PUBLISH YOUR RESEARCH IN THE MYANMAR MEDICAL JOURNAL

The aim of the journal n The Myanmar Medical Journal, instituted solely for the purpose of advancing medical science, serves as one of the main forums for the publication of original research papers in the field of medicine and health in Myanmar, hence possible source of reference for domestic health events. n The journal also aims to serve as a medium for “continuing medical education” for medical practitioners. As such, it publishes case reports, review and educational articles, abstracts, and articles of general interest. n Being the official publication of the Myanmar Medical Association, the journal functions as forum to disseminate views on health issues and to promote discussions in order to improve health care services in the country.

Guidelines for submission of manuscripts The manuscript must be accompanied by a letter stating the category to which the manuscript belongs, and that it has not been submitted to any other journal. For original article, the research should be carried out within the past 5 years. Preparation of manuscripts 1) The manuscript is to be submitted electronically. 2) Authors should provide a statement saying the study was approved by the relevant ethical committee and it has not been published. Ethical clearance by the body concerned should be submitted as required. 3) Authors should clearly declare conflict of interest issues with regards to the conduct of the research. 4) Manuscript should include the title, author(s) designation, abstract, introduction, methods, findings, discussion and conclusions, references, tables, figures, and photographs (if any) in that order. Pages, including those for figures and tables should be numbered. Text of the final article should not be more than 5 pages. 5) Manuscript should be prepared and rechecked in the language setting with "English (United Kingdom)" to consistent with the Journal language. Title page: The title of the manuscript should consist of fewest possible words that describe the content or purpose of the paper (omit all superfluous words such as “A study of ……..”, “Observations on ……….”, etc.). Author(s) designation:the full name(s) of the author(s), the academic designations and affiliations, contact address(es) including phone numbers and email addresses. Abstract: Concisely stated (not more than 200 words) and should be on separate subtitles; background including aim and objectives, methods (scope of the investigation), results (the summary), conclusion(s) and key words. Body: The body of the manuscript should include sections such as introduction, methods, findings, discussions and conclusions of the study. Tables and figures: Tables and figures should be numbered and titled in the sequence mentioned in the text. They are to be provided on separate sheets. Percentages are to be shown as nearest 2 decimal places. References All references cited in the text (identified with Arabic numeral superscripts) must be in Vancouver style and listed in numerical order (by which they were cited and marked in Arabic numeral superscripted) in References section following the text. Each reference should include the following in the order given: the name(s) of the author(s), the title of the article cited, name of the journal (full or in abbreviations in accordance with the Index Medicus), the year of publication, volume number in bold type, and first and last page numbers. For books, title of book, name of editors, Myanmar number of edition, publisher and place of publication should also be included. The following is the Vancouver format link: https://www.imperial.ac.uk/media/ imperial-college/administration-and- support-services/library/public/vancouver.pdf Medical Examples: • Miller AC, Harvey JE. Guidelines for the management of spontaneous pneumothorax. British Medical Journal (or Br Med J) 1993; 307: 114-116. Journal The Journal of the Myanmar Medical Association nd • Pickup JC, Williams G (eds). Textbook of Diabetes. 2 ed. 1997. Blackwell Science, Oxford. pp Published since 1953 25-26. Quarterly publication • SIGN website ib diabetic neuropathy Authors are responsible in making sure that the manuscripts submitted for publication are free of Volume. 62, No. 3 ISSN 2664-2387 September, 2020 plagiarized materials. References are to be correctly cited when using materials from previously published papers and articles. If plagiarism is detected the manuscript will be rejected for Editorial Editor-in-Chief publication in this Journal. Prof. Yin Yin Soe The manuscript is to be submitted in the form of hard copy (print form) as well as soft copy Risk Management in Health Care Editorial Board Members (CD) that is to be sent to: Prof. Aye Aye Gyi Yin Yin Soe ...... 5 Prof. Aye Maung Han The Editor Prof. Hlaing Mya Win Myanmar Medical Journal, Myanmar Medical Association AP Dr. Kyaw Swa Mya No. 249, Thein Phyu Road, Mingalar Taung Nyunt Township, Yangon, Myanmar Research Papers Prof. Kyu Kyu Maung E-mail: [email protected], [email protected]. Prof. Moe Moe Tin Serum calcium as a marker of disease severity Dr. Myo Khin The right to revise or reject any manuscript is reserved. Once accepted and published, it becomes in adult dengue infection Prof. Rai Mra the property of the Myanmar Medical Association. Prof. Win Maw

Guidelines for preparation of case report Zaw Lynn Aung, Moe Thuzar Htun, Managing Editors Tay Zar Tun Myint ...... 9 Dr. Sun Tun Case report to be published in MMJ should conform with the format below. Dr. Thein Thein Myint

• Title of the case report should be short and interesting. Do not include “a case report” in the Knowledge, attitude and practices of parents issued by: title. of children with respiratory infection on Myanmar Medical Association, • Summary Up to 150 words summarizing the case presentation and outcome (this will be freely 249, Theinbyu Road, Cough Etiquette Mingalar Taung Nyunt Township, available online) Yangon, Myanmar. • Background should highlight why this case is important and the reason for writing this case Htin Lin, Theingi Win Myat, Khaing Moe Aung, Phone: 951-380899, 388097, 394141 report. Myat Mozar Kham, Nang Sarm Hom, 15 Fax: 951-378863 • Case presentation mentioning salient presenting features and past medical, social and family Thida Kyaw and Yin Yin Khaing ...... Email: [email protected], history. [email protected] • Investigations carried out mentioned according to the time line when the tests were done and Web: www.mmacentral.org Effect of Water on Obesity: Systematic Review the underlying reason(s) for doing the tests. Design Layout: • Differential diagnosis is to be mentioned if relevant. and Meta-analysis MMA Publishing House • Treatment provided. If the patient is involved in a clinical trial this fact is to be mentioned. Ei Mon Phyo, Kyaw Swa Mya ...... 24 Published by: • Outcome of the treatment and follow up treatment (if relevant). Dr. Kyaw Lynn (Mye 01304) • Patient’s perspective (optional but encouraged) Printed by: • Discussion should include a very brief review of similar published cases. Taunggyi Press (Mye 01116) • Learning points and take home message in short. (3 to 5 bullet points - this is a required field) Distribution: Free access • References should be in Vancouver style (Please reference related articles) • Tables, figures and pictures to be numbered and labeled. Editorial Perceptions of wholesale dealers and smokers towards health warnings of Risk Management in Health Care tobacco products: cigarettes and cheroots, Myanmar Yin Yin Soen Than Sein, Le Le Win, Aung Pye Phyo, Yin Thet Nu Oo, Kyaw Lwin Show, Kyaw Thu Hein ...... 38 Risk management is the identification, evaluation, and prioritization of risks which is defined as the effect of uncertainty on objectives, followed by coordinated and economical application of resources to minimize, monitor, and control the probability or Potential effectiveness of telephone consultation and triage in primary impact of unfortunate events or to maximize the realization of opportunities. healthcare service Risk management includes any activity, process, or policy to reduce liability Phyo Wai Htun, Kaung Set Aung, Swam Saung Oo, Kyaw Thu Hein, Kyaw Ko Ko Htet exposure from both a patient safety and a financial perspective; it is vital that health and Saw Saw ...... 45 centers conduct risk management activities aimed at preventing harm to patients and reducing medical malpractice claims1. Historically, risk management started in the Review industry. It then expand to all over the world involving health care, engineering, oil and natural gas, aerospace projects and natural disaster managements. Neglected and Emerging Helminthic Infections: Worldwide and in Myanmar Risk management in healthcare consists of the clinical and administrative systems, processes, and reports employed to detect, monitor, assess, mitigate, and prevent risks. Win Win Maw ...... 58 By employing risk management, healthcare organizations pro-actively and systematically safeguard patient safety as well as the organization’s assets, market share, accreditation, Case Reports reimbursement levels, brand value, and community standing. Life-threatening severe hypercalcaemia in patient with Graves’ disease and Deployment of healthcare risk management has traditionally focused on the Myasthenia gravis important role of patient safety and the reduction of medical errors that jeopardize an organization’s ability to achieve its mission and protect against financial liability. However, Hlaing Mya Win, May Kyi Oo, Tay Zar Tun Myint, Sandar Lwin ...... 68 with the expanding role of healthcare technologies, increased cyber security concerns, the fast pace of medical science, and the industry’s ever-changing regulatory, legal, political, A Lady with peculiar liver tumour and reimbursement climate, healthcare risk management has become more complex over time2.

Thet Nwe Oo, Win Naing ...... 73 To expand the role of risk management across the organization, hospitals and other healthcare facilities are adopting a more holistic approach called Enterprise Risk Obituary Management (ERM). ERM includes traditional aspects of risk management including patient safety and medical liability and expands them with a “big picture” approach to Dr. U Maung Ko ...... 78 risk across the organization2. ERM encompasses eight risk domains which are operational, clinical and patient 80 Professor Ko Ko Hla ...... safety, strategic, financial, human capital, legal and regulatory, technological, environmen- tal and infrastructure-based hazards. Professor Myint Maung Maung ...... 81 Critical Risks Facing the Healthcare Industry are cyber risk, healthcare infections, Letters to the Editor invitation...... 83 telemedicine, violent accidents in hospitals, alarm and fatigues.

n Retired Professor, Department of Obstetrics and Gynaecology, University of Medicine (1) Yangon, Editor-in-Chief, Myanmar Medical Journal Corresponding author: [email protected]

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There are 5 risk management process steps combined to deliver a simple and effective risk Implementation of risk management is by assigning a risk management team with management process3. risk manager who is responsible for seeing potential problems; and each multidisciplinary team members should report risks that he/she foresees, creating anonymous risk reporting • Step 1: Risk identification channel. • Step 2: Risk analysis • Step 3: Risk evaluation or ranking The team should maintain live project risk database, preparing mitigation plans • Step 4: Risk treatment for risks that are chosen to be mitigated, and summarize: planned and faced risks, • Step 5: Risk monitoring and review effectiveness of mitigation activities, and effort spent for the risk management. Risk identification is to identify potential risks. Risks are about events that, when Risk communication is a complex cross-disciplinary academic field related tocore triggered, cause problems or benefits. It can start with the source of our problems and values of the targeted audiences. A primary goal of risk communication is to improve those of our competitors (benefit), or with the problem consequences. collective and individual decision making. Risk communication is somewhat related to crisis communication. Risk analysis is related to identified threats. For example: the threat of abuse of confidential information or the threat of human errors, accidents and casualties. Risk management is not primarily about avoiding or mitigating claims; rather, it is a tool for improving the quality of care. Poor-quality care may lead to litigation, so Once risks have been identified, they must then be assessed as to their potential risk management should reduce outcomes that induce claims but this is not its sole or severity of impact (generally a negative impact, such as damage or loss) and to the pro- primary purpose. Risk management is also as much about learning from claims as it is bability of occurrence. Therefore, in the assessment process it is critical to make the about mitigating claims. best educated decisions in order to properly prioritize the implementation of the risk management plan. Risk management in Healthcare in Myanmar The stage immediately after completion of the risk assessment phase consists There are no formal risk management teams in healthcare in Myanmar, although of preparing a risk treatment plan, which should document the decisions about how there are patient safety and quality improvement and quality healthcare guidelines each of the identified risks should be handled. Techniques to manage the risk fall into issued by Department of Health. Hospital administrative personnels, senior clinicians and one or more of these four major categories; avoidance (eliminate, withdraw from or not Myanmar Medical Council are responsible for risk management and litigations. Food and become involved), reduction (optimize - mitigate), sharing (transfer - outsource or insure), Drug Administration of the Ministry of Health and Sports regulates the pharmaceutical retention (accept and budget). sector and medical devices. National Health Laboratory also has a quality control system. Initial risk management plans will never be perfect. Practice, experience, and It is high time for individual health care sectors to establish risk management actual loss results will necessitate changes in the plan and contribute information to teams with multidisciplinary team members to enhance patient safety, reduce claims and allow possible different decisions to be made in dealing with the risks being faced. This is litigations and improve quality of healthcare. FDA should also strengthen its capacity to followed by risk evaluation, monitoring and review. regulate pharmaceuticals and medical devices.

Risk management in health care includes clinical risk management in public and Conclusion private hospitals and health centres e.g. negligence, substandard care, human errors, Risk management is not simply about the reporting of patient safety incidents. system errors, pharmaceutical sector including development, manufacturing, distribution, Incident reporting is a form of the identification of risk. There are other ways of identifying inspection, and submission/review processes throughout the life cycle of drug substances, risk, and identified risks have to be analyzed, treated and monitored. Risk management drug products, biological and biotechnological products (including the use of raw materials, is more effective when resources are used to minimise the occurrence of patient safety solvents, excipients, packaging and labeling materials in drug products, biological and incidents instead of ‘fire fighting’ after things have gone wrong. Scenario training (‘fire biotechnological products), assessment of microbiological contamination in relation to drill’) is one example of proactive risk management. The misconception is that risk mana- pharmaceutical products and clean room manufacturing environments. Also included are gement is the business of service managers and of little concern to working clinicians. Risk medical devices, cyber security, emerging infections e.g. Covid-19 risk management, and management is actually the business of all stakeholders in the organization, clinicians and occupational health. non-clinicians alike in view of patient safety.

Page 6 September 2020 - Vol: 62, No. 3 September 2020 - Vol: 62, No. 3 Page 7 Myanmar Medical Journal Research Papers In summary, standardizing the approach of health systems’ efforts to improve the safety, quality and efficiency of health care is vital. Strategies to reduce risks include Serum calcium as a marker of disease severity in adult dengue infection a systematic approach to education and training of health care personnels, use of risk- Zaw Lynn Aungl, Moe Thuzar Htunn, Tay Zar Tun Myint« stratification tools and decision support, or performance reporting have all shown to be effective. It is expected that the adoption of such systematic improvements will help to Abstract coordinate and improve the complex, interdisciplinary delivery of healthcare in Myanmar. Background: The number of adult dengue infection is increasing in our country, Myanmar, in recent years. Due to the nature of the disease, it usually presents with different clinical References presentations accompanied by the unpredictable clinical outcomes. Therefore, early 1. WHO Patient Safety Curriculum Guide for Medical Schools. WHO, Geneva, 2009. recognition of severe dengue infection is extremely essential to reduce mortality rate 2. What is risk management in healthcare. NEJM Catalyst, April 25, 2018. in adult dengue infection. This study was aimed to detect the level of serum corrected https://catalyst.nejm.org/doi/full/10.1056/CAT.18.0197 calcium between 5-7 day of fever that can be used as a laboratory predictor for the severity of adult dengue infection. 3. WHO guidelines on quality risk management. World Health Organization Technical Method: The study design was hospital based cross-sectional analytical study. Sixty-four Report Series (2013), 981: 61-92. adult dengue patients from medical wards of Yangon General Hospital and New Yangon General Hospital were enrolled. In this study, seropositive adult dengue patients were chosen according to inclusion and exclusion criteria. Then, the study population was divided into two groups (severe and non-severe) by predefined working definition. Results: Among 64 cases of adult dengue infection, 40 patients (62.5%) suffered severe infection whereas 24 patients (37.5%) were non-severe infection. This study showed that there was significant difference in mean Calcium (Ca) level between severe and non- severe adult dengue infection, given that it was significantly lower in the severe group (mean 2.18 mmol/L) than in the non-severe group (mean 2.31 mmol/L) (p = 0.013). Conclusions: In predicting the severity of adult dengue infection, the cut-off level for serum Ca level was 2.25 mmol/L with sensitivity 82.5% and specificity 50%. Therefore, serum Ca level may be used as a marker to detect the severity of adult dengue infection in routine clinical practice. Keywords: Adult dengue infection, Serum calcium

Introduction Dengue fever, one of the most rapidly spreading arboviral infections in the world, is transmitted by the vector, female Aedes mosquitoes. It is due to infection with one of the 4 different dengue serotypes (DENV 1 to 4). It is a small single stranded ribonucleic acid virus and it belongs to the flavi virus family. The number of incidence of dengue infection has enormously increased around the world in recent years. One recent study estimated that 390 million dengue infections

l Professor/Head, Department of Internal Medicine, University of Medicine (1) Yangon n Consultant Physician, Medical Unit (3), Yangon General Hospital « Specialist Assistant Surgeon (Internal Medicine), Medical Unit (3), Yangon General Hospital Corresponding author: [email protected]

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occurred per year (95% credible interval 284-528 million), of which 96 million (67-136 Objective million) manifest clinically (with any severity of disease). Another study of the prevalence 1. To identify the severity of dengue infection by monitoring daily clinical parameters and of dengue estimates that 3.9 billion people, in 128 countries, are at risk of infection with measuring Haematocrit, Platelet count and Liver enzymes in adult dengue patients 1 dengue viruses. 2. To measure the level of serum calcium in adult dengue patients 2.9 million dengue episodes and 5,906 deaths were estimated annually in South- 3. To find out the relationship between serum calcium level and severity of adult dengue east Asia region causing an annual economic burden of $950 million.2 These episodes are infection

related to increased distribution ofAedes aegypti, and to the increase in urban population Methodology in the cities of Southeast Asia.3

This is a hospital based cross-sectional analytical study that was carried out during Myanmar is a tropical country where Aedes aegypti is widespread in both urban the period from January 2017 to December 2017. It included 64 patients with confirmed and rural areas. Dengue was first notified in 1964. First outbreak occurred in Yangon in 1970 dengue infection admitted to General Medical Wards of Yangon General Hospital and and then spread to States and Regions in 1974. Since 1970, Myanmar had experienced New Yangon General Hospital. All patients had to undergo daily clinical assessment and dengue outbreaks caused by all four types of dengue viruses.4 The highest number of laboratory parameters including corrected serum calcium during day 5th to 7th of fever. The cases and deaths were recorded in 2009 (24,285 cases and 444 deaths). Adult dengue mean calcium level between severe and non-severe dengue infection was compared at infection is increasing in recent years. Adult dengue cases, 181 in 2013, 132 in 2014, 406 the time of discharge from hospital for statistical significance. in 2015, 145 in 2016 and 616 in 2017 were admitted to YGH.5 According to prognostic indicator of dengue infection by Surangrat (2013), the Expert consensus groups in Latin America (Havana, Cuba, 2007), SEA (Kuala following definitions are made.7, 9 Lumpur, Malaysia, 2007) and at WHO headquarters in Geneva in 2008 agreed that “Dengue Confirmed dengue - Probable dengue case plus either NS1 Ag or IgM or both positive is one disease entity with different clinical presentations, often with unpredictable clinical Severe dengue - Confirmed dengue plus one of the following: evolution and outcome”. Clinical features of adult dengue infection are often described according to three phases: the febrile phase, critical phase and the convalescent • Bleeding manifestation phase. Severe clinical disease manifestations such as vascular fluid leakage, bleeding, • Narrow Pulse Pressure < 20 mmHg or Systolic pressure < 90 mmHg encephalopathy and shock are seen during the critical phase which begins around day 4 • Clinical evidence of plasma leakage (ascites ± pleural effusion) to 7 of the illness. When treated, dengue haemorrhagic fever (DHF) has a mortality rate of • Hct > 45% in male, Hct > 40% in female 2-5%, but when left untreated, the mortality rate is as high as 50%.6 • Platelet < 50,000 unit Data entry and summarization was done by electronic data processing using SPSS Haematological parameters; haematocrit (Hct) and platelet count, biochemical software. This study was done according to the guidelines issued by Research and Ethical parameters; serum alanine aminotransferase (ALT) and serum aspirate aminotransferase Committee, University of Medicine 1, Yangon. (AST) were measured for severity assessment in this study. These laboratory indicators are used to predict the severity of adult dengue infection in the course of the illness.7 Results Serum calcium is essential for cardiac and circulatory function in human. Calcium A total of 64 patients with adult dengue infection were included in the study. entry via neuronal calcium channels is important for neurotransmission and calcium Figure 1. Frequency of non-severe and severe dengue infection plays a critical role in the smooth functioning of the autonomic nervous system. Changes in calcium homeostasis might play a role in the pathogenesis of shock in patients with dengue infection. Autonomic dysfunction might also contribute to hypotension in dengue shock syndrome (DSS). The mean serum corrected calcium level was significantly lowered in patients with DHF than in patients with uncomplicated dengue fever (DF).8 This study attempted to find out the usefulness of serum calcium as a maker of disease severity in adult dengue infection.

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Table 1. Calcium Level by severity of dengue infection This table shows the sensitivity and specificity of different serum calcium levels in prediction of the severity of dengue infection. If a patient had serum calcium level < 2.25 No Minimum Maximum Mean SD t p value mmol/L, the sensitivity to predict the severe dengue infection is 82.5% and specificity is Severe Dengue 40 2.0 2.4 2.18 0.08 2.653 0.013 50.0%. Non severe Dengue 24 2.1 3.2 2.31 0.23 Total 64 2.0 3.2 2.23 0.16 Discussion In the patients with non-severe dengue infection, mean calcium level was 2.31 The mean serum calcium level among the severe dengue patients was 2.18 mmol/L mmol/L. The mean serum calcium level in the severe dengue patients was 2.18 mmol/L which was significantly lower than that in non-severe patients (mean serum calcium level which is significantly lower than that of non-severe dengue patients (p = 0.013). - 2.31 mmol/L) (p = 0.013). This finding is similar to the study done by Murugan in 2016 Figure 2. Receiver Operating Characteristic (ROC) curve for serum calcium to predict the and the study done by Constantine in 2013 which showed significant low calcium level in severity of dengue infection patients with severe dengue infection.10, 11 Receiver Operating Characteristic (ROC) curve for serum calcium to predict the severity of dengue infection was done in this study and serum calcium level < 2.25 mmol/L can be used as a marker to predict severe dengue infection with the sensitivity of 82.5% and specificity of 50%. Although there has been significant difference in mean calcium value between severe and non-severe dengue infection, there were some limitations in this study. Firstly, the study population might not represent the whole adult dengue population in Myanmar. Secondly, the result from current study cannot be compared with the previous ones because there is no similar study of serum calcium as dengue severity marker in Myanmar.

