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Official Journal of Anuradhapura Clinical Society http://amj.sljol.info Anuradhapura Medical Journal 2017 Volume 11 Issue 1 Yala ISSN: 2279-3771 An Unusual Case of Dengue Heamorrhagic Fever Complicated with Scrotal Haematoma See Page 19

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Page 1: ISSN: 2279-3771 Anuradhapura Medical Journal

Official Journal of Anuradhapura Clinical Society

http://amj.sljol.info

Anuradhapura Medical Journal

2017 Volume 11 Issue 1 Yala

ISSN: 2279-3771

An Unusual Case of Dengue Heamorrhagic Fever Complicated with Scrotal Haematoma See Page 19

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Editorial Board

Editor Prof. Suneth Agampodi MBBS, MSc, MD, MPH, FRSPH Department of Community Medicine, Faculty of Medicine and Allied Sciences Rajarata University of Sri Lanka Tel +94252226252, M +94777880096 E-mail: [email protected]

Editorial Board Members Dr. Anjana Silva MBBS, M.Phil (Perad.) PhD (Monash) Department of Parasitology Faculty of Medicine and Allied Sciences Rajarata University of Sri Lanka Saliyapura 50008, Sri Lanka. Tel: +94252226388 , +94714400313 E-mail: [email protected]

Dr. C. Sampath Paththinige, MBBS, MSc, PGCME Department of Anatomy, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka Tel: +94252234465, Mobile: +94759251072 E-mail: [email protected]

Dr. Daminda Domingoarachchi. MBBS, MS Teaching Hospital, Anuradhapura Tel: +9477206 5966 E-mail: [email protected]

Dr. Ajith Kumara Dissanayaka MBBS, MD, MRCOG Department of Gynecology and Obstetrics Faculty of Medicine and Allied Sciences Rajarata University of Sri Lanka Tel: +9471296 2245 E-mail: [email protected]

Dr. Jagath Ranasinghe MBBS, MD Lady Ridgway Hospital for Children Dr. Danister De Silva Mawatha, Colombo Tel: +9477739 8238 E-mail: [email protected]

Dr. Buddhika Wijerathne MBBS, PGDipPH, FRSPH Melbourne, Australia E-mail: [email protected]

Dr. Sujanthi Wickramage MBBS, MPhil Department of Physiology Faculty of Medicine and Allied Sciences Rajarata University of Sri Lanka Email: [email protected]

Dr. Anuprabha Wickramasinghe. MBBS, MD Department of Psychiatry Faculty of Medicine and Allied Sciences Rajarata University of Sri Lanka Tel: +9471941 5822 E-mail: [email protected]

Editorial Assistants Dr. Janith N Warnasekara MBBS, PGDipPH, FRSPH Department of Community Medicine Faculty of Medicine and Allied Sciences RajarataUniversityofSriLanka.Tel:+94252226252,+94713181238E-mail:[email protected]

Dr. Ranjan Ganegama. MBBS Teaching Hospital Anuradhapura Tel: +9471362 3702 Email: [email protected] Anuradhapura Medical Journal strives to be a forum for all health professionals to publish original research and review articles in their area of expertise. The Anuradhapura Medical Journal is a peer-reviewed, medical journal published by Anuradhapura Clinical Society (ACS). The Anuradhapura Medical Journal publishes articles in clinical medicine, public health and health promotion

Anuradhapura Medical Journal is a peer-reviewed, open access journal

All communication should be address to The Editor, Anuradhapura Medical Journal Department of Community Medicine, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka

For submission instructions and all other information visit: http://amj.sljol.info/about/submissions/

e-ISSN 2345-9719 (Online)

Anuradhapura Medical Journal is available online at : http://amj.sljol.info/

Anuradhapura Medical Journal is Published by Anuradhapura Clinical Society, Teaching Hospital Anuradhapura, Sri Lanka.

Copyright and copying © All are open access articles distributed under the Creative Commons Attribution License Attribution 4.0 International (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Anuradhapura Medical Journal is a member of Committee on Publication Ethics (COPE)

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Google scholar DOAJ Index Medicus for WHO South-East Asia (IMSEAR) Global Index Medicus (by WHO Headquarters, Geneva). Hinari This text is printed on acid-free paper

Printed by Ananda Press, Colombo 13

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Anuradhapura Medical Journal Volume 11 Issue 1 2017 Yala

Published Biannually

Editorial Can the Success of Primary Health Care in Sri Lanka be Maintained? Jane Brandt Sørensen, Flemming Konradsen, Suneth Agampodi

01-03

Original Articles Factors Affecting Respiratory Function of Rice Millers in Anuradhapura District Wickramage SP, Rajaratne AAJ, Udupihille M

04-10

Brief Report Is Cancer Screening a Priority among Adult Females in Sri Lanka? Warnasekara YPJN, Gamakumbura MK, Koonthota SD, Liyanage LSK, Lakpriya BAD, Agampodi SB

11-13

Case Reports Impulse Control Disorder in a 4-Year-Old Child Ellapola A, Sumanasena B

14-15

A Patient with Heroin Withdrawal Presenting with Newly Onset Seizures Basnayake BMDB, Kannangara T, Wickramasinghe WMASR, Wijesena SN

16-18

An Unusual Case of Dengue Haemorrhagic Fever Complicated with Scrotal Haematoma Premathilake PNS, Kularatne WKS, Senadhira SDN, Bandara WRSM

19-22

A Rare Presentation of Guillain-Barre Syndrome: Pharyngeal Cervical-Brachial Variant Mohamed Nadheem

13-24

Review More Shades of Grey Than Black and White: A Brief Review of Management of Anorectal Fistula Seneviratne RW, Kumara MMJK, De Silva PV

25-30

Lung function assessment in preschool children; a review of the utility of basic spirometry, interrupter technique and forced oscillation technique Rajapakse SI, Yasaratne D, Amarasiri L

31-36

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Editorial Can the Success of Primary Health Care in Sri Lanka be Maintained? Jane Brandt Sørensen1,2 , Flemming Konradsen1,2, Suneth Agampodi3 1 Department of Public Health, University of Copenhagen, Denmark 2 South Asian Clinical Toxicology Research Collaboration (SACTRC), Sri Lanka 3 Department of Community Medicine, Rajarata University of Sri Lanka, Sri Lanka

Key words: Alma-Ata Declaration, Primary Health Care, Sri Lanka, Non-communicable diseases Copyright: © 2017 Sørensen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Funding: None Competing interest: None Correspondence: [email protected] DOI: http://doi.org/10.4038/amj.v11i1.7645 This year marks the 40th anniversary of the Alma-Ata Declaration, adopted at the International Conference on Primary Health Care in 1978. The Declaration focused on health as ‘a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity’ and recommended a cross-sectoral approach to promote health (1,2). It highlighted the inequality of health statuses between countries as unacceptable and noted how health for all was a human right. A key element was that of Primary Health Care (PHC) and how it should be incorporated in national health systems to achieve universal health care for all (1). Currently, universal health coverage is on the agenda through the Sustainable Development Goals (SDGs), where the aim is to ensure healthy lives and promote well-being for all (3).

Building upon Sri Lanka’s policies of free access to government provided health care services since the 1930s, the country signed the Alma-Ata Declaration in 1978 (2). Sri Lanka’s health system has served as a role model for successful implementation of PHC for a number of years (4). Specifically, it has used community-based health services supported by the PHC system (5). For instance, Sri Lanka improved rural health centres by staffing them

with competent midwives, thereby bringing health services closer to rural families and reducing the need for beds in urban referral hospitals (4). The significant focus on PHC has had a profound effect on health in the country, especially in regards to maternal and child health, immunization and control of major infectious diseases (2). Regardless of economic fluctuations, Sri Lanka has managed to maintain a satisfactory level of health (6). Life expectancy at birth has continuously risen and is currently 75 years (72 years for men and 78 years for women), which is considerably higher than the WHO regional average of 67 years (7). Furthermore, under-five mortality and maternal mortality has decreased significantly over the years (7).

The question is however, whether it is possible to keep this position as a PHC role model among low- and middle-income countries. Sri Lanka has one of the fastest aging populations in South Asia. It is estimated that the population over 60 will double within the next 25 years (8). This brings additional health requirements of elderly people in a system with limited social security (6) as well as decreasing family support. Such changes in the demographic composition also brings an epidemiological

Abstract This year marks the 40th anniversary of the Alma-Ata Declaration, adopted at the International Conference on Primary Health Care in 1978. Building upon Sri Lanka’s policies of free access to government provided health care services since the 1930s, the country signed the Alma-Ata Declaration in the same year. Since then, Sri Lanka’s health system has served as a role model for successful implementation of PHC for a number of years. The question is however, whether it is possible to keep this position as a PHC role model among low- and middle-income countries. We highlighted here some of those challenges and the way forward.

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transition. Over the past decades, the relative importance of communicable, maternal and perinatal diseases have decreased and today more than 75% of deaths in Sri Lanka are caused by non-communicable diseases (NCDs) (9). Also, causes of injuries have changed with an increasing importance of traffic related injuries (7).

This epidemiological transition requires a significant transformation of the PHC system in Sri Lanka with updated health policies and services to ensure an adequate response to the new demands. A recent World Bank assessment concluded that there was no evidence yet that Sri Lanka is performing well in terms of managing NCDs, nor that the health system, as it is currently configured, is well positioned to do so. The rapid epidemiological transition further calls for educating a greater number of health professionals in established as well as new fields of professions. The current capacity at the training institutions may not be equipped to fulfil future demands. This will influence a key component of the health care system building blocks - the human resources - and are likely to affect the greatest on the rural population (10).

Expenditure on health as a share of gross domestic product (GDP) has decreased in Sri Lanka in recent years where spending on health has grown slower than the overall economy and currently stand at approximately 3% of GDP (11). The Government spending on health has remained at around 8% of the budget for the past 10 years (11). Around the year 2006, Sri Lanka had the lowest dependency rate, which provided a window of opportunity for a favourable impact on the economy. However, Central Bank of Sri Lanka data clearly shows that Sri Lanka has not used the demographic dividend effectively (12). This missed opportunity will be an additional burden to the health care system. With the increasing pressure from the demographic and epidemiological transitions in Sri Lanka, it is questionable if government expenditure on health can be maintained at 8% without affecting universal access to health care.

Sri Lanka has a moderate incidence of catastrophic expenditure, with around 5% of the population spending more than 10% of their entire budget on health. However, high out-of-pocket expenditure (almost 40% of current health expenditure) (2) and high utilization of the private sector, even among low income groups, means that in spite of access to free state health care the actual cost of some drugs, investigations and surgeries may place a significant burden on households (13).

The ongoing epidemiological transition may without investments and health reforms result in patients, who in

even greater numbers, bypass lower-level government health facilities, if not equipped to deal with the specific requirements of NCDs. Also, going forward without an intensification of government health care reforms the role of the private health care sector is likely to grow further. The private sector already plays an important role in Sri Lanka and make up approximately 55% of total spending of healthcare, especially in the context of outpatient curative care (14). According to estimations made by PricewaterhouseCoopers (PWC) out of pocket expenditure make up 86% of private expenditure on healthcare with the remainder relatively evenly split between private and employer insurance. A further move towards private care may place pressure on the households in terms of out-of-pocket payments. In addition to the growing private clinical services, the private pharmaceutic and diagnostic sectors are growing 14-17% per year (14). Clearly, the private sector offers a growing and needed service. However, the universal access have to be addressed politically to ensure an equilibrium in services and to not undermine access to health care for already marginalized urban, remote-rural and estate communities.

The need to invest in effective preventive strategies for NCDs is of paramount importance to reduce the financial burden on private households and government budgets. The current PHC system will need to incorporate such efficient preventive approaches to remain relevant. In addition to the range of important cardio-metabolic disease, mental health challenges will also have to see further investments to reduce not only individual suffering but also the tremendous burden on the society. In sum, to achieve the SDG targets for health and the aim of ‘leaving no one behind’, the PHC services of Sri Lanka will need to develop further in order to address the changing needs of the population. References 1. World Health Organization member states.

Declaration of Alma-Ata - International Conference on Primary Health Care, Alma-Ata, USSR, 6-12 September 1978 [Internet]. 1978. Available from: http://www.who.int/publications/almaata_declaration_en.pdf

2. Alliance for Health Policy and Systems Research, World Health Organization. Primary Health Care Systems (PRIMASYS) - Case study from Sri Lanka [Internet]. World Health Organization; 2017. Available from: http://www.who.int/alliance-hpsr/projects/alliancehpsr_srilankaprimasys.pdf

3. United Nations. Sustainable Development Goals [Internet]. Sustainable Development Knowledge

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Platform. 2015. Available from: https://sustainabledevelopment.un.org/sdgs

4. Rohde J, Cousens S, Chopra M, Tangcharoensathien V, Black R, Bhutta ZA, et al. 30 years after Alma-Ata: has primary health care worked in countries? The Lancet. 2008 Sep;372(9642):950–61.

5. Senanayake S, Senanayake B, Ranasinghe T, Hewageegana NSR. How to strengthen primary health care services in Sri Lanka to meet the future challenges. J Coll Community Physicians Sri Lanka. 2017 Jun 2;23(1):43.

