen et al. did not address the operational non-clin- lished university mergers throughout different regions of the ical aspects of the merger in departments such as finance, quality world that have occurred in diverse educational and managerial assurance, human resources, legal affairs, and purchasing. They contexts. Mergers are not an uncommon phenomenon among the argued that merger of specified system departments was easier higher education setting.29 and quicker than the integration of the clinical departments and It is out of the scope of this article to discuss the pros and cons provided “economies of scale without loss of market share”.24 of mergers, but rather this paper illustrates other countries’ experiences and how mergers can be managed in order to obtain the best How many phases and levels have been considered in the merger results. Managers should be aware that a merger is an evolution- process? ary process with different stages and levels and challenges and Royston, Hinings, and Brown have defined three phases for a problems may occur at some time during organizational changes. merger: 1) courtship in which the need for organizational combi- Different experiences worldwide have shown that a merger is one nation is recognized; 2) consummation which consists of planning of the most noteworthy dealings an organization may engage in. the merger and its implementation; and 3) post-merger during We found tacit (not explicit) evidence stating that solving the which the institutionalization occurs. The courtship phase corre- problems of organizational fragmentation and increasing control sponds to a planning phase in which organizational fitting or com- from the Ministry of Health and Medical Education on the overall patibility is neglected and strategic fitting is the primary focus. direction of health system performance in Tehran were the pri-

738 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 A. Ahmadvand, K. Heidari, S. H. Hosseini, et al. mary reasons for the TUMS, SBMU and IUMS merger. Future sake of merging, but that integration should be encouraged to a research may show other reasons for this event or may determine certain extent where and when it makes sense to attain particular if the objectives of this merger have been met. program goals”.24 An academic institution may cease to exist after a merger or at As no formal assessment of achievements from the TUMS, least may lose its pre-merger identity. In this regard the merger SBMU, and IUMS merger has been published at the time of this can be painful with many wounds that need to be healed. Har- article, we cannot explicitly discuss the elements of success in man claims that the more widespread practice is “taking-over” this merger or effects of this merger on organizational outcomes. another institution rather than a merger and that there are few true, However, according to recommendations, the greatest lesson to be factual mergers that occur in educational and commercial enter- learned is that large geographical distance will prolong the time prises.7 Although we have been unable to assign an unambiguous period of the merger process at all levels of integration and it is typology of merger to this specific experience in Iran, however in crucial to take this challenge into account during and after the in- appearance, patterns of horizontal, twin-partner, involuntary, and tegration process.14,23 In addition, attention to cultures and more single-sector mergers could be found in the departments within importantly, sub-cultures should not be neglected, incorporating each university. the involvement of all academic staff from leaders to managers, It is a general observation to anticipate that it takes a long time among others. A successful merger process also depends on atten- (perhaps over ten years) for the new institution formed by a merg- tive interactions with the external environment and the provision er to function as a unified and integrated identity. This consider- of an internal dynamic environment which fosters satisfaction and ably challenges the intent of efficiency as a purpose and reason to productivity of the entire staff.31 merge. There is no one best way to bring about a merger. 30 Because the experiences of managerial changes in universities Socio-cultural integration acts as an important stage in the post- are not well documented or published in most developing coun- merger process, particularly in the institutional setting and aca- tries (including Iran), we did not have access to all relevant lit- demic staff integration. Successful mergers need to identify and erature on mergers in countries such as ours. We have presumed adjust the cultures of pre-merger organizations in an attempt for that in some cases it might be the condition that a merger was integration of the cultures with the goal of reaching a common the consequence of an external policy and not directly related to culture in terms of its values, beliefs and norms over a short or the outcome of the interests mentioned in our study; however, we long duration and at different levels within the organization (Box extracted those sections that were in accordance with our explor- 1).13 This is more difficult in academic compared to non-academic atory perspective of the merger process. organizations. This stage of integration needs more time and effort As the three universities based in Tehran were (and the two new when compared with physical or procedural integration. Cultural organizations still are) involved in health care and service pro- integration begins with a superficial integration such as adminis- vision to their specific catchment areas in addition to human re- trative rules and evolves to deeper levels which necessitate new source functions (specifically, education and research functions), definitions of the new organizational culture. Internalization of the it was not our intent to assess how to deal with the merger with merger needs to pay attention to all these levels. According to the regards to health care provision and the financial aspects of these Greenwood categorization,25 this merger experience has rapidly organizations. These specific functions should be studied in future entered the “post-merger” phase and has not evolved inclusively research activities. through previous phases of “courtship” for need assessment and Not all case studies followed formal protocols, but relied chief- “consummation” for planning. This may cause a specific gap to ly on qualitative evaluation. However as a result of the lack of be developed which delays evolution of the most important phase comprehensive case studies on university mergers, we included of the merger, the “socio-cultural” or “kernel” phase according to semi-structured case studies in our review process. Some of the Shrivastava26 and Wang.27 presented information in published articles was based on experts Factors associated with the relative success of the clinical merg- and/or key-informant interviews, their expertise and judgment.32 er were as follows: “constant communication among the leader- We located a few studies that were similar to our situation. How- ship and staff”; “flexibility in developing the leadership models”; ever, the generalization of results pertaining to organizations with “patience and lack of complaint in having activities advance over different settings and culture needs additional consideration. time” which caused trust to develop among senior leaders and We anticipate the production of additional research projects by superior managers; “presence of a senior executive arrangement scholars to evaluate organizational change and practical policy- whose decision-making power and authority is accepted”; and the making processes as well as institutional and system transforma- principle that “no clinical service should be integrated just for the tions. TUMS is the largest medical university in Iran, which con-

Box 1: Case study of a successful merger. During and just after the merger of two medical schools which led to the establishment of the Allegheny University of Health Sciences, faculty and staff encountered major changes, all with frustrations and fears because they were somewhat uncertain about the new direction of the established university. However, in the early phases of the merger process which was the most critical stage, faculties of the two merged academic organizations were brought together to plan the Generalist Physician Initiative (GPI) and apply for a grant from The Robert Wood Johnson Foundation. Although the new merged school was awarded the GPI grant in the middle of its complex merger, the GPI application action had a deep impact not only on the merger of those two schools, but also on the consequently evolved educational enterprise. Ross et al. explained that the GPI provided a center of attention with an apparent set of goals and this single, pervasive attempt had a significant effect on the formation of a unified faculty in a recently-united school of medicine.13

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 739 Challenges and Success Factors in University Mergers and Academic Integrations sists of more than 10 schools, approximately 70 research centers, 13. Ross LL, Appel MH, Kelliher GJ. The role of the generalist physician with more than 2000 academicians and 19000 students at different initiative in the merger of Hahnemann University and Medical Col- lege of Pennsylvania. Acad Med. 1999; 74: S16 – S23. levels. There are over 80 different disciplines for post-graduate 14. Kyvik S. The merger of non-university colleges in Norway. High education at TUMS. Thus it is readily possible for newly-formed Educ. 2002; 44: 53 – 72. schools, departments and research centers to be evaluated as case 15. Hall M, Symes A, Luescher T. The Governance of Merger in South studies in both qualitative and quantitative research. African Higher Education. Research Report prepared for the Council on Higher Education: Council on Higher Education; 2004. 16. Maisch B. A paradigm change in German academic medicine. Merger Conflicts of interest and privatization as exemplified with the university hospitals in Mar- The authors of this study are studying and/or working for Tehran burg and Giessen. Herz. 2005; 30: 153 – 158. University of Medical Sciences, one of the universities engaged in 17. Normile D. Hong Kong. Science university fears merger could weak- en research program. Science. 2003; 301: 1316 – 1317. this recent merger experience. 18. Bates LJ, Santerre RE. A time series analysis of private college clo- sures and mergers. Rev Indust Organiz. 2000; 17: 267 – 276. 19. Hansmann H. The Ownership of Enterprise. Cambridge, MA: Har- Acknowledgment vard University Press; 1996. 20. Scherer FM, Ross D. Industrial Market Structure and Economic Per- The authors wish to acknowledge the efforts by Dr. Fatemeh Ra- formance. Boston: Houghton Mifflin Company; 1990. jabi MD, Assistant Professor of Social Medicine for her efforts in 21. Harman K. Merging divergent campus cultures into coherent educa- reviewing the literature and at the beginning of this study. tional communities: Challenges for higher education leaders. High Educ. 2002; 44: 91 – 114. 22. Vaara E. Constructions of cultural differences in post-merger change References processes: a sensemaking perspective on Finnish-Swedish Cases. Management. 2000; 3: 81 – 110. 23. Norgard JD, Skod OJ. The importance of geography and culture in 1. Vaara E. On the Discursive Construction of Success/Failure in Narra- mergers: a Norwegian institutional case study. High Educ. 2002; 44: tives of Post-Merger Integration. Organiz Stud. 2002; 23: 211 – 248. 73 – 90. 2. Harman G. The Dawkins Reconstruction of Australian higher educa- 24. Cohen JR, Dowling M, Gallagher JS. The trials, tribulations, and relation. High Educ Pol. 1989; 2: 1 – 14. tive success of the ongoing clinical merger of two large academic hos- 3. Lang D. A lexicon of inter-institutional cooperation. High Educ. 2002; pital systems. Acad Med. 2001; 76: 675 – 683. 44: 153 – 183. 25. Royston G, Hinings CR, Brown J. Merging Professional Service 4. Mulvey TM. An Analysis of the Mergers of American Institutions of Firms. Organiz Sci. 1994; 5: 239 – 257. Higher Education [dissertation]. Amherst: University of Massachu- 26. Shrivastava P. Postmerger Integration. J Bus Strategy. 1986; 7: 65 – setts Amherst; 1993. 76. 5. Goedegebuure L. Mergers in Higher Education: A Comparative Per- 27. Wang W. Merger and development: strategic thinking of post-merger spective. Utrecht: Lemma; 1992. university reform. Chin High Educ Reform. 1998; 12: 18 – 20. 6. Yuzhuo C. Academic Staff Integration in Post-Merger Chinese Higher 28. Krug JA, Shill W. The big exit: executive churn in the wake of M&As. Education Institutions. Finland: Tampere University; 2007. J Bus Strategy. 2008; 29: 15 – 21. 7. Harman K, Meek VL. Introduction to special issue: “Merger revis- 29. Dobbins M, Knill C, Vogtle EM. An analytical framework for the ited: international perspectives on mergers in higher education”. High cross-country comparison of higher education governance. High Educ. 2002; 44: 1 – 4. Educ. 2011; DOI 10.1007/s10734-011-9412-4. 8. 2011. Available from: URL: http://www.mehrnews.com/FA/newsde- 30. Makgoba MW. Merger Report 2007. KwaZulu-Natal: University of tail.aspx?NewsID=1396192 [Accessed October 26, 2012] KwaZulu-Natal; 2007. Available from: http://www.ukzn.ac.za/publi- 9. 2010. Available from: URL: http://publicrelations.tums.ac.ir/news/de- cations/merger%20report_low%20res_web1.PDF [Accessed Octo- tail.asp?newsID=19786 [Accessed October 26, 2012] ber 26, 2012] 10. Jessop WJ. Medical education and the University merger. J Ir Med 31. McGinnis RA, McMillen W, Gold JP. Merging two universities: the Assoc. 1968; 61: 45 – 48. Medical University of Ohio and the University of Toledo. Acad Med. 11. O’Malley E. The University merger and the medical services. J Ir Med 2007; 82: 1187 – 1195. Assoc. 1968; 61: 60 – 61. 32. Welsh JF. The role of governing boards in college and University 12. Draper P. The merger of United Kingdom colleges of nursing with Mergers. In: Martin IJ, Samels J, editors. Merging Colleges for Mu- university departments of nursing: prospects, problems and promises. tual Growth. Baltimore: The Johns Hopkins University Press; 1994. J Adv Nurs. 1996; 23: 215 – 216.

740 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 K. Zendehdel, M. Marzban, A. Nahvijou

Original Article Six-fold Difference in the Stomach Cancer Mortality Rate between Northern and Southern Iran

1 2,3 1 4 Kazem Zendehdel MD PhD• , Maryam Marzban , Azin Nahvijou MD , Nahid Jafari MD

Abstract Background: Stomach cancer is the most common cancer in Iran. A multi-ethnic population and wide variation in the environmental risk factors may lead to variations in cancer risk within this country. We have designed an ecological study and evaluated geographical variation regarding mortality from stomach cancer and its established risk factors in Iran. Methods: We used the Iranian National Causes of Death Registry and estimated the age-standardized mortality rates (ASMR) of stomach cancer in 29 Iranian provinces, stratified by sex and area of residence (rural/urban). Results: The average ASMR of stomach cancer among Iranian males was 15 per 100,000 and for females it was 8.1 per 100,000. The highest and lowest mortality rates were observed in Kurdistan with an ASMR of 29.1 per 100,000 in northwestern Iran and Hormozgan that had an ASMR of 5.0 per 100,000 in southern Iran. Males had approximately a two-fold higher ASMR compared to females, as did rural residents when compared with urban residents. The prevalence of H. pylori infection was about 90% in the province of Ardabil (a high-risk area) and 27% in the province of Sistan-Baluchistan (a low-risk area). Conclusions: The wide geographical variation and high mortality rate of stomach cancer in Iran is likely due to differences in the exposure to the environmental risk factors among people living in the high- and low-risk areas, particularly H. pylori infection, a well-established risk factor of stomach cancer.

Keywords: Cancer, epidemiology, Iran, mortality, stomach

Cite the article as: Zendehdel K, Marzban M, Nahvijou A, Jafari N. Six-fold Difference in the Stomach Cancer Mortality Rate between Northern and Southern Iran. Arch Iran Med. 2012; 15(12): 741 – 746.

Introduction deserts located in the central and southern regions of the country.9 Such a large variation in ethnicity and environmental factors indi- tomach cancer is the second highest cause of cancer mortal- cate potential differences in the risk profile of the Iranian popula- ity worldwide.1 Although the incidence rate of stomach can- tion with regards to different cancers, including stomach cancer. S cer has decreased in the Western world, its incidence and Screening and treatment of H. pylori, the most important risk mortality have increased or remained stable in middle and low factor for stomach cancer, is recommended as the most reason- income countries.2 Stomach cancer is usually diagnosed in very able risk reduction strategy for its prevention in high-risk popula- advanced stages and its prognosis is poor. Efforts to improve the tions according to the Asia-Pacific Consensus Guideline in 2008.3 treatment outcome of stomach cancer have been discouraging. However, implementation of this recommendation is challenging Therefore, stomach cancer prevention is prioritized, particularly due to economical and practical reasons. Most people are infected in high-risk areas.3 with H. pylori in high-risk areas. In Ardabil Province, H. pylori in- According to Globocan 2008, stomach cancer is the most com- fection has been estimated to be approximately 90%.10 Therefore, mon cancer in Iran.1,4 While high incidence rates of stomach cancer epidemiological studies are warranted to define high-risk groups have been reported from different geographic areas in Iran,5,6 Ard- and explore new options for stomach cancer prevention. abil Province in northwestern Iran has the highest rates of stomach Ecological studies and evaluation of the geographic patterns and cancer for both males [age-standardized incidence rate (ASR) = 50 epidemiology of stomach cancer may help measure the exact bur- per 100,000] and females (ASR = 24 per 100,000).7 On the other den of stomach cancer in Iran and identify high-risk regions that hand ASRs for stomach cancer are considerably low in Kerman need efficient interventions. Results from this type of study will Province, which is located in the central part of the country.8 lead to appropriate priority setting for research and cancer control Iran has a multi-ethnic population of over 70,000,000 with a programs. In addition, this study aims to evaluate the potential wide variation in climate and environmental factors, such as cold, link between patterns of stomach cancer mortality in Iran and geo- mountainous weather in the northwest and west, high humidity in graphical distribution of H. pylori infection. the Caspian Littoral area in the north, and dry, hot weather in the Materials and Methods Authors’ affiliations: 1Cancer Research Center, Cancer Institute, Tehran Uni- versity of Medical Sciences, Tehran, Iran. 2Research Center for Modeling in Health, Kerman University of Medical Sciences, Kerman, Iran. 3Research Center Due to a lack of validity and completeness of the nationwide for Traditional Medicine and History of Medicine, Shiraz University of Medical cancer registry,11 we used the nationwide mortality registry to 4 Sciences, Shiraz, Iran. Ministry of Health and Medical Education, Tehran, Iran. study the geographical pattern of stomach cancer in Iran. We fur- •Corresponding author and reprints: Kazem Zendehdel MD PhD, Cancer Re- search Center, Cancer Institute, Tehran University of Medical Sciences, Tehran ther studied the association of observed variations with the estab- 13145-158, I. R. of Iran. E-mail: [email protected] lished risk factors. Accepted for publication: 15 August 2012

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 741 Stomach Cancer Mortality in Iran

females, respectively. Figure 1 presents the pattern of ASMRs National Mortality Registry for stomach cancer among males in 29 Iranian provinces. The After administrative planning, mortality data from different northern part of the country, particularly the northwestern region, provinces was compiled and analyzed centrally by the Iranian showed a considerably higher mortality rate for stomach cancer Ministry of Health and Medical Education. The first report on than provinces located in the southern and central regions of Iran. cause-specific mortality rate published in 1998 was based on mor- Among males, the ASMR for stomach cancer was 15 per tality data from four provinces. Later, the registration activity was 100,000. Stomach cancer comprised 23.6% of the total cancer extended to other provinces and subsequent reports covered more deaths (Table 1). The highest ASMR was observed in Kurdistan areas. From 2000–2003 the registry covered 10, 18, 19, and 23 (29.1), followed by East (27.6) and West Azerbaijan (26.1) Prov- provinces, respectively. In 2004 and 2005 the mortality registry inces. In contrast, ASMRs for stomach cancer were considerably covered almost the entire country and reported the cause-specific low in the southern parts of the country, including Hormozgan crude mortality rates for 29 provinces. To date, Tehran Province (5.0), Sistan-Baluchistan (5.3), and Bushehr (5.5) Provinces. The (the capital), with a population of 10,000,000 (about 14% of the mortality rate was also relatively low in the central part of the country), has not been covered in the mortality registry.12 In order country, including Yazd (7.1), Kerman (7.1), Khuzestan (8.2), Is- to estimate the total number of deaths nationwide we added 10% fahan (8.4), and Fars (8.8) Provinces. of the reports to stratify the rate for both males and females, and for residential areas (rural/urban). The classification of rural and urban areas was based on the official classification and definitions provided by the Ministry of Health. In this study, we used cancer mortality data from the latter period (2004–2005).

Systematic review of the prevalence of H. pylori infection We found no nationwide data that evaluated the pattern of H. pylori infection prevalence in Iran. Thus we systematically searched English (PubMed, ISI) and Farsi (SID, Magiran) databases and retrieved all published data regarding the prevalence of H. pylori infection in different parts of Iran. We only included papers that reported the prevalence of H. pylori infection among healthy individuals over the age of 40 years. Excluded from the analyses were studies that evaluated the prevalence among the younger age groups and children. In addition, studies that evaluated H. pylori infection among any disease population were excluded. If a study evaluated H. pylori infection among different age groups, we estimated the prevalence among the older age group based on data presented in the papers. Since we located only a few papers that met our inclusion criteria, we could only qualitatively evaluate the potential role of H. pylori infection in the pattern of stomach cancer with regards to age-standardized mortality rates (ASMRs).

Statistical analyses We divided the number of stomach cancer mortalities by the total population of each province and estimated the crude mortality rates for stomach cancer. We estimated ASMRs for stomach Figure 1. Geographical pattern of age-standardized mortality rate (ASMR) cancer in 29 Iranian provinces using the age distribution of the per 100,000 for stomach cancer among Iranian males. Note: There were 13 standard world population. We performed stratified analyses by no mortality data in the national mortality registry for the capital province sex and residence to determine the mortality rates for males and (Tehran), located in the central part of the country. females and rural/urban residents. In addition we studied the frequency of stomach cancer mortality relative to the total cancer A decreasing gradient from the north to the south was also ob- mortality in each region. The ASMRs were categorized into four served among females. The highest ASMRs were recorded in strata (< 10, 10–14, 15–20, 20–24, and > 25 per 100,000) and the Kurdistan (18.0), Ilam (15.9), West Azerbaijan (14.6), and East estimates were placed on a map of Iran using ArcGIS software Azerbaijan (13.6), whereas provinces located in the southern and (version 9.2) in order to provide a graphical representation of the central part of the country such as Hormozgan, Sistan-Baluch- mortality rate. We used STATA statistical software for analyses. istan, Southern Khorasan, Isfahan, Bushehr, Kerman, and Yazd had lower ASMRs for stomach cancer among females (Table 1). Results The ASMR for stomach cancer among females (8.1 per 100,000) was about half of the rate noted for males (15.0 per 100,000; Fig- In overall 12,804 stomach cancer death occurred in two years ure 2). (2004–2005) in Iran, 8579 were males and 4225 were females Stratified analysis according to residence showed that the ASMR (Table 1). This data indicate that annually about 4000 and 2000 in rural areas (21.5) was two-fold the rate in urban areas (10.6; death due to stomach cancer occur among Iranian males and Figure 3). The mortality rate among males who resided in rural

742 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 K. Zendehdel, M. Marzban, A. Nahvijou

Table 1. Age-standardized mortality rate (ASMR) of stomach cancer among males in urban and rural areas of 29 provinces in Iran from.

Males Females Province No. of cases* Percentage of all No. of cases* Percentage of all ASMR ASMR (2004–2005) cancer deaths (2004–2005) cancer deaths

Kurdistan 366 33.8 29.1 194 31.5 18.0 27.6 320 26.9 14.6 West Azarbaijan 611 28.8 East Azarbaijan 915 26.2 26.1 447 20.3 13.6 Zanjan 214 30.8 25.3 94 25.0 10.8 Kohgilouyeh B 96 45.3 23.7 32 37.7 8.5 North Khorasan 139 27.4 21.2 73 24.4 12.1 Ardabil 225 33.3 21.0 114 32.6 11.7 Charmahal 132 31.7 18.9 67 30.9 10.8 Ilam 79 24.0 18.0 55 29.6 15.8 Semnan 100 21.8 17.1 42 15.6 7.3 Khorasan Razavi 792 27.6 17.1 378 21.2 8.8 Mazandaran 483 27.3 17.0 214 21.2 7.9

Gilan 443 26.6 16.7 191 21.2 7.3 Lorestan 229 27.1 15.5 136 26.8 11.4 Markazi 207 22.1 14.3 108 18.8 7.5 Kermanshah 242 20.0 14.2 119 17.7 7.8 Hamadan 225 27.0 13.0 109 22.0 7.1 Ghom 96 17.7 12.0 53 14.7 7.1 Golestan 130 19.9 11.3 58 14.3 5.5 Qazvin 104 18.9 10.8 77 20.3 8.6 South Khorasan 61 22.3 10.6 23 12.9 3.6 Fars 329 19.0 8.8 185 17.0 5.4 Isfahan 380 15.9 8.4 191 11.8 4.3 Khuzestan 234 16.0 8.2 130 14.2 5.0 Kerman 149 14.4 7.1 97 14.5 4.7 Yazd 67 11.5 7.1 38 8.8 4.7 Boushehr 38 10.7 5.6 27 9.1 4.6 Sistan 74 23.6 5.3 38 19.4 3.3 Hormozgan 47 19.1 5.0 24 14.5 2.3 Overall** 7207 23.6 15.0 3634 22.1 8.1 Tehran (estimated) 1372 — 15.0 591 — 8.1 Overall (Iran) 8579 23.6 15.0 4225 22.1 8.1 ASMR =Age Standardized Mortality Rate; *Number of cases for two years, 2004 and 2005; **No. of stomach cancer deaths for Tehran Province was estimated as an average of the mortality rate based on the other 29 provinces in the 14% of the population living in Tehran. areas of Kurdistan was 45 per 100,000, while the overall ASMR Discussion among urban residents was 20.4 per 100,000. However, ASMRs among rural and urban residents in Sistan and Baluchistan, Ker- We found extremely high mortality rates for stomach cancer in man, Yazd, Khuzestan, and Ghom Provinces were almost equal. Iran, particularly among males who resided in the northwestern part of the country. There was a clear north to south gradient in the H. pylori infection mortality rate of stomach cancer that ranged from 29.1/100,000 in We found only eight published reports on the prevalence of H. Kurdistan Province in northwestern Iran to 5/100,000 in Hormoz- pylori infection among healthy Iranians over 40 years of age (Ta- gan Province in the southern part of Iran. A similar pattern was ble 2). The highest prevalence was observed in the high-risk Ard- observed for females. abil Province located in the northwestern region (89.2%)10 and the Despite several strengths of our findings, this study was ham- lowest prevalence was observed in the low-risk Sistan-Baluch- pered by a few limitations. First, the mortality registry is still new istan Province in southeastern Iran (27%).14 However, the preva- in Iran and the validity and completeness of the data for cancer lence was high in both Qazvin (87.5%) and Kerman (62%–85%) diagnosis has not yet been evaluated. Stomach cancer in its ad- Provinces, which have been determined to be medium (ASMR: vanced stages with distant metastases to other organs (including 10.8/100,000; Qazvin) and low-risk (ASMR: 7/100,000; Kerman) the liver, lymph nodes, lungs, and bones) might be misdiagnosed regions for stomach cancer.15,16 and the type of cancer may be recorded as “unknown” on the

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 743 Stomach Cancer Mortality in Iran

Figure 2. Age-standardized mortality rates (ASMR) of stomach cancer in Figure 3. Age-standardized mortality rates (ASMR) of stomach cancer 29 provinces among Iranian males and females. in 29 provinces among Iranian males stratified by residential place (rural/urban areas).

Table 2. Prevalence of H. pylori infection among Iranian general population over the age of 40 years who reside in various provinces of Iran. Risk of stomach Author, year Area Province Age (years) Sample size Prevalence (%) cancer Malekzadeh R, 200410 Northwestern Ardabil High > 40 1101 89 Sheikholeslami H., 2004*25 Northwestern Ghazvin High > 40 120 88 Babamahmoudi F, 2001*26 North Mazandaran High > 40 N/A 75 Ghadimia R, 200427 North Babol High Mean≈50 130 80 Alizadeh A, 200928 West Hamadan High > 40 570 82 Jafarzadeh A, 2006*16 Central Kerman Low 41–60 60 85 Zahedi MJ, 2002*15 Central Kerman Low > 35 113 62 Metanat M, 201014 Southeast Sistan-Baluchistan Low > 30 85 27 *These papers were in Farsi and published in local journals. death certificate, leading to an underestimation of the mortality non-differential. Although nationwide population-based cancer rate. On the other hand, clinically diagnosed cancers arising from registration does not exist in Iran, available reports from popula- other intra-abdominal organs such as colorectal, hepatic, small in- tion-based cancer registries have supported our findings. testine, and the pancreas might be registered as stomach cancer on The ASR of stomach cancer was elevated in Ardabil Province the death certificates, which would inflate the mortality rate. -Al (ASR: 51.8/100,000),7,18 however, it was relatively low in Ker- though misclassification of cancer types may exist, the mortality man Province (ASR: 10.2/100,000).8 Therefore, notwithstanding registry has been established based on a systematic approach and some reservations, we have concluded that the observed pattern gradually extended from 5 to 29 provinces.12 We have used the lat- and variations in the mortality rates of stomach cancer are reliable est mortality registry data from 2004 and 2005 when the registry for policy making and priority setting. covered most of the provinces in Iran and reached relatively op- A nearly six-fold excess mortality rate of stomach cancer in timal accuracy and completeness. In addition, cancer is a chronic the northern part of Iran warrants a causal explanation. H. py- disease and misclassification in the death registry is less likely lori infection is the strongest established risk factor for stomach compared to other causes of death.17 Finally, because of the central cancer.19,20 A pooled analysis of data from 12 nested case-control administration of the mortality registry, over- or underestimations studies has shown a six-fold excess risk of stomach cancer due of cancer mortality in different geographical regions should be to H. pylori infection after ten years of follow-up.19 We may link

744 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 K. Zendehdel, M. Marzban, A. Nahvijou the geographical variation in the risk of stomach cancer in Iran to logical studies are required to see if the observed pattern could be the variation in the prevalence of H. pylori infection. Although associated with tobacco use in Iran. few studies have evaluated the prevalence of H. pylori infection Recent Asia-Pacific consensus guidelines recommend that in the healthy Iranian adult population, available data support our screening and eradication of H. pylori infection (screen and treat expectations. A population-based survey in Ardabil Province has strategy) is the most reasonable risk reduction strategy for gastric shown that 90% of the people who reside in this high-risk region cancer prevention in high-risk populations.3 In a cross-sectional are infected with H. pylori. The same study has shown that in this endoscopic survey, an evaluation of H. pylori by histology and area 40% of the inhabitants live with atrophic gastritis, a strong rapid urease test has shown that about 90% of people who re- predictive intermediate risk factor for stomach cancer which is sided in Ardabil Province were H. pylori infected.10 Based on the associated with H. pylori infection.10 We have also found a sig- Asia-Pacific guideline, most Iranian males who reside in high-risk nificantly lower prevalence of H. pylori infection in Sistan-Balu- provinces should undergo eradication of H. pylori infection. Al- chistan Province (27%), which is a very low-risk area for stomach though the cost effectiveness and feasibility of the recommended cancer in southeastern Iran.14 However, in the low-risk Kerman strategy should be studied in Iran, it would be more reasonable to Province the prevalence of H. pylori infection is relatively high at target more high-risk groups and select a limited population for 60%–80%.15,16 Further epidemiological data on the prevalence of screening in these areas. There are proposals to measure levels of H. pylori from different parts of Iran may uncover the role of this serum pepsinogen I (PGI) and pepsinogen II (PGII) and use the infection in the observed geographical patterns of stomach cancer low serum PGI and PGI/PGII ratio as a marker to detect high-risk in Iran. H. pylori strains that contain the Cag-A gene are known groups of people with atrophic gastritis for further investigation to cause more extensive inflammation in stomach mucosa and an- and active surveillance.24 Population-based case-control and co- tibodies against Cag-A persist long after eradication.20,21 Due to hort studies in high-risk areas may also uncover etiologic factors a variation in the ethnic groups that reside in high- and low-risk for stomach cancer in Iran and assist with designing an appropri- areas, studies on the association of host genetic factors and sus- ate prevention program. ceptibility genes to high-risk infection may be of assistance. In conclusion, the large geographical variation and high mortal- A north to south decreasing gradient in the incidence rate of ity rate of stomach cancer in Iran could be linked to H. pylori stomach cancer has been previously reported in Europe and infection, smoking, living in a rural area, and a history of lack of Asia.22 The difference in Europe is 1.5-fold, where Europe is a refrigerator use. However, well-designed, large scale case-control known low-risk area for stomach cancer. However, in Japan and and cohort studies, particularly in high-risk areas, are warranted to China, which are both high-risk countries for stomach cancer, a make a firm inference about the role of these factors on the etiol- different geographical pattern has been reported. While a mod- ogy of stomach cancer. Until achieving an appropriate and cost- est geographical variation in the incidence rate of stomach can- effective prevention program, we suggest primary prevention cer was reported in Japan, an up to seven-fold difference in the programs in the high incidence areas, including public awareness incidence rate of stomach cancer was reported in China, which about stomach cancer risk factors. Decreasing salt intake, using ranged from 145 per 100,000 in Changel Province to about 20 fridge to keep the food, decreasing tobacco consumption, in- per 100,000 in Beijing.21 Most of the high incidence areas were creasing consumption of fresh fruits and vegetables and etc. may located in the mid-western parts of China, which included Gansu, decrease risk of stomach cancer. In addition, people and health Henan, Hebei, Shanxi, and Shaanxi Provinces. Although factors care system should follow-up the gastric sign and symptoms sug- associated with socioeconomic status might account for a part of gesting H. pylori infection, peptic ulcer, and cancer. We further this geographical pattern, the reasons behind such a large regional suggest conducting etiologic research in such a setting. The large variation within a country have not been explained. In Iran, so- geographical variation in the incidence of stomach cancer in I.R. cioeconomic status in the high and low incidence areas is similar. of Iran and the differences in the life style and ethnicity of people However, the high-risk areas in the northern part are mountain- who live in the high- and low-risk areas creates a unique oppor- ous with a cold and humid climate, while the low-risk areas in tunity for epidemiological and clinical research. Results of these the central and southern part of the country have a dry and warm types of research may shed additional light on etiology and pre- climate which results in a large variation in life style, nutrition vention strategies for stomach cancer in the I.R. of Iran. habits, and food preservation methods, among others. In addition, All authors declare no conflict of interest. people from different ethnicities in the high- and low-risk areas have differing genetic factors which may also play an important Acknowledgments role in the epidemiology of stomach cancer in Iran. Other established risk factors for gastric cancer include tobacco This study was funded by a grant from Tehran University of smoking, low consumption of fruits and vegetables, lack of a Medical Sciences (No.: 87-01-51-6953). We thank the Health refrigerator at home, low socioeconomic status, male sex, high Network Development Center and the Ministry of Health and salt consumption, nutritional exposures, a positive family history Medical Education for their generous help in addition to provid- of cancer, ethnicity, and genetic factors.22 Tobacco smoking has ing national mortality data. been shown to increase the risk for stomach cancer. In a meta- analysis, this risk of stomach cancer among smokers compared References to non-smokers increased by 1.5 to 2.5-fold, with a somewhat 23 higher estimate in males than females. Few case-control studies 1. Ferlay J, Shin H, Bray F, Forman D, Mathers C. GLOBOCAN 2008, have shown a weak association between smoking and stomach Cancer Incidence and Mortality Worldwide. Lyon, France: Interna- cancer in Iran.24 In addition to cigarette smoking, hookah smoking tional Agency for Research on Cancer; 2010. 2. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. is practiced among Iranian men and women. Further epidemio- CA Cancer J Clin. 2005; 55: 74 – 108.

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 745 Stomach Cancer Mortality in Iran

3. Fock KM, Talley N, Moayyedi P, Hunt R, Azuma T, Sugano K, et health care centers of Kerman City in 2000. J Kerman Univ Med Sci. al. Asia-Pacific consensus guidelines on gastric cancer prevention. J 2002; 9: 140 – 145. Gastroenterol Hepatol. 2008; 23: 351 – 365. 16. Jarfarzadeh A, Sajadi M, Rashidinejad H. Prevelance of IgA Anti-H. 4. Sadjadi A, Nouraie M, Mohagheghi MA, Mousavi-Jarrahi A, pylori antbody among blood donors in Rafsanjan City, Iran. Tabib-e- Malekezadeh R, Parkin DM. Cancer occurrence in Iran in 2002, an in- Shragh. 2006; 8: 101 – 109. ternational perspective. Asian Pac J Cancer Prev. 2005; 6: 359 – 363. 17. Parkin D, Chen V, Frelay J, Storm H. Comparability and Quality Con- 5. Mohagheghi MA, Mosavi-Jarrahi A, Malekzadeh R, Parkin M. Can- trol in Cancer Registration. Lyon: International Agency for Research cer incidence in Tehran metropolis: the first report from the Tehran on Cancer; 1994. Population-based Cancer Registry, 1998–2001. Arch Iran Med. 2009; 18. Babaei M, Jaafarzadeh H, Sadjadi AR, Samadi F, Yazdanbod A, Fal- 12: 15 – 23. lah M, et al. Cancer incidence and mortality in Ardabil: report of an 6. Babaei M, Mousavi S, Malek M, Tosi G, Masoumeh Z, Danaei N, ongoing population-based cancer registry in Iran, 2004–2006. Iranian et al. Cancer occurrence in Semnan Province, Iran: results of a pop- J Publ Health. 2009; 38: 35–45. ulation-based cancer registry. Asian Pac J Cancer Prev. 2005; 6: 159 19. Helicobacter and Cancer Collaborative Group. Gastric cancer and – 164. Helicobacter pylori: a combined analysis of 12 case control studies 7. Sadjadi A, Malekzadeh R, Derakhshan MH, Sepehr A, Nouraie M, nested within prospective cohorts. Gut. 2001; 49: 347 – 353. Sotoudeh M, et al. Cancer occurrence in Ardabil: results of a popu- 20. Persson C, Jia Y, Pettersson H, Dillner J, Nyren O, Ye W. H. pylori lation-based cancer registry from Iran. Int J Cancer. 2003; 107: 113 seropositivity before age 40 and subsequent risk of stomach cancer: a – 118. glimpse of the true relationship? PLoS One. 2011; 6: e17404. 8. Sadjadi A, Zahedi M, Darvish Moghadam S, Nouraie M, Alimoham- 21. Lin Y, Ueda J, Kikuchi S, Totsuka Y, Wei WQ, Qiao YL, et al. Com- madian M, Ghrbani A, et al. The first population-based cancer survey parative epidemiology of gastric cancer between Japan and China. in Kerman Province of Iran. Iranian J Pub Health. 2007; 36: 26 – 34. World J Gastroenterol. 2011; 17: 4421 – 4428. 9. Akbari M, Zolfeghari H. A geopolitical analysis of ethnicity in Iran, 22. Nyren O, Adami HO. Stomach cancer. In: Adami HO, Hunter D, with an emphesis and opportunities. Geopoilitics Quarterly. 2009; 5: Trichopoulos D, eds. Textbook of Cancer Epidemiology. New York: 45 – 69. Oxford University Press; 2008. 10. Malekzadeh R, Sotoudeh M, Derakhshan MH, Mikaeli J, Yazdan- 23. Tredaniel J, Boffetta P, Buiatti E, Saracci R, Hirsch A. Tobacco smok- bod A, Merat S, et al. Prevalence of gastric precancerous lesions in ing and gastric cancer: review and meta-analysis. Int J Cancer. 1997; Ardabil, a high incidence province for gastric adenocarcinoma in the 72: 565 – 573. northwest of Iran. J Clin Pathol. 2004; 57: 37 – 42. 24. Malekzadeh R, Derakhshan MH, Malekzadeh Z. Gastric cancer in 11. Zendehdel K, Sedighi Z, Hassanloo J, Nahvijou A. Improving qual- Iran: epidemiology and risk factors. Arch Iran Med. 2009; 12: 576 ity of cancer registration in Iran. Part 1: evaluation and comparison – 583. of cancer registration results in the country. Hakim Res J. 2010; 12: 25. Shekholeslami H, Ghasemi-Barghi R, Mousavi H. Comparison of 42 – 49. prevelence of Helicobacter pylori Infection in Urban and Rural Area 12. Naghavi, Jafari N. Pattern of Mortality in 29 Provinces of Islamic Re- of Ghazvin. J Ghazvin Univ of Med Sci. 2004: 47 – 51. public of Iran Year for Year 2005 [in Persian]. Tehran: Iranina Minis- 26. Babamahmoodi F, Ajami A, Kalhor M, Shafeei G, Khalilian A. Se- try of Medical Education; 2008. roepidemiology if H pylori infection in Sari Cirt of Iran in 2001. J 13. Jensen O, Parkin DM, Maclenan R, Muir CS, Skeet RG. Cancer Reg- Mazandaran Univ Med Sci. 2004; 43: 39 – 48. istration: Principles and Methods. Lyon: IARC press; 1991. 27. Ghadimi R, Taheri H, Suzuki S, Kashifard M, Hosono A, Esfandiary 14. Metanat M, Sharifi-Mood B, Izadi S. Prevalence of Helicobacter Py- I, et al. Host and environmental factors for gastric cancer in Babol, lori infection in healthcare workers. Turk J Med Sci. 2010; 40: 965 the Caspian Sea Coast, Iran. Eur J Cancer Prev. 2007; 16: 192 – 195. – 969. 28. Alizadeh A, Ansari S, Ranjbar M, Shalmani HM, Habibi I, Firouzi M, 15. Zahedi M, Darvishmoghadam S, Atapoor M,. Prevalence of H. Py- et al. Seroprevalnece of Helicobacter Pylori in Nahavand: a Popula- lori infection among patients and general population referering to the tion-Based Study. East Mediter Health J. 2009; 15: 129 – 135.

746 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 S. J. Masoumi, F. Khademolhosseini, D. Mehrabani, et al.

Original Article Correlation of Quality of Life with Gastroesophageal Reflux Dis- ease amongst Qashqai Nomads in Iran

Seyed Jalil Masoumi MD1,2, Farnaz Khademolhosseini MD1, Davood Mehrabani PhD1,3, Fariba Moradi MD4, Amir Ahmad Mostaghni MD1, Najaf Zare PhD5, Ali Montazeri PhD6, Mehdi Saberi-Firoozi MD•1,7

Abstract Background: Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal diseases encountered in today’s clinic practice. GERD symptoms are troublesome and disruptive to the physical, social and emotional well-being of many patients. This is a cross-sectional study performed on Qashqai nomads of Fars Province in southern Iran to determine the impact of GERD on quality of life. Methods: We randomly selected 748 subjects over the age of 25 years. Subjects completed two questionnaires conducted by interviews. The first one consisted of questions on gastroesophageal reflux symptoms. The second questionnaire was the Short Form Health Survey (SF-36), a generic health-related quality of life instrument that consists of 36 items divided into eight dimensions. It has a 0- to 100-point scale where higher scores show better functioning and well-being. Results: Of 748 Qashqai migrating nomads who participated in the study, 717 subjects )mean age: 43 ± 14.2 years) completed the GERD questionnaire and only 372 subjects completed the SF-36 questionnaire due to their busy lifestyles, and GERD was reported in 106 subjects (28.5%). For all dimensions of SF-36, the mean score was consistently lower in patients with GERD compared to non-GERD subjects (P < 0.001). The dimension most frequently impaired was role-physical (40.9 vs. 77.3) followed by role-emotional (44.7 vs. 77.5), physical functioning (66.9 vs. 84.6), and general health (46.8 vs. 63.8). An association existed between impairment in quality of life and frequency (P < 0.05), but not severity, of GERD symptoms. Conclusion: In this group of Qashqai nomads, all dimensions of health-related quality of life as measured by the SF-36 questionnaire were meaningfully impaired in subjects with symptomatic GERD compared to non-GERD subjects. There was an association between impaired quality of life and frequency, but not severity, of GERD.

Keywords: GERD, Iran, nomads, quality of life

Cite the article as: Masoumi SJ, Khademolhosseini F, Mehrabani D, Moradi F, Mostaghni AA, Zare N, Montazeri A, Saberi-Firoozi M. Correlation of Quality of Life with Gastroesophageal Reflux Disease amongst Qashqai Nomads in Iran. Arch Iran Med. 2012; 15(12): 747 – 750.