Conclusion 95% Confidence Interval In patients with adult dengue infection, mean calcium level was 2.31 mmol/L in Area under the curve (AUC) p value Lower Bound Upper Bound non-severe group and in severe group was 2.18 mmol/L which was significantly lower 0.711 0.006 0.576 0.846 than that of non-severe dengue patients (p = 0.013). Serum corrected calcium with cut-

off level of < 2.25 mmol/L indicates severity of dengue infection (sensitivity 82.5% and Receiver Operating Characteristic (ROC) curve was constructed by computing specificity 50%). Therefore, doing further study with large sample size may support the sensitivity and specificity of the serum calcium to predict the severity of dengue infection. usefulness of serum corrected calcium as a marker for predicting the severity of dengue As with any other diagnostic test, there is a trade-off between the sensitivity and the false positive rate (1-specificity). The curves lie significantly above the 45 degree line of unity. infection in near future. As the area under the curve is 0.711, calcium is a fair indicator in predicting severity. Conflict of interest: There is no conflict of interest. Table 2. Sensitivity and specificity of serum calcium to predict the severity of dengue infection References Serum Calcium (mmol/L) Sensitivity Specificity < 1.00 0 100.0 1. Cogen JE. Dengue and severe dengue, WHO (2018). < 2.05 2.5 100.0 http://www.who.int/newsroom/fact-sheets/detail/dengue-and-severe-dengue. < 2.15 37.5 83.3 2. Guzman MG, Harris E. Dengue. Lancet (2015): 385 (9966); 453-465. < 2.25 82.5 50.0 doi: 10.1016/S0140-6736(14)60572-9. < 2.35 97.5 29.2 3. Tantawichien T. Dengue fever and dengue haemorrhagic fever in adults. Southeast < 2.45 100.0 16.7 Asian J trop med public health (2015): 46 (1); 79-98. < 2.85 100.0 4.2 < 4.20 100.0 0 Page 12 September 2020 - Vol: 62, No. 3 September 2020 - Vol: 62, No. 3 Page 13 Myanmar Medical Journal Myanmar Medical Journal

4. Ming CK, Soe Thein, Thaung U, Tin U, Khin Saw Myint, Than Swe, Halstead SB and Knowledge, attitude and practices of parents of children with respiratory Diwan AR. Clinical and laboratory studies on hemorrhagic fever in Burma, 1970- infection on Cough Etiquette 1972. Bulletin of World Health Organization (1974): 51; 227-235. Htin Linl, Theingi Win Myatl, Khaing Moe Aungl, Myat Mozar Khaml, Nang Sarm Homl, 5. Register of Medical Record Department, Yangon General Hospital (2013-2017). Thida Kyawl and Yin Yin Khaingl

6. Shepherd SM. Dengue (2017). https://emedicine.medscape.com/article/215840- Abstract overview. Introduction: Cough etiquette (CE) can effectively reduce aerosol concentration of 7. Surangrat P, Wisitwong A, Tawichasri C, Patumanond J. Prognostic indicators of pathogens although it cannot break the chain of infection completely. The objective was dengue infection severity. International Journal of Clinical Pediatrics (2013 June): to assess the knowledge, attitude and practice on CE among parents of children with 2 (1); 12-18. respiratory infection. 8. Khwaja Nazim Uddin, Musa AKM, Wasim Md Mohosinul Haque, Rene Suzan Claude Methods: A descriptive study was conducted at Outpatient Department of Yangon Sarker, Shaheen Ahmed AKM. A follow up on biochemical parameters in dengue Children Hospital during January-October 2019. Demographic, knowledge, attitude and patients attending Birdem hospital.Ibrahim Medical College Journal (2008): 2 (1); practice data on CE were collected from 115 participants by face to face interview. 25-27. doi: 10.3329/imcj.v2i1.2928. Results: Only 32 participants (28%) had knowledge of CE. Main sources of knowledge were posters in buses (38%), hospitals and clinics (38%) and television channels (28%). 9. World Health Organization, Regional Office for South-East Asia (2011). Compre- One hundred and seven participants (93%) accepted that proper CE was important for hensive Guideline for Prevention and Control of Dengue and Dengue Haemorrhagic public health. Of them, 66 participants (62%) thought that it was important for controlling Fever. Revised and expanded edition. WHO Regional Office for South-East Asia. spread of tuberculosis. About half of 115 participants usually cough directly into open air. https://apps.who.int/iris/handle/10665/204894. Twenty six participants (23%) coughed into fist and another 23% into bare hand. Only three 10. Constantine GR, Rajapakse S, Ranasinghe P, Parththipan B, Wijewickrama A, participants (2%) coughed into hand using tissue paper whereas one participant (1%) into Jayawardana P. Hypocalcaemia is associated with disease severity in patients with upper sleeve. There was no significant association between demographic characteristics dengue. J Infect Dev Ctries 2014: 8 (9); 1205-1209. doi.org/10.3855/jidc.4974. of participants and their knowledge, attitude and practice on CE. 11. Murugan MR, Pillai M. Hypocalcaemia: A Marker of Severe Dengue. Amrita Journal Conclusion: Participants’ knowledge and practice on CE of participants was not satisfactory of Medicine, 2016: 12 (1); 25-29. although their attitude was good. Keyword: Cough Etiquette, Knowledge, Attitude, Practice

Introduction Cough is a common medical complaint that causes about 30 million clinical visits per year worldwide.1 A single cough may produce hundreds of droplet nuclei and it can spread them as far as six feet. Each droplet nucleus contains about 1-10 TB bacilli or millions of viral particles which can be easily transmitted from person to person.2, 3, 4 Although immunization is considered as a main strategy of preventive measure in controlling spread of respiratory infections, there are many respiratory diseases for which effective vaccines are not available including severe acute respiratory syndrome (SARS) associated corona- virus infection, middle east respiratory syndrome (MERS) associated coronavirus infection and Nipah virus (NiV) infection.5, 6, 7 In late December 2019, an infection due to a new strain of coronavirus (COVID-19) was first found in Wuhan, China and spread worldwide rapidly. Within two months, it affected about 113,700 people with 4,000 deaths in China and other affected countries.8 Regarding influenza, there have been four pandemics l Virology Research Division, Department of Medical Research, Myanmar Corresponding author: [email protected]

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(Spanish flu, Asian flu, Hong Kong flu, Russian flu) which occurred inth 20 century and most of their life time. After completion of data collection, the interviewers demonstrated one pandemic (H1N1pdm09) in 21st century.9 Although seasonal influenza vaccines are details of CE to participants who did not know about CE. Data entry and analysis were commercially available worldwide, the vaccine efficacy cannot be predetermined due to done by SPSS version 15.0. Chi-square Test was applied to determine the significance of unpredictable match between vaccine strains and circulating strains of influenza virus.10 association between categorical variables. Any association with P value less than0.05 Apart from viral respiratory infections, prevalence of drug-resistant bacterial respiratory were considered to be statistically significant. Ethical approval for conduct of this study infections is currently increasing with time. Among them, drug resistant tuberculosis is was obtained from Ethics Review Committee of Department of Medical Research. currently threatening public health globally. In Myanmar, incidence of multi-drug resistant Results tuberculosis (MDR-TB) increased from 4% and 18% of new cases and previously treated cases, respectively in 2002-2003 to 5% and 27% in 2012-2013.11, 12 In such critical situations, A total of 115 parents participated in the study. Seventy one participants (62%) cough etiquette plays an important role in reducing transmission of these infections and were males and 44 (38%) were females. Approximately 58% of participants were aged controlling their outbreaks. between 30-39 years and 51% were of high school level of education. Among 115 participants, only 32 participants (28%) had knowledge on CE. Health education poster Cough etiquette (CE) can reduce aerosol concentration of pathogens effectively in buses, hospitals and clinics and television channels were found as main sources of the although it cannot disturb the chain of infection completely.13, 14 In Myanmar, health knowledge of them accounting for 38%, 38% and 28%, respectively (Figure 1, Figure 2). education of cough etiquette is being given to people through television channels and Figure 1. Distribution of participants by Figure 2. Different sources of knowledge of CE of posters whereas cough campaigns are being carried out among some peoples such as knowledge of CE (n = 115) participants (n = 32) school aged children. However, many adults seem to cover cough wrongly or did not seem to cover it at all even in crowded area. Since there has been very limited data on Myanmar people’s knowledge, attitude and practice on cough etiquette, they should be explored for generation of information to support the infection and outbreak control programmes of respiratory infections in Myanmar. Therefore, this study was conducted with general objective to determine the knowledge, attitude and practice of parents of children with respiratory infection on CE.

Methods A cross-sectional descriptive study was conducted at Outpatient Department (OPD) of Yangon Children Hospital from January to October 2019. Parents whose children were clinically suspected to have respiratory infections and attended OPD were recruited One hundred and seven out of 115 participants (93%) accepted that CE was in the study. Children having cough or sore throat with fever were considered as clinically important for public health. Of them, 66 participants (62%) knew that it was important for suspected respiratory infection cases. Health care persons such as doctors, nurses and controlling spread of tuberculosis (Figure 3, Figure 4). medical technologists were excluded from this study for better assessment of CE of the Figure 3. Distribution of participants Figure 4. Various perspectives of participants on majority of general population. by attitude on CE (n=115) importance of CE (n = 107) Investigators visited OPD on every Monday, Wednesday and Friday within the office hour and recruited all parents of children who met the criteria mentioned above. After getting participants’ informed consent, interview was conducted in a separate room in OPD which was comfortable for the participants in answering their cough behaviour confidentially. Demographic data except the name of participants and data on knowledge, attitude and practice on CE were collected by face to face interview using the following semi-structured questionnaires (Annex). Before developing close questions regarding CE, investigators asked 20 individuals of various educational levels open ended questions. In assessing participants’ practice on cough, participants were requested to freely demonstrate how they usually coughed in

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Fifty nine participants (51%) usually coughed directly into open air without age group was equal in-between the group of participants who practised CE properly. covering mouth at all. Twenty six participants (23%) coughed into fist and another 26 However, age group of 30-49 years was more common than age group of 18-29 years in participants into bare hand without using tissue paper. Only three participants (2%) the group of participants who did not practise CE properly. In both group of participants coughed into hand using tissue paper whereas one participant (1%) coughed into upper who practised CE properly and who did not practise it, participants of high school and sleeve. Thus, the participants who covered cough properly accounted for only 3% (Figure university level education were more common than group of other educational level. Any 5 & Figure 6). significant association was not seen between practice on CE and participants’ sex, age and Figure 5. Distribution of participants by various practices on cough (n = 115) education. Therefore, it was found that participants’ knowledge, attitude and practice on CE was not correlated to their demographic characteristics such as sex, age and education level. Male participants, participants of age 30-49 years and participants of high school and university education were common in the both groups of knowledge of CE, both groups of attitude on CE and both groups of practice on CE. Therefore, any significant association was not seen between demographic characteristics of participants (sex, age group, education level) and participants’ knowledge, attitude and practice on CE (Table 1).

Table 1. Correlation between demographic characteristics of participants and their knowledge, attitude and practice on CE (n = 115)

Knowledge of CE Attitude on CE Practice on CE Had Didn’t P Thought Didn’t P Practised Did not P knowledge have value CE was think CE value CE practise value knowledge important was properly CE important properly Figure 6. Various cough practices of the people Sex Male 21 50 66 5 1 70 0.59 0.96 0.12 Female 11 33 41 3 3 41 Age Group 18-29 yrs 14 23 33 4 2 35 0.09 0.26 0.44 30-49 yrs 18 60 74 4 2 76 Education level Illiterate 1 5 6 0 0 6 Primary 5 12 16 1 0 17 Middle 3 18 0.38 19 2 NA 0 21 NA High school 23 48 66 5 4 67 and above

NA: not applicable In both groups of participants who knew about CE and who didn’t know about CE, Discussion males were more common than females, age group of 30-49 years were more common than age group of 18-29 years and group of high school and university level education were Cough is a violent expulsion of air due to stimulation of sensory nerve endings in more common than group of other educational level. There was no significant association the airway and hence,can be difficultly controlled.15 To reduce the airborne concentration between knowledge of CE and participants’ sex, age and education. Regarding practice on of pathogens and minimize the spread of airborne infections, Centers for Disease Control CE, females were more common than males in group who practised CE properly whereas and Prevention (CDC) has recommended the cough etiquette maneuvers such as covering males were more common than females in group who did not practise it properly. However, the mouth with tissue paper or wearing face mask on cough or coughing into upper sleeve age preponderance was not significant among the participants (P = 0.12). Distribution of when a person coughs.16 In this study, most of the participants did not practice these

Page 18 September 2020 - Vol: 62, No. 3 September 2020 - Vol: 62, No. 3 Page 19 Myanmar Medical Journal Myanmar Medical Journal maneuvers properly and even did not know how to do it although they knew the hazards Limitations of uncovered cough and although some parents have school-aged children who had the Hospital based study with small sample size may affect generalized validity of the proper knowledge on CE. Therefore, both health education and training on CE should be findings. given to general population especially adults. Since existing cough campaigns are being carried out among some school aged children, they should be expanded nationwide to Recommendations cover adult population. Knowledge of participants on CE was not associated with age, • Health education and training on CE should be given to all adult population regardless sex or education level of participants because no persons in this study were health care of their gender and education level. persons and CE had not been included in the syllabus of their basic education. The findings • Detail explanation of the principle of cough etiquette should be done in giving health suggested that health education and training on CE should be given to all adult population education to people. regardless of their gender and education level. • Education programs of CE should be given to people via social media. Posters in buses, television (TV) channels, hospitals and clinics were found as important sources of knowledge of cough etiquette suggesting that health education Acknowledgement programme of cough etiquette should be frequently displayed on every local TV channel We would like to thank medical superintendent of YCH and medical doctors of and CE posters should be more displayed in all buses and hospitals or clinics. As social OPD and parents of children who participated in this study. media are now having considerable potentials as tools for health promotion, such education programs should also be displayed on reliable web pages of social media.17 References Since many ceremonies are frequently held in Myanmar, distribution of pamphlets 1. Sharma S, Hashmi MF, Alhajjaj MS. Cough. https://www.ncbi.nlm.nih.gov/books/ of CE in such ceremonies can also help in promoting knowledge of young adult on CE. NBK493221/ Although majority of participants did not have enough knowledge of CE, they knew quite 2. Republic of Myanmar, Ministry of Health and Sports. National Tuberculosis Manage- well that infections like tuberculosis can spread by uncovered cough. They obtained such ment Guidelines, 2014. 8-9. knowledge from health education program of tuberculosis. Adding CE topic into health education poster of tuberculosis may be beneficial to community in promoting people’s 3. Roy CJ, Milton DK. Airborne transmission of communicable infection - the elusive knowledge of CE. pathway. New England Journal of Medicine, 2004; 350 (17): 1710-1712. Approximately half of participants did not cover cough at all whereas another 4. CDC. How flu spreads. www.cdc.gov/flu/about/disease/spread half utilized their hands wrongly to cover cough such as coughed directly into bare hand 5. Jiang S, He Y and Liu S. SARS Vaccine Development. Emerging Infectious Diseases. without using tissue or coughed into his or her fist. Those participants thought that 2005 Jul; 11 (7): 1016-1020. doi: 10.3201/eid1107.050219 such cough was safe although it was not. If the participants had respiratory infections, 6. WHO. Middle East respiratory syndrome coronavirus (MERS-CoV), Online Questions microorganisms could spread from their hands to many objects that they touched. From those objects, the infections could be transmitted to other people who touched and Answers. www.who.int/features/qa/mers-cov/en the contaminated objects. This is because microorganisms such as influenza viruses can 7. WHO. Nipah virus: How to protect yourself. www.searo.who.int/bangladesh/nipah/ survive on hard and nonporous objects for up to 48 hours and a person’s hand can touch en/ his or her face especially mouth, nose and eyes up to twenty times per hour.18, 19 Therefore, 8. WHO. Novel Coronavirus (2019-nCoV) situation report 50. details of principle and effectiveness of CE should be thoroughly explained in giving health https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation- education to general population. reports Conclusion 9. Beveridge WI. The chronicle of influenza epidemics. History and Philosophy of the Life Sciences CE is an easy but important factor in controlling spread of respiratory infections. In , 1991 Jan; 13 (2): 223-234. this study, participants’ knowledge and practice on CE of participants was not satisfactory 10. CDC. Vaccine Effectiveness: How Well Do the Flu Vaccines Work? https://www.cdc. although their attitude was good. The information generated will be useful for controlling gov /flu/vaccines-work/vaccineeffect spread of respiratory infections including tuberculosis, pandemic influenza, COVID-19 and their outbreaks.

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11. Sabai Phyu, Thandar Lwin, Ti Ti and Win Maung. Drug-resistant tuberculosis in Annex: Questionnaire (Knowledge, Attitude and Practice of Parents of children with Respiratory Yangon, Myanmar. Infectious Diseases, 2005; 37 (11-12): 846-851. Infection on Cough Etiquette) https://doi.org/10.1080/00365540500265065 12. National TB program and who country office (Myanmar). Guidelines for the manage- ment of drug resistant tuberculosis (dr-tb) in Myanmar, 2017: 1-2. 13. Wood ME. Face masks and cough etiquette reduce the cough aerosol concentration of pseudomonas aeroginosa in people with cystic fibrosis. American Journal of Respiratory Critical Care Medicine, 2018; 197 (3): 348-355. 14. Zayas G, Chaing MC, King M. Effectiveness of cough etiquette maneuvers in disrupt- ing the chain of transmission of infectious respiratory diseases. BMC Public Health, 2013; 13: 811. doi: 10.1186/1471-2458-13-811. www.ncbi.nih.gov/m/pubmed/24010919/ 15. Editorial. Physiology and treatment of cough. Thorax, 1990; 45: 425-430. 16. CDC. Influenza (Flu), Respiratory infection control measure. www.cdc.gov/flu/professionals/infectioncontrol/resphygiene 17. Korda H and Itani Z. Harnessing social media for health promotion and behavior change. Health Promotion Predict, 2011; 14 (1): 15-23. 18. Bean B, Moore BM, Sterner B, Peterson LR, Gerding DN and Balfour HH Jr. Survival of influenza viruses on environmental surfaces.Journal of Infectious Diseases, 1982; 146 (1): 47-51. 19. Kwok YLA, Gralton J, McLaws ML. Face touching: a frequent habit that has implications for hand hygiene. American Journal of Infection Control, 2015; 43 (2): 112-114. doi: 10.1016/j.ajic.2014.10.015.