6. Kumara AS, Samaratunge R. Patterns and determinants of out-of-pocket health care expenditure in Sri Lanka: evidence from household surveys. Health Policy Plan. 2016 Oct 1;31(8):970–83.

7. World Health Organization. Sri Lanka: WHO statistical profile [Internet]. World Health Organization; 2015. Available from: http://www.who.int/gho/countries/lka.pdf?ua=1

8. The World Bank. Sri Lanka to Improve Its Primary Healthcare Services [Internet]. The World Bank. 2018. Available from: https://www.worldbank.org/en/news/press-release/2018/06/27/sri-lanka-improve-its-primary-healthcare-services

9. World Health Organization. Sri Lanka - Noncommunicable Diseases (NCD) Country Profiles , 2014 [Internet]. 2014. Available from: http://www.who.int/nmh/countries/lka_en.pdf?ua=1

10. Smith O. Sri Lanka: Achieving Pro-Poor Universal Health Coverage without Health Financing Reforms.

Washington DC: World Bank Group; 2018. Report No.: Universal Health Coverage Study Series No. 38.

11. World Health Organization, South-East Asia. Health financing profile 2017 - Sri Lanka [Internet]. 2017. Available from: http://apps.who.int/iris/bitstream/handle/10665/259644/HFP-SRL.pdf?sequence=1&isAllowed=y

12. Central Bank of Sri Lanka. Economic and Social Statistics of Sri Lanka 2018 [Internet]. Central Bank of Sri Lanka, Statistics Department; 2018. Available from: https://www.cbsl.gov.lk/sites/default/files/cbslweb_documents/statistics/otherpub/economic_and_social_statistics_of_SL_2018_e_0.pdf

13. de Silva A, Ranasinghe T, Abeykoon P. Universal health coverage and the health Sustainable Development Goal: achievements and challenges for Sri Lanka. WHO South-East Asia J Public Health. 2016;5(2):82.

14. PricewaterhouseCoopers. The Health sector of Sri Lanka [Internet]. The Embassy of the Kingdom of the Netherlands; 2014. Available from: https://www.rvo.nl/sites/default/files/2016/01/Health%20sector%20in%20Sri%20Lanka.pdf

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Research Article

Factors Affecting Respiratory Function of Rice Millers in Anuradhapura District Wickramage SP1 , Rajaratne AAJ2, Udupihille M1 1 Department of Physiology, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Sri

Lanka 2Department of Physiology, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka

Key words: Rice millers, Lung functions, Occupational lung disease, Spirometry, Lung function norms Copyright: © 2017 Wickramage SP et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Funding: Financial assistance provided by the Rajarata University research grants RJT/R&P/2009/Med/R/04, RJT/RP&HDC/2012/Med.&Alli.Sci./R/04 and RJT/RP&HDC/2013/Med.&Alli.Sci./R/01 and National Research Council (Grant 06/67) are gratefully acknowledged. Competing interest: None Correspondence: [email protected] DOI: http://doi.org/10.4038/amj.v11i1.7644

Abstract Introduction Rice is the most important crop cultivated in Sri Lanka and rice milling is the largest agro-based industry in the country. Objectives To compare lung functions of rice millers and controls with predicted normal values for Sinhalese and to determine the effects of rice husk dust on lung functions of rice millers in relation to length (years) of exposure. Methods Rice millers (male: 84, female: 84) and controls (male: 84, female: 84) were selected and matched for determinants of lung functions. Data were collected via a validated questionnaire and spirometry. Observed mean lung functions were compared with lung function norms published for non-smoking Sinhalese. Results Most of the male millers and controls were smokers while none of the females were. All mean lung functions tested FVC, FEV1, PEFR and FEF25-75%, were significantly lower than the predicted values among male millers. While some lung functions were significantly reduced in female millers and male controls, all were comparable with predicted values in female controls. Duration of employment in rice mills was significantly and inversely related to FVC and FEV1 of millers. Conclusions Observed deficiencies in lung functions of rice millers were probably caused by occupational exposure to rice husk dust and tobacco smoke. The cumulative effect of the two were found to be more harmful than each alone. Wearing face masks, worker education and adequate ventilation in mills are recommended. Advantages of cessation of smoking should be further stressed to communities of lower socioeconomic and educational backgrounds.

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Introduction Respiratory diseases associated with agriculture were among the first recognized occupational health hazards in the world (1). Olaus Magnus, as early as in 1555, warned about the dangers of inhaling grain dusts (1). This risk was again noted in 1713 by the Italian Physician Bernardino Ramazzini in his seminal work De Morbis Artificum Diatriba (Diseases of Workers) (1). According to Buchan and Kramer (1980) (2) Ramazzini found that nearly all the workers engaged in sifting and measuring grain developed shortness of breath and rarely reached old age.

Although respiratory health hazards were first recognized in the early ages, it has only been in the 20th century that this problem has been carefully studied and documented. In general, the investigation of agricultural health hazards in the world has always got secondary treatment when compared to the investigation of hazards in mining and other heavy metal industries. Nevertheless, these agricultural health hazards are of serious concern (1).

Rice (Oryza sativa) is the major staple food in the Sri Lankan diet (3) and also of more than one quarter of the world’s population (4). At present, rice occupies about 34% (780,000 hectares) of the total cultivated area in Sri Lanka (5). It is grown as a wetland crop in all the districts in the country in irrigated paddy fields. Rice milling is the process by which paddy is converted to rice. The main steps in rice milling include air and sun drying of the paddy, cleaning, hulling/de-husking, separating, polishing and grading (6). All these steps generate dust, especially hulling, polishing and air and sun drying of the paddy. Rice milling in Sri Lanka is primarily a small to medium scale industry with very little formal control of working conditions by the government. Therefore, almost no protective measures are taken by these paddy mill workers against inhalation of rice husk dust. Furthermore, the average mill worker, with his low level of education, is ignorant of potential harmful effects of inhalation of various dust particles and is reluctant to adopt safety precautions (7).

A cross sectional study carried out among Malaysian rice millers showed significantly higher prevalence of respiratory symptoms among rice millers than the controls. These symptoms included chest tightness (34.9%), morning phlegm (31.7%), shortness of breath (31.7%) and morning cough (19%) (8). Meanwhile, of a group of 150 Pakistani rice millers 18.7% had lung function changes attributable to obstructive lung disease, while 4% had features of restrictive lung disease (9). Furthermore, Indian rice millers were found to have significantly lower Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second (FEV1) and Peak Expiratory Flow Rate

(PEFR) when compared with controls (10). Similar findings were observed in another Indian study with 42.6% of the studied rice mill workers showing evidence of respiratory morbidity and 10.7% having decreased PEFR (11).

While rice is the single most important crop cultivated in Sri Lanka (5) and rice milling is the largest agro-based industry in the country (12), the occupational health of the Sri Lankan rice millers has not been adequately studied. The present study was carried out with the aim of gaining better understanding of the impact of the rice husk dust exposure on the Sri Lankan rice millers. It was carried out in the mainly agricultural Anuradhapura district of Sri Lanka where 64.2% of the district’s labour force is employed in the agricultural sector (13). The objective of this study was to compare the lung function variables of the rice millers and controls with the predicted normal values for the Sinhalese population and to determine the effects of rice husk dust on lung functions of rice millers in relation to length (years) of exposure.

Materials and Methods The study was carried out in Anuradhapura district. Anuradhapura is primarily an agricultural district with most of the resident people are engaged in rice farming activities. It is estimated that 182,834media to large scale rice farmers are living in Anuradhapura district currently. Rice production from the area during Yala season 2017 was nearly 30,000 MT. In the current study, the subject group comprised of 84 male and 84 female rice millers selected from rice mills in 11 out of the 22 divisional secretariat divisions in Anuradhapura district through convenient sampling. Each selected rice miller was employed in rice mills for a total period of 2 years or more. The control group was made up of 84 males and 84 females employed as security guards and cleaners in Rajarata University of Sri Lanka.

The millers were excluded from the study if they were found to have acute respiratory tract infection, or were on treatment for acute respiratory tract infection, at the time of testing. The exclusion criteria also included having had a prior history of respiratory disease with lasting complications or frequent exacerbations affecting current respiratory function, or a history of cardiac illness with complications affecting current respiratory function. The millers were also left out of the study if, at the time of testing, they were found to suffer from respiratory or cardiovascular disease not possibly related to occupational dust exposures. The millers with dental abnormalities with difficulties in sealing lips around the mouth piece to perform spirometry, and the millers who were not actively

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involved in the milling process, such as cooks and clerical staff of the larger mills, were also excluded from the study.

Data was collected via an interviewer administered validated respiratory symptom and occupational history questionnaire and spirometry. Each participant’s respiratory function was assessed via spirometry. A Spirolab II (Medical International Research, Rome, Italy) portable spirometer was used for this purpose, and the measurements were taken according to the guidelines published by the American Thoracic Society (14). Spirometry was performed twice on each individual. On the rice millers, it was performed once in the morning, before the start of day’s work, and once in the afternoon, after the workers had been exposed to the rice husk dust for over 4 hours. Data was collected from the rice millers fulfilling the selection criteria employed in 43 rice mills. Similarly, in the controls too spirometry was performed once in the morning and once in the afternoon. Of the lung function measurements recorded by the spirometer, FVC, FEV1, FEV1/FVC ratio, PEFR and FEF25-75% (Average Mid-expiratory Flow Rate) were used in the comparisons. The spirometer was calibrated using a fixed volume 3-liter calibration syringe (A-M systems, USA). This calibration was done following its use on 2 or 3 mills.

The data gathered in the lung function assessment were entered in a computerized data base (Excel, TMMicrosoft). The entered data sheet was double checked comparing with the questionnaires to ensure correct data entry. The data analysis was carried out using SPSSTM version 17.0 (Statistical Product and Service Solutions, Chicago) software. Prior to analyses, the normal distribution of the data sets were ascertained by applying statistical tests of normality such as Anderson-Darling, Ryan-Joiner and

Kolmogorov-Smirnov.

The average normal predicted lung function values published by Udupihille (1995) (15) for the healthy non-smoking Sinhalese adults of similar age and height were utilized to compare the observed values. The predicted lung functions were calculated for each individual using the published equations (15) and the means of the predicted values were obtained. To calculate the predicted FEV1 the equation used was: FEV1 = (0.02) Height (cm) + (- 0.023) Age (years) + (- 0.139)

These means of the predicted values were compared with the means of the observed values by using one sample t tests. Multiple linear regression analyses were carried out to assess the contributory factors to the lung functions of the rice millers.

Ethical clearance for the study was obtained from the Research, Ethics and Higher Degrees Committee of the Faculty of Medicine & Allied Sciences, Rajarata University of Sri Lanka. All the millers and the controls recruited for this study were given explanations about the aims of the study and the extent of the participants’ contribution, by the principal investigator, and their written informed consent was taken prior to their participation. Results

Means age of the males and the females from rice miller group was 44.8 ± 11.1 and 44.7 ± 8.7 years respectively (Table 1).

Table 1: Comparison of factors determining lung volumes and capacities of rice millers and controls

Factors Male Female

Millers Controls p-value Millers Controls p-value

Age (years)* (mean ± SD) 44.8 ± 11.1 41.6 ± 11.4 0.063 44.7 ± 8.7 42.3 ± 8.6 0.074

Height (cm)* (mean ± SD) 165.4 ± 6.4 167.1 ± 5.6 0.294 151.0 ± 7.6 152.7 ± 6.9 0.282

Weight (kg)* (mean ± SD) 59.7 ± 9.8 62.6 ± 11.1 0.69 53.0 ± 10.8 55.3 ± 9.9 0.143

Tobacco smoking status (pack year index)* (mean ± SD) 5.7 ± 7.9 4.3 ± 7.3 0.247 0 0 -

Passive smoking status** None to mild % (n) 61.9% (52) 83.3% (70) 0.002 82.1% (69) 89.3% (75) 0.186

Moderate to severe % (n) 38.1% (32) 16.7% (14) 17.9% (15) 10.7% (9)

Exposure to other agricultural dusts**

Exposed % (n) 63% (53) 52% (44) 0.160 37% (31) 31% (26) 0.415

Non-exposed % (n) 37% (31) 48% (40) 63% (53) 69% (58)

Socioeconomic status** Education standard No/Primary education % (n)

20.2% (17) 3.6% (3) 0.001 29.8% (25) 14.3% (12) 0.016

Secondary education % (n) 79.8% (67) 96.4% (81) 70.2% (59) 85.7% (72)

Marital status Single/divorced/separated/widowed % (n)

10.7% (9) 14.3% (12) 0.484 26.2% (22) 9.5% (8) 0.005

Married % (n) 89.3% (75) 85.7% (72) 73.8% (62) 90.5% (76)

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None of the females were smokers while 66% from the male rice miller group and 64% from the male control group were smokers with 5.7 ± 7.9 and 4.3 ± 7.3 pack years respectively. Controls had a higher educational level than the millers in both the male and female groups (Table 1).