Introduction Indeed, one of the most common reasons for consultation for upper gastrointestinal diseases is the impact of symptoms on everyday astroesophageal reflux disease (GERD) is one of the most life.10 common gastrointestinal diseases encountered in the daily We have performed this cross-sectional study on Qashqai no- G clinical setting.1 Although it is generally believed to occur mads of Fars Province in southern Iran to determine the effect of less frequently in Asia, its incidence and prevalence are predicted GERD on their quality of life. Qashqai nomads are one of the three to rise to the level seen in Western countries.2,3 According to a pop- minorities of nomads that reside in Fars Province. The Qashqai has ulation-based study in Tehran, Iran, the prevalence of GERD is the highest population of all the nomad tribes in this area. Qashqai noticeably higher than reports from other Asian studies.4-6 Depend- migrate between winter quarters near the Persian Gulf and sum- ing on the population that has been studied, the prevalence of primer quarters in the plateaus of the Zagros Mountains, located in mary GERD symptoms such as heartburn (i.e., a burning feeling northern Fars Province. These nomads speak predominantly Turk- behind the breast bone) or acid regurgitation (i.e., an acid taste in ish and have their own traditions. Their life style differs from ur- the mouth) varies between 9% and 42%.7 GERD symptoms are ban and rural residents, as they live with their animals and move a troublesome and disruptive to the physical, social, and emotional distance of more than 500 kilometers in search of pasture for their well-being of many patients.8 An international expert panel defined cattle, possibly entering other provinces. The Qashqai do not ex- “GERD as reflux symptoms sufficient to impair patients’ lives.9” perience the same stresses as urban residents, nor do they consume the same food. They live in tents and are more active physically Authors’ affiliations: 1Gastroentrohepatology Research Center, Shiraz University than urban people. of Medical Sciences, Shiraz, Iran. 2Department of Nutrition, School of Public Health We have previously studied the prevalence of GERD in this and Nutrition, Shiraz University of Medical Sciences, Shiraz, Iran. 3Stem cell and Transgenic Technology Research Center, Shiraz University of Medical Science, population and found that 33% had reflux that occurred at least Shiraz, Iran. 4Office of Vice Chancellor for Health Affairs, Shiraz University of once per week over the preceding year.11 We have also reported Medical Sciences, Shiraz, Iran. 5Department of Statistics, Faculty of Medicine, 6 the significant negative impact of irritable bowel syndrome (IBS) Shiraz University of Medical Sciences, Shiraz, Iran. Iranian Institute for Health 12 Sciences Research, Tehran University of Medical Sciences, Tehran, Iran. 7Digestive symptoms on quality of life in the same population. Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran. •Corresponding author and reprints: Mehdi Saberi-Firoozi MD, Gastroentero- hepatology Research Center, Nemazee Hospital, Shiraz University of Medical Scienc- Patients and Methods es, PO Box 71935-1311, Shiraz, Iran. Tel: +98-711-6474263, Fax: +98-711-6474263, E-mail: [email protected]; [email protected] In a population-based study, 748 subjects were selected by the Accepted for publication: 25 July 2012 cluster random sampling method based on socio-economic sta-

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 747 Quality of Life and GERD in Southern Iran tus census data from the five tribal groups, subgroups and family The second questionnaire completed for the subjects was the subdivisions of the Qashqai migrating nomads in Fars Province, Short Form Health Survey (SF-36). This is a well-known generic southern Iran. health-related quality of life instrument that has been translated into Shiraz University of Medical Sciences Ethics Committee ap- many languages.16,17 SF-36 has also been translated and validated proved this project. After coordination with the Fars Nomadic Af- in Iran.18 It consists of 36 items divided into eight dimensions: fairs Organization and in the presence of a guide to the Qashqai physical functioning, role-physical, bodily pain, general health, nomadic areas, we visited the subjects in their tents and discussed vitality, social functioning, role-emotional, and mental health. By the purpose of the research project in their native language. All definition, role-physical and role-emotional are the role limitations subjects were then invited to visit the health center at their summer as a result of physical and emotional difficulties, respectively. A 0- quarters and a written consent was obtained from each participant. to 100-point scale is used to transform the scores for each dimen- The study was conducted during the summer of 2007. We in- sion, and higher scores show better functioning and well-being.19 terviewed all subjects older than 25 years and of both genders to Information was entered into a computer database and we used complete two questionnaires. The interviewers were familiar with the SPSS version 11.5 (Chicago, IL) for data analysis. the language and had received intense training. One questionnaire Due to large sample size and continuity of variables in the ques- consisted of questions on gastroesophageal reflux symptoms. Its tionnaire for comparison of GERD/non-GERD and frequent ver- validity and reliability had been previously determined and con- sus infrequent GERD, we used the student’s t-test. P < 0.05 was firmed.13 The two principal GERD symptoms in the questionnaire considered significant; however, the results of the nonparametric included heartburn, a burning feeling in epigastrium that rises Mann-Whitney U test were not different from the student’s t-test. through the chest in substernal area; and regurgitation, liquid coming back into the mouth leaving a bitter or sour taste. A subject was Results said to suffer from GERD when they reported heartburn and/or acid regurgitation in the preceding year with a frequency of at least Of 748 Qashqai nomads who participated in the study, 717 sub- once a week, irrespective of severity or duration.9,14,15 jects completed the GERD questionnaire (response rate: 96%). We categorized subjects into three groups according to the sever- Subjects consisted of 284 (39.6%) males and 433 (60.4%) females. ity of GERD: i) mild (treatment was not required), ii) moderate The mean age was 43.1 ± 14.2 years (range: 25–85). GERD had a (treatment was required but daily activities were not restricted), prevalence of 33% (n = 237) in this population. 372 subjects com- and iii) severe (daily activities were restricted or there was a need pleted the SF-36 questionnaire (response rate: 50%). There were for life style changes). Subjects with GERD symptoms underwent fewer respondents to this questionnaire due to participants’ lack additional evaluation and treated by the physicians in the research of time and the need to return to tending their animals and daily team. We determined the frequency of reflux as the number of re- routine. Of 372 subjects who completed the SF-36 questionnaire, flux or regurgitation episodes experienced by the patient on a daily, 106 (28.5%) had GERD. weekly, or monthly basis. Table 1 shows the health-related quality of life for subjects who

Table 1. Correlation between health-related quality of life and gastroesophageal reflux disease (GERD) in Qashqai nomads of Fars Province in southern Iran. Mean (SD) With GERD (n = 106) Without GERD (n = 266) P-value Physical functioning 66.9 (28.1) 84.6 (23.8) < 0.001 Role-physical 40.9 (47.1) 77.3 (39.1) < 0.001 Body pain 63.1(22.4) 76.5 (16.4) < 0.001 General health 46.8 (19.9) 63.8 (18.5) < 0.001 Social functioning 68.5 (68.5) 81.4 (19.8) < 0.001 Role-emotional 44.7 (47.7) 77.5 (39.2) < 0.001 Vitality 55.3 (21.3) 65.7 (18.1) < 0.001 Mental health 52.7 (20.1) 66.4 (18.9) < 0.001 Physical component summary (PCS) 54.4 (22.7) 75.6 (19.8) < 0.001 Mental component summary (MCS) 55.3 (21.8) 72.8 (18.8) < 0.001

Table 2. Health-related quality of life in Qashqai nomads according to frequency of GERD. Mean (SD) Mild-to-moderate GERD (n = 52) Severe GERD (n = 54) P-value Physical functioning 70.0 (26.9) 65.1 (29.6) 0.385 Role-physical 39.4 (46.2) 45.8 (48.7) 0.489 Body pain 60.6 (22.1) 66.3 (22.6) 0.193 General health 46.5 (22.6) 49.0 (18.3) 0.535 Social functioning 56.5 (22.8) 55.7 (20.2) 0.849 Role-emotional 64.9 (22.9) 72.9 (19.9) 0.058 Vitality 41.6 (47.0) 49.3 (49.2) 0.412 Mental health 53.0 (20.8) 53.8 (20.6) 0.848 Physical component summary (PCS) 54.1 (24.0) 56.5 (22.6) 0.590 Mental component summary (MCS) 54.0 (23.1) 57.9 (20.9) 0.362 Mild-to-moderate: ≤ 2 times/week; Severe: > 2 times/week

748 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 S. J. Masoumi, F. Khademolhosseini, D. Mehrabani, et al. completed the SF-36 according to the presence or absence of determine treatment needs in newly diagnosed patients as well as GERD. In all dimensions of the SF-36, the mean score was con- those who need more effective treatment.28 sistently lower in patients with GERD compared to those with There were a few limitations in this study that should be consid- no GERD symptoms, which was statistically significant. As seen ered in interpretation of the results. First, the definition of GERD in Table 2, the mental (MCS) and physical component summary was not consistent with other studies that often used the ROME cri- (PCS) scores are actual summaries of the eight dimensions of the teria. Second, the information used to determine GERD symptoms SF-36. The MCS score dropped from 72.8 in non-GERD subjects and quality of life in the study subjects was collected through self- to 55.3 in GERD subjects (P < 0.001). There was a similar decline reporting. Third, only half the subjects agreed to complete the SF-36 in PCS score, from 75.6 (non-GERD) to 54.4 (GERD; P < 0.001). questionnaire which could have created some bias in the results. In Of 372 subjects who completed the SF-36 questionnaire, 106 this group of Qashqai nomads of Fars Province, all dimensions of (28.5%) had GERD. We categorized these subjects into two groups health-related quality of life as measured by the SF-36 question- according to frequency of GERD. Mild-to-moderate GERD naire were meaningfully impaired in those who had GERD symp- subjects experienced reflux at least twice in a one week period. toms compared to non-GERD subjects. Those with severe GERD had reflux more than twice weekly. In Quality of life impairment was associated with the frequency, but a comparison between patients with mild-to-moderate and severe not severity of GERD. GERD, none of the SF-36 dimensions showed any significant differences between the two groups (Table 2). There were no signifi- References cant differences between the two groups in any of the physical and mental dimensions of SF-36. 1. Dent J, El-Serag HB, Wallander MA, Johansson S. Epidemiology of gastroesophageal reflux disease: a systematic review. Gut. 2005; 54: 710 – 717. Discussion 2. Ang TL, Fock KM, Ng TM, Teo EK, Chua TS, Tan J. A comparison of the clinical, demographic and psychiatric profiles among patients with Health-related quality of life is an individual’s perception of erosive and non-erosive reflux disease in a multi-ethnic Asian country. the functional effect of an illness and its therapy on himself or World J Gastroenterol. 2005; 11: 3558 – 3561. 19,20 3. Goh KL, Chang CS, Fock KM. Gastroesophageal reflux disease in herself. We found lower health-related quality of life scores Asia. J Gastroenterol Hepatol. 2000; 15: 230 – 238. as measured by the SF-36 questionnaire in nomadic subjects 4. Nouraie M, Radmard AR, Zaer-Rezaii H, Razjouyan H, Nasseri- with GERD symptoms. This impairment occurred in all aspects Moghaddam S, Malekzadeh R. Hygiene could effect GERD preva- of health-related quality of life. Subjects with GERD reported a lence independently: a population based study in Tehran. Am J Gastro- enterol. 2007; 102: 1353 – 1360. role-physical score of 40.9 compared with 77.3 for those without 5. Nasseri-Moghaddam S, Mofid A, Ghotbi MH, Razjouyan H, Nouraie GERD. In role-emotional, the score was 44.7 (GERD) versus 77.5 M, Ramard AR, et al. Epidemiological study of gastro-oesophageal re- (non-GERD), in physical functioning it was 66.9 (GERD) versus flux disease: reflux in spouse as a risk factor.Aliment Pharmacol Ther 2008; 28: 144 – 153 84.6 (non-GERD), and for general health the score was 46.8 for 6. Kinoshita Y, Wong BC. Systematic review on epidemiology of gastro- GERD versus 63.8 for those without GERD. esophageal reflux disease in Asia. Clin Gastroenterol Hepatol. 2006; Other authors supported findings of this study. According to Mc- 4: 398 – 407. Dougall et al., SF-36 scores were worse in GERD patients than 7. Nilsson M, Johnsen R, Ye W, Hveam K, Lagergern J. Prevalence of 21 gastroesophageal reflux symptoms and the influence of age and sex. in the general population. Similarly, in the US, subjects with Scand J Gastroenterol. 2004; 39: 1040 – 1045. frequent or nocturnal GERD had significantly lower SF-36 MCS 8. Wicklund I. Review of the quality of life and burden of illness in gas- and PCS scores compared to the general population.22 A Canadian troesophageal reflux disease.Dig Dis. 2004; 22: 108 – 114. population-based study also showed significantly lower MCS and 9. Dent J, Armstrong D, Delaney B, Moayyedi P, Talley NJ, Vakil N. Symptom evaluation in reflux disease: workshop background, process- PCS scores in individuals who had functional heartburn according es, terminology, recommendations, and discussion outputs. Gut. 2004; to Rome II criteria.23 In Germany, both physical and psychosocial 53: iv1 – iv24. aspects of health-related quality of life were significantly impaired 10. Jones R, Liker H, Ducrotte P, Ballard K. Reasons why individuals with in patients with GERD symptoms.24 symptoms of gastroesophageal disease seek medical attention. Gut. 2005; 54: A63. It has been reported that in patients with GERD, the presence 11. Mostaghni A, Mehrabani D, Khademolhosseini F, Masoumi SJ, Mo- of symptoms for two days per week is enough to impair health- radi F, Zare N, et al. Prevalence and risk factors of gastroesophageal related quality of life.9 This impairment is strongly associated with reflux disease in Qashqai migrating nomads, southern Iran. World J the patient’s perception of symptom frequency.25 This is consistent Gastroenterol. 2009; 15: 961 – 965. 12. Masumi SJ, Moradi F, Mehrabani D, Khademolhosseini F, Mostaghni with the results of our study which have shown a lower quality of A, Zare N, et al. Prevalence and quality of life in Qashqai migrating life score in patients with GERD in comparison to those with non- nomads with irritable bowel syndrome in southern Iran. Iran Red Cres- GERD. According to Wiklund et al., there is a significant correla- cent Med J. 2009; 11: 403 – 407. 13. Saberi-Firoozi M, Khademolhosseini F, Yousefi M, Mehrabani D, Zare tion between a decrease in well-being and the severity of heartburn N. Risk factors of gastroesophageal reflux disease in Shiraz, southern 25 and acid regurgitation. Similarly, Dimenas and colleagues have Iran. World J Gastroenterol. 2007; 13: 5486 – 5491. reported that increased severity of heartburn and regurgitation led 14. Dent J, Bran J, Fendrick AM, Fennerty MB, Janssens J, Kahrilas PJ, to decreased health-related quality of life scores.26 We did not find et al. An evidence-based appraisal of reflux disease management- the Genval Workshop Report. Gut. 1999; 44: S1 – S16. any significant differences in quality of life between subjects with 15. Dent J, Jones R, Kahrilas P, Talley NJ. Management of gastro-oesopha- severe GERD and those with mild-to-moderate GERD. geal disease in general practice. BMJ. 2001; 322: 344 – 347. Flook and Wiklund believe that health-related quality of life is 16. Bullinger M. German translation and psychometric testing of the SF-36 now a component of the GERD definition and its improvement Health Survey: Preliminary results from the IQOLA Project. Soc Sci 27 Med. 1995; 41: 1359 – 1366. reveals successful therapeutic intervention. By recognizing the 17. Taft C, Karlsson J, Sullivan M. Performance of the Swedish SF-36 ver- effect of GERD symptoms on patients’ lives, practitioners can sion 2.0. Qual Life Res. 2004; 13: 251 – 256.

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18. Montazeri A, Goshtasebi A, Vahdaninia M, Gandek B. The Short Form – 1993. Health Survey (SF-36): Translation and validation study of the Iranian 24. Kulig M, Leodolter A, Vieth M, Schulte, Jaspersen, Labenz J, et al. version. Qual Life Res. 2005; 14: 875 – 882. Quality of life in relation to symptoms in patients with gastro-esopha- 19. Ekberg H, Kyllonen L, Madsen S, Grave G, Solbu D, Holdaas H. In- geal reflux disease-an analysis based on the ProGERD initiative. Ali- creased prevalence of gastrointestinal symptoms associated with im- ment Pharmacol Ther. 2003; 18: 767 – 776. paired quality of life in renal transplant recipients. Transplantation. 25. Wiklund I, Carlsson J, Vakil N. Gastroesophageal reflux symptoms and 2007; 83: 282 – 289. well-being in a random sample of the general population of a Swedish 20. Spilker B. Quality of Life and Pharmacoeconomics in Clinical Trials. community. Am J Gasatroenterol. 2006; 101: 18 – 28. 2nd ed. Philadelphia: Lippincott-Raven Publishers; 1996. 26. Dimenas E, Glise H, Hallerback, Hernqvist H, Svedlund J, Wiklund I. 21. McDougall NI, Johnston BT, Kee F, Collins JS, McFarland RJ, Love Well-being and gastrointestinal symptoms among patients referred to AH. Natural history of reflux oesophagitis: a 10-year follow up of its endoscopy owing to suspected duodenal ulcer. Scand J Gastroenterol. effect on patients symptomatology and quality of life. Gut. 1996; 38: 1995; 30: 1046 – 1052. 481 – 486. 27. Flook NW, Wiklund I. Accounting for the effect of GERD symptoms 22. Farup C, Kleinman L, Sloan S, Ganoczv D, Chee E, Lee C, et al. The on patients’ health-related quality of life: supporting optimal disease impact of nocturnal symptoms associated with gastroesophageal reflux management by primary care physicians. Int J Clin Pract. 2007; 61: disease on health-related quality of life. Arch Intern Med. 2001; 161: 2071 – 207828. 45 – 52. 28. Jones R, Coyne K, Wiklund I. The Gastro-oesophageal Reflux Dis- 23. Irvine EJ, Ferrazzi S, Pare P, Thompson WG, Rance L. Health-related ease Impact Scale: a patient management tool for primary care. Aliment quality of life in functional gastrointestinal disorders: focus on consti- Pharmacol Ther. 2007; 25: 1451 – 1459. pation and resource utilization. Am J Gastroenterol. 2002; 97: 1986

750 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 M.Babakhanian, Z. Alam Mehrjerdi, Y.Shenaiy

Original Article Sexual Dysfunction in Male Crystalline Heroin Dependents before and after MMT: A Pilot Study

Masaudeh Babakhanian MA•1,2, Zahra Alam Mehrjerdi MA3, Yahya Shenaiy MD4

Abstract Background: Sexual dysfunction (SD) is a common problem among chronic opiate dependents. The purpose of this study is to examine the prevalence of SD and to investigate whether there is a change in SD after six months of methadone maintenance treatment (MMT) compared with baseline. Methods: We recruited 30 patients mean age 34.5 years from an MMT center in Damghan, Iran. Patients underwent structured interviews that consisted of the following: (i) socio-demographic characteristics, drug use, and sexual behavior ; (ii) the International Index of Erectile Function (IIEF-15) test for SD; (iii) the Zung test for depression; and (iv) analysis of serological status. Results: Overall, 8% of participants reported no SD, 69% reported mild to moderate SD, and 23% reported severe SD upon admission. After completion of the MMT program, these results decreased to 61% and 20%, respectively. In comparison with admission, the mean IIEF- 15 score showed moderate improvement from 16.77 ± 7.08 to 21.8 ± 6.40 (P = 0.003). The mean IIEF-15 score for intercourse satisfaction completely improved from12.20 ± 4.55to 15 ± 3.76 (P = 0.001). Slight improvements were noted in the mean IIEF-15 score for sexual desire which increased from 5.10 ± 2.28 to 6.57 ± 2.12 (P = 0.017) and the mean IIEF-15 score for overall satisfaction which increased from 5.10 ± 2.29 to 6.58 ± 2.12 (P = 0.017). However, the mean IIEF-15 score for orgasmic function very slightly decreased from 4.73 ± 4.50 to 4.57 ± 1.92 (P = 0.191), which showed no statistically significant improvement after MMT. There was no relation with depression. Conclusion: The findings of this study reveal a prevalence of SD and improvements in some aspects of SD in patients after six months of MMT. Patients should be screened for SD at the onset of opioid replacement treatment. Future studies on SD should examine the potential benefits of androgen replacement, hormone assay and the role of psychosocial factors.

Keywords: Crystalline heroin, male, MMT, sexual dysfunction

Cite the article as: Babakhanian M, Alam Mehrjerdi Z, Shenaiy Y. Sexual Dysfunction in Male Crystalline Heroin Dependents before and after MMT: A Pilot Study. Arch Iran Med. 2012; 15(12): 751 – 755.

Introduction to moderate erectile dysfunction and 18% reported severe erectile dysfunction.5 exual dysfunction (SD) is a common problem among ad- The paucity of research on SD among patients on MMT in Iran dicted Iranian opiate users who undergo methadone mainte- and in other countries is a crucial concern. Assessment of SD in S nance treatment (MMT), but only a few studies on SD with these patients is important because identification and management methadone-treated patients have been undertaken in Iran and in of SD can increase compliance to the treatment procedure, the ef- other countries. As a result, the importance of SD has been under- fectiveness of which, as is well-known, is associated with more estimated. Research studies in other countries have found that up doses and a longer duration of treatment.6 The present study is de- to 87% of women and 85% of men who enter MMT have reported signed to examine the prevalence of SD and to investigate whether sexual difficulties while using heroin.1 Nevertheless, many patients there is a change in SD after six months of MMT compared with with sexual problems do not report this issue to clinicians2 and baseline. many clinicians feel uncomfortable about dealing with sexual problems.3 Of the few Iranian studies conducted on SD, Tatari and Materials and Methods colleagues in their study on 157 drug dependent subjects in Ker- manshah, Iran have found the prevalence rates of erectile function Participants to be 60.5% and sexual desire to be 70.70%.4 The study was conducted in the outpatient Cheraghiyan Center, An Italian study on the prevalence of erectile function among which is the most active center that provides MMT for opiate abus- 201 male patients at seven methadone and buprenorphine mainte- ers in Damghan, Iran. We recruited participants through poster pre- nance treatment centers showed that 24% of patients reported mild sentation. Married men aged 20–50 years who were chronic smokers of crystalline heroin for six months before study entry and who Authors' affiliations: ¹Department of Social Work, Baradaran-e Rezaee Hospital, had a literacy of at least eight years were eligible to enter the study. Semnan University of Medical Sciences, Damghan, Iran. ²Department of Social Initially, 70 males who were on the waiting-list for admission to Work, University of Welfare Sciences and Rehabilitation, Tehran, Iran. ³Rose Psy- chiatric Center, Tehran, Iran. Methadone Maintenance Treatment Ward, Cher- MMT were selected, however, 13 left MMT because of relapse, aghiyan MMT Center, Damghan, Iran. 10 referred to methamphetamine, 9 did not take methadone per- •Corresponding author and reprints: Masaudeh Babakhanian MA, Department manently as prescribed by the Cheraghiyan Center physician, and of Social Work, Baradaran-e Rezaee Hospital, Semnan University of Medical Sci- ences, Damghan, Iran. Telefax: +98-232-523-5111, 8 consumed psychiatric and other medications as determined by E-mail: [email protected] urine testing. Therefore, the total number of participants was 30 Accepted for publication: 30 May 2012 crystalline heroin users during the six month study period. All par-

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 751 SD in Male Crystalline Heroin Dependents Before and After MMT

Table 1. Participants’ characteristics (n = 30). Variables Characteristics Mean ± SD Frequency (%) Age 34.5 ± 4.2 Employed 29(97.7) Personal and social characteristics Employment Unemployed 1(3.3) < 12 years 18(60) Education 12 years 10(33) > 12 years 2(7) Living with Spouse 30(100) Marriage age 25 ± 6.1 Marital status Married 30(100) Lifetime opioid use 30(100) History of drug use Lifetime stimulant us 8(26.6) Lifetime hallucinogen use 1(3.3) Age of first opioid use 22.1 ± 4.3 Age of first crystalline heroin smoking 28 ± 5.1 Length of addiction 6 ± 2.1 No depression 10(33.3) Depression Mild 14(46.7) Moderate 6(20) Negative 30(100) HIV¹ Serology of infectious disease Positive 0 Negative 30(100) HBV² Positive 0 Negative 30(100) HCV³ Positive 0 1 30(100) Number of partners Sexuality More 0 Yes 0 Extra marital sex last month No 30(100) Average number of sex before MMT 4 ± 4.1 Average number of sex after MMT 6 ± 3.2 Yes 16(53.3) Condom use No 14(46.7) ¹Human immunodeficiency virus; ²Hepatitis B virus; ³Hepatitis C virus ticipants were interviewed using the Structured Clinical Interview intercourse satisfaction (15), and overall satisfaction (10). Higher for DSM-IV (SCID-I)7 and met DSM-IV criteria8 for heroin de- scores indicate less dysfunction. pendence. Participants were asked not to use antidepressants, neu- The reliability and validity of IIEF-15 were approved in Iran in roleptics, antipsychotics, sedatives, anxiolytics, and antiandrogens the study on the Farsi International Index of Erectile Dysfunction during the study because of the negative effects of these medica- and Doppler Ultrasonography that evaluated male impotence.10 tions on sexual function and the possibility of inference with the The Zung Self-rating Depression Scale (SDS)11 was also admin- study procedure and aims. Participants who were diagnosed with istered at admission to MMT to assess depression as a crucial and comorbid drug and alcohol use, severe hypertension and stress, prevalent factor influencing SD. The Zung SDS is an index with hormonal problems due to medical or surgical conditions such as mild depression at a score of 50–59, moderate depression at 60–69 testicular surgery, or who suffered from neurological, metabolic and severe depression over 70. Analysis of serological status was and arteriopathic problems such as diabetes were excluded because also part of a scheduled entry medical examination to diagnose of the negative effects of these problems with the study procedure. viral infections that influenced the sex hormone system and ex- All participants were provided with written consent forms. Partici- cluded participants who were infected with human immunodefi- pation was voluntary and confidential. The study was approved by ciency virus (HIV), hepatitis B virus and hepatitis C virus. Two the Institutional Review Board of University of Welfare Sciences urine samples were randomly taken each month for a multi-drug and Rehabilitation. urine test to control for drug and medication use other than methadone in participants. Interview and serological status A structured interview was administered which included ques- Statistical analysis tions on socio-demographics, drug use details, and sexual behavior. A series of analyses were conducted by performing the Mann- In addition, the International Index of Erectile Function (IIEF-15)9 Whitney U test to reveal the changes that participants reported was administered upon admission to MMT and after six months in their SD at admission to MMT (baseline) compared with six of MMT. The IIEF-15 is a reliable multidimensional scale test that months of methadone treatment (post-test). explores various aspects of SD. The test is self-administered and has 15 questions that examine 5 scales of erectile function, orgas- Results mic function, sexual desire, intercourse satisfaction and overall satisfaction. Maximum mean scores for the IIEF-15 are as follows: Patient characteristics and prevalence of erectile dysfunction (ED) erectile function (30), orgasmic function (10), sexual desire (10), The study included 30 married males who were between 24–47

752 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 M.Babakhanian, Z. Alam Mehrjerdi, Y.Shenaiy

Figure 1. Erectile function before and after MMT. Figure 2. Orgasmic function before and after MMT.

Figure 3. Sexual desire before and after MMT. Figure 4. Intercourse satisfaction before and after MMT.

Figure 5. Overall satisfaction before and after MMT. years old (mean: 34.5; SD = 4.2). The majorities of participants SD prevalence (P > 0.05). The baseline ED mean score in IIEF were employed and had education levels of less than 12 years or was 16.77, which showed a moderate prevalence for ED among diploma. Participants were on methadone maintenance at a mean participants that positively increased to 21.8 in the post-test (Fig- dose of 6.62 mg/day for the first month of treatment (range: 4.03– ure 1). Further analysis showed a moderate improvement in ED 14.12 mg; 26% above 10.9 mg). The dose was gradually increased among participants after taking methadone (Z score = -2.933; U to 14.12 mg/day during the remaining five months of the study score = 252; P value ≤ 0.003) compared with baseline (Table 2). (range: 10.9–31.28 mg; 25% above 19.17 mg). The mean for sex- The baseline orgasmic functions mean score was 4.73, which in- ual intercourse upon admission to MMT was 4 (SD = 4.1) times dicated the presence of a moderate orgasmic problem among par- per month, which increased to 6 (SD = 3.2) times per month at ticipants that remained almost unchanged (4.57) in the post-test the end of six months of MMT. Participants reported that sexual (Figure 2). Further analysis showed that orgasmic function did not activity was limited to their spouses who were not drug users and change after taking methadone (Z score = -1.308; U score = 364; P no risky behavior was reported within six months before entry to value ≥ 0.191) compared to baseline (Table 2). The baseline sexual MMT (Table1). desire score was 5.10, which increased moderately to 6.57 in the post-test (Figure 3). Further analysis revealed a slight improve- Prevalence of sexual dysfunction (SD) ment in sexual desire among participants after taking methadone At baseline, 8% of the participants reported no SD, 69% reported (Z score = -2.396; U score = 289.500; P value ≤ 0.017) compared mild to moderate SD, and 23% reported severe SD, which de- with baseline (Table 2). The baseline intercourse satisfaction score creased to 61%, and 20%, respectively, after six months of MMT. was 12.20, which was moderate and significantly increased to a The median age score for SD was 30 years and the mean age score score of 15 in the post-test, which indicated no problems with in- for SD prevalence was 32.5 (SD = 2.3) years. Age, education, tercourse satisfaction in the post-test (Figure 4). Further analysis employment, drug use history, depression scores in Zung (SDS), revealed intercourse satisfaction among participants completely methadone dose and treatment duration were not associated with improved after taking methadone (Z score = -3.175; U score = 236;

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 753 SD in Male Crystalline Heroin Dependents Before and After MMT

Table 2. IIEF scores of ED and related sexual aspects in baseline and after six months of MMT (n = 30). Variable Characteristics Mean SD U Z P-value Baseline 16.77 7.08 — — — Erectile function Post-test 21.8 6.40 252.000 -2.933 0.003 Baseline 4.73 4.50 — — — Orgasmic function Post-test 4.57 1.92 364.000 -1.308 0.191 Baseline 5.10 2.28 — — — Sexual desire Post-test 6.57 2.12 289.500 -2.396 0.017 Baseline 12.20 4.55 — — — Intercourse satisfaction Post-test 15 3.76 236.000 -3.175 0.001 Baseline 5.10 2.29 — — — Overall satisfaction Post-test 6.58 2.12 289.500 -2.396 0.017

P value ≤ 0.001) compared with baseline (Table 2). cho-intervention and marital therapy. The baseline overall satisfaction score was 5.10 which increased One notable aspect of our study was the improvement in inter- moderately to 6.58 in the post-test (Figure5). Further analysis course satisfaction among participants after MMT, which we have revealed overall sexual satisfaction among participants slightly found no similar study. This result may be partly due to the low improved after taking methadone (Z score = -2.396; U score = severity of this problem among participants who have been easily 289.500; P value ≤ 0.017) compared with baseline (Figure 5). influenced by the positive pharmaceutical effects of methadone on sex hormones and is subject to further study. Discussion Several limitations existed in this study. This was across-sectional research without a control group, hormone assay and monthly The present study was one of the few Iranian studies on SD evaluation by IIEF-15. We used baseline sexual status to compare among male crystalline heroin abusers on MMT. We have found a with post-test results of sexual function among participants. It was prevalence of SD among participants on MMT. This study finding difficult to draw a conclusion and direct causal effect between supported other research findings that repeatedly emphasized the methadone use and improvement in SD from our observations in prevalence of SD as a common problem among opiate dependent this pilot study. Additional studies with larger samples and with patients who referredfortreatment.5,12 In the current study, the se- less dropout rates are necessary. verity of some aspects of SD among participants decreased mod- The traditional, religious atmosphere of Damghan crucially erately after six months of extensive methadone treatment. The limited the study sample size, therefore this study on SD was a mechanism of action of methadone on SD caused by chronic use pilot study. Indeed, among a few opiate use treatment clinics in of crystalline heroin has not been determined; however, we have Damghan, no clinic agreed to cooperate with us and many patients noted improvements in some aspects of SD among participants. refused participation in the study because of traditional negative This might be partially a result of the gradual effects of methadone views on reporting SD in Damghan. Thus the study population was on the sex hormone system during treatment which supports the limited to the government operated Cheraghiyan MMT Center and fact that the constant-state pharmacokinetic properties of metha- as a result the study findings may not be generalizable to the entire done result in adaptation and normalization of the endocrine sys- population of opiate-dependent patients who have participated in tem and body’s neuroendocrine function.13 an MMT program in Damghan. Furthermore, our data was based We found orgasmic dysfunction was moderately prevalent on self-reporting that lacked objective evidence however we ad- among participants at baseline. This finding was consistent with ministered the IIEF-15, which is recognized as the gold standard the research of Palha and Esteves who studied SD among101 her- in evaluating SD.15 We evaluated SD at an appropriate time, in the oin addicts and found that 60% of men in their study had problems sixth month, when our extensive interviews with patients showed in achieving orgasms.14 In our study this problem did not improve they frequently reported having adjusted to both the methadone during MMT and might have been partially due to the number of dose and treatment conditions in the MMT program. The present years orgasmic dysfunction was present in participants. Additional study found no relationship between demographics, drug use his- treatment such as androgen replacement therapy might be neces- tory, methadone dose and duration of MMT to improvement in SD sary. In addition, this might have been the result of a variety of psy- which supported the findings of a pioneer study.2 Nevertheless, a chological and interpersonal factors not reported by participants higher methadone dose and longer duration of MMT in compari- that needed intervention. son with a low dose and shorter MMT duration in experimental We found low sexual desire and overall satisfaction to be mod- and control groups are subjects for future studies on SD in male erately prevalent among participants. This finding supported the patients, particularly when some well-known studies have claimed study of Palha and Esteves on heroin dependents who found that the reverse effects of methadone treatment on certain aspects of 75% of men in their study complained of low libido, 71% reported sexual function such as libido and orgasmic function.16,17 altered sexual arousal and 72% had reduced sexual satisfaction.14 SD is an important concern for many patients on MMT and a In the current study these problems slightly improved after partici- good opiate use treatment program will need to address this issue. pants took methadone. Androgen replacement18 and pharmacological treatment19 may be The long-term side effects of crystalline-heroin dependence on effective approaches for these patients while psycho-intervention decreased libido were likely to be the core feature of sexual desire for patients and counseling programs for couples may be useful. and overall satisfaction that possibly required additional therapies such as medications that influence sexual desire and satisfaction References or possibly were attributable to the disrupted affective and sexual relationship of participants with their spouses, which required psy- 1. Goldsmith DS, Hunt DE, Lipton DS, Strug DL. Methadone folklore: beliefs about side effects and their impact on treatment. Human Org.

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1984; 43: 330 – 340. evaluation of male impotence [in Persian]. Iran J Surg. 2006; 14: 25 2. Hanbury R, Cohen M, Stimmel B. Adequacy of sexual performance – 31. in men maintained on methadone. Am J Drug Alcohol Abuse. 1977; 11. Zung WWK. From art to science: the diagnosis and treatment of de- 4: 13 – 20. pression. Arch Gen Psychiatry.1973; 29: 328 – 337. 3. Risen CB. A guide to taking a sexual history. J Psychiatr Clin N Am. 12. Hallinan R, Byrne A, Agho K, McMahaon C, Tynan P, Attia J. Erectile 1995; 18: 39 – 53. dysfunction in men receiving methadone and buprenorphine mainte- 4. Tatari F, Farniya V, Faghiyeh Nasiri R, Najafi F. The effects of Trazo- nance treatment. J Sex Med. 2008; 5: 684 – 692. done on erectile function in patients on methadone maintenance treat- 13. Martin J, Payte JT, Zweben JE. Methadone maintenance treatment: a ment; 2010. Available from: URL: www.kums.ac.ir/article-fa-78.html primer for physicians. J Psychoactive Drugs.1991; 23: 165 – 176. 5. Quaglio G, Lugoboni F, Pattaro C, Melara B, Mezzeelani P, Des Jarlais 14. Palha AP, Esteves M. A study of the sexuality of opiate addicts. J Sex DC. Erectile dysfunction in male heroin users, receiving methadone Marital Ther. 2002; 28: 427 – 437. and buprenorphine maintenance treatment. Drug and Alcohol Depend. 15. Rosen RC, Althof SE, Giuliano F. Research instruments for the diagno- 2008; 94: 12 – 18. sis and treatment of patients with erectile dysfunction. Urology. 2006; 6. Strain E, Bigelow G, Liebson I, Stitzer M. Moderate vs. high-dose 68 (suppl 3A): S6 – S16. methadone in the treatment of opioid dependence: a randomized trial. 16. Teusch L, Scherbaum N, Bohme H, Bender S, Eschmann-Mehl G, JAMA.1999; 281: 1000 – 1005. Gastpar M. Different patterns of sexual dysfunctions associated with 7. First MB, Pincus HA. Classification in psychiatry: ICD-10 v. DSM-IV. psychiatric disorders and psychopharmacological treatment. Results A response. Br J Psychiatry. 1999; 175: 205 – 209. of an investigation by semi structured interview of schizophrenic and 8. American Psychiatric Association. Diagnostic and Statistical Manual neurotic patients and methadone-substituted opiate addicts. Pharmaco- of Mental Disorder: DSM-IV. 4th ed. Washington, DC: American Psy- psychiatry.1995; 28: 84 – 92. chiatric Association; 1994. 17. Brown R, Balousek S, Mundt M, Fleming M. Methadone maintenance 9. Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A. and male sexual dysfunction. J AddictionDis.2005; 24: 91 – 106. The international index of erectile function (IIEF): a multidimensional 18. Daniell HW. Sex hormone deficiency in depressed patients receiving scale for assessment of erectile dysfunction. Urology. 1997; 49: 822 opioids. Arch Intern Med. 2004; 164: 804. – 830. 19. Nurnberg HG, Hensley PL, Gelenberg AJ, Fava M, Lauriello J, Paine 10. Mehraban D, Shabaninia Sh, Naderi Gh, Isfahani F. Farsi International S. Treatment of antidepressant-associated sexual dysfunction with Index of Erectile Dysfunction and Doppler Ultrasonography in the sildenafil: a randomized controlled trial.JAMA. 2003; 289: 56 – 64.

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 755 Waiting Time for Specialist Consultation in Tehran

Original Article Waiting Time for Specialist Consultation in Tehran

Afsoon Aeenparast PhD•1, Faranak Farzadi MD PhD1, Farzaneh Maftoon MD PhD1

Abstract Background: Waiting time is an important indicator of patient satisfaction and the quality of care. The aim of this study is to determine the waiting time in physician offices in Tehran, Iran. Methods: This was a cross-sectional study. The target population of this study consisted of specialist and subspecialist offices in Tehran. We used a census sampling method to study the population. Data of 5475 physicians was extracted from data banks, of which 43.4% were not accessible. Thus 3098 cases were included and analyzed. We conducted telephone interviews to gather data, which was subsequently analyzed using SPSS software. Results: Out of the 3098 physicians interviewed, 2585 were specialists (83.4%); the remaining were subspecialists. The mean waiting time for a patient’s first visit to a specialist was 4.30 days (SD = 8.10) and for subspecialists it was 7.61 days (SD = 13.98). Discussion: The average waiting time in our study was less than a week for specialists and almost a week for subspecialists. The health system in Iran has not established a complete referral system and with this situation, waiting time may have adverse effects on the health of patients. Thus studying and managing waiting time in some medical specialties or regions is a priority in our country.

Keywords: Clinic visit, medical specialties, outpatient care, waiting list

Cite the article as: Aeenparast A, Farzadi F, Maftoon F. Waiting Time for Specialist Consultation in Tehran. Arch Iran Med. 2012; 15(12): 756 – 758.

Introduction primary care physician and the specialist consultation. Other references define the waiting list as a list that patients are enrolled in s an important determinant of patient satisfaction, waiting once they opt to pursue an elective procedure, assuming that they time has gained increasing attention in the field of health cannot get this procedure performed immediately. They mentioned A care services.1 Waiting time is a barrier for patient access to that “waiting time” or “wait time” for these patients is more dif- care and it is an important performance indicator of health systems. ficult to define. A common definition is the length of time between It is also an important measure of how well the health care system when a patient is placed on a waiting list and when the service is responds to patient needs.2–4 Waiting for care can lead to patient received.9,10 suffering, strained doctor-patient relationships, and significant pa- The Singapore Ministry of Health define two types of waiting tient dissatisfaction.5 However, there is no agreement on how to set time as the key indicators of service quality at specialist outpatient wait time targets and prioritize wait lists.5,6 clinics (SOC): waiting time for an SOC appointment and waiting Defining waiting time and selecting its scope is the first step in time for an SOC consultation. The first is defined as the time period determining and prioritizing waiting time. Different countries have from booking the first appointment at the SOC to the actual ap- studied waiting time using various definitions, which may differ pointment date, whereas the second is defined as the time from the with respect to their health system processes. The difference be- patient registration at the clinic to the first contact with the doctor.11 tween countries, of course, is the amount of waiting time7 of which As waiting time definitions and measurements may differ from the main cause for differences lies in selecting the start and end one health system to another, the reasons for long waiting times point of the waiting time. These differences can result in dramati- may differ as well. There are three main causes for long special- cally different measurements for waiting times.8–10 ist waiting times, namely the nature of healthcare services, which Most studies have focused on three distinct waiting periods: are inherently variable and sometimes unpredictable; the shortage waits to see the specialist, waits to receive hospital-based services, of public sector specialists in some areas to meet rising demand; and total waiting time. In these studies the waiting time for special- and lack of discipline in adhering to an appointment system.11 ist consultation has been defined as the time between the referral Wait time management has been studied in many contexts, such as from the primary care practitioner to the consultation. In the early radiation oncology, critical care, intensive care, limb arthroplasty, 1990s, this definition was introduced in the National Health Ser- emergency department, and surgery. Many countries have tried to vice in the United Kingdom to ensure the comparability of national reduce wait times through formal wait time reduction strategies.3,5 waiting time statistics for specialist consultations. Specialist wait- In publicly funded health care wait lists are commonly used to ing times have also been defined as the time between the visit to the manage access to elective procedures, raising concerns about the delay in necessary treatment.12 However, in other healthcare sys- Authors’ affiliation: 1Health Services Management Research Group, Mother tems, public involvement in wait time management efforts is very and Child Health Research Center, Iranian Institute for Health Sciences Research, 3,13 ACECR, Tehran, Iran. limited. •Corresponding author and reprints: Afsoon Aeenparast PhD, No. 23, Nazari This study aims to measure physician waiting time in different St. Felestin St., P.O. Box: 13145-1756, Tehran, Iran. Tel: +98-21-66480804, medical specialties and subspecialties in Tehran, Iran. Fax: +98-21-66480805, E-mail: [email protected] Accepted for publication: 14 August 2012

756 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 A. Aeenparast, F. Farzadi, F. Maftoon

Table 1. Characteristics of physicians. Specialist Subspecialists Pearson Total P-value N (%) N (%) Chi-square Sex Male 2017 (78.0) 444 (86.5) 2461 (79.4) Female 568 (22.9) 69 (13.5) 637 (20.60) 19.03 < 0.0001 Total 2585 (100.0) 513 (100.0) 3098 (100.0) Faculty member Yes 359 (36.9) 276 (53.9) 1229 (39.7) No 947 (36.7) 97 (18.9) 1044 (33.8) Unavailable 685 (26.6) 140 (27.3) 825 (26.5) 71.34 < 0.0001 Total 2585 (100.0) 513 (100.0) 3098 (100.0) Office geographical location North 843 (32.6) 237 (46.2) 1080 (34.9) South 90 (3.5) 4 (0.8) 94 (3.0) West 181 (7.0) 13 (2.5) 194 (6.3) East 348 (13.5) 39 (7.6) 387 (12.5) Center 1119 (43.3) 220 (42.9) 1339 (43.2) Unavailable 4 (0.2) 0 (0.0) 4 (0.1) 58.33 < 0.0001 Total 2585 (100.0) 513 (100.0) 3098 (100.0)

Table 2. Waiting time for first visit. Average waiting time in days Median waiting time N Range P-value (SD) (days) Specialist 2585 4.3 (8.1) 2.0 0–120 Subspecialist 513 7.61 (14.0) 3.0 0–150 < 0.0001 Total 3098 4.85 (9.42) 2.0 0–150

Materials and Methods Results

This was a cross-sectional study. The target population of the In this study, we interviewed 3098 physicians. Of these, 2585 study consisted of specialists and subspecialists who practice in were specialists (83.4%) and the remaining 513 were subspecial- Tehran. In this study we used the census sampling method. In order ists (16.6%). to prepare a list of physicians, we used data from two important Study results showed that most physicians (79.4%) were male physician data banks, the Islamic Republic of Iran Medical Coun- (78.0% for specialists and 86.5% for subspecialists). Faculty mem- cil and the White Book. Information about 5475 physicians was bers comprised 39.7% of all physicians, of which 36.9% were spe- extracted from these data banks. After telephone interviews, we cialists and 53.9% were subspecialists. determined that 313 cases were either retired, had immigrated, or Analyzing the distribution of doctors’ offices in Tehran showed were no longer alive. An additional 1921 cases were inaccessible, that the concentration of offices was higher in center of the city for 135 cases did not accept new patients, and 8 cases refused to be all physicians (43.2%). This information is summarized in Table 1. interviewed. Thus, we included and analyzed 3098 cases. Some The study findings show that the mean waiting time of patients physicians had more than one clinic or office; in this case only one for the first visit with specialists was 4.30 (SD = 8.10) days, with a office was randomly selected. median of 2.00 days. For subspecialists the mean was 7.61 (SD = Waiting time in this study was defined as the time between the 13.98) days and the median was 3.00 days. Comparison of means call for registration and the appointment date. The criterion was in these groups showed that waiting time for subspecialist first visits the nearest date for visiting a new patient according to physician’s was statistically higher than for specialists (P < 0.0001; Table 2). waiting list. The questionnaire consisted of ten questions: source of informa- Discussion tion, physician’s name, physician’s sex, office phone number, office address, type of specialty, faculty member, contact date, ex- The average waiting time in our study was less than a week for amination date, and number of other offices, clinics, and outpatient specialists and almost a week for subspecialists. More descriptive centers. We extracted the initial six questions from the data banks analyses showed that only 2% of specialists and 5% of subspecial- and the remainders of questions were completed by telephone in- ists had long waiting lists (more than four weeks). A comparison of terviews. A total of three staff members assisted with administer- our findings with the estimation from other countries with public ing the questionnaire. All staff members were trained and used a health care systems showed that patients in Tehran experienced uniform method for data gathering. less wait times. Most doctors’ offices are open on weekday afternoons, thus phone For example, in 2003 and 2005 the Canadian self-reported wait- contacts were made between 4–9 pm on all weekdays. When we ing time was about four weeks for a specialist visit for a new illness were unable to establish contact, the calls were repeated on other or condition.14 The results of another survey in this field showed working days and in the morning. that in Canada nearly half (46%) of the patients had waited less From July to December 2010, the data were recorded in the than a month for their initial specialist consultation. An additional sheets after quality control. SPSS statistical software was used for 40% waited one to three months, and 14% waited more than three data analysis. months.9,10 Outpatient waiting list statistics of the Department of Health of England in 2008 showed that from all 876,327 patients

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 757 Waiting Time for Specialist Consultation in Tehran waiting for their first outpatient appointment following a general community hospital: application of a computer simulation. China Med practitioner referral, about 70% waited less than four weeks.15 The J (Engl.). 2010; 123: 574 – 580. 2. Lungen M, Stollenwerk B, Messner P, Lauterbach KW and Gerber A. above statistics were obtained from countries with public health Waiting times for elective treatments according to insurance status: a structures in which waiting times were a main problem in their randomized empirical study in Germany. Int J Equity Health. 2008; health care systems. In these countries, general practitioners pro- 7: 1 – 7. vide patients’ care during their waiting time to be visited by spe- 3. Millin N. Performance report of west Gloucestershire Primary Care Trust Board. Available from: URL: www.westglospct.org.uk/board- cialist. If their situation worsened, patients could consult with a nov04/item10i.pdf [Accessed 10 April 2010] general practitioner and see a specialist sooner than the standard 4. Queensland Health. Policy framework for specialist outpatient servic- waiting period.16 es, Queensland government; 2004. Available from: URL: http://www. Waiting time in countries with health insurance systems is less qphci.qld.gov.au/qphci_pdf/QPHCI_Exhibit328-12.pdf [ Accessed 12 April 2012] than in countries with public health. In a 2005 survey of very ill 5. Bruni RA, Laupacis A, Levinson W, Martin DK. Public views on a patients that was conducted in six developed countries, the United wait time management initiative: a matter of communication. BMC States and Germany had less waiting times to see a specialist than Health Serv Res. 2010; 10: 228 – 237. 17 6. Canadian Medical Association. The taming of the queue: toward a cure the United Kingdom, Canada, Australia, and New Zealand. In for health care wait times, Discussion Paper July 2004. Available from: another study in the United States, cardiology, dermatology, ob- URL: http://www.rehabmed.ualberta.ca/spa/LTC_Waitlists/tame.pdf stetrics/gynecology, and orthopedic surgery waiting times were [Accessed 2 January 2011] estimated. The study results showed that in all cities among all 7. Chua KP, Rutledge J. Waiting Lists in Canada: Reality or Hype? 2005. Available from: URL: http://www.amsa.org/studytours/WaitingTimes_ the specialties, the average wait was 20.5 days. Appointment wait primer.pdf [Accessed 11 August 2012] times have increased on average by more than a week since the 8. Kisken T. Waiting time doesn’t mesh in different Ventura county ERs. survey was last conducted in 2004.18 Available from: URL: http://www.vcstar.com [ Accessed 10 October Studying waiting times in different health systems has shown 2011] 9. O’Neill BJ, Brophy JM, Simpson CS, Sholdice MM, Knudtson M, that in systems with complete referral systems, at the first level, Ross DB, et al. General commentary on access to cardiovascular care patients did not experience extended wait times for their first visit in Canada: Universal access but when? Treating the right patient at the to a general practitioner or family physician. At this level patients right time. Can J Cardiol. 2005; 21(14): 1272 – 1276 were screened to detect if they had a critical disease such as cancer. 10. Carrière G, Sanmartin C. Waiting time for medical specialist consultations in Canada, Statistics Canada; 2007. Available from: URL: http:// This screening led to reduce the delay in patients’ diagnosis and www.statcan.gc.ca/pub/82-003-x/2010002/article/11144-eng.htm#a3 treatment. [Accessed 24 November 2011] In our health system patients are not supported by a referral sys- 11. Waiting times in specialist outpatient clinics of restructured hospitals tem, thus waiting lists should be shorter in order to avoid the ad- and specialty centers, Ministry of health, Singapore; 2007. Available from: URL: http://he.ecitizen.gov.sg/content/dam/he_ecit/pdf/OP_on_ verse effects of delayed diagnosis and treatment. Thus studying Waiting_Times_for_New_SOC_Appointments.pdf [ Accessed 24 No- waiting times in different medical specialties and different regions vember 2011] would provide essential information that can give policy makers a 12. Levy AR, Sobolev BG, Hayden R, Kiely M, FitzGerald JM, Schechter MT. Time on wait lists for coronary bypass surgery in British Colum- more complete picture of the present situation and assist them to bia, Canada, 1991 – 2000. BMC Health Serv Res. 2005; 5: 22 – 32. better plan and manage the health system. 13. Lewis S, Barer ML, Sanmartin C, Sheps S, Shortt SED, McDonald PW. Ending waiting-list mismanagement: principles and practice, Can Med Assoc J. 2000; 162(9): 1297 – 1300. Acknowledgment 14. WillCox S, Seddon M, Dunn S, Edwards RT, Pearse J, Tu JV. Mea- suring and reducing waiting times: a Cross-National Comparison Of This article is based on "Rewiring specialists' and subspecialists' Strategies, Health Affairs. 2007; 26(4): 1078 – 1087. waiting lists in Tehran" research project. This study is funded by 15. Department of Health. Commissioner based hospital waiting times for 1st outpatient appointment, Quarter 2 2008/09, United Kingdom. Avail- Iranian Academic Center for Education, Cultural and research able from: URL: http://www.performance.doh.gov.uk/waitingtimes/ (ACECR) and planed and implemented by Institute for Health [Accessed 24 November 2011] Sciences Research (IHSR). The authors would like to thank every 16. Sanmartin C. Toward Standard definitions of waiting times for health body that contributes in this study. care services. Health Care Management Forum. 2003; 16(2): 49-53. 17. The commonwealth Found. International comparison: access and timeliness. Available from: URL: http://www.commonwealthfund.org/Per- formance-Snapshots/International-Comparisons/International-Com- parison--Access---Timeliness.aspx [ Accessed 24 November 2011] References 18. Thompson E. Waiting times to see doctor are getting longer. USA To- day. 2009. Available from: URL: http://www.usatoday.com/news/ 1. Chen BL, Li ED, Yamawuchi K, Kato K, Naganawa S, Miao WJ. Im- health/2009-06-03-waitingtimes_N.htm [Accessed 24 November 2011] pact of adjustment measures on reducing outpatient waiting time in a

758 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 M. Jalili, K. Shalileh, A. Mojtahed, et al.