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Effect of Water on Obesity: Systematic Review and Meta-analysis How drinking water intervention might play a role in weight reduction Water intake and thermogenesis Ei Mon Phyo|, Kyaw Swa Myan Drinking 500 ml of water in 14 healthy normal-weight men and women brings Abstract about increased metabolic rate by 30% within 10 minutes, reaching maximum after 30- Introduction: Obesity and obesity related diseases have been important health problems. 40 minutes with total thermogenesis response of 100 kJ4. According to a randomized Objective: It was to review the trials using drinking water as intervention to reduce weight controlled cross-over trial study in overweight men and women, drinking 500 ml water and to find out whether there is effectiveness of drinking water in overweight and obesity, could increase energy expenditure by 24% over 60 minutes after ingestion while there for weight reduction. was no effect in the comparator group drinking iso-osmotic saline and 50 ml water5. These Methodology: Studies for meta-analysis were selected according to inclusion criteria using two studies showed that drinking 500 ml of water could increase energy expenditure, electronic data-bases and hand-searching of theses, dissertations, term papers, protocol and consumption of different compositions of carbohydrate and fat could have different and research papers from January 1980 to January 2018. The study was registered at effects on male and female since the oxidation rate of carbohydrate and fat is different by PROSPERO and Myanmar Health Research Registry (MHRR). Systematic review and meta- gender. analyses were performed using the selected randomized controlled trials and quasi- experimental studies on reduction of weight using drinking water as an intervention. Water intake and hunger Results: Meta-analysis for weight loss interventions included eight studies on 998 partici- According to a cross-over randomized study in 19 healthy adults which assess pants. It showed that water intervention was not effective in reducing weight compared the gastric distension over time in response to small water load (50 ml) and large water to the comparator group with a standardized mean difference (SMD) - 0.02 kg (95%CI: load (350 ml) after standard meal, decreased hunger (p = 0.023) and increased fullness -0.27 to 0.23), (p = 0.86); high heterogeneity (I2 = 70%). In sub-group analysis according to (p = 0.030) were significantly more for large water load compared to small water load6. similar intervention which used 500 ml of drinking water before main meals and 250 ml of However, the underlying mechanism was not clear. water after meals, there was a significant reduction of weight in water group with SMD of -0.32 kg (95%CI -0.59 to -0.04), (p = 0.02); (I2 = 0%). Water intake and satiety Conclusion: Although meta-analyses of primary and secondary outcomes did not show The biochemical changes of hormones and peripheral peptides involved in significant effectiveness in the water group compared to the comparator group for all appetite and satiety upon water intake are not much known. Ghrelin, a known peptide included studies, there was significant weight reduction in the water group in subgroup which stimulates appetite, is mainly produced in stomach and smaller amounts from analysis comprising only three similar intervention studies which used drinking water other gastrointestinal parts, lung, immune cells, placenta, ovary, testis and kidney. Ghrelin before and after meals. level increases before meals and decreases after meals7. Ghrelin is produced when there Keywords: overweight, obesity, weight loss, weight reduction, water is no meal in the stomach as initiation for appetite stimulant, and decreases when the Introduction stomach is stretched with meals. This could be a mechanism of water intake in appetite control since ghrelin level may decrease when the stomach is full of fluid water. Obesity and obesity-related diseases have been a global burden. According to the global, regional and national prevalence of overweight and obesity in children and Water and energy intake adults from 1980 to 2013, body mass index (BMI) of both men and women has increased In experimental laboratory study involving visits 4 times done in 49 participants, over time. There was also an increasing trend of overweight and obesity in children and comparing the control group which drinks 500 ml of water 3.5 hours before lunch, and adolescents both in developed and developing countries1. In WHO 2014 report on non- group drinking two or three 500 ml bottles of water in the morning before lunch, it was communicable diseases, global deaths increased by two million, having 38 million global observed that water could suppress energy intake in normal weight participants but not deaths due to obesity-related diseases. It is estimated to increase to 52 million by 20302. in overweight or obese participants8. In obese older adults using laboratory test meals, Obesity is one of the factors causing diabetes, cancer, cardiovascular diseases. Weight loss 9 of at least 5% of initial weight in type 2 diabetes could result in decrease of HbA1 C level by water intake 500 ml before meals reduces energy intake at a breakfast meal . However, in 0.6% to 1.2%, improvement in blood lipid profile and blood pressure3. Hence, effective and another study using laboratory meals in healthy non obese young participants (21 to 35 low-cost intervention is needed to reduce the prevalence of non-communicable diseases. years old) and older participants (60 to 80 years old), pre-meal water intake reduces the 10 | Department of Nutrition and Food Safety, University of Public Health, Yangon energy intake in older participants but not in young participants . This could be due to n Department of Biostatistics and Medical Demography, University of Public Health, Yangon physiological differences between young and old age. The pre-meal water consumption Corresponding author: [email protected] Page 24 September 2020 - Vol: 62, No. 3 September 2020 - Vol: 62, No. 3 Page 25 Myanmar Medical Journal Myanmar Medical Journal may be helpful in reducing food intake in both old and young people. This may be and filtered according to inclusion criteria. Handsearching of theses, dissertations, term supported by the study carried out in 14 lean young males which showed that water papers, protocols and research papers was conducted in libraries of University of Public preload increased fullness and satisfaction and decreased hunger after trial11. Health, University of Medicine (1) and (2), Yangon, Department of Medical Research. Both British and American English words were used for search strategy using electronic Water intake as substitution databases. Weight is defined as participants’ body weight measured in grams, kilograms, According to observational studies, one possible mechanism of water in lowering pounds. Change in weight or Body Mass Index (BMI) measurements made at baseline, body weight may be due to lower total energy intake since sugar-sweetened beverages during trial, end of the trial and follow up records were assessed. Keywords used for were replaced with zero calorie water12, 13. search were “weight”, “overweight”, “obesity”, “obes*”, “body mass index”, “BMI”. For Therefore, the possible mechanisms of water intake in weight loss and weight anthropometric measures other than weight are skinfold thickness, waist circumference, body composition which are ratio of fat to fat free mass or percentage of body fat. control are possible increase of thermogenic effect, possibly decreased level of appetite Keywords used for search were “anthropometry”, “anthro*”, “measure*”, “skinfold”, stimulant ghrelin when stomach is stretched full with water fluid, substitution of sugar “waist”, “circumference”, “composition”, “fat”, “lipid”, “adipose”. sweetened beverages with water to reduce total energy intake, possible increase of satiety and reduction in energy intake. Hence, effect of water in obesity needs to be examined Caloric intake is the same as energy intake. It can be described in studies either as whether drinking water can be used to reduce weight, and how it can be used to reduce calories or kilocalories. Keywords used for search were “intake”, “consumption”, “calories”, weight, and how drinking water intervention has effects on anthropometric measures. “calor*”. Hunger is the feeling of discomfort due to lack of food, coupled with desire to eat. Studies described hunger in rating scale. Keyword used for search was “hunger”. Satiety Methods is the feeling or state of being sated or satisfaction and fullness. It is described in studies The study obtained ethical approval from Institutional Technical and Ethical as rating scale either as numeric or visual scale. Keywords used for search were “satiety”, Review Board, University of Public Health, Yangon, ITERB (2018/Research/5). The study “sati*”. Thermogenesis is production of heat in human body, measured with substrate protocol was registered at PROSPERO (CRD 42018091514) and MHRR (PLRID-00836_V3). oxidation rate and energy expenditure. Keywords used for search were “thermogenesis”, “thermo*”, “heat”, “energy”, “oxidation”. Adverse effects are water intoxication or sleep Inclusion Criteria disturbing nocturnal micturition or other adverse events described in included studies. Randomized controlled clinical trials and quasi-experimental trials in participants In PubMed clinical trials, for the above 28 keywords, each keyword was used of all ages, both overweight and obese participants, either healthy or with comorbid in advance search by selecting title/abstract in option, using “AND” boolean operator diseases were included. Types of interventions included were oral intake of water (either with “water”. The searches were also made with “hydration” instead of water using the cold or warm or hot water) as an intervention for weight reduction, either additional or same combination. In Science Direct and Cochrane Library Cochrane Central Register of non-additional daily water intake at specific times which has been carried out for at least Controlled Trials (CENTRAL), searches were conducted using the same combination used 2 weeks of intervention. Trials of fluid consumption for disease conditions such as urinary in PubMed in advanced search option by selecting abstract, title, keywords. tract infections, bladder cancer or certain medication, rather than for reducing weight were excluded. In Global Health Library - Global Index Medicus, boolean operators were used to search with keywords in title, abstract, subject in quick search and selecting title, abstract Full-text articles in English and the other languages which can be translated into in advanced search using the 28 key words, “water”, “randomized”, “trials”, “quasi”. English using online translation were searched and filtered according to inclusion criteria. When only abstract was available, the abstracts were reviewed whether the information In WHO International Clinical Trials Registry Platform (WHO, ICTRP) search, available was according to the inclusion criteria. This systematic review included RCTs the searches were made by placing each keyword of “overweight”, “obesity”, “obes*”, and quasi-experimental studies obtained from search strategies using keywords in a wide “weight”, “body mass index”, “BMI” in condition and “water” in intervention boxes of range of electronic databases, handsearching, and also assessing risk of bias. Studies advanced search. Those six keywords were used in combination with “aqua*”, “drink”, “H O”, “hydration” in intervention search box. included were dated from January 1980 to January 2018. 2 For Union Catalogue of Myanmar Health Science Libraries, search was done in Search Methods thesis, dissertation, term paper, journal, protocol, book, research paper in the Union Both electronic databases and handsearching were used for search strategy. Catalogue of Myanmar Health Science Libraries. Included institutions for search are Languages which can be translated into English using online translation were searched University of Medicine (1) Yangon, University of Medicine (2) Yangon, University of Page 26 September 2020 - Vol: 62, No. 3 September 2020 - Vol: 62, No. 3 Page 27 Myanmar Medical Journal Myanmar Medical Journal

Medicine, Mandalay, University of Medicine, Magway, University of Medicine, Taunggyi, Risk of bias Defence Services Medical Academy, University of Dental Medicine, Yangon, University Quality of the studies was assessed based on risk of bias including use of randomi- of Dental Medicine, Mandalay, University of Public Health, University of Community zation, allocation concealment, blinding of participants and investigators, completeness of Health, Magway, University of Pharmacy, Yangon, University of Pharmacy, Mandalay, outcome data, reporting and other potential bias according to description in the Cochrane University of Medical Technology, Yangon, University of Medical Technology, Mandalay, Handbook for Systematic Review of Interventions15, 16. University of Nursing, Yangon, University of Nursing, Mandalay, University of Traditional Differences between Protocol and Review Medicine, Mandalay. Keywords used were “water”, “aqua”, “drink”, “H2O”, “hydration”, “weight”, “overweight”, “obesity”, “obese”, “body mass index”, “BMI”, “anthropometry”, The studies were selected according to inclusion criteria of the protocol. In “anthropometric”, “measure”, “measures”, “measurement”, “skinfold”, “waist”, “circum- protocol, the studies using water as intervention for weight loss were included and did ference”, “fat”, “lipid”, “adipose”, “composition”, “consumption”, “intake”, “calorie”, not mention about weight maintenance studies. In the review, the studies with weight “calories”, “hunger”, “fullness”, “satiety”, “thermo”, “thermogenic”, “thermogenesis”, loss intervention using water which continued as weight loss maintenance were analyzed “heat”, “energy”, “oxidation”, “randomised”, “randomized”, “trials”, “quasi”. as subgroup-analysis. When there are more than two types of intervention in the study, the fluid with lowest energy calories was chosen as the comparator group. For Myanmar Medical Resource Centre: ProQuest Health Research Premium Collection, ProQuest Dissertations & Theses Global, advanced search option wasused Summary measures as (Title/Abstract) “water” AND “weight” (Anywhere), (Title/Abstract) “hydration” AND Standardised mean difference (SMD) with 95% CI was expressed for continuous “weight” (Anywhere), (Title/Abstract) “water”. In Google Scholar, advanced search option outcomes with different measurement scales. was used in title of the article. Key Words used were: “water”, “hydration”, “drink”, “weight”, “obesity”, “obese”, “body mass index”, “BMI”. In interventional studies of Clinical Trials. gov, keywords used were “weight”, “overweight”, “obesity”, “obese”, “obes*”, “body mass index”, “BMI”, “water”. Outcomes Primary outcome was change in body weight and secondary outcomes were change in waist circumference, body fat percentage, total fat mass, total fat-free mass, hip circum-ference, subcutaneous adipose tissue and visceral adipose tissue composition, caloric intake, hunger, satiety, thermogenesis, adverse effects. Data Extraction and Management Studies were selected according to inclusion criteria. Any discrepancies for the selection of studies among two review authors were solved by discussions and achieving consensus. Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) Flow Diagram was used for presenting and selection of studies14. In dealing with duplicates, the article with most complete data was used. Quantitative Systematic Review which includes meta-analysis was carried out. The data were entered into Review Manager 5.3 and SMD with 95% confidence interval (95%CI) was calculated with random effect model. Dealing with missing data We attempted to contact the study author of Larnkjaer 2015 study via the contact information of published article by sending an email. The Larnkjaer 2015 studywas excluded since the required data cannot be extracted from the published article. However, From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). the study may probably not alter the finding since the study was assessment of the effect Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. of intake of 1 L per day of skimmed milk, casein, whey or water on body composition and PLoS Med: 6 (6); e1000097. doi:10.1371/journal.pmed1000097, for more information, visit www. prisma-statement.org. leptin in overweight adolescents. Page 28 September 2020 - Vol: 62, No. 3 September 2020 - Vol: 62, No. 3 Page 29 Myanmar Medical Journal Myanmar Medical Journal

Results 2. Primary outcome: Change in BMI (kg/m2) between baseline and final measurements in water group versus comparator group 1. Primary outcome: Changes in weight in kilogram between baseline and final measurements in water group versus comparator group Figure 2.1. Forest plot of comparison: Change in BMI between baseline and final measurements in water group versus comparator group after weight loss intervention Figure 1.1. Forest Plot of Comparison: Change in weight between baseline and final measurements in water group versus comparator group after weight loss intervention

Footnote: +: Low risk of bias, ?: Unclear risk of bias, –: High risk of bias The meta-analysis for change in BMI in weight-loss intervention studies included four studies of 407 participants. It showed that water intervention was not effective in Footnote: +: Low risk of bias, ?: Unclear risk of bias, –: High risk of bias reducing BMI compared to the comparator group with SMD - 0.13 kg/m2 (95% CI: -0.33 to Primary outcome is change in weight, and according to pre-defined outcome 0.06), (p = 0.18); (I2 = 0%) (Fig. 2.1). measurements in the proposal, meta-analyses of weight changes and BMI changes were Figure 2.2 Forest plot of comparison: Change in BMI between baseline and final measurements carried out. The meta-analysis for change in weight in weight loss interventions included in water group versus comparator group after weight loss and weight maintenance intervention eight studies of total 998 participants. It showed that water intervention was not effective in reducing weight compared to the comparator group with SMD - 0.02 kg (95%CI: -0.27 to 0.23), (p = 0.86); high heterogeneity (I2 = 70%) (Fig. 1.1).

Figure 1.2. Forest plot of comparison: Change in weight between baseline and final measurements in water group versus comparator weight loss and weight maintenance intervention

Footnote: +: Low risk of bias, ?: Unclear risk of bias, –: High risk of bias The meta-analysis for change in BMI in both weight loss and weight maintenance interventions included six studies with a total of 517 participants. The result showed that the intervention was not effective in reducing BMI compared to comparator group with SMD - 0.16 kg/m2 (95% CI: -0.33 to 0.01), (p = 0.07); (I2 = 0%) (Fig. 2.2).

3. Subgroup analysis according to similar intervention Footnote: +: Low risk of bias, ?: Unclear risk of bias, –: High risk of bias Among total studies for weight loss intervention, only three studies used similar The meta-analysis for change in weight in both weight loss and weight maintenance intervention, which is drinking 500 ml water before meals (Dennis 2010 and Parretti 2015) interventions included 11 studies of total 1330 participants. It demonstrated that there and drinking 250 ml water after meals (Madjd 2016). was no more effectiveness in weight change of water group compared to the comparator group with a SMD 0.02 kg (95%CI: -0.23 to 0.27), (p = 0.85). There was also a high level of heterogeneity (I2 = 78%) (Fig. 1.2).

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Figure 3.1. Change in weight in kilogram between baseline and final measurements in meta-analyses of the primary outcome (change in weight). Therefore, subgroup analysis interventions using water 500 ml before meals or 250 ml after meals of weight loss intervention studies that used similar intervention was carried out. Only three studies used a similar intervention of water intake before meals or after meals. It showed a significant weight reduction in the water group than the comparator group. This finding shows that drinking water before main meals or after meals could have potential for weight loss. Many systematic reviews were conducted to assess the association between water consumption and body weight outcomes, with different study designs. There were controversial results regarding the effects of water intake and body weight changes

Footnote: +: Low risk of bias, ?: Unclear risk of bias, –: High risk of bias not only in the systematic review of the cross-sectional studies but also inconsistent A meta-analysis was done using three studies in which 500 ml drinking water results were observed in the systematic review of three randomized trials without meta- before meals or 250 ml after meals were used as an intervention. A total of 206 participants analysis17. In the systematic review of four longitudinal studies and nine cross sectional were included, and the result showed that there was a significant weight reduction in studies about the association between water consumption and body weight outcomes in water group than the comparator group with SMD - 0.32 kg (95% CI -0.59 to -0.04), (p = children and adolescents, the effects of water intake upon body weight were controversial 0.02); (I2 = 0%) (Fig. 3.1). Meta-analysis of two studies (Dennis 2010 and Parretti 2015) and there was no meta-analysis to reveal the pooled effect18. Similarly, in the systematic which use 500 ml of drinking water prior to three main meals for 12 weeks also showed review of impact of water intake on energy intake and weight status, the findings were a significant reduction in weight (kg) in water group than comparator group after weight inconclusive for the impact of water intake on energy intake and body weight19. However, loss intervention, with SMD of - 0.40 kg (95%CI: -0.76 to -0.05) (p = 0.03); I2 = 0% (Figure the most consistent finding was that sugar sweetened beverages increased significantly not shown). energy intake compared to water intake. The studies included in the previous systematic review were of different study designs and most were observational longitudinal studies Figure 4. Funnel plot of comparison for change in weight in water group versus comparator group after weight loss intervention and cross-sectional studies. The funnel plot is symmetrical. In the total of 11 studies of our systematic review and meta-anlysis, five studies Therefore, it does not suggest that did not have an objective indicator for adherence check. The objective indicators used publication bias affects this outcome. for adherence check of water intake were both urine volume and specific gravity at six The study assessed the other months and 12 months of the study period in two studies, urine osmolality check in secondary outcomes of change in two studies and specific gravity in two other studies. Moreover, the intervention using waist circumference, body fat per- drinking water may have poor adherence to increased water intake throughout the study centage, total fat mass, total fat- and compliance with recommendations such as avoidance of other beverages. There will free mass, total energy intake. The also be a difference in the total intake of other beverages depending on weather, physical meta-analysis results showed no activity, diet pattern, salt intake. The lack of compliance checks for increased water intake significant reduction in the water and avoidance of other beverages in the included studies might influence the study's non- group in comparison with the com- significant findings by under-reporting or over-reporting of water intake. parator group (Figures not shown). The study assessed secondary outcomes of change in waist circumference, body fat percentage, total fat mass, total fat-free mass, total energy intake but cannot assess Discussion the other secondary outcomes which are satiety score, hip circumference, subcutaneous In the total 11 included studies, interventions were different individually, and adipose tissue, and visceral adipose tissue composition, because of only one study for the studies had at least three months of the intervention period. There was no study each outcome. These studies showed no significant difference between the water group which carried out a method of drinking water only to lose weight. In meta-analyses of and comparator group for the satiety, the relative amount of subcutaneous abdominal primary outcomes and secondary outcomes, there was no significant change in weight adipose tissue, the accumulation of visceral adipose tissue, liver fat, muscle fat, and hip in the water group compared to the comparator group. There was high heterogeneity in circumference. There were two studies (Dennis 2010, Parretti 2015) which assessed Page 32 September 2020 - Vol: 62, No. 3 September 2020 - Vol: 62, No. 3 Page 33 Myanmar Medical Journal Myanmar Medical Journal

fullness. However, the scale used for assessment was different and cannot be analyzed. Circulating Triglycerides and the Prevalence of Metabolic Syndrome in Obese but Not in Although there were three studies (Dennis 2010, Peters 2014 and Peters 2016) which Overweight Mexican Women in a Randomized Controlled Trial. The Journal of Nutrition. assessed hunger, these studies used different subjective scales and hence meta-analysis 2014; 144 (11): 1742-1752. https://pubmed.ncbi.nlm.nih.gov/25332472/ cannot be performed. Madjd 2016 Madjd A, Taylor M, Delavari A, Malekzadeh R, Macdonald I, Farshchi H. Beneficial effects Conclusion and Recommendations of replacing diet beverages with water on type 2 diabetic obese women following a hypo- Although meta-analyses of primary and secondary outcomes did not show energetic diet: A randomized, 24-week clinical trial. Diabetes, Obesity and Metabolism. significant effectiveness in the water group compared to the comparator group for all 2016; 19 (1): 125-132. https://dom-pubs.onlinelibrary.wiley.com/doi/abs/10.1111/dom. included studies, there was significant weight reduction in the water group in subgroup 12793 analysis with only three similar intervention studies which use drinking water before and Madjd 2018 after meals. Hence, the study concluded that drinking water 500 ml before the main meals Madjd A, Taylor M, Delavari A, Malekzadeh R, Macdonald I, Farshchi H. Effects of replacing might have the potential for weight loss. More randomized controlled trials with large diet beverages with water on weight loss and weight maintenance: 18-month follow-up, sample size using drinking water only for weight loss with the control of the potential risk randomized clinical trial. International Journal of Obesity. 2018; 42 (4): 835-840. http:// of bias is warranted to confirm the effect of drinking water upon weight loss. dx.doi.org/10.1038/ijo. 2017.306 Maersk 2012 Declaration of Conflict of Interest - We declare there is no conflict of interest. Maersk M, Belza A, Stødkilde-Jørgensen H, Ringgaard S, Chabanova E, Thomsen H et al. Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat Authors Contribution depot: a 6-month randomized intervention study.The American Journal of Clinical Nutrition. Conceptualization|, n, Formal Analysis|, n, Funding Acquisition|, n, 2012; 95 (2): 283-289. https://academic.oup.com/ajcn/article/95/2/283/4576708 |, n |, n | | | Methodology , Investigation , Software , Validation , Visualization Parretti 2015 Parretti H, Aveyard P, Blannin A, Clifford S, Coleman S, Roalfe Aet al. Efficacy of water Acknowledgement preloading before main meals as a strategy for weight loss in primary care patients with We would like to thank Prof. Dr. Khay Mar Mya, retired Rector of the University obesity: RCT. Obesity. 2015; 23 (9): 1785-1791. https://onlinelibrary.wiley.com/doi/full/ of Public Health, Yangon, for permission to carry out the study and her kind support. 10.1002/oby.21167 Funding for this study is from Implementation Research Grant, Ministry of Health and Peters 2014 Sports, Myanmar. Peters J, Wyatt H, Foster G, Pan Z, Wojtanowski A, Vander Veur S et al. The effects of

water and non-nutritive sweetened beverages on weight loss during a 12-week weight References loss treatment program. Obesity. 2014; 22 (6): 1415-1421. https://pubmed.ncbi.nlm.nih. Included studies for systematic review gov/24862170/ Akers 2012 Akers J, Cornett R, Savla J, Davy K, Davy B. Daily Self-Monitoring of Body Weight, Step Peters 2016 Count, Fruit/Vegetable Intake, and Water Consumption: A Feasible and Effective Long- Peters J, Beck J, Cardel M, Wyatt H, Foster G, Pan Z et al. The effects of water and non- Term Weight Loss Maintenance Approach. Journal of the Academy of Nutrition and nutritive sweetened beverages on weight loss and weight maintenance: A randomized Dietetics. 2012; 112 (5): 685-692.e2. http://dx.doi.org/10.1016/j.jand.2012.01.022 clinical trial. Obesity. 2016; 24 (2): 297-304. https://onlinelibrary.wiley.com/doi/full/ 10.1002/oby.21327 Dennis 2010 Dennis E, Dengo A, Comber D, Flack K, Savla J, Davy K et al. Water Consumption Increases Tate 2012 Weight Loss During a Hypocaloric Diet Intervention in Middle-aged and Older Adults. Tate D, Turner-McGrievy G, Lyons E, Stevens J, Erickson K, Polzien K et al. Replacing Obesity. 2010; 18 (2): 300-307. http://dx.doi.org/10.1038/oby.2009.235 caloric beverages with water or diet beverages for weight loss in adults: main results of the Choose Healthy Options Consciously Everyday (CHOICE) randomized clinical trial. The Hernández-Cordero 2014 American Journal of Clinical Nutrition. 2012; 95 (3): 555-563. https://pubmed.ncbi.nlm. Hernández-Cordero S, Barquera S, Rodríguez-Ramírez S, Villanueva-Borbolla M, González nih.gov/22301929/ de Cossio T, Dommarco J et al. Substituting Water for Sugar-Sweetened Beverages Reduces