The outcomes obtained for male millers, female millers, male controls and female controls are shown in tables 2, 3, 4 and 5 respectively. All mean lung functions tested FVC, FEV1, PEFR and FEF25-75%, were significantly lower than the predicted values among male millers. While some lung functions were found to be significantly reduced in the female millers and male controls, all the lung functions tested were compatible with the predicted values among female controls.

Contributory factors to lung functions of millers as identified from multiple linear regression are shown in Table 4. The significant contributions of the already recognized determinants such as age, gender, height and weight on lung functions were confirmed by the analysis.

The duration of employment in rice mills was significantly and inversely related to the FVC and FEV1 values of the millers. Among other factors tested, the mean pack year index of smoking was significantly associated with FEV1 and PEFR, while the exposure to other agricultural dusts was significantly associated wit FEV1 of the millers.

Discussion

The present study has confirmed that the cardiorespiratory health of the rice millers employed in Anuradhapura district, irrespective of gender, is adversely affected. In the current study, for comparisons, the lung function norms published for the Sinhalese by Udupihille in 1995 (15) were used. These norms predict the expected lung function values for normal, healthy, non smoking, Sinhalese individuals, depending on their age, height and sex. Most of the lung functions of female as well as male millers used in the current study were lower than the respective norms.

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These norms which were published over twenty years ago, could be expected to have changed to a certain degree over the two decades due to changes in environmental factors including air pollution, socioeconomical factors, the changes in people’s dietary habits, exercise etc. Further, Udupihille has used the data collected from non-smoking Sinhalese individuals to establish the lung function norms. However, in the current study, the majority of the male subjects and controls were smokers and as such, the results could have been adversely affected.

Despite these obvious limitations, many lung functions of the millers were found to be significantly lower than the predicted norms. While the female controls had mean lung functions comparable to norms, the mean FVC and FEV1 of the male controls were significantly lower, probably owing to tobacco smoking. The female millers' lung functions were likely to have been affected due to the exposure to rice husk dust while the male millers were probably affected due to the combined effect of rice husk dust and tobacco smoke.

When air pollutants are breathed into the lungs, the harmful particles which bypass the lung defense mechanisms such as hairs in nostrils, mucus membrane lining the nasal passage and pharynx and ciliary action, may get trapped in the alveoli, causing a localized inflammatory response. Enzymes such as elastase are released during this inflammatory response, causing alveolar septal disintegration. The inflammatory response also causes impairment of lung defense mechanisms and disruption of lung tissue repair mechanisms. This may lead to significant deformities in lung architecture, including loss of lung elastic recoil, leading to functional consequences. A similar chronic inflammatory response in the lungs can be expected due to long term exposure to rice husk dust. This may play a role in chronic reductions in lung functions in those exposed to rice husk dust.

Smokers are known to develop prominent restrictive changes in lungs with the tobacco smoke destroying lung elastic tissue and preventing full expansion of lungs, thus leading to emphysema. They may also develop chronic obstructive airway changes as tobacco smoke causes inflammation driven pathologies in the lungs, giving rise to progressive airflow limitation. Both active and passive smoking can cause damage to the lungs. It has been shown that smokers are affected by the exposure to rice husk dust far worse than non smokers (16)(17). Tobacco smoke contains more than 7000 chemicals, most of which are toxic to cilia, the tiny hair-like processes lining the airways (18). The toxins in the inhaled smoke would slow down the ciliary action, paralyze them, and finally destroy them, thereby hindering their sweeping action of mucus. This would cause the mucus to build up in the airways, giving rise to long standing cough and phlegm in the chest. A multiple regression analysis confirmed the significant contributions from the already recognized determinants such as age, gender, height and weight on lung functions. The total number of years employed in rice mills were significantly inversely correlated with FVC and FEV1 of the rice millers.

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This study has shown that rice millers employed in Anuradhapura district, Sri Lanka, irrespective of gender, have significantly reduced lung functions when compared with the norms predicted for the healthy, non-smoking Sinhalese individuals. These adversities were probably caused by the occupational exposure to rice husk dust, and the combined effect of rice husk dust and tobacco smoke. Duration of employment in rice mills was inversely related to the FVC and FEV1 values of the millers. The present study has reconfirmed the harmful effects of tobacco smoke on the lung functions. The cumulative effect of grain dust and tobacco smoke was found to be more harmful than each alone. Measures employed by the mill workers during work to avoid direct contact with dust, such as wearing of face masks, are recommended. Also, measures need to be taken to standardize, implement and maintain adequate ventilation in mills (i.e. fixing of dust extraction fans) and also to educate Sri Lankan rice millers regarding this preventable harm they are unknowingly exposing themselves to. Introduction of a rice mills hygiene protocol should prove to be beneficial. The advantages of cessation of smoking should be further stressed to communities of lower socioeconomic and educational backgrounds.

Acknowledgements

The authors sincerely thank Prof D.J. Weilgama and Dr B.T.B. Wijerathne for their contribution in manuscript preparation and Ms K.D.N. Karunarathne and the Temporary Lecturers and the non-academic staff of the Department of Physiology for their assistance during data collection.

References

1. Respiratory health hazards in agriculture. Am J Respir Crit Care Med. 1998;158(5):2.

2. Buchan RM, Kramer GD. A Field Test of a Procedure for the Identification of Protein-Bearing Particles in Grain Elevator Air. 1980.

3. Palipane KB. Milling and quality improvement in rice, Institute of Post Harvest Technology, Anuradhapura. 2003.

4. Lim HH, Domala Z, Joginder S, Lee SH, Lim CS, Abu Bakar CM. Rice millers’ syndrome: a preliminary report. Br J Ind Med. 1984 Nov;41(4):445–9.

5. International Rice Research Institute. Sri Lanka Rice Knowledge Bank. International Rice Research Institute. 2007.

6. Hathurusinghe CP. Paddy Milling Survey 2006. Colombo: Hector Kobbekaduwa Agrarian Research and Training Institute; 2007.

7. Dassanayake BK, Ratnatunga KC, Karunaratne KI, Nandadeva D, Nanayakkara SDI, Rajaratne AAJ. The effect of occupational exposure to paddy husk dust on the respiratory health of paddy mill workers in Sri Lanka. Proc Perad Univ Res Sess Sri Lanka. 2007;12(1):146–7.

8. Musa R, Naing L, Ahmad Z, Kamarul Y. Respiratory health of rice millers in Kelantan, Malaysia. Southeast Asian J Trop Med Public Health. 2000 Sep;31(3):575–8.

9. Singh SK, Nishith SD, Tandon GS, Shukla N, Saxena SK. Some observations on pulmonary function tests in rice mill workers. Indian J Physiol Pharmacol. 1988;32(2):152–7.

10. Bhat MR, Ramaswamy C. A comparative study of lung functions in rice mill and saw mill workers. Indian J Physiol Pharmacol. 1991;35(1):27–30.

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11. Prakash S, Manjunatha S, Shashikala C. Morbidity patterns among rice mill workers: A cross sectional study. Indian J Occup Environ Med. 2010;14(3):91–3.

12. Rafeek MIM, Mahrouf ARM, Samaratunga PA. Rice marketing system: implication for rice quality improvement and issue of affordability. 2003.

13. Department of Census and Statistics. Sri Lanka labour force survey. Annual Report - 2010 (with Provincial and District Level Data), Ministry of Finance and Planning. 2010.

14. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardisation of spirometry. Eur Respir J. 26:319–38.

15. Udupihille M. Spirometric and flow standards for healthy adult non-smoking Sri Lankans belonging to the Sinhalese ethnic group. Ann Hum Biol. 1995;22(4):321–36.

16. Cotton DJ, Graham BL, Li KY, Froh F, Barnett GD, Dosman JA. Effects of grain dust exposure and smoking on respiratory symptoms and lung function. J Occup Med. 1983;25(2):131–41.

17. Ye TT, Huang JX, Shen YE, Lu PL, Christiani DC. Respiratory symptoms and pulmonary function among Chinese rice-granary workers. Int J Occup Environ Health. 1998;4(3):155–9.

18. American Cancer Society. Harmful chemicals in tobacco products [Internet]. 2017. Available from: https://www.cancer.org/cancer/cancer-causes/tobacco-and-cancer/carcinogens-found-in-tobacco-products.html

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Warnasekara YPJN et al. AMJ 2017 Open Access

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Brief Report Is Cancer Screening a Priority among Adult Females in Sri Lanka? Warnasekara YPJN 1 , Gamakumbura MK1, Koonthota SD1, Liyanage LSK1, Lakpriya BAD1, Agampodi SB2 1 Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka 2 Department of Community Medicine, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka

Key words: Cervical cancer, Breast cancer, Screening, Sri Lanka, Knowledge Copyright: © 2017 Warnasekara YPJN et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Funding: None Competing interest: None Correspondence: [email protected] DOI: http://doi.org/10.4038/amj.v11i1.7639

Introduction The concept of the Well Woman Clinic (WWCs) was first introduced to Sri Lanka in 1996 to screen women for non-communicable diseases including reproductive system malignancies; breast and cervical cancers. This was done as part of a reproductive health programme promoted by international agencies at the International Conference on Population and Development in Cairo in 19941. At present, WWCs are operating throughout the country, at all Medical Officer of Health (MOH) areas, on fortnightly or monthly basis. At these clinics, women over 35 years of age get screened for cervical and breast cancers, hypertension and diabetes mellitus.

Breast and cervical cancers are the most common malignancies among women in the world as well as in Sri Lanka. According to the National Cancer Control Unit data, the estimated age adjusted annual incidence for breast and cervical malignancies in Sri Lanka was 23 and 8.4 per 100,000 respectively in 2010. The lifetime risk of having a

breast cancer among Sri Lankan women is 2.1%. Screening for breast cancer is considered effective in Low and Middle Income Countries (LMICs) where the size of the tumour is considerably large at presentation. Unlike other malignancies, the survival rates of cervical cancer patients are high when identified at early stages. While the WWC services are available for early detection, more than 30% of breast cancers diagnosed in Sri Lanka in 2007 were in the stage IIIA or later showing a late presentation. These women were either not using or not aware of cancer screening services. It has been more than 20 years since the WWC was first introduced to the Sri Lankan health sector. Yet, published data on awareness and utilization of the services of the WWC is scarce. The purpose of the present study was to determine the awareness and utilization of breast and cervical cancer and WWC services among women aged more than 35 years.

Abstract Cancer is the second leading cause of death in the world. Proper utilization of available services is of utmost importance in preventing cancer in low and middle-income countries. We assessed the use of well women clinic (WWC) screening services for cervical and breast cancer prevention in a sample of females attending the largest religious festival in Sri Lanka. Of the 3,116 women studied, although 1,895 (60.8%) were aware of the WWC services, only 578 (18.5%) had ever used it. Awareness on breast and cervical carcinoma were 2,874 (92.2%) and 2,609 (83.7%) respectively. Of the 217 professionals or associate professionals in the study sample, 190 (87.6%) were aware of the WWCs compared to only 58.8% among the 2,899 women falling under the categories of other occupations and housewives. Clinic attendance was also significantly higher amongst professionals and associate professionals compared to women in other occupational categories and housewives (40.1% versus 16.9%). Use of well woman clinic services are low and new strategies are needed to improve awareness and participation in this program.

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Materials and Methods This study was conducted on the 6th of June 2012 in the sacred city of Anuradhapura on the ‘Poson Poya day’, the largest Buddhist gathering in the country. Every year, an average of 800,000 Buddhists and non-Buddhists participate in religious activities in Anuradhapura on this day, coming from nearly every district in Sri Lanka. We conducted a rapid spot survey using a short questionnaire at the sacred city of Anuradhapura using a convenient sample, while the pilgrims were waiting to enter one of the sacred places. The survey was conducted as a part of a massive health promotion and awareness program on breast and cervical cancers initiated by the medical undergraduates of the Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka. The target group included women aged 35 years and above, similar to the target group of the WWC.

Results A total of 3,116 females from 22 districts were interviewed. Mean age of the study sample was 52.6 years (SD 10.3 years). All districts, except Jaffna, Kilinochchi and Mulativu districts, were represented in the study sample. Of the 3,116 women studied, 2,874 (92.2%) reported that they have at least heard the condition ‘breast carcinoma’ and 2,609 (83.7%) of ‘cervical carcinoma’. Although a majority of women expressed awareness of these malignancies, only 1,150 women (36.9%) were aware that they belonged to the high-risk age group for breast cancer. For cervical cancer, this percentage was 32.4% (n=1,011). Of the women surveyed, 1,895 (60.8%) were aware of the WWC services, but only 578 (18.5%) had ever used it.

Of the 217 professionals or associate professionals in the study sample, 190 (87.6%) were aware of the WWC compared to only 58.8% among the 2,899 women falling under the categories of other occupations and housewives. Clinic attendance was also significantly higher among the professionals and associate professionals compared to women in other occupational categories and housewives (40.1% versus 16.9%). Women aged 50 years or younger (n=1349) had a significantly higher awareness of the WWC program (67.1%) while only 56.0% of women over 50 years of age (n=1767) reported awareness. In addition, a slightly higher percentage of younger women have attended the WWCs compared to the older women (20.2% versus 17.45%).