Original Article Identifying Causes of Laboratory Turnaround Time Delay in the Emergency Department

Mohammad Jalili MD1, Keivan Shalileh MD•1, Ali Mojtahed MD1, Mohammad Mojtahed MD1, Maziar Moradi-Lakeh MD2

Abstract Background: Laboratory turnaround time (TAT) is an important determinant of patient stay and quality of care. Our objective is to evaluate laboratory TAT in our emergency department (ED) and to generate a simple model for identifying the primary causes for delay. Methods: We measured TATs of hemoglobin, potassium, and prothrombin time tests requested in the ED of a tertiary-care, metropolitan hospital during a consecutive one-week period. The time of different steps (physician order, nurse registration, blood-draw, specimen dis- patch from the ED, specimen arrival at the laboratory, and result availability) in the test turnaround process were recorded and the intervals between these steps (order processing, specimen collection, ED waiting, transit, and within-laboratory time) and total TAT were calculated. Median TATs for hemoglobin and potassium were compared with those of the 1990 Q-Probes Study (25 min for hemoglobin and 36 min for potassium) and its recommended goals (45 min for 90% of tests). Intervals were compared according to the proportion of TAT they comprised. Results: Median TATs (170 min for 132 hemoglobin tests, 225 min for 172 potassium tests, and 195.5 min for 128 prothrombin tests) were drastically longer than Q-Probes reported and recommended TATs. The longest intervals were ED waiting time and order processing. Conclusions: Laboratory TAT varies among institutions, and data are sparse in developing countries. In our ED, actions to reduce ED waiting time and order processing are top priorities. We recommend utilization of this model by other institutions in settings with limited resources to identify their own priorities for reducing laboratory TAT.

Keywords: Health care quality assurance, hospital administration, hospital emergency service, hospital laboratories, length of stay

Cite the article as: Jalili M, Shalileh K, Mojtahed A, Mojtahed M, Moradi-Lakeh M. Identifying Causes of Laboratory Turnaround Time Delay in the Emergency Department. Arch Iran Med. 2012; 15(12): 759 – 763.

Introduction causes of delay in laboratory TAT in different situations. We believe that, due to gaps in the level of technological sophistication he College of American Pathologists defines laboratory and differences between administrative systems, models generated turnaround time (TAT) as “the period of time from test or- in one country for the assessment of TAT may not be applicable in T dering to the time the results are made to the emergency another. department (ED).1” As one of the components of total patient In this study, we present a simple model for identification of the length of stay in the ED,2 reduction of laboratory TAT reduces ED causes of laboratory TAT delay that can be used in different set- stay,3,4 improves ED efficiency,5 and enhances patient safety and tings and countries with different levels of resource availability. satisfaction.6 On the other hand, laboratory tests have been report- We have used this model to evaluate laboratory TAT for hemoglo- ed as one of the causes of ED overcrowding.7 The well-known bin, serum potassium, and prothrombin time in a crowded tertiary 1990 Q-Probes Study8 reported a median TAT (defined as the inter- care ED, and then attempted to identify those steps of the process val from blood-draw to reporting of results) of 25 min for hemo- that have the most significant role in prolonging TAT. globin and 36 min for serum potassium (these two tests had been selected as surrogates for hematology and biochemistry tests, re- Materials and Methods spectively). The study suggested a median TAT (with the aforementioned definition) of 45 min for 90% of specimens as a reason- In this cross-sectional study, we measured and analyzed TAT able goal for the majority of ED tests. for hemoglobin, serum potassium, and prothrombin time using a The strategy for reducing TAT toward a desired goal should be modified, integrated adaptationof two previous models for study- based on identifying the causes of delay in TAT and taking actions ing laboratory TAT. One is the model used by Fernandes et al.,9 to eliminate them.2,9 Nevertheless, since the resources for interven- which incorporated the interval between the physician’s blood- tion are usually limited, it is wise to first address those steps with draw order into the Q-Probes sequence and compared the medians the greatest impact. The comparison of data from different settings with those of the Q-Probes. The other model, used by Sinreich and worldwide may provide invaluable knowledge as to the potential Marmor,2 has a holistic approach to the entire process of patient turnaround from admission to discharge, part of which is labora- Authors’ affiliations: 1Department of Emergency Medicine, Tehran University tory investigation, and measures the impact of each step on the of Medical Sciences, Tehran, Iran. 2Department of Community Medicine, Tehran University of Medical Sciences, Tehran, Iran. total length of stay. •Corresponding author and reprints: Keivan Shalileh MD, Department of The setting of our study was the ED of a tertiary-care university- Emergency Medicine, Tehran University of Medical Sciences, Keshavarz Blvd., affiliated teaching hospital with an annual census of more than Tehran 1419731351, Iran. Tel: +98-21-6119 2240; Fax: +98-21-6690 4848, E-mail: [email protected]. 24000 admissions. We calculated TATs for hemoglobin and serum Accepted for publication: 25 July 2012 potassium, which were used in Q-Probes as surrogates for hema-

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 759 Causes of Laboratory Turnaround Time Delay in ED tology and biochemistry investigations, respectively. In addition (not employees of our institution) were hired and, after receiving to the above tests, we included prothrombin time as another he- appropriate training, were equipped with digital timers (synchro- matologic test that is commonly requested but not as frequently nized every eight hours with the hospital computer system) to re- as hemoglobin. The laboratory instruments used for measuring cord the data in standard sheets at real time. This team worked hemoglobin, potassium, and prothrombin time were the Sysmex in three, 8-hour shifts, beginning from 06:00 every day, to avoid K-450 Hematology Analyzer (Sysmex Corp, Kobe, Japan) with a coincidence with the healthcare personnel shift changes at 07:00 manufacturer-reported throughput of 80 specimens/h; the IL 943 and 19:00. The physicians were also equipped with the same tim- Flame Photometer (Instrumentation Laboratory Co., Lexington, ers and charted their orders accordingly. MA, USA) with a throughput of 90 specimens/h; and TECO Coa- To avoid the Hawthorne effect, we used the strategy suggested tron M2 Coagulation Analyzer (TECO GmbH, Neufahrn, Ger- by Campbell et al.13; i.e., we informed the personnel about the many) with a throughput of 70 specimens/hr. The manufacturer- research nature of the operations in advance and requested them reported throughputs exclude the time necessary for centrifuge of not to change their performance. Patient anonymity was secured+ potassium specimens prior to biochemical analysis.10–12 We per- through assigning numbers to patients. The collection of data did formed this study over a consecutive one-week period in August not impede or change the direction of patient management, and no of 2010, beginning at 06:00. The choice of this specific time of risks were inflicted on the patients. The study was approvedby the year was made by comparing patient flow rates in different months Ethics Committee of the Research Division of the Department of of the year from the hospital database, of which August appeared Emergency Medicine. to approximate the average. Statistical analysis was performed using SPSS version 13.0 All tests for serum potassium, hemoglobin, and prothrombin time (SPSS Corp., Chicago, IL). Collected data (time points) were requested in our ED during the aforementioned period were stud- typed into the computer by the authors and the time intervals cal- ied. Incomplete tests (due to hemolysis, lost specimen, etc.) and culated accordingly, in minutes. A problem encountered during those for which part or all of the data was missing were excluded. analysis was that the times of physician order, test registration by According to the ED rules of practice, all orders are stat by default. nurse, and specimen availability did not consistently follow a lin- Figure 1 depicts a flowchart of the different steps in the entire ear order; e.g., in some cases, especially for more critical patients, process, which includes six time points with five time intervals. the recorded time of registration by nurse or specimen availability As comprehensive electronic records are not available in our was sooner than the physician order. In this case, we assumed that hospital, the time of physician order is only manually written by to save time, laboratory analyses were performed immediately fol- the physician in patient charts. Thus we have retrospectively ab- lowing verbal orders, therefore the interval(s) were corrected to stracted this information. The time of registration of the test by zero. the nurse, specimen arrival at the laboratory, and the time of re- The total TAT for each test was calculated as the algebraic sum sult availability are logged into the hospital computer network and of all five time intervals.The Q-Probes Study discovered that TAT therefore could be derived from that network. The time at which data have non-normal distribution and therefore reporting medians the specimen was ready and then dispatched from the ED were not (instead of means) for central tendency and interquartile ranges routinely recorded. For these, a team of healthcare professionals (instead of standard deviations) for dispersion is more appropri-

Figure 2. Box plots of turnaround times for different tests and different hours of the week. The dotted reference line represents the Q-Probes goal Figure 1. Flowchart of different steps in the laboratory turnaround process. of 45 min. Key to colored boxes: grey, all tests; black, tests overlapping Boxes denote time points, while arrows denote time intervals. with peak hours; white, tests outside peak hours.

760 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 M. Jalili, K. Shalileh, A. Mojtahed, et al. ate. The Q-Probes also recommended that institutional TATs be The highest interval-to-TAT ratio belonged to ED waiting for reported as the percentage of tests for which TATs are shorter than hemoglobin and prothrombin and to the within-laboratory inter- the Q-Probes goal (45 min). Along with reporting our TATs in the val for potassium. On the other hand, specimen collection was the above format, we reconfirmed the presumption of non-Gaussian shortest interval and had the lowest interval-to-TAT ratio (Figure distribution for our data using a one-sample Kolmogorov-Smirnov 4). test. We then performed a logarithmic transformation [ln (TAT – We found that slightly more than half of all tests (240 of 435, order processing time + 1)] to normalize data for both potassium 55.17%) overlapped with peak hours. Median TAT and interval-to- and hemoglobin and to compare them with the same logarithmic TAT ratios did not change considerably in these hours compared to transformation of Q-Probes medians (25 min for hemoglobin and other periods, but the percentages of tests meeting the goal were 36 min for potassium) using a one-sample t-test. The order pro- considerably lower (Figures 2 and 3). cessing time was subtracted since it was not included in the 1990 Q-Probes. Since the 1990 Q-Probes did not collect data for pro- Discussion thrombin time, no such statistical comparison was possible for this test. Our report shows high TATs (compared to Q-Probes goals) for The impact of each interval on the total TAT was defined as the our center at the time of the study. Intervals can be expressed in ratio of each time interval over total TAT (interval-to-TAT ratio). In two ways: minutes (length of each interval) and interval-to-TAT this regard, a longer interval will have a larger ratio, which shows ratios. The latter is better at explaining the impact of each interval its greater impact on prolongation of TAT. on the total TAT compared to other intervals. This can be of benefit By reviewing patient flow rates from the hospital database, the in identifying the intervals which should be addressed first if TAT period between 19:00 and 01:00 of the next day and the weekends is to be reduced. (from 06:00 on Thursday to 06:00 on Saturday) were identifiedas As the within-laboratory interval depends on the laboratory in- peak hours, and separate analysis of tests with intervals overlap- strument used and the inherent features of specimen processing, ping with these periods were also performed. we did not compare this interval among different test types. For instance, the need to centrifuge potassium specimens prior to bio- Results chemical analysis causes the within-laboratory interval for this test to be longer than those of hemoglobin and prothrombin,14 as was Data for 551 tests were collected, of which 116 were excluded the case in our study. In contrast, using a newer automated com- due to hemolysis (N = 14, potassium specimens), test cancellation plete blood counter with a higher throughput was probably the rea- (N = 61), lost specimens (N = 14), and incomplete data (N = 27). son for shorter within-laboratory intervals for hemoglobin (Figure As seen in Figure 2, the TATs for hemoglobin (N = 132) had a 4). With this interval ignored, the other intervals followed a similar median of 170 min (113–269.5), serum potassium (N = 172) had a pattern among the three test types. median of 225 min (167.25–324.5), and prothrombin (N = 128) of The ED waiting time had the largest interval-to-TAT ratio and 195.5 min (121.25–270.25). These data revealed that our medians hence was the longest interval. This was probably due to the lack were much higher than Q-Probes reported medians (P < 0.001 for of a mechanical tube system for carrying specimens, which ne- both hemoglobin and potassium). The same drastic gap was noted cessitated manual transport of specimens by personnel. Because for the percentage of tests that met the Q-Probes goal of 45 min dedicated technology or personnel for specimen transport were not (Figure 3). available, each collected specimen was kept in the ED until an or-

Figure 3. Percentage of tests meeting the Q-Probes benchmark of 45 min. Key to colored boxes: grey, all tests; black, tests overlapping with peak hours; white, tests outside peak hours.

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 761 Causes of Laboratory Turnaround Time Delay in ED

Figure 4. Interval-to-turnaround time ratios. derly was able to carry the tubes to the lab. This conclusion was equipment are subject to interdepartmental coordination and pro- further supported by the 1993 Q-Probes finding, which showed vision of adequate financial support, focusing on the out-of-labo- that implementation of a mechanical tube system considerably re- ratory aspects of TAT, which depend primarily on ED functioning, duced TAT compared to courier transport,14 and by reports which seems more productive. Future studies should focus on more de- showed that the presence of a point-of-care ED laboratory further tailed processing of different intervals. decreased TAT.4,15,16 We also had a relatively large number of excluded tests which The second longest among out-of-laboratory intervals was order was partly resulted from the absence of electronic records and ne- processing. Overcrowding is usually a challenge faced by our ED, cessitated manual recording of data by our team. Such data could with many patients lying on stretchers placed between licensed ED have been attained readily and more precisely from electronic re- beds and in the corridors. This problem partly results from national cords. In this regard, we made every effort to train and organize regulations which forbid hospitals to halt admitting new patients, our team in order for them to record as much data as possible, par- irrespective of the number of patients in the ED. We believe that ticularly in times of ED overcrowding. On the other hand, due to this excessive burden may impede certain processes, such as order budget constraints we could not provide synchronized time stamps processing, which solely depend on the limited number of clinical for our team so we had to manually synchronize all timers on a ED staff. This may have contributed to the prolongation of the ED regular basis as accurately as possible. waiting interval. There are no electronic records that cover all the The benchmarks we used for comparison dated back to 1990. parts of patient care in our hospital, so nurses need to manually ac- However, to the best of our knowledge, no newer official bench- cess patient charts to check physician orders and may be impeded marks have been announced by the College of American Patholo- by other personnel using the charts at the same time. gists or other similar institution after the 1990 Q-Probes study, The specimen collection interval was the shortest interval (again which is still being referred to in the current literature.9 with within-laboratory ignored). Fernandes et al.9 believed that Finally, as this study has been performed in a single institution as specimen collection by nurses was the reason for prolongation of a pilot study in Iran, the external validity of its results is question- this interval in their study, and suggested that assigning dedicated able. Conduction of similar studies in other centers will help to personnel for drawing blood would reduce this time. This conclu- recognize differences between institutions, and larger nationwide sion was confirmed in our study, where dedicated personnel were studies will definitely provide more valid data that can be general- hired for specimen collection and assisted by nurses at times of ized to most institutions in the country. overcrowding. Overall, the differences between our reported TATs and Q-Probes The effect of overcrowding on total TAT can be seen when we goals suggest that much needs to be done to improve TATs in our look at the lower percentage of hemoglobin and potassium tests institution. Regional ED laboratory TAT data is sparse,15 and to meeting the 45 min goal during peak hours. the best of our knowledge no similar study has been conducted in There are several potential limitations to our study. The major countries with limited resources. To improve ED TATs, we suggest limitation is that we did not measure the within-laboratory interval that similar studies be performed on a national scale to determine (including accession, queuing, and specimen processing intervals). achievable goals for each country and to design feasible improve- Since revising laboratory procedures and upgrading laboratory ment interventions. As for our institution, the introduction of a me-

762 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 M. Jalili, K. Shalileh, A. Mojtahed, et al. chanical tube system, launching point-of-care laboratories in the department throughput and decreases emergency medical services di- ED, installing fully functional electronic records, and modification version: a simulation model. Acad Emerg Med. 2008; 15: 1130 – 1135. 6. Gelrud J, Burroughs H, Koterwas J. Emergency care center turnaround of ED throughput regulations or increasing the number of person- time--an improvement story. J Healthc Qual. 2008; 30: 31 – 38. nel are recommended. 7. Derlet RW, Richards JR. Overcrowding in the nation’s emergency departments: complex causes and disturbing effects. Ann Emerg Med. 2000; 35: 63 – 68. Acknowledgments 8. Howanitz PJ, Steindel SJ, Cembrowski GS, Long TA. Emergency department stat test turnaround times. A College of American Patholo- This work was funded by Tehran University of Medical Sciences. gists’ Q-Probes study for potassium and hemoglobin. Arch Pathol Lab The authors are deeply indebted to Dr. Peyman Jafari, Assistant Med. 1992; 116: 122 – 128. 9. Fernandes CM, Worster A, Hill S, McCallum C, Eva K. Root cause Professor of Biostatistics at Shiraz University of Medical Sciences, analysis of laboratory turnaround times for patients in the emergency for his invaluable comments and advice on statistical analysis. department. CJEM. 2004; 6: 116 – 122. 10. Sysmex K-4500 Hematology Analyzer. Selangor: Sysmex Malaysia; c2010. Available from: URL: http://www.sysmex.com.my/default. References aspx?rd=TRUE&pagename=K-4500 [Accessed 10 October 2010] 11. IL 983 Flame Photometer. Brussels: Instrumentation Laboratory Co; 1. Definitions used in past Q-Probes studies 1989–2008). ( Northfield: c2010. Available from URL: http://www.instrumentationlaboratory. College of American Pathologists; c2008. Available from: URL: http:// com/benelux/Products%20Services/Clinical%20Chemistry/Instru- www.cap.org/apps/docs/q_probes/q-probes_definitions.pdf [Accessed ments/IL%20943.aspx [Accessed 10 October 2010] 27 July 2010]. 12. Coatron M2 coagulation analyzer. Neufahm: TECO GmbH. Available 2. Sinreich D, Marmor Y. Ways to reduce patient turnaround time and from URL: http://www.teco-gmbh.com/english/prod_m2.pdf [Ac- improve service quality in emergency departments. J Health Organ cessed 10 October 2010] Manag. 2005; 19: 88 – 105. 13. Campbell JP, Maxey V, Watson WA. Hawthorne effect: implications 3. Holland LL, Smith LL, Blick KE. Reducing laboratory turnaround for prehospital research. Ann Emerg Med 1995; 26: 590 – 594. time outliers can reduce emergency department patient length of stay: 14. Steindel SJ, Howanitz PJ. Changes in emergency department turn- an 11-hospital study. Am J Clin Pathol. 2005; 124: 672 – 674. around time performance from 1990 to 1993. A comparison of two 4. Lee-Lewandrowski E, Corboy D, Lewandrowski K, Sinclair J, McDer- College of American Pathologists Q-probes studies. Arch Pathol Lab mot S, Benzer TI. Implementation of a point-of-care satellite laboratory Med 1997; 121: 1031 – 1041. in the emergency department of an academic medical center. Impact on 15. Dhatt G, Manna J, Bishawi B, et al. Impact of a satellite laboratory on test turnaround time and patient emergency department length of stay. turnaround times for the emergency department. Clin Chem Lab Med Arch Pathol Lab Med. 2003; 127: 456 – 460. 2008; 46: 1464 – 1467. 5. Storrow AB, Zhou C, Gaddis G, Han JH, Miller K, Klubert D, Laidig 16. Lee-Lewandrowski E, Lewandrowski K. Perspectives on cost and out- A, Aronsky D. Decreasing lab turnaround time improves emergency comes for point-of-care testing. Clin Lab Med 2009; 29: 479 – 489.

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 763 Epidemiology of Four Main Nosocomial Infections in Iran

Original Article Epidemiology of Four Main Nosocomial Infections in Iran during March 2007 – March 2008 based on the Findings of a Routine Sur- veillance System

Seyed Mohsen Zahraei MD MPH•1, Babak Eshrati MD PhD2, Hosein Masoumi Asl MD MPH1, Zahra Pezeshki MS1

Abstract Background: Annually, around six million patients are admitted to hospitals in Iran. Information about the prevalence of nosocomial infections (NIs) is necessary for both appropriate management and establishment of preventative measures in hospitals. This article is based on the findings of the Nosocomial Infection Surveillance System (NISS) which has been providing information on NIs in Iran since March 2007. Methods: NISS covers 95 hospitals throughout Iran, each with over 200 beds. There are four main infections: urinary tract infection (UTI), surgical site infection (SSI), bloodstream infection (BSI) and pneumonia (PNEU) included in NISS. Reports are completed on forms that have been provided based on national guidelines. In all selected hospitals there is one designated nurse who conducts infection control activities and is trained in the detection and reporting of NIs based on NISS guidelines. Results: During March 2007 – March 2008, a total of 1,879,356 patients were admitted to the selected hospitals. The total detected NIs were 10557 with a prevalence of 0.57%. Of these, UTI was the most prevalent infection (32.2%) and BSI was the least (16.3%). Based on gender, females had more UTI, whereas PNEU was the highest in males. Of reported NIs, 9% were detected in children less than five years of age and included BSI (45%), PNEU (20%), SSI (19%) and UTI (16%). There were 26% reported NIs in the age group over 65 years, of which the most prevalent infections were UTI (42%) followed by PNEU (31%), SSI (15%) and BSI (12%). NIs were most often detected in intensive care units (ICUs; 26.7%), followed by surgery wards (12.8%). Conclusion: In comparison with other studies and the World Health Organization (WHO) estimates, the rate of NIs appears to be less according to NISS. NISS has the capability to provide basic information for efficient management and control measures, in addition to indicating variations in NIs based on gender, age and location (hospital ward). In order to have a more realistic estimate of NIs and strengthen NISS, it is advisable to conduct a point prevalence study.

Keywords: Iran, nosocomial infections, prevalence

Cite the article as: Zahraei SM, Eshrati B, Masoumi Asl H, Pezeshki Z. Epidemiology of Four Main Nosocomial Infections in Iran during March 2007 – March 2008 based on the Findings of a Routine Surveillance System. Arch Iran Med. 2012; 15(12): 764 – 766.

Introduction NIs. According to regulations proposed by the Ministry of Health and Medical Education, each hospital must have an active hospital osocomial infections (NIs) are important in terms of their infection control committee. In this regard the Nosocomial Infec- potential for high mortality, morbidity and elevated hospi- tion Surveillance System (NISS) was initiated in March 2007. NISS N tal costs.1–3 In the pediatric intensive care unit (ICU) alone, is based on a guideline prepared by the Iranian Center of Disease the mean cost of bloodstream hospital-acquired infections is ap- Control (ICDC). The aim of this paper is to report an overview of the proximately $39000 to $50000 per year.4–6 The prevalence of hos- results of NISS and discuss details regarding reported NIs by gender, pital-acquired infections varies from 5% in Europe and North age group and location (hospital wards). America to 40% in Sub-Saharan Africa, Latin America and parts of Asia.7 According to a survey by the World Health Organization Materials and Methods (WHO) that has been conducted in 14 countries, 8.7% of hospital inpatients suffer from NIs.8 In Iran there are over 100,000 hospital This was a prospective surveillance study, the results of which beds in 830 hospitals and approximately 6 million patients admit- were reported according to NISS guidelines from the ICDC. All ted annually (unpublished data). hospitals with more than 200 beds were included in the surveil- In order to control hospital-acquired infections, effective programs lance system regardless to the type of them (governmental or pri- are needed; however without information about the prevalence of vate) and it means that all large hospitals at the country are covered NIs the burden of estimation and effective programming for NIs is by NISS. Participation of the hospitals in NISS was mandatory. In almost impossible.8,9 There were limited studies about NIs in Iran, Iran, 95 out of 830 hospitals (non-random sample) were consid- which supposed 8%–10% prevalence rate,10,16,17 however additional ered sentinel sites and required to report their NIs cases to ICDC. information is needed to determine the country-wide presence of As such, all provinces are involved in NISS. Authors’ affiliations: 1Center for Communicable Diseases Control, Ministry of All patients diagnosed with NIs are registered, their informa- Health and Medical Education, Tehran, Iran. 2Health Deputy of Arak University tion recorded and reported to district health centers and then to the of Medical Sciences, Arak, Iran. ICDC at the end of each month. Each hospital in the NISS sends a •Corresponding author and reprints: Seyed Mohsen Zahraei MD MPH, Minis- try of Health Building, Hafez and Jomhoori crossroad, Tehran, Iran, NIs reporting form to the district health center for data review and Tel: +98-216-670-5031, Fax: +98-216-670-0143, analysis by the public health authorities. At the district level, all E-mail: [email protected] data are entered into the ICDC portal site. Accepted for publication: 19 September 2012

764 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 S. M. Zahraei, B. Eshrati, H. Masoumi Asl, et al.

ICU 26.7 Surgery 12.8 Internal 8.2 Orthopedics 6.4 Neurology 5.5 NICU 5.2 Burn 4.8 Neurosurgery 3.8 CCU 2.9 Gynecology 2.7 Nephrology 2.7 Hospital Ward Hospital Cardiology 1.8 Hematology 1.7 Infectious Diseases 1 Oncology 1 Others 9.7

0 5 10 15 20 25 30 Percentage Figure 1. Relative frequencies of four selected nosocomial infections (NIs) according to hospital ward.

Table 1. Frequency of different types of nosocomial infections (NIs) in different age groups. n (%) Age group (years) BSI* PNEU* SSI* UTI* Total 0–4 433 (46) 180 (19) 177 (19) 150 (16) 940 (100) 5–14 91 (20) 84 (19) 144 (33) 125 (28) 444 (100) 16–64 681 (11) 1470 (24) 2095 (33) 1972 (32) 6398 (100) 65+ 336 (12) 863 (31) 424 (15) 1152 (42) 2775 (100) Total 1721 2597 2840 3399 10557 *BSI = bloodstream infection; PNEU = pneumonia; SSI = surgical site infection; UTI = urinary tract infection. The definition of NIs according to NISS is a patient hospitalized (56.5%) males. The mean age of female was 44.84 (SD = 24.67) longer than 48 hours with a confirmed infection (clinical and/or years and for males it was 42.67 (SD = 24.69; P = 0.001). Out of laboratory) not present or incubating at the time of admission.10 10557 NIs patients, there were 3399 (32.2%) with UTI, most of Definitions are the same as standard definitions that have been whom (2456) were symptomatic. Other types of NIs resulted from published by the Centers for Disease Control and Prevention.11 SSI (n = 2840; 26.9%), PNEU (n = 2597; 24.6%), and BSI (n = For the beginning phase of the surveillance in order to have ease 1721; 16.3%). of reporting there are only four NIs selected, which comprise more The frequency of NI types differed between females and males. than 70% of all NIs.10 Cases are registered according to the site In females the numbers of NIs were: UTI (n = 1795; 39%), SSI (n of infection so that the following four main types of infections = 1194; 26%), PNEU (n = 884; 19%), and BSI (n = 719; 16%). In are reported: urinary tract infection (UTI), pneumonia (PNEU), males it was: PNEU (n = 1704; 28%), SSI (n = 1649; 28%), UTI bloodstream infection (BSI) and surgical site infection (SSI). Data (n = 1600; 27%), and SSI (n = 1012; 17%). The relative frequency pertaining to patients’ sex and age along with location (ward of ad- of detected NIs during the study period according to hospital ward mission) are also recorded in the forms by trained, selected nurses. is shown in Figure 1. ICUs (26.7%) had the most NIs, followed by We have used central and distributional measures for data analy- surgery wards (12.8%). The relative frequency of NIs by age group sis in this study. In order to show the difference in measures among and type of infection is shown in Table 1. The most common type of the different groups we used the Mann-Whitney tests. All differ- NIs in patients under the age of 5 years was BSI, in 5 to 64 years it ences were considered statistically significant with P < 0.05. We was SSI, whereas UTI was the most common in those over the age used SPSS (version 16) for data analyses. Confidentiality of the of 65 years (Table 1). The most prevalent type of infection in ICUs gathered data was maintained and there was no patient identifying was PNEU (51%), followed by UTI (25%), BSI (14%), and SSI information recorded. (10%). In Neonatal ICUs, BSIs (47%) were the most common type of infections followed by PNEU (31%), UTI (15%), and SSI (7%). Results Discussion During March 2007 – March 2008, a total of 1,879,356 patients were admitted to the selected hospitals. At the same time, there The advantage of NISS is its countrywide coverage such that in were approximately 10557 reported NIs cases from 95 hospitals every province there are at least two or three hospitals involved across different provinces of Iran. According to the results of in the surveillance system, which provides an overview of NIs in 10557 questionnaires, 10105 (96.8%) were from hospitals affili- Iran. However there are some limitations to the NISS. First, the ated with the Ministry of Health, 7 (0.1%) were private hospitals, NISS includes only four main NIs, second there is no tracking sys- and 146 (1.4%) were Ministry of Welfare hospitals. There was no tem for the follow up of discharged patients, and finally the data type of hospital reported in approximately 299 (2.8%) question- of hospitalized patients, with the exception of those categorized naires. NIs cases were reported from 1,879,356 patients hospital- with NIs, are not gathered. As a result, NISS is able to provide the ized in the above mentioned hospitals (about 5.67 per 1000 hos- frequency but not the rate of NIs with regards to gender, age and pitalizations). There were 4592 (43.5%) female patients and 5965 hospital wards.

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 765 Epidemiology of Four Main Nosocomial Infections in Iran

According to results from the first year of NIs surveillance in Iran Conflict of interest the reported rate of hospital-associated infections was low com- The authors state that they have no conflict of interest. pared to estimates from other studies. Although the prevalence of NIs reported in several studies ranged from 6% to 28% (USA: References 6%, Belgium: 7.1%, Italy: 6.7%, Uganda: 28%, and Shiraz, Iran: 10%), the findings from NISS reported 0.57% for hospital-associ- 1. Abdel-Fattah MM. Nosocomial pneumonia: risk factors, rates and ated infections in Iran.12–16 However, this low estimation has been trends. East Mediter Health J. 2008; 14: 546 – 555. 2. Eapen CE, Thomas K, Cherian AM, Jeyaseelan L, Mathai D, John G. possibly attributed to the weakness of the surveillance system in Predictors of mortality in a medical intensive care unit. Natl Med J following up patients after discharge. Follow up is very important India. 1997; 10: 270 – 272. for SSI patients, particularly taking into consideration the rapid 3. Raka L, Zoutman D, Mulliqi G, Krasniqi S, Dedushaj I, Raka N, et al. discharge of elective surgery patients at less than 48–72 hours after Prevalence of nosocomial infections in high-risk units in the university clinical center of Kosova. Infect Control Hosp Epidemiol. 2006; 27: admission. These patients are not usually followed. Additionally 421 – 423. NISS does not include all NIs therefore under the best of circum- 4. Slonim AD, Kurtines HC, Sprague BM, Singh N. The costs associated stances we could only find a 70% real prevalence of NIs. Finally, with nosocomial bloodstream infections in the pediatric intensive care The NISS is a routine surveillance system not a scientific survey unit. Pediatr Crit Care Med. 2001; 2: 170 – 174. 5. Elward AM, Hollenbeak CS, Warren DK, Fraser VJ. Attributable cost hence underreporting is common. of nosocomial primary bloodstream infection in pediatric intensive The results of our study showed that most reported NIs cases care unit patients. Pediatrics. 2005; 115: 868 – 872. were from the ICU. In two another studies performed in Shiraz 6. Dominguez TE, Chalom R, Costarino AT Jr. The impact of adverse (Iran) in 2001 and 2005, most cases were reported from ICUs and patient occurrences on hospital costs in the pediatric intensive care unit. 16,17 18,19 Crit Care Med. 2001; 29: 169 – 174. burn units, which were similar to other studies. This was 7. Lynch P, Jackson M, Preston GA, Soule BM. Infection Prevention With possibly due to more susceptible cases and the longer duration of Limited Resources. Chicago: ETNA Communications; 1997. hospitalizations in these units. 8. WHO, world alliance for patient safety, WHO Guidelines on Hand Hy- According to our study the most prevalent NIs was UTI. Lyy- giene in Health Care, 2005, WHO/EIP/SPO/QPS/05.2 9. Lyytikäinen O, Kanerva M, Agthe N, Möttönen T, Ruutu P; Finnish tikäinen et al. in a nationwide study reported the most prevalent Prevalence Survey Study Group. Healthcare-associated infections in hospital-acquired infection was SSI followed by UTI.9 This differ- Finnish acute care hospitals: a national prevalence survey, 2005. J ence in results might be due to underreporting of SSI and the dif- Hosp Infect. 2008; 69: 288 – 294. 10. Massomi Asl H. National Guideline of Nosocomial Infections Surveil- ference in selecting hospitals between these studies. In the current lance. Tehran: Iranian Center of Disease Control, Ministry of health study, the only inclusion criterion for hospital selection was the and medical education; 2006: 8 – 10. number of beds. However, similarities existed between our find- 11. Horan T, Gaynes R. Surveillance of nosocomial infections. In: Mayhall ings and those of other studies. For example Reilly et al. conducted C, ed. Hospital Epidemiology and Infection Control. Atlanta, GA: Lip- pincott Williams & Wilkins; 2004: 1659 – 1689 a point prevalence study in Scotland in 2005-6 which showed that 12. Weinstein RA. Nosocomial infection update. Emerg Infect Dis. 1998; 20 UTI was the most common NIs, followed by SSI. The main in- 4: 416 – 420. fection in all age groups was UTI, followed by SSI, PNEU and 13. Gordts B, Vrijens F, Hulstaert F, Devriese S, Van de Sande S. The 2007 BSI. However the frequency of infections in children less than five Belgian national prevalence survey for hospital-acquired infections. J Hosp Infect. 2010; 75: 163 – 167. years of age differed. In this age group the main infection was BSI 14. Lanini S, Jarvis WR, Nicastri E, Privitera G, Gesu G, Marchetti F, et al. followed by PNEU, SSI, and UTI which supported the findings by Healthcare-associated infection in Italy: annual point-prevalence sur- Rutledge-Taylor et al. in Canada in 2009.21 veys, 2002–2004. Infect Control Hosp Epidemiol. 2009; 30: 659 – 665. Based on our findings, young children and the elderly might be 15. Greco D, Magombe I. Hospital acquired infections in a large north Ugandan hospital. J Prev Med Hyg. 2011; 52: 55 – 58. more affected with NIs than other age groups. However, since we 16. Lahsaeizadeh S, Jafari H, Askarian M. Healthcare-associated infection did not have access to the exact numbers of admissions by age in Shiraz, Iran 2004–2005. J Hosp Infect. 2008; 69: 283 – 287. we could not confirm this observation. Among the elderly, those 17. Askarian M, Hosseini RS, Kheirandish P, Memish ZA. Incidence of with chronic diseases, the immunocompromised, and those with urinary tract and bloodstream infections in Ghotbeddin Burn Center, Shiraz 2000-2001. Burns. 2003; 29: 455 – 459. extended hospitalizations in addition to overall higher hospital ad- 18. Gosling R, Mbatia R, Savage A, Mulligan JA, Reyburn H. Prevalence mission rates could account for increased NIs seen in this popula- of hospital-acquired infections in a tertiary referral hospital in northern tion. Tanzania. Ann Trop Medical Parasitol. 2003; 97: 69 – 73. 19. Smyth ET, McIlvenny G, Enstone JE, Emmerson AM, Humphreys H, Fitzpatrick F, et al. Four Country Healthcare Associated Infection Conclusion Prevalence Survey 2006: overview of the results. J Hosp Infect. 2008; According to the results of our study it seems that the sensitivity 69: 230 – 248. of NISS compared with studies from other countries18–22 is low in 20. Reilly J, Stewart S, Allardice GA, Noone A, Robertson C, Walker A, et al. Results from the Scottish National HAI Prevalence Survey. J Hosp Iran. We need to conduct a validation study such as a point-prev- Infect. 2008; 69: 62 – 68. alence study in order to get more accurately estimate the extent 21. Rutledge-Taylor K, Matlow A, Gravel D, Embree J, Le Saux N, John- of hospital-acquired infections which would result in better pri- ston L, et al. A point prevalence survey of health care-associated infec- oritization of allocated resources.22 Due to the continuity of NISS tions in Canadian pediatric inpatients. Am J Infect Control. 2012; 40: 491 – 496. these findings could be very important in presenting the trend of 22. Klevens RM, Edwards JR, Richards CL Jr, Horan TC, Gaynes RP, Pol- infections. It can provide important indicators to the responsible lock DA, et al. Estimating health care-associated infections and deaths authorities to enable planning and evaluation of the infection con- in U.S. hospitals, 2002. Public Health Rep. 2008; 122: 160 – 166. trol activities in hospitals. In addition, NISS is a recently established system and needs strengthening to produce more appropriate results.

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Original Article A Qualitative Evaluation of Men Living with HIV: Views on Condom Use

Homeira Fallahi MD MPH PhD1*, Sedigheh Sadat Tavafian PhD•2, Farideh Yaghmaie PhD3, Ebrahim Hajizadeh PhD4, Ali Rastegarpour MD1, Maryam Fouroghi MD5

Abstract Background: Unprotected sexual activity is an important reason for the currently growing incidence of HIV infection in Iran. Recognizing barriers to safe sexual practice and affordance of behavioral changes can improve planning for condom promotion. The main objective of our study is to evaluate the opinions of HIV-positive men on condom use. Methods: Our study was performed at three behavioral disease consultation clinics (HIV care clinics) in Tehran, Iran. Participants were initially selected among HIV-positive male patients by convenience sampling and narrowed-down by maximum diversity sampling in order to obtain the number of patients that would express various viewpoints regarding barriers and benefits to condom use. Data were collected using in-depth semi-structured individual interviews. All interviews were recorded and transcribed, and the codes were extracted after reviewing them several times. Results: In this study, 22 HIV-positive men with a mean age of 37.5 ± 7.3 years were interviewed. Participants mentioned the prevention of HIV and sexually transmitted diseases as a benefit of condom use. However, most named decreased sexual satisfaction as the most important reason for not using condom. Because of decreased sexual satisfaction and unpleasantness, 9% of participants had not used condom during sexual intercourse. Conclusion: The most important reason for not using condom was decreased sexual satisfaction. This study has indicated a need for consultations with HIV-positive and at risk populations to change their attitudes towards condom use and demonstrate the advantages of condom. To achieve this, government programs and media should be utilized.

Keywords: Condom, HIV-AIDS, Iran, qualitative research

Cite the article as: Fallahi H, Tavafian SS, Yaghmaie F, Hajizadeh E, Rastegarpour A, Fouroghi M. A Qualitative Evaluation of Men Living with HIV: Views on Condom Use. Arch Iran Med. 2012; 15(12): 767 – 771.