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Wong 2017 12. Murakami K, Sasaki S, Takahashi Y, Uenishi K. Intake of water from foods, but not Wong J, Ebbeling C, Robinson L, Feldman H, Ludwig D. Effects of Advice to Drink 8 Cups of water from beverages, is related to lower body mass index and waist circumference Water per Day in Adolescents With Overweight or Obesity. JAMA Pediatrics. 2017; 171 (5): in free-living humans [corrected]. Nutrition. 2008 June; 24 (10): 925-932. DOI: e170012. https://pubmed.ncbi.nlm.nih.gov/28264082/ 10.1016/j.nut.2008.04.002

Other References 13. Fresán U, Gea A, Bes-Rastrollo M, Ruiz-Canela M, Martínez-Gonzalez MA. Substitution models of water for other beverages, and the incidence of obesity 1. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, and weight gain in the SUN Cohort. Nutrients. 2016 Oct; 8 (11): 688. doi: 10.3390/ regional, and national prevalence of overweight and obesity in children and adults nu8110688. during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014 May; 384 (9945): 766-781. http://www.thelancet.com/article/ 14. Moher D, Liberati A, Tetzlaff J, Altman DG. Systematic Reviews and Meta- S0140673614604608/fulltext Analyses: The PRISMA Statement. Annu Intern Med. 2009 Aug; 151 (4): 264-9. doi: 10.7326/0003-4819-151-4-200908180-00135. 2. WHO. Global on noncommunicable diseases, 2014. 15. Higgins JP, Green S. Cochrane Handbook for Systematic Reviews of Interventions. 3. Franz MJ, Boucher JL, Rutten-Ramos S, VanWormer JJ. Lifestyle Weight-Loss Cochrane Handbook for Systematic Reviews of Interventions: Cochrane Book Intervention Outcomes in Overweight and Obese Adults with Type 2 Diabetes: A Series. 2008. 196-202. Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Acad Nutr Diet. 2015; 115 (9): 1447-1463. http://dx.doi.org/10.1016/j.jand.2015.02.031 16. Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomized trials. BMJ. 4. Boschmann M, Steiniger J, Hille U, Tank J, Adams F, Sharma AM, et al. Water- 2011; 343 (7829): 1-9. Induced Thermogenesis. J Clin Endocrinol Metab. 2003 Dec; 88 (12): 6015-9. doi: 10.1210/jc.2003-030780. 17. Muckelbauer R, Sarganas G, Gruneis A, Muller-Nordhorn J. Association between water consumption and body weight outcomes: a systematic review. Am J Clin 5. Boschmann M, Steiniger J, Franke G, Birkenfeld AL, Luft FC, Jordan J. Water drinking Nutr. 2013 Aug; 98 (2): 282-299. induces thermogenesis through osmosensitive mechanisms. J Clin Endocrinol Metab. 2007 Aug; 92 (8): 3334-7. doi: 10.1210/jc.2006-1438. 18. Muckelbauer R, Gortmaker SL, Libuda L, Kersting M, Clausen K, Adelberger B, et al. Changes in water and sugar-containing beverage consumption and body weight 6. Camps G, Veit R, Mars M, de Graaf C, Smeets PA. Just add water: Effects of added outcomes in children. Br J Nutr. 2016 Jun; 115 (11): 2057-66. gastric distention by water on gastric emptying and satiety related brain activity. Appetite. 2018; 127: 195-202. https://doi.org/10.1016/j.appet.2018.04.023 19. Daniels MC, Popkin BM. Impact of water intake on energy intake and weight status: A systematic review. Nutr Rev. 2010; 68 (9): 505-521. 7. Austin J, Marks D. Hormonal regulators of appetite. Int J Pediatr Endocrinol. 2009; 2009: 141753. doi: 10.1155/2009/141753.

8. McKay NJ, Belous I V., Temple JL. Increasing water intake influences hunger and food prefe-rence, but does not reliably suppress energy intake in adults. Physiol Behav. 2018; 194: 15-22. http://linkinghub.elsevier.com/retrieve/pii/S0031938418302051 9. Davy BM, Dennis EA, Dengo AL, Kelly L, Davy KP, Davy BM, et al. Water Consumption Reduces Energy Intake at a Breakfast Meal in Obese Older Adults. J Am Diet Assoc. 2008 Jul; 108 (7): 1236-1239. doi: 10.1016/j.jada.2008.04.013 10. Van Walleghen EL, Orr JS, Gentile CL, Davy BM. Pre-meal water consumption reduces meal energy intake in older but not younger subjects. Obesity. 2007 Jan; 15 (1): 93-99. doi: 10.1038/oby.2007.506. 11. Corney RA, Sunderland C, James LJ. Immediate pre-meal water ingestion decreases voluntary food intake in lean young males. Eur J Nutr. 2016 March; 55 (2): 815-819. doi: 10.1007/s00394-015-0903-4.

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Perceptions of wholesale dealers and smokers towards health warnings related conditions with 1.2 million people being exposed to second-hand smoke[1]. In of tobacco products: cigarettes and cheroots, Myanmar 2003, World Health Organization (WHO) developed a Framework Convention for Tobacco Control (FCTC) which includes guidelines to reduce tobacco use and packaging and t | n v « Y Than Sein , Le Le Win , Aung Pye Phyo , Yin Thet Nu Oo , Kyaw Lwin Show , Kyaw Thu Hein labeling of tobacco products[2]. Moreover, many countries advocated legal requirements with regard to health warnings in the tobacco products[3]. Abstract Background: Tobacco use has been increasing among all age groups. This study attempted In Myanmar, the WHO STEP wise approach to surveillance (STEP) survey in to identify the presence of pictorial and health warnings among tobacco products and 2014 reported that approximately 26% of people were current smokers[4]. And tobacco understand the perceptions of whole sale dealers and consumers towards those warnings. accounted for one in five of all deaths[5]. Moreover, tobacco use has been increasing among all ages[6]. In order to reduce tobacco consumptions, Myanmar stipulated The Methods: This cross-sectional study was conducted by observation of 42 wholesale shops and in-depth interviews (IDIs) with 41 dealers and 31 adult smokers during 2018 and 2019 Control of Smoking and Consumption of Tobacco Product Law in 2006 and Ministerial notification on the requirement to place warning labels, and tax stamp on the packages in 5 major cities of Myanmar with tobacco production. of tobacco product was issued in 2016[7-9]. Ever since the tobacco control law has been Results: Some brands of cheroot had warnings, but these varied among different brands enacted and the notification issued, whether tobacco manufacturers follow the guidance in terms of pictorial presentation of cancerous lung and text messages; also in the shape of the legislation is unknown, which would have effect in reducing tobacco consumption. of packing and the number of cheroots per pack. The respondents noticed the annual In this context, the present study attempted to identify the presence of health warnings change in picture on cigarette packs. The majority of dealers were more aware of pictorial on tobacco products, and the perceptions towards pictorial and health warnings displayed and text warnings than smokers, mainly for the cigarettes. With regards to text warning in the tobacco products. messages, most could only mention about the age restriction. While dealers, cigarette sellers in particular, viewed that their business was declining since sale power of tobacco Methods products was reduced due to raising of tax and other factors, especially the presence of A cross-sectional, mixed-methods study was conducted at the main local markets pictorial warning after proclamation of tobacco law. Meanwhile, the smokers explained from Yangon, Mandalay, Myingyan, Bago and Taunggyi where dry goods are sold. These that the pictures were scary but this would not be effective to make them quit or reduce cities were chosen purposively because these cities widely manufacture local tobacco smoking. product like cheroot, and have a number of markets selling tobacco products[10]. Forty Conclusion: The health warnings are considered to be ineffective for the chronic smokers two whole sale shops selling cigarettes and/or cheroots from the main local public market but seemed to be effective for the beginners. Reinforcement and encouragement for were identified for observation, and among those shops, 41 dealers from those whole using officially identified pictures, proper display of health warnings, and modifying the sale shops and 31 adult smokers (18 years or older) around the market who gave consent shapes of packaging among the local cheroot industries are needed. were recruited by convenient sampling. Pre-tested in-depth interview guide was used to Keywords: tobacco, perception, health warning, pictorial warning explore their perception on health warnings, awareness to the tobacco law and opinion on the effectiveness of health warnings. Observation checklist was applied to the whole Introduction sale shops to collect the cigarette and cheroot brands sold, prices and format used for Tobacco use is one of the biggest global public health concerns with about 1.1 health warnings. Descriptive analysis was done for socio-demographic characteristics, and billion smokers living in 2018 and of them, around 80% live in low- and middle-income cigarette and cheroot prices and thematic analysis was done for qualitative results. Ethical countries[1]. It is the most important preventable risk factor for many non-communicable approval was obtained from University of Public Health (UPH-IRB 2018/Research/50) and infectious diseases. More than eight million people die every year due to tobacco dated 30 November 2018.

t President, People’s Health Foundation Findings | Deputy Director (Retired), Department of Medical Research n Research Officer, Medical Statistics Division, Department of Medical Research Table 1 described the background characteristics of the respondents. Majority v Deputy Director, Health Systems Research Division, Department of Medical Research of dealers were involved in tobacco business for years and sold either cigarettes only or « Research Officer, Health Systems Research Division, Department of Medical Research Yangon both cigarettes and cheroots. Regardless of the tobacco types, all smokers recruited were Y Research Officer, Epidemiology Research Division, Department of Medical Research (Pyin Oo Lwin Branch) males and one in three smokers (29.03%) had been smoking for more than 30 years. Corresponding author: [email protected]

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Table 1. Socio-demographic characteristics of respondents involved in in-depth interviews (IDIs) Years of smoking tobacco Not relevant Not relevant 1 - 10 12 (38.71) Characteristics Whole sale dealers (n = 41) Smokers (n = 31) 11 - 30 10 (32.26) Frequency Percentage Frequency Percentage > 30 9 (29.03) Age (in years) 20 - 30 3 (7.32) 10 (32.26) Market availability of cigarettes and cheroots 31 - 40 5 (12.19) 4 (12.90) 41 - 50 7 (17.07) 9 (29.03) During the period of data collection, 26 cigarette brands and 60 cheroot brands 51 - 60 6 (14.63) 6 (19.35) were observed selling in the study cities. Generally, the price of a cigarette pack (20 > 60 6 (14.63) 2 (6.45) sticks per pack) of these 26 cigarette brands ranged from 250 Kyats to 2500 Kyats. In the Unknown 14 (34.15) 0 (0) markets at all sampled cities, cigarette brands mostly available were “Red Ruby” followed Sex by “Premium Gold”. Around 95% of cigarette brands displayed not only text messages, Male 21 (51.22) 31 (100) Female 20 (48.88) 0 (0) ingredients, pictorial warning in Myanmar language but also included tax stamp. Cigarette Education brands without proper pictorial warnings and text messages were also found. According Illiterate 0 (0) 1 (3.23) to wholesale dealers, these cigarette brands were mostly smuggled, being told by the Can read and write 1 (2.44) 1 (3.23) wholesale dealers during in-depth interviews (IDIs). Passed primary school 2 (4.88) 4 (12.90) Passed middle school 1 (2.44) 13 (41.94) Regarding cheroots, the price of a bundle/pack of 50 sticks ranged between Kyats Passed high school 3 (7.32) 7 (2.26) 400 to 6400. “Kyal Ni” and “Shwe Pyi Soe” were the most available brands in the markets, Graduated 18 (43.90) 4 (12.90) but there was lack of uniformity in either text message or its occupied percentage as Unknown 16 (39.02) 1 (3.23) instructed by the Ministry of Health and Sports (MoHS). Although 70% of cheroot brands Type of respondent Not relevant Not relevant Owner 36 (87.80) included pictorial warning, half of them printed a picture of a cancerous lung over the Relative of owner 4 (9.76) years, in the absence of official instruction by MoHS. Each cheroot brand had different Employee 1 (2.44) formats of the picture of cancerous lung and text messages, packing shapes (i.e., rectangle, Type of tobacco sold Not relevant Not relevant circle, square, etc.), and number of cheroots per pack. Additionally, individual cheroot Cigarette 16 (39.02) rolls, and bundles of rejected quality cheroot were found with absence of the warnings. Cheroot 7 (17.07) Both 18 (43.90) The consumption of tobacco products varied depending on the smokers’ preference on types of tobacco, brands and their tastes. Duration of selling tobacco Not relevant Not relevant Less than one year 6 (14.63) 1 - 10 11 (26.83) Awareness of health warnings in tobacco products 11 - 30 10 (24.39) Generally, dealers were more likely to be aware of health warnings than smokers, > 30 4 (9.76) mostly pictorial warnings. Majority of dealers and smokers noticed health warnings on Unknown 10 (24.39) most brands of cigarette packs and some cheroot brands. Most dealers and smokers could Occupation Not relevant Not relevant Government staff 6 (19.35) mention more on age restriction of smoking compared to health risks and ingredient Taxi driver 13 (41.94) descriptions. Only a few knew about tax stamp and Tobacco Law. Several dealers and Own small business 4 (12.90) smokers were aware of the annual change in the pictorial warning on cigarette packs. Student 1 (3.23) However, except for a picture of throat cancer, they could identify other pictures. Dependent 4 (12.90) Manual worker 3 (9.68) Perceptions towards health warnings of tobacco products Type of tobacco smoked Not relevant Not relevant Cigarette 4 (12.90) During IDIs, the smokers explained that the pictures were scary, but there might Cheroot 4 (12.90) be no effect on wanting to quit/reduce smoking among them. Majority of sellers and Both 23 (74.19) smokers of both cigarette and cheroot considered pictures of cheek and cancerous lung as the most scary ones. On the other hand, picture of throat cancer was regarded as the

Page 40 September 2020 - Vol: 62, No. 3 September 2020 - Vol: 62, No. 3 Page 41 Myanmar Medical Journal Myanmar Medical Journal least scary one; they thought the picture was showing a patient intubated with oxygen, Discussion whereby many respondents could not relate it to smoking. The picture of a cancerous lung The majority of respondents were not much interested in health warnings. was deemed more appropriate; majority of both types of respondents appreciate that Additionally, qualitative findings underscored that there might be no remarkable impact while tongue cancer was mainly a concern for betel chewers, lung cancer mostly affected in tobacco consumption due to health warning on the packs / bundles. Instead, health the smokers. problems, influences of family members and personal determination to quit tobacco were One of the dealers who was a graduate and who had been selling cigarettes for 20 the reasons for a slight reduction in consumption among the smokers. The obsession years expressed that presenting the ugly pictures on the cigarette packs could reduce sale, of long-term smokers to tobacco products, easy accessibility to buy tobacco products, and described his opinion widely as follows. availability of most brands of cheroot bundles and individual stick of cigarettes/cheroots with no warnings, were the main factors for this issue. One study done in India among “First, it was a picture of par-saung (cheek cancer), but it should be for betel chewers. Next, a picture of tongue cancer. Cigarette packs with these pictures were smokeless tobacco products found similar finding that poor quality of pictures and [11] considered as unpleasant things for giving presents to wedding attendees. Rural people absence of warnings on the products could not achieve the desired impact . didn’t buy them, especially at Kachin state and it became zero market. My selling power With regards to the effect of health warnings for smoking-related cancers, several had reduced about 70%. These pictures are the main cause for this. It also affected the studies including the present study found that there was dissuasion effect even among border market, because we couldn’t sell cigarettes with pictures there. The second outcome smokers: pictures were considered not only as superior to the text only warnings, they is increasing the price of cigarettes. Now, there are only 2 cigarette shops in this bazaar, were viewed as effective in motivating smoking cessation and preventing initiation of previously there were 10 shops. However, I support the showing pictures as a warning to smoking as well[11 - 15]. lengthen life expectancy. Nowadays, most die at about 60 years of age.” Conclusions Opinion towards the effect of health warnings In conclusion, in study areas, the health warnings were considered to be ineffective As for the effect of health warnings, the dealers and smokers had similar opinions for chronic smokers but seemed to be effective for the beginners. However, dissemination namely getting mixed messages regarding new packages and recognition of health risks. of health warnings about tobacco products through different channels would be beneficial Current health warnings on packages were considered to be ineffective for chronic for the beginner smokers. Providing reinforcement and encouragement to follow legis- smokers but seemed to be effective for the beginners. The main reason revealed in IDIs lations to the local cheroot industries is critical, for using official identified pictures, for reduction in smoking was due to either disapproval of family members, and health proper display of health warnings and modifying the shapes of packing. Furthermore, problems or a combination of both, rather than due to the warnings. At the same time, collaboration among different ministries need to be strengthened to control smuggled smokers were still purchasing tobacco products. Dealers, particularly the cigarette sellers, tobacco products. viewed that their business was declining since sale of tobacco products was reduced due to raised taxation and other factors, especially the presence of pictorial warning after Disclosure statement proclamation of tobacco law. Meanwhile, most of the smokers stated the presence of The authors declare no conflict of interest. health warning would not be effective to quit smoking. References “I reduce the number of cigarettes from one pack to 4 rolls a day because I feel 1. World Health Organization (2019). Tobacco Key Facts. https://www.who.int/news- tired easily after years of smoking. As I’m a taxi driver, it’s not good for me driving tired.” room/fact-sheets/detail/tobacco. A 29-year-old graduate smoker 2. World Health Organization (2003). WHO Framework Convention on Tobacco “The smokers already recognized that smoking is harmful for them. Whether there Control. Geneva. doi:10.1590/S1135-57272003000400005 is a picture or not, they will smoke. Whatever the type of picture is used, they will smoke without looking it. Even if the price is increased, those who can afford will smoke. I think 3. Deborah Arnott. Implementation of picture warnings on tobacco products. Action the picture alone is not enough. People should obey the Tobacco Law. Health education Smok. Heal. 2008. https://ash.org.uk/media-and-news/press-releases-media-and- should be given widely at schools to prevent children from starting to smoke.” news/1-october-2008-implementation-of-picture-warnings-on-tobacco-products/. A graduate cigarette dealer

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4. Latt TS, Zaw KK, Ko K,et al. National survey of Diabetes Mellitus and risk factors for Potential effectiveness of telephone consultation and triage in primary NCD in Myanmar. Yangon, 2014. healthcare service

5. World Health Organization (2018). Fact Sheet 2018, Myanmar. Phyo Wai Htunn, Kaung Set Aungn, Swam Saung Oon, Kyaw Thu Hein|, Kyaw Ko Ko Htet| and | 6. World Bank Group (2019). Myanmar Overview of Tobacco Use, Tobacco Control Saw Saw Legislation, and Taxation. A Country Brief. Abstract 7. Ministry of Health (2006). The Control of smoking and consumption of Tobacco Background: Medical consultation on telephone has been used in many countries since Product Law. two decades ago. It was proved by some studies to be effective in cutting down the 8. Ministry of Health and Sports (2016). Order of printing warning images and taxes unnecessary patients’ visits to the health care providers. The 7887 Healthcare Call Centre on the packages of tobacco products. is the primary healthcare call centre in Myanmar that has been delivering healthcare consultation services by trained and licensed doctors on telephone to the Myanmar Posts 9. Than Sein. A review of Tobacco Use: tobacco industry and tobacco taxation in and Telecommunications (MPT) mobile phone users in Myanmar since October, 2016, Myanmar. People’s Health Foundation and Southeast Asia Tobacco Control Alliance, by using standardized telephone triage protocols and the national healthcare guidelines 2015. from the Ministry of Health and Sports of Myanmar. 10. Than Sein. Why Tobacco economics? Presentations at Training Seminar on Tobacco Objectives: (1) To determine the service utilization status of ‘7887’ healthcare call centre Economics, May 14-15, 2018. PHF Office, Yangon. by the population in Myanmar (2) To estimate the effectiveness of telephone consultation 11. Talreja K, Rajpurohit L, Thawani P. Effect of statutory and pictorial health warning and triage in primary healthcare service in the community. among people consuming tobacco products in Pune city, India - a questionnaire Method: We analyzed 1494 randomized telephone consultations representative of study. The journal of Community Health Management. 2016 April - June; 3 (2): 75- incoming calls at ‘7887’ Healthcare Call Centre within the period of July, 2017 to June, 79. 2018. 12. Malick Shahbaz Ahmad Tahir. Impact of pictorial warning on cigarette packs. Results: Out of 944 patients who consulted with ‘7887’ doctors, 779 (82.5%) of them ADGROUP, Islamabad, 2009. were between 15 - 64 years of age and from a wide range of occupational backgrounds. 13. Heydari GR, Ramezankhani A, Talishi F. The impacts of cigarette packing pictorial 173 (52%) of all townships in Myanmar have utilized the call centre at least once in study period with 40.6% and 11.7% from Yangon and Mandalay divisions, respectively. Top warning labels on smokes in the city of Tehran. Tanaffos 2011; 10 (1): 40-47. five consultation categories were general medicine (23%), adolescent and reproductive 14. Suci Puspita Ratih and Dewi Susanna. Perceived effectiveness of pictorial health health (14%), health education purpose (10%), aesthetics and dermatology (9%) and warnings on changes in smoking behavior in Asia: a literature review. BMC Public gastrointestinal (9%). The top specific complaints found in each of the above categories Health (2018); 18: 1165. https://doi.org/10.1186/s12889-018-6072-7. were fever, menstruation-related complaints, miscellaneous health education questions, 15. Woelbert E, Hombres B, et al. Pictorial health warnings and wear-out effects: skin lesions and abdominal pain/discomfort, respectively. Nearly 80% did not need any evidence from a web experiment in 10 European countries. http://dx.doi.org/ referral. The referred cases were mostly those which needed specialists’ assessment and 10.1136/tobaccocontrol-2018-054402. were often directed by the call centre to private healthcare institutions. 933 (two-thirds) of 1362 patients were managed by telephone counseling including health education without prescribing any medicine. Conclusion: Telephone consultation seems to be an effective way in reducing unnecessary hospital or clinic visits with standardized telephone triage system at primary care level. Moreover, service providers can make use of telephone consultation in provision of counseling and health education services for the community. n Medical Department, 7887 Healthcare Call Centre, Yangon, Myanmar | Department of Medical Research (Pyin Oo Lwin Branch), Myanmar Corresponding author: [email protected] Page 44 September 2020 - Vol: 62, No. 3 September 2020 - Vol: 62, No. 3 Page 45 Myanmar Medical Journal Myanmar Medical Journal