Discussion This study shows that less than 20% of women aged over 35 years have ever participated in screening for breast and cervical cancers through WWC. In addition, there was a

significant difference in awareness and usage of WWC by social class and age. Findings of this study show that even after 16 years of establishment, WWCs do not have the expected coverage. A pervious study from Gampaha showed that only around 2.2% women had ever undergone clinical breast examination in 20072. Even among healthcare workers in Sri Lanka, the use of cancer screening services was reported as less than 20%3. Service utilization and knowledge on these two malignancies vary widely in other developing countries in the region. Norlaili et al reported that even in rural Malaysia the use of clinical services for screening is around 56%4. In Turkey, the general public’s5, university students’6 and health workers’7,8 knowledge, practice of self-breast examination and the use of clinical services was much higher than the values reported in our study. However, in Nepal9, where the socio-economic conditions are more similar to Sri Lanka, the knowledge and the use of screening services was reported to be much poor compared to the current study. As described by Vitharan et al, one reason for this underutilization would be the substandard services provided through these clinics, and the need for training of healthcare workers10. The finding of probable social disparity on awareness and use of WWC services in the current study is not a fact that was expected. Previous studies on the use of public health services in Sri Lanka shows that there was no social disparity on using public health services11. This finding may be due to the lack of knowledge on malignancies in the lower socio-economic group. Even though Sri Lankan women possess high health literacy and the participation in maternal and child health services is nearly hundred percent, non-communicable disease prevention is yet to develop as a priority among them. This should be a priority in the Sri Lankan settings, especially due to the epidemiological and demographic transitions the country is going through.

Even though these study findings cannot be generalized to the whole Sri Lankan population due to the use of non-probability sampling method, the large study sample representing 22 districts in the country provides credible information on the inadequate use of WWC services. It is evident that more awareness on reproductive malignancies is needed in order to motivate more women to seek out the services that are readily available to them.

Acknowledgements We acknowledge the Medical Students Union of Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka and all the students of the faculty who participated in the health promotion program.

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References

1. Cohen SA, Richards CL. The Cairo consensus: population, development and women. Fam Plann Perspect 1994; 26(6): 272-7.

2. Vithana PV, Ariyaratne M, Jayawardana P. Quality of breast cancer early detection services conducted by well woman clinics in the district of Gampaha, Sri Lanka. Asian Pac J Cancer Prev 2013; 14(1): 75-80.

3. Nilaweera RI, Perera S, Paranagama N, Anushyanthan AS. Knowledge and practices on breast and cervical cancer screening methods among female health care workers: a Sri Lankan experience. Asian Pac J Cancer Prev 2012; 13(4): 1193-6.

4. Norlaili AA, Fatihah MA, Daliana NF, Maznah D. Breast cancer awareness of rural women in Malaysia: is it the same as in the cities? Asian Pac J Cancer Prev 2013; 14(12): 7161-4.

5. Karadag G, Gungormus Z, Surucu R, Savas E, Bicer F. Awareness and practices regarding breast and cervical cancer among Turkish women in Gazientep. Asian Pac J Cancer Prev 2014; 15(3): 1093-8.

6. Karadag M, Iseri O, Etikan I. Determining Nursing Student Knowledge, Behavior and Beliefs for Breast Cancer and Breast Self-examination Receiving Courses with Two Different Approaches. Asian Pac J Cancer Prev 2014; 15(9): 3885-90.

7. Yurdakos K, Gulhan YB, Unalan D, Ozturk A. Knowledge, attitudes and behaviour of women working in government hospitals regarding breast self examination. Asian Pac J Cancer Prev 2013; 14(8): 4829-34.

8. Andsoy, II, Gul A. Breast, cervix and colorectal cancer knowledge among nurses in Turkey. Asian Pac J Cancer Prev 2014; 15(5): 2267-72.

9. Sathian B, Nagaraja SB, Banerjee I, et al. Awareness of Breast Cancer Warning Signs and Screening Methods among Female Residents of Pokhara Valley, Nepal. Asian Pac J Cancer Prev 2014; 15(11): 4723-6.

10. Vithana PV, Hemachandra NN, Ariyaratne Y, Jayawardana PL. Qualitative assessment of breast cancer early detection services provided through well woman clinics in the district of Gampaha in Sri Lanka. Asian Pac J Cancer Prev 2013; 14(12): 7639-44.

11. Agampodi SB, Amarasinghe DA. Private sector contribution to childhood immunization: Sri Lankan experience. Indian J Med Sci 2007; 61(4): 192-200.

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Ellapola A et al. AMJ 2017 Open Access

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Case Report Impulse Control Disorder in a 4-Year-Old Child Ellapola A1, Sumanasena B2 1Consultant Psychiatrist, Teaching Hospital, Anuradhapura 2Consultant Dermatologist, Teaching Hospital, Anuradhapura

Key words: Munchausen by proxy, Kleptomania, Trichotillomania, Pyromania Copyright: © 2017 Ellepola et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Funding: None Competing interest: None Correspondence: [email protected] DOI: http://doi.org/10.4038/amj.v11i1.7613

Case Report A 4-year-old pre-school boy was referred to the Child and adolescent Psychiatry clinic, Teaching Hospital, Anuradhapura by the Consultant Dermatologist. The referred child presented with multiple abrasions and lacerations over his face and both upper limbs. His face was severely deformed due to multiple scratch marks. His mother had difficulty in managing the child’s repetitive scratching and skin picking, especially over the face and upper limbs. Child screamed with pain due to infected wounds. He was not cooperative for the interview. Collateral history was taken from his mother and siblings. There was no history to suggest ADHD, Autistic Spectrum Disorder, Intellectual Disability or Munchausen by proxy.

There was a clear history of recurrent extreme urges to pick the skin and scratch his face for 6 months duration. He could not resist the impulse to damage his skin. This child failed to avoid the act despite painful injuries to him. There was evidence of increasing anxiety prior to the act. He felt tension and arousal before skin picking and scratching. He experienced a sense of gratification and relief following the act. There was no evidence of provocation before the urges and impulses. He did not have any feeling of regret, remorse or guilt about the behaviour. Episodes of such acts were pervasive and persistent. It took place during the clinical examination as well.

Figure 01: Injured skin due to scratching

His family members were severely distressed by the condition. The child’s mother showed signs of depression due to her only son’s behaviour. There were recurrent infections due to repetitive scratching and skin picking over infected wounds. Dermis was exposed in multiple areas on his face and upper limbs. There were more injuries on his left upper limb and left side of the face as he mainly used his right hand for scratching and skin picking.

Abstract An atypical case of impulse control disorder in a 4-year-old boy was diagnosed and successfully managed with a Second Generation antipsychotic in this case report

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It was difficult to treat the child with behavioural strategies due to his age, limited rapport and parents’ level of education. A trial of Risperidone 0.5 mg was started in the child and adolescent outpatient clinic. Review in two weeks showed a marked improvement of his condition. A significant proportion of his facial and upper limb injuries were healed. There were no infected wounds. The frequency of scratching and picking behaviour had gone down. The child was not crying or screaming anymore. His family members showed happiness and a sense of hope for the child’s future.

Discussion Individuals with impulse control disorders cannot avoid behaviours that might bring harm to themselves or others. There’s increasing anxiety before the action and feeling relief or happiness following the action. The disorder is characterized by an inability to control one’s actions, and results in a negative impact on the person.

The DSM-IV recognizes pathological gambling, kleptomania, trichotillomania, intermittent explosive disorder, and pyromania as impulse control disorders(1). Diagnostic criteria have been proposed for pathological skin picking, compulsive sexual behaviour and compulsive buying, which are classified under impulse control disorders not otherwise specified (NOS)(1).

A study in 2005 concluded that impulse control disorders are common among psychiatric inpatients(2). In this study 30.9% of adult psychiatric inpatients were diagnosed with at least one impulse control disorder1. The most common impulse control disorders were compulsive buying [9.3%], kleptomania [7.8%], and pathological gambling [6.9%](2). The Disorder is relatively common among adolescents and adults, and can often be effectively treated with behavioural and pharmacological therapies(3). A study of 791 college students demonstrated the common nature of these disorders in general population (10.4%) (Odlaug and Grant, 2010). Dopamine receptor agonist drugs are found to associate with serious impulse control disorders(4).

Pharmacological treatment for impulse control disorders have been relatively understudied(3). There are no FDA-approved medication for any impulse control disorder(3). Antidepressants, mood stabilizers and antipsychotics have been studied with mixed results(3). Large-scale, placebo-controlled, comparative pharmacological treatment studies need to be completed to find the most effective treatments for impulse control disorders(3).

The child with an impulse control disorder in this case report improved with treatment with second-generation antipsychotic medication.

References

1. American Psychiatric Association. Task Force on DSM-IV. Diagnostic and statistical manual of mental disorders : DSM-IV-TR. [Internet]. American Psychiatric Association; 2000 [cited 2018 Sep 3]. 943 p. Available from: https://books.google.lk/books/about/Diagnostic_and_Statistical_Manual_of_Men.html?id=3SQrtpnHb9MC&redir_esc=y

2. Grant JE, Levine L, Kim D, Potenza MN. Impulse Control Disorders in Adult Psychiatric Inpatients. Am J Psychiatry [Internet]. 2005 Nov [cited 2018 Sep 3];162(11):2184–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16263865

3. Schreiber L, Odlaug BL, Grant JE. Impulse control disorders: updated review of clinical characteristics and pharmacological management. Front psychiatry [Internet]. 2011 [cited 2018 Sep 3];2:1. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21556272

4. Weiss HD, Pontone GM. Dopamine Receptor Agonist Drugs and Impulse Control Disorders. JAMA Intern Med [Internet]. 2014 Dec 1 [cited 2018 Sep 3];174(12):1935. Available from: http://archinte.jamanetwork.com/article.aspx?doi=10.1001/jamainternmed.2014.4097

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Basnayake BMDB et al. AMJ 2017 Open Access

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Case report

A Patient with Heroin Withdrawal Presenting with Newly Onset Seizures Basnayake BMDB1 , Kannangara T1, Wickramasinghe WMASR1, Wijesena SN1 1Department of Medicine, Teaching Hospital Kandy, Sri Lanka

Key words: Seizures, heroin withdrawal, Sri Lankan Copyright: © 2017 Basnayake BMDB et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Funding: None Competing interest: None Correspondence: [email protected] DOI: http://doi.org/10.4038/amj.v11i1.7619

Introduction Heroin addiction, a serious health and social problem around the world, is associated with significant morbidity and mortality. Heroin (diacetylmorphine) which is highly addictive is derived from the seedpod of the poppy plant (Papaver somniferum). Heroin abuse depends on multiple factors including genetic and psychosocial factors (1). Seizures are often seen in substance abusers. It may be due to direct causes like intoxication or withdrawal and due to indirect causes such as CNS infection, stroke, cerebral trauma and metabolic derangement (2). Seizures due to heroin withdrawal are less common than in withdrawal from sedatives like barbiturates. However in critically ill patients who have been treated with sedatives and narcotics, sudden withdrawal of narcotic drugs may be a significant causative factor for newly-onset seizures (3). We report a patient with heroin withdrawal presented with newly onset seizure episodes.

Case report A 38-year-old previously healthy male presented with four episodes of generalized tonic clonic seizures within 2 days. These episodes were associated with frothing, tongue bites

and post ictal drowsiness, but no urinary or faecal incontinence was present. In between seizure attacks he regained consciousness. He did not report a history of fever, head trauma or recent alcohol or other drug abuse. He was a heroin addict for 15 years (daily usage) and had withdrawn for 4 days as he was under a rehabilitation program. On examination he had bite marks on the tongue. There was no neck stiffness or neurological deficits. Fundoscopy was normal. Pulse rate was 76 beats/min. Blood pressure was 110/70 mmHg. Other system examinations were unremarkable. Investigations showed haemoglobin of 14.5 g/dl, platelets 224×109/L, WBC 8.1×109/L with normal red cell indices. He was normoglycemic. Erythrocyte sedimentation rate (ESR) was 08 mm in first hour with C-reactive protein (CRP) 6 mg/dl. Blood and urine cultures were negative. Serum sodium, potassium, calcium and magnesium levels were 144 mmol/L, 3.8 mmol/L, 2.35 mmol/L (2.1-2.55) and 0.9 mmol/L (0.7-1.0) respectively. Serum creatinine was 1.02 mg/dl (0.9- 1.3). Blood urea level was 3.66 mmol/L. Liver function tests including liver enzymes, total protein with serum albumin and total bilirubin with fractions were normal. Coagulation profile was normal. Alkaline

Abstract Heroin addiction needs to be considered a chronic medical illness with a serious health burden and psychosocial problems worldwide. Heroin withdrawal may manifest with a variety of clinical features ranging from simple nausea, vomiting, cramps, seizures, collapse and coma. We report a 38-year-old previously healthy man who was a heroin addict for fifteen years, presented with recurrent episodes of seizure attacks following heroin withdrawal. He did not require long term anticonvulsant treatment for seizure control

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phosphatase and gamma GT were within the normal ranges. Urine full report was normal. Significant changes were not detected in chest radiograph, electrocardiogram and 2D echocardiogram. Non contrast and contrast CT Brain were normal. Cerebrospinal fluid analysis was unremarkable. Electroencephalography (EEG) showed intermittent bilateral rhythmic slow wave activity in the delta range. The findings were suggestive of diffuse cortical dysfunction consistent with an encephalopathic state. But no definite epileptiform abnormality was seen. He was started on sodium valproate which was omitted after 4 days according to neurological opinion. He was discharged without drugs and advised to continue the rehabilitation program. During the follow up at medical clinic for one year, no further fits or adverse neurologic sequelae were encountered.