Introduction Official reports show that as of October 23, 2011, a total of 23497 people have been diagnosed with HIV/AIDS across Iran. Of these, ince the beginning of the AIDS epidemic approximately 60 91.3% were males and 8.7% were females. The 25–34 year age million person worldwide have been infected with HIV, group has the highest number (43.7%) of infected individuals and S and 25 million have died of HIV-related causes.1 A report shared use of hypodermic needles among injecting drug users is on the HIV epidemic in the Middle East and North Africa (MENA) the most common mode of infection (69.8%). Unprotected sexual shows that while the overall HIV prevalence in the region is still contact (10.1%), mother-to-child transmission (0.9%) and transfu- low, the rise in new infections since 2001 has put the MENA region sion of contaminated blood (1%) are additional modes of transmis- among the top two regions in the world with the fastest growing sion. In 18.2% of cases the mode of transmission is unknown.5 HIV epidemy.2 However, the number of cases whose mode of transmission is Advances in HIV care have resulted in prolonged life expectancy unclear has steadily increased in recent years. According to one for people living with HIV (PLWH), which predisposes higher theory, unreported transmissions among sexual contacts due to the number HIV-positive persons to unsafe sexual practices. This pro- fear of stigma may be responsible for this increase.6 vides the dual risk of HIV transmission to HIV-negative sexual During the past few years, the prevalence of AIDS in Iran has partners and transmission of other sexually transmitted infections grown from a low-level status to a concentrated prevalence. While to the infected parties. Therefore, controlling unsafe sexual activi- intravenous (IV) drug use has been introduced as the primary route ties in HIV-positive persons has not only become a necessity, but a of HIV transmission,5 the lack of information surrounding sexual main concern in HIV prevention.3,4 conduct in Iran has rendered statistics unreliable.7 In addition, there Authors’ affiliations: 1Shahid Beheshti University of Medical Sciences, Teh- is much concern that the pattern of HIV transmission in Iran may ran, Iran, 2Department of Health Education, Faculty of Medical Sciences, Tar- be changing towards a trend of increasing transmission by sexual biat Modares University, Tehran, Iran, 3Department of Nursing, Shahid Beheshti intercourse. Numerous studies in Iran have demonstrated that low University of Medical Sciences, Faculty of Nursing and Midwifery, Tehran, Iran, 4Department of Biostatistics, Faculty of Medical Sciences, Tarbiat Modares Uni- rates of condom use in high-risk populations range from 11% to 8–10 versity, Tehran, Iran, 5Iranian Research Centre for HIV/AIDS, Tehran University 64.8%. Studies in other countries have shown that the percent- of Medical Sciences, Tehran, Iran. age of condom use among PLWH is not desirable.11,12 This is con- •Corresponding author and reprints: Sedigheh Sadat Tavafian PhD, Tarbiat Modares University, P. O. Box: 14115-111, Tehran, Iran. Tel: +98-21-82884547, sidered to be a challenge in the prevention of HIV. E-mail: [email protected] Considering that the rate of condom use is not satisfactory in Iran, Accepted for publication: 27 June 2012 thus identifying barriers to safe sexual practice among high-risk *These authors contributed equally to this work groups may assist in planning preventive interventions.

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 767 Men Living With HIV: Views on Condom Use

The Health Belief Model (HBM) is one of the models used to coding, and analysis of some of the interviews by other experts).18 implement interventions for reducing high-risk sexual behaviors.13 Ethical approval was granted by Tehran and Shahid Beheshti This model takes into consideration the barriers and affordance of Medical Universities. All participants gave oral consent to enter behavioral changes. In addition to its perceptions on susceptibility, the study. Patient confidentiality was observed by omitting demo- severity, benefit, barriers and self-efficacy, and cues to action and graphic data from the typed interviews and participants were al- their relations to safe sexual contacts.14 lowed to discontinue participation at any time. Few studies have examined the attitudes of HIV-positive persons A total of 22 participants entered into the study. The time of each towards condom use in Iran,15 and since cultural differences play a interview session varied and ranged between 41 to 90 minutes. In- large role in such perceptions, barriers to condom use may widely terviews were held uninterrupted in an isolated room. Interviews differ among various cultures.16 and data analysis were performed by colleagues who had taken Qualitative research is a scientific approach to evaluate beliefs adequate courses in qualitative research. Data analysis was based and identify the causes of behavior in everyday life which can as- on content analysis. sist human beliefs. The advantage of qualitative research is that it gives weight to participants’ viewpoints and maintains the capac- Results ity for explanation, description, and discovery during interviews.17 The present study uses a qualitative approach to evaluate the Socio-demographic characteristics viewpoints of HIV-positive men regarding condom use, based on Of the 22 HIV-positive male participants, 11 were single, 9 were the HBM. This article is part of a widespread study of behavioral married, and 2 were divorced. Participants mean age was 37.5 ± changes regarding condom use which has been undertaken in Iran. 7.1 years (range: 27–53 years). Fourteen (74%) participants had reached the disease stage of AIDS and were under anti-retroviral Materials and Methods therapy. The main risk activity responsible for infection was IV drug use. Ten of the participants had both a history of IV drug use Sample and unprotected sexual activity; two only reported unprotected This study recruited patients who referred to three behavioral sexual contact. Although aware of their infection with HIV, 9 par- disease consultation clinics (HIV care clinics) in Tehran, Iran dur- ticipants reported unprotected sexual activity during the previous ing a nine month period from May 2010 to February 2011. Par- year and 2 reported unprotected contact during their last sexual en- ticipants were selected from among HIV-positive male patients counter. Participants’ demographic and behavioral characteristics by convenience sampling, then narrowed-down by maximum di- are seen in Table 1. versity sampling in order to obtain a sample that would express various viewpoints regarding barriers and benefits to condom use. Table 1. Demographic and behavioral characteristics of participants. Interviews were continued until the point of data saturation was Variable Males (n = 22) accomplished. 19–29 (3) 30–39 (11) Age (years) Data collection 20–49 (6) We conducted in-depth interviews questions which were open- Over 50 (2) ended. The questions were based on the constructs of the HBM in Single (11) Marital status Married (9) order to obtain information regarding participants’ perception of Divorced (2) susceptibility, severity, benefit, barriers, and self-efficacy, as well Unemployed (8) as cues to actions related to safe sexual contacts. This study only Employment Employed (13) assessed perceptions to the benefits and barriers of condom use. Retired (1) After obtaining consent from all participants, their demographic Education Uneducated (2) and personal information were recorded on paper. The remainder Elementary (3) of the interview was conducted with a voice recorder. Interviews Lower secondary (6) Upper secondary-diploma (10) were later listened to and transcribed verbatim. At this stage, con- Further education (1) tent analysis was performed. Interview texts were reviewed mul- Imprisonment Positive (19) tiple times and after acquaintance with the contents, codes were record Negative (3) extracted and categorized, and main themes identified. Used condom during last sexual contact (11) The findings of this study were supported by adherence to the Sexual contact Without sexual contact in last year (9) following criteria to evaluate the rigor and trustworthiness of the Did not use condom during last sexual contact (2) Methadone maintenance treatment (9) qualitative data: i) credibility (gaining participant trust and sup- History of drug Narcotics anonymous recovery (11) port, researcher involvement with the data, the use of peer opin- addiction No addiction record (2) ions and allowing for separate coding, investigator triangulation by having more than one person interpret the data, and method Intravenous drug addiction (10) History of high Unprotected sexual relationship (2) triangulation using interviews, observation, and studying patients’ risk behavior Intravenous drug addiction and unprotected sexual records); ii) transferability (precise descriptions of the participants relationship (10) that included sampling, time and place of data collection, and maximum diversity sampling); dependability (an external check Participants’ opinions on condom use and simultaneous coding by another researcher to find probable We investigated participants’ viewpoints on the following ques- discrepancies); and iii) conformability (returning the interviews to tions: 1) “What is a condom and what is your idea about using it?”; participants and controlling data with participants, reevaluation of 2) “What are the benefits of condom?”; 3) “Why do some people

768 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 H. Fallahi, S. S. Tavafian, F. Yaghmaie, et al.

Table 2. Themes and subthemes about the benefits and barriers of condom use. Themes Subthemes Codes Perceived benefits Condom is an individual health device. Internal Makes people feel comfort benefits Prevention of transmitted HIV/AIDS and sexually transmitted diseases. External Condom is a contraceptive for the prevention both of pregnancy and the birth of a child with benefits AIDS. Perceived barriers Decreased sexual satisfaction. No need for condom use couples if one of the couples is HIV negative. Individual beliefs Failure of condom use during sexual contact. Shyness of buying condom. Access/availability of condom No condom access at the beginning of intercourse. Condoms are expensive. Condom Low quality and no variety of condom in Iran. not use condom?”; and 4) “In your opinion, what are the barriers Access/availability of condom to condom use?”. One-fourth of the infected men mentioned diffidence towards Participants’ viewpoints were divided into two groups of themes buying condom as a main barrier. Some thought that if the sales about the benefits of and barriers to condom use. Each theme was person at a drugstore were female, a situation can occur where shy- divided into subthemes and codes. Participants presented a range ness may impede the purchase of condom. of factors as benefits and barriers to condom use, of which the One-fourth of our participants mentioned limited access to con- most important were that it was a safe method for the prevention dom when needed due to the distance to the nearest drugstore or of diseases, but also caused reduced sexual satisfaction. Age and the drugstore being closed. A 28-year-old recently married man educational status had no effect on the responses. The themes and who had been infected by unprotected sexual activity said: “There subthemes are seen in Table 2. aren’t enough condoms, or there’s no drugstore in the neighbor- hood, or it just may be noon and we tell ourselves to just forget Benefits it. And on one of these contacts that we say ‘just forget it’, it hap- Internal benefits pens.” One-fourth of patients stated that the condom is a protective The cost of condom was referred to by two of the HIV-positive health device. A patient pointed out that: “Condom will protect us men: “Buying condom has become a routine cost for me. When I because we have a deficient immune system, thus we have to use it have to buy a box of condoms for 35,000 Rials every week, every for saving health.” (40-year-old, married) Only one of our partici- ten days, I may be able to pay for them now, but it can be a cause pants mentioned that condom has a good mentally effect. [for not using them]. I know people who can’t pay 3,500 a week.” (51-year-old, married) External benefit Most participants mentioned the role of condom on preventing Condom sexually transmitted diseases and HIV infection. For instance, one Infected men believed that the quality standards of condom were of the participants stated that: “I am infected by HIV and I have not adequate in Iran. to use condom as a preventing device for AIDS, gonorrhea, and “These condom they make in Iran, they just change the scent and hepatitis.” (36-year-old, single) taste. What good is that? Foreign condoms are something else… Some of the patients mentioned the role of condom as contracep- We don’t have those in Iran. Iranian condoms are no good. They tive device. For example: “Since I have infection, I shouldn’t have break, they burst and they come off.” (36-year-old) any children and I shouldn’t get my wife pregnant. We have to prevent babies born to HIV positive mothers.” Discussion (47-year-old, divorced) In this study, of all HIV-infected male, almost half mentioned a Barriers history of IV drug use along with unprotected sexual activity be- Individual beliefs fore infection and two mentioned a history of unprotected sexual Participants presented a spectrum of factors as barriers to con- contact as the only possible method of transmission. This, in itself, dom use. The most commonly mentioned barrier to condom use has emphasized the importance of condom use in high-risk sexual in this study was decreased sexual satisfaction. Examples: “I have activities. More than half of the infected subjects were unmarried; been used condom twice but I didn’t feel satisfy so I don’t like to use any unprotected sexual contact would be considered high-risk, it again.” (37-year-old, single) which could contribute to the overall spread of HIV in the commu- Some men believed that there might not be a need to use condom nity. In the Middle East, of all people who recognize the protective when their partner was HIV-positive. One of the patients stated effect of condom against HIV transmission, only a few actually that: “If the person is positive, I don’t know…, I don’t think there’s a use them. Within the group that uses condom, only a few use them need [to use condom].” (36-year-old infected man, single) Finally, consistently. Even in high-risk groups for which condom use is a two of the infected men stated the possibility of condom failure as priority, the rate of condom use is low.19 a barrier. Viewpoints of participants have been divided into the two themes of benefits and barriers to condom use. The most important benefit

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 769 Men Living With HIV: Views on Condom Use was the relationship to the prevention of sexual diseases, including In Drop In Centers (DIC) and at the Positive Club where HIV-pos- HIV, and the most important barrier to condom use was related to itive or at-risk populations may refer, condoms are placed where the reduction in sexual satisfaction. anyone can take them. Since such centers are only open on work Among the 13 men who did report sexual activity, 2 (15%) re- days and during working hours, installing vending machines for ported unprotected contact on their last sexual intercourse, despite condom in front of drugstores or supplying condom in department being aware of their infection with HIV. A number of HIV-positive stores and supermarkets could be helpful. persons who were aware of their diagnosis failed to use protection In addition, the quality and variety of available condom in the for sexual contacts.20–23 market should be assessed and if necessary, improved, to ensure Rahmati Najarkolaei et al.24 performed a qualitative study on that none of the concerns regarding failure, physical side effects, HIV-positive patients in Iran. The researchers also reported a num- and reduced sexual satisfaction remain valid. ber of HIV-positive persons who were aware of their diagnosis, yet Although we have attempted to overcome most limitations in this failed to use protection for sexual contacts. These results supported study, there are a number of drawbacks, many of which are general the existence of certain barriers to condom use. Considering that limitations seen in qualitative research. One limitation is that the there were no existing studies that evaluated the views of HIV- study sample in qualitative research is usually small and cannot positive persons towards condom use in Iran, this study was de- be directly generalized to the overall population. Our study sub- signed to identify these barriers in person who were aware of their jects were patients that had referred to consultation clinics for HIV, diagnosis; most who had experienced high-risk behaviors for HIV. therefore they were not representative of the entire community of The most commonly mentioned and most important barrier to HIV patients and families. Those that do not refer to such clin- condom use in this study was decreased sexual satisfaction. In one ics may be culturally or socio-economically different populations. study on Iranian female sex workers, it was revealed that although Another drawback was that although all measures were taken to many clients wished to use condom when engaging in sexual con- gain the participants’ trust during interviews, participants may still tact with a sex worker, a larger number preferred contact without have not spoken their uncensored intentions and beliefs due to the condom. The main reasons mentioned in this study for reluctance controversial and personal nature of the study. towards condom use included decreased sexual satisfaction, incon- The Islamic Republic of Iran has been a leading country in HIV venience for anal contact, as well as dislike and fear of condom.25 prevention and treatment in MENA. The main objective for con- Another study on IV drug users showed condom use to be very low dom use is its efficacy in the prevention of sexually transmitted among Tehran drug addicts despite good access and availability, diseases. According to the results of this study, we should em- presumably due to the decrease in sexual sensation.26 Decrease is phasis critical role of condom using against sexually transmitted sexual satisfaction has also been mentioned as an influential factor diseases. Behavioral disease consultation clinics that are important in various studies both in Iran and other countries.27,28 This similar- places for consultation, training and education of HIV-positive and ity between findings has shown that people strongly believe which other high risk groups should be established.33 condom reduce sexual satisfaction. Educational programs and con- High risk populations should be specifically considered to be ed- sultation may be able to target this attitude and emphasize on the ucated. Other factors are can be overcome by precise planning and benefits of condom use in return for the drawbacks, particularly for intervention by policy makers along with availability of condom in high-risk groups. medical and social centers. In the Middle East, drugstores constitute the main source for obtaining condom.19 Since in Iran the condoms are frequently located Conflict of interest: None in the cosmetics section rather than the pharmacy, it is not uncommon for the salesperson in this section to be a woman. This could Acknowledgments cause the shyness that some mentioned in the current study. Peltzer on his study based on HBM has mentioned the shyness of buying The authors would like to express their appreciation to the par- condom from the opposite sex.29 ticipants of this study for their willingness to participate. In Hingson’s study based on HBM there was a relation between condom use and the barriers to condom use. People who did not References believe in the barriers to condom use such as shyness and reduction in sexual satisfaction used condom 2.4 times more than others.30 1. UNAIDS. AIDS Epidemic Global Facts and Figures Factsheet. Avail- Adih and colleagues performed their study based on the social able from: URL: Ahttp://www.unaids.org/en/media/unaids/contentas- learning theory and HBM. They determined that if there was more sets/dataimport/pub/factsheet/2009/20091124_fs_global_en.pdf [Ac- cessed May 9, 2011]. satisfaction on condom use and less sensitivity to barriers, the use 2. UNAIDS. Available from: URL: http://www.unaids.org/en/resources/ of condom would be three times more than the control group.31 presscentre/featurestories/2011/december/20111204menareport/ [Ac- Thus, it might be argued that awareness of the benefits of condom cessed May 4, 2011]. 32 3. Kestern N, Hospers H, Kok G. Sexual risk behavior among HIV-pos- among high risk population is guaranteed . itive men who have sex with men: a literature review. Patient Educ By overcoming these barriers, condom use can be improved couns. 2007; 65: 5 – 20. among men. Different strategies, such as the educational-behav- 4. Zekan S, Novotny TE, Begovac J. Unsafe sexual behavior among HIV- ioral strategy have been suggested. Education and consultation can infected patients in Croatia, 2006: prevalence and associated factors. AIDS Behav. 2008; 12: S86 – S92. change many of the negative attitudes towards condom use. 5. Center for Disease Control, Office of the Deputy for Public Health, Another recommended strategy is the provision of easy and free Ministry of Health and Medical Education of the IR Iran. HIV/AIDS access to condom. Currently, in behavioral disease consultation in Iran (Cumulative Statistics). Tehran: Ministry of Health and Medi- clinics condoms are distributed for free. To avoid awkwardness cal Education of the IR Iran; 2011. Available from: URL: http://port. health.gov.ir/mfdc.cdc [Accessed September 29, 2011] for patients, sometimes condoms are offered by the consultants. 6. National AIDS Committee Secretariat, Ministry of Health and Medical

770 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 H. Fallahi, S. S. Tavafian, F. Yaghmaie, et al.

Education. On Monitoring of the United Nations General Assembly 20. Kalichman SC. Psychological and social correlates of high-risk sexual Special Session on HIV and AIDS 2010. Available from: URL: http:// behavior among men and women living with HIV/AIDS. AIDS Care. www.unaids.org/en/dataanalysis/monitorin gcountryprogress/2010pr 1999; 11: 415 – 428. ogressreportssubmittedbycountries/iran-2010-country-progress-report 21. Norman LR. Predictors of consistent condom use: a hierarchical analy- [Accessed April 9, 2011] sis of adults from Kenya, Tanzania and Trinidad. Int J STD AIDS. 2003; 7. Gheiratmand R, Navipour R, Mohebbi MR, Mallik AK. Uncertainty 14: 584 – 590. on the number of HIV/AIDS patients: our experience in Iran. Sex 22. Strebel A, Cloete A, Simbayl L. Social aspect of HIV/AIDS and health Transm Infect. 2005, 81: 279 – 280. four-country report on formative research into the development of a 8. Zargooshi J. Characteristics of gonorrhoea in Kermanshah, Iran. Sex HIV behavioral risk reduction intervention for PLWHA Botswana, Le- Transm Infect. 2002; 78: 460 – 461. sotho, South Africa and Swaziland. HSRC (Human Sciences Research 9. Zamani S, Kihara M, Gouya MM, Vazirian M, Ono-Kihara M, Raz- Council). Available from: URL: http://www.hsrc.ac.za/HAST-Projects. zaghi EM, et al. Prevalence of and factors associated with HIV-1 infec- phtml [Accessed Jun 9, 2011] tion among drug users visiting treatment centers in Tehran, Iran. AIDS. 23. Coleman SM, Rajabiun S, Cabral H, Bradford J, Tobias C. Sexual risk 2005; 19: 709 – 716. behavior change among persons newly diagnosed with HIV: the impact 10. Ramezani Tehrani F, Malek-Afzali H. Knowledge, attitudes, and prac- of targeted outreach interventions among Hard-to-reach population. tices concerning HIV/AIDS among Iranian at-risk sub-populations. AIDS Patient Care STDs. 2009; 23: 636 – 645. East Mediterr Health J. 2008; 14: 142 – 156. 24. Rahmati Najarkolaei F, Niknami S, Amin Shokravi F, Ahmadi F. Per- 11. Loubiere S, Peretti-Watel P, Boyer S, Blanche J, Abega S, Spire B. HIV ception and behaviors of HIV/AIDS patients: qualitative research [in disclosure and unsafe sex among HIV-infected women in Cameroon: Persian]. Behbood. 2009; 13: 220 – 234. results from the ANRS-EVAL study. Soc Sci Med. 2009; 69: 885 – 891. 25. Ministry of Health and Medical Education. Center control disease. Fi- 12. Bedimo AL, Kissinger P. Understanding barriers to condom usage nal Report of Rapid Assessment Research Project on Women’s Risk among HIV-infected African American women. J Association Nurses Behaviors in Female Sex Workers in two areas of IRAN [in Persian]; AIDS. 1998; 9: 48 – 58. 2008. 13. Lance Coleman C. Health beliefs and high-risk sexual behaviors 26. Razzaghi EM, Rahimi Movaghar A, Mohammad K, Hosseini M. A among HIV-infected African American men. Appl Nurs Res. 2007; 20: qualitative study of risky sexual behavior in injecting drug users in Teh- 110 – 115. ran [in Persian]. J Sch Publ Health Inst of Publ Res. 2003; 2: 1 – 10. 14. Iriyama S, Nakahara S, Jimba M, Ichikawa M, Wakai S. AIDS health 27. Sunmola AM. Sexual practices, barriers to condom use and its con- beliefs and intention for sexual abstinence among male adolescent stu- sistent use among long distance truck drivers in Nigeria. AIDS Care. dents in Kathmandu, Nepal: a test of perceived severity and suscepti- 2005; 17: 208 – 221. bility. Public Health. 2007; 121: 64 – 72. 28. Bogart L, Kral A, Scott A, Anderson R, Flynn N, Gilbert M, et al. Con- 15. Eshrati B, Taghizadeh Asl R, Dell CA, Afshar P, Millson PM, Kamali dom attitudes and behaviors among injection drug users participating M, et al. HIV transmission among Iranian prisoners: initial support for in California Syringe Exchange Programs. AIDS Behav. 2005; 9: 423 providing education on the benefits of harm reduction practices.Harm – 432. Reduct J. 2008; 5: 1 – 7. 29. Peltzer K. Factors affecting condom use among junior secondary 16. Cha ES, Doswell WM, Kim KH, Charron-Prochownik D, Patrick TE. school pupils in South Africa. Health Sa Gesondheid. 2000; 5: 37 – 44. Evaluating the Theory of Planned Behavior to explain intention to en- 30. Hingson RW, Strunin L, Berlin BM, Heeren T. Beliefs about AIDS, gage in premarital sex amongst Korean college students: a question- use of alcohol and drugs, and unprotected sex among Massachusetts naire survey. Int J Nurs Stud. 2007; 44: 1147 – 1157. adolescents. AJ P H. 1990; 80: 295 – 299. 17. Godin G, Naccache H, Pelletier R. Seeking medical advice if HIV 31. Adih WK, Alexander CS. Determinants of condom use to prevent HIV symptoms are suspected. Qualitative study of beliefs among HIV-neg- infection among youth in Ghana. J Adolesc Health. 1998; 24: 63 – 72. ative gay men. Can Fam Physician. 2000; 46: 861 – 868. 32. Volk JE, Koopman C. Factors Associated with Condom use in Kenya: 18. Polit DF, Beck CT. Nursing Research, Method, Appraisal and Utiliza- A test of the Health Belief Model. AIDS Educt Prev 2001; 13: 495 – tion. 5th ed. Philadelphia: Lippincott Co; 2006: 332 – 336. 508. 19. The world Bank Report. Characterizing the HIV/AIDS Epidemic in the 33. Mattson M. Impact of HIV test counseling on college students’ sexual Middle East and North Africa Time for Strategic Action; 2010. Avail- beliefs and behaviors. Am J Health Behav. 2002; 26: 121 – 136. able from: URL: http://issuu.com/world.bank.publications/docs/97 80821381373 [Accessed May 28, 2011]

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 771 Current Status of Liver Transplantation

Review Article Current Status of Liver Transplantation

Reza F. Saidi MD FICS FACS•1

Abstract Liver transplantation (LTx) is the treatment of choice for patients with end-stage liver disease (ESLD). Improvement in outcomes (allograft and patient survival) has led to widespread use of LTx worldwide. However, new problems that include severe organ shortage, recurrence of primary disease, opportunistic infections, and development of de novo malignancies are the major problems affecting further implementation of LTx.

Keywords: Indications, immunosuppression, liver transplantation, outcomes, results

Cite the article as: Saidi RF. Current Status of Liver Transplantation. Arch Iran Med. 2012; 15(12): 772 – 776.

Brief history of liver transplantation (LTx) model of end stage liver disease (MELD) was developed based The first successful liver transplantation (LTx) was performed in on three objective criteria that included bilirubin, creatinine, and the United States by Thomas Starzl in Denver, Colorado in 1967.1 international normalized ratio (INR) levels and implemented in the With increasing numbers of patients on the waiting list, transplan- US. Changes to the organ allocation policy in 2002 reduced the tation of partial liver grafts from living donors has evolved to in- number of adult patients on the LTx waiting list, decreased wait crease the donor pool. Strong et al. performed the first successful list mortality, and increased the number of patients who received living-donor liver transplantation (LDLT) in 1989, when they im- simultaneous liver-kidney transplantations (SLK).4 Because of the planted a left lateral liver segment into a pediatric patient.2 The first huge heterogeneity among centers in the size of the waiting list and LTx was performed in Iran at Shiraz University in 1992.3 Since organ availability, as well as large distances and numbers of cen- then, more than 1000 cases have undergone LTx with acceptable ters, the model for organ allocation in the US was set to be patient- results. There has been gradual, yet slow development of new pro- based rather than center-based. In this model, patient-specific crite- grams in Tehran, Mashhad, and Kerman in Iran. ria were developed to prioritize patients; thereby, donors would be allocated to patients, not centers or physicians. This scoring system Indications and contraindications for LTx correlated well with the mortality of those who suffered from liver Patients with end-stage liver disease (ESLD) should be consid- disease. Since implementation of MELD, the wait list mortality ered for LTx if they can survive perioperatively and comply with has declined. The disadvantage of this system is the complexity of the extensive multidisciplinary workup. As shown in Tables 1 and calculation and the existence of certain conditions in which there is 2, the indications for LTx in adults and children differ. The main in- a low MELD score despite the high priority in certain patients who dication for adult LTx in the US is hepatitis C virus (HCV), which need LTx (i.e., those with hepatocellular carcinoma or metabolic counts for 60% of LTx in American adults. diseases). These patients have currently been listed with excep- Lack of patient compliance, poor psychological support, absence tional MELD scores after approval by regional committees. of sobriety, active drug abuse, advanced cardiovascular or pulmo- Increased public awareness, improved efficiency of the dona- nary diseases, uncontrolled sepsis, irreversible multiple organ fail- tion process, greater expectations for transplantation, expansion ure, AIDS, and active cancer are contraindications for LTx. of the living donor pool, and the development of standardized donor management protocols have led to unprecedented rates of Liver allocations in the United States organ procurement and transplantation. Despite attempts by the Before 2002, liver allocation was based on Child’s Score (CS). Organ Donation and Transplant Collaborative and the marked in- Nevertheless, CS was not a good tool to measure disease severity crease in the number of deceased donors early in the effort, the in patients waiting for LTx because it could not differentiate be- number of deceased donors rose modestly. Our study has shown tween patients with progressively abnormal laboratory values. Ad- a decrease in the number of living donors since 2004 in addition ditionally, the clinical parameters of the CS are based on subjective to the decrease in donation after brain death (DBD) since 2006. measures such as ascites or encephalopathy, which are influenced Although the number of deceased donors per million population by clinical interpretation. Also, this allocation has led to increased (pmp) increased from 22.9 pmp in era 1 to 26.3 in era 2, there was mortality on the list as CS was not predictive of a patient’s disease a significant change in donor characteristics. For years, Spain has severity and the chances of dying without LTx. Therefore, in 2002, maintained the highest rate of deceased organ donation worldwide. The rate increased from 14.3 donors pmp in 1989 to 33–35 donors Author’s affiliation: 1Department of Surgery, University of Massachusetts Medi- pmp in recent years. This was the result of the creation of a national cal School, Worcester, MA, USA. transplant organization in 1989 and development of a coordinated •Corresponding author and reprints: Reza F. Saidi MD FICS FACS, Division of Organ Transplantation, Department of Surgery, University of Massachusetts network of highly motivated in-hospital medical doctors placed in Medical School, 55 Lake Avenue North, S6-426, Worcester MA, 01655. charge of the donation process, and detection and management of Tel: (508) 334-2023, Fax: (508) 856-1102, donors. E-mail: [email protected] Accepted for publication: 5 September 2012 The decline in live donors could be due to loss of income while

772 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 R. F. Saidi

Table 1. Indication for liver transplantation (LTx) in adults. Liver cirrhosis caused by viruses such as HBV, HCV, HDV Alchoholic cirrhosis Cryptogenic cirrhosis Cholestatic liver disorders Primary sclerosing cholangitis Primary biliary cirrhosis Secondary sclerosing cholangitis Metabolic/genetic disorders α-1 antitrypsin deficiency Wilson disease Hemochromatosis Familial amyloidotic polyneuropathy Fulminant hepatic failure: Acetaminophen, toxins, mushroom Malignancy Hepatocellular carcinoma Hepatoblastoma Hemangio endothelioma Hilar cholagiocarcinoma Liver metastases of neuroendocrine tumors Others Severe liver trauma Budd-Chiari syndrome

Table 2. Indications for liver transplantation (LTx) in children. Biliary artesia Alagille syndrome α-1 antitrypsin deficiency Wilson disease Crigler-Najjar syndrome Metabolic/genetic disorders Tyrosinemia type I Gylcogenosis type III, IV Urea cycle defects Neonatal hemochromatosis Congenital hepatic fibrosis Cystic fibrosis Fulminant hepatits Hepatoblastoma off work after the procedure, potential future insurability issues, volume, peak donor serum sodium level > 155 mEq/L, use of high and expenses that may not be covered by insurance. The decline dose or multiple vasopressor agents, prolonged intensive care unit in liver live donation could be due to donor death or implication of stay, and long cold ischemia time (> 12 hr).5–7 the MELD system. The decline in DBD donors can be attributed to increases in the number and percentage of marginal donors and do- Living-donor liver transplantation (LDLT) nation after cardiac death (DCD). The observed increase in DCD Living-donor liver transplantation (LDLT) is an established treat- also explains, in part, the fewer number of organs per donor that ment for ESLD. In Asian countries, approximately 90% of donor are recovered and transplanted. For DCD livers, there is a high rate organs for LTx are obtained from live donors, as the deceased do- of biliary strictures that have been attributed to the period of warm nor rate is low due to social and religious factors. The US has the ischemia that occurs between withdrawal of donor life support and highest rate of donation worldwide after Spain. The peak of adult organ preservation. This leads to a reduction in graft survival and LDLT was in 2001, but the sudden death of a living donor postop- an increase in the need for retransplantation. On the other hand, eratively in New York led to a continual decline in the numbers of marginal liver allografts have been shown to be associated with LDLT in the US.4 increased hospital costs.4 LDLT has some well-documented advantages, including the use of a graft from a healthy donor with minimal ischemic time, the Types of LTx ability to schedule surgery electively, a reduced risk of the recipi- The majority of livers are procured from deceased donors. Nev- ent dying on the waiting list, and it allows for the recipient to be ertheless, the increasing number of patients dying on the waiting medically stabilized. Disadvantages of LDLT are the higher rate of list due to the shortage of livers has prompted the transplant com- surgical complications for both the donor and recipient and a po- munity to use more organ resources. Their effort to expand the do- tential risk of small-for-size syndrome. LDLT carries inherent risks nor pool has provided alternative ways of organ supply, including for the healthy donor. Therefore, careful selection of the donor and using live donors, split-LTx, and utilization of expanded criteria recipient is crucial to minimize risks and complications, and to ob- donors (ECD). The ideal, general donor criteria include donor age tain an acceptable outcome.7–10 ≤ 50 years, normal liver values, hemodynamic stability, and no sys- Initially donors undergo psychosocial evaluation to assure there temic infections or cancers. Nonetheless, the increasing number of is no coercion. Next, donors are evaluated by clinical examination patients who need a suitable organ and the current organ shortage and serologic testing for liver disease, renal disease, viral hepatitis, has pushed the transplant community to utilize ECD livers. The and human immunodeficiency virus (HIV). The second stage is definition of ECD liver allograft is not universal and somewhat comprised of diagnostic studies to evaluate the vascular and biliary center-based. An ECD liver might be considered but not limited to anatomy of the donor. Several options for preoperative imaging are the following: donor age > 65 years, steatosis > 30% of the graft available and include non-invasive modalities such as multi-phase

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 773 Current Status of Liver Transplantation computed tomography, duplex ultrasonography, and magnetic and need for retransplantation.11 resonance imaging. The third phase can consist of a percutaneous liver biopsy. Many centers perform liver biopsies either routinely Split-liver transplantation (SLT) or selectively. Split-liver transplantation (SLT) is two allografts that have been The ideal candidates for LDLT are usually those patients who are created from a single deceased donor liver allograft. This technique not extremely sick from ESLD and typically have MELD scores has been developed to address organ shortages. However, the tech- < 20. One of the most difficult problems to tackle in the expansion nical and logistic issues in both donors and recipients prevent its of LDLT to adults is graft size to avoid small-for-size syndrome worldwide usage. SLT accounts for only 4% of LTx in the US. (SFSS). This is manifested as the constellation of persistent ascites, While splitting was originally performed as an ex vivo bench pro- coagulopathy, prolonged cholestasis, and poor bile production in cedure, in situ liver splitting was introduced to decrease cold isch- the absence of a technical cause. emic time (CIT) and prevent blood loss after reperfusion. It had The pathophysiology of SFSS is not well described but might be been feared that prolonged surgical time and increased blood loss related to allograft size, portal hyperperfusion or venous outflow associated with in situ splitting of the livers might negatively affect obstruction. The graft-to-recipient weight ratio (GRWR) should be the function of other solid organs procured from the same donor. at least 0.8%. However, in stable donors in situ splitting can be accomplished The Adult-to-Adult Living Donor Liver Transplantation Cohort without significant negative effects on the remaining organs. Study (A2ALL) is a consortium of liver transplant centers in the Left-lateral-segment (LLS) or left-split grafts have mainly been United States that have a primary goal of comparing outcomes of transplanted into children and right split or right trisegment (RTS) adult-to-adult LDLT versus deceased donor liver transplantation grafts into adults, both with excellent outcomes. Rogiers et al. re- (DDLT). In its first detailed report on 385 cases, 90-day graft sur- ported the results of 100 livers split in situ which resulted in 190 vival was 87%, with a one-year graft survival of 81%. The out- grafts for transplantation. LLS grafts were transplanted into the pe- comes were characterized by frequent biliary complications (30% diatric recipients and RTS grafts were transplanted into older chil- early, 11% late) and a 13% graft failure because of vascular com- dren and adults. Patient and graft survivals equaled those of 1086 plications, primary non-function (PNF), and sepsis. Marcos et al. recipients who received whole livers from deceased donors.12,13 have compared the outcomes after adult-to-adult LDLT to those who underwent DDLT, using nationwide databases. The one- and Immunosuppression three-year patient survival rates after LDLT (89.1% and 80.3%) Immunosuppressive therapy includes induction and maintenance were similar to those after DDLT (85.7% and 77.7%). Graft sur- therapy. The induction agents are added to the standard immunosup- vival rates at one [79.3% (LDLT) and 70.1% (DDLT)] and three pressive agents to prevent or reduce the incidence of early rejection [80.7% (LDLT) and 71.1% (DDLT)] years were also similar. How- rates following LTx.14 Induction therapy consists of anti-CD25-re- ever, the severity of illness was substantially lower in LDLT recipi- ceptor antibodies (basiliximab, daclizumab), an anti-CD52 mono- ents compared to DDLT recipients.10 clonal antibody (alemtuzumab), or depleting polyclonal antibodies It has been suggested that HCV replication might be increased in (thymoglobulin or ATG). The standard immunosuppressive regi- reduced-size LDLT grafts, but the data is controversial. The major men is a triple therapy regimen that consists of calcineurin inhibi- concern in adult-to-adult LDLT is the adequacy of the graft size. tors (CNI; cyclosporine or tracrolimus), steroids, and MMF. CNI Although harvesting a larger graft carries a higher risk for the do- are the cornerstone of the immunosuppressive regimen in most nor, a residual liver volume of 30% can be tolerated by the donor in liver transplant centers. Nevertheless, therapy with CNIs is asso- the absence of steatosis and right-lobe grafts have become standard ciated with adverse effects such as nephrotoxicity, neurotoxicity, for adult LDLT. 8–10 hypertension, hyperkalemia, and hyperlipidimia. Corticosteroids To minimize donor risk, use of the left lobe has been popularized are considered to be a fixed part of initial and maintenance treat- in the US and Asia. Although single center data has shown compa- ment for LTx patients. Because of the dose-dependent side effects rable outcomes using the right versus the left lower lobe, analysis that include osteoporosis, diabetes, Cushing syndrome, hyperten- of the US experience has revealed lower allograft and patient sur- sion, and hyperlipidemia, as well as steroid promotion of viral rep- vival when using left lobes due to the high rate of complications lication (HBV, HCV), tapering and discontinuation of the therapy

Table 3. Commonly used immunosuppressive agents in liver transplantation (LTx) and their target pathways. Immunosuppressive agent Mechanism of action Maintenance immunosuppression Inhibits cytokine transcription by antigen presenting cell, Selective lysis of Corticosteroids immature cortical thymocytes Calcineurin inhibitors (CNI): Inhibits signal 2 transduction via T-cell receptor (Cyclosporine and tacrolimus) mTOR* inhibitors: Inhibits signal 3 transduction via IL-2 receptor (Sirolimus, rapamycin, everolimus) Azathioprine Inhibits purine and DNA synthesis Mycophenolic acid Inhibits purine and DNA synthesis Induction immunosuppression Antithymocyte globulin (ATG) Causes depletion and receptor modulation in T-cells Anti IL-2 alpha chain receptor antibodies: Inhibits T-cell proliferation to IL-2 (Basiliximab, daclizumab) Causes depletion of thymocytes, T-cells, B-cells (not plasma cells) and Anti-CD52 monoclonal antibodies monocytes *Mammalian target of rapamycin

774 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 R. F. Saidi

Table 4. Surgical complications following liver transplantation (LTx).

Complication (incidence) Treatment Hepatic artery thrombosis (HAT; 4%–6%) Early (within seven days) Retransplantation Late Biliary drainage, ERCP Portal vein thrombosis (PVT; 1%–3%) Thrombectomy Hepatic vein/IVC thrombosis (1%) Thrombectomy Biliary complications (15%–25%) Bile leak Drainage, revision Bile duct stricture ERCP*/stenting, operative revision Intra-abdominal abscess (5%) Drainage *ERCP: Endoscopic retrograde cholangiopancreatography

have been recommended during six months post-transplantation. to-duct (DD) technique can be used for LDLT, an extraintestinal The adverse effects of MMF include bone marrow suppression, anastomosis can be avoided, the continuity is more physiological gastrointestinal symptoms, and slight increase of the incidence of than that of RYCJ, and preservation of the sphincter function of lymphoproliferative diseases, as well as opportunistic infections. the lower bile duct may reduce the risk of enteric reflux into the Table 2 shows common immunosuppressive agents used in LTx. biliary tract. 17 Medical complications include infection (pneumonia, urinary Postoperative complications tract infections, cholangitis and intra-abdominal abscesses).18 The Postoperative complications can be divided into surgical (Table 4 causes of early infection during the first month after LTx are ex- and medical complications. The surgical complications after LTx are acerbated pre-transplant infection in the recipient as a result of im- further categorized as vascular, biliary, and other complications. 15–17 munosuppression, infection in the allograft, and similar infections The incidence of early (with seven days after LTx) hepatic artery that would occur in non-immunosuppressed patients undergoing thrombosis (HAT) is 4%–6%, and necessitates retransplantation as comparable surgeries such as wound, pulmonary, biliary, and uri- damage to the bile duct is severe enough to cause a lack of col- nary tract infections, which account for more than 95% of the in- lateral flow. Arterial complications include anastomosis bleeding fections. Infections in the first six months following LTx include and acute or chronic stenosis/occlusion due to thrombosis, steal the residual effects of technical problems and earlier infections, syndrome, and aneurysm. Early HAT arterial occlusion and throm- infection with immunomodulating viruses (CMV, EBV, HBV, bosis are the result of technical defects and preservation injuries, HCV, and HIV), and opportunistic infections. Infections more than respectively. Late occlusion may be caused by preexistent stenosis. six months post-LTx result from community-acquired respiratory Late HAT can be asymptomatic (due to collateral flow) or presents viral infections (80%), recurrent chronic infection with HBV or as biliary complications such biloma, leak or strictures. HCV, and opportunistic infections in patients with poor allograft Portal vein thrombosis (PVT) is a rare event, occurring in 1%–3% function and excessive immunosuppression. of transplantations. PVT requires re-exploration and thrombecto- Primary non-function (PNF) can be multifactorial and is ob- my to salvage the allograft. Hepatic vein/IVC thrombosis results served in 3%–4% of cases.19 PNF is described as graft failure from technical problems or recurrence of underlying disease such within ten days which necessitates retransplantation. Nevertheless, as Budd-Chiari syndrome. The allograft can be salvaged by repeat according to the proposed United Network for Organ Sharing Cri- surgery and thrombectomy.15 teria, PNF is defined as signs of graft non-function that include Bile duct reconstruction has been labeled the ‘Achilles’ heel’ of AST ≥ 5000 U/L along with either INR ≥ 3.0 or the presence of LTx.16,17 Despite progress in surgical techniques, organ preserva- acidosis within ten days post-transplant. Donor factors related to tion and immunosuppressive management, biliary complications PNF are extended donor criteria such as age, steatosis, hyperna- still frequently occur after LTx and have a high risk of significant tremia, high-dose multiple inotropic therapy, prolonged intensive mortality and morbidity. Anastomotic problems have been the ma- care, and non-heart-beating donor. The procurement criteria are jor reason for biliary complications despite various innovations prolonged cold ischemia time. for biliary reconstruction that have been achieved for whole organ LTx. Biliary reconstruction in LDLT using partial liver grafts is Follow-up still a matter of debate. In the past, Roux-en-Y choledochojejunos- All patients are routinely followed at least weekly for the first tomy (RYCJ) was the standard technique for biliary reconstruc- month after LTx. Initial follow ups include blood tests and duplex tion as the majority of LDLT recipients had biliary atresia. Recent ultrasound of the transplanted organ to monitor for patency of vas- reports on biliary complications have shown an incidence of 12% culature, rejection and infection. If rejection is suspected, a liver to 28% after RYCJ in LDLT recipients. The disadvantages of this biopsy should be performed. Today, HCV recurrence is an im- technique are the comparatively long operative time, possibly portant, yet unresolved problem after LTx. LTx recipients are at higher risk of contamination as a result of spillage of enteric con- higher risk than the general population for malignancy due to im- tents, the non-physiologic nature of the re-established bilioenteric, munosuppression. There are no specific guidelines for screening. and the frequent inability to access the anastomosis endoscopically The most common neoplasms are skin cancer and post-transplant during the post-operative period. In contrast, duct to duct choled- lymphoproliferative disease (PTLD) Cancers, cardiovascular, in- ochocholedochostomy (DDCC) reconstruction is the technique of fectious, and recurrent diseases are the most common causes of choice for biliary anastomosis in whole organ LTx. When the duct- patient death over the long term.