Introduction Established in 2016 and partnering with Myanmar Posts and Telecommunications Telephone consultation is the process where calls are received, assessed and (MPT), ‘7887’ Healthcare Call Centre is being operated by qualified, licensed and trained managed by giving advice or by referral to a more appropriate healthcare service.1 It has medical doctors, who are assigned as telephone agents in provision of the services with been used by some countries since more than two decades ago.2, 3, 4 24/7 access. With the primary target on the general public residing in remote areas of Myanmar who have transportation and financial constraints, it aims to be beneficial for National Health Service (NHS) Direct made the UK a world leader in telephone those with middle and low socio-economic status. consultation. Established in 1998, this free 24 hour nurse-led help line annually received The medical doctors at ‘7887’ provide informative health education, and consu- around five million telephone calls asking for medical advice, of which 60% were solved ltation based on the caller’s symptoms, and address general and/or specific health queries. without referral needs and below 0.01% complained. NHS Direct was effective in Chronic disease monitoring and follow-up are also found to be feasible. Moreover, the decreasing the workload of NHS and GPs.4 Between 2009 and 2010, NHS Direct prevented doctors correct any misbeliefs and misconception, and provide medical second opinions. 2.4 million primary care appointments and 1.6 million emergency visits by ambulance. It ‘7887’ serves as a front line medical service provider that lays down a triage system cost £ 90 million annually5, but saved approximately £ 213 million.6 nationwide. Triage system is established to assess the severity level of patients’ conditions M-health is defined as mobile Information and Communication Technology (ICT) and refer them to most appropriate hospitals and clinics nearby. Furthermore, the doctors rd for healthcare which signifies the evolution of emerging wireless e-health systems via 3 provide safe home remedies, prescribe over-the-counter drugs and deliver first aid advice. th 7 and 4 Generation (3G and 4G) mobile networks. Straight forwardly, it is the provision of The doctors have all the necessary resources to keep pace with the recent and latest healthcare services through mobile devices. medical research, knowledge and treatment protocols. All voice calls are recorded for the The majority of the population in Myanmar are living in rural areas (approximately purpose of delivering training and evaluation to the doctors and for quality control (QC). 70% of total population) and have limited access to adequate healthcare services.8 Limited The main goals of this study are (1) To determine the service utilization status access to healthcare facilities has a negative impact on their quality of life owing to un- of ‘7887’ healthcare call centre by the population in Myanmar (2) To estimate the met health needs, delay in receiving appropriate care, lack of preventive services, and effectiveness of telephone consultation and triage in primary healthcare service in the hospitalizations that could have been prevented. ICT can act as a catalyst to stimulate community.

Myanmar’s developmental catch-up plans to leapfrog the intermediate stages of the conventional bricks-and-mortar route in other principal industries including health sector. Materials and methods M-health that saves time, energy and cost from individual to national level is proposed A cross-sectional descriptive study was conducted by using the telephone as a countrywide-accessible tool to fulfill the health needs of Myanmar inhabitants by consultation data of the ‘7887’ Healthcare Call Centre from July, 2017 to June, 2018. overcoming geographical boundaries. The data were derived from the representative months of all three seasons in Myanmar (March for the Summer, July for the Rainy season and November for the Winter). Totally, In analysis of industry in Myanmar, there are a handful of companies and 1494 randomized incoming telephone consultations were analyzed. individuals striving for health-related telephone services. These included health sections of general call centres (1876 and 1212), and RH (Reproductive Health) hot lines under MMA Data collection procedure (Myanmar Medical Association) and some NGOs (Non-Governmental Organizations). The medical data from the telephone consultation with the patients/clients at However, the former cannot pay enough attention to the health industry, and the latter ‘7887’ Healthcare Call Centre are recorded in the Customer Relationship Management lacks CSFs (Critical Success Factors) (e.g., 24 hour service). Poor marketing also resulted (CRM) system, a call centre platform’s user-interface, which is used as an electronic in low awareness. Thus, many potential customers and M-health initiatives remain under medical record (EMR) of all incoming telephone calls at the call centre. served by the incumbents. This forms the gap for Trust Oo M-health Enterprise to establish ‘7887’ Healthcare Call Centre with the aim of becoming a fruitful entrepreneurial service All the recorded data were collected again systematically in separate columns provider that fulfills the health needs of the poor in Myanmar. This digitally-delivered according to their categories such as (1) age, gender, marital status, occupation, township healthcare makes use of a world-class health-specific telephone service line that remotely and states/regions for socio-geographic characteristics of callers, (2) medical complaints provides effective and consistent health information and expert advice, and/or timely and call deposition types for common health complaints consulted at the call centre and referral to recommended healthcare units. (3) referral status, providing health education and counselling and drugs prescribed (Over- The-Counter drugs, usually for minor ailments) for response of the call centre in the Excel file. Page 46 September 2020 - Vol: 62, No. 3 September 2020 - Vol: 62, No. 3 Page 47 Myanmar Medical Journal Myanmar Medical Journal

Data in July and November of 2017 and in March of 2018 were collected as a point- Table I. Socio-geographic characteristics of the patients who called the ‘7887’ Healthcare Call period study, which reflects the general call composition pattern at ‘7887’ Healthcare Call Centre by themselves Centre.

Data management and analysis Excel data format was transformed into SPSS data entry type. Data was analyzed by using SPSS version 20.0. Information on socio-geographic characteristics, medical com- plaints of callers, response of call centre was described in frequency and percentage. The call deposition types were categorized into 18 specialties (General Medicine, General Surgery, Cardiology, Respiratory, Gastrointestinal, Urology, Infectious Diseases and Sexually transmitted diseases (STDs), Orthopaedics and Traumatology, Eye Ear Nose and Throat (EENT), Adolescent and Reproductive Health, Aesthetics and Dermatology, Non-Judgemental Counseling, Psychiatry, Health Education Purpose, Health Directory, Drugs Inquiry, Foods and Dental). Top five call deposition types and their related medical complaints are presented Table II. Townships with the highest frequency of calls are presented on map (Fig. 1) and Table I.

Ethical consideration The ethical approval was obtained from Institutional Review Board of Department of Medical Research.

Results Socio-geographic characteristics of the callers People from all age groups to the maximum age of 95 years have utilized the call centre in study period. When we divided their age groups into three standardized age groups as depicted in the Myanmar national census report,9 such as child population (Less than 15 years old), productive population (15 to 64 years) and the aged population (65 years and above), 779 (82.5%) of 944 patients with known age data were from the productive or working age group (Table I). 114 (12.1%) were from the child population and 51 (5.4%) from the elderly population, respectively. Out of 1051 patients with known gender data, proportions of males and females were 502 (47.8%) and 549 (52.2%), respectively (Table I). With regards to the locations of the callers, overwhelming majority of them were Only 10 (1%) of 1362 patients who called the call centre by themselves disclosed from Yangon and Mandalay divisions, representing 40.6 % and 11.7 %, respectively (Table their marital status. Therefore, we did not have sufficient data for analysis of this parameter. I). 173 (52%) of all townships in Myanmar have utilized the call centre at least once in the 27.8 percent (15/54) of patients with known occupational status were dependent, study period (Table I). The townships with the highest number of calls were from Insein, representing the majority (Table I). However, people from a wide range of occupational Mawlamyaing, Thingangyun, Monywa, Hlaing Tharyar, Hpakant, Mayangone, Hlaing, backgrounds, totaling 13 categories, consulted. The second majority were company staff, Kamaryut, Pyay, Tarmwe and Taunggyi, with the absolute call frequencies of 17, 15, 15, constituting 14.8% (8/54). Manual workers represented therd 3 majority and constituted 14, 13, 13, 13, 11, 11, 11, 11 and 10 respectively (Figure 1). 85% (62/73) of all townships 13% (7/54). in the combined regions of Yangon and Mandalay divisions have utilized the call centre at least once in study period (Table I). However, only 43% (111/257) of all townships in the

Page 48 September 2020 - Vol: 62, No. 3 September 2020 - Vol: 62, No. 3 Page 49 Myanmar Medical Journal Myanmar Medical Journal combined regions excluding Yangon and Mandalay divisions have utilized the call centre health-related health inquiries. Other commonest complaints in this category were mens- (Table I). This data showed half-fold reduction in the call centre service utilization reach truation-related symptoms such as irregular menstruation and painful menstruation among townships in the regions excluding Yangon and Mandalay divisions. (17%), vaginal itchiness/discharge (9%), vaginal bleeding (8%), family planning (6%) and sexual dysfunction (5%) (Table II). 95% (126/133) of calls in health education purpose Figure 1. Townships with the highest number of calls at ‘7887’ Healthcare Call Centre. category presented with no complaints, but just raising miscellaneous health education The numbers in parenthesis are the absolute numbers of calls from the respective townships. questions and inquiries. In aesthetics and dermatology, 42% were skin lesions. 26% were without special complaints, probably for questions related to beauty and lifestyle. 12% and 10% were skin itchiness and acne, respectively (Table II). In gastrointestinal category, top complaints without any known diagnosis were abdominal pain/discomfort (45%), loose motion (17%) and constipation (9%), respectively (Table II). Table II. The major categories of telephone consultations of the patients at ‘7887’ Healthcare Call Centre (also known as Disposition types) and their presenting complaints

Presenting complaints or problems of the callers Out of 18 consultation categories, top five were general medicine (23%), ado- lescent and reproductive health (14%), Health Education Purpose (10%), Aesthetics and Dermatology (9%), Gastrointestinal (9%). Health Directory calls constituted 5.8%. Non- Judgemental counseling calls represent only 0.7% (10) (Table II). 90 (7%) of the patients presented with an already known disease (diagnosis). Top complaints in general medicine were non-specific symptoms (11%), fever (10%), body aches and tenderness (8%), headache (7%), dizziness (6%), cough (4%) (Table II). In adolescent and reproductive health, nearly one-third (59/190) of the consultations were reproductive

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Response of the call centre to the callers Out of total randomized data, 132 (8.8%) were not directly from the patients, but 1050 (77.1%) of the patients did not have to be referred (Table III). Out of 312 from a third party such as family member, relative or friend. Among third party callers, 80 referred cases, 258 (83%) of referred cases were directed by the call centre to private (61%) were parents of the patients, representing the majority. Among them, 62.5% of the healthcare facilities and 19 (6%) were to the public healthcare institutions, whereas parents were mother and 37.5% were father. 18 (14%) were spouse of the patient, out of 35 (10%) were to an unknown service sector (Table III). 229 (49.4%) were referred to which, 67% were husband and 33% were wife. 16 (12%) were children of the patient and, specialists and 83 (one-fourth) were referred to the general practitioners (GPs) (Table III). among them, 37.5% were son and 62.5 % were daughter. Another one-fourth (75) were referred to unspecified specialty (Table III). Probably, they Finally, among 387 callers who mentioned how they knew the ‘7887’ call centre, included those cases which were referred to a hospital where they can be subsequently 205 (53%) said they knew it from the Short Message Service (SMS) message, 85 (22%) triaged or referred to an appropriate specialty by the hospital staff. 23% of the referred specialists were general physicians, 15% were obstetricians and gynaecologists, 12% were from the television commercial (TVC) and 43 (11.1%) from the social media such as Face- general surgeons and 8% were dermatologists (Table III). book. Two-thirds of the patients (68.5%) were managed by telephone consultation Discussion including health education and counseling without prescribing any medicines (Table III). The rest of the managed patients (31.5%) were given non-prescription (over-the-counter) Our findings revealed that telephone consultation service delivered by aCall medicines. Centre in the community is one of the possible ways to reduce the patients’ unnecessary Table III. Response of the ‘7887’ Healthcare Call Centre to the patients visits to hospitals or clinics, by providing safe and comprehensive medical consultation, counseling and health education services. The ‘7887’ Healthcare Call Centre is utilized mainly by people of working age with diverse types of occupations. Its services are utilized by half of the townships across the country. Telephone consultation service reduces workload of health care providers and thus presence of a healthcare call centre can be regarded as an auxiliary service for existing health care delivery system in Myanmar. Telephone consultation has been proven by some previous studies as an effective way to cut down unnecessary patients’ visits to the GPs.1, 4 This ideology seemed to be supported by our current results that the majority of the patients at ‘7887’ call centre did not have to be referred to any other healthcare facility, but rather managed by telephone consultation itself (Table III). If the outcome is actually beneficial, it will be very helpful and reassuring to those patients who are in the far-flung areas with much difficulty in access to physical healthcare units at the time of their sickness. However, our data was still limited in that there were no follow-up inquiry outbound calls to the patients after the telephone consultation by the Call Centre, with regards to their actual compliance with our referral or non-referral. Thus, many studies are still needed to confirm this assumption i.e the merit of call centre by making follow-up outbound calls to the patients. Another previous study also presented that telephone consultation could reduce the necessity of the home visits by the doctors to the patients.10 Therefore, the majority of the published data on healthcare call centres prompted the fact that presence of a healthcare call centre can provide the patients in the community with an effective In patients with a known disease, the top diseases consulted were haemorrhoids, and, probably, efficient triage system, thereby reducing the workload of the healthcare hepatitis B infection, diabetes mellitus, rheumatoid arthritis, chicken pox, stroke, bronchial providers in a way that effective telephone consultation prevents unnecessary healthcare asthma, fatty liver, gastritis, hepatitis C infection, alcoholic liver disease, cirrhosis of liver, facility visits by the patients. Moreover, the majority of the patients consulted by the ‘7887’ epilepsy, ischaemic heart disease, renal disease, renal stone, tuberculosis, urinary tract call centre were not prescribed any medicine unless really necessary (Table III). Most of infection, according to the largest-to-smallest proportion sequence (Data not shown). Page 52 September 2020 - Vol: 62, No. 3 September 2020 - Vol: 62, No. 3 Page 53 Myanmar Medical Journal Myanmar Medical Journal

the cases were just managed quite well on telephone by health education, counseling and Regarding the geographical location of the patients who utilized the call centre, necessary advices on appropriate home remedies. It reflects the fact that the ‘7887’ call we do not have clear data that can distinguish between the urban versus rural regions of centre is trying to ensure safe medical consultation to the community, while avoiding the the callers. However, our data showed that townships with highest number of calls are risks of prescribing medications on telephone as much as possible. Even if the medication clustered in the city of Yangon (Figure 1). It raised a question whether the patients from is needed as in cases of severe pain and fever, the medicines prescribed by the call centre the urban areas are more prone to use the Call Centre service and more research studies were usually over-the-counter medicines that do not actually need a medical doctor’s are needed for an unbiased and objective answer for that. prescription. However, the data is still insufficient on the patients' safety and satisfaction In contrast with most other published data, our study measured the interventions regarding telephone consultation. Follow-up studies are needed. rather than the actual outcomes. Therefore, more studies are required to know the actual The fact that the overwhelming majority of the patients who consulted with impact of the call centre on the community before we make any unbiased statement of its the call centre were in the productive or working age group (Table I), correlates with the effectiveness, efficiency and safety scientifically. previous published data that older people, ethnic minorities and other disadvantaged Patient satisfaction was often utilized by some studies of the GP consultation as groups under-use the telephone consultation service.5 One reason may be because their preferred outcome of interest.10 Although some studies suggested positive patient elderly people have less cognitive ability to dial a hot line number. Another reason may satisfaction with telephone consultation, more studies with sufficient data are still needed be because the elderly generation have less familiarity with the ICT. However, we also to make a conclusion on this. Moreover, patient satisfaction does not always imply patient found that patients from all age groups have utilized the call centre service, although safety because of the difference in their health education level and concepts compared to their utilization frequencies differed. It should be pointed out that the call centre service healthcare providers. Furthermore, one study in Germany claimed that most healthcare is easy-to-use for all age groups as long as the users understand about the call centre call centres running in Germany failed to meet the criteria for evidence-based health service. 65.6% of the population in Myanmar are in the economically productive age information delivery.11 However, many consultation situations have to be handled slightly group.9 Therefore, the actual call centre service utilization may encompass all age groups, differently on telephone because of the differing mode of communication. Therefore, although their frequencies are quite different because of disproportionate number of the further studies are still needed to objectively determine the patient satisfaction and working age population in Myanmar. safety, regarding telephone consultation. So far, the ‘7887’ call centre has not received any Slight preponderance of the female gender among the patients (Table I) correlated major complaints by the patients as far as the patient safety and the call centre’s service with the national census data of Myanmar (51.78% and 48.22% for females and males, outcome are concerned. In any case, we want to emphasize that telephone consultation respectively).9 Therefore, we consider that there is no gender-based difference in the call cannot always substitute face-to-face consultation of the patient in a real setting. It should centre service utilization in Myanmar, considering that more female population resides in rather be used as a reliable and probably safe alternative in the situations where patients Myanmar. cannot have access to a healthcare provider physically (e.g., some rural areas of Myanmar with limited healthcare access). The marital status data of the patients were insufficient for any discussion in this study, because some people in Myanmar probably did not want to disclose their marital 90 (7%) of the patients presented with an already diagnosed disease. It reflects status. It may be due to cultural and confidential reasons. Therefore, further effective presence of the health-seeking behavior among the patients who utilized the ‘7887’ studies are still needed on this socio-demographic parameter. call centre. Therefore, telephone consultation can serve as a remote channel of health education and counseling services to those group of patients who are seeking health Our data revealed that patients from a wide range of occupational categories advice for their diagnosed diseases (e.g., consultation for a second opinion). utilized the call centre service (Table I). It means that the call centre service is used readily by people from all walks of life. In other words, the ‘7887’ call centre service is user- Since the goal of the ‘7887’ call centre is to contribute to the Universal Health friendly to people of occupational groups in any place at any time. A significant population Coverage (UHC) in Myanmar by enabling delivery of healthcare service to all regions of of dependent people among the patients (Table I) suggests the assumption that people Myanmar, awareness of the call centre service by everyone in Myanmar is critical. Our who are not working have more time to focus on and utilize the call centre service, study revealed that the call centre advertisement via SMS messaging system is the most especially those patients who are at home while their family members are at work places. effective way to raise its awareness, as long as the SMS can be delivered to everyone in all (e.g., housewives). regions of Myanmar, uniformly.

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Finally, telephone consultations should be accessible through all mobile phone 4. Lattimer V, George S, Thompson F, Thomas E, Mullee M, Turnball J, et al. Safety network operators in the future, so that it increases its effectiveness and supportiveness and effectiveness of nurse telephone consultation in out of hours primary care: in healthcare service delivery system in Myanmar. Further studies are also needed to have randomised controlled trial. BMJ 1998; 317: 1054‐1059. more clear data on the service impact of the call centre on the community as a whole 5. Steve G. NHS Direct audited: customer satisfaction, but at what price? BMJ 2002; such as its effectiveness, efficiency, patient safety, patient satisfaction, the workload 324: 558. relief in the healthcare providers, etc. Cooperation with international research centres, particularly the primary healthcare research centres, with experience in the healthcare 6. Gaffney B, Heymann T. NHS Direct plays a major role. BMJ 2010; 341: c4700. call centre research, is also recommended to have more productive research data on the 7. Ubiquitous M-Health Systems and the Convergence Towards 4G Mobile Technologies. international level. A national hot line for telephone consultation service should also be In: M-Health: Emerging Mobile Health Systems (2006). Istepanian CS, Pattichis RSH established in Myanmar, similar to the NHS Direct in the UK. and Laxminarayan S. (eds). Springer Science and Business Media Inc., New York, pp 3-14. Conclusion 8. Saw YM, Win KL, Shiao LW, et al. Taking stock of Myanmar’s progress toward the The ‘7887’ Healthcare Call Centre is utilized mainly by people of working age with health-related Millennium Development Goals: current roadblocks, paths ahead. diverse types of occupations. Its services are utilized by half of the townships across the Int J Equity Health, (2013); 12: 78. doi:10.1186/1475-9276-12-78 country. Telephone consultation seems to be an effective way in reducing unnecessary hospital or clinic visits and serves as a standardized telephone triage system at primary 9. The 2014 Myanmar Population and Housing Census. The Union Report (Volume 2): care level; although further studies are needed to accurately know its social impact. It Main Census Report (May, 2015), p. 1. can be regarded as an auxiliary service for existing primary health care service delivery 10. Bunn F, Byrne G, Kendall S. The effects of telephone consultation and triage on system in Myanmar. Moreover, service providers can make use of telephone consultation healthcare use and patient satisfaction: a systematic review. Br J Gen Pract. 2005; in provision of counselling and health education services for the community. 55 (521): 956-961. Conflict of Interest 11. Albrecht M, Isenbeck F, Kasper J, Mühlhauser I, Steckelberg A. The Foundation in Evidence of Medical and Dental Telephone Consultations. Dtsch Arztebl Int. 2016; Three of the authors were the medical doctors employed at the ‘7887’ Healthcare 113 (22-23): 389-395. doi:10.3238/arztebl.2016.0389 Call Center and this study was a collaboration between the ‘7887’ Healthcare Call Center and the Department of Medical Research of Myanmar. However, these authors clearly declare and certify that they do not have any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent- licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in the paper.