Discussion Heroin is a highly addictive opioid drug which is used by millions of addicts globally. Drug or heroin addiction is a chronic, relapsing disorder. These patients have compulsive drug-seeking and drug-taking behavior. Chronic usage of heroin will cause central nervous system changes which lead to tolerance, physical dependence, sensitization, craving, and relapse (4). If the patient reduces or ceases heavy and prolong heroin use it will cause substance-specific syndrome (5). Clinical features of heroin withdrawal syndrome include muscle cramps, arthralgia, anxiety, nausea, vomiting, diarrhea, malaise, mydriasis, piloerection, diaphoresis, rhinorrhea, lacrimation, insomnia and less commonly confusion, convulsions, collapse and coma. The half-life of the opioid causing withdrawal syndrome determines the onset and duration of symptoms. In heroin withdrawal, symptoms peak in 36-72 hours and may last for 7-10 days (6)(7).

Long term activation of opioid receptor increases the activity of adenylyl cyclase, tyrosine hydroxylase and cAMP dependent protein kinase A. Also increased phosphorylation of gene transcription factors such as cAMP–responsive element–binding protein (CREB) and ∆FosB occur due to chronic activation of opioid receptors. The resultant up regulation of cAMP signaling pathways is a homeostatic response to the chronic inhibition of the locus ceruleus by opioids and is a cornerstone in withdrawal. Locus ceruleus develops tolerance to the inhibitory effect of opioids in long term exposure. When there is a withdrawal state the inhibitory effect of opioids is lost and it leads to adrenergic over activation as the firing of locus ceruleus neurons are unopposed. Then it manifests as withdrawal features. Structural changes in neurons can occur due prolonged exposure to heroin which

may also contribute to withdrawal symptoms such as seizures (4)(8)(9)(10).

There are many causative factors for seizures. Mainly in adults it can be due to metabolic disorders (eg: uremia, hepatic failure, electrolyte abnormalities, hypoglycemia and hyperglycemia), illicit drug abuse, withdrawal from alcohol and drugs, trauma, brain tumors and other space occupying lesions, and infectious diseases (11)(12). In our patient other main causes were excluded. So the seizure etiology was directed towards heroin withdrawal.

Main objectives of patient care in heroin withdrawal are to relieve distress, avoid severe withdrawal manifestations, maintain proper compliance in ongoing treatment, disturb the pattern of heavy and regular drug use and assist in resolving other associated problems. Non-pharmacological therapies mainly focus on patient assessment, treatment matching and psychosocial support. One of the basic principles in managing drug withdrawal is to use an agent from the same pharmacologic class or one with a degree of cross-tolerance. Drugs used in pharmacological management are d-propoxyphene, clonidine, levo-acetyl-methadol, methadone and buprenorphine. Each drug has their own benefits and disadvantages, and due to poor efficacy and side effects some drugs have been taken out from the management (5)(7)(13). However, long-term anticonvulsant prophylaxis is usually not indicated in patients with seizures where the aetiology is suspected or diagnosed to be solely drug/ heroin withdrawal (2).

Conclusion Even though seizures are a less common manifestation in heroin withdrawal, medical professionals need to keep in mind the possibility of developing seizures due to withdrawal as heroin use is widespread and increasing. Management of heroin withdrawal syndrome requires multidisciplinary approach including pharmacological therapy, psychosocial support, continuous monitoring and follow up. According to our knowledge, patients with heroin withdrawal presenting with newly onset seizures have not previously been reported in Sri Lanka.

Consent Informed written consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review with the Editor-in-Chief of this journal.

Competing interests The authors declare that they have no competing interests.

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Acknowledgement We wish to appreciate Dr. PNS Premathilake for reading through the manuscript and the invaluable corrections she made to it.

References

1. Alexander G. Schauss, PhD F. Attenuation of Heroin WithdrawalSyndrome by the Administration ofHigh-Dose Vitamin C. J Orthomol Med [Internet]. 2012;27(04):189–97. Available from: https://www.researchgate.net/publication/236834375_Attenuation_of_heroin_withdrawal_syndrome_by_the_administration_of_high-dose_vitamin_C

2. Brust JCM. Seizures and substance abuse: treatment considerations. Neurology [Internet]. 2006 Dec 26 [cited 2018 Sep 2];67(12 Suppl 4):S45-8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17190922

3. Wijdicks EF, Sharbrough FW. New-onset seizures in critically ill patients. Neurology [Internet]. 1993 May [cited 2018 Sep 2];43(5):1042–4. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8492924

4. Camí J, Farré M. Drug Addiction. N Engl J Med [Internet]. 2003 Sep 4 [cited 2018 Sep 2];349(10):975–86. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12954747

5. April 2014 National Guidelines for Medication-Assisted Treatment of Opioid Dependence [Internet]. 1968 [cited 2018 Sep 2]. Available from: www.gldesign.com.au

6. Devlin RJ, Henry JA. Clinical review: Major consequences of illicit drug consumption. Crit Care [Internet]. 2008 [cited 2018 Sep 2];12(1):202. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18279535

7. Miller NS, Gold MS. Management of withdrawal syndromes and relapse prevention in drug and alcohol dependence. Am Fam Physician [Internet]. 1998 Jul [cited 2018 Sep 2];58(1):139–46. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9672434

8. Rasmussen K, Beitner-Johnson DB, Krystal JH, Aghajanian GK, Nestler EJ. Opiate withdrawal and the rat locus coeruleus: behavioral, electrophysiological, and biochemical correlates. J

Neurosci [Internet]. 1990 Jul [cited 2018 Sep 2];10(7):2308–17. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2115910

9. He L, Fong J, von Zastrow M, Whistler JL.

Regulation of opioid receptor trafficking and morphine tolerance by receptor oligomerization. Cell [Internet]. 2002 Jan 25 [cited 2018 Sep 2];108(2):271–82. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11832216

10. Sklair-Tavron L, Shi WX, Lane SB, Harris HW, Bunney BS, Nestler EJ. Chronic morphine induces visible changes in the morphology of mesolimbic dopamine neurons. Proc Natl Acad Sci U S A [Internet]. 1996 Oct 1 [cited 2018 Sep 2];93(20):11202–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8855333

11. McGraw-Hill Medical: Current Diagnosis & Treatment | How to Buy [Internet]. [cited 2018 Sep 2]. Available from: http://www.cmdt2016.com/book.html

12. Chapter 369. Seizures and Epilepsy | Harrison’s Principles of Internal Medicine, 18e | AccessMedicine | McGraw-Hill Medical [Internet]. [cited 2018 Sep 2]. Available from: https://accessmedicine.mhmedical.com/content.aspx?bookid=331&sectionid=40727185&jumpsectionID=40763603

13. Nigam AK, Ray R, Tripathi BM. Buprenorphine in opiate withdrawal: a comparison with clonidine. J Subst Abuse Treat [Internet]. [cited 2018 Sep 2];10(4):391–4. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8257551

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Case Report An Unusual Case of Dengue Haemorrhagic Fever Complicated with Scrotal Haematoma: Premathilake PNS1, Kularatne WKS1, Senadhira SDN1, Bandara WRSM2 1Department of Medicine, Teaching Hospital, Kandy 2Department of Radiology, Teaching Hospital, Kandy

Key words: Dengue fever, Hemorrhage, Uncommon complication, Scrotal haematoma, Sri Lankan Copyright: © 2017 Premathilake PNS et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Funding: None Competing interest: None Correspondence: [email protected] DOI: http://doi.org/10.4038/amj.v11i1.7626

Introduction Dengue has posed a major socioeconomic and public health burden on national as well as international grounds. It is currently regarded the most important arboviral infection worldwide as half the global population lives in areas at risk of the disease and approximately 50% of this live in dengue endemic countries (1)(2). The previous estimated annual global incidence of 50-100 million infections per year has shown a dramatic rise in recent studies. Currently it is estimated at 390 million dengue infections per year (3). Of the total one hundred and twelve outbreaks recorded from 2010 to 2015 worldwide, the largest number was observed in Southeast Asia (4). Last year, Sri Lanka faced the heaviest dengue epidemic and the average number of cases showed a 4.3-fold alarming rise compared to the average numbers from 2012 to 2016 (5). This highly prevalent infectious disease has numerous complications and bleeding is a well-known complication with detrimental effects in severe dengue infection. We report a rare case of scrotal haematoma in a patient with dengue haemorrhagic fever (DHF).

Case report A 14-year-old previously healthy boy presented with fever, body aches and headache for three days during the dengue epidemic season in 2017. There was no known past history

of dengue infection. Examination was unremarkable apart from fever and mild dehydration. Dengue non-structural protein (NS) 1 test was positive. On admission the full blood count revealed a white cell count of 3.3 x 109/L with haemoglobin of 15g/dL, haematocrit 44.7% and a platelet count of 153x109/L. He became fever free since the fourth day of the illness. On the fifth day of illness he entered the critical phase with the lowest platelet count being 14 x 109/L. He developed a right sided moderate pleural effusion, confirmed by ultrasound scan along with mild ascites and pericholecystic fluid. On the seventh day of the illness following the critical phase, he complained of acute onset painful swelling of the right scrotum over a few hours duration. The swelling was not associated with fever spikes or preceding trauma and there were no other bleeding manifestations. The right hemi scrotum was swollen and tender but there was no increased warmth or skin oedema. AST was 37 IU/L and ALT 19 IU/L. Activated partial thromboplastin time and international normalized ratio were within normal ranges. C reactive protein was 3.7 mg/dL (<10). The ultrasound scan of the scrotum revealed a right sided hydrocoele measuring 11 cubic centimeters in volume with floating echogenic material suggestive of clotted blood [figure 1]. Bilateral testes were normal in size, echogenicity and vascularity. As the swelling was non-progressive, he was managed

Abstract Dengue is an important arboviral disease with a spectrum ranging from asymptomatic disease to fatal haemorrhagic fever and shock syndrome. Bleeding is a well-known complication that may range from skin petechiae to fatal hemorrhages. We report a rare case of spontaneous scrotal haematoma in a 14-year-old boy with dengue haemorrhagic fever.

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conservatively with scrotal support. The platelet count was in the rising and the oedema was non progressive, hence he was not treated with platelet transfusions. Oral Tranexamic acid and prophylactic antibiotics were started. With supportive treatment he made a complete clinical recovery and was discharged from the hospital and no further complications were encountered.

Figure 1. Right sided hydrocoele with floating echogenic material suggestive of clotted blood

Discussion Dengue virus is a single stranded RNA virus that belongs to the Flaviviridae family under the genus Flavivirus. It has four closely related serotypes namely, DENV-1, DENV-2, DENV-3, and DENV-4. It is an arboviral infection transmitted through infected Aedes species mosquito. Infection with each serotype confers lifelong immunity to the specific serotype but cross immunity is only partial and temporary (2).

Dengue can manifest as a wide spectrum ranging from mild asymptomatic illness to severe and fatal disease including DHF and shock syndrome. Only 5% of all cases of dengue turn out to be haemorrhagic fever and shock syndrome (6).

Pathogenesis of bleeding in DHF is not yet properly understood. The suggested mechanism includes an enhanced immune response by the host. It is thought to be primarily mediated by skewed T cell cytokines which were initially primed by an asymptomatic primary infection by dengue virus. This results in severe disease and DHF in second infection with dengue virus. The resulting manifestations include an endothelial dysfunction and increased vascular permeability, thrombocytopenia and platelet dysfunction and disseminated intravascular coagulation (7)(8). Furthermore, in DHF, thrombin triggers the intrinsic pathway of the coagulation cascade

resulting in activation of coagulation factor XI. This activates factors IX and X resulting in further formation of thrombin. The inadequacy of factor XI, thrombin, thrombin-activatable fibrinolysis inhibitor feedback loop causes a homeostatic defect resulting in an imbalance between coagulation and fibrinolysis (9).

Bleeding in dengue can range from harmless petechial skin hemorrhages to life threatening gastrointestinal, genitourinary, pulmonary, muscle and cerebral hemorrhages (10).

In literature, retroperitoneal haematomas, rectus sheath haematomas, abdominal haematomas and spontaneous hemoperitoneum have previously been described with DHF (6)(7)(10)(11)(12)(13). However, spontaneous scrotal haematoma in DHF has not previously been reported.

Other scrotal manifestations of dengue are seldom reported in literature. A rare but self-limiting acute scrotal oedema with dengue is described in several cases (14) (15). The pathology is presumed to be due to inflammatory mediators against the dengue antigen. Acute epididymo-orchitis is another recognized complication (16).