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 775 Current Status of Liver Transplantation

Figure 1. Short-term and long-term results of liver transplantation in United States.

liver: risk factors for poor function after orthotopic liver transplantation. Hepatology. 1994; 20: 829 – 838. Outcomes after LTx 6. Mehrabi A, Fonouni H, Müller SA, Schmidt J. Current concepts in Several factors relevant to post-transplant outcomes following transplant surgery: liver transplantation today. Langenbecks Arch Surg. LTx can be classified as donor, recipient, operative, and postop- 2008; 393: 245 – 260. erative factors. The following donor parameters are predictors of 7. Busuttil RW, Tanaka K. The utility of marginal donors in liver transplantation. Liver Transplant. 2003; 9: 651 – 663. poor outcome: advanced age, high BMI, cause of brain death (par- 8. Hashimoto K, Miller C. The use of marginal grafts in liver transplanta- ticularly stroke), length of hospitalization, use of pressors, liver tion. J Hepatobiliary Pancreat Surg. 2008; 15: 92 – 101. function, sodium level, reduced/split grafts, steatosis, and cold 9. Ben-Haim M, Emre S, Fishbein TM, Sheiner PA, Bodian CA, Kim- ischemia time. The recipient parameters include urgent status, re- Schluger L, et al. Critical graft size in adult-to-adult living donor liver transplantation: impact of the recipient’s disease. Liver Transpl. 2001; nal dysfunction, age, ventilation requirement, and HCV. Operative 7: 948 – 953. factors are the amount of blood loss and blood product administra- 10. Marcos A, Fisher RA, Ham JM, Shiffman ML, Sanyal AJ, Luketic VA, tion, the lack of immediate bile production, low urine output, CIT et al. Right lobe living donor liver transplantation. Transplantation. > 12 hr and warm ischemia time > 35 min. Finally, postoperative 1999; 68: 798 – 803. 11. Saidi RF, Jabbour N, Li Y, Shah SA, Bozorgzadeh A. Is left lobe adult- indicators are parameters such as elevated ALT and AST, serum to-adult living donor liver transplantation ready for widespread use? bilirubin, serum creatinine, and prothrombin time. The US experience (1998–2010). HPB (Oxford). 2012; 14: 455 – 460. Liver transplant survival has increased over the past decade. 12. Rogiers X, Malago M, Gawad K, Jauch KW, Olausson M, Knoefel According to Figure 1, those who have received a liver from a WT, et al. In situ splitting of cadaveric livers. The ultimate expansion of a limited donor pool. Ann Surg. 1996; 224: 331 – 339. deceased donor had the following unadjusted graft survival rates: 13. Ghobrial RM, Yersiz H, Farmer DG, Amersi F, Goss J, Chen P, et al. three-month (91.2%), one-year (84.3%), five-year (68.4%), and Predictors of survival after in vivo split liver transplantation: analysis of ten-year (54.1%); unadjusted patient survival rates were as fol- 110 consecutive patients. Ann Surg. 2000; 232: 312 – 323. lows: three-month (94.3%), one-year (88.4%), five-year (73.8%), 14. Kaufman DB, Shapiro R, Lucey MR, Cherikh WS, Ray TB, Dyke DB. Immunosuppression: practice and trends. Am J Transplant. 2004; 20 and ten-year (60.0%). 4(suppl 9): 38 – 53. 15. Settmacher U, Nussler NC, Glanemann M, Haase R, Heise M, Bechstein WO, et al. Venous complications after orthotopic liver trans- References plantation. Clin Transplant. 2000; 14: 235 – 241. 16. Tung BY, Kimmey MB. Biliary complications of orthotopic liver trans- 1. Starzl TE, Groth CG, Brettschneider L, Penn I, Fulginiti VA, Moon JB, plantation. Dig Dis. 1999; 17: 133 – 144. et al. Orthotopic homotransplantation of the human liver. Ann Surg. 17. Saidi RF, Elias N, Ko DS, Kawai T, Markmann J, Cosimi AB, Hertl M. 1968 ; 168: 392 – 415 Biliary reconstruction and complications after living-donor liver trans- 2. Strong RW, Lynch SV, Ong TH, Matsunami H, Koido Y, Balderson plantation. HPB. 2009; 11: 505 – 509. GA. Successful liver transplantation from a living donor to her son. N 18. Fishman JA. Infection in solid-organ transplant recipients. N Engl J Engl J Med. 1990; 322: 1505 – 1507. Med. 2007; 357: 2601 – 2614. 3. Nikeghbalian S, Aliakbarian M, Kazemi K, Shamsaee Far A, Sale- 19. Johnson SR, Alexopoulos S, Curry M, Hanto DW. Primary non func- hipour M, Bahreini A, et al. Clinical experience in organ transplant tion (PNF) in the MELD Era: an SRTR database analysis. Am J Trans- from the shiraz transplant center: 2011. Exp Clin Transplant. 2012; 10: plant. 2007; 7: 1003 – 1009. 307 – 309. 20. Thuluvath PJ, Guidinger MK, Fung JJ, Johnson LB, Rayhill SC, Pel- 4. Saidi RF. The Faltering solid organ donor pool in the United States. letier SJ. Liver transplantation in the United States, 1999–2008. Am J World J Surg. Aug 30, 2012 [In press]. Transplant. 2010; 10: 1003 – 1019. 5. Strasberg SM, Howard TK, Molmenti EP, Hertl M. Selecting the donor

776 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 D. Jafari, F. Najd Mazhar

Case Report Osteoid Osteoma of the Trapezoid Bone

Dawood Jafari MD1, Farid Najd Mazhar MD•1

Abstract Osteoid osteoma is a benign, bone-forming tumor that rarely involves the carpal bones. We report a case of osteoid osteoma of the trapezoid carpal bone with extension to the adjacent second metacarpal bone. Chronic wrist pain and local tenderness were the major clinical signs and symptoms. In chronic wrist pain osteoid osteoma and the possibility of extension to the adjacent bones should be considered.

Keywords: Carpal bone, metacarpal, osteoid osteoma, trapezoid

Cite the article as: Jafari D, Najd Mazhar F. Osteoid Osteoma of the Trapezoid Bone. Arch Iran Med. 2012; 15(12): 777 – 779.

Introduction opsy through a dorsal approach. We used a small drill bit and fine osteotome to remove the involved area, which included the adjacent steoid osteoma is a benign bone tumor that rarely localizes articular surface of the trapezoid. The biopsy specimen had a highly to the carpal bones.1,2 Wrist pain usually is the main com- vascular reddish nidus embedded in normal bone (Figure 5). We no- O plaint and because it rarely involves the carpal bone, diag- ticed that the articular surface of the second metacarpal was eroded nosis is often delayed. It has been reported in the scaphoid and lu- and softened (Figure 6). Following curettage, we sent the specimen nate areas; however, the trapezoid is an exceedingly rare location from the base of the second metacarpal in a separate container for for osteoid osteoma. Bifocal involvement of adjacent carpal bones pathologic analysis. The results of the histologic examinations of has been reported previously but to the best of our knowledge ex- both biopsy specimens indicated osteoid osteoma (Figure 7). Since tension of osteoid osteoma through the joint to adjacent bone has we had only one nidus at the CT scan and involvement of both trap- not been mentioned in the literature. ezoid and second metacarpal bone were indicated by MRI, we assumed that this was an osteoid osteoma of the trapezoid bone which Case report crossed the joint with extension to the second metacarpal bone. Pain reduced dramatically following surgery and the patient has remained The patient was a 42-year-old right-handed male who presented to pain-free. the hand clinic with complaints of right wrist pain since 15 months previous. Initially, the pain was dull and increased in intensity after Discussion physical activity. He underwent casting twice because of the possible diagnosis of occult ganglion and sports injury. At that time, Primary bone tumors rarely arise from the wrist and if present the physical examination and imaging studies were normal according majorities (86%) are benign. The most common histological type to his history. After a couple of months the pain became more in- of tumor is osteoid osteoma.3 Osteoid osteoma has been initially tense and increased in severity at night. He took nonsteroid anti- reported in 1935 by Jaffe.4 The long bones are frequently involved inflammatory medications such as Naproxen for pain reduction. At by osteoid osteoma, whereas bones in the hands and wrists are af- the first clinic visit, his right hand appeared normal. Range of motion fected in only 6%–13% of cases. Approximately 10% of osteoid was equal in both right and left upper extremities. There was local osteomas involve the small bones of the hands and feet, with a tenderness noted on the dorsum of his right wrist at the base of the greater frequency in the hands. In the hands, the phalangeal bones second metacarpal bone. All routine lab tests were within normal are more frequently involved.5 Involvement of the carpal bones limits. Wrist X-rays were reported as normal (Figure 1). A bone scan is rare. The scaphoid is the most common site of carpal bone in- revealed increased uptake at the base of the second metacarpal bone volvement followed by other bones such as the capitate, lunate and trapezoid area (Figure 2). CT scan demonstrated dense nidus at and hamate.6 Involvement of the trapezoid is extremely rare but the trapezoid adjacent to the base of the second metacarpal (Figure has been reported previously.7,8 The least common which has been 3). MRI showed a focal lesion (15 mm) at the distal portion of the reported by Alcalay et al. is bifocal involvement of the adjacent trapezoid at the carpometacarpal joint level which was indicative of carpal bones.9 Patients with carpal bone osteoid osteoma usually bone marrow edema of the trapezoid; involvement of a small por- present with wrist pain and no remarkable past medical history. tion of the sub-articular aspect of the base of the second metacarpal Symptoms may resemble tenosynovitis or the pain may be attrib- bone was suggested (Figure 4). All signs and symptoms and imaging uted to a recent trauma or sports injury. Pain usually worsens at studies were indicative of a primary diagnosis of osteoid osteoma night and can be reduced or eliminated by aspirin or other non- of the trapezoid. Therefore, the patient underwent curettage and bi- steroidal anti-inflammatory drugs. In most cases primary imaging studies such as plain X-rays appear normal and the classic appear- Authors’ affiliation: 1Department of Hand Surgery, Shafa Yahyaian Rehabilita- tion Center, Tehran University of Medical Sciences, Tehran, Iran. ance of nidus with a sclerotic rim is a rare presentation with osteoid •Corresponding author and reprints: Farid Najd Mazhar MD, Department of osteoma of the carpal bones.10 In a technetium-99m bone scan, the Hand Surgery, Shafa Yahyaian Rehabilitation Center, Baharestan Sq., Mojahedin- lesion is detected as an intense well-defined focal area of increased e-Islam Ave., Tehran, Iran. Tel: +98-912-146-3048; +98-21-335-42022, 11,12 E-mail: [email protected] uptake in all three phases. CT scan with thin slices will usually Accepted for publication: 18 April 2012 show the nidus. Thin-slice CT is the most specific, whereas MRI is

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 777 Trapezoid Osteoid Osteoma

Figure 3. CT scan indicating involvement of the trapezoid adjacent to the joint.

Figure 1. AP X-ray of the right hand. Figure 2. Bone scan with increased uptake at the area of the trapezoid and base of the second metacarpal bone.

Figure 4. MRI scan showing involvement of the Figure 5. Trapezoid specimen showing hyper- Figure 6. The base of second metacarpal bone trapezoid and base of the second metacarpal bone. vascular central area embedded by normal bone. is eroded.

Figure 7. Pathology of the tumor (H&E, ×40). the most sensitive imaging study for investigation of carpal bone the best of our knowledge extension of osteoid osteoma across osteoid osteoma.13 Bone edema can be demonstrated by MRI and a joint is a new behavior by this tumor that has not been report- intraosseous edema with soft tissue changes related to the syno- ed in the English literature. We believe that this exceedingly vitis generate high-intensity signals on T2-weighted fat-saturated rare behavior is possible in this location because the trapezoid images. With variable signs and symptoms the diagnosis in most and second metacarpal bone intimately join to each other, with cases is not easy. Diagnosis is usually delayed and in many cir- a very small space between the two articular surfaces. Osteoid cumstances patients undergo unnecessary investigations and even osteoma should be in the differential diagnosis list of chronic surgical interventions.8,9,14 According to most authors the technique wrist pain, particularly in young males. In treating osteoid oste- of choice in treatment of osteoid osteoma is open surgery and thor- oma of the carpal bones, the possibility of its extension through ough curettage after preoperative CT scanning.1 the joint to adjacent bone should be considered in order to pre- This is a report of a rare case of osteoid osteoma in the trap- vent its recurrence. ezoid carpal bone which is a very rare location for this benign tumor. In this case osteoid osteoma from the trapezoid showed Financial support: None extension through the joint to the second metacarpal bone. To We received written contest of patient to publish the case.

778 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 D. Jafari, F. Najd Mazhar

References 10: 175 – 177. 8. Girard J, Becquet E, Limousin M, Chantelot C, Fontaine C. Osteome osteoide de l’os trapezoide: a propos d’un cas et revue de la literature 1. Laffosse J M, Tricoire J L, Cantagrel A, Wagner A, Puget J. Osteoid [in French]. Chir Main. 2005; 24: 35 – 38. osteoma of the carpal bones. Two case reports. Joint Bone Spine. 2006; 9. Alcalay M, Clarac JP, Bontoux D. Double osteoid–osteoma in adjacent 73: 560 – 563. carpal bones. A case report. J Bone Joint Surg. 1982; 64A: 779 – 780. 2. Carroll RE. Osteoid osteoma in the hand. J Bone Joint Surg. 1953; 10. Marcuzzi A, Leti acciaro A, Landi A. Osteoid osteoma of the hand and 35A: 888 – 893. wrist. J Hand Surg. 2002; 27B: 440 – 443. 3. Murray PM, Berger RA, Inwards CY. Primary neoplasms of the carpal 11. Shewring DJ, Savage R, Thomas G. Experience of the early use of bones. J Hand Surg. 1999; 24A: 1008 – 1013. Technetium 99 bone scintigraphy in wrist injury. J Hand Surg.1994; 4. Jaffe H. “Osteoid osteoma”: a benign osteoblastic tumor composed of 19B: 114 – 117. osteoid and atypical bone. Arch Surg. 1935; 31: 709 – 728. 12. Smith FW, Gilday DL. Scintigraphic appearances of osteoid osteoma. 5. Dorfman HD, Czerniak B. Benign Osteoblastic Bone Tumors. Bone Radiology. 1980; 137: 191 – 195. Tumors. Missouri: Mosby; 1998: 85 – 103. 13. Assoun J, Richardi G, Railhac JJ, Baunin C, Fajadet P, Giron J, et al. 6. De Smet L, Brys P, Fabry G, Baert A. An unusual localization and Osteoid osteoma: MR imaging versus CT. Radiology. 1994; 191: 217 presentation of an osteoid osteoma. Acta Orthop Belg. 1997; 63: 128 – 223. – 131. 14. Kreitner KF, Low R, Mayer A. Unusual manifestation of an osteoid 7. Tricoire JL, Duport M, Puget J, Mazieres B, Chiron P, Utheza G. Oste- osteoma of the capitate. Eur Radiol. 1999; 9: 1098 – 1100. oid osteoma of the trapezoid bone. Ann Chir Main Memb Super. 1991;

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 779 Chorea-Acanthocytosis

Case Report Chorea-acanthocytosis: Report of Three Cases from Iran

Siamak Karkheiran MD1, Benedikt Bader MD2, Mohammad Roohani MD1,3, Adrian Danek MD2, Gholam Ali Shahidi MD•1,3

Abstract Chorea-acanthocythosis (ChAc) is an inherited neurodegenerative disorder characterized by movement disorders, neuropsychiatric dis- turbances, neuropathy, myopathy, seizures and acanthocytosis accompanied by an elevated serum creatine kinase (CK) level. Its causative gene (VPS13A) produces chorein which is absent in ChAc patients as evaluated by Western blot assay. We report the first three Iranian patients whose disease has been confirmed by chorein Western blot. Our cases presented with heterogeneous courses of ChAc. A high sense of clinical awareness in approaching patients with deteriorating and/or multiple abnormal movements that are accompanied by other neurological signs such as neuropathy, myopathy, seizures and high serum CK level will support an early diagnosis of this disease. We also emphasize on the presence of axial flexion/extension spasms as a good clinical sign for narrowing differential diagnosis.

Keywords: Acanthocytosis, chorea-acanthocytosis, feeding dystonia, trunk flexion

Cite the article as: Karkheiran S, Bader B, Roohani M, Danek A, Shahidi GA. Chorea-acanthocytosis: Report of Three Cases from Iran. Arch Iran Med. 2012; 15(12): 780 – 782.

Introduction to wear gum shields. These abnormal movements generalized over the next three years. His speech became slurred and gradually un- horea-acanthocytosis (ChAc) is a rare autosomal recessive intelligible. His wife reported intermittent motor tics, impulsivity neurodegenerative disorder caused by mutations in the and memory decline. At age 48, he had generalized chorea, dysar- C VPS13A gene that codes for chorein.1,2 It is characterized thria, dysphagia, feeding dystonia and bruxism. Muscle strength by chorea, neuropathy, seizures, neuropsychiatric disorders and was normal and tendon reflexes were elicitable with normal touch cognitive decline in association with acanthocytosis.3,4 The course and position sensations. During the last follow up at age 50, the of the disease consists of heterogeneous manifestations during its patient was hypokinetic with hesitation in walking, postural in- early stages,5 such as dystonia and psychosis,6 and may take many stability and falls. Saccades were hypometric and pursuits were years to evolve into its classic features.7 Laboratory investigations fragmented, but in full range. Speech was dysarthric and difficult commonly reveal elevated creatine kinase (CK) and lactate dehy- to understand. Tongue protrusion dystonia was seen occasionally drogenase (LDH) levels.1 As the causative gene is very large (73 and he frequently pushed out the gum shields during examina- exons) and has no specific hot spot, genetic confirmation of ChAc tion. Although muscle strength remained normal, deep tendon re- is difficult.1,8 Thus, evaluation of chorein levels in the erythrocyte flexes were reduced. Laboratory investigation revealed a regular membranes by Western blot is a useful alternative.9,10 Absent or level of acanthocytes in routine wet preparations, elevated CK reduced levels of chorein are highly suggestive of ChAc.9 to 220 U/L (normal < 177 U/L) and bilateral caudate atrophy on a brain CT scan. Chorein Western blot revealed an absence of Case Reports chorein (Figure 1).

Case 1 Case 2 This 48-year-old man referred to our clinic for abnormal gait, This 41-year-old man (P1 in Figures 1 and 3) reported his first bruxism and tongue biting. He was born to unrelated parents. The generalized seizure during sleep at age 17 years, after which he early years of his life were unremarkable. At the age of 37 years, remained seizure-free without antiepileptic treatment. At the age this patient experienced his first generalized seizure while asleep, 38, he developed abnormal gait and dyskinesia in his right leg. for which he received a variety of antiepileptic drugs [sodium val- Over the next two years, symptoms progressed rapidly and he had proate (1200 mg/d), carbamazepine (1200 mg/d), and topiramate difficulty in talking, swallowing and walking with frequent falls. (200 mg/d)]. Despite treatment, he had poor seizure control. Ad- Meanwhile, he experienced two generalized seizures that were ditionally, he noticed difficulty in walking and abnormal posturing controlled successfully with sodium valproate. At age 39, he was of his right leg at age 45. Soon after, he developed involuntary seen for the first time in our clinic with generalized chorea, abnor- tongue and jaw movements. Cheek and tongue biting forced him mal wide-based gait, generalized hypotonia and areflexia, dysarthria, dysphagia, tongue protrusion and feeding dystonia without 1 Authors’ affiliations: Movement Disorders Clinic, Rasool Akram Hospital, tongue biting. In the last follow up at age 41, his chorea and dysar- Tehran University of Medical Sciences, Tehran, Iran, 2Neurologische Klinik und Poliklinik, Klinikum der Universität München, Munich, Germany, 3Department thria worsened. In oculomotor examination, pursuits were normal of Neurology, Rasool Akram Hospital, Tehran University of Medical Sciences, and saccades had intermittent initiation delay and gaze palsy to the Tehran, Iran. right side. In the sitting position, frequent trunk and head backward •Corresponding author and reprints: Gholam Ali Shahidi MD, Movement Disorders Clinic, Rasool Akram Hospital, Tehran University of Medical Sciences, extensions resulted in the patient knocking his head on the wall. Tehran, Iran. E-mail: [email protected] Gait was severely unstable with sudden knee and trunk flexions. Accepted for publication: 18 April 2012

780 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 S. Karkheiran, B. Bader, M. Roohani, et al.

Figure 1. Chorein Western blot analysis. Arrow indicates the expected height of a normal full length chorein band at 360 kDa. The dotted line separates two independent Western blots.

Figure 2. T2 weighted brain MRI of case 3 dis- Pedigree of case 2. P1 (index patient) = chorea + epilepsy + Figure 3. playing bilateral caudate atrophy (white arrows) flexion/extension; P2 = asymptomatic + reduced chorein; P3 = epilepsy; and ventricular enlargement. P4, P5 = progressive epilepsy + encephalopathy.

Laboratory investigations revealed acanthocytosis, elevated LDH IU/L). Brain MRI showed bilateral caudate atrophy (Figure 2) and and CK levels and bilateral caudate atrophy on the brain MRI scan. an EEG revealed bitemporal polyspike paroxysms. Chorein was An electrophysiological study demonstrated sensory-motor axonal absent in Western blot analysis (Figure 1). polyneuropathy. Chorein was absent (Figure 1). The patient and his six brothers were born to healthy unrelated parents (Figure 3). Discussion His elder brother was normal until he drowned in the sea at age 12. One asymptomatic brother (P2) was also tested by chorein The combination of chorea and other movement disorders, sei- Western blot and a reduction of chorein was confirmed (Figure 1). zures, neuropathy and neuropsychiatric symptoms in association Another brother (P3) was diagnosed with epilepsy at the age of 30. with elevated CK levels is strongly suggestive of ChAc. He had no chorein according to Western blot assay. The last two Seizures are common in ChAc and appear in approximately 40% siblings developed epilepsy at age 1 year with progressive men- of patients,7 though they may appear late, even after abnormal tal and physical regression (P4, P5). Both became bedridden and movements6,7 or very early as presenting signs.11,12 Al-Asmi et al. died during sleep at age 6, most likely as a consequence of seizure- have reported two French-Canadian families who had temporal induced asphyxia. lobe epilepsy as an early manifestation of ChAc.11 All were adults when seizures began and the gap between seizure and involuntary Case 3 movements was less than 15 years. On the other hand, Scheid et A 28-year-old woman referred to our clinic for evaluating her al. described two cases of young onset ChAc with one 14-year old phonic and motor tics and tongue biting. She was born to consan- patient initially presenting with temporal lobe epilepsy.12 In cases guineous parents and her childhood development was unremark- 1 and 2 described here, seizures were the presenting symptoms. able. Her symptoms began at age 15 with phonic tics (chicken like Notably, in case 2 the first seizure occurred 21 years before the sounds). During a period of approximately one decade, her symp- appearance of abnormal movements. Two of the brothers of case toms progressed slowly with mild motor tics and choreic move- 2 (P4, P5) had progressive epilepsy and encephalopathy with psy- ments. At age 25, she developed dysarthria and dysphagia with chomotor retardation at very young ages which most likely led to hypersalivation and drooling. One year later, feeding dystonia and their demise in early childhood. Whether they suffered from an- tongue biting worsened. She lost 30 kg of weight in three years due other disease or died as a result of ChAc remains unsolved as no to dysphagia. Between ages 26 and 28, she experienced two gen- material for genetic or chorein Western blot analysis was available. eralized seizures that were completely controlled with lamotrigine However, it was possible that homozygous or heterozygous muta- and phenobarbital. Gum shields and botulinum toxin type A (Dys- tions in VPS13A were the underlying causes for this very early port; Ipsen, UK) injections into the genioglossus muscle mod- clinical manifestation as heterogeneity within the same family has erately improved self-mutilation. At last follow up, examination also been described.5 revealed normal gait, mild choreic movements in her face, mild Axial symptoms such as head drops, truncal flexions and back- phonic tics, generalized hypotonia and hyporeflexia, postural in- ward extensions have been reported previously in patients with stability and mild kyphosis with intermittent head drops in the sit- ChAc.13 In a recently published article, Schneider et al. empha- ting position. Speech was slurred with marked drooling. As seen sized that sudden axial flexion/extension movements were features in Table 1, laboratory investigations showed elevated levels of strongly suggestive of ChAc.14 Case 2 described here showed se- acanthocytes, CK (233 U/L) and LDH (533U/L; normal: < 350 vere axial symptoms with position dependency and pattern shift-

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 781 Chorea-Acanthocytosis ing during walking and sitting. In the sitting position, backward 2. Ueno S, Maruki Y, Nakamura M, Tomemori Y, Kamae K, Tanabe H, et extension of the neck and trunk were predominant while standing al. The gene encoding a newly discovered protein, chorein, is mutated in chorea-acanthocytosis. Nat Genet. 2001; 28: 121 – 122. and walking were marked by sudden knee and truncal flexions. 3. Walker RH, Jung HH, Dobson-Stone C, Rampoldi L, Sano A, Tison F, Despite lack of definite phenomenology, forward movements ap- et al. Neurologic phenotypes associated with acanthocytosis. Neurol- peared similar to negative myoclonic atony while backward ex- ogy. 2007; 68: 92 – 98. tensions had a dystonic appearance. Chorea or positive myoclonic 4. Danek A, Dobson-Stone C, Velayos-Baeza A, Monaco A. The pheno- type of chorea-acanthocytosis: a review of 106 patients with VPS13A jerks could be responsible for axial symptoms due to muscle con- mutations. Mov Disord. 2005; 20: 1678. tractions. 5. Lossos A, Dobson-Stone C, Monaco AP, Soffer D, Rahamim E, New- Absence of acanthocytosis in the first case might be the result of a man JP, et al. Early clinical heterogeneity in choreoacanthocytosis. non-standardized methodology in preparing and evaluating blood Arch Neurol. 2005; 62: 611 – 614. 6. Hardie RJ, Pullon HW, Harding AE, Owen JS, Pires M, Daniels GL, smears. Using the recommended method by Storch et al. increas- et al. Neuroacanthocytosis: a clinical, haematological, and pathological es the chance of finding acanthocytes.15,16 However, determining study of 19 cases. Brain. 1991; 114: 13 – 49. chronically elevated CK levels in serum independent from recent 7. Rampoldi L, Danek A, Monaco AP. Clinical features and molecular bases of neuroacanthocytosis. J Mol Med. 2002; 80: 475 – 491. seizures is a more reliable method. 8. Dobson-Stone C, Danek A, Rampoldi L, Hardie RJ, Chalmers RM, For rare disorders with clinical heterogeneity and variable course Wood NW, et al. Mutational spectrum of the CHAC gene in patients of disease, a high sense of clinical awareness is necessary. Distinc- with chorea-acanthocytosis. Eur J Hum Genet. 2002; 10: 773 – 781. tive clinical features such as tongue protrusion and feeding dysto- 9. Dobson-Stone C, Velayos-Baeza A, Filippone LA, Westbury S, Storch A, Erdmann T, et al. Chorein detection for the diagnosis of chorea- nia, axial flexion/extension, chorea, multisystem involvement and acanthocytosis. Ann Neurol. 2004; 56: 299 – 302. elevated CK are strong clues for ChAc in particular or neuroacan- 10. Kurano Y, Nakamura M, Ichiba M, Matsuda M, Mizuno E, Kato M, thocytosis in general.17,18 In such cases, chorein Western blot as- et al. In vivo distribution and localization of chorein. Biochem Biophys say should be performed. Harirchian et al.19 reported the first case Res Commun. 2007; 353: 431 – 435. 11. Al-Asmi A, Jansen AC, Badhwar A, Dubeau F, Tampieri D, Shustik C, of ChAc in Iran, followed by two other reports by Nikkhah et al. et al. Familial temporal lobe epilepsy as a presenting feature of choreo- and Ghoreishi et al.20,21 In the latter report, Ghoreishi et al. pointed acanthocytosis. Epilepsia. 2005; 46: 1256 – 1263. out to paroxysmal oromandibular dyskinesia in their patient that 12. Scheid R, Bader B, Ott DV, Merkenschlager A, Danek A. Develop- was unmasked by Botulinum toxin injection, however they neither ment of mesial temporal lobe epilepsy in chorea-acanthocytosis. Neu- rology. 2009; 73: 1419 – 1422. defined nor described the condition precisely. Then, presence of 13. Walker RH, Danek A, Dobson-Stone C, Guerrini R, Jung HH, Lafon- such phenomenon in ChAc is in doubt and more observations are taine A, et al. Developments in neuroacanthocytosis: Expanding the needed for its confirmation. In addition, in all above reports di- spectrum of choreatic syndroms. Mov Disord. 2006; 21: 1794 – 1805. agnosis was based on clinical features and certain laboratory tests 14. Schneider SA, Lange AE, Moro E, Bader B, Danek A, Bhatia KP. Characteristic head drops and axial extension in advanced chorea- without molecular and genetic confirmation. Our report is the first acanthocytosis. Mov Disord. 2010; 25: 1487 – 1504. case series from Iran with molecular confirmation of the clinical 15. Feinberg TE, Cianci CD, Morrow JS, Pehta JC, Redman CM, Huima diagnosis. T, et al. Diagnostic tests for choreoacanthocytosis. Neurology. 1991; 41: 1000 – 1006. 16. Storch A, Kornhass M, Schwarz J. Testing for acanthocytosis - a pro- Acknowledgments spective reader-blinded study in movement disorder patients. J Neurol. 2005; 252: 84 – 90. Chorein Western blot is available free of charge. Please see 17. Bader B, Walker RH, Vogel M, Prosiegel M, McIntosh J, Danek A. Tongue protrusion and feeding dystonia: a hallmark of chorea-acantho- more information at http://www.euro-hd.net/html/na/submodule cytosis. Mov Disord. 2010; 25: 127 – 129. or inquire by E-mail: [email protected]. The diagnostic test is 18. Chauveau M, Damon-Perriere N, Latxague C, Spampinato U, Jung H, supported by the Advocacy for Neuroacanthocytosis Patients, Lon- Burbaud P, et al. Head drops are also observed in McLeod syndrome. Mov Disord. 2011; 26: 1562 – 1563. don, UK and the Center for Neuropathology and Prion research 19. Harirchian MH, Maghbooli M, Shirani A. A case of choreoacanthocy- (Prof. H. Kretzschmar), Munich, Germany. tosis with marked weight loss: impact of orolingual dyskinesia. Neurol India. 2006; 54: 296 – 297. 20. Nikkhah K, Sasan Nezhad P, Shirdel A, Chekni F. Case report; presen- References tation of one patient with neuroacanthocytosis. Med J Mashhad Univ Med Sci. 2008; 51: 75 – 78. 1. Rampoldi L, Dobson-Stone C, Rubio JP, Danek A, Chalmers RM, 21. Ghoreishi A, Bayati A, Bozrgi A, Ghabaee M, Ghaffarpour M, Ghorei- Wood NW, et al. A conserved sorting-associated protein is mutant in shi A. Paroxysmal dyskinesia followed by Botulinum toxin injection chorea-acanthocytosis. Nat Genet. 2001; 28: 119 – 120. in a case with neuroacanthocytosis. Iran J Neurol. 2009; 7: 549 – 553.

782 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 M.T. Rajabi, S.S. Hosseini, F. Bazvand, et al.

Photoclinic

Figure1.The patient’s eyes at presentation.

Figure 2. Orbital CT scan.

Figure 3. Orbital MRI.

Figure 4. A histopathologic view of the patient’s lesion (H&E, and ×100).

Cite the article as: Rajabi MT, Hosseini SS, Bazvand F, Tabatabaie SZ, Rajabi MB. Photoclinic. Arch Iran Med. 2012; 15(12): 783 – 784.

A 27-year-old man referred for progressive right eye ptosis since ptosis. There was an isodense mass with bone erosion in the supe- one year. Inferior globe displacement and proptosis of the right rotemporal area of the right orbit with intracranial extension that upper lid was apparent. His left eye had congenital constant esotro- remained extradural despite its extension and size as noted on CT pia and was amblyopic with only finger count vision. Limitations scan (Figure 2). Indentation and displacement of the globe was in adduction and elevation, in addition to poor levator function visible. For better evaluation, we performed an MRI scan, which were noted upon examination (Figure 1). Macular wrinkling in the revealed a non-enhancing hyperintense lesion seen in T1-weighted OD and a cup-to-disc ratio of 0.8 with intraocular pressure of 18 and T2-weighted MRI (Figure 3). The lesion had a sharp border with mmHg in both eyes were additional findings. no infiltration and invasion to the orbital soft tissues. There was intra- Orbital imaging was performed to evaluate his progressive pro- cranial extension of the tumor but the duramater was obviously intact. Orbitotomy through the lateral upper lid crease was performed Mohammad Taher Rajabi MD1, Seyedeh Simindokht Hosseini MD•1, Fate- meh Bazvand MD1, Syed Ziaeddin Tabatabaie MD1, and revealed a large cyst that had a chocolate color mixed with yel- Mohammad Bagher Rajabi MD1 low pointy material. Pulses conducted through the brain were visible 1 Authors’ affiliation: Eye Research Center, Farabi Eye Hospital, Tehran Univer- due to bone erosion and the connection between the cranial fossa and sity of Medical Sciences, Tehran, Iran. •Corresponding author and reprints: Seyedeh Simindokht Hosseini MD, Eye the cyst. The pathology slide is presented in Figure 4. Research Center, Farabi Eye Hospital, Qazvin Square, Tehran 1336616351, Iran. Tel: +98-215-542-1006, Fax: +98-215-541-6134, What is your diagnosis? E-mail: [email protected] Accepted for publication: 29 June 2012 See the next page for diagnosis.

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 783 Photoclinic

Photoclinic Diagnosis: Cholesterol Granuloma

Cholesterol granuloma is a granulomatous foreign body reaction Drainage and total removal of granulomatous tissue via an ante- around cholesterol crystals with or without a surrounding fibrous rior or occasionally lateral orbitotomy is one management option. capsule.1,2 There is a positive history of previous trauma in some Curettage of the lesion from the bone and periosteum is essential cases. Different organs, such as the breasts, lungs, kidneys, peri- for the prevention of recurrence4; however, some authors believe toneum, petrous apex and orbit are previously reported locations that complete curettage is not necessary.9 of presentation.1 An osteolytic lesion1,3 most often located in the superior temporal part of the orbital cavity with involvement of the References frontal bone is a typical presentation for orbital cholesterol granuloma. Erosion of the orbital roof and extradural spread into the 1. Alsuhaibani AH, Al-Rubaie K, Al-Khiary H, Nerad JA. Different pat- anterior cranial fossa is a possibility.2 Of the theories that attempt terns of orbital roof involvement by holesterol granuloma. Middle East Afr J Ophthalmol. 2011; 18: 333 – 335. to explain its etiology, hematocele formation is the most popular. 2. Chow LP, McNab AA. Orbitofrontal cholesterol Granuloma. J Clin In this theory, when a hematoma is formed in the subperiosteal Neurosci. 2005; 12: 206 – 209. space of the frontal bone and is not absorbed in time, the blood 3. Rosca T, Bontas E, Veladescu T, St. Tihoan V, Gherghescu G. Clinical becomes degraded and organized. Giant cells approach this area controversy in orbitary cholesteatoma. Ann Diagn pathol. 2006; 10: 4,5 89 – 94. and a granulomatous reaction occurs. Cholesterol crystals and 4. Loeffler KU, Kommerell G. Cholesterol granuloma of the orbit-patho- multinucleated giant cells can be found in the specimens of cho- genesis and surgical management. Int Ophthalmol. 1997; 21: 93 – 98. lesterol granuloma. 5. Selva D, Phipps SE, O’Connell XJ, White VA, Rootman J. Pathogen- Diplopia on upgaze, aching pain in the orbit, blurred vision, pro- esis of orbital cholesterol granuloma. Clin Experiment Ophthalmol. 2003; 31: 78 – 82. gressive proptosis, inferior displacement of the globe and limited 6. Karim MM, Inoue M, Hayashi Y, Nishizaki M, Hanioka K, Imai Y, Ito upgaze are the prevalent reported manifestations.2Intracranial ex- H, Yamamoto M. Orbital cholesterol granuloma with destruction of the tension can cause neurologic findings such as headaches,6 which lateral orbital roof. Jpn J Ophthalmol. 2000; 44: 179 – 182. 7. Hill CA, Moseley IF. Imaging of orbitofrontal cholesterol granuloma. were absent in the current case despite the large intracranial exten- Clin Radiol. 1992; 46: 237 – 242. sion. 8. Dickey JB, Mullenix CD, O’Grady RB. Atypical magnetic resonance The typical finding on CT scan is a non-calcifying mass lesion findings in an orbitofrontal cholesterol granuloma. Ophthal Plast Re- isodense with brain.7 No sclerotic margins are apparent.2 On MRI, constr Surg.1992; 8: 215 – 220. 9. McNab AA, Wright JE. Orbitofrontal cholesterol granuloma. Orbit. a hyperintense lesion on both T1-weighted and T2-weighted im- 2004; 23: 49 – 52. ages is found, which does not enhanced with gadolinium.8

784 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 M. Saffari, A. H. Pakpour

History of Medicine in Iran Avicenna’s Canon of Medicine: A Look at Health, Public Health, and Environmental Sanitation

Mohsen Saffari PhD1, Amir H. Pakpour PhD•2,3

Abstract Avicenna, a renowned Persian Muslim scientist has written numerous scientific papers and valuable medical books that are respected worldwide. For centuries his masterpiece, the “Canon of Medicine”, has been used as a major medical reference. The Canon, as a prime encyclopedia on medicine is comprised of five books. In the introduction to the Canon, Avicenna has described the purpose of medicine as the preservation of health if it is already attained and its restoration when it is lost. He defines health as a trait or state, which results in the normal functioning of the human body and presumes that health is a steady state, whilst disease is more of a variable concept. Thus when- ever we depart from a healthy state, we approach disease. A comparison of current views regarding definitions of health, disease and their components as defined by Avicenna could open new horizons for ancient, traditional medicine. The Canon contains numerous implications concerning the infrastructures of public health-related issues. For example the specifications of healthy water and air are well described in the “Canon of Medicine”. To enable a better understanding of Avicenna’s viewpoints about public health, we have briefly reviewed his perspective on the topics of health, disease, and environmental sanitation concerning water and air.

Keywords: History of medicine, Iran, public health

Cite the article as: Saffari M, Pakpour AH. Avicenna’s Canon of Medicine: A Look at Health, Public Health, and Environmental Sanitation. Arch Iran Med. 2012; 15(12): 785 – 789.

Introduction Sina, was translated into Latin in the 12th century and used as a major reference in medical education from the 12th until the 17th bn Sīnā, whose full name is Abu ‘Ali al-Husayn ibn ‘Abd Al- centuries.6,7 The Canon includes five books and ten parts, where lah ibn Sina, is also known in the West as Avicenna. Avicenna each book relates to one medical issue.6 I was a well-known Persian and a Muslim scientist1 who was This review discusses the concepts of health and public health in considered to be the father of early modern medicine. Avicenna the Canon as well as Avicenna’s views about public health. created an extensive corpus of work during Islam’s Golden Age. During his time, he was regarded as a prominent physician and Health and public health philosopher who influenced the world through his valuable works.2,3 Dante, in his epic poem “Divine Comedy”, equated him Before embarking on a discussion of Avicenna’s views it is nec- with Hippocrates and Galen.4–6 essary to have a clear understanding of the terms “health” and Ibn Sina was born in 980 A.D. (Safar 370 A.H.) in a village in “public health”. Although in existence for approximately 60 years, Afshaneh near Bukhara (in present Uzbekistan). He was born into the World Health Organization’s (WHO) definition of health is still a Persian family.7,8 At a young age he enthusiastically read books relevant and defined as: “a state of complete physical, mental and related to medicine, performed empirical works to treat patients, social well-being and not merely the absence of disease”.11 How- and gradually became an outstanding physician.9 About 1012 CE; ever, this definition is limited in that it is impossibly idealistic and c. 402 AH, Ibn Sina began to write his masterpiece, the “Canon unobtainable for most people.12 of Medicine” which he finished while living in Hamadan (present In 1920 CEA Winslow, a Professor of Public Health at Yale Uni- day Iran).10 versity, defined public health as follows: “Public health is the sci- After considerable influence in the medical world in addition to ence and art of 1) preventing disease, 2) prolonging life, and 3) the compilation of masterful books and papers, and doing promi- promoting health and efficiency through organized community ef- nent studies, Ibn Sina died of colic in 428 A.H. (1037 A.D.). He fort for a) the sanitation of the environment, b) the control of com- was buried in Hamadan, Iran9,10 where his tomb is currently a fa- municable infections, c) the education of the individual in personal mous tourist attraction. hygiene, d) the organization of medical and nursing services for The “Canon of Medicine” or “Qanoun fi Tib” is considered a early diagnosis and preventive treatment of disease, and e) the de- medical masterpiece. The Canon, which is the largest work by Ibn velopment of social machinery to ensure that everyone is provided with a standard of living adequate for the maintenance of health. Authors’ affiliations:1 Department of Health Education, Baqiyatallah University of Medical Sciences, Tehran, Iran. 2Qazvin Research Center for Social Determi- Indeed, these should be so organized as to enable every citizen to nants of Health, Qazvin University of Medical Sciences,Qazvin, Iran. 3Depart- enjoy his birthright of health and longevity”.13 ment of Public Health, Qazvin University of Medical Sciences, Qazvin, Iran. In the opening section to the Canon, Avicenna has described •Corresponding author and reprints: Amir H. Pakpour PhD, Department of public health, Faculty of Health, Qazvin University of Medical Sciences, Shahid the purpose of medicine (Tib) as the preservation of health if it Bahonar Blvd., Qazvin, Iran. Tel: +98-281-333-8127, Fax: +98-281-334,5862, is already attained and its restoration when it is lost.14 Moreover, E-mail: [email protected] he has argued against the assertion that there were there are three Accepted for publication: 8 August 2012

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 785 Avicenna’s View on Public Health states in the health continuum: bodily health, a disease state, and store it when it is lost”, he divided medicine (Tib) into two parts. the third which was neither healthy nor diseased. Instead, he em- Part 1 concerns knowledge of regulating the body with the intent to phasized only two states for the human body, healthy and diseased. maintain its health. This is often called hygiene and is also known He stressed that it was irrelevant to speak of the third state, which as primary prevention. Part 2 pertains to knowledge of manag- was merely an invention that described a ‘decline in health’ and in ing the diseased body and the methods for restoring it to health,14 reality was encompassed by the diseased state.14 which refers to knowledge of treatment, or secondary and tertiary Avicenna further defined health as: “The beauty of the body-long prevention. Thus, medicine is the sum of hygiene and treatment. hair, clear complexion, fragrance and form”14 or in other words a Avicenna regarded medicine to be an extensive range of the fol- trait or state that resulted in normal functioning of its subject (hu- lowing elements; temperaments; humors; simple and compound man body).14 Since he has considered ‘decline in health’ to be di- organs and their faculties; physical, vital and psychic functions; rectly opposed to health, we infer that he took into account health the states of the body with regards to health, disease and the in- as being a range or sliding scale. He has presumed that health is termediate state; and the means thereof, such as food, drink, air, a steady state, whilst disease is more of a variable concept (i.e., water, countries, residence, depletion, retention, occupations, hab- declining health). Thus when we move away from the healthy its, physical and psychic movements, age, and sex; foreign matters state, we approach disease. However, Avicenna did not reject oth- that access to the body; and preservation of health and treatment ers opinions about the state of the human body, particularly with of diseases by means of regimens for food and drink, choice of regards to the proposed third state. He has written on behalf of air, regulations of movement and rest, use of drugs and surgeries.14 Galen: “The states of the human body, according to Galen, are Avicenna mentioned the basic goal of health as the preservation three: Health, it is a state which helps to maintain the functions of of moderation. He has written: “We may say that in the art of pre- the human body through (proper balance) of its temperament and serving health the basic thing is the moderation of the aforemen- composition in a correct and sound manner. Disease, it is that state tioned general and essential causes. But of them greater attention of the human body which is contrary to the aforementioned state. is paid towards the moderation of seven things: moderation of tem- Then there is a state in which, according to him (Galen), there is perament; selection of the articles of food and drink; depuration of neither health nor disease: neither the health is perfect nor the dis- superfluity; protection of the constitution (of the body); purity of ease is absolute such as the bodies of the old and the convalescent the inhaled air; proper clothing; moderation of physical and psy- and of children.”14 chic movements which include, in one way or another, sleep and Avicenna has defined disease as an abnormal condition for the wakefulness”.14 However, he did not consider moderation as a sta- human body. As written in the Canon, “this is an abnormal un- ble concept, nor did he set limitations for health. “You have learnt natural state of the human body, in virtue of which injurious ef- from what has already been described that there is no set limit for fects result.”14- Avicenna distinguished between symptom, cause, equability of health. Nor is any temperament in perfect state of and disease14 - where he expressed the symptom as a phenomenon health or equability at a given time, rather it stands somewhere in that followed an abnormal condition. Abnormal was considered to the middle.”14 be something harmful to the physis (nature), such as the pain of Avicenna believed that the aim of health was to guide the human colic, or not harmful, such as the excessive redness of the cheeks body towards attaining an advanced age, or natural span of life. In when associated with pneumonia. He exemplified the differences other words, a healthy man should die from old age rather than as as follows: “Putrescence (putrefying) is an example of cause, fever the result of a disease. is an example of disease, whilst an example of symptom is thirst Avicenna stated that signs of health showed equability of tem- and headache.”14 perament and evenness of structure. Avicenna believed that diseases had causes. In the Canon, it is He has divided the evenness of structure into three categories, i) written: “The word cause in medical works, refers to that which substantial which involve some of the signs of evenness of struc- initiates a given state of human body, or maintains a fixity of such ture and include constitution, position, quantity, and number; ii) a state.”14 According to Avicenna, medical science deals with the accidental, such as beauty and comeliness; and iii) final which are human body in terms of health and decline in health, as knowledge those with complete functions and perfect continuance. In other of anything is acquired and completed by learning about its causes. words, a perfectly functioning organ is a healthy organ.14 Provided such causes exist, it is necessary to determine the causes It can be concluded that according to Avicenna functionally defi- of health and disease.14 Therefore, it would seem that Avicenna cient organs are unhealthy organs. maintained an epidemiological view regarding diseases and health. According to Avicenna, equable temperament exists in healthy Indeed, he has stated that the causes might be visible or invisible, people. He has described equable temperament as the sense that and categorized these causes as follows: i) material comprise the quantities of opposite qualities combine in equal degrees of poten- substances on which health and disease depend; ii) efficient relate cy such that the temperament becomes a quality, which is exactly to those which alter or maintain the states of human body such as their mean. He states the signs of equable temperament to be: “a air, food, and sleep; iii) formal causes include temperaments, as balanced feel of the body with respect to heat, cold, dryness, moist- well as faculties that follow temperaments, and compositions. Avi- ness, softness and hardness; a balance of color between whiteness cenna has defined temperament as a quality that results from the and redness; a body grown moderate in bulkiness and leanness, interaction of opposite qualities present in elements that consist of but inclined to bulkiness; the blood vessels are neither too deep nor minute particles such that most particles from each of the elements superficial, and separated from the flesh; the hair is neither profuse may touch most of the other particles;14 and iv) final causes which nor scanty and curly nor straight. The organs are healthy and the are functions.14 functions are perfect”.14 Although Avicenna has described health and disease in two short “A person having these qualities is popular, cheerful, gay; moder- sentences, “to preserve health if it is already attained” and “to re- ate in his desire for food and drink, has good digestion of food in