References 1. Bunn F, Byrne G, Kendall S. Telephone consultation and triage: effects on health care use and patient satisfaction. Cochrane Database of Systematic Reviews 2004, Issue 3. Art. No. CD004180. DOI: 10.1002/14651858.CD004180.pub2. 2. Marklund B, Bengtsson C. Medical advice by telephone at Swedish health centres: who calls and what are the problems?. Fam Pract 1989; 6 (1): 42‐46. 3. Bondo CM, Frede O. Out of hours service in Denmark: evaluation five years after reform. BMJ 1998; 316: 1502.

Page 56 September 2020 - Vol: 62, No. 3 September 2020 - Vol: 62, No. 3 Page 57 Myanmar Medical Journal Review Ascaris lumbricoides has worldwide distribution. Trichuris trichiura(whip worm) Neglected and Emerging Helminthic Infections: Worldwide and in Myanmar is endemic in Central Africa, Southern India, and Southeast Asia. Hookworms, Ancylostoma duodenale is endemic in Middle East, North Africa, India, Europe, Australia; Necator Win Win Mawv americanus is found mostly in the Americas, Sub-saharan Africa, East Asia and Southeast Introduction Asia. Strongyloides stercoralis is endemic in Africa, South America, and Southeast Asia and dogs are potential reservoirs.3 Neglected tropical diseases (NTDs) are a group of bacterial, parasitic, viral, and fungal infections that are prevalent in many of the tropical and sub-tropical developing A recent review on the global burden of STH infection revealed that nearly 70% of countries where poverty is rampant. According to CDC and WHO there are 20 neglected the infections occur in Asia.Ascaris was the commonest STH with an overall prevalence of tropical diseases including 9 helminthic infections: 4 nematode infections (soil-transmitted 18% followed by Trichuris (14%) and hookworm (12%). Hookworm prevalence was highest helminthiasis, dracunculosis, lymphatic filariasis and onchocerciasis); 2 cestode infections in Laos, Vietnam and Cambodia.3 (cysticercosis, echinococcosis) and 3 trematode infections (schistosomiasis, fascioliasis, In Myanmar, prevalence of STH infection between 1969 and 1990 was 61-98%; 1 and food borne trematodiasis). ascariasis dominated over many years. Changing patterns of prevalence of soil-trans- Some of the helminthic infections including zoonoses are emerging in new mitted helminths was seen after the introduction of mass drug administration in 2006 geographic areas now. An emerging infectious disease is one that is caused by a newly with reducing total prevalence, higher prevalence rate for trichuriasis and a shift to adult discovered infectious agent or by a newly identified variant of a known pathogen, which population. In 2012, 7 years after implementation of mass drug administration, total has emerged and whose incidence in humans has increased during the last two decades prevalence of STH was reduced to 21% from 69.7% in 2003; ascariasis fell to 5.8% from and is threatening to increase in the near future.2 48.5%; trichuriasis to 18.6% from 57.5%; hookworm infection to 0.3% from 6.5% among 1,000 school children in 4 selected areas.4 Soil-transmitted helminth (STH) infections In Myanmar, prevalence of hookworm infection is < 6%. However, high infection Distribution and disease burden Worldwide and in Myanmar rate was seen among miners working at Mawlamyine Antimony mine (31%) and at No. 1 STH infections are among the most prevalent neglected tropical diseases (NTD) copper project Monywa (16%) (1981), persons from Shwe Pyithar slum area (44.8%), and worldwide caused by nematodes namely Ascaris lumbricoides, Trichuris trichiura, hook- persons who dig gold in Shwe Gyin (13.7%). Hookworms detected were identified to be worm and Strongyloides stercoralis. They are transmitted by eggs or larvae present in the Necator americanus by DNA sequencing.5, 6, 7 & 8 human faeces, which contaminate the soil. Over 1.45 billion people worldwide are infected The overall prevalence rates of Strongyloides (< 3%) in Myanmar population is with STH. Globally, an estimated 438.9 million people were infected with hookworm, low compared to that of greater Mekong region (17.5% in Cambodia, 23.7% in Thailand, 819.0 million with Ascaris lumbricoides and 464.6 million with Trichuris trichiura in 2010. 26.2% in Lao PDR, 44.7% in Northern Cambodia). Higher prevalence was seen in some At least 370 million people worldwide are infected with Strongyloides stercoralis.3 populations; 15.8% and 13% in miners from Mawlamyine and Monywa, respectively, in Clinical manifestations of ascariasis include Loeffler’s syndrome (eosinophilic 1981, 5.7% in some rural areas of the Lower Myanmar diagnosed by culture method pneumonitis); protein energy malnutrition, urticaria and intestinal colic, intestinal obst- in 2015, 5% in persons from Shwe Pyithar slum area, Yangon and 3.7% in HIV infected ruction/perforation, biliary obstruction, and cholecystitis in high worm burden cases and patients from Mingalardon Specialist Hospital in 2016.5, 6, 9, 10 that of trichuriasis include rectal prolapse and blood and mucous diarrhea in chronic cases. Creeping eruption and anaemia are the presenting features of hookworm infestation. Risk Emerging Soil-transmitted Helminth (STH) infections persons include bare footed persons, farmers, mine workers, children and those who Zoonotic ascariasis - A. suum, is transmitted by ingestion or inhalation of eggs from pig. consume unwashed contaminated salad leaves. Pigs are the main source of human cases of ascariasis in some parts of the world where Strongyloides stercoralis accounts for 90% of strongyloidiasis. Autoinfection leads human ascariasis is not endemic. Farmers are risk persons. The two species A. lumbri- to hyperinfection and disseminated strongyloidiasis with case-fatality rates near 90% in coides and A. suum can only be differentiated by molecular methods. Both can cause cross immunocompromised persons.3 infections. Emerging infection with a hybrid genotype, intermediate between A. suum/A. lumbricoides was reported from Italy in 2010. v Professor/Head (Retired), Department of Microbiology, University of Medicine (2) Yangon Corresponding author: [email protected]

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Zoonotic trichuriasis are caused by Trichuris vulpis (Dog whipworm) and Trichuris suis (Pig Two cestode infections (cysticercosis, echinococcosis) whipworm). Infection is acquired through ingestion of infective embryonated eggs and Distribution and Disease burden Worldwide and in Myanmar contact with infected dogs. Infections with Trichuris vulpis in school children have been Echinococcosis has worldwide distribution. Definitive hosts are domestic and reported from Thailand (10%) in 2010 and Mexico in 2012. There is no reported case in wild carnivores (e.g. dog). E. granulosus causes hydatid cysts and E. multilocularis causes 11 Myanmar. alveolar echinococcosis. Cysts can be found mainly in the liver and lungs, less frequently, Zoonotic Hookworms. Ancylostoma caninum causes human eosinophilic enteritis; Ancy- the central nervous system, bones, kidneys, spleen, muscles and behind the eye. Humans lostoma brazilense causes larva migrans; Ancylostoma ceylanicum causes Traveller’s contract the disease by ingestion of food and drinks contaminated with eggs. Risks include diarrhoea. Ancylostoma ceylanicum attributed to 6-23% of human intestinal hookworm contact with infected dogs and cats and sheep farming.3 infections in Asia. It is prevalent in South East Asia, India and Taiwan. Close contact Cysticercosis is endemic in Latin America, South and South-East Asia. Ingestion of with dogs and cats predisposes to infection. Emerging human infections with zoootic A. food contaminated with Taenia solium eggs may result in cysticercosis in the muscles, skin, ceylanicum in Lower Myanmar (2 cases in Mon State, 1 case in Bago Region) was observed eyes and the central nervous system. Neurocysticercosis is one of the causes of epilepsy 8 in 2015, detected by molecular method. worldwide and can be fatal.

Tissue and lymphatic nematodes In Myanmar, asymptomatic cysticercosis cases of pigs and humans were detected Distribution and Disease Burden Worldwide and in Myanmar by Ab detection and prevalence was 4.7% in pig farmers in Ayarwaddy delta region; 15.93% in farmed pigs (58/364) and 23.15% in owners of infected pigs (47/203 households) in Lymphatic filariasis (LF) is caused by W. bancrofti (responsible for more than 90% Naypyitaw. By meat inspection, 23.67% (71/300) of pigs in Naypyitaw were found to have of the infections worldwide);B. malayi (endemic in several Asian countries), and B. timori cysticercosis.13, 14 (seen only in Indonesia). It is transmitted through the bite of any of Culex, Anopheles and 3 Aedes species mosquitoes. Emerging cestodes The disease is endemic in 73 countries. Over 120 million are infected in 2000 Neotropical echinococcosis is emerging in South American countries. Three in the world. According to 2013 data, approximately 41.7 million people are at risk of human cases of unicystic echinococcosis (Echinococcus oligarthrus) and 106 cases of poly- infection with LF in Myanmar and the disease is endemic in middle Myanmar. However, cystic echinococcosis (Echinococcus vogeli) from 12 countries have been reported. Liver after 6 rounds of mass drug administration (MDA) the overall prevalence of infection was failure and death occur if left untreated.3 reduced from 2-25% to 2.63% as detected by antigenaemia and from 5.2% to 1.03% by Porcine cysticercosis, caused by Taenia solium, is emerging in the Eastern and microfilaraemia in endemic area (Amarapura, Patheingyi, Tada-U and Wundwin townships Southern Africa (ESA) regions due to significantly increased pig production in the past of the Mandalay Region) in 2018.12 decade. It affects pig production and poses a serious public health risk for the population, Onchocerciasis (River Blindness) can be found in parts of Africa, Arabia, Central especially in resource-poor communities. Emerging infection with hybrid ofT. saginata/T. America, Northern South America, and Mexico. More than 30 million people are infected asiatica was reported from Laos PDR.15 with this parasite in Africa alone. Adult worms of Onchocerca volvulus live in subcutaneous tissues and larvae migrate to eyes causing blindness. It is transmitted by the bite of an Three trematode infections (schistosomiasis, fascioliasis, and food borne trematodiasis) infected black fly (Simulium) which breeds near rivers. Animal reservoirs have not been Distribution and Disease Burden Worldwide and in Myanmar found and no vaccine is currently available.3 Schistosomiasis is transmitted by contact with freshwater bodies infested with Dracunculosis - Endemic areas during the 1980s were in African, Eastern Medite- schistosome cercariae that are released from intermediate host snails. rranean and South-East Asia regions. From January to August 2014, a total of 82 cases Hepatointestinal schistosomiasis were reported from South Sudan, Chad, Mali and Ethiopia. People contract dracunculosis by drinking water containing infected copepods. Dracunculus medinensis adult females Schistosoma mansoni is endemic in Africa, Middle East, Venezuela, Brazil and S. (80 cm long) reside in the subcutaneous tissue and causes a blister and ulcer. No specific intercalatum and S. guineensis are commonly found in Africa. Schistosoma japonicum drug is used to treat dracunculosis. Extracting the adult female worm from the patient is the most prevalent in Asia followed by Schistosoma mekongi (in Mekong delta) and by wrapping the worm around a stick at the skin surface; and wrapping and winding the Schistosoma malayensis. Currently, schistosomiasis is endemic in 6 Asian Countries: worm a few centimeters each day is the treatment. Boiled or filtered or larvae-killing Schistosoma japonicum in China, the Philippines, Indonesia; Schistosoma mekongi mainly chemical treated water can be used to prevent the disease.3 Page 60 September 2020 - Vol: 62, No. 3 September 2020 - Vol: 62, No. 3 Page 61 Myanmar Medical Journal Myanmar Medical Journal

in Cambodia, Lao PDR (since 1957) and Schistosoma malayensis in Malaysia (since 1973). Food borne trematodiases are caused by liver flukes, lung flukes and intestinal flukes Myanmar is emerging as 7th endemic country of Schistosoma mekongi in Asia. Japan is Food borne trematodiasis is an emerging public health problem, and prevalent the only country in Asia free from this disease, and Thailand has broken the transmission in Southeast Asia and the Western Pacific region. However, higher transmission dynamics chain. Hepatointestinal schistosomiasis presents with chronic diarrhoea; dysentery and have been observed in many other areas, as the result of expansion of aquaculture.3 jaundice. Ectopic migration of schistosomes to brain; mainly by S. japonicum, and to spinal cord by S. mansoni causes cerebral schistosomiasis. Ectopic migration to the lungs Liver flukes - Clonorchiasis and opisthorchiasis are strongly associated with lead to chronic pulmonary schistosomiasis with features of pulmonary hypertension, hepatomegaly, cholangitis, fibrosis of the periportal system, cholecystitis, gallstones, corpulmonale, and massive hemoptysis.3 and cholangiocarcinoma. Humans become infected by ingesting the metacercariae in uncooked or partially cooked fish. Clonorchis sinensis is prevalent in northern Vietnam, Genitourinary schistosomiasis Korea, China and the Russian Far East and Opisthorchis viverrini or O. felineus is endemic in Vietnam, Laos, Thailand and Cambodia.3 Causal agent, S. haematobium, is prevalent in Africa and Middle East. Orchitis and prostatitis are the presenting features of genitourinary schistosomiasis inmale. Throughout the world, 700 million people are at risk of infection with these two Cervical lesions in female are sometimes mistaken for cervical carcinoma. Genitourinary liver flukes. Up to 15 million people are infected withC. sinensis in China alone; 10 million schistosomiasis and cervical carcinoma can coexist in female. Person with genitourinary people are infected with O. viverrini in Thailand and Lao PDR. schistosomiasis has increased chance of contracting HIV infection. Bladder cancer and In Thailand, it is estimated that 6 million people are infected with O. viverrini. An bleeding from varicose veins in the oesophagus are causes of death. overall prevalence of O. viverrini infection of the four regions of Thailand during 1980- In Myanmar, infection with schistosomes has been reported since 2012. A 1981 was 14%. Prevalence in the Northeast, the Central, the North and the South regions total of 23.8% of 315 residents of Inlay Lake were Schistosoma (Ig G) positive. 4% of (8/ of Thailand are 34.6%, 6.3%, 5.6%, and 0.01%, respectively. The highest incidence of liver 204) participants and 3.1% of (22/698) tested people in Shwe Gyin were found to have fluke-associated liver cancer in the world is in Khon Kaen, Northeast Thailand. schistosomiasis by stool examination. Among 1,734 suspected patients in the Rakhine In Myanmar, this emerging infection with O. viverrini was first reported from 3 state, 30% was S. mansoni IgG positive and 24% was urinary antigen positive. Eggs of district of Yangon Shwe Pyithar, South and North Dagon in 2015 (0.7%; 14/2,057), followed S. mekongi (6%); S. japonicum (4%), S. haematobium (1%) were detected in 327 - stool by Shwe Gyin in 2016-2017 (4.2%; 25/698). In Lower Myanmar (Bago area, Mon state and samples and S. mansoni antigen was detected in 8% in urine samples in Sittwe.16, 7 Yangon), overall prevalence was 9.3% (34/364) in 2017. Local prevalence was 18.9% in Fascioliasis - It occurs worldwide. F. hepatica (‘sheep liver fluke’) is found in Bago area, 5% in Mon state and 3.6% in Yangon.18, 19 Europe, the Middle East, and Asia and emerging infections with F. gigantica (“Giant liver Opisthorchis viverrini eggs were detected in pigment stones and feces of 82 year fluke”) have been reported from parts of Asia and Africa, as well as Hawaii and Iran. Hybrid old lady with gall bladder cancer from Dike-Oo Township admitted to North Okkalapa forms (Fg/Fa) occurs in Central Asia, East Africa, Japan, India, Korea, the Philippines, and General and Teaching Hospital in 2017.20 Iran. Consumption of raw watercress with metacercaria causes infection with Fasciola spp. Nonspecific symptoms such as abdominal pain, nausea, vomiting, hepatomegaly, Paragonimiasis (Lung fluke) - More than 50 species of Paragonimus have been described fever, cough with peripheral eosinophilia and elevated serum amylase level may develop from Asia, America and Africa. Paragonimus westermani is found in Korea, Japan, China, in fascioliasis. Larva may migrate to eyes, brain, pancreas, and subcutaneous tissues. In Taiwan, Malaysia, Indonesia, Philippines and India and Paragonimus heterotremus chronic cases, cholangitis, cholecystitis, and pancreatitis may occur.3 occurs in Southeast Asia and Southern China. Seven species, namely, P. heterotremus, P. westermani, P. siamensis, P. bangkokensis, P. harinasutai, P. paishuihoensis and P. Emerging Triclabendazole (drug of choice) resistant cases were reported from macrorchis have been reported from Thailand. P. pseudoheterotremus has recently been Australia, Ireland, UK and the Netherland. In Myanmar, first detection of F. gigantia (Fg reported from Thailand. Around 20 million people get infected; the prevalence is higher in type) and hybrid type (Fh/Fg type) among infected cattle and buffaloes at slaughter houses men than in women, and in young children than adults; 20.9% prevalence in children and of Yangon, Lashio, and Myitkyina was reported in 2011. Among 88 adult flukes, 80 were 4.1% in adults in Arunachal Pradesh in India (2007) and 0.2-11.3% prevalence in Vietnam, identified molecularly as F. gigantia (Fg type) (91%) and 8 flukes obtained from one host majority of whom are children (2013).3 of Myitkyina were hybrid type (Fh/Fg type) (9%). Hybrid type (Fh/Fg type) is common in China, indicating existence of imported cases from China.17 The disease can be contracted by consumption of raw or improperly cooked (pickled) freshwater crabs or crayfish. Major clinical manifestation resembles pulmonary

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tuberculosis. Other manifestations include cerebral paragonomiasis (mainly caused by P. reported. Mebendazole resistance in Necator americanus was reported from Mali, Pyrental westermani); abdominal paragonomiasis and cutaneous paragonomiasis.3 pamoate resistant Ancylostoma duodenale from North western Australia and praziquental (PZQ) reduced susceptibility in Schistosome reported from Northern Senegal (CR - 18%). In 2013, researchers from Thailand detected metacercariae of P. heterotremus and Farmers in Paraguay gave up sheep farming due to pan drug resistant helminthes.24 P. pseudoheterotremus in crab samples from northern and central parts of Thailand, from Surat Thani Province, Thailand and Myawaddy Province, Myanmar by morphology and Prevention and control molecular methods. Therefore, members of P. heterotremus and P. pseudoheterotremus These helminthic infections can be prevented and controlled by preventive complex seem to be widespread among crabs with possible human infections in Thailand chemotherapy (Taeniasis, Fascioliasis, STH); treatment; vector control such as snails 21 and the Thai-Myanmar border region. (fascioliasis, schistosome); meat inspection, improving sanitation, vaccination (Taeniasis; In Myanmar, there was no reported human case before 2016. However, eggs of echinococcosis) and WASH (water, wearing shoes, sanitation and hygiene) for STH. Paragonimus species were detected in 2% of 698 stool samples during October 2016 to Wearing shoes reduces hookworm infection by an average of 71%, access to a household March 2017 in Shwe Gyin Township.7 latrine reduces risk of infection with roundworm and whipworm by more than 40%, hand washing with soap after defecation and before eating can reduce risk of infection with all Echinostomiasis (intestinal flukes) is acquired by ingestion of metacercaria (cysts three STH species by more than 30%, households that have piped water access have a stages) of Echinostoma species’ in raw fish, snail, frogs, particularly the tadpole stage markedly reduced risk of infection (43% to 60%).25 and vegetables. Human cases are mostly from SE Asia and East Asia. Infection may be asympatomatic or manifests as diarrhoea, anaemia, abdominal pain and in severe cases Reducing the burden of disease caused by NTDs is essential for improvement in health of the world population. With the aim to support and build momentum of action ulceration of the intestinal wall. Echinostomiasis is an emerging helminthic infection in against NTDs, the first "World Neglected Tropical Diseases Day" was marked on January Myanmar. Six cases were reported from Hlaing Thar Yar and North Dagon townships, 30, 2020. The slogan is "Beat NTDs: For good For all".26 Yangon, Myanmar in 2015 (n = 1,443 school children).22 Fasciolopsiasis is endemic in Asia and Indian subcontinent. Fasciolopsis buski, References mainly resides in human duodenum, jejunum causing intestinal ulceration and obstruction. 1. Mitra AK and Mawson AR. Neglected Tropical Diseases: Epidemiology and Global Pig farming and consumption of fresh water plant are risk factors. Burden. Trop. Med. Infect. Dis. 2017; 2: 36. doi:10.3390/tropicalmed2030036