A number of other conditions may cause bleeding into the scrotum. Scrotal haematomas due to haemorrhages involving the spermatic cord, varicoceles and adrenals have been reported in the literature (17)(18)(19). Furthermore Henoch–Schönlein syndrome, trauma and anticoagulant therapy have been associated with bleeding in the spermatic cord (20)(21). But in our patient there was no history of trauma or any of the above and ultrasonography ruled out varicocele.

Potential complications of scrotal haematoma include compressive damage affecting the viability of testes and infection. A rare scenario of massive spontaneous haematoma leading to haemorrhagic shock has been reported once (22).

Conclusion Scrotal haematoma in DHF is a very rare manifestation which in this case was self-limiting, but potentially can lead to compressive complications that may irreversibly affect the viability of testes. Awareness and close monitoring for such rare complications is the cornerstone of prevention and appropriate timely management. To our knowledge this is the first case of DHF complicated with spontaneous scrotal haematoma.

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References

1. Gubler DJ. Dengue, Urbanization and Globalization: The Unholy Trinity of the 21(st) Century. Trop Med Health [Internet]. 2011 Dec [cited 2018 Sep 3];39(4 Suppl):3–11. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22500131

2. Wilder-Smith A, Murray MB, Quam M. Epidemiology of dengue: past, present and future prospects. Clin Epidemiol [Internet]. 2013 Aug [cited 2018 Sep 3];5:299. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23990732

3. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, et al. The global distribution and burden of dengue. Nature [Internet]. 2013 Apr 7 [cited 2018 Sep 3];496(7446):504–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23563266

4. Guo C, Zhou Z, Wen Z, Liu Y, Zeng C, Xiao D, et al. Global Epidemiology of Dengue Outbreaks in 1990–2015: A Systematic Review and Meta-Analysis. Front Cell Infect Microbiol [Internet]. 2017 Jul 12 [cited 2018 Sep 3];7:317. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28748176

5. WHO | Dengue fever – Sri Lanka. WHO [Internet]. 2018 [cited 2018 Sep 3]; Available from: http://www.who.int/csr/don/19-july-2017-dengue-sri-lanka/en/

6. Parmar NM, Patel MD, Negi SS, Savani CM, Desai NL, Patel AP. Spontaneous hemoperitoneum review article. Available from: http://medind.nic.in/gaa/t15/i2/gaat15i2p19.pdf

7. Ameer A, Arachchi WK, Jayasingha P. Psoas haematoma complicating dengue haemorrhagic fever: a case report. Gall Med J [Internet]. 2009 Oct 8 [cited 2018 Sep 3];14(1):83. Available from: https://gmj.sljol.info/article/10.4038/gmj.v14i1.1188/

8. Woodland DL, Winslow GM. Immunity to emerging pathogens. Immunol Rev [Internet]. 2008 Oct 1 [cited 2018 Sep 3];225(1):5–8. Available from: http://doi.wiley.com/10.1111/j.1600-065X.2008.00695.x

9. Lee I-K, Liu J-W, Yang KD. Clinical and laboratory characteristics and risk factors for fatality in elderly patients with dengue hemorrhagic fever. Am J Trop Med Hyg [Internet]. 2008 Aug [cited 2018 Sep 3];79(2):149–53. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18689614

10. Kaur H, Girgila K. Rectus sheath haematoma complicating dengue haemorrhagic fever-a case report. Int J Res Med Sci Kaur H al Int J Res Med Sci [Internet]. 2017 [cited 2018 Sep 3];5(1):354–6. Available from: www.msjonline.org

11. Singh J, Singh H, Sukhija G, Jagota R, Bala S. Retroperitoneal Haematoma in a Patient with Dengue Haemorrhagic Fever: A Rare Case Report. J Clin Diagn Res [Internet]. 2016 Nov [cited 2018 Sep 3];10(11):OD01-OD02. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28050423

12. Kumar A, Mondal S, Sethi P, Manchanda S, Biswas A, Wig N. Spontaneous iliopsoas haematoma in a patient with dengue haemorrhagic fever (DHF): A case report. J Vector Borne Dis [Internet]. 2017 [cited 2018 Sep 3];54(1):103–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28352053

13. Malaria Research Centre (India) KJ, Shovkat R, Samoon HJ. Journal of vector borne diseases. [Internet]. Vol. 52, Journal of Vector Borne Diseases. Malaria Research Centre (Indian Council of Medical Research); 2003 [cited 2018 Sep 3]. 339-341 p. Available from: https://www.cabdirect.org/cabdirect/abstract/20163201068

14. Dengue fever associated with acute scrotal oedema: two case reports [Internet]. [cited 2018 Sep 3]. Available from: http://www.jpma.org.pk/full_article_text.php?article_id=2832

15. Kumar KJ, Nataraj B, Anitha C, Santhoshkumar M. Dengue fever associated with acute scrotal oedema. Sri Lanka J Child Heal [Internet]. 2015 Sep 12 [cited 2018 Sep 3];44(3):176. Available from: https://sljch.sljol.info/article/10.4038/sljch.v44i3.8021/

16. Abdulla M, Alungal J, Nagabhushan K, Narayan R. Dengue fever presenting as epididymo-orchitis. Indian J Heal Sci [Internet]. 2016 [cited 2018 Sep 3];9(3):322. Available from: http://www.ijournalhs.org/text.asp?2016/9/3/322/196337

17. PRIME PubMed | Spontaneous idiopathic hematoma of the spermatic cord: a report of 2 case [Internet]. [cited 2018 Sep 3]. Available from: https://www.unboundmedicine.com/medline/citation/7463571/Spontaneous_idiopathic_hematoma_of_the_spermatic_cord:_a_report_of_2_cases_

18. Aliabadi H, Cass AS. Nontraumatic rupture of varicocele. Urology [Internet]. 1987 Apr [cited 2018 Sep 3];29(4):421–2. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3564216

19. Gonçalves R, Abuabara A, Abuabara RFF, Feron CA. Scrotal hematoma as a sign of adrenal hemorrhage in newborns. Sao Paulo Med J [Internet]. 2011 Mar [cited 2018 Sep 3];129(2):113–5. Available from:

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http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-31802011000200011&lng=en&tlng=en

20. Crosse JE, Soderdahl DW, Schamber DT. &quot;Acute scrotum&quot; in Henoch-Schönlein syndrome. Urology [Internet]. 1976 Jan [cited 2018 Sep 3];7(1):66–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/1246772

21. Handmaker H, Mehn WH. Hemorrhage into spermatic cord and testicle simulating incarcerated inguinal hernia. An unusual complication of anticoagulation therapy. IMJ Ill Med J [Internet]. 1969 Jun [cited 2018 Sep 3];135(6):697–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/4182068

22. Burnand K, Viswanath S, Kumar V, Chitale S. Acute spontaneous scrotal haematoma presenting with haemorrhagic shock: a case report. Ann R Coll Surg Engl [Internet]. 2012 Jan [cited 2018 Sep 3];94(1):e1-2. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22524901

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Nadheem M. AMJ 2017 Open Access

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Case Report A Rare Presentation of Guillain-Barre Syndrome: Pharyngeal Cervical-Brachial Variant Mohamed Nadheem 1 1National Hospital of Sri Lanka

Key words: Guillain-Barre Syndrome, Pharyngeal-cervical-brachial variant, Sri Lanka Copyright: ©. 2017 Nadheem M. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Funding: None Competing interest: None Correspondence: [email protected] DOI: http://doi.org/10.4038/amj.v11i1.7626 Introduction Guillain-Barre Syndrome (GBS) is an acute immune mediated polyneuropathy. It includes a heterogeneousgroup of disorders with various subtypes and variants. GBS is clinically characterized by symmetrical, generalized ascending weakness with areflexia due to peripheral nerve involvement. Pharyngeal-cervical-brachial (PCB) variant is a rare form of Guillain–Barré syndrome and presents with a rapidly progressive oropharyngeal and cervico brachial weakness with areflexia predominantly of the upper limbs. Lower limb muscle power is usually preserved or only mildly affected. Here we report a classical case of PCB variant of GBS affecting a 70-year-old.

Case report A 70-year-old known hypertensive woman on treatment presented with weakness of left upper limb, more proximal than distal, progressed into weakness of right upper limb and subsequently left lower limb for 4 days duration. Lower limb weakness was less severe compared to the upper limbs. She had difficulty in swallowing for a similar duration, with mild respiratory discomfort. There was no preceding diarrhoeal illness but she described a respiratory illness one month ago.

On examination she was conscious and oriented. Facial power, eye movements and pupillary response were normal. Palatal movements were impaired. There was

weakness of neck muscles with neck flexion of 3/5. Single breath count was more than 25. Shoulder abduction was 2/5 on the right and 1/5 on the left. Distal upper limb power was 2/5 on the left and 3/5 on the right. Power in the lower limbs was 4/5. There was global are flexia with no sensory involvement. Plantar response was flexor bilaterally and there was no demonstrable fatigability or ataxia.

She was afebrile with a blood pressure of 140/80 mmHg and pulse rate of 80 bpm. Cardiovascular, respiratory and abdominal examinations were unremarkable.

Her baseline blood investigations were as follows. White cell count 12.3x109/L, platelet count 197x109/L, serum potassium 4.2 mmol/L, serum sodium 138 mmol/L, , fasting blood glucose 103 mg/dl and serum creatinine 57 umol/L. Haemoglobin level was 13.9g%, Liver function tests were normal. Chest radiograph was unremarkable. Viral panel (EBV, CMV, herpes virus), cultures for Salmonella, Shigella and Campylobacter jejuni and serological examination for mycoplasma pneumonia were negative. Neurophysiological studies done on day 3 of admission indicated motor conduction abnormalities with conduction blocks, and sensory responses were normal suggesting GBS. Cerebrospinal fluid (CSF) examination on day 08 of illness revealed typical “albumino cytological dissociation” with no white or red blood cells. The protein

Abstract Guillain-Barre syndrome is characterized by acute onset symmetrical, generalized, ascending weakness with areflexia. It has wide variety of subtypes according to the involvement of muscle and nerve groups. We describe a case of 70 year old lady developing a rare form of GBS, the pharyngeal-cervical-brachial variant of the disease.

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level was high at 60 mg/dl, with normal glucose. CSF cultures and gram stain were unremarkable.

With clinical and neurophysiological evidence, a diagnosis of PCB variant of GBS was made and the patient was initiated on intravenous immunoglobulin 2mg/kg over 5 days. Strict monitoring of respiratory functions was done with respirometer observing for potential complications. Over the following 10 days, with physiotherapy and supportive care, she made a remarkable recovery with upper limb power of 4/5, normal lower limb strength, neck flexion and normal swallowing.

Discussion Guillain-Barre syndrome is characterized by bilaterally symmetrical ascending paralysis, absence of deep tendon reflexes, sensory loss, cytoalbuminologic dissociation in cerebrospinal fluid and typical findings in nerve conduction studies.

In 1986, Ropper (1) described the first patients who developed rapidly progressive oropharyngeal, neck and shoulder weakness, with relative sparing of the lower limbs in the absence of sensory disturbance and, mimicked like descending paralysis seen in botulism although relative sparing of the lower limbs were initially thought as the hallmark of the disease some patients were later described to have minimal limb weakness as in our patient.

According to the proposed new criteria for the PCB variant of GBS (2), our patient fulfilled all the features required for the diagnosis. She had relatively symmetrical oropharyngeal weakness, neck weakness, arm weakness and arm areflexia. There was absence of ataxia, disturbed consciousness and prominent leg weakness. She had a monophasic illness pattern and interval between onset and nadir of oropharyngeal or arm weakness was around 2 weeks and there was absence of identifiable alternative diagnosis.

In addition to these she had other strongly supportive features such as, antecedent infectious symptoms, cerebrospinal fluid analysis showing albumino cytological dissociation, neurophysiological evidence of neuropathy.

GBS is one of the auto immune illness preceded by an infectious illness. Auto antibodies against specific

neuronal gangliosides have been implicated in the pathogenesis of different GBS variants. The strongest association for PCB is the presence of IgG anti-GT1a antibodies and is thought to be a useful marker in supporting the diagnosis (3) In our case serological assays were not available in our country.

The presence of additional ophthalmoplegia and ataxia indicates overlap with Fisher syndrome. This is the commonest association with the variant

Patients with pure PCB were more likely to require intubation than those with overlap syndromes and this correlated with degree of bulbar involvement (3). Fortunately, our patient did not need ventilation.

Conclusion PCB variant of GBS should be remembered in patients with symptoms of bulbar and upper extremity weakness not only for early diagnosis but also to plan treatment early and follow up potential complications. Due to the unfamiliarity with PCB variant, clinical picture is often misdiagnosed as brainstem stroke, myasthenia gravis or botulism.