786 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 M. Saffari, A. H. Pakpour his stomach, liver and vessels, which are assimilated in the body, temperatures, which may further be mediated by the lethal effects and has normal excretion of the superfluous matter through proper of UV radiation in sunlight that act near the surface of spring water. passages”.14 This further confirms Avicenna’s recommendation. According to Avicenna there are eight different forms for an Avicenna also wrote of the qualities of water from higher moun- equable temperament. Moreover, he has stated that ‘equable’ is a tainous regions where he believed that this water was fresh and term used by physicians in their discussions and does not mean a considered sweet. Such water is light in weight. It is quick to cool balance in weight, but rather an equitable distribution. It is a very down and warm up because it is rarefied, and it is cold in winter wide term that is not confined within any limits (except those of and warm in summer with no taste or odor. This water is quickly excess and deficiency), but neither is it random.14 passed through the epigastrium and easy to cook with.14 It is apparent from the writings of Avicenna that the definitions he Avicenna has proposed a method for water quality evaluation has given depend on numerous conditions and a given definition based on its weight and added that light water is better in most will not be constant for all individuals and all conditions. Rather, cases. According to Avicenna, there were two ways to clarify wa- the definitions offered by Avicenna should be seen as existing in a ter’s weight, namely with the aid of a measure or simply by taking flexible format. This can be understood in the context of the WHO two pieces of linen or cotton wool of equal weight and soaking definition of health, which is similar to that described by Avicenna them into two different kinds of water. The pieces of linen/wool where he has written that the manner of health is unstable: “nor is were then to be thoroughly dried and weighed. The water from the any temperament in perfect state of health or equability at a given lighter of the two linen/cotton-wool samples was considered the time, rather it stands somewhere in the middle”.14 better in terms of quality.14 Avicenna has defined compatibility as an individual’s perception Avicenna introduced distillation, filtration, and boiling to puri- of a complete, intact and moderate temperament. In other words, fy hard water. This was noteworthy since physicians at that time a person perceives himself/herself as moderate in temperament thought that when water was boiled, its attenuated part was evapo- and whole health. Likewise, a person who feels that they have lost rated and the dense part was left behind. They believed there was his/her temperament and therefore does not have a natural tem- no point in boiling water because it would only become harder. perament should be called incompatible.14 Thus the perception of However, despite criticism from other physicians, Avicenna be- health can be interpreted as an improvement in temperament. lieved boiled water was beneficial, for example it was less flatulent This definition closely approximated with the WHO definition and more easily ingested.14 of quality of life. WHO defines quality of life as “an individual’s Avicenna was also aware that temporary hardness could be re- perception of their position in life in the context of the culture and moved by boiling. He wrote: “Boiling first removes the hardness value systems in which they live and in relation to their goals, ex- produced by cold. Then the particles of water become well rar- pectations, standards, and concerns”.15 Both definitions emphasize efied till it becomes thin in consistency. Thus it is possible for the an individual’s perception. heavy earthy particles mixed in water to be separated from it. They The following section focuses on another aspect mentioned in the sink down in water and are thus separated from it in the form of Canon, namely public health and environmental sanitation. sediment. There remains only water which is nearer to the simple water.”14 Water Today it is accepted that temporary hardness when caused by hy- drogen carbonate (or bicarbonate) ions can be removed by boiling. Avicenna was aware of the importance of water hygiene. He un- For example calcium bicarbonae, which is often present in tempo- derstood that water was a substance with different properties, and rary hard water may be boiled to remove hardness. In this process, therefore classified water according its qualities. Avicenna has also a scale forms on the inside of the container in a process known as stated that water is a part of all foods and drinks; however, he did “furring”. This scale is composed of calcium carbonate and the re- not consider it to be nutritious. He has argued that a nutritious thing action for dissociation is as follows: Ca (HCO3)2 → CaCO3 + CO2 is that which is potentially blood and has the remote ability of be- + H2O. Also, according to WHO guidelines, boiling water serves coming a part of an organ of the human body.14 as an effective means to reduce microbial contamination, some- 16 “Water is of different kinds, not because of its aquosity but purely thing that could easily threaten public health. watery substance, and because of what is mixed with it and the conditions which dominate it. The best water is that of springs not Air all springs but springs on pure earth which is not dominated by any condition or polluted by extraneous elements, or springs which are Avicenna considered air to be an element, in fact even a light ele- on rocky ground and thus they do not putrefy as easily as those on ment. He believed that elements were simple bodies which were pure earth”.14 also primary substances of human and non-human bodies alike. According to Avicenna springs provide the best water for health. He advised physicians to learn about the various types of elements, He has defined healthy water as water that is not dominated by any including fire, air, earth and water.14 condition or polluted by extraneous elements and is not putrefied.14 Clean air is considered to be a basic requirement for human health This definition closely approximates the WHO’s current definition and well-being. Poor air quality principally affects the respiratory of safe drinking water, in that it “should not represent any signifi- and cardiovascular systems. Therefore individuals who spend a lot cant risk to health over a lifetime of consumption, including differ- of time outside when the air quality is poor increase their exposure ent sensitivities that may occur between life stages”.16 According to to air pollutants and increase their risk of illness or disease. Avicenna, running spring water should be exposed to the sun and Avicenna has devoted an entire section in the Canon to the effects wind. He believed these elements imparted purity to spring water. of air on the human body, believing air is one of the factors that It has been said that microorganisms decay at a faster rate at higher affects human health and promote disease. He states that inhala-

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 787 Avicenna’s View on Public Health tion of fresh or good air is one of the principles of health. He has for healthy water, he neglected to explain which qualities may neg- considered some of the qualities of good air to be that with which atively affect water.20 In contrast to Dioscorides, Avicenna’s defini- foreign matter (i.e., vapors and smoke) is not mixed, is open to tion of healthy water closely approximates the current definition of the sky, and not closed by walls and roofs. Good air is fresh and safe drinking water mentioned earlier.16 Moreover, Avicenna has pure, not mixed with vapors that rise from lakes, ponds, ditches, believed that the traveler is more exposed to illness from the diver- damp land, fields of vegetables [particularly those in which cab- sity of drinking water rather than the foods consumed. Thus he has bage and rocket seed (Jirjir) are grown], dense forests, yew trees, recommended that travelers should filter water repeatedly, and boil walnut trees, fig trees, and not mixed with putrid air. Clean air is and percolate it.14 These are current recommendations by interna- not troublesome for breathing and not suffocating.14 tional health organizations. For example the Center for Disease Avicenna also considered air pollution and classified abnor- Control and Prevention (CDC), in a brochure designed to travelers, mal changes in air in two ways: i) a change in the substance of recommends that if boiling water is not possible, combined filtra- air where the substance becomes morbid, but not in such a way tion and chemical disinfection could be the most effective patho- that any of its quality has grown in intensity or decreased and ii) a gen reduction method for safe drinking water when travelling.21 change in air quality. Avicenna described air quality in greater detail. He devoted nu- He named polluted air as morbid air and has believed that putre- merous pages in the Canon to air believed that inhalation of clear faction of air occurs in the same way as the putrefaction of foul, air was an effective factor for health. He proposed that some par- stagnant water. Intelligently, he could differentiate between pure ticles which cause diseases could be airborne. Until that time, air- simple air and that which surrounds us, defining pure simple air borne diseases had not been recognized. Thus he opened a new that air which could not be putrified. In contrast, contaminated air window in epidemiology by his works. In other words he has pro- is a mass that is spread out in the atmosphere and comprises ele- vided a major base for the diagnosis and treatment of many com- mental air, watery vapor, terrestrial particles which ascend through municable diseases, including tuberculosis and influenza. smoke and dust, and fiery particles. Such air is prone to putrefac- Today we know that the air plays an important role in developing tion as its many substances may become corrupted.14 respiratory diseases, which is not solely related to particles trans- Avicenna has observed that the putrefaction of air coincided with ferred by air, but also air quality. For example, air temperature is the appearance of diseases, in particular epidemics. This was in an influential factor in the emergence or severity of diseases. In itself not so unusual, as for some time, it had been widely held asthma, it is believed that cold air causes more severe conditions.22 that air caused specific diseases such as cholera. It was not until This issue has been observed by Avicenna over one millennium much later that Dr. Snow, in the 1850’s, demonstrated that cholera before the statement that fresh air should be of a normal tempera- entered a body only by means of water, not by air.17 ture. An ancient idea regarding the causation and spread of diseases Another important point from Avicenna regarding air is that pol- considered that air did not act as a medium for the spread of dis- lutants are the major causes of air putrefaction and have a consider- ease; rather air itself contained miasma or pollution.18 This view able role in disease occurrence. Although Avicenna has supported supported and rationalized the divine origins of disease. the miasma theory, however, he knew that external factors such Herodian, an ancient author, believed that a medical disaster as vapors, particles or smoke lead to the development of miasma. which happened in army camps was caused by poor diet and the This perspective is now strengthened by the status of air pollution inability of the troops to adjust to a new climate and its hot, stifling particularly in industrial and populous cities, as the rate of disease air.19 Yet, modern epidemiologists attribute this problem to some in areas is not comparable to villages and less polluted areas.23 forms of disease transmission, such as shigellosis or another type Avicenna’s productive life had many positive impacts for present of bacillary dysentery. medical progressions. By reviewing his valuable medical works it However, Avicenna did not believe that air caused specific dis- can be concluded that Avicenna was ahead of his time. Up to the eases such as cholera. Instead, he believed that epidemics and 17th century, many of his compilations have been taught in univer- putrefaction of air mostly occurred towards the end of the sum- sities worldwide. He has devoted a part of his famous book, the mer and during the autumn. Thus, he has stated that changes in air “Canon of Medicine”, to public health and provided highly sys- quality, as an intolerable excess of heat or cold, would most likely tematic knowledge on the definition of health, disease, and their result in the destruction of crops and animal life. Avicenna consid- features which are comparable to today’s knowledge. By his exact ered changes in the properties of air to exert a negative effect on the description of air and water specifications and qualities we note his human body, placing them in a state of “disorder”. He believed that scholastic and precise viewpoint on scientific affairs with regards disorder occurred when the body humors became putrid, and that to public health and sanitation, an insight needed by today’s re- the putrefaction of the humors was a direct effect of putrid air. Thus searchers and scientists. Avicenna has concluded that abnormal warm and cold airs are not good for healthy persons.14 References In the following section, we compare Avicenna’s views with other authors regarding public health. 1. Hayes AW. Principles and Methods of Toxicology. 5th ed. New York: As mentioned, Avicenna has declared that water has certain prop- Informa Healthcare; 2008: 16. 2. Smith RD. Avicenna and the Canon of medicine: a millennial tribute. erties and he classified waters according to its qualities. Yet, Peda- West J Med. 1980; 133: 367 – 370. nius Dioscorides believed that water analysis was difficult. He has 3. Tan SY. Medicine in stamps. Avicenna (980–1037): prince of physi- proposed qualifications for optimal water: purity, sincerely sweet, cians. Singapore Med J. 2002; 43: 445 – 446. lacking in other qualities, does not remain in the digestive system 4. Rafiabadi HN. Saints and Saviours of Islam. New Delhi: Sarup & 20 Sons; 2005: 273. for very long, and is not inflative nor spoiled. 5. Pollock F, (Translator). The divine comedy by Dante Alighieri. London: Despite that Pedanius Dioscorides mentioned valuable properties 303 Chapman and Hall; 1854: 21.

788 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 M. Saffari, A. H. Pakpour

6. Shoja MM, Tubbs RS, Loukas M, Khalili M, Alakbarli F, Cohen-Gadol tion. 2006. Available from: URL: http://www.who.int/water_sanita- AA. Vasovagal syncope in the Canon of Avicenna: the first mention of tion_health/dwq/gdwq3rev/en/ [ Accessed 4 February 2012] carotid artery hypersensitivity. Int J Cardiol. 2009, 29; 134: 297 – 301. 17. Koch T. John Snow, Hero of Cholera: RIP. CMAJ. 2008; 178: 17 – 36. 7. Khan A. Avicenna (Ibn Sina): Muslim Physician and Philosopher of 18. Gibson AD. Miasma Revisited - the Intellectual History of Tropical the Eleventh Century. New York: Rosen Publishing Group; 2006: 11 Medicine. Aust Fam Physician. 2009; 38: 57 – 59. 8. Boorstin DJ. The discoverers. New York: Random House; 1983: 346. 19. Valerie M, Hope EM. Death and Disease in the Ancient City. New 9. Nafisi S. The Avicenna`s job, thought and life [In Persian]. Tehran: York: Routledge; 2000. Asatir press; 2005: 15. 20. Osbaldeston TA, Dioscorides DMM. Five Books in One Volume: New 10. Parvin M. Avicenna and I: the journey of spirits. Bethesda: Ibex Pub- Modern English Translation. Johannesburg: Ibidis Press; 2000: 753 – lishers; 2006: 151 – 152. 754. 11. World Health Organization. Constitution of the World Health Organi- 21. A Guide to Drinking Water Treatment and Sanitation for Backcountry zation - Basic Documents, Forty-fifth edition, Supplement, 2006. & Travel Use [database on the Internet]. Centers for Disease and Con- 12. Lewis DM. WHO definition of health remains fit for purpose. BMJ. trol and Prevention (CDC); 2012. Available from: URL: http://www. 2011; 343: 53-57. cdc.gov/healthywater/drinking/travel/backcountry_water_treatment. 13. Viseltear AJ. “C.-E.A. Winslow and the early years of public health at html [Accessed 4 October 2012] Yale, 1915-1925”. Yale J Biol Med. 1982; 55:137 – 151. 22. Piacentini GL, Peroni D, Crestani E, Zardini F, Bodini A, Costella S, et 14. Avicenna. The Canon of Medicine of Avicenna [Translated to English al. Exhaled air temperature in asthma: methods and relationship with by: Oskar Cameron]. NewYork: AMS Press INC; 1973. markers of disease. Clin Exp Allergy. 2007; 37: 415 – 419. 15. World Health Organization. Measuring quality of life: the development 23. Orazzo F, Nespoli L, Ito K, Tassinari D, Giardina D, Funis M, et al. Air of the World Health Organization Quality of Life Instrument (WHO- pollution, aeroallergens, and emergency room visits for acute respira- QOL). Geneva: WHO; 1993. tory diseases and gastroenteric disorders among young children in six 16. Guidelines for drinking-water quality, 3th ed. incorporating first and Italian cities. Environ Health Perspect. 2009; 117: 1780 – 1785. second addenda [database on the Internet]. World Health Organiza-

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 789 Excerpts from Persian Medical Literature

Excerpts from Persian Medical Literature

Audit of Transfusion-related Practices and Equipment in 102 Hospitals

Blood banks are the link between blood centers and hospitals. A blood transfusion organization places emphasis on the application of standard operating procedures (SOPs), the use and calibration of blood bank equipment, and preventive measures for probable risks and mistakes. The current study has evaluated 102 blood banks according to practices and equipment, and then categorized the evaluated blood banks into three groups based on their scores. Data were analyzed by SPSS version 19.5 using descriptive statistics. In 31% of the hospitals evaluated blood banks were independently located; however, in the remainder of hospitals studied blood banks shared their spaces with other laboratories. In the equipment domain, 88% of the hospitals had a serofuge, 63% had a separate water bath, 67% had a blood banking refrigerator, 42% had a freezer for plasma and 22% had a platelet shaking incubator. In terms of the practice domain, 88% of hospitals had SOPs, 82% met the standard practice for cross-matching, and only 8% performed antibody screening. The majority of hospitals (70%) were categorized as good, with acceptable conditions for transfusion-related practice and equipment. Authors: Asgaripoor F, Mirrezaei SM, Hajibeyghi B, Chegini A, Ahangari H, Firouzi HR. Source: Laboratory & Diagnosis. 20l2; 3(16): 5 – 9.

Efficacy of Ciprofloxacin-Doxycycline vs. Rifampin-Doxycycline in Brucellosis

Brucellosis, a worldwide disease, is endemic in Iran and associated with chronic disabilities in humans. Treatment with combination therapy leads to recovery from symptoms, shortening of the symptomatic interval, and decrease in the rate of relapse and drug resistance. Considering the use of rifampin in the treatment of tuberculosis and the necessity for an alternative treatment in regions endemic for both tuberculosis and brucellosis, we have compared the efficiency of the World Health Organization (WHO) standard regimen of rifampin-doxycycline (RD) versus ciprofloxacin-doxycycline (CD) for the treatment of brucellosis. This randomized controlled trial was performed on 90 patients affected with brucellosis who referred to the Infectious Disease Clinics at Arak University of Medical Sciences. We randomly divided patients into two groups, DR and CD. Patients in the DR group received doxycycline (100 mg, bid) and rifampin (300 mg, bid) for eight weeks. Those randomized to the CD group received doxycycline (100 mg, bid) and ciprofloxacin (500 mg, bid) for eight weeks. During treatment, we evaluated patients for relief of symptoms, drug side effects, and performed laboratory analyses. In this study the rate of symptom relief and laboratory findings in both groups were similar. There were 93.2% of DR patients and 83.9% of CD patients who experienced symptom relief (P=0.182). Drug side effects were not significant in either group and did not lead to discontinuation of therapy. Due to the similarity in efficacy of CD and DR regimens in the treatment of brucellosis and considering the use of rifampin in regions with a high prevalence of tuberculosis, we recommend the CD regimen as an appropriate treatment. Authors: Didgar F, Sarmadian H, Zarin Far N, Rafiee M, Choghae M. Source: The Journal of Zanjan University of Medical Sciences. 2012; 20(80): 12-19.

Segmented Regression Model to Analyze the Trend for Tuberculosis Incidence in Iran, 1964–2008

A study of the trend in changes in observed rates provides valuable information for needs assessment, planning, reload programs and determination of indicators in each country. The main objective of this paper is to determine the changes in the trend in tuberculosis (TB) incidence rate in Iran by applying the segmented regression model. In this study, we used the segmented linear regression model to analyze the trend in changes in the pattern of TB incidence during the past 44 years (1964–2008) in Iran. We used the least squares method, permutation test, and Bayesian Information Criteria to determine, which of the two segment regression models and poison regression would be better. Data were analyzed by Joinpoint 3.4 and SAS 9.1 software. According the permutation test, there were two breakpoints over 1977 and 1993 (P = 0.0108). There was a decline in incidence rate of TB during the first 11 years of the review with an annual percentage decrease of 10.1%. For the second segment, the rate increased at 4.3% per year. For the end segment, the TB incidence rate again declined by 4.5% per year. The average annual change in TB incidence rate in Iran for at least ten years has been estimated to decline at a rate of 4.5% per year. The findings of this study have shown that the incidence rate of TB decreased after 1992, which seemed faster than the decline estimated by the International TB Control Program. This shows the success of both TB prevention and treatment programs in Iran. Authors: Arsang SH, Kazemnejad A, Amanj F. Source: Iranian Journal of Epidemiology. 2011; 7(3): 6 – 12.

790 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 Excerpts from Persian Medical Literature

Obstructive Sleep Disorders and Dental Growth in Children

Obstructive sleep disorders and their effects on dental and maxillofacial growth have long been debated. Adenotonsillar hypertrophy, as the most common cause of obstructive sleep disorders, with its consequent impact on dental growth has recently gained greater attention. Its treatment may help prevent or reverse these effects. In this cross-sectional study, we enrolled 120 children. Of these, 60 were assigned to undergo adenotonsillectomy for obstructive sleep disorders and then compared with 60 children with no obstructive sleep disorders. Both groups were matched in terms of gender and age. We used dental casts and caliper measurements. Crowding of the upper and lower teeth, anterior open bite, posterior cross bite, overjet, class II malocclusion, and width of upper and lower dental arches were documented and compared. Differences were found in crowding of the upper and lower teeth, anterior open bite, posterior cross bite, overjet, class II malocclusion, and width of the upper and lower dental arches. This study suggests there is an effect of obstructive sleep disorders on dental growth, which is probably due to the long term impact of the position of the head, mandible and tongue to keep the airway open during oral breathing. Authors: Fattahi Bafghi A, Fathololoomi MR, Nohi S, Asghar Peyvandi A, Goljanian Tabrizi A, Nasirzadeh Bafghi R. Source: Journal of Medical Council of Islamic Republic of Iran. 2011; 30(1): 36 – 41.

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 791 Letters to the Editor

Letters to the Editor

Critical Assessment of the Progress of Medical another way to improve Iran`s contributions to the world of sci- Sciences in Iran and Turkey ence.

Dear Editor: Conflict of Interest: None In a recent issue of AIM, I read the article on the progress of medical sciences in Iran and Turkey with great interest.1 The au- Farzaneh Aminpour PhD thors discussed effective contributions to the production of sci- Medical Education Research Center, Isfahan University of Medical Scienc- es, Isfahan, Iran; School of Health Management and Medical Information ence in developing countries. Additionally, they have criticized the Sciences, Tehran University of Medical Sciences, Tehran, Iran. requirement for academic promotion in both countries that man- E-mail: [email protected] dates researchers publish papers in indexed English journals without consideration for the novelty and originality of the research. References I would like to point out that focus on increasing the number of indexed scientific articles is neither an ideal nor a perfect approach 1. Massarrat S, Kolahdoozan S. Critical assessment of progress of medi- to improve a country’s contribution to the world of science. Over cal sciences in Iran and Turkey: the way developing countries with lim- emphasizing the quantity of scientific papers would encourage ited resources should make effective contributions to the production of science. Arch Iran Med. 2011; 14: 370 – 377. short-term trials, eliminate long-term interventional studies, and 2. Aminpour F, Kabiri P. Science production in Iran: the Scenario of Ira- possibly reduce the quality of medical research. nian medical journals. J Res Med Sci. 2009; 14: 313 – 322. However, according to numerous studies and statistics, there has 3. Butler D, Arslan A. Islam and science: the data gap. Nature. 2006; 444: 26 – 27. been a remarkable advancement in the number of scholarly pub- 4. Revival in Iran. Nature. 2006; 442: 719 – 720. 2–4 lications in Iran during recent years. In 2010, scientific publica- 5. MacKenzie D. Iran showing fastest scientific growth of any country. tions in Iran showed an 11-fold increase over the world average, New Scientist 18 February 2010. Available from: URL: http://www. the largest increase of any country.5 In 2011, Iran had approximate- newscientist.com/article/dn18546 [Accessed January 9, 2012] 6. Van Noorden R. 365 days: 2011 in review. Nature. 201; 480: 426 – 429. ly a 20% increase in the number of published articles compared to 7. Aminpour F, Kabiri P, Boroumand MA, Keshtkar AA, Hejazi SS. Ira- 2010. This was the largest growth in terms of scientific publica- nian Medical Universities in SCIE: evaluation of address variation. tions worldwide and has placed Iran among the top 40 countries Scientometrics. 2010; 85: 53 – 63. according to the number of published research papers.6 Undoubt- 8. Academic Ranking of World Universities. Available from: URL: http:// www.shanghairanking.com [Accessed January 9, 2012] edly, such an improvement could not guarantee the quality of re- 9. The Thomson Scientific Journal Selection Process. Available from: search in any country. However this has a definite impact on the URL: http://thomsonreuters.com/products_services/science/free/es- improvement in Iran’s academic credibility and scientific position says/journal_selection_process [Accessed January 9, 2012] in recent years. 10. MEDLINE Journal Selection. Available from: URL: http://www.nlm. nih.gov/pubs/factsheets/jsel.html [Accessed January 9, 2012] Scientific productivity, as a major scientometric indicator, deter- 11. Aminpour F. The contribution of academic journals to the university mines the academic position of countries and universities and is an scientific productivity.J Isfahan Med Sch. 2011; 29: 367 – 375. important criterion in ranking world universities.7 According to the Academic Ranking of World Universities (ARWU) conducted by Author’s Reply: Shanghai Jiao Tong University, papers indexed by ISI indices such In her letter to the editor, Dr. Aminpour referredt our article pub- as Science Citation Index Expanded (SCIE) and Social Science lished in AIM (Arch Iran Med. 2011; 14: 370 – 377), where she Citation Index (SSC) comprise 20% of the total ranked weight.8 has proposed that the lack of citation and low quality of Iranian At the present time there are a few Iranian medical journals in- scientific publications is not the only problem; instead, enhancing dexed by ISI Web of Science. These journals have only a few cita- the publishing standards of journals in an attempt to improve the tions by medical researchers, which have resulted in low impact indexing status of Iranian medical journals is important. factors. It is noteworthy to mention that low quality of content is In our evaluation report, we did not consider the publications in not the only problem. Numerous Iranian medical journals suffer non-indexed Iranian journals, but only those indexed in ISI. We because they ignore some of the basic publishing standards man- compared articles that had both high and low citations and con- dated by prestigious databases such as the minimal requirements cluded that publications which dealt with regionally occurring for inclusion and indexing. Journals could be included in ISI or diseases would be considered by the international audience and Medline only if they adhere to the standards of regular and timely achieve a high citation rate. We have emphasized that the high publishing, expressive titles and abstracts for papers, a specialized number of scientific journals and articles published are not repre- review procedure, devotion to ethical guidelines, disclosing con- sentative of the growth in scientific performance within Iran. It is flicts of interest, opportunity for comments and oppositions, and a waste of time in terms of academic personnel and financial re- appropriate retractions.9,10 Nevertheless, most Iranian medical resources of a country to focus on publications that copy known facts searchers publish their articles in domestic journals.11 The indexing previously published in journals from developed countries and not status of a journal has a direct impact on the visibility and the rate to conduct innovative research in fields important for promoting of citations to that journal. Thus, developing executive strategies to the health of our nation. enhance publishing standards and indexing status of Iranian medical journals as well as their quality of content should be considered

792 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 Letters to the Editor

Sadegh Massarrat MD from 2337 to 21477 (19140 submissions increase), however, the Digestive Diseases Research Institute, Shariati Hospital, Tehran University rate of acceptance decreased from 20.5 to 19.2 (1.3% decrease). of Medical Sciences, Tehran, Iran. This problem is not solely limited to Iran, but rather it is a global problem which might be a result of the disproportionate increase Challenges to Our Goals, What are the Pitfalls in in acceptances compared to the increase in numbers of submis- the Way of Publishing Scientific and Medical Pa- sions. Thomson Reuters has reported that even with a considerable pers? increase in journals and their publication numbers, there has been a decline in acceptance rate during 2005–2010 of approximately Dear Editor: 4%. Our country, as a third world nation, is rapidly developing. Thus • We lack experts who can evaluate articles. Numerous research- research in all scientific areas can assist with attaining its develop- ers do not have the capability to properly evaluate articles because mental goals. I have read the valuabe article by Dr. Sadegh Mass- they have limited information and experience regarding journal rat and Dr. Shadi Kolahdoozan ( Arch Iran Med. 2011; 14: 370 specifications, impact factors, and the process of submission. In – 377).1 We are in a competition with Turkey to become the top addition some researchers overestimate the value of their article country in scientific publications in the Middle East. and send it for high impact journals, which will lead to rejection of As seen in this article, there is a large disparity between Iran and the article. Conversely, others underestimate their article's value, Turkey in terms of published articles. However, this gap is dimin- sending it to lower impact journals where the article will be ac- ishing yearly, as our scientists are providing new, worthwhile pub- cepted and published when it could have been published in a more lications that assist us in reaching our goals. valuable journal. Based on the last report by Thomson Reuters in April 2012,2 Iran • We lack experienced people who can submit articles and com- had the third position in ranking of gross increase in submissions municate with international journals. There are over 5000 medi- during 2005–2010. According to this report the total number of cine-related journals indexed in two of the most important medical submissions by Iranian researchers in the Scholar One Manuscript indexes (Medline and ISI). Indexed journals are not only published submission system was 19140 submissions, a 1.4% increase. Tur- in the United States, Europe and Iran. Totally, there are about 196 key during this period submitted 14111 manuscripts, which was a countries of which a large number have at least one indexed jour- 0.8% decrease. What is the gap between data analyzed by Dr. Mas- nal. Turkey appears to have worked on this problem. In an internet sarrat and that from Thomson Reuter? We know that most indexed search of indexed journals, if you search through each unknown journals in developing countries, in addition to a considerable international indexed journal you can find some Turkish and also number of journals in Western countries do not use the Scholar Chinese articles, which indicates that Turkish researchers conduct One Manuscript system, and in these years the numbers of such searches of all indexed journal with the intent to maximize their journals has been increased significantly. Then this shows the fo- choices for submission. cus of Turkish scientists on these journals too; the matter that our Hopefully we will increase our articles to be published in indexed scientists have less knowledge about it and the numbers of such journals and reach our scientific goals by both targeted investments journals or their submission systems. For example, none of our and the use of experts in the field of article evaluation and submis- country’s indexed journals are working with the Scholar One Man- sion. uscript system and have their specific submission system software that this situation is similar in other developing countries’ indexed Behnam Baghianimoghadam MD•, Mohammad Hosein Baghianimogha- journals too. dam PhD Research and Clinical Center for Infertility, Shahid Sadoughi University of After careful attention to previously published articles and jour- Medical Sciences, Yazd, Iran. nals to which our scientists have submitted articles, we see some deficiencies in our policies in publishing articles. During 2011, References based on a good design, most of the Iranian indexed medical journals increased their issues. Journals such as Iranian Red Crescent 1. Massarrat S, Kolahdoozan S. Critical assessment of progress of med- Medical Journal, Hepatitis Monthly, Journal of Research in Medi- ical sciences in Iran and Turkey: the way developing coun- cal Science, Iranian Journal of Public Health, Acta Medica Irani- tries with limited resources should make effective contributions to the ca, and Archives of Iranian Medicine are now published monthly production of science. Arch Iran Med. 2011; 14: 370 – 377. 2. ‌‌‌Global Publishing Changes in Submission Trends and the Impact on also Iranian Journal of Nephrology and Iranian Journal of Re- Scholarly Publisher. Thomson Reuters, April 2012. Available from: productive Medicine are publishing bimonthly. This enables us to URL: http://scholarone.com/media/pdf/GlobalPublishing_WP.pdf increase both our publications and citations. However, we need to do more. Author’s Reply: As a researcher who consults with Iranian scientists to publish In a letter to AIM, Baghianimoghadam et al. claim that there is their articles in indexed journals, I have some suggestions based a gap between the number of scientific submissions between Tur- on my experiences: key and Iran in 2012 as noted by Thomson Reuters and the results • Large numbers of our research projects in universities are a from our paper (Arch Iran Med. 2011; 14: 370 – 377). The results waste of time. Numerous dissertations and research proposals of Thomson Reuters are obtained over a five-year period (2005– are produced only for graduation and do not give suggestions to 2010), whereas our assessment refers only to submissions from a solve research problems. These publications have no value for in- one-year period. dexed journals. Thus it is necessary to adopt regulations to prevent The authors are correct in assuming that most university research such publications. Based on a new report by Thomson Reuters, projects are conducted with the intent for graduation, not for prob- although the numbers of our country's submissions have increased lem solving. Unfortunately university academic members have in-

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 793 Letters to the Editor adequate salaries and are obligated to seek employment outside of This can be only achieved when research centers and universities the universities to meet their living expenses. Thus they lack time are allowed the freedom to elect their leaders and make decisions to focus on research and mentor students in important scientific without outside influence. projects which are time consuming. This implies that the Iranian Dr. Baghianimoghadam and his colleague have mentioned that government should increase the research budget to the level which Iranian researchers lack experience evaluating the importance of is common in developing countries, in a range from 2% to 5% of their research work. This can be accomplished when Iranian re- the GDP. China and South Korea have increased their research searchers establish an intensive, permanent connection and col- budgets over the last ten years, which has resulted in dramatic laboration with scientific researchers outside Iran who work in progress in the field of research and science production for both renowned research centers. countries. In addition to the increase in research budget, we need structural change in order to build an atmosphere of security in es- Sadegh Massarrat MD tablishing research centers which would enable the participation of Digestive Research Institute, Shariati Hospital, Tehran University of Medical highly qualified Iranian researchers from all regions of the world. Sciences, Tehran, Iran.

794 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 Subject Index to Volume 15

Abbreviated injury scale, Arch Iran Med. 2012; Med. 2012; 15(2): 76 - 78. Children, Arch Iran Med. 2012; 15(8): 485 – 487. 15(5): 317 – 319. Atypical presentation, Arch Iran Med. 2012; 15(4): Children, Arch Iran Med. 2012; 15(9): 560 – 563. Academic Medical Centers, Arch Iran Med. 2012; 253 – 256. Chlamydia trachomatis, Arch Iran Med. 2012; 15(12): 736 – 740. Autopsy, Arch Iran Med. 2012; 15(7): 418 – 421. 15(3): 171 – 175. Acanthocytosis, Arch Iran Med. 2012; 15(12): 780 Bahrain, Arch Iran Med. 2012; 15(8): 485 – 487. Choledochoduodenostomy, Arch Iran Med. 2012; – 782. Balanced translocation, Arch Iran Med. 2012; 15(4): 15(5): 275 – 278. Acute abdomen, Arch Iran Med. 2012; 15(4): 253 249 – 252. Choledochojejunostomy, Arch Iran Med. 2012; – 256. Basic fibroblast growth factor,Arch Iran Med. 2012; 15(5): 275 – 278. Acute lymphoblastic leukemia, Arch Iran Med. 15(9): 553 – 556. Choledocholithiasis, Arch Iran Med. 2012; 15(5): 2012; 15(6): 352 – 355. Behavior of general practitioners, Arch Iran Med. 275 – 278. Acute renal failure, Arch Iran Med. 2012; 15(11): 2012; 15(4): 223 – 227. Cholesterol, Arch Iran Med. 2012; 15(9): 549 – 552. 729 – 730; 15(6): 384 – 386. Behçet disease, Arch Iran Med. 2012; 15(8): 485 – Chorea-acanthocytosis, Arch Iran Med. 2012; Adipose tissue, Arch Iran Med. 2012; 15(8): 495 – 487. 15(12): 780 – 782. 499. Biopsy, Arch Iran Med. 2012; 15(7): 418 – 421. Chromosomal abnormality, Arch Iran Med. 2012; Adolescents, Arch Iran Med. 2012; 15(3): 142 – Bladder tumor, Arch Iran Med. 2012; 15(9): 572 – 15(4): 232 – 234. 145. 574. Chronic disease, Arch Iran Med. 2012; 15(2): 70 - Adrenal gland, Arch Iran Med. 2012; 15(5): 328 – Blood donor, Arch Iran Med. 2012; 15(2): 88 - 90. 75. 330. Body mass index, Arch Iran Med. 2012; 15(7): 400 Chronic mucocutaneous candidiasis, Arch Iran Adult, Arch Iran Med. 2012; 15(9): 538 – 544. – 403. Med. 2012; 15(7): 452 – 454. Adults, Arch Iran Med. 2012; 15(1): 22 – 26. Bone density, Arch Iran Med. 2012; 15(2): 82 - 84. Chronic tics, Arch Iran Med. 2012; 15(2): 76 - 78. Aging, Arch Iran Med. 2012; 15(8): 462 – 468. Bone, Arch Iran Med. 2012; 15(1): 59 – 62. Cigarette, Arch Iran Med. 2012; 15(5): 283 – 289. Airplane crash during approach, Arch Iran Med. Breast cancer, Arch Iran Med. 2012; 15(8): 504 – Cirrhosis, Arch Iran Med. 2012; 15(8): 472 – 476. 2012; 15(5): 317 – 319. 507. Clinic visit, Arch Iran Med. 2012; 15(12): 756 – 758. Alanine aminotransferase, Arch Iran Med. 2012; Breast carcinoma, Arch Iran Med. 2012; 15(6): 366 Clinic, Arch Iran Med. 2012; 15(8):491 – 494. 15(4):247 – 248. – 369. Clinical features, Arch Iran Med. 2012; 15(1): 22 – Albumin, Arch Iran Med. 2012; 15(2): 85 - 87. Bronchoscopy, Arch Iran Med. 2012; 15(3): 128 – 26. Alloimmunization, Arch Iran Med. 2012; 15(3): 162 130. Clinical trial, Arch Iran Med. 2012; 15(8): 472 – – 165. Brucella, Arch Iran Med. 2012; 15(11): 723 – 725. 476. Alloplast, Arch Iran Med. 2012; 15(4): 235 – 238. Brucellosis, Arch Iran Med. 2012; 15(5): 303 – 305. Colorectal Cancer (CRC), Arch Iran Med. 2012; Amniocentesis, Arch Iran Med. 2012; 15(3): 162 – Burn wounds, Arch Iran Med. 2012; 15(11): 670 – 15(11): 726 – 728. 165; 15(7): 449 – 451. 673. Compartment syndrome, Arch Iran Med. 2012; Amphotericin B, Arch Iran Med. 2012; 15(7): 429 Cancer registry, Arch Iran Med. 2012; 15(4): 196 – 15(6): 387 – 388. – 432. 200. Complications, Arch Iran Med. 2012; 15(5): 325 – Amplatzer™ ASD closure device, Arch Iran Med. Cancer, Arch Iran Med. 2012; 15(12): 741 – 746. 327. 2012; 15(11): 693 – 695. Candida albicans, Arch Iran Med. 2012; 15(7): 452 Condom, Arch Iran Med. 2012; 15(12): 767 – 771. Amygdala, Arch Iran Med. 2012; 15(9): 557 – 559. – 454. Confounder, Arch Iran Med. 2012; 15(8): 508 – 516. Analgesia, Arch Iran Med. 2012; 15(6): 387 – 388. Candida spp., Arch Iran Med. 2012; 15(1): 27 – 31. Congenital anomalies, Arch Iran Med. 2012; 15(4): Aneurysm, Arch Iran Med. 2012; 15(2): 113 - 114. Cardiovascular disease, Arch Iran Med. 2012; 15(6): 228 – 231. Animal bites, Arch Iran Med. 2012; 15(6): 356 – 346 – 351. Congenital heart defect, Arch Iran Med. 2012; 360. Cardiovascular diseases, Arch Iran Med. 2012; 15(2): 113 - 114. Anterior cruciate ligament, Arch Iran Med. 2012; 15(9): 531 – 537. Congenital hypothyroidism, Arch Iran Med. 2012; 15(4): 219 – 222. Cardiovascular risk factors, Arch Iran Med. 2012; 15(3): 136 – 141. Anterior cruciate ligament, Arch Iran Med. 2012; 15(8): 469 – 471. Connexin26, Arch Iran Med. 2012; 15(1): 49 – 51. 15(8): 495 – 499. Carpal bone, Arch Iran Med. 2012; 15(12): 777 – Conservative breast surgery, Arch Iran Med. 2012; Anthracosis, Arch Iran Med. 2012; 15(3): 128 – 130. 779. 15(8): 504 – 507. Anthropometric characteristics, Arch Iran Med. Case-control study, Arch Iran Med. 2012; 15(9): Cost-benefit analysis, Arch Iran Med. 2012; 15(3): 2012; 15(11): 681 – 687. 538 – 544. 136 – 141. Antifungals, Arch Iran Med. 2012; 15(1): 27 – 31. CD133+ cells, Arch Iran Med. 2012; 15(1): 32 – 35. Crystalline heroin, Arch Iran Med. 2012; 15(12): Antioxidant, Arch Iran Med. 2012; 15(11): 674 – CD30, Arch Iran Med. 2012; 15(3): 146 – 150. 751 – 755. 680. CD82/KAI1, Arch Iran Med. 2012; 15(11): 707 – Cystic fibrosis, Arch Iran Med. 2012; 15(7): 449 – Antithyroid drugs, Arch Iran Med. 2012; 15(8): 477 712. 451. – 484. Celiac disease, Arch Iran Med. 2012; 15(6): 342 – Cytogenetic study, Arch Iran Med. 2012; 15(4): 232 Anxiety, Arch Iran Med. 2012; 15(5): 290 – 297; 345. – 234. 15(5): 306 – 311. Cell culture, Arch Iran Med. 2012; 15(3): 171 – 175. Cytokines, Arch Iran Med. 2012; 15(11): 688 – 692; Apolipoprotein-AI, Arch Iran Med. 2012; 15(9): Cell therapy, Arch Iran Med. 2012; 15(7): 422 – 428. 15(3): 146 – 150. 549 – 552. Central nervous system, Arch Iran Med. 2012; Cytotoxic, Arch Iran Med. 2012; 15(11): 696 – 701. Appropriateness, Arch Iran Med. 2012; 15(1): 8 – 15(7): 452 – 454. Depression, Arch Iran Med. 2012; 15(5): 290 – 297; 13. Central obesity, Arch Iran Med. 2012; 15(3): 131 – 15(5): 306 – 311. Arteriovenous fistula, Arch Iran Med. 2012; 15(2): 135. DFNB1, Arch Iran Med. 2012; 15(1): 49 – 51. 113 - 114. Cervical dysplasia, Arch Iran Med. 2012; 15(9): 572 Diabetes mellitus, Arch Iran Med. 2012; 15(8): 469 Arthritis, Arch Iran Med. 2012; 15(9): 549 – 552. – 574. – 471. Arthropathy, Arch Iran Med. 2012; 15(2): 82 - 84. Cervical esophagus, Arch Iran Med. 2012; 15(5): Diabetic ketoacidosis, Arch Iran Med. 2012; 15(1): ARX gene, Arch Iran Med. 2012; 15(6): 361 – 365. 298 – 302. 55 – 58. Aspergillus, Arch Iran Med. 2012; 15(7): 429 – 432. Cesarean section, Arch Iran Med. 2012; 15(1): 4 – 7. Diagnosis, Arch Iran Med. 2012; 15(8):491 – 494. Assessment, Arch Iran Med. 2012; 15(2): 79 - 81. Cesarean section, Arch Iran Med. 2012; 15(1): 8 – Diet quality, Arch Iran Med. 2012; 15(6): 346 – 351. Assisted reproductive techniques, Arch Iran Med. 13. Diet, Arch Iran Med. 2012; 15(3): 131 – 135. 2012; 15(4): 228 – 231. Chemotherapy, Arch Iran Med. 2012; 15(7): 413 – Diffusion weighted MRI, Arch Iran Med. 2012; Atherosclerosis, Arch Iran Med. 2012; 15(11): 688 417. 15(8): 469 – 471. – 692. Chest wall, Arch Iran Med. 2012; 15(8): 517 – 519. Diphtheria, Arch Iran Med. 2012; 15(3): 181 – 186. Attention deficit hyperactivity disorder, Arch Iran Child, Arch Iran Med. 2012; 15(4):247 – 248. Disposition index, Arch Iran Med. 2012; 15(4): 239 Med. 2012; 15(9): 560 – 563. Children, Arch Iran Med. 2012; 15(2): 76 - 78. – 246. Attention deficit/hyperactivity disorder, Arch Iran Children, Arch Iran Med. 2012; 15(6): 342 – 345. Dominant, Arch Iran Med. 2012; 15(1): 49 – 51.