Fasciolopsiasis emerged in 2004 and reemerged in 2014 in Myanmar. Fasciolopsis 2. Mostafavi E. Emerging and reemerging infectious diseases (2016). eggs were detected in the stool of three (1.67%) cases of pre-primary schools children https://www.researchgate.net/publication/295855084. from North Okkalapa Township, Yangon division (n = 180) and two cases among healthy 3. Abdeltawabi MS, Seddik NE and Salem HK. World Wide Epidemiology of Helminhic pregnant women (n = 383) in Shwe Kyin township, Bago division, Myanmar in 2004 and Infection, 2017. DOI:10.5772/67273. https://www.intechopen.com/books/human- 7 2014, respectively. helminthiasis/world-wide-epidemiology-of-helminths-infection Food-borne minute intestinal flukes (Haplorchis spp, Symnophylloides seoi, Hete- 4. Aung Tun, Su Mon Myat, Gabrielli AF and Montresor A. Control of soil-transmitted rophyes spp, Metagonymus, Gastrodiscoides homonis, Haneropsolus bonni and Prostho- helminthiasis in Myanmar: results of 7 years of deworming. Tropical Medicine and dendrium molenkampi etc) can be identified in Egypt, Middle East, South East Asia, Korea, International Health (2013); 18 (8): 1017-1020. doi:10.1111/tmi.12130 and India. The mode of infection is eating raw or pickled fish.3 Infection can cause mucous 5. Khin Ohn Lwin, Min Zaw. Geohelminths infection in two mining communities in secretion, malabsorption, protein losing enteropathy, B deficiency, intestinal ulceration 12 Moulmein and Monywa township. Burma Medical Journal (1981); 27 (4): 58-69. and intestinal obstruction. Migration to heart resulting in fatal myocarditis, valvular damage and to other organs (brain) have also been reported. In Myanmar, more than 7 6. Thet Soe Hlaing & Khine Khine Su. Soil transmitted helminthic infestation among rd species of MIF metacercariae were detected in fish (264 fish / 12 species tested) from a people in urban slum area of Shwe Pyi Thar Township, Yangon. 23 Myanmar local market of Yangon. No human cases were reported.23 Military Medical Conference, 2016; p. 10. 7. Kay Thwe Han, Khin Thet Wai, Kyin Hla Aye, Khine Wah Kyaw, Wai Phyo Maung & Tin Emerging anthelminthic resistance is the most important problem in sheep Oo. Emerging neglected helminthiasis and their determinants of multiple infections farming countries: Australia, South Africa and South America. Emergence of anthelmintic in Shwegyin Township, Myanmar: A cross-sectional study. Tropical Medicine and drugs resistance to all the major groups among gastrointestinal nematodes has been Health, 2019; 47: Article number: 1. DOI:10.1186/s41182-018-0133-6 Page 64 September 2020 - Vol: 62, No. 3 September 2020 - Vol: 62, No. 3 Page 65 Myanmar Medical Journal Myanmar Medical Journal

8. Win Pa Pa Aung, Thi Thi Htoon, Htay Htay Tin, Sanpool O, Jongthawin J, Sadaow L, 17. Ichikawa M, Bawn S, Ni Ni Maw, Lat Lat Htun, Myint Thein, Aung Gyi, Kyaw Sunn, Phosuk I, Ropai R, Intapan PM and Maleewong W. First Molecular Identifications of Katakura K, Itagaki T. Characterization of Fasciola spp. in Myanmar on the basis of Necator americanus and Ancylostoma ceylanicum Infecting Rural Communities in spermatogenesis status and nuclear and mitochondrial DNA markers. Parasitology Lower Myanmar. Am. J. Trop. Med. Hyg, 2017; 96 (1): 214-216. International (2011); 60: 474-479. 9. Myo Pa Pa Thet Hnin Htwe Aung, Hino A, Khine Mar Oo, Kyu Kyu Win, Maruyama H, 18. Sohn WM, Jung BK, Hong SJ, Lee KH, Park JB, Kim HS, Cho S, Thi Thi Htoon, Htay Htay Wah Win Htike and Nagayasu E. Prevalence and associated risk factors of Strongy- Tin, Chai JY. Low-Grade Endemicity of Opisthorchiasis, Yangon, Myanmar. Emerging loides stercoralis infection in Lower Myanmar.Tropical Medicine and Health (2018); Infectious Diseases (2019); 25 (7): 1435-1437. 46: 43. doi: 10.1186/s41182-018-0126-5. 19. Win Pa Pa Aung, Thi Thi Htoon, Htay Htay Tin, Kyi Kyi Thinn, Sanpool O, Jongthawin 10. Soe Moe Thu Win (2017). Study of Strongyloides stercoralis in HIV infected patients J, Sadaow L, Phosuk I, Rodpai R, Intapan PM, Maleewong W. First report and mole- from Mingaladon Specialist Hospital. Ph.D Thesis, Medical Microbiology, University cular identification of Opisthorchis viverrini infection in human communities from of Medicine (1) Yangon. Lower Myanmar. PLoS One. 2017; 12: e0177130. http://dx.doi.org/10.1371/journal. 11. Areekul P, Putaporntip C, Pattanawong U, Sitthicharoenchai P, Jongwutiwes S. pone.0177130 Trichuris vulpis and T. trichiura infections among school children of a rural community 20. Khin Lay Cho, Mya Mya Lwin, Nyo Me May Thyn. Liver Fluke’s eggs in Gallstones of in northwestern Thailand: the possible role of dogs in disease transmission. Asian a patient with Gall Bladder Cancer.Myanmar Medical Journal (2017); 59 (3): 72-78. Biomedicine (2010); 4 (1): 49-60. DOI:10.2478/abm-2010-0006 21. Sanpoo O, Intapan PM, Thanchomnang T, Janwan P, Nawa Y, Blair D and Maleewong 12. Benjamin FR, Dickson ID, Patricia M, Graves ID, Ni Ni Aye, Thet Wai Nwe, Tint Wai, W. Molecular Variation in the Paragonimus heterotremus Complex in Thailand and San San Win, Myint Shwe, Douglass JID, Bradbury RS, McBride WJ. The prevalence Myanmar. Korean J Parasitol (2013 ); 51 (6): 677-681. http://dx.doi.org/10.3347/ of lymphatic filariasis infection and disease following six rounds of mass drug kjp.2013.51.6.677 administration in Mandalay Region, Myanmar. PLOS Neglected Tropical Diseases, 22. Thi Thi Htoon, Thanda Tun, Khin Yi Oo, Win Thein, Htay Htay Tin, Chai JY, Yong TS, (2018); 12 (11): e0006944. https://journals.plos.org or https://doi.org/10.1371/ Sohn WM. Status of infection with soil-transmitted helminths among primary school journal.pntd.0006944 children in three selected townships of Yangon Region. Myanmar Health Science 13. Wai Yan Min (2018). Seropositivity ofTaenia solium Immunoglobulin G and Associated Research Journal (2015); 27 (3): 221-226. factors among pig rearers residing at Kan Gyi Daung township, Ayeyarwaddy region. 23. Chai JY, Sohn WM, Na BK, Park JB, Jeoung HG, Hoang EH, Thi Thi Htoon, Htay Htay M.Med.Sc (Microbiology) Thesis, University of Medicine (2) Yangon. Tin. Zoonotic Trematode Metacercariae in Fish from Yangon, Myanmar and Their 14. Khaing TA, Bawm S, Wai SS, Htut Y, Htun LL. Epidemiological survey on porcine Adults Recovered from Experimental Animals. Korean J Parasitol (2017); 55 (6): 631- cysticercosis in Nay Pyi Taw area, Myanmar. J Vet Med. (2015); 2015: 340828. 641. doi: 10.1155/2015/340828 24. Geerts S and Gryseels B. Drug Resistance in Human Helminths: Current Situation 15. Marcello Otake Sato, Megumi Sato, Tetsuya Yanagida, Jitra Waikagul, Tiengkham and Lessons from Livestock. Clinical Microbiology Reviews, (2000); 13 (2): 207-222. Pongvongsa, Yasuhito Sako, Surapol Sanguankiat, Tipparayat Yoonuan, Sengchanh 25. Ogden S, Gallo K, Davis S, Mcguire C, Meyer E, Addiss D, Haddad D. Wash and the Kounnavang, Satoru Kawai, Akira Ito, Munehiro Okamoto, Kazuhiko Moji. Taenia neglected tropical diseases: A manual for WASH implementers: Myanmar. 2013 solium, Taenia saginata, Taenia asiatica, their hybrids and other helminthic https:/www.childrenwithoutworms.org> MMR WASH NTD Manual infections occurring in a neglected tropical diseases' highly endemic area inLao 26. Editorial. 2020: a crucial year for neglected tropical diseases. The Lancet (2019); 394 PDR. PLoS Negl Trop Dis (2018); 12 (2): e0006260. https://doi.org/10.1371/journal. (10215): 2126. DOI:https://doi.org/10.1016/s0140-6736(19)33070-3 pntd.0006260 16. Htin Zaw Soe, Cho Cho Oo, Tin Ohn Myat and Nay Soe Maung. Detection of Schisto- soma Antibodies and exploration of associated factors among local residents around Inlay Lake, Southern Shan State, Myanmar. Infectious Diseases of Poverty (2017); 6: Article number 3. DOI 10.1186/s40249-016-0211-0

Page 66 September 2020 - Vol: 62, No. 3 September 2020 - Vol: 62, No. 3 Page 67 Myanmar Medical Journal Case Reports Case Presentation Life-threatening severe hypercalcaemia in patient with Graves’ disease and Myasthenia gravis A 59-year old woman, married, residing in Oatpho, was admitted to Medical Unit (3), Yangon General Hospital (YGH) on 14.9.2019 with chief complaint of bilateral lower Hlaing Mya Wint, May Kyi Oo«, Tay Zar Tun Myintv, Sandar Lwinn limbs weakness for 3 weeks. There were no features of urinary and bowel incontinence and no history of preceding injury to back. There was no history of tingling and numbness Summary sensation, headache, blurred vision, fits and memory disturbance. She admitted that she

had weight loss of 10 lbs over 1 month period despite of normal appetite. There were no A 59-year old woman presented with bilateral lower limbs weakness for 3 weeks. significant symptoms apart from occasional palpitation. There was no history of similar On arrival, her GCS was 15/15, afebrile, and vital signs were stable. The motor power attack before. There was no family history of hyperthyroidism. of both lower limbs was 3/5 proximally and 5/5 distally without sensory impairment. She had diffuse goitre, atrial fibrillation. The initial investigations were consistent with On arrival to YGH, her GCS was 15/15, afebrile and there was no pallor or jaundice. hyperthyroidism due to Graves’ disease and she was treated accordingly with anti-thyroid Pupils were equal and light reflex was present and there were no cranial nerve palsies. On medications. 3 days later, she became confused. At that time, serum corrected calcium motor examination, proximal power was 3/5 and distal power was 5/5 on both lower level was found to be increased. After treatment with adequate hydration and intravenous limbs with normal tone, normal reflexes and bilateral flexor plantar response. On neck zoledronic acid, her conscious level returned to normal. Although she was treated with examination, there was diffuse goitre without bruit. There was atrial fibrillation with the oral carbimazole, her proximal muscle weakness was not much improved. Due to the heart rate around 110 beats per minute. There were no eye signs such as proptosis and later awareness of fatigability and bilateral partial ptosis, we started the trial with oral exophthalmos. pyridostigmine and her weakness became improved. Acetylcholine receptor antibody was negative and the result of nerve conduction study was compatible with myasthenia gravis. Initial Investigations and Treatment The final diagnosis was life-threatening severe hypercalcaemia with underlying Graves’ Based on the history, physical examinations and the following investigations, our disease and generalized Myasthenia Gravis. Currently, the patient’s condition improved clinical diagnosis was proximal myopathy due to hyperthyroid. Investigations performed well with multidisplinary team approach. on the later days showed hyperthyroidism due to Graves’ disease with suppressed TSH < 0.05 (0.2-4.5) with increased Free T4 34.5 (9-21) and increased anti-TSH receptor Background antibody level of 18.79 IU/L (< 1.58). Blood for complete picture showed Hb - 9.6 g/dL (11.5-16.5), WBC - 9.39 x 109/L (4-11) and platelet count of 206 x 109/L (150-400). Renal The commonest causes of hypercalcaemia in clinical practice are primary hyper- function and liver function tests were within normal limits. The random blood glucose parathyroidism and malignancy associated hypercalcaemia. Although hyperthyroidism is level was 105 mg/dl. ECG showed atrial fibrillation with the heart rate of around 110/min one of the causes of hypercalcaemia, it is known to cause a relatively mild hypercalcaemia. and CXR showed cardiomegaly. She was given oral Carbimazole 10 mg TDS together with It is seen in approximately one-fifth of the cases with hyperthyroidism.1 An increase in Propranolol 20 mg BD. bone turnover and mobilization of calcium from bone into the circulation are the main mechanisms responsible for hypercalcaemia associated with hyperthyroidism.2 Since Later Progress Graves’ disease is an autoimmune disease, it is necessary to find out other autoimmune On 3rd day of admission, she became confused and GCS dropped to 13/15 with associations such as vitiligo, type I diabetes mellitus and myasthenia gravis. We described impaired orientations to time, place and person. Vital signs were stable and no fever. There here a case of life-threatening severe hypercalcaemia due to Graves’ disease accompanied was no focal neurological deficit and fundoscopic examination revealed no abnormal with myasthenia gravis. finding. The following investigations were done at that time and we found increased calcium level of 3.95 mmol/L (2.2-2.6) with normal serum phosphate 4.3 mg/dL (2.48- 4.34). To exclude structural lesion in the brain, NECT (head) was performed and the result t Professor of Medicine, Medical Unit (3), Yangon General Hospital showed lacunar infarct (Lt temporal region). « Consultant Physician, Medical Unit (3), Yangon General Hospital v First Assistant Physician, Medical Unit (3), Yangon General Hospital n 2nd year Post-graduate Student (Internal Medicine), University of Medicine (1), Yangon Corresponding author: [email protected]

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Due to the presence of life-threatening severe hypercalcaemia, she was treated Outcome of treatment and follow up with adequate hydration and IV Zoledronic acid (IV Zoledronic acid 4 mg with NS 100 cc Her symptoms improved well after giving oral Pyridostigmine 60 mg TDS and she over 20 mins). 5 days after giving IV Zoledronic acid, serum corrected calcium returned to was discharged from hospital on 1.10.2019. Currently, she is taking oral Pyridostigmine normal limit (Ca - 2.375 mmol/L). The patient’s conscious level also returned to normal at 60 mg TDS, Carbimazole 10 mg TDS, Prednisolone 10 mg OD and Diltiazem 30 mg BD. Her that time. thyroid function test is within normal limit on regular follow-up clinic and she can do her Further Investigations normal daily activities well. To exclude the other possible causes of hypercalcaemia apart from hyper- Discussion thyroidism, we did the following tests. Parathyroid hormone (PTH) was within normal limit Hypercalcaemia, defined as serum calcium levels above 2.7 mmol/L (10.5 mg/dL), 14.35 pg/ml (16-69). USG (neck) showed multiple iso-hypo-echoic nodules in both lobes is a usually mild and well-tolerated clinicopathologic entity. Primary hyperparathyroidism of thyroid glands. No abnormality was detected on USG (abdomen and pelvis). Thyroid is the most common cause of hypercalcaemia seen in ambulatory patients and is usually scan revealed hyperfunctioning diffuse goiter. asymptomatic. Hypercalcaemia associated with malignancy tends to be more frequently symptomatic and is the most common cause of hypercalcaemia in hospitalized patients. To rule out the occult malignancy in the chest and to exclude bone metastases, Together, these two entities constitute 90% of the cases of hypercalcaemia.3 contrast enhanced computed tomography (CECT) (neck and chest) and bone scan were performed. CECT (Neck and Chest) showed thyroid gland enlargement with no features of We presented in this patient with life-threatening and symptomatic hypercal- malignancy; bilateral basal chest infection and lung cysts at superior segment of left lower caemia due to the effect of hyperthyroidism after ruling out other possible causes. Thyroid lobe. Bone scan revealed degenerative changes in L 5 vertebra. hormones are known to increase bone resorption and formation with predominance of the bone resorption. That is also the main mechanism leading to elevated serum calcium Multidisciplinary consultations levels seen in hyperthyroid patients.4 Increased interleukin-6 levels and hyperadrenergic Patient’s weakness was not improved well despite giving the anti-thyroid state induced by thyrotoxicosis are also implicated in hypercalcaemia.5 Indeed, thyroid medications. Due to later awareness of the presence of bilateral partial ptosis, we hyperfunction is usually associated with mild hypercalcaemia. Life threatening hypercal- considered the additional cause of weakness (neuromuscular junction problem) in caemia is rare in hyperthyroidism. this patient. The positive fatigability test was also detected and trial treatment with For second discussion of autoimmune association, the prevalence of autoimmune pyridostigmine was given to patient. Later, we consulted with neurology team for further thyroid disease is higher in myasthenia gravis patients compared to the general populations. special tests such as nerve conduction study and electromyography. Similar case reports are noted in a 20 year-old lady in Senegal and a 28 year-old man 6, 7 t Acetylcholine receptor Ab - negative in India. The reasons for the co-occurrence of the two conditions have not yet been t Nerve Conduction Study & Electromyography - positive stimulated single fiber EMG elucidated. The chemokine CXCL 10 and its receptor CXCR 3 seem to play an important role in the pathogenesis of systemic or organ specific autoimmune disease. The estimated Accordingly, she was diagnosed as generalized myasthenia gravis combined with frequency of the association is variable. 2-3% of those with hyperthyroidism also have Graves’ disease. We continued further investigations for autoimmune associations. Then; myasthenia gravis and 2-17% of those with myasthenia gravis suffer thyrotoxicosis.7 In we consulted with endocrinology team for possible association with Addison’s disease. our patient, her proximal muscles weakness was not improved by anti-thyroid drug and t Fasting Morning Cortisol (8 am) - 279.5 nmol/L (166-507) occurrence of positive fatigability test directed us to continue further investigations and t ACTH - 19.76 pg/ml (7.2-63.3) seek alternative answers. Therefore, we approached diagnosis following not only Occam’s t 30 mins after IM 250 ug of synathen, Morning Cortisol (8:30 am) - 498.3 nmol/L razor but also Hickam’s dictum principle. Consequently, we can diagnose and manage the Results were not compatible with Addison’s disease. As for other autoimmune patient properly and prevent the complications. diseases, she has no features of vitiligo, normal blood sugar. Finally the patient was Learning point and take home message diagnosed as life-threatening severe hypercalcaemia due to Grave’s disease associated with Generalized Myasthenia Gravis. t Awareness of severe life-threatening hypercalcaemia in Graves’ disease t Awareness between autoimmune association between Graves’ disease and Myasthenia Gravis

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t Myasthenia gravis should be thought of if a patient with Graves’ disease does not A Lady with peculiar liver tumour improve well despite adequate control of thyroid function « t t Diagnostic approach: Occam’s razor Vs. Hickam’s dictum Thet Nwe Oo , Win Naing t Occam’s razor - RULE OF SIMPLICITY - When diagnosing a given injury, ailment, illness, Summary or disease, a doctor should strive to look for the fewest possible causes that will account for all the symptoms. Back in 2018, a sixty-three year old lady presented with abdominal mass for about t Hickam’s dictum – Counter argument to the use of Occam’s razor - A man can have as 3 weeks. With a clinical diagnosis of liver tumour, she was investigated with abdominal many diseases as he damn well pleases USG, CT imaging and tumour markers. On evaluation, she had large liver mass in right t If your patient’s condition does not improve with treatment, don’t stick to your lobe of liver with a few small lesions in both lobes, absence of hepatitis viral markers and diagnosis even it can explain well – Search satisfying.8 negative tumour markers. In view of the ambiguous diagnosis, liver biopsy was taken and found to have rare tumour in liver. References Introduction 1. Baxter JD, Bondy PK. Hypercalcaemia of thyrotoxicosis. The Annals of Internal Medicine 1966; 65: 429-442. Hepatocellular carcinoma tumours (HCC) are common in Myanmar on grounds of high alcohol consuming habit, endemic for chronic viral hepatitis infections, and dietary 2. Reddy PA, Harinarayan CV, Sachan A, Suresh V, Rajagopal G. Bone disease in thyro- aflatoxin exposure. Interestingly, some rare tumours are found as differential diagnosis of toxicosis. The Indian Journal of Medical Research 2012; 135: 277-286. HCC. 3. Mefkure Ozkaya H, Ela Keskin F, Asmaz Haliloglu O, Elif Senel T, Kadioglu P.Life- Threatening Hypercalcaemia due to Graves’ Disease and Concomitant Adrenal Failure: Case presentation A Case Report and Review of the Literature. Case Rep Endocrinol, 2015; 2015: 684648. A 63 year old lady complained of abdominal discomfort and had noticed the mass doi: 10.1155/2015/684648 in upper abdomen for three weeks on August, 2018. Apart from abdominal discomfort, 4. Pantazi H, Papapetrou PD. Changes in parameters of bone and mineral metabolism her well-being was not disturbed, with good appetite and stable weight. There was no during therapy for hyperthyroidism. The Journal of Clinical Endocrinology and history of jaundice, vomiting, fever, chills, ascites nor oedema. She had no significant past Metabolism 2000; 85 (3): 1099-1106. https://doi.org/10.1210/jcem.85.3.6457 medical and surgical history. 5. Korytnaya E, Rao NG, Mayrin JV. An unusual case of hypercalcaemia associated with Her vital signs (heart rate, blood pressure, respiratory rate and body temperature) Graves’ disease and vitamin D deficiency.Clinical Medicine Insight: Endocrinology and were stable. All her systemic examinations were normal except non tender large mass in Diabetes 2011; 4: 25-28. right hypochondrial and epigastric regions merging with the liver. Laboratory investigations revealed normal liver function with mild hypochromic microcytic anaemia. CXR, hepatitis 6. Imran M, Mir Y, Aiffa A, Kudyar RP. Autoimmune thyroid disease with myasthenia screen, alpha-fetoprotein, carcinoembryonic antigen and cancer antigen 19-9 were all gravis in a 28-year-old male: a case report. Cases Journal 2009; : 8766. 2 unremarkable. 7. Abdoulaye Pouye, Diatou Guèye Dia, Souhaibou Ndongo, Atoumane Faye, Nafissatou Abdominal ultrasound showed huge hepatomegaly with echogenic mass in Diagne Sakho and Fatou Samba Diago Ndiaye. Graves’ disease associated with right lobe and multiple hypoechoic lesions in both lobes. CT imaging showed one large myasthenia gravis: a case report. Internal Medicine Insight 2014; . DOI: http://dx.doi. 2 hypodense mass in the right lobe measuring 13.2 cm x 16.1 cm x 19.2 cm with few small org/10.7243/2052-6954-2-4 hypodense masses in both lobes of liver. Some have central enhancing nodules, small 8. O’Sullivan ED, Schofield SJ. Cognitive bias in clinical medicine.Journal of Royal College fluid-fluid level and calcifications. Main portal vein, spleen and gall bladder are normal of Physicians of Edinburgh 2018; 48: 225-232. with no evidence of biliary obstruction nor ascites.