References

1. Ropper AH. Unusual clinical variants and signs in Guillain-Barré syndrome. Arch Neurol [Internet]. 1986 Nov [cited 2018 Sep 2];43(11):1150–2. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2946281

2. Wakerley BR, Yuki N. Pharyngeal-cervical-brachial variant of Guillain-Barre syndrome. J Neurol Neurosurg Psychiatry [Internet]. 2014 Mar 1 [cited 2018 Sep 2];85(3):339–44. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23804237

3. Nagashima T, Koga M, Odaka M, Hirata K, Yuki N. Continuous Spectrum of Pharyngeal-Cervical-Brachial Variant of Guillain-Barré Syndrome. Arch Neurol [Internet]. 2007 Oct 1 [cited 2018 Sep 2];64(10):1519. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17923636

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Seneviratne RW et al. AMJ 2017 Open Access

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Review

More Shades of Grey Than Black and White: A Brief Review of Management of Anorectal Fistula SeneviratneRW1, KumaraMMJK1, De Silva PV1 1Faculty of Medicine, University of Ruhuna, Sri Lanka Key words: Perianal fistula, perianal abscess, recurrent fistula, fistula plug Copyright: © 2017 Seneviratne RW et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Funding: None Competing interest: None Correspondence: [email protected] DOI: http://doi.org/10.4038/amj.v11i1.7609 Introduction Anorectal fistula described initially by Hippocrates continues to plague surgeons and patients alike since the dawn of civilization. Although true prevalence is unknown due to distracting presence of more common hemorrhoids, it is at least twice common in men as a result of higher density of perianal glands. Almost third of the perianal abscesses develop fistula and those growing Escherichia coli and Bacteroids have a higher chance for an associated fistula than the ones growing staphylococci (1).

It can be considered a chronic phase in anorectal sepsis characterized by ongoing discharge, intermittent pain and abscess formation which may discharge spontaneously(2). More than 90% of fistulas are caused by crypto-glandular infection, thus their internal openings are always at the level of pectinate line (1)(2). However, sepsis may spread up and secondary openings caused by spontaneous discharge or surgery may potentially occur anywhere (1). Although rare to produce fatal complications, quality of life of patients are seriously affected by frequent smelly

Abstract Search for ideal treatment of perianal fistula which will fulfill the objectives of low recurrence rate, minimal incontinence and good quality of life continues. Widely used methods for declination of fistula is include examination under anesthesia (EUA), endoanal ultrasound (EUS) and MRI, which is the gold standard. Wide range of procedures have been developed from simple ones such as loose seton to sphincter saving fistula plugs ending with extreme options such as temporary or permanent fecal diversion. Innovative therapeutic techniques such as the use of laser and adipose stem cells have shown some successes but require more advancements and improvements before been accepted in to wider practice.

While simple fistulas can be managed without much difficulty options for complex ones need careful selection. Sphincter saving options are widely preferred. Success of Ligation of intersphincteric fistula tract (LIFT) appears to be popular. Endorectal advancement flap (ERAF) is accepted by many as the Gold standard for treatment of recurrent complex anal fistula. Many surgeons judiciously combine different techniques employing them sequentially or simultaneously to enhance success rate and mitigate disadvantages. Repeated operations are performed without much hesitation provided they are sphincter saving as healing can arrive at any stage of the disease. Management of fistulas associated with Crohn’s disease is a particularly complex entity requiring multidisciplinary involvement and multimodality treatment.

Research continues seeking more successful options but it appears unlikely that given the variability in presentation and complexity of the disease a single successful method of treatment will ever be found for management of perianal fistula.

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discharges, poor healing, recurrent septic episodes and repeated surgeries.

Adherence to standard principles of the management of any fistula such as control of sepsis, care of nutritional status, delineation of anatomy and performing appropriate surgical procedures (SNAP) is vital for effective management of this troublesome disease. The range of treatment modalities is increasing and many a research has been directed a clear indication of the absence of proven effective management strategy. Main objectives of all of them are to eradicate sepsis, promote healing, minimize recurrence and ensure good quality of life(2). Simple low fistulas are often managed successfully by simply laying open with very high rate of success. However, surgery on complex ones could incur serious and permanent damage to sphincter mechanism inviting incontinence due to intertwining anatomical relationship between fistular tract and sphincter mechanism. This has led to popularization of sphincter saving options such as fistula plug and Ligation of intersphincteric fistular tract (LIFT).

Many surgeons categorize fistulas with following features as complex (3): Traverse more than 30% of external sphincter, Recurrent fistulas, Fistulas with branching tracts, Anterior fistulas associated with previous obstetric injury in women, Pre-existing incontinence, Local irradiation and Pre-existing Crohn’s disease.

Assessment of the fistula Accurate preoperative anatomical assessment is of clear benefit in complex fistulas although examination under anesthesia (EUA) and intraoperative assessment usually suffice in simple fistulas. Even some complex ones can be delineated by good clinical examination, sometimes under anesthesia with the help of simple tools such as fistula probe, hydrogen peroxide or methylene blue. Fistulogram has a limited role and MRI and endoanal ultrasound (EUS) are required in some complex cases (3).

Endoanal ultrasound (EAU) Study by Choen et al (1991) showed that EUA is equal to manual assessment in diagnosing intersphicteric and trans sphincteric tracts but score less than manual examination in assessing primary superficial, suprasphuincteric and extrasphincteric tracts or secondary supralevator and infralevator tracts (4).

Recent studies have been more promising aided by technological improvements. Injection of hydrogen peroxide is suggested as an adjunct, which will make fistular tracts hyperechoic and thus better visualized (5). Wang et al (2014) found 3D EAU, which gave over 95%

accuracy for identification of internal opening and identification of secondary tracts, which was significantly superior to traditional manual/probe technique (6).

CT Fistulogram CT scans, even with limitations on resolution, are much more accessible globally than MRIs. Injection of gastrografin to fistula tract with rectum filled with air to aid resolution is crucial for the success of a CT fistulogram. Even 3D films can be obtained which will greatly assist planning of surgery (7). Liang et al (2013) showed the high value of CT fistulogram in depicting perianal anatomy and delineating tracts (8). This has a limitation in being a painful and invasive procedure and somewhat inferior to MRI in imaging qualities in general, although it has a few advantages such as better visualization of gas filled abscess cavities.

MRI Although usually reserved for certain complex fistulas due to cost and availability issues, MRI is considered the gold standard in preoperative assessment of anorectal fistula. T2 weighted sequence is the most informative. MRI allows classification of fistula according to Park’s or Morris’s classification, location of internal and external openings, deep abscesses, long extensions, state of anorectal wall, peri-rectal spaces as well as the damages of the internal sphincter (9). MRI can decide the response to medical therapy, risk of incontinence, procedure of choice as well as the need for referral to a specialized surgeon (10). Surgery based on MRI can reduce further recurrence by 75% (11).

The spectrum of techniques There are many interventional surgical methods available to treat perianal fistula which has shown variable success and complications. These are measured by parameters such as time taken to heal, associated pain in between, rate of recurrence and incontinence scoring systems.

As no clearly successful method exists, surgeons select techniques depending on their experience, as well as patient and disease characteristics. It is worth examining different modalities available in some detail. It is noted that surgeons tend to use certain low success procedures as the first line due to the simplicity and low risk. In addition, to build on advantages and to negate minuses, surgeons seem to use more than one method either simultaneously or sequentially. In fact, repeated procedures, same or different, are known to bring about success at some point (12).

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Fistulectomy This simple procedure of laying the tract open is used for low anal fistulas and found to be very effective. Even those which traverse lower third of external sphincter, can be operated with less than 10% incontinence rate (2).

Seton wire This oldest approach, first described by Hippocrates, is noted for low risk on sphincter mechanism (13). Surgical suture or rubber strand is passed through the fistular tract and taken out via anus followed by a knot tied outside. This allows drainage over time as well as possible closure of branching tracts. Loose Seton with high recurrence rate after removal is favoured over more successful but painful tight Seton, which cuts slowly through the sphincter, leaving a trail of healing by fibrosis (13). Sometimes two Setons are used for two partial fistulotomy dividing a long tract in the middle.

Seton is considered useful to drain a tract and sometimes to convert a complex fistula to a single tract. In this role it is widely used as an adjunct to many other definitive treatment methods.

Combined Partial Fistulectomy and electro-cauterization of intersphincteric tract This preferred technique of the authors involves excision of distal fistular tract to external sphincter, electro cauterization of intersphincteric part and simple closure of internal opening. A 92.5% healing rate after a 19 month follow up was detected by Shafik et al in their 2014 study (14). This appears to be a simple and effective sphincter saving procedure.

Ligation of Intersphincteric Fistula Tract (LIFT), Bio-LIFT and modified LIFT LIFT involves approaching a fistula up to the interspincteric plane after identification of the internal opening via Hydrogen peroxide injection or probe. Fistula is divided and ligated with two absorbable sutures, distal tract excised and interspincteric plain drained. Preceding drainage for 6 to 12 weeks with loose Seton is advised to control sepsis and optimize the outcome.

Limura et al (2015) reports a success rate of 76.5% on a 6-month follow up (13). Based on a systematic review of 498 patients, Yassin et al (2013) reports a healing rate of 71% with a mean follow up period ranging from 4-19.5 months (15). A mean healing rate of 74.6% was recorded in a 592 patient review by Vergera-Fernandez and Espino-Urbina in 2013 (16). Study by Madbouly et al comparing successes of LIFT versus mucosal advancement flap for the treatment of intersphincteric fistula gives comparable

results for healing rate, recurrence, continence and quality of life (17)

More recently, bio prosthetic grafts are used to reinforce the tied end of the retaining potion of the tract. This covers 1 cm in all directions from the tied end of the fistula tract and is secured in place to external sphincter with absorbable sutures to prevent migration. Han et al (2013) described a healing rate of 95 % with healing time less than one month without any noteworthy postoperative complications (18). Although median operative time is about 20 minutes, bio-LIFT procedure has drawbacks in wider dissection and cost.

Endorectal advancement flap (ERAF) A flap of rectal mucosa and part of internal sphincter with a broad vascular base is advanced to cover the internal opening without tension. Excision of infected cryptic glands improve the results. This is considered by many as the Gold standard for treatment of recurrent complex anal fistulas. Although it does not involve division of the sphincter mechanism, minor incontinence is seen in 31% and major in 12% (2).

A study by Ortiz and Marzo (2000 Dec) involving 103 patients, where Fistulectomy is combined with Endorectal advancement flap, gives 93% healing rate. Incontinence issues were seen in 8% (19).

Fibrin glue Although initial studies appeared promising for these injections of glue with its fibroblast attracting and scaffold producing qualities, follow up studies showed decreased healing rates most probably due to the fluid nature of the material (20, 21). However, as the procedure is simple and minimally invasive, it could be employed at early attempts to promote healing, as approximately one third of the patients can avoid having more extensive procedures (20). Fibrin glue is an option in management of long, narrow and persistent fistular tracts (20). They also have a role in providing cover for internal opening following other procedures.

Anal fistula plug (AFP) This lyophilized porcine derived small intestinal submucosal plug acts as a scapholding for fibroblasts facilitating tissue healing. It has been used for anorectal fistulas following its success with thoracic and abdominal wounds. After fistular tract is curetted and irrigated with Hydrogen peroxide, apex of the cone shaped plug is tied to a probe and dragged from the internal opening to external before its internal end is fixed to mucosa via a figure of eight absorbable suture. Johnson et al (2006) concluded a success rate of 87% in a comparative study with fibrin

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glue closure which scored 40% (21). However subsequent studies were disappointing and consensus conference held in 2007 decided that AFP is suitable for transsphincteric anal fistulas without any acute inflammation or infection with special attention on the technique.

In order to circumvent implant extrusion and other problems with AFP, polyglycolic acid based absorbable GORE BioA fistula plug with disk and six attached arms was developed. This can be suitably shaped to fit in to fistular tract with a disk fixed to the internal opening and covered with mucosa and arms extend along the branches of tracts. Ratto et al (2012) has reported a success rate of 72.7% out of a 11 patient study (22). No large studies are available to measure its success.

Laser closure of fistula Drainage of abscesses and application of loose Seton precedes this novel technique. This involves closure of the internal opening with advancement flap followed by mechanical cleaning, insertion and activated withdrawal of laser emitting wire causing destruction of infected epithelium as well as shrinkage of the tract. A study by Wilhelm ( 2011) gives 81% healing rate while providing minimal trauma to the sphincter mechanism (23). Giamendo, in a similar study, gives a lesser figure of 71.4% for primary healing and conclude laser closure as safe, simple, minimally invasive and sphincter saving (24).

Video assisted anal fistula treatment This operation involves two phases. In phase one rigid video-fistuloscope is used to identify the main tract, secondary tracts, abscess cavities and the internal opening. In phase two the instrument is used for clipping of internal opening followed by electro-cauterization of the tract on the way out. In some, an advancement flap may be used to cover internal opening. Meinero et al (2014) found 70% healing after one year follow up of 203 patients without any incontinence (25). However this novel technique needs further studies and is suitable for only certain type of fistulas.