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 795 Doppler ultrasonography, Arch Iran Med. 2012; – 135. Hyperthyroidism, Arch Iran Med. 2012; 15(8): 477 15(3): 162 – 165. Genotype, Arch Iran Med. 2012; 15(7): 446 – 448. – 484. Drug combinations, Arch Iran Med. 2012; 15(9): Genotyping, Arch Iran Med. 2012; 15(2): 88 - 90. ICD-85, Arch Iran Med. 2012; 15(11): 696 – 701. 531 – 537. GERD, Arch Iran Med. 2012; 15(12): 747 – 750. Iliopsoas abscess, Arch Iran Med. 2012; 15(4): 253 Drug utilization review, Arch Iran Med. 2012; 15(2): GJB2, Arch Iran Med. 2012; 15(1): 49 – 51. – 256. 85 - 87. Glycemic target range, Arch Iran Med. 2012; 15(4): Imipenem, Arch Iran Med. 2012; 15(11): 670 – 673. Dyslipidemia, Arch Iran Med. 2012; 15(8): 462 – 239 – 246. Immunohistochemistry, Arch Iran Med. 2012; 468. Golestan, Arch Iran Med. 2012; 15(4): 196 – 200. 15(6): 366 – 369. E. coli, Arch Iran Med. 2012; 15(5): 312 – 316. H.pylori-eradication, Arch Iran Med. 2012; 15(11): Immunophenotyping, Arch Iran Med. 2012; 15(1): Early-onset multiple sclerosis, Arch Iran Med. 2012; 664 – 669. 36 – 42. 15(6): 381 – 383. H1N1, Arch Iran Med. 2012; 15(1): 55 – 58. Immunosuppression, Arch Iran Med. 2012; 15(12): E-cadherin, Arch Iran Med. 2012; 15(11): 707 – 712. Hamstring tendons, Arch Iran Med. 2012; 15(4): 772 – 776. Effect modifier, Arch Iran Med. 2012; 15(8): 508 – 219 – 222. In vitro fertilization (IVF), Arch Iran Med. 2012; 516. Harm reduction, Arch Iran Med. 2012; 15(5): 283 15(4): 228 – 231. Empowerment, Arch Iran Med. 2012; 15(2): 79 - 81. – 289. Incidence, Arch Iran Med. 2012; 15(6): 356 – 360. Endobronchial metastasis, Arch Iran Med. 2012; HCV, Arch Iran Med. 2012; 15(5): 271 – 274. Indications, Arch Iran Med. 2012; 15(12): 772 – 15(8): 520 – 522. HDL, Arch Iran Med. 2012; 15(9): 549 – 552. 776. Endoscopic, Arch Iran Med. 2012; 15(3): 157 – 161. Head trauma, Arch Iran Med. 2012; 15(9): 583 – Infant mortality, Arch Iran Med. 2012; 15(1): 4 – 7. Endoscopy, Arch Iran Med. 2012; 15(3): 177 – 178; 584. Infants, Arch Iran Med. 2012; 15(4): 228 – 231. 15(8): 488 – 490. Health care quality assurance, Arch Iran Med. 2012; Inflammation, Arch Iran Med. 2012; 15(3): 166 – Energy intake, Arch Iran Med. 2012; 15(11): 681 – 15(12): 759 – 763. 170. 687. Health Facility Acquisition, Arch Iran Med. 2012; Inflammatory factor, Arch Iran Med. 2012; 15(8): Energy reporting, Arch Iran Med. 2012; 15(11): 681 15(12): 736 – 740. 462 – 468. – 687. Health Facility Merger, Arch Iran Med. 2012; Influenza, Arch Iran Med. 2012; 15(1): 55 – 58. Enuresis, Arch Iran Med. 2012; 15(11): 702 – 706. 15(12): 736 – 740. Information resources, Arch Iran Med. 2012; 15(4): Epidemiology, Arch Iran Med. 2012; 15(12): 741 – Health, Arch Iran Med. 2012; 15(7): 394 – 399. 223 – 227. 746; 15(2): 76 - 78; 15(6): 356 – 360. Health-related quality of life, Arch Iran Med. 2012; Injury severity score, Arch Iran Med. 2012; 15(5): Epileptic seizure, Arch Iran Med. 2012; 15(6): 381 15(8): 504 – 507. 317 – 319. – 383. HeLa cancer cells, Arch Iran Med. 2012; 15(11): Insulin resistance, Arch Iran Med. 2012; 15(4): 239 Epileptogenesis, Arch Iran Med. 2012; 15(9): 557 696 – 701. – 246. – 559. Hemolytic uremic syndrome, Arch Iran Med. 2012; Inta-aortic balloon pump, Arch Iran Med. 2012; ERCP, Arch Iran Med. 2012; 15(5): 275 – 278. 15(11): 729 – 730. 15(6): 387 – 388. Ergonomic hazards, Arch Iran Med. 2012; 15(6): Hemophilia A, Arch Iran Med. 2012; 15(2): 82 - 84. Intensive care unit, Arch Iran Med. 2012; 15(9): 568 370 – 374. Hemophilia B, Arch Iran Med. 2012; 15(2): 82 - 84. – 571. Erythropoietin, Arch Iran Med. 2012; 15(9): 553 – Hemorrhagic diathesis, Arch Iran Med. 2012; 15(5): Interaction, Arch Iran Med. 2012; 15(8): 508 – 516. 556. 303 – 305. Interferon, Arch Iran Med. 2012; 15(1): 43 – 48. Esophageal cancer, Arch Iran Med. 2012; 15(4): 196 Hemosiderosis, Arch Iran Med. 2012; 15(2): 91 - 94. Internal transcribed spacer, Arch Iran Med. 2012; – 200; 15(5): 298 – 302. Hepatitis B quality of life questionnaire version 1.0, 15(3): 151 – 156. Esophagus, Arch Iran Med. 2012; 15(1): 18 – 21. Arch Iran Med. 2012; 15(5): 290 – 297. Interview, Arch Iran Med. 2012; 15(4): 205 – 209. Estrogen receptors, Arch Iran Med. 2012; 15(6): Hepatitis B virus, Arch Iran Med. 2012; 15(2): 88 Intestines, Arch Iran Med. 2012; 15(1): 36 – 42. 366 – 369. - 90. Intracytoplasmic sperm injection (ICSI), Arch Iran E test, Arch Iran Med. 2012; 15(7): 429 – 432. Hepatitis B virus, Arch Iran Med. 2012; 15(7): 446 Med. 2012; 15(4): 228 – 231. Evaluation, Arch Iran Med. 2012; 15(2): 79 - 81; – 448. Intrauterine transfusion, Arch Iran Med. 2012; 15(7): 394 – 399. Hepatitis C virus, Arch Iran Med. 2012; 15(1): 43 15(3): 162 – 165. Factor analysis, Arch Iran Med. 2012; 15(3): 131 – – 48. Iran, Arch Iran Med. 2012; 15(1): 14 – 17. 15(1): 22 135; 15(5): 290 – 297. Hepatotoxicity, Arch Iran Med. 2012; 15(11): 674 – 26; 15(12): 741 – 746; 15(12): 747 – 750; 15(12): Faculty, Arch Iran Med. 2012; 15(2): 79 - 81. – 680. 764 – 766; 15(12): 767 – 771; 15(12): 785 – 789; Fast food, Arch Iran Med. 2012; 15(6): 346 – 351. Herpes virus 4, Arch Iran Med. 2012; 15(1): 36 – 42. 15(2): 70 - 75; 15(3): 181 – 186; 15(4): 196 – 200; Fatigue, Arch Iran Med. 2012; 15(5): 290 – 297. Heurobrucellosis, Arch Iran Med. 2012; 15(8):491 15(4): 259 – 262; 15(5): 271 – 274; 15(5): 320 – Fatty liver, Arch Iran Med. 2012; 15(7): 418 – 421. – 494. 324; 15(6): 342 – 345; 15(6): 361 – 365; 15(6): 370 Feeding dystonia, Arch Iran Med. 2012; 15(12): 780 High risk group, Arch Iran Med. 2012; 15(5): 271 – 374; 15(6): 381 – 383; 15(7): 446 – 448; 15(9): – 782. – 274. 545 – 548; 15(9): 564 – 567. Fetal anemia, Arch Iran Med. 2012; 15(3): 162 – History of medicine, Arch Iran Med. 2012; 15(12): Iron overload, kidney, Arch Iran Med. 2012; 15(2): 165. 785 – 789. 91 - 94. Fibrosarcoma, Arch Iran Med. 2012; 15(1): 59 – 62; History, Arch Iran Med. 2012; 15(3): 181 – 186. Irradiated cartilage, Arch Iran Med. 2012; 15(4): 15(8): 520 – 522. HIV/AIDS, Arch Iran Med. 2012; 15(1): 59 – 62; 235 – 238. Figula ASD closure device, Arch Iran Med. 2012; 15(12): 767 – 771. Isfahan, Arch Iran Med. 2012; 15(6): 381 – 383. 15(11): 693 – 695. Honey, Arch Iran Med. 2012; 15(11): 674 – 680. Isolated vertigo, Arch Iran Med. 2012; 15(8): 469 Fish consumption, Arch Iran Med. 2012; 15(9): 545 Hospital administration, Arch Iran Med. 2012; – 471. – 548. 15(12): 759 – 763. Itraconazole, Arch Iran Med. 2012; 15(7): 429 – Follows up, Arch Iran Med. 2012; 15(1): 32 – 35. Hospital emergency service, Arch Iran Med. 2012; 432. Foreign body, Arch Iran Med. 2012; 15(3): 177 – 15(12): 759 – 763. Jejunum, Arch Iran Med. 2012; 15(7): 433 – 438. 178. Hospital laboratories, Arch Iran Med. 2012; 15(12): Karyotyping, Arch Iran Med. 2012; 15(4): 232 – Frequency, Arch Iran Med. 2012; 15(6): 381 – 383. 759 – 763. 234. Fungal infections, Arch Iran Med. 2012; 15(7): 452 Human papillomavirus, Arch Iran Med. 2012; 15(9): Karyotyping, Arch Iran Med. 2012; 15(4): 249 – – 454. 572 – 574. 252. Gap junctions, Arch Iran Med. 2012; 15(1): 49 – 51. Human, Arch Iran Med. 2012; 15(1): 36 – 42. Kidney, Arch Iran Med. 2012; 15(2): 70 - 75. Garlic extract, Arch Iran Med. 2012; 15(2): 99 - 101. Hyaline cartilage, Arch Iran Med. 2012; 15(8): 495 Knowledge translationas, Arch Iran Med. 2012; Gastric varice, Arch Iran Med. 2012; 15(3): 157 – – 499. 15(4): 223 – 227. 161. Hydatid cyst, Arch Iran Med. 2012; 15(5): 328 – Laboratory diagnosis, Arch Iran Med. 2012; 15(1): Gastrointestinal stromal tumor, Arch Iran Med. 330. 22 – 26. 2012; 15(5): 325 – 327. Hyperechogenic bowel, Arch Iran Med. 2012; Legume intake, Arch Iran Med. 2012; 15(9): 538 – General Health Questionnaire (28), Arch Iran Med. 15(7): 449 – 451. 544. 2012; 15(4): 201 – 204. Hypertension, Arch Iran Med. 2012; 15(5): 328 – Leishmania major, Arch Iran Med. 2012; 15(3): 151 General obesity, Arch Iran Med. 2012; 15(3): 131 330. – 156.

796 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 Length of stay, Arch Iran Med. 2012; 15(12): 759 National program, Arch Iran Med. 2012; 15(5): 320 Prevalence, Arch Iran Med. 2012; 15(12): 764 – – 763. – 324. 766; 15(3): 142 – 145; 15(4): 205 – 209; 15(5): 271 Lipopolysaccharide, Arch Iran Med. 2012; 15(9): N-butyl-2-cyanoacrylate, Arch Iran Med. 2012; – 274. 557 – 559. 15(3): 157 – 161. Primary prevention, Arch Iran Med. 2012; 15(9): Liver cirrhosis, Arch Iran Med. 2012; 15(6): 375 – Neonatal screening, Arch Iran Med. 2012; 15(3): 531 – 537. 377. 136 – 141. Progesterone receptors, Arch Iran Med. 2012; 15(6): Liver lesion, Arch Iran Med. 2012; 15(4):247 – 248. Neonate, Arch Iran Med. 2012; 15(9): 568 – 571. 366 – 369. Liver Metastasis, Arch Iran Med. 2012; 15(11): 726 Nephelometry, Arch Iran Med. 2012; 15(2): 70 - 75. Prognosis, Arch Iran Med. 2012; 15(11): 707 – 712. – 728. Nephrolithiasis, Arch Iran Med. 2012; 15(4):247 – Program, Arch Iran Med. 2012; 15(2): 79 - 81. Liver transplant, Arch Iran Med. 2012; 15(6): 375 248. Proinflammatory,Arch Iran Med. 2012; 15(11): 688 – 377. Nested PCR, Arch Iran Med. 2012; 15(7): 446 – 448. – 692. Liver transplantation, Arch Iran Med. 2012; 15(12): Neurobrucellosis, Arch Iran Med. 2012; 15(11): 723 Pseudomonas aeruginosa, Arch Iran Med. 2012; 772 – 776. – 725. 15(11): 670 – 673. Lymphoma, Arch Iran Med. 2012; 15(1): 36 – 42. Nicotine, Arch Iran Med. 2012; 15(5): 283 – 289. Psychiatry, Arch Iran Med. 2012; 15(4): 210 – 213. Magnesium, Arch Iran Med. 2012; 15(5): 306 – 311. Nitric oxide, Arch Iran Med. 2012; 15(7): 404 – Psychosis, Arch Iran Med. 2012; 15(11): 723 – 725. Magnetic resonance imaging, Arch Iran Med. 2012; 408. Public health, Arch Iran Med. 2012; 15(12): 785 – 15(2): 91 - 94. NMDA, Arch Iran Med. 2012; 15(7): 404 – 408. 789. Male, Arch Iran Med. 2012; 15(12): 751 – 755. NMNE, Arch Iran Med. 2012; 15(11): 702 – 706. Pulmonary tuberculosis, Arch Iran Med. 2012; Mass casualty incidents, Arch Iran Med. 2012; Nomads, Arch Iran Med. 2012; 15(12): 747 – 750. 15(1): 22 – 26. 15(5): 317 – 319. Non-antifungals, Arch Iran Med. 2012; 15(1): 27 – QTc, Arch Iran Med. 2012; 15(6): 375 – 377. Maternal mortality, Arch Iran Med. 2012; 15(1): 14 31. QTd, Arch Iran Med. 2012; 15(6): 375 – 377. – 17. Non-communicable diseases, Arch Iran Med. 2012; Qualitative research, Arch Iran Med. 2012; 15(12): Maternal mortality, Arch Iran Med. 2012; 15(1): 4 15(5): 320 – 324. 767 – 771. – 7. Non-Hodgkin’s lymphoma, Arch Iran Med. 2012; Quality of life, Arch Iran Med. 2012; 15(12): 747 – Maxilla, Arch Iran Med. 2012; 15(1): 59 – 62. 15(8): 520 – 522. 750; 15(4): 214 – 218. Meckel’s diverticulum, Arch Iran Med. 2012; 15(5): Normal LK cells, Arch Iran Med. 2012; 15(11): 696 Quality-adjusted life years, Arch Iran Med. 2012; 325 – 327. – 701. 15(3): 136 – 141. Mediator, Arch Iran Med. 2012; 15(8): 508 – 516. Nosocomial infections, Arch Iran Med. 2012; Questionnaire, Arch Iran Med. 2012; 15(5): 279 – Medical specialties, Arch Iran Med. 2012; 15(12): 15(12): 764 – 766. 282. 756 – 758. NSCLC, Arch Iran Med. 2012; 15(11): 707 – 712. Rabies, Arch Iran Med. 2012; 15(6): 356 – 360. Medpor, Arch Iran Med. 2012; 15(4): 235 – 238. Ophthalmia neonatorum, Arch Iran Med. 2012; Radioactive iodine, Arch Iran Med. 2012; 15(8): Melamine, Arch Iran Med. 2012; 15(4):247 – 248. 15(3): 171 – 175. 477 – 484. Mental disorders, Arch Iran Med. 2012; 15(4): 205 Oral lesions, Arch Iran Med. 2012; 15(3): 142 – 145. Radiotherapy, Arch Iran Med. 2012; 15(4): 214 – – 209. Oral microorganism, Arch Iran Med. 2012; 15(2): 218. Mental health situation, Arch Iran Med. 2012; 15(4): 99 - 101. RAM, Arch Iran Med. 2012; 15(1): 8 – 13. 201 – 204. Oral mucositis, Arch Iran Med. 2012; 15(7): 413 – Randomization, Arch Iran Med. 2012; 15(8): 508 – Mentorship, Arch Iran Med. 2012; 15(4): 259 – 262. 417. 516. Mesenchymal stem cells, Arch Iran Med. 2012; Osteoarthritis, Arch Iran Med. 2012; 15(7): 422 – Randomized trial, Arch Iran Med. 2012; 15(11): 664 15(7): 422 – 428; 15(8): 495 – 499. 428; 15(8): 495 – 499. – 669. Metabolic syndrome, Arch Iran Med. 2012; 15(8): Osteoid osteoma, Arch Iran Med. 2012; 15(12): 777 Rat, Arch Iran Med. 2012; 15(9): 553 – 556. 462 – 468; 15(9): 538 – 544. – 779. Rate, Arch Iran Med. 2012; 15(9): 568 – 571. Metacarpal, Arch Iran Med. 2012; 15(12): 777 – Osteoporosis, Arch Iran Med. 2012; 15(2): 82 - 84. Real-time PCR, Arch Iran Med. 2012; 15(6): 352 – 779. Outcomes, Arch Iran Med. 2012; 15(12): 772 – 776. 355. Metallo-beta-lactamases, Arch Iran Med. 2012; Outpatient care, Arch Iran Med. 2012; 15(12): 756 Reconstruction, Arch Iran Med. 2012; 15(4): 219 – 15(11): 670 – 673. – 758. 222. Methimazole, Arch Iran Med. 2012; 15(8): 477 – Paracetamol, Arch Iran Med. 2012; 15(11): 674 – Regression, Arch Iran Med. 2012; 15(8): 508 – 516. 484. 680. Reliability, Arch Iran Med. 2012; 15(5): 279 – 282; Micro-angiopathic hemolytic anemia, Arch Iran Paraoxonase, Arch Iran Med. 2012; 15(9): 549 – 15(5): 290 – 297. Med. 2012; 15(11): 729 – 730. 552. Research, Arch Iran Med. 2012; 15(7): 394 – 399. Middle cerebral artery, Arch Iran Med. 2012; 15(3): Pathology, Arch Iran Med. 2012; 15(7): 418 – 421. Resting metabolism, Arch Iran Med. 2012; 15(11): 162 – 165. PC12 cells, Arch Iran Med. 2012; 15(7): 404 – 408. 681 – 687. Midwifery, Arch Iran Med. 2012; 15(1): 4 – 7. PCR, Arch Iran Med. 2012; 15(3): 171 – 175. Results, Arch Iran Med. 2012; 15(12): 772 – 776. Migrating motor complexes (MMCs), Arch Iran Percutaneous ASD closure, Arch Iran Med. 2012; RFLP, Arch Iran Med. 2012; 15(3): 151 – 156. Med. 2012; 15(7): 433 – 438. 15(11): 693 – 695. Rheumatoid, Arch Iran Med. 2012; 15(9): 549 – Mild, Arch Iran Med. 2012; 15(9): 583 – 584. Persian, Arch Iran Med. 2012; 15(5): 279 – 282. 552. MMT, Arch Iran Med. 2012; 15(12): 751 – 755. Physical activity, Arch Iran Med. 2012; 15(5): 279 Rhinoplasty, Arch Iran Med. 2012; 15(4): 235 – 238. MNE, Arch Iran Med. 2012; 15(11): 702 – 706. – 282. Risk factors, Arch Iran Med. 2012; 15(9): 531 – 537; Modified radical mastectomy,Arch Iran Med. 2012; Physicians, Arch Iran Med. 2012; 15(6): 370 – 374. 15(9): 560 – 563; 15(9): 568 – 571. 15(8): 504 – 507. Pittsburgh Sleep Quality Index (PSQI), Arch Iran Risk modeling, Arch Iran Med. 2012; 15(1): 18 – 21. Morphine, Arch Iran Med. 2012; 15(7): 404 – 408. Med. 2012; 15(2): 95 - 98. Robot, Arch Iran Med. 2012; 15(8): 488 – 490. Mortality, Arch Iran Med. 2012; 15(12): 741 – 746. Plasmacytoma, Arch Iran Med. 2012; 15(8): 517 – Saddle nose, Arch Iran Med. 2012; 15(4): 235 – 238. Mouse, Arch Iran Med. 2012; 15(7): 433 – 438. 519. Saliva flow,Arch Iran Med. 2012; 15(4): 214 – 218. Mouth, Arch Iran Med. 2012; 15(3): 142 – 145. Plasmid, Arch Iran Med. 2012; 15(5): 312 – 316. Saliva, Arch Iran Med. 2012; 15(2): 99 - 101. MTT assay, Arch Iran Med. 2012; 15(11): 696 – 701. Pneumococcal vaccine, Arch Iran Med. 2012; 15(8): Salt reduction, Arch Iran Med. 2012; 15(5): 320 – Multi Institutional Systems, Arch Iran Med. 2012; 500 – 503. 324. 15(12): 736 – 740. Poisoning, Arch Iran Med. 2012; 15(4): 210 – 213. School of medicine, Arch Iran Med. 2012; 15(4): Musculoskeletal diseases, Arch Iran Med. 2012; Polycystic kidney disease, Arch Iran Med. 2012; 259 – 262. 15(6): 370 – 374. 15(6): 384 – 386. Secondary amenorrhea, Arch Iran Med. 2012; 15(4): Mycosis fungoides, Arch Iran Med. 2012; 15(3): Polypill, Arch Iran Med. 2012; 15(9): 531 – 537. 232 – 234. 146 – 150. PPIP-PCR, Arch Iran Med. 2012; 15(3): 151 – 156. Secundum atrial septal defect, Arch Iran Med. 2012; Myeloma, Arch Iran Med. 2012; 15(8): 517 – 519. Precancerous lesions, Arch Iran Med. 2012; 15(11): 15(11): 693 – 695. Myocardial infarction, Arch Iran Med. 2012; 15(1): 664 – 669. Sedation, Arch Iran Med. 2012; 15(6): 387 – 388. 32 – 35. Prediction, Arch Iran Med. 2012; 15(9): 545 – 548. Sequencing, Arch Iran Med. 2012; 15(2): 88 - 90. Nasopharyngeal carrier, Arch Iran Med. 2012; Prenatal asphyxia, Arch Iran Med. 2012; 15(11): Serological screening, Arch Iran Med. 2012; 15(6): 15(8): 500 – 503. 729 – 730. 342 – 345.

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 797 Seroprevalence, Arch Iran Med. 2012; 15(5): 271 – 736 – 740. 384 – 386. 274. t(6;16), Arch Iran Med. 2012; 15(4): 249 – 252. Tumorigenesis, Arch Iran Med. 2012; 15(3): 166 – Serotype, streptococcus pneumonia, Arch Iran Med. t(8;11), Arch Iran Med. 2012; 15(4): 249 – 252. 170. 2012; 15(8): 500 – 503. Tehran Lipid and Glucose Study, Arch Iran Med. UBE2Q2, Arch Iran Med. 2012; 15(6): 352 – 355. Severe thrombocytopenia, Arch Iran Med. 2012; 2012; 15(6): 346 – 351. Ubiquitin conjugating enzyme, Arch Iran Med. 15(5): 303 – 305. Tehran, Arch Iran Med. 2012; 15(4): 201 – 204. 2012; 15(6): 352 – 355. Sexual dysfunction, Arch Iran Med. 2012; 15(12): Tehran, Arch Iran Med. 2012; 15(5): 283 – 289. Ultrasonography, Arch Iran Med. 2012; 15(4):247 751 – 755. Thalassemia, Arch Iran Med. 2012; 15(2): 91 - 94. – 248. Silymarin, Arch Iran Med. 2012; 15(11): 674 – 680. Theory of planned behavior, Arch Iran Med. 2012; Urological abnormalities, Arch Iran Med. 2012; Skin flap survival, Arch Iran Med. 2012; 15(9): 553 15(9): 545 – 548. 15(11): 702 – 706. – 556. Therapy, Arch Iran Med. 2012; 15(2): 85 - 87. UTI, Arch Iran Med. 2012; 15(5): 312 – 316. Skin manifestations, Arch Iran Med. 2012; 15(1): Thiamine, Arch Iran Med. 2012; 15(5): 306 – 311. Vaccination, Arch Iran Med. 2012; 15(6): 356 – 360. 43 – 48. Third never palsy, Arch Iran Med. 2012; 15(9): 583 Validity, Arch Iran Med. 2012; 15(5): 279 – 282; Sleep disorders, Arch Iran Med. 2012; 15(2): 95 - – 584. 15(5): 290 – 297. 98. Thyroid function, Arch Iran Med. 2012; 15(7): 400 Ventilator-associated pneumonia, Arch Iran Med. Smoking, Arch Iran Med. 2012; 15(7): 400 – 403. – 403. 2012; 15(9): 568 – 571. Sociodemographic factors, Arch Iran Med. 2012; Thyroidectomy, Arch Iran Med. 2012; 15(8): 488 – Virulence genes, Arch Iran Med. 2012; 15(5): 312 15(11): 681 – 687. 490. – 316. Solitary rib tumor, Arch Iran Med. 2012; 15(8): 517 Thyrotropin, Arch Iran Med. 2012; 15(3): 136 – 141. Voriconazole, Arch Iran Med. 2012; 15(7): 429 – – 519. Thyrotropine, Arch Iran Med. 2012; 15(7): 400 – 432. Soy foods, Arch Iran Med. 2012; 15(8): 462 – 468. 403. Waiting list, Arch Iran Med. 2012; 15(12): 756 – Spinal tuberculosis, Arch Iran Med. 2012; 15(4): Toothbrush, Arch Iran Med. 2012; 15(3): 177 – 178. 758. 253 – 256. Tourette’s syndrome, Arch Iran Med. 2012; 15(2): Xerostomia, Arch Iran Med. 2012; 15(4): 214 – 218. Sporadic colorectal cancer, Arch Iran Med. 2012; 76 - 78. X-linked intellectual disability, Arch Iran Med. 15(3): 166 – 170. Transplantation, Arch Iran Med. 2012; 15(1): 32 – 2012; 15(6): 361 – 365. Squamous cell carcinoma, Arch Iran Med. 2012; 35. Youth, Arch Iran Med. 2012; 15(4): 210 – 213. 15(1): 18 – 21. Trapezoid, Arch Iran Med. 2012; 15(12): 777 – 779. Zinc sulfate, Arch Iran Med. 2012; 15(7): 413 – 417. Squamous cell carcinoma, Arch Iran Med. 2012; Treatment, Arch Iran Med. 2012; 15(3): 157 – 161. Zinc supplementation, Arch Iran Med. 2012; 15(8): 15(5): 298 – 302. Treatment, Arch Iran Med. 2012; 15(5): 283 – 289. 472 – 476. Squamous dysplasia, Arch Iran Med. 2012; 15(1): Treatment, Arch Iran Med. 2012; 15(8):491 – 494. Zinc, Arch Iran Med. 2012; 15(5): 306 – 311. 18 – 21. Trends of change, Arch Iran Med. 2012; 15(4): 201 α-globin chain variants, Arch Iran Med. 2012; 15(9): Stomach, Arch Iran Med. 2012; 15(12): 741 – 746. – 204. 564 – 567. Subjective sleep quality, Arch Iran Med. 2012; TRPV1, Arch Iran Med. 2012; 15(7): 433 – 438. α-thalassemia, Arch Iran Med. 2012; 15(9): 564 – 15(2): 95 - 98. Trunk flexion, Arch Iran Med. 2012; 15(12): 780 – 567. Suicide, Arch Iran Med. 2012; 15(4): 210 – 213. 782. β-cell number, Arch Iran Med. 2012; 15(4): 239 – Survival, Arch Iran Med. 2012; 15(11): 726 – 728. Tuberculosis, Arch Iran Med. 2012; 15(3): 128 – 246. System, Arch Iran Med. 2012; 15(7): 394 – 399. 130. Systems Integration, Arch Iran Med. 2012; 15(12): Tuberous sclerosis, Arch Iran Med. 2012; 15(6):

798 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 Author Index to Volume 15

Aarabi Mohsen, Arch Iran Med. 2012; 15(4): 196 Alatab Sudabeh, Arch Iran Med. 2012; 15(2): 70 – Baghaban Eslaminejad Mohamadreza, Arch Iran – 200. 75. Med. 2012; 15(7): 422 – 428. Abbaszadegan Mohammad R., Arch Iran Med. Alavian Seyed Moayed, Arch Iran Med. 2012; Baghaie Mehdi, Arch Iran Med. 2012; 15(3): 151 – 2012; 15(4): 249 – 252. 15(3): 189 – 192. 156. Abdi Salman, Arch Iran Med. 2012; 15(2): 76 – 78; Alavi-Naini Roya, Arch Iran Med. 2012; 15(1): 22 Baghbanian Mahmud, Arch Iran Med. 2012; 15(9): 15(9): 560 – 563. – 26. 585 – 586. Abdi Seifollah, Arch Iran Med. 2012; 15(11): 693 Alborzi Abdolvahab, Arch Iran Med. 2012; 15(7): Bagheri Lankarani Kamran, Arch Iran Med. 2012; – 695. 429 – 432. 15(1): 14 – 17; 15(1): 55 – 58. Abdinia Babak, Arch Iran Med. 2012; 15(8): 500 – Alinejad Halimeh, Arch Iran Med. 2012; 15(3): 142 Bagheri Yazdi Seyed Abas, Arch Iran Med. 2012; 503. – 145. 15(4): 201 – 204. Abdolrahimi SafarAli, Arch Iran Med. 2012; 15(11): Alizadeh Ghavidel Alireza, Arch Iran Med. 2012; Baghianimoghadam Behnam, Arch Iran Med. 2012; 693 – 695. 15(2): 113 - 114. 15(12): 792 – 794. Abedi Mahboobeh, Arch Iran Med. 2012; 15(11): Aloosh Mehdi, Arch Iran Med. 2012; 15(8): 469 – Baghianimoghadam Mohammad Hosein, Arch Iran 731 – 732. 471. Med. 2012; 15(12): 792 – 794. Abedini Seyed Sedigheh, Arch Iran Med. 2012; Amani Davar, Arch Iran Med. 2012; 15(9): 572 – Bahador Maryam, Arch Iran Med. 2012; 15(4): 214 15(6): 361 – 365. 574. – 218. Abnet Christian C., Arch Iran Med. 2012; 15(1): Amini Massoud, Arch Iran Med. 2012; 15(3): 131 – Bahadoran Zahra, Arch Iran Med. 2012; 15(6): 346 18 – 21. 135; 15(9): 560 – 563. – 351. Abtahi Seyed-Hossein, Arch Iran Med. 2012; 15(6): Aminpour Farzaneh, Arch Iran Med. 2012; 15(12): Bahadori Moslem, Arch Iran Med. 2012; 15(3): 181 381 – 383. 792 – 794. – 186. Acar Murat, Arch Iran Med. 2012; 15(6): 384 – 386. Amiri Shahrokh, Arch Iran Med. 2012; 15(2): 76 – Baharvand Hossein, Arch Iran Med. 2012; 15(1): Adabi Khadijeh, Arch Iran Med. 2012; 15(3): 162 78; 15(9): 560 – 563. 32 – 35. – 165. Amiri Zohreh, Arch Iran Med. 2012; 15(9): 538 – Bahrainian Abdolmajid, Arch Iran Med. 2012; Aeenparast Afsoon, Arch Iran Med. 2012; 15(12): 544. 15(8): 477 – 484. 756 – 758. Amouzegar Atieh, Arch Iran Med. 2012; 15(7): 400 Bahreini Elham, Arch Iran Med. 2012; 15(9): 549 Afjeh Seyyed Abolfazl, Arch Iran Med. 2012; 15(9): – 403. – 552. 568 – 571; 15(3): 171 – 175. Anbara Taha, Arch Iran Med. 2012; 15(4): 257 – Bakhtiary Afsaneh, Arch Iran Med. 2012; 15(8): Afshar Ahmadreza, Arch Iran Med. 2012; 15(5): 258. 462 – 468. 317 – 319. Angadi Punnya V., Arch Iran Med. 2012; 15(1): 59 Banihashemi Sussan, Arch Iran Med. 2012; 15(6): Afshinmajd Siamak, Arch Iran Med. 2012; 15(4): – 62. 361 – 365. 205 – 209. Ansari Moghaddam Alireza, Arch Iran Med. 2012; Baradaran Eftekhari Monir, Arch Iran Med. 2012; Aggarwal Sourabh, Arch Iran Med. 2012; 15(2): 15(7): 413 – 417. 15(7): 394 – 399. 115 - 116. Anvarinejad Mojtaba, Arch Iran Med. 2012; 15(5): Baran Ali İrfan, Arch Iran Med. 2012; 15(5): 303 – Agha Azza M., Arch Iran Med. 2012; 15(11): 674 312 – 316. 305. – 680. Arasteh Majid, Arch Iran Med. 2012; 15(2): 82 - 84. Barghi Mohammad Reza, Arch Iran Med. 2012; Aghajanzadeh Manouchehr, Arch Iran Med. 2012; Arbabi-kalati Farshid, Arch Iran Med. 2012; 15(7): 15(9): 572 – 574. 15(3): 179 – 180. 413 – 417. Barkhordari Khosro, Arch Iran Med. 2012; 15(6): Aghamolaei Teamur, Arch Iran Med. 2012; 15(9): Arbabi-kalati Fateme, Arch Iran Med. 2012; 15(7): 387 – 388. 545 – 548. 413 – 417. Basiri HosseinAli, Arch Iran Med. 2012; 15(11): Aghasadeghi Kamran, Arch Iran Med. 2012; 15(6): Argani Hassan, Arch Iran Med. 2012; 15(9): 549 – 693 – 695. 375 – 377. 552. Bazvand Fatemeh, Arch Iran Med. 2012; 15(12): Aghdami Naser, Arch Iran Med. 2012; 15(7): 422 Asghari Alimohamad, Arch Iran Med. 2012; 15(2): 783 – 784. – 428. 95 - 98. Behjati Farkhondeh, Arch Iran Med. 2012; 15(6): Aghdami Nasser, Arch Iran Med. 2012; 15(1): 32 Ashrafi Mandana, Arch Iran Med. 2012; 15(5): 290 361 – 365. – 35. – 297. Bhardwaj Naveen, Arch Iran Med. 2012; 15(2): 115 Ahmad Zaiton, Arch Iran Med. 2012; 15(8): 462 – Atay Ahmet Engin, Arch Iran Med. 2012; 15(6): - 116. 468. 384 – 386. Bhatt Pooja, Arch Iran Med. 2012; 15(1): 59 – 62. Ahmadi Amin, Arch Iran Med. 2012; 15(9): 557 – Atri Morteza, Arch Iran Med. 2012; 15(6): 366 – Binici İrfan, Arch Iran Med. 2012; 15(5): 303 – 305. 559. 369. Birang Shirin, Arch Iran Med. 2012; 15(4): 210 – Ahmadi Ebrahim, Arch Iran Med. 2012; 15(4): 228 Attaranzadeh Armin, Arch Iran Med. 2012; 15(4): 213. – 231. 232 – 234. Bishehsari Faraz, Arch Iran Med. 2012; 15(3): 166 Ahmadi Hossein, Arch Iran Med. 2012; 15(1): 32 – Aykut Ayca, Arch Iran Med. 2012; 15(7): 449 – 451. – 170. 35; 15(9): 553 – 556. Azad Fariborz, Arch Iran Med. 2012; 15(4): 232 – Bojdi Amin, Arch Iran Med. 2012; 15(11): 723 – Ahmadvand Afshin, Arch Iran Med. 2012; 15(4): 234. 725. 205 – 209. Azadbakht Leila, Arch Iran Med. 2012; 15(6): 340 – Bordbar Mohammad-Reza, Arch Iran Med. 2012; Ahmadvand Alireza, Arch Iran Med. 2012; 15(12): 341; 15(8): 460 – 461. 15(6): 352 – 355. 736 – 740. Azarkeivan Azita, Arch Iran Med. 2012; 15(2): 91 Borghei Mojgansadat, Arch Iran Med. 2012; 15(9): Akbari Mohammad Taghi, Arch Iran Med. 2012; - 94. 572 – 574. 15(9): 564 – 567. Azizi Fereidoun, Arch Iran Med. 2012; 15(3): 189 – Borhan-Mojabi Katayoun, Arch Iran Med. 2012; Akbarian Abdorrasoul, Arch Iran Med. 2012; 15(1): 192;15(5): 279 – 282; 15(6): 346 – 351; 15(7): 400 15(2): 99 - 101. 2 – 3; 15(3): 189 – 192. – 403; 15(8): 477 – 484; 15(9): 538 – 544. Boroumand Mohammad Ali, Arch Iran Med. 2012; Akbarzadeh Elahe, Arch Iran Med. 2012; 15(6): 389 Azizi Mohammad Hossein, Arch Iran Med. 2012; 15(11): 670 – 673; 15(9): 553 – 556. – 390. 15(11): 733 – 734; 15(3): 181 – 186; 15(4): 259 – Bozorg-Ghalati Farzaneh, Arch Iran Med. 2012; Akbas Halit, Arch Iran Med. 2012; 15(6): 384 – 386. 262. 15(6): 352 – 355. Akercan Fuat, Arch Iran Med. 2012; 15(7): 449 – Babakhanian Masaudeh, Arch Iran Med. 2012; Broumand Behrooz, Arch Iran Med. 2012; 15(2): 451. 15(12): 751 – 755. 70 - 75. Akhlaghi Zhamak, Arch Iran Med. 2012; 15(9): 557 Badakhsh Mohammad Hossein, Arch Iran Med. Chapman Jeremy, Arch Iran Med. 2012; 15(2): 102 – 559. 2012; 15(1): 4 – 7. - 106. Akhlaghpoor Shahram, Arch Iran Med. 2012; 15(2): Bader Benedikt, Arch Iran Med. 2012; 15(12): 780 Chenari Nooshafarin, Arch Iran Med. 2012; 15(8): 91 - 94. – 782. 495 – 499. Alam Mehrjerdi Zahra, Arch Iran Med. 2012; Badiee Parisa, Arch Iran Med. 2012; 15(7): 429 – Cuevas Luis E., Arch Iran Med. 2012; 15(1): 22 – 15(12): 751 – 755. 432. 26.

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 799 Cui Dejun, Arch Iran Med. 2012; 15(1): 36 – 42. 381 – 383. Ghanbarian Arash, Arch Iran Med. 2012; 15(5): 279 Dabirzadeh Mansour, Arch Iran Med. 2012; 15(3): Faghih Zahra, Arch Iran Med. 2012; 15(8): 495 – 499. – 282. 151 – 156. Fahimi Fanak, Arch Iran Med. 2012; 15(2): 85 - 87. Ghanei Mostafa, Arch Iran Med. 2012; 15(7): 394 – Dalir Mojtaba, Arch Iran Med. 2012; 15(5): 290 – Fahimi Hossein, Arch Iran Med. 2012; 15(5): 298 – 399. 297. 302. Gharebaghiyan Ahmad, Arch Iran Med. 2012; 15(2): Danaei Goodarz, Arch Iran Med. 2012; 15(9): 531 – Fahimi Saman, Arch Iran Med. 2012; 15(2): 110 – 88 - 90. 537. 112; 15(5): 320 – 324. Gharib Atousa, Arch Iran Med. 2012; 15(7): 455 – Danek Adrian, Arch Iran Med. 2012; 15(12): 780 – Fakhari Ali, Arch Iran Med. 2012; 15(2): 76 - 78. 456. 782. Falah Masoumeh, Arch Iran Med. 2012; 15(1): 49 – Ghasemi Firoozabadi Saghar, Arch Iran Med. 2012; Dastgardy Ebrahim, Arch Iran Med. 2012; 15(3): 162 51. 15(6): 361 – 365. – 165. Falahat Katayoun, Arch Iran Med. 2012; 15(7): 394 Ghavami Yaser, Arch Iran Med. 2012; 15(1): 49 – 51. Davoudikia Ali-Asghar, Arch Iran Med. 2012; 15(1): – 399. Ghazaey Saeedeh, Arch Iran Med. 2012; 15(4): 249 22 – 26. Fallah Fatemeh, Arch Iran Med. 2012; 15(3): 171 – – 252. Dawsey Sanford M., Arch Iran Med. 2012; 15(1): 175. Gholami Kheirollah, Arch Iran Med. 2012; 15(7): 18 – 21. Fallah Rastegar Yalda, Arch Iran Med. 2012; 15(11): 409 – 412. Dawsey Sanford M., Arch Iran Med. 2012; 15(11): 731 – 732. Gholami Roya, Arch Iran Med. 2012; 15(1): 4 – 7. 713 – 722. Fallahi Amin, Arch Iran Med. 2012; 15(6): 356 – 360. Gholipour Mohammad Ali, Arch Iran Med. 2012; Dawsey Sanford M., Arch Iran Med. 2012; 15(2): Fallahi Homeira, Arch Iran Med. 2012; 15(12): 767 15(8): 495 – 499. 118 - 119. – 771. Ghorbanihaghjo Amir, Arch Iran Med. 2012; 15(9): Deghatipour Marzie, Arch Iran Med. 2012; 15(7): Fallahpour Morteza, Arch Iran Med. 2012; 15(11): 549 – 552. 413 – 417. 729 – 730. Ghoreishi Fatemeh Sadat, Arch Iran Med. 2012; Dehghan Padideh, Arch Iran Med. 2012; 15(3): 162 Farahmand Fatemeh, Arch Iran Med. 2012; 15(6): 15(4): 205 – 209. – 165. 342 – 345. Ghotb Sayeh, Arch Iran Med. 2012; 15(6): 342 – 345. Dehghanian Amirreza, Arch Iran Med. 2012; 15(8): Farajnia Safar, Arch Iran Med. 2012; 15(7): 446 – Golmirzaei Javad, Arch Iran Med. 2012; 15(2): 76 - 523 – 524. 448. 78. Dehnadi Moghadam Anoush, Arch Iran Med. 2012; Fararouei Mohammad, Arch Iran Med. 2012; 15(5): Golozar Asieh, Arch Iran Med. 2012; 15(1): 18 – 21. 15(3): 179 – 180. 271 – 274. Golzarand Mahdieh, Arch Iran Med. 2012; 15(6): Delphi Ladan, Arch Iran Med. 2012; 15(7): 404 – Fareed Eman, Arch Iran Med. 2012; 15(8): 485 – 487. 346 – 351. 408. Farhadi Mohammad, Arch Iran Med. 2012; 15(1): 49 Goni Vijay, Arch Iran Med. 2012; 15(4): 253 – 256. Delshad Hossein, Arch Iran Med. 2012; 15(7): 400 – 51; 15(2): 95 - 98. Gopinathan Nirmal Raj, Arch Iran Med. 2012; 15(4): – 403. Farjad Reza, Arch Iran Med. 2012; 15(7): 422 – 428. 253 – 256. Delshad Maryam, Arch Iran Med. 2012; 15(5): 279 Farrokh Donya, Arch Iran Med. 2012; 15(11): 731 – Habibi Ehsan, Arch Iran Med. 2012; 15(11): 670 – – 282. 732. 673. Demirtas Gülsah Selvi, Arch Iran Med. 2012; 15(7): Farrokhi Babak, Arch Iran Med. 2012; 15(9): 572 – Habibi Elham, Arch Iran Med. 2012; 15(7): 394 – 449 – 451. 574. 399. Derakhshan Mohammad H., Arch Iran Med. 2012; Farshad Shohreh, Arch Iran Med. 2012; 15(5): 312 – Habibi Zohreh, Arch Iran Med. 2012; 15(7): 452 – 15(11): 662 – 663. 316; 15(7): 429 – 432. 454. Djalalinia Shirin, Arch Iran Med. 2012; 15(7): 394 Farzadfar Farshad, Arch Iran Med. 2012; 15(9): 531 Haddadi Pedram, Arch Iran Med. 2012; 15(7): 429 – 399. – 537. – 432. Dousti Samaneh, Arch Iran Med. 2012; 15(7): 409 Farzadi Faranak, Arch Iran Med. 2012; 15(12): 756 Hadi Negin, Arch Iran Med. 2012; 15(8): 504 – 507. – 412. – 758. Hadjibabaie Molouk, Arch Iran Med. 2012; 15(7): Du Peng-Fei, Arch Iran Med. 2012; 15(4): 247 – 248. Fayazzadeh Ehsan, Arch Iran Med. 2012; 15(9): 553 409 – 412. Duygu Fazilet, Arch Iran Med. 2012; 15(5): 303 – – 556. Hafezi Mohsen, Arch Iran Med. 2012; 15(4): 201 – 305. Fazel Iraj, Arch Iran Med. 2012; 15(11): 726 – 728. 204. Duygu Fazilet, Arch Iran Med. 2012; 15(8):491 – Fazeli Roghayeh, Arch Iran Med. 2012; 15(1): 32 – Hafizi Ali,Arch Iran Med. 2012; 15(11): 729 – 730. 494. 35; 15(7): 422 – 428. Haghdoost Ali Akbar, Arch Iran Med. 2012; 15(3): Ebrahimi Sedigheh, Arch Iran Med. 2012; 15(2): 79 Fener Neslihan, Arch Iran Med. 2012; 15(8): 520 – 136 – 141. - 81. 522. Haghdoost Ali-Akbar, Arch Iran Med. 2012; 15(4): Eftekhar Ardebili Hasan, Arch Iran Med. 2012; Firoozi Ata, Arch Iran Med. 2012; 15(11): 693 – 695. 214 – 218. 15(1): 8 – 13. Firozi Iraj, Arch Iran Med. 2012; 15(11): 693 – 695. Haghollai Fedyeh, Arch Iran Med. 2012; 15(1): 8 – Eftekhari Ali, Arch Iran Med. 2012; 15(5): 317 – 319. Foroumadi Alireza, Arch Iran Med. 2012; 15(1): 27 13. Eilami Owrang, Arch Iran Med. 2012; 15(5): 271 – – 31. Hajhossein Talasaz Azita, Arch Iran Med. 2012; 274. Forouzanfar Mohammad Hossein, Arch Iran Med. 15(2): 85 - 87. Emadedin Mohsen, Arch Iran Med. 2012; 15(7): 422 2012; 15(3): 136 – 141. Hajialilo Mehrzad, Arch Iran Med. 2012; 15(9): 549 – 428. Fouladgar Atoosa, Arch Iran Med. 2012; 15(11): 729 – 552. Emamdjomeh Hessamaldin, Arch Iran Med. 2012; – 730. Hajizadeh Ebrahim, Arch Iran Med. 2012; 15(12): 15(1): 49 – 51. Fouroghi Maryam, Arch Iran Med. 2012; 15(12): 767 767 – 771. Emami Habib, Arch Iran Med. 2012; 15(5): 283 – – 771. Haj-Sheykholeslami Arghavan, Arch Iran Med. 289. Galal Reem M., Arch Iran Med. 2012; 15(11): 674 2012; 15(11): 664 – 669. Entezari-Maleki Taher, Arch Iran Med. 2012; 15(7): – 680. Hajyhosseinloo Majid, Arch Iran Med. 2012; 15(5): 409 – 412. Garcia Garcia Guillermo, Arch Iran Med. 2012; 317 – 319. Eshraghian Ahad, Arch Iran Med. 2012; 15(3): 157 15(2): 102 - 106. Hakemi Monirossadat, Arch Iran Med. 2012; 15(2): – 161. Gerami Hoshang, Arch Iran Med. 2012; 15(3): 179 70 - 75. Eshrati Babak, Arch Iran Med. 2012; 15(12): 764 – – 180. Hallikeremath Seema R., Arch Iran Med. 2012; 766. Geramizadeh Bita, Arch Iran Med. 2012; 15(3): 189 15(1): 59 – 62. Esmaeilzadeh Majid, Arch Iran Med. 2012; 15(5): – 192; 15(6): 389 – 390; 15(8): 523 – 524. Hamid Mohammad, Arch Iran Med. 2012; 15(9): 275 – 278. Geranmayeh Siamak, Arch Iran Med. 2012; 15(3): 564 – 567. Esmaillzadeh Ahmad, Arch Iran Med. 2012; 15(3): 179 – 180. Hamidpour Laleh, Arch Iran Med. 2012; 15(3): 157 131 – 135; 15(6): 340 – 341; 15(8): 460 – 461. Ghabeli Juibary Ali, Arch Iran Med. 2012; 15(1): 52 – 161. Estakhri Arezoo, Arch Iran Med. 2012; 15(11): 726 – – 54. Hamzehloo Gholamreza, Arch Iran Med. 2012; 728; 15(5): 290 – 297. Ghaderi Abbas, Arch Iran Med. 2012; 15(8): 495 – 15(3): 136 – 141. Etebary Sahabeh, Arch Iran Med. 2012; 15(5): 306 499. Hanachi Parichehr, Arch Iran Med. 2012; 15(8): 462 – 311. Ghafouri Ali, Arch Iran Med. 2012; 15(5): 275 – 278. – 468. Etemadi Arash, Arch Iran Med. 2012; 15(1): 18 – 21. Ghalehbaghi Babak, Arch Iran Med. 2012; 15(2): Hantooshzadeh Sedigheh, Arch Iran Med. 2012; Etemadifar Masoud, Arch Iran Med. 2012; 15(6): 95 - 98. 15(1): 8 – 13.