« Senior Consultant Hepatologist, Department of Hepatology, Yangon Speciality Hospital t Professor & Head of Department of Hepatology, Yangon Speciality Hospital Corresponding author: [email protected]

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Having mild hypochromic microcytic anaemia in elderly patient, she was also Fig 1. MRI T1 W1 phase subjected to upper gastrointestinal endoscopy to rule out any occult primary lesion in the gastrointestinal tract, which revealed no significant finding. In this clinical picture of elderly lady presenting with abdominal discomfort, accompanied by firm liver mass of about 20 cm in diameter, with normal hepatic and cholestatic function, coagulation profile, normal results of tumour markers and atypical finding in imaging, the following differential diagnoses were considered.

Differential Diagnosis 1. Fibrolamellar carcinoma 2. Variants of HCC 3. Hepatic Adenomatosis The case was discussed in the Hepato-Biliary Clinic joint meeting in collaboration with Department of Hepatobiliary surgery and Department of Radiology. In view of the Fig 2. MRI T2 W1 phase atypical radiological imaging pattern, she was offered a diagnostic percutaneous liver biopsy where the lesion was judged unresectable. The histopathology report revealed a rare pathology of fibrous tumour of the liver. The histologic sections reveal presence of a well circumscribed tumour. It is composed of fascicles of spindled fibroblasts with tapered nuclear ends. There is no evidence of nuclear atypia, hyperchromasia nor mitotic activity. Hyalinised collagen bundles were interspersed within the tumour. Immunohistochemistry study was not proceeded. The patient was followed-up regularly on an outpatient basis every 4 to 6 months with tumour markers and USG scans. Twenty-three months after diagnosis, the patient was still doing well, having normal tumour markers with no evidence of spread nor liver decompensation. Recheck MRI liver was taken on July 2020 to know any extent or progression of the disease. This revealed the same finding as the previous CT imaging. One large and Fig 3. MRI Delayed phase small hypointense areas were seen in both lobes of the liver at T1 W1. The largest one measures about 11.3 cm x 17.2 cm at segment V and VIII of the liver. They are hyperintense at T2 W1. There is slight nodular enhancement noted at delayed phase images. Three small progressive enhancing nodules are also seen at segment II of the liver. Main portal vein is compressed. Gall bladder is normal with no biliary ductal dilatation. There is no lymphadenopathy nor free fluid.

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Discussion when resection is incomplete or pathological examination reveals features of malignancy.2 Space occupying lesions in liver are not uncommonly encountered in our In the present case, surgery is not feasible because of tumour extent involving both lobes daily practices. Most lesions turn out to be definitely diagnosed and treated. Inrare of the liver. occasions, clinical, biochemical or radiological findings are not specific and cannot be Learning Points diagnosed definitely. Their unusualness, image manifestations and non-specific clinical t Some liver tumours , atypical for imaging patterns, need histopatological assessment presentation make early diagnosis difficult and the diagnosis was largely made through a to get a definite diagnosis. histopathological assessment. t Multidisplinary team approach is essential in some diagnostic dilemma cases. In the present case, the diagnosis of fibrous tumour was based on characteristic Conclusion histological features, i.e. high cellular proliferation of typical spindle fibroblast cells. Low mitotic rate, no nuclear atypia, and cellular pleomorphism are in keeping with benign In the present case, a rare liver tumour was diagnosed with the help of our collea- gues; hepatobiliary surgeons, radiologists and histopathologists. lesion. This was evidenced by the favorable course of the patient, who has been doing well and disease progression free for nearly two years up to now. References Immunohistochemically, the staining of CD34, vimentin, and B-cell lymphoma 2 1. Barnoud R, Arvieux C, Pasquier D, Pasquier B, Letoublon C. Solitary fibrous tumour (Bcl-2) is necessary for distinguishing Solitary fibrous tumours (SFTs) from others, such as of the liver with CD34 expression. Histopathology 1996; 28: 551-554. primary hepatocellular carcinoma (CD34 - negative), leiomyoma (smooth-muscle actin - positive and CD34 - negative), inflammatory pseudotumour (forms fibrous tissue made by 2. Changku J, Shaohua S, Zhicheng Z & Shusen Z. Solitary Fibrous Tumour of the Liver: collagen fibers with fibro and myofibroblast and plasma cells) and fibrosarcoma (forms a Retrospective Study of Reported Cases.Cancer Investigation, 2006; 24 (2): 132-135. “herring bone” pattern).1 https://doi.org/10.1080/07357900500524348 Solitary fibrous tumours (SFTs) are soft tissue neoplasms of mesenchymal origin, 3. Chen and Slater. Solitary fibrous tumour of the liver - report on metastasis and local typically found in the pleura but are rarely distributed to extrapleural sites. According to the recurrence of a malignant case and review of literature. World Journal of Surgical World Health Organization (WHO) classification in 2013, extrapleural SFTs are considered as Oncology. 2017: 15: 27. fibroblastic/myofibroblastic neoplasms with intermediate, rarely metastasizing biological 4. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F (eds). Extrapleural solitary 4 behavior. Solitary fibrous tumours of the liver (SFTLs) are unusual neoplasms with few fibrous tumour. In: WHO classification of tumours of soft tissue and bone. WHO 2, 5, 6, 7, 8, 10 cases reported in the world literature. As a result of their extreme rarity, overall Classification of Tumours,th 4 Edition, Volume 5, 2013, IARC, France, 74-78. experience of SFTLs is limited and whether the SFTL should be classified as a benign or malignant tumour remains controversial. There is female preponderance of 2:1 with the 5. Korkolis DP, Apostolaki K, Aggeli C, et al. Solitary fibrous tumour of the liver expressing ages of affected individuals ranging from 16 to 83 years. The mean age at diagnosis is 55 CD34 and vimentin: a case report. World J Gastroenterol, 2008 Oct; 14 (40): 6261- years and the average follow-up period reaches 27 months. Most SFTLs are usually found 6264. as giant lesions growing in either the right or the left lobe of a non-cirrhotic liver, causing 6. Kottke-Marchant K , Hart WR, Broughan T. Localized fibrous tumour (localized non-specific symptoms of fullness and pressure, gastrointestinal obstruction, weight loss fibrous mesothelioma) of the liver. Cancer 1989 Sep; 64 (5): 1096-1102. or hypoglycemia.2, 7 7. Liu Q et al. Primary solitary fibrous tumours of liver: a case report and literature Most SFTLs are benign but there have been a handful of reports on malignant review. Diagnostic Pathology, 8: Article number 195 (2013). cases with local recurrences and metastatic spread.3, 9 Diagnosis is typically made with 8. Patra S, Vij M, Venugopal K, Rela M. Hepatic solitary fibrous tumour: Report of a rare histopathological findings and immunohistochemical examination. Investigation of SFTLs case. Indian J Pathol Microbiol (2012); 55: 236-238. can be difficult with non-specific radiological features and biopsy of radiological liver lesions remains controversial due to the risk of inconclusive results. Radical surgical removal of 9. Shu Q et al. Case Report Malignant solitary fibrous tumour of the liver: a case report. the tumour with clear margins of resection is the mainstay of treatment. Although an SFTL Int J Clin Exp Pathol 2019; 12 (6): 2305-2310. is not a primarily malignant disease, it seems to be of utmost importance that tumour- 10. Yugawa et al. Solitary fibrous tumour in the liver: case report and literature review. free resection margins be achieved in order that locoregional recurrence is prevented. Surgical Case Reports; 5: Article number 68 (2019). Postoperative chemotherapy or radiotherapy should not be necessary and is reserved for Page 76 September 2020 - Vol: 62, No. 3 September 2020 - Vol: 62, No. 3 Page 77 Myanmar Medical Journal Obituary On first April 1974, he was promoted as Head and Consultant Pathologist/Lecturer in Dr. U Maung Ko (1930-2020) Department of Clinical Pathology of YGH. As Senior Histopathologist, he’s responsible for M.B.,B.S; D.C.P (London); D.Path (England) performing 250 to 300 autopsies and approximately (6,500) surgical biopsies per annum. SAMA 1634 As Head of Department, his role included Administrative responsibilities of the Department of Clinical Pathology with (62) Technical Staff including two full time and one part time Dr. U Maung Ko was born on 1st December, 1930 Consultants and six Assistant Pathologists. The department provided more than 300,000 at Wetlet Town, Shwe Bo District. He received tests per annum. He’s also serving as Chairman of School of Medical Technology, Institute his primary education in St. Peter High School in of Paramedical Science, Yangon and producing 12-20 Medical Laboratory Technologists Mandalay since 1936 until he passed Matriculation per year. He also organized for the Medical Technologists to have further postgraduate exam in 1949. He has achieved M.B.,B.S degree training of laboratory technology abroad to achieve AIMLT and FIMLS. Sayagyi Dr. U in 1956 from the Faculty of Medicine, University Maung Ko, as Head of Clinical Pathology Department of YGH, together with Section Head of of Rangoon. After one year internship, he joined Haematology Section, Sayamagyi Dr. Daw Khin Mar Mar and Section Head of Microbiology public service in 1957 and served as Assistant Section, Sayamalay Dr. Daw Khin Mar Mar have provided optimal and utmost support District Health Officer in Health Department, for Clinicians for the best treatment of all patients at that time. Because of their spirit of Mandalay Division for two years responsible for administration and supervision of rural coordination and cooperation with various disciplines of medical and surgical disciplines health centers and maternal and child health centers. In April 1959, he was selected to and excellent laboratory back up and service, that period can be labelled as “Golden Era be trained in Pathology in United Kingdom on a State Scholarship program and posted at of Clinical Pathology.” Even the great surgeons like Professor U Thein Nyunt and Professor Pathology Department of Rangoon General Hospital for (6) months before leaving for UK U Maung Maung Sein, the famous physicians like Professor U Reggie Ba Pe and Professor in late September 1959. From 1st October 1959 to 30th September 1960, he was trained Daw Hnin Yi have frequently come down to Clinical Pathology Department personally to as a postgraduate student in Group Medical Laboratory, Kingston-upon Thames Hospital, discuss about the difficult and problematic cases. Surrey, England. Sayagyi has met Dr. Daw Saw Tha, another lady doctor who’s also in the In 1988, when there’s a democratic uprising of the country, Sayagyi U Maung Ko and two same Hospital for Postgraduate Pathology Training at the same time and they married in Daw Khin Mar Mars were the very active demonstrators and supporters together with 1960 at London. Then from 1st October 1960 to 30th April 1963, he continued his Pathology the people. Being a very straightforward, disciplined and outspoken intellectual, Sayagyi training in Department of Clinical Pathology, Royal Free Hospital School of Medicine, and didn’t want to continue to work under military regime and he asked for resignation from University of London. He was also serving as Honorary Assistant Lecturer in Royal Free the government post and he was granted retirement, after (32) years’ service, before the Hospital responsible for teaching of practical classes for undergraduate medical students. age of 60 years. He achieved D.C.P (London) as well as D.Path (England) (Diploma in Pathology) in 1961. Even after retirement, Sayagyi U Maung Ko kept in touch with his colleagues, trainees and (In those days, only diploma courses were conducted and awarded in the field of Clinical students and gave his histopathology and haematology service at Mya Yadanar Private Pathology). Nursing Home and acting as patron of Association of Clinical Pathology (ACP) under After coming back from postgraduate training in UK in 1963, he served as Assistant Patho- Myanmar Medical Association (MMA) providing necessary advise, guidance and support logist in Department of Clinical Pathology in RGH till 1967 and then he was promoted and to the next generation Pathologists. transferred to National Health Laboratory as Consultant Pathologist/Assistant Director. Sayagyi U Maung Ko was a good leader and administrator, efficient and competent His role involved administration and supervision of all health laboratories in the whole Clinical Pathologist/Histopathologist, dedicated trainer and educator who has nurtured country. At the same time, he also served as Histopathologist responsible for (2000) and mentored hundreds of Pathologists, Medical Technologists and Technicians for our surgical biopsies per annum and supervision of Haematology and Biochemical laboratory country. He’s very much loved and respected by his colleagues, staff, trainees and students as well. From 1970, he also worked as Part-time Neuropathologist in YGH. In addition to because of his sense of responsibility, sincerity, patriotism and moral character. the post as Chief of NHL, he was also Head of Medical Laboratory Grade I School producing around 30 trainees per year. At the same time, he was appointed as Part-time Lecturer Sayagyi Dr U Maung Ko peacefully passed away on 10th May 2020, 00:45 am at his in Department of Pathology of Institute of Medicine (1) Yangon involving teaching of residence, 12/B, Inya Road, Kamaryut Township, Yangon and he will definitely be dearly Haematology and General Pathology to Third MB students and Training and teaching of missed by thousands of his loved and beloved ones. Candidates in Postgraduate Diploma in Pathology Course. Sayagyi is survived by two daughters: Khin Nwe Oo and Khin Nwe Than; one son, Aung Naing Ko and one granddaughter Dr. Mie Thu Ko.

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Professor Ko Ko Hla (1940-2020) Professor Myint Maung Maung (1942-2020) M.B.,B.S, MRCP (UK), FRCP (Edin) M.B.,B.S (MDY), MRCOG, FRCOG (London), Hon Dr.Med.Sc (General Medicine) F.A.C.S (USA), F.I.C.S (USA), F.I.B.A (Cambridge), Hon Dr.Med.Sc (YGN) Professor Ko Ko Hla was born on 5th December 1940 in Yangon. He graduated from Faculty of Medicine, Yangon th University in 1964. He was elected as a Member of the Prof. Myint Maung Maung was born on 26 November Royal College of Physicians of UK in 1971, and as a Fellow 1942 to U Shwin and Daw Thaung in Shwe Bo. He of the Royal College of Physicians of Edinburgh in 1986. He matriculated in 1958 and obtained M.B.,B.S degree from was honored with the Degree of Doctor of Medical Science Institute of Medicine Mandalay in 1965, his MRCOG from the Institute of Medicine (2) Yangon. in 1974, FRCOG in 1986 from the Royal College of

Obstetricians and Gynaeco-logists, London. He received He started his career as a Demonstrator in the Department F.A.C.S (USA) from American College of Surgeons USA in of Anatomy, Institute of Medicine (1) Yangon from 1965- 1988, F.I.C.S from Internal college of Surgeons USA in 1999, Hon Dr.Med.Sc from Institute 1967. He then served as Civil Assistant Surgeon in Myingyan (1967-68) and Yangon General Hospital (1968-69). After MRCP training as a Colombo plan scholar in UK (1970-72) he of Medicine 2, Yangon in 1999. worked as a Specialist Assistant Physician in North Okkalapa General Hospital (1972- He started his career as an Army Medical Officer, Defence Services General Hospital, 74) and Kayin State Hospital, Hpa-an (1975-76). He was then promoted as a Consultant Mingladon in 1965. He served as Military Doctor for 26 years as Consultant and Head, Physician/Lecturer, and posted to Monywa General Hospital (1978-85), Mandalay General Wing Commander for Family Wing including the front line field service; Clinical Professor, Hospital (1985-87) and Worker’s Hospital, Yangon (1987-89). He became a Clinical Department of Obstetrics and Gynaecology, Institute of Medicine 2, Yangon 1989-1990; Professor of Medicine at the University of Medicine (2) Yangon in 1989, and then Head Professor and Head, Department of Obstetrics and Gynaecology, Institute of Medicine 2, of the Department of Medicine of the University of Medicine (2) from 1991 until his Yangon 1990-1997. Senior Medical Superintendent & Professor of Obstetrics and Gynae- retirement in 2000. cology from 1997 to 2004. He was Professor Emeritus of Department of Obstetrics and Although Professor Ko Ko Hla spanned his career as a General Physician, his true passion Gynaecology, University of Medicine 2, Yangon after his retirement. was Clinical Haematology. He provided full support morally as well as with acquiring He established reproductive health activities in 14 States and Divisions and nine Military human resources, in establishing the Departments of Clinical Haematology in both Divisions including Co Co Island and Preparis Island. He received training in Obstetrics and University of Medicine 1 and 2 Yangon and for this endeavour, he is being regarded as Gynaecological (OG) ultrasound at Queen Mother’s Hospital, Glasgow under Professor one of the founding members of Clinical Haematology in Myanmar. His other interests are Tropical Diseases, especially malaria and heat related disorders. He acted as Chairman of Ian Donald, the father of Obstetrics ultrasound, in 1972-1974. He was the pioneer of OG the Internal Medicine Society of Myanmar Medical Association from 1996 to 1999. ultrasound in DGSH. He also started the use of partogram for monitoring of labour in the 1980s. He also initiated diagnostic laparoscopy and laparoscopic sterilization in DSGH in As a person, Professor Hla was regarded as a kindhearted and unpretentious gentleman. 1985. He was trained in surgical skills by OG Prof. U Shwe Tin and his surgical technique He was stoical to his colleagues, solicitous to his protégés and compassionate to his and style is one of the best. His teaching style was also unique, clear and concise. patients. He was always ready to compromise for the best interest of his patients. He followed the principles and teachings of both Lord Buddha and Jesus Christ. He has mentored many outstanding Obstetricians and Gynaecologists. He has special interest in foetal medicine; infertility; gynaecological oncology and medical education. He Professor Hla endured a long illness which rendered him bed-bound in his final years. had introduced the use of vacuum aspiration for evacuating a large hydatidiform mole to With the conscientious care of his devoted wife, he survived those days with full dignity Professor Ian Donald. It was mentioned in the book, Practical Obstetric Problems by Ian rd and passed away peacefully on 3 July 2020. Donald, 5th edition in 1979 and Prof. Myint Maung Maung was very proud of this.

He was honoured with Sit Hmu Htan Kaung Medal; WHO Visiting Scientist Award, Si Man Htoo Choon (Medal for Excellent Performance in Administrative Field (Second Class) in 2000 and Theik Pa Kyaw Swa award on Independence day 2019.

Page 80 September 2020 - Vol: 62, No. 3 September 2020 - Vol: 62, No. 3 Page 81 Myanmar Medical Journal Letters to the Editor He was a member of Myanmar Academy of Medical Science (MAMS); Myanmar News and Media Council, Myanmar National literature Award Selection Committee and Vice Presi- An Invitation to submit dent of Election Commission, Myanmar Medical Association (MMA); President, Obstetrics Letters to the Editor & Gynaecology Society, MMA, 1996-99; Patron, Obstetrics & Gynaecology Society, MMA, 2000 to 2020; member of Myanmar Writers and Journalist Association (MWJA); Chairman Myanmar Medical Journal will include the letters to the editor section in the of RCOG Reference Committee (Myanmar), 1997 to 2007. He was an examiner and Jury coming issues. Those who wish to comment on an article published in Myanmar Medical for undergraduate and postgraduate examinations. Journal will now have an opportunity to do so. He was also a member of Asia Oceania Federation of Obstetricians & Gynaecologists Please note that Letters to the editor should be no more than 500 words with (AOFOG); International Federation of Obstetricians & Gynaecologists (FIGO) and other a maximum of five references. They must be received within (6) months of an article's International and National Societies and Associations. He was an avid golfer and Patron of publication. Letters received after the deadline will not be considered; those accepted will Myanmar Golf Federation. be sent to the author(s) of the article under discussion for reply. Further comment beyond the author's (s') reply to the letter will not be considered. Authors will be notified about Prof. Lt. Colonel Myint Maung Maung is survived by his beloved wife Senior Consultant the disposition of their letters. All accepted letters will be edited. Radiologist Dr. Khin Swe Tin and two daughters. His demise is a great loss to Obstetrical and Gynaecological Community in Myanmar. Be sure to write your full name (and title, if relevant) and to include your address, phone number, and e-mail address.

The letter is to be submitted electronically [email protected] and [email protected].

Please send your letters to:

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