Adipose derived stem cells (ASC) Multi-potent mesenchymal stem cells, derived via liposuction from adipose tissue, were injected in doses of 20-60 million cells and retained in place with fibrin glue or similar material. ASC properties of suppressing inflammation and promoting differentiation were expected to facilitate healing of the fistula. The few studies conducted so far have not shown ASC to be significantly superior to treatment with fibrin glue alone (13)(26). Further research and developments are wait for this novel technique.

Management of perianal fistula in Crohn’s disease Perianal fistulas in Crohn’s disease is one of the most difficult to manage requiring multidisciplinary approach among which physicians, surgeons and radiologists play a vital role. Although medical therapy such as antibiotics, immunosuppressants, anti-TNF Alpha combined with control of sepsis by simple drainage including seton wires tend to control most of the fistulas about 25% are likely to require surgery at some stage (27). Sphincter saving minimally invasive procedures are used due to persisting cause, increasing the likelihood of recurrent operations as well as potential sphincter damage. Younger presenting age, Crohn’s colitis and presence of high fistulas are markers of prolonged troublesome disease (28). Ultimate measures in management of any fistula such as proctectomy and fecal diversion may need to be employed more frequently in Crohn’s associated fistula (29).

Other Procedures Variation of techniques employed by surgeons in the management of anorectal fistula are only matched by variations in presentation. However, resistant complex fistulas leading to severe deterioration of patient’s quality of life may force the hand of the surgeon and heart of the patient towards risky and drastic measures such as division and repair of the sphincter, temporary defunctioning colostomy or even an abdomino-perineal resection.

Conclusion Search for the ideal treatment of perianal fistulas which will fulfill the objectives of low recurrence rate, minimal incontinence and good quality of life continues. Adherence to standard principals of the management of any fistula such as control of sepsis, care of nutritional status, delineation of anatomy and performing of appropriate surgical procedure (SNAP) is vital for the effective management of this troublesome disease. Wide range of procedures have been developed from simple ones such as loose seton to sphincter saving fistular plugs ending with extreme options such as temporary or permanent fecal diversion. Innovative therapeutic techniques such as the use of laser and adipose stem cells have shown some successes, but require more advancements and improvements before being accepted in to wider practice.

While simple fistulas can be managed without much difficulty, options for complex ones need careful selection. Sphincter saving options are widely preferred over risky traditional ones involving extensive dissection. Success of Ligation of intersphincteric fistular tract (LIFT) seems to stimulate development of modifications for the technique. Endorectal advancement flap (ERAF) is accepted by many as the Gold standard for treatment of recurrent complex anal fistulas. Another trend is that many surgeons

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judiciously combine different techniques employing them sequentially or simultaneously to enhance the success rate and mitigate disadvantages. Surgeons do not appear to be deterred by having to do repeated operations, provided they are sphincter saving as success can be achieved at any stage. Management of fistulas associated with Crohn’s disease is a particularly complex entity requiring multidisciplinary involvement and multimodality treatment.

The field of management of perianal fistulas is wide open for further research and developments. It appears unlikely that, given the complexity of disease, a single successful method of treatment will ever be found for management of perianal fistulas.

References

1. Sheikh P. Controversies in fistula in ano. Indian J Surg [Internet]. 2012 Jun [cited 2018 Sep 1];74(3):217–20. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23730047

2. Song KH. New techniques for treating an anal fistula. J Korean Soc Coloproctol [Internet]. 2012 Feb [cited 2018 Sep 1];28(1):7–12. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22413076

3. Sileri P, Giarratano G, Franceschilli L, Limura E, Perrone F, Stazi A, et al. Ligation of the Intersphincteric Fistula Tract (LIFT): A Minimally Invasive Procedure for Complex Anal Fistula. Surg Innov [Internet]. 2014 Oct 6 [cited 2018 Sep 1];21(5):476–80. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24201738

4. Choen S, Burnett S, Bartram CI, Nicholls RJ. Comparison between anal endosonography and digital examination in the evaluation of anal fistulae. Br J Surg [Internet]. 1991 Apr 1 [cited 2018 Sep 1];78(4):445–7. Available from: http://doi.wiley.com/10.1002/bjs.1800780418

5. Cheong DM, Nogueras JJ, Wexner SD, Jagelman DG. Anal endosonography for recurrent anal fistulas: image enhancement with hydrogen peroxide. Dis Colon Rectum [Internet]. 1993 Dec [cited 2018 Sep 1];36(12):1158–60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8253014

6. Wang Y, Ding J, Zhao K, Ye H, Zhao Y, Zhao Y, et al. [Value of three-dimensional endoanal ultrasonography for anal fistula assessment]. Zhonghua Wei Chang Wai Ke Za Zhi [Internet]. 2014 Dec [cited 2018 Sep 1];17(12):1183–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25529948

7. Liang C, Lu Y, Zhao B, Du Y, Wang C, Jiang W. Imaging of anal fistulas: comparison of computed

tomographic fistulography and magnetic resonance imaging. Korean J Radiol [Internet]. 2014 [cited 2018 Sep 1];15(6):712–23. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25469082

8. Liang C, Jiang W, Zhao B, Zhang Y, Du Y, Lu Y. CT imaging with fistulography for perianal fistula: does it really help the surgeon? Clin Imaging [Internet]. 2013 Nov [cited 2018 Sep 1];37(6):1069–76. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23958432

9. Cuenod CA, de Parades V, Siauve N, Marteau P, Grataloup C, Hernigou A, et al. [MR imaging of ano-perineal suppurations]. J Radiol [Internet]. 2003 Apr [cited 2018 Sep 1];84(4 Pt 2):516–28. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12844075

10. Joyce M, Veniero JC, Kiran RP. Magnetic resonance imaging in the management of anal fistula and anorectal sepsis. Clin Colon Rectal Surg [Internet]. 2008 Aug [cited 2018 Sep 1];21(3):213–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20011419

11. Halligan S, Buchanan G. MR imaging of fistula-in-ano. Eur J Radiol [Internet]. 2003 Aug [cited 2018 Sep 2];47(2):98–107. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12880990

12. Tyler KM, Aarons CB, Sentovich SM. Successful Sphincter-Sparing Surgery for All Anal Fistulas. Dis Colon Rectum [Internet]. 2007 Oct [cited 2018 Sep 2];50(10):1535–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17674105

13. Limura E, Giordano P. Modern management of anal fistula. World J Gastroenterol [Internet]. 2015 Jan 7 [cited 2018 Sep 2];21(1):12–20. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25574077

14. Shafik AA, El Sibai O, Shafik IA. Combined partial fistulectomy and electro-cauterization of the intersphincteric tract as a sphincter-sparing treatment of complex anal fistula: clinical and functional outcome. Tech Coloproctol [Internet]. 2014 Nov 26 [cited 2018 Sep 2];18(11):1105–11. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25154751

15. Yassin NA, Hammond TM, Lunniss PJ, Phillips RKS. Ligation of the intersphincteric fistula tract in the management of anal fistula. A systematic review. Color Dis [Internet]. 2013 May [cited 2018 Sep 2];15(5):527–35. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23551996

16. Vergara-Fernandez O, Espino-Urbina LA. Ligation of intersphincteric fistula tract: what is the evidence in a review? World J Gastroenterol [Internet]. 2013 Oct 28 [cited 2018 Sep 2];19(40):6805–13. Available

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from: http://www.ncbi.nlm.nih.gov/pubmed/24187455

17. Madbouly KM, El Shazly W, Abbas KS, Hussein AM. Ligation of Intersphincteric Fistula Tract Versus Mucosal Advancement Flap in Patients With High Transsphincteric Fistula-in-Ano. Dis Colon Rectum [Internet]. 2014 Oct [cited 2018 Sep 2];57(10):1202–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25203377

18. Han JG, Yi BQ, Wang ZJ, Zheng Y, Cui JJ, Yu XQ, et al. Ligation of the intersphincteric fistula tract plus a bioprosthetic anal fistula plug (LIFT-Plug): a new technique for fistula-in-ano. Color Dis [Internet]. 2013 May [cited 2018 Sep 2];15(5):582–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23067044

19. Ortiz H, Marzo J. Endorectal flap advancement repair and fistulectomy for high trans-sphincteric and suprasphincteric fistulas. Br J Surg [Internet]. 2000 Dec [cited 2018 Sep 2];87(12):1680–3. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11122184

20. Zmora O, Mizrahi N, Rotholtz N, Pikarsky AJ, Weiss EG, Nogueras JJ, et al. Fibrin glue sealing in the treatment of perineal fistulas. Dis Colon Rectum [Internet]. 2003 May [cited 2018 Sep 2];46(5):584–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12792432

21. Johnson EK, Gaw JU, Armstrong DN. Efficacy of Anal Fistula Plug vs. Fibrin Glue in Closure of Anorectal Fistulas. Dis Colon Rectum [Internet]. 2006 Mar [cited 2018 Sep 2];49(3):371–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16421664

22. Ratto C, Litta F, Parello A, Donisi L, Zaccone G, De Simone V. Gore Bio-A® Fistula Plug: a new sphincter-sparing procedure for complex anal fistula. Color Dis [Internet]. 2012 May [cited 2018 Sep 2];14(5):e264–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22288601

23. Wilhelm A. A new technique for sphincter-preserving anal fistula repair using a novel radial

emitting laser probe. Tech Coloproctol [Internet]. 2011 Dec 16 [cited 2018 Sep 2];15(4):445–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21845480

24. Giamundo P, Geraci M, Tibaldi L, Valente M. Closure of fistula-in-ano with laser - FiLaCTM: an effective novel sphincter-saving procedure for complex disease. Color Dis [Internet]. 2014 Feb [cited 2018 Sep 2];16(2):110–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24119103

25. Meinero P, Mori L, Gasloli G. Video-Assisted Anal Fistula Treatment. Dis Colon Rectum [Internet]. 2014 Mar [cited 2018 Sep 2];57(3):354–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24509459

26. Herreros MD, Garcia-Arranz M, Guadalajara H, De-La-Quintana P, Garcia-Olmo D, FATT Collaborative Group. Autologous Expanded Adipose-Derived Stem Cells for the Treatment of Complex Cryptoglandular Perianal Fistulas. Dis Colon Rectum [Internet]. 2012 Jul [cited 2018 Sep 2];55(7):762–72. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22706128

27. Burri E, Vavricka SR. Der anale Crohn. Ther Umschau [Internet]. 2013 Jul [cited 2018 Sep 2];70(7):417–28. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23798025

28. Iesalnieks I, Glaß H, Kilger A, Ott C, Klebl F, Agha A, et al. Perianale Crohn-Fisteln. Der Chir [Internet]. 2009 Jun 24 [cited 2018 Sep 2];80(6):549–58. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19387561

29. Sordo-Mejia R, Gaertner WB. Multidisciplinary and evidence-based management of fistulizing perianal Crohn’s disease. World J Gastrointest Pathophysiol [Internet]. 2014 [cited 2018 Sep 2];5(3):239. Available from: http://www.wjgnet.com/2150-5330/full/v5/i3/239.htm

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Review article

Lung function assessment in preschool children; a review of the utility of basic spirometry, interrupter technique and forced oscillation technique

Rajapakse SI1 Yasaratne D2, Amarasiri L3

1 Department of Physiology, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka

2 Faculty of Medicine, University of Peradeniya 3 University of Colombo.

Keywords: spirometry, interrupter technique, forced oscillation technique, obstructive airway disease, asthma Copyright: ©. 2017 Rajapakse et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Funding: None Competing interest: None Correspondence: [email protected] DOI: http://doi.org/10.4038/amj.v11i1.7641 Received: 01 September 2018 Accepted revised version: September 2018 Published: September 2018

Introduction

Objective assessment of lung functions in preschool children is vital not only because significant development and maturation occurs in the lungs during this period1 but also because clinically a clear evidence based demarcation between isolated non-significant episodes of respiratory symptoms and pathognomonic symptoms is vital for the management. However, preschool children is a challenge. They are too old to ethically justify routine sedation prior

to lung function assessment, as in infants, and also, they are too young to be able to focus sufficiently and perform elaborate respiratory manoeuvers required by commonly used lung function tests in older children and adults2. Evidence synthesis of different types of techniques is valuable in providing patient care as well as in planning further studies. The purpose of this review is to evaluate three commonly used pulmonary function tests, viz. basic spirometry, interrupter technique and forced oscillation

Objective lung function assessment in preschool children is a challenge; the mechanics of the lungs are changing rapidly with advancing age and maturation, the population is too old to ethically justify routine sedation prior to lung function assessment, as in infants, and also, they are too young to be able to focus sufficiently and perform elaborate respiratory manoeuvers required by commonly used lung function tests in older children and adults. But, clinically, a clear evidence based demarcation between isolated non-significant episodes of respiratory symptoms and pathognomonic symptoms is vital for the management. Even though many different lung function techniques are commonly used in the assessment of preschool children, the purpose of this review is to evaluate three commonly used pulmonary function tests, viz. basic spirometry, interrupter technique and forced oscillation technique in order to assess their usefulness in preschool children. We conclude that contrary to common misbelief, ample evidence exists that preschool children are capable of performing lung function tests. Basic spirometry, which stood the test of time, remains one of the most commonly used lung function tests. The interrupter technique and the forced oscillation techniques are quickly gathering reputation as