800 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 Harden Paul, Arch Iran Med. 2012; 15(2): 102 - 106. Jalili Mohammad, Arch Iran Med. 2012; 15(12): 759 Kolahi Sousan, Arch Iran Med. 2012; 15(9): 549 – Hashemi Taheri Amirpejman, Arch Iran Med. 2012; – 763. 552. 15(3): 128 – 130. Janani Leila, Arch Iran Med. 2012; 15(11): 688 – 692. Koruk Suda Tekin, Arch Iran Med. 2012; 15(8):491 Hashemieh Mozhgan, Arch Iran Med. 2012; 15(2): Japoni Aziz, Arch Iran Med. 2012; 15(5): 312 – 316; – 494. 91 - 94. 15(7): 429 – 432. Kotrashetti Vijayalakshmi S., Arch Iran Med. 2012; Hayatshahi Alireza, Arch Iran Med. 2012; 15(7): 409 Javadi Mohammad Reza, Arch Iran Med. 2012; 15(1): 59 – 62. – 412. 15(7): 409 – 412. Kouhkan Azam, Arch Iran Med. 2012; 15(1): 32 – 35. Heidari Kazem, Arch Iran Med. 2012; 15(12): 736 Javadi-Paydar Mehrak, Arch Iran Med. 2012; 15(7): Krishnan Vibhu, Arch Iran Med. 2012; 15(4): 253 – – 740. 404 – 408. 256. Heidarnazhad Hassan, Arch Iran Med. 2012; 15(3): Jiang Mingde, Arch Iran Med. 2012; 15(1): 36 – 42. Kuo Chin-Chi, Arch Iran Med. 2012; 15(1): 63 – 64. 124 – 127. Joob Beuy, Arch Iran Med. 2012; 15(7): 459. Kyavar Madjid, Arch Iran Med. 2012; 15(2): 113 - Hejazi Hossien, Arch Iran Med. 2012; 15(3): 151 – Joulaei Hassan, Arch Iran Med. 2012; 15(6): 378 – 114. 156. 380. Lan Yu, Arch Iran Med. 2012; 15(11): 707 – 712. Hemati Hosein, Arch Iran Med. 2012; 15(3): 179 – Joulaei Hassan, Arch Iran Med. 2012; 15(8): 526 – Lankarani Kamran B., Arch Iran Med. 2012; 15(3): 180. 527. 189 – 192; 15(6): 378 – 380; 15(8): 526 – 527. Hessami Zahra, Arch Iran Med. 2012; 15(5): 283 – Kahrizi Kimia, Arch Iran Med. 2012; 15(6): 361 – Larijani Bagher, Arch Iran Med. 2012; 15(2): 70 - 75. 289. 365. Lee Yeong Yeh, Arch Iran Med. 2012; 15(11): 662 Hiradfar Mehran, Arch Iran Med. 2012; 15(11): 702 Kakoei Shahla, Arch Iran Med. 2012; 15(4): 214 – – 663. – 706. 218. Lei Zhou, Arch Iran Med. 2012; 15(11): 707 – 712. Hogg-Kollars Sabine, Arch Iran Med. 2012; 15(6): Kale Alka D., Arch Iran Med. 2012; 15(1): 59 – 62. Li Gandi, Arch Iran Med. 2012; 15(1): 36 – 42. 338 – 339. Kamangar Farin, Arch Iran Med. 2012; 15(4): 194 – Li Jinnan, Arch Iran Med. 2012; 15(1): 36 – 42. Holakouie Naieni Kourosh, Arch Iran Med. 2012; 195; 15(8): 508 – 516; 15(9): 575 – 582. Lotfi Mohsen, Arch Iran Med. 2012; 15(11): 696 – 15(3): 136 – 141. Kamrava Seyed Kamran, Arch Iran Med. 2012; 701. Honarvar Behnam, Arch Iran Med. 2012; 15(1): 55 15(2): 95 - 98. Lu Ling, Arch Iran Med. 2012; 15(4): 247 – 248. – 58. Karagah Touba, Arch Iran Med. 2012; 15(2): 99 - Maadani Mohssen, Arch Iran Med. 2012; 15(11): Hong Jong Chul, Arch Iran Med. 2012; 15(8): 488 101. 693 – 695. – 490. Karami Maryam, Arch Iran Med. 2012; 15(5): 290 MacMahon Stephen, Arch Iran Med. 2012; 15(7): Hossein Rashidi Batool, Arch Iran Med. 2012; 15(1): – 297. 439 – 445. 8 – 13. Karbaschian Zohreh, Arch Iran Med. 2012; 15(11): Madan Wafa, Arch Iran Med. 2012; 15(8): 485 – 487. Hosseini Marziyeh, Arch Iran Med. 2012; 15(5): 312 688 – 692. Madani Abdoulhossain, Arch Iran Med. 2012; 15(9): – 316. Karimi Abbasali, Arch Iran Med. 2012; 15(6): 387 – 545 – 548. Hosseini Mostafa, Arch Iran Med. 2012; 15(2): 70 - 388. Madani-Civi Manouchehr, Arch Iran Med. 2012; 75. Karimi Abdollah, Arch Iran Med. 2012; 15(3): 171 – 15(1): 32 – 35. Hosseini S. Hamed, Arch Iran Med. 2012; 15(12): 175; 15(8): 500 – 503; 15(9): 568 – 571. Maftoon Farzaneh, Arch Iran Med. 2012; 15(12): 736 – 740. Karimi Heidar, Arch Iran Med. 2012; 15(2): 99 - 101. 756 – 758. Hosseini Seyed Ali Reza, Arch Iran Med. 2012; Karimian Morteza, Arch Iran Med. 2012; 15(5): 306 Maharlouei Najmeh, Arch Iran Med. 2012; 15(1): 15(1): 52 – 54. – 311. 14 – 17. Hosseini Seyedeh Simindokht, Arch Iran Med. 2012; Karkheiran Siamak, Arch Iran Med. 2012; 15(12): Mahbobi Farshid, Arch Iran Med. 2012; 15(4): 235 15(12): 783 – 784. 780 – 782. – 238. Hosseini-Esfahani Firoozeh, Arch Iran Med. 2012; Karsen Hasan, Arch Iran Med. 2012; 15(5): 303 – Mahdavinejad Arezou, Arch Iran Med. 2012; 15(4): 15(6): 346 – 351; 15(9): 538 – 544. 305; 15(8):491 – 494. 210 – 213. Hosseini-Moghaddam Seyed Mohammadmehdi, Kati Mahmut, Arch Iran Med. 2012; 15(8):491 – 494. Mahmoodzadeh Habibollah, Arch Iran Med. 2012; Arch Iran Med. 2012; 15(9): 572 – 574. Kav Taylan, Arch Iran Med. 2012; 15(3): 176. 15(4): 257 – 258. Hossein-Nezhad Arash, Arch Iran Med. 2012; 15(11): Kazandi Mert, Arch Iran Med. 2012; 15(7): 449 – Mahmoudi Laleh, Arch Iran Med. 2012; 15(3): 177 688 – 692. 451. – 178. Hosseinpour-Niazi Somayeh, Arch Iran Med. 2012; Keify Fatemeh, Arch Iran Med. 2012; 15(4): 249 – Mahmoudi Mahmoud, Arch Iran Med. 2012; 15(1): 15(9): 538 – 544. 252. 8 – 13. Hosseinzadeh-Attar Mohammad Javad, Arch Iran Keshtkar Abbasali, Arch Iran Med. 2012; 15(4): 196 Mahmoudian Saeid, Arch Iran Med. 2012; 15(1): 49 Med. 2012; 15(11): 688 – 692. – 200. – 51. Houshmand Massoud, Arch Iran Med. 2012; 15(1): Khabazi Alireza, Arch Iran Med. 2012; 15(9): 549 – Majdzadeh Reza, Arch Iran Med. 2012; 15(12): 736 49 – 51. 552. – 740. Hu Bo, Arch Iran Med. 2012; 15(4): 247 – 248. Khademi Hooman, Arch Iran Med. 2012; 15(4): 194 Majdzadeh Reza, Arch Iran Med. 2012; 15(4): 223 Hu Peng, Arch Iran Med. 2012; 15(4):247 – 248. – 195. – 227. Huang Chun-Chieh, Arch Iran Med. 2012; 15(1): 63 Khademolhosseini Farnaz, Arch Iran Med. 2012; Majed Masoud, Arch Iran Med. 2012; 15(8): 469 – – 64. 15(12): 747 – 750. 471. Islami Farhad, Arch Iran Med. 2012; 15(2): 70 - 75. Khajavi Mohammad Reza, Arch Iran Med. 2012; Malek Ayyoub, Arch Iran Med. 2012; 15(9): 560 – Ismail-Beigi Faramarz, Arch Iran Med. 2012; 15(4): 15(6): 387 – 388. 563. 239 – 246. Kharaghani Roghieh, Arch Iran Med. 2012; 15(5): Malekafzali Hossein, Arch Iran Med. 2012; 15(7): Jadali Farzaneh, Arch Iran Med. 2012; 15(7): 455 – 283 – 289. 394 – 399. 456. Khatami Gholam Reza, Arch Iran Med. 2012; 15(6): Maleki Zahra, Arch Iran Med. 2012; 15(6): 366 – Jadali Zohreh, Arch Iran Med. 2012; 15(1): 43 – 48. 342 – 345. 369. Jafari Dawood, Arch Iran Med. 2012; 15(12): 777 – Khatibian Morteza, Arch Iran Med. 2012; 15(5): 269 Malekzadeh Fatemeh, Arch Iran Med. 2012; 15(2): 779. – 270. 70 - 75. Jafari Elham, Arch Iran Med. 2012; 15(9): 531 – 537. Khodakarami Nahid, Arch Iran Med. 2012; 15(1): Malekzadeh Reza, Arch Iran Med. 2012; 15(1): 18 Jafari Nahid, Arch Iran Med. 2012; 15(12): 741 – 4 – 7. – 21; 15(11): 713 – 722;15(11): 733 – 734; 15(2): 746. Khorgami Zhamak, Arch Iran Med. 2012; 15(4): 257 70 - 75; 15(4): 196 – 200; 15(5): 290 – 297; 15(5): Jafarzadehpour Ebrahim, Arch Iran Med. 2012; – 258; 15(5): 275 – 278. 320 – 324; 15(6): 340 – 341; 15(7): 392 – 393; 15(7): 15(4): 228 – 231. Khosravani Abdolmajid, Arch Iran Med. 2012; 15(5): 418 – 421. Jahanbani Jahanfar, Arch Iran Med. 2012; 15(3): 142 271 – 274. Mane Deepa R., Arch Iran Med. 2012; 15(1): 59 – 62. – 145. Khosravi Alireza, Arch Iran Med. 2012; 15(5): 320 Manoharan Sakthivel Rajan, Arch Iran Med. 2012; Jahangard-Rafsanjani Zahra, Arch Iran Med. 2012; – 324. 15(4): 253 – 256. 15(2): 85 - 87. Khosravi Boroujeni Hossein, Arch Iran Med. 2012; Marzban Maryam, Arch Iran Med. 2012; 15(12): 741 Jahangir Shahrbanoo, Arch Iran Med. 2012; 15(7): 15(3): 131 – 135. – 746. 422 – 428. Kiani Reza, Arch Iran Med. 2012; 15(11): 693 – 695. Masjedi Mohammad Reza, Arch Iran Med. 2012; Jalali Farzad, Arch Iran Med. 2012; 15(8): 462 – 468. Kojuri Javad, Arch Iran Med. 2012; 15(2): 79 - 81. 15(5): 283 – 289.

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 801 Masoumi Asl Hosein, Arch Iran Med. 2012; 15(12): 15(4): 257 – 258. 777 – 779. 764 – 766. Mohammadnejad Leila, Arch Iran Med. 2012; 15(7): Najmabadi Hossein, Arch Iran Med. 2012; 15(6): Masoumi Seyed Jalil, Arch Iran Med. 2012; 15(12): 446 – 448. 361 – 365. 747 – 750. Mohammadpoorasl Asghar, Arch Iran Med. 2012; Nakhaei Mahdieh, Arch Iran Med. 2012; 15(4): 214 Massarrat Sadegh, Arch Iran Med. 2012; 15(1): 27 15(2): 76 - 78. – 218. – 31; 15(11): 664 – 669; 15(11): 726 – 728; 15(12): Mohammadzadegan Reza, Arch Iran Med. 2012; Namazi Mohammad Hassan, Arch Iran Med. 2012; 792 – 794; 15(4): 265 – 266. 15(5): 312 – 316. 15(9): 528 – 530. Mazaherioun Maryam, Arch Iran Med. 2012; 15(11): Mohseni Meysam, Arch Iran Med. 2012; 15(7): 452 Namiri Mehrnaz, Arch Iran Med. 2012; 15(1): 32 – 688 – 692. – 454. 35. Mazloomi Ezat, Arch Iran Med. 2012; 15(1): 14 – 17. Mojtahed Ali, Arch Iran Med. 2012; 15(12): 759 – Naseri Mitra, Arch Iran Med. 2012; 15(11): 702 – Mehrabani Davood, Arch Iran Med. 2012; 15(12): 763. 706. 747 – 750. Mojtahed Mohammad, Arch Iran Med. 2012; 15(12): Nasseri-Moghaddam Siavosh, Arch Iran Med. 2012; Mehrabi Yadollah, Arch Iran Med. 2012; 15(8): 477 759 – 763. 15(2): 118 - 119. – 484. Mokhtari Maral, Arch Iran Med. 2012; 15(5): 328 – Nasseri-Moghaddam Siavosh, Arch Iran Med. 2012; Mehran Ladan, Arch Iran Med. 2012; 15(7): 400 – 330. 15(3): 177 – 178. 403. Mokhtari Mehrdad, Arch Iran Med. 2012; 15(9): 557 Nasseri-Moghaddam Siavosh, Arch Iran Med. 2012; Mehrbod Noushin, Arch Iran Med. 2012; 15(9): 583 – 559. 15(4): 259 – 262. – 584. Mokri Mehrdad, Arch Iran Med. 2012; 15(6): 366 – Nategh Rakhshandeh, Arch Iran Med. 2012; 15(2): Mehrdad Ramin, Arch Iran Med. 2012; 15(6): 370 – 369. 107 - 109. 374. Momenan Amir Abbas, Arch Iran Med. 2012; 15(5): Nateghi Mohammad Reza, Arch Iran Med. 2012; Mehregan Fatemeh Fereshteh, Arch Iran Med. 2012; 279 – 282. 15(4): 228 – 231. 15(4): 210 – 213. Momtahen Mahmood, Arch Iran Med. 2012; 15(11): Nazhvani Dehghani Seifollah, Arch Iran Med. 2012; Merat Shahin, Arch Iran Med. 2012; 15(5): 269 – 693 – 695. 15(8): 495 – 499. 270; 15(5):268; 15(7): 418 – 421. Monabati Ahmad, Arch Iran Med. 2012; 15(6): 352 Nedaeifard Leila, Arch Iran Med. 2012; 15(4): 228 Miri Seyed Mojtaba, Arch Iran Med. 2012; 15(7): – 355. – 231. 452 – 454. Montazeri Ali, Arch Iran Med. 2012; 15(12): 747 – Nedjat Saharnaz, Arch Iran Med. 2012; 15(4): 223 – Mirmesdagh Yalda, Arch Iran Med. 2012; 15(2): 113 750. 227. - 114. Moossavi Shirin, Arch Iran Med. 2012; 15(3): 166 – Nematollahi Nemat, Arch Iran Med. 2012; 15(3): Mirmiran Parvin, Arch Iran Med. 2012; 15(6): 346 – 170. 128 – 130. 351; 15(9): 538 – 544. Moradhaseli Saeed, Arch Iran Med. 2012; 15(11): Nikbakhsh Novin, Arch Iran Med. 2012; 15(5): 298 Mirmohammadsadeghi Hammid, Arch Iran Med. 696 – 701. – 302. 2012; 15(3): 151 – 156. Moradi Ali, Arch Iran Med. 2012; 15(8): 523 – 524. Nikeghbalian Saman, Arch Iran Med. 2012; 15(6): Mir-Nasseri Mohammad Mehdi, Arch Iran Med. Moradi Fariba, Arch Iran Med. 2012; 15(12): 747 – 389 – 390. 2012; 15(6): 342 – 345. 750. Niknam Ramin, Arch Iran Med. 2012; 15(3): 177 – Mirzaei Farzaneh, Arch Iran Med. 2012; 15(4): 249 Moradi-Lakeh Maziar, Arch Iran Med. 2012; 15(12): 178. – 252. 759 – 763. Nikoo Azita, Arch Iran Med. 2012; 15(3): 146 – 150. Mirzaei Mahboobeh, Arch Iran Med. 2012; 15(11): Morovvati Hasan, Arch Iran Med. 2012; 15(11): 696 Nikseresht Brito Eduardo Flávio Oliveira, Arch Iran 664 – 669. – 701. Med. 2012; 15(8): 517 – 519. Mirzaie Fatemeh, Arch Iran Med. 2012; 15(3): 162 Morse Douglas E., Arch Iran Med. 2012; 15(3): 142 Nikseresht Sara, Arch Iran Med. 2012; 15(5): 306 – – 165. – 145. 311. Mirzatolooei Fardin, Arch Iran Med. 2012; 15(4): Morshedizadeh Maryam, Arch Iran Med. 2012; Nikvarz Mehran, Arch Iran Med. 2012; 15(2): 82 - 219 – 222. 15(6): 370 – 374. 84. Moazami Goodarzi Habib, Arch Iran Med. 2012; Mosarrezai Arash, Arch Iran Med. 2012; 15(8): 469 Nobakht-Haghighi Ali, Arch Iran Med. 2012; 15(2): 15(3): 128 – 130. – 471. 70 - 75. Moazzami Kasra, Arch Iran Med. 2012; 15(1): 32 – Moshfe Mohammad Jafar, Arch Iran Med. 2012; Nojomi Marzieh, Arch Iran Med. 2012; 15(2): 95 - 35. 15(3): 157 – 161. 98. Modabbernia Amirhossein, Arch Iran Med. 2012; Moshkani Farahani Maryam, Arch Iran Med. 2012; Noorbala Ahmad Ali, Arch Iran Med. 2012; 15(4): 15(5): 290 – 297. 15(1): 32 – 35. 201 – 204. Modaresi Vajiheh, Arch Iran Med. 2012; 15(6): 342 Moshrefi Behnaz, Arch Iran Med. 2012; 15(8): 472 Nouraie Mehdi, Arch Iran Med. 2012; 15(7): 418 – – 345. – 476. 421. Moeini Mahsa, Arch Iran Med. 2012; 15(7): 429 – Mostafazadeh Babak, Arch Iran Med. 2012; 15(4): Nouraie Seyed Mehdi, Arch Iran Med. 2012; 15(4): 432. 210 – 213. 196 – 200. Moghadami Mohsen, Arch Iran Med. 2012; 15(1): Mostaghni Amir Ahmad, Arch Iran Med. 2012; Nouri Soudabeh, Arch Iran Med. 2012; 15(4): 228 – 55 – 58. 15(12): 747 – 750. 231. Moghadasali Reza, Arch Iran Med. 2012; 15(7): 422 Moussavi Taha, Arch Iran Med. 2012; 15(2): 107 - Ojaghi Zahra, Arch Iran Med. 2012; 15(2): 113 - 114. – 428. 109. Oruc Memduh, Arch Iran Med. 2012; 15(6): 384 – Moghimi Sedigheh, Arch Iran Med. 2012; 15(1): 4 Mozafari Kermani Ramin, Arch Iran Med. 2012; 386. – 7. 15(4): 228 – 231. Osia Mohammad Ali, Arch Iran Med. 2012; 15(4): Mohagheghi Abbas, Arch Iran Med. 2012; 15(9): 528 Mpntazeri Ghodratollah, Arch Iran Med. 2012; 15(6): 228 – 231. – 530. 356 – 360. Ostad Rahimi Alireza, Arch Iran Med. 2012; 15(8): Mohamadkhani Ashraf, Arch Iran Med. 2012; Nabavizadeh Fatemeh, Arch Iran Med. 2012; 15(5): 472 – 476. 15(11): 664 – 669. 306 – 311. Ostovaneh Mohammad Reza, Arch Iran Med. 2012; Mohamadkhani Ashraf, Arch Iran Med. 2012; 15(7): Naderi Ali, Arch Iran Med. 2012; 15(2): 82 - 84. 15(9): 528 – 530. 459. Naderi Hamid Reza, Arch Iran Med. 2012; 15(11): Ostovar Rahim, Arch Iran Med. 2012; 15(1): 8 – 13. Mohammad Hosseini Negar, Arch Iran Med. 2012; 723 – 725. Ouyang Qin, Arch Iran Med. 2012; 15(1): 36 – 42. 15(1): 27 – 31. Nadim Abolhassan, Arch Iran Med. 2012; 15(2): 107 Owji Ali Akbar, Arch Iran Med. 2012; 15(6): 352 – Mohammad Taher, Arch Iran Med. 2012; 15(12): 783 - 109. 355. – 784. Naghili Behrooz, Arch Iran Med. 2012; 15(7): 446 Owlia Parviz, Arch Iran Med. 2012; 15(7): 394 – 399. Mohammadalizadeh Sakineh, Arch Iran Med. 2012; – 448. Ozkinay Ferda, Arch Iran Med. 2012; 15(7): 449 – 15(4): 214 – 218. Nahvijou Azin, Arch Iran Med. 2012; 15(12): 741 – 451. Mohammadi Mehdi, Arch Iran Med. 2012; 15(1): 746. Ozupekce Suleyman, Arch Iran Med. 2012; 15(6): 22 – 26. Najafi Iraj,Arch Iran Med. 2012; 15(2): 70 - 75. 384 – 386. Mohammadifard Noushin, Arch Iran Med. 2012; Najafi Mohammad Reza, Arch Iran Med. 2012; Pajoumand Abdolkarim, Arch Iran Med. 2012; 15(4): 15(5): 320 – 324. 15(9): 583 – 584. 210 – 213. Mohammadnejad Atefeh, Arch Iran Med. 2012; Najd Mazhar Farid, Arch Iran Med. 2012; 15(12): Paknejad Omalbanin, Arch Iran Med. 2012; 15(3):

802 Archives of Iranian Medicine, Volume 15, Number 12, December 2012 128 – 130. Rashtchizadeh Nadereh, Arch Iran Med. 2012; 15(9): Saliminejhad Mehrdad, Arch Iran Med. 2012; 15(11): Pakpour Amir H., Arch Iran Med. 2012; 15(12): 785 549 – 552. 664 – 669. – 789. Rastegarpour Ali, Arch Iran Med. 2012; 15(12): 767 Samira Alizadeh, Arch Iran Med. 2012; 15(9): 549 Parivar Kazem, Arch Iran Med. 2012; 15(7): 446 – – 771. – 552. 448. Rastgar Jazii Ferdous, Arch Iran Med. 2012; 15(7): Sanaei Dashti Anahita, Arch Iran Med. 2012; 15(8): Park Heon Soo, Arch Iran Med. 2012; 15(8): 488 – 459. 500 – 503. 490. Razmkhah Mahboobeh, Arch Iran Med. 2012; 15(8): Sanati HamidReza, Arch Iran Med. 2012; 15(11): Pasa Semir, Arch Iran Med. 2012; 15(6): 384 – 386. 495 – 499. 693 – 695. Patel Anushka, Arch Iran Med. 2012; 15(7): 439 – Razmpa Ebrahim, Arch Iran Med. 2012; 15(4): 235 Saniee Parastoo, Arch Iran Med. 2012; 15(1): 27 – 445. – 238. 31. Paz Bruno César Silva, Arch Iran Med. 2012; 15(8): Reece Albert Stuart, Arch Iran Med. 2012; 15(9): 588 Santos Vitorino Modesto dos, Arch Iran Med. 2012; 517 – 519. – 590. 15(8): 517 – 519. Pazoki Marzieh, Arch Iran Med. 2012; 15(3): 128 – Rezaeifar Parisa, Arch Iran Med. 2012; 15(8): 472 – Sarbazi Narges, Arch Iran Med. 2012; 15(5): 279 – 130. 476. 282. Pedramnia Shahrzad, Arch Iran Med. 2012; 15(1): Rezaei-Ghaleh Nasrollah, Arch Iran Med. 2012; Sarkari Bahador, Arch Iran Med. 2012; 15(5): 271 – 27 – 31. 15(5): 279 – 282. 274. Peikan-Heirati Masoumeh, Arch Iran Med. 2012; Rezvan Neda, Arch Iran Med. 2012; 15(11): 688 – Sarrafzadegan Nizal, Arch Iran Med. 2012; 15(5): 15(7): 418 – 421. 692. 320 – 324. Peykari Niloofar, Arch Iran Med. 2012; 15(7): 394 Rismanchi Mojtaba, Arch Iran Med. 2012; 15(1): 55 Sarvghad Mohammad Reza, Arch Iran Med. 2012; – 399. – 58. 15(11): 723 – 725. Pezeshki Zahra, Arch Iran Med. 2012; 15(12): 764 Roohani Mohammad, Arch Iran Med. 2012; 15(12): Sarzaeem Ali, Arch Iran Med. 2012; 15(11): 696 – – 766. 780 – 782. 701. Pharoah Paul, Arch Iran Med. 2012; 15(2): 110 – 112; Roshanaei Mohsen, Arch Iran Med. 2012; 15(6): 352 Sattarzadeh Tabrizi Mahboubeh, Arch Iran Med. 15(5): 320 – 324. – 355. 2012; 15(11): 670 – 673. Pisoodeh Karim, Arch Iran Med. 2012; 15(4): 219 – Roshandel Gholamreza, Arch Iran Med. 2012; Sayyah Mohammad, Arch Iran Med. 2012; 15(9): 222. 15(11): 713 – 722; 15(4): 196 – 200. 557 – 559. Poorkaveh Atefeh, Arch Iran Med. 2012; 15(5): 290 Rostami Kamran, Arch Iran Med. 2012; 15(6): 338 Sedaghat Seyed Mehdi, Arch Iran Med. 2012; 15(4): – 297. – 339. 196 – 200. Pouraram Hamed, Arch Iran Med. 2012; 15(5): 320 Rostami Nejad Mohammad, Arch Iran Med. 2012; Seghatoleslam Atefeh, Arch Iran Med. 2012; 15(6): – 324. 15(6): 338 – 339. 352 – 355. Pourdamghan Nasim, Arch Iran Med. 2012; 15(4): Rostampour Farshad, Arch Iran Med. 2012; 15(6): Seif El-Nasr Mona M., Arch Iran Med. 2012; 15(11): 214 – 218. 356 – 360. 674 – 680. Pourgholi Leila, Arch Iran Med. 2012; 15(11): 670 Rouhipour Alaleh, Arch Iran Med. 2012; 15(7): 455 Seifirad Soroush, Arch Iran Med. 2012; 15(3): 128 – 673. – 456. – 130. Pourreza Abolghasem, Arch Iran Med. 2012; 15(1): Sabaeian Behnam, Arch Iran Med. 2012; 15(1): 55 Seifirad Soroush, Arch Iran Med. 2012; 15(9): 549 8 – 13. – 58. – 552. Pourshahid Omid, Arch Iran Med. 2012; 15(1): 55 – Saberi-Firoozi Mehdi, Arch Iran Med. 2012; 15(12): Seifoddin Mahsan, Arch Iran Med. 2012; 15(1): 4 – 7. 58. 747 – 750. Semnani Shahryar, Arch Iran Med. 2012; 15(11): 713 Poustchi Hossein, Arch Iran Med. 2012; 15(5): 290 Sabouri Ghannad Masoud, Arch Iran Med. 2012; – 722; 15(4): 196 – 200. – 297. 15(6): 356 – 360. Sepanlou Sadaf G., Arch Iran Med. 2012; 15(1): 2 Poustchi Hossein, Arch Iran Med. 2012; 15(5):268. Sabzehei Mohammad Kazem, Arch Iran Med. 2012; – 315(3): 189 – 192; 15(7): 392 – 393; 15(7): 418 – Rabbani Shahram, Arch Iran Med. 2012; 15(9): 553 15(9): 568 – 571. 421; 15(9): 531 – 537. – 556. Sadegfard Majid, Arch Iran Med. 2012; 15(9): 560 Sepehriseresht Saeed, Arch Iran Med. 2012; 15(11): Rabiei Samira, Arch Iran Med. 2012; 15(11): 681 – – 563. 670 – 673. 687. Sadeghian Hakimeh, Arch Iran Med. 2012; 15(1): Sepehrmanesh Zahra, Arch Iran Med. 2012; 15(4): Rad Maryam, Arch Iran Med. 2012; 15(4): 214 – 218. 32 – 35. 205 – 209. Raees-Jalali Ghanbar-Ali, Arch Iran Med. 2012; Sadeghipour Hamid Reza, Arch Iran Med. 2012; Shafaeizadeh Shila, Arch Iran Med. 2012; 15(3): 131 15(3): 181 – 186. 15(5): 306 – 311. – 135. Rafiei Tabatabaei Sedigheh, Arch Iran Med. 2012; Sadjadi Alireza, Arch Iran Med. 2012; 15(4): 196 – Shahbazi Mohammad, Arch Iran Med. 2012; 15(6): 15(3): 171 – 175. 200. 378 – 380. Rahimi Kazem, Arch Iran Med. 2012; 15(7): 439 – Sadrizadeh Bijan, Arch Iran Med. 2012; 15(2): 107 Shahbazkhani Bijan, Arch Iran Med. 2012; 15(9): 445. - 109. 585 – 586. Rahimi-Sharbaf Fatemeh, Arch Iran Med. 2012; Saedi Babak, Arch Iran Med. 2012; 15(4): 235 – 238. Shahidi Gholam Ali, Arch Iran Med. 2012; 15(12): 15(3): 162 – 165. Saeidi Sandra, Arch Iran Med. 2012; 15(11): 664 – 780 – 782. Rahjoo Taban, Arch Iran Med. 2012; 15(9): 572 – 669. Shahidi Mehdi, Arch Iran Med. 2012; 15(11): 664 – 574. Safai Akbar, Arch Iran Med. 2012; 15(4): 232 – 234. 669. Rahmat Asmah, Arch Iran Med. 2012; 15(8): 462 – Safari Mir Bahram, Arch Iran Med. 2012; 15(5): 317 Shahraki Touran, Arch Iran Med. 2012; 15(6): 342 468. – 319. – 345. Rahmati Atieh, Arch Iran Med. 2012; 15(2): 70 - 75. Saffari Mohsen, Arch Iran Med. 2012; 15(12): 785 Shahzadeh Fazeli Abolhassan, Arch Iran Med. 2012; Rahmati Reza, Arch Iran Med. 2012; 15(7): 433 – – 789. 15(4): 228 – 231. 438. Şahin Füsun, Arch Iran Med. 2012; 15(8): 520 – 522. Shakeri Nezhat, Arch Iran Med. 2012; 15(9): 538 – Rahvar Mostafa, Arch Iran Med. 2012; 15(6): 352 – Saidi Farrokh, Arch Iran Med. 2012; 15(5): 298 – 544. 355. 302. Shakeri Ramin, Arch Iran Med. 2012; 15(2): 70 - 75. Rajabi Saidi Reza F., Arch Iran Med. 2012; 15(12): 772 – Shakerian Farshad, Arch Iran Med. 2012; 15(11): Rajabi Mohammad Bagher, Arch Iran Med. 2012; 776. 693 – 695. 15(12): 783 – 784. Sajedinejad Sima, Arch Iran Med. 2012; 15(5): 320 Shalileh Keivan, Arch Iran Med. 2012; 15(12): 759 Rajabian Banafshe, Arch Iran Med. 2012; 15(11): – 324. – 763. 729 – 730. Salahi Rasool, Arch Iran Med. 2012; 15(2): 70 - 75. Shamshiri Ahmad Reza, Arch Iran Med. 2012; 15(3): Rakhshani Naser, Arch Iran Med. 2012; 15(11): 664 Salamzadeh Jamshid, Arch Iran Med. 2012; 15(7): 136 – 141; 15(3): 171 – 175; 15(9): 568 – 571. – 669. 409 – 412. Shaneshin Mahboubeh, Arch Iran Med. 2012; 15(11): Ranjbar Reza, Arch Iran Med. 2012; 15(5): 312 – Salavati Ali, Arch Iran Med. 2012; 15(9): 553 – 556. 681 – 687. 316. Saleh Al Mosawi Zakiya, Arch Iran Med. 2012; Shariat Mamak, Arch Iran Med. 2012; 15(3): 162 – Rashidian Arash, Arch Iran Med. 2012; 15(1): 8 – 13. 15(8): 485 – 487. 165; 15(6): 366 – 369. Rashidkhani Bahram, Arch Iran Med. 2012; 15(11): Salehi Negar, Arch Iran Med. 2012; 15(11): 693 – Sharifi Asghar, Arch Iran Med. 2012; 15(5): 271 – 681 – 687. 695. 274.

Archives of Iranian Medicine, Volume 15, Number 12, December 2012 803 Sharifi Hassan Pasha, Arch Iran Med. 2012; 15(5): 428. Yarahmadi Shahin, Arch Iran Med. 2012; 15(3): 136 290 – 297. Tahami Zanjani Nafiseh,Arch Iran Med. 2012; 15(3): – 141. Sharifi Hooman, Arch Iran Med. 2012; 15(5): 283 – 171 – 175. Yari Fatemeh, Arch Iran Med. 2012; 15(2): 88 - 90. 289. Talaie Haleh, Arch Iran Med. 2012; 15(4): 210 – 213. Yassin Zaitun, Arch Iran Med. 2012; 15(8): 462 – Sharifi Masoud, Arch Iran Med. 2012; 15(2): 99 - Talei Abdolrasol, Arch Iran Med. 2012; 15(8): 504 – 468. 101. 507; 15(8): 523 – 524. Yeganeh Mehrnoush Hassas, Arch Iran Med. 2012; Sharifi Zohreh,Arch Iran Med. 2012; 15(2): 88 - 90. Taskıran Huseyin, Arch Iran Med. 2012; 15(5): 303 15(7): 455 – 456. Sharifian Mostafa, Arch Iran Med. 2012; 15(7): 455 – 305. Yekta Zahra, Arch Iran Med. 2012; 15(5): 317 – 319. – 456. Taslimi Shervin, Arch Iran Med. 2012; 15(5): 290 – Yildiz Pinar, Arch Iran Med. 2012; 15(8): 520 – 522. Sharma Alka, Arch Iran Med. 2012; 15(2): 115 - 116. 297. Yisheng Tao, Arch Iran Med. 2012; 15(11): 707 – Sharma Vishal, Arch Iran Med. 2012; 15(2): 115 - Tavafian Sedigheh S., Arch Iran Med. 2012; 15(12): 712. 116. 767 – 771; 15(9): 545 – 548. Yourdkhani Fatemeh, Arch Iran Med. 2012; 15(6): Sheibani Kourosh, Arch Iran Med. 2012; 15(2): 91 Tavakkoly Fard Arezou, Arch Iran Med. 2012; 15(3): 342 – 345. - 94. 171 – 175. Yousefi Vahid, Arch Iran Med. 2012; 15(8): 477 – Sheikholeslami Farhad, Arch Iran Med. 2012; 15(8): Tavakolian Atefeh, Arch Iran Med. 2012; 15(1): 27 484. 477 – 484. – 31. Yousefshahi Fardin, Arch Iran Med. 2012; 15(6): 387 Shenaiy Yahya, Arch Iran Med. 2012; 15(12): 751 – Tavares Leal Cristina, Arch Iran Med. 2012; 15(8): – 388. 755. 517 – 519. Yousefzadeh Kheirnagsh Rana, Arch Iran Med. 2012; Sheybani Fereshte, Arch Iran Med. 2012; 15(11): 723 Tavassoli Maryam, Arch Iran Med. 2012; 15(6): 375 15(7): 446 – 448. – 725. – 377. Zahedmehr Ali, Arch Iran Med. 2012; 15(11): 693 – Sheykholeslami Arghavan, Arch Iran Med. 2012; Tayebi Meybodi Ali, Arch Iran 695. 15(4): 265 – 266. Thapa Babu Ram, Arch Iran Med. 2012; 15(4): 253 Zahraei Mohsen, Arch Iran Med. 2012; 15(2): 107 - Shirkavand Afshan, Arch Iran Med. 2012; 15(2): 91 – 256. 109. - 94. Tigh Dennerlein Jack, Arch Iran Med. 2012; 15(6): Zahraei Seyed Mohsen, Arch Iran Med. 2012; 15(12): Shiva Farideh, Arch Iran Med. 2012; 15(3): 171 – 370 – 374 764 – 766. 175; 15(9): 568 – 571. Toghae Mansoureh, Arch Iran Med. 2012; 15(8): 469 Zakeri Zeinab, Arch Iran Med. 2012; 15(1): 14 – 17. Shiwu WU, Arch Iran Med. 2012; 15(11): 707 – 712. – 471. Zaki Hala F., Arch Iran Med. 2012; 15(11): 674 – 680. Shojaiefard Abolfazl, Arch Iran Med. 2012; 15(5): Toghraie Fatemehsadat, Arch Iran Med. 2012; 15(8): Zamiri Nima, Arch Iran Med. 2012; 15(1): 55 – 58. 275 – 278. 495 – 499. Zamirian Mahmood, Arch Iran Med. 2012; 15(6): Shokoohi Mostafa, Arch Iran Med. 2012; 15(2): 82 Tohidi Maryam, Arch Iran Med. 2012; 15(8): 477 – 375 – 377. - 84. 484. Zare Maryam, Arch Iran Med. 2012; 15(3): 131 – Siavoshi Farideh, Arch Iran Med. 2012; 15(1): 27 – Tootian Semiramis, Arch Iran Med. 2012; 15(4): 249 135. 31. – 252. Zare Mirakabadi Abbas, Arch Iran Med. 2012; Soltanipour Sohail, Arch Iran Med. 2012; 15(8): 504 Torabi Nezhad Simin, Arch Iran Med. 2012; 15(8): 15(11): 696 – 701. – 507. 495 – 499. Zare Najaf, Arch Iran Med. 2012; 15(12): 747 – 750. Somi Mohammad Hossein, Arch Iran Med. 2012; Tsai Ching-Wei, Arch Iran Med. 2012; 15(1): 63 – 64. Zarei Mahboubeh, Arch Iran Med. 2012; 15(4): 210 15(8): 472 – 476. Tuna Ömer, Arch Iran Med. 2012; 15(5): 325 – 327. – 213. Sotoudeh Anvari Maryam, Arch Iran Med. 2012; Turan Volkan, Arch Iran Med. 2012; 15(7): 449 – Zarrindast Mohammad Reza, Arch Iran Med. 2012; 15(11): 670 – 673; 15(9): 553 – 556. 451. 15(5): 306 – 311; 15(7): 404 – 408. Sotoudeh Masoud, Arch Iran Med. 2012; 15(7): 418 Vasei Mohammad, Arch Iran Med. 2012; 15(4): 232 Zendehdel Kazem, Arch Iran Med. 2012; 15(12): 741 – 421. – 234. – 746. Sotoudehmanesh Rasoul, Arch Iran Med. 2012; Vasheghani Farahani Ali, Arch Iran Med. 2012; Zendehdel Nasrin, Arch Iran Med. 2012; 15(11): 664 15(5): 275 – 278; 15(7): 418 – 421. 15(11): 688 – 692. – 669. Sozen Selim, Arch Iran Med. 2012; 15(5): 325 – 327. Vousooghi Nasim, Arch Iran Med. 2012; 15(7): 404 Zeraatian Nejad Davani Sam, Arch Iran Med. 2012; Squire S. Bertel, Arch Iran Med. 2012; 15(1): 22 – 26. – 408. 15(5): 328 – 330. Stolte Manfred, Arch Iran Med. 2012; 15(11): 664 – Vyas Sameer, Arch Iran Med. 2012; 15(4): 253 – 256. Zhang Chuan-Rong, Arch Iran Med. 2012; 15(4): 669. Wang Jing, Arch Iran Med. 2012; 15(4): 247 – 248. 247 – 248. Tabatabaee Marzieh, Arch Iran Med. 2012; 15(5): Wenqing Song, Arch Iran Med. 2012; 15(11): 707 – Zhang Min, Arch Iran Med. 2012; 15(4): 247 – 248. 271 – 274. 712. Zheng Shumei, Arch Iran Med. 2012; 15(1): 36 – 42. Tabatabaei-Malazy Ozra, Arch Iran Med. 2012; Wiwanitkit Viroj, Arch Iran Med. 2012; 15(7): 459. Zhiyan Narges, Arch Iran Med. 2012; 15(4): 249 – 15(4): 223 – 227. Xu Hui, Arch Iran Med. 2012; 15(1): 36 – 42. 252. Tabatabaie Syed Ziaeddin, Arch Iran Med. 2012; Xue Linyun, Arch Iran Med. 2012; 15(1): 36 – 42. Ziaie Shadi, Arch Iran Med. 2012; 15(2): 85 - 87. 15(12): 783 – 784. Yaghmaie Farideh, Arch Iran Med. 2012; 15(12): 767 Ziyaeyan Maziar, Arch Iran Med. 2012; 15(7): 429 Tabibi Narjes, Arch Iran Med. 2012; 15(4): 232 – – 771. – 432. 234. Yapan-Gharavi Mina, Arch Iran Med. 2012; 15(2): Tabrizi Nasim, Arch Iran Med. 2012; 15(6): 381 – 70 - 75. 383. Yapıcı Kubilay, Arch Iran Med. 2012; 15(5): 303 – Taghavi Seyed Alireza, Arch Iran Med. 2012; 15(3): 305. 157 – 161. Yapici Kubilay, Arch Iran Med. 2012; 15(8):491 – Taghiyar Leila, Arch Iran Med. 2012; 15(7): 422 – 494.

804 Archives of Iranian Medicine, Volume 15, Number 12, December 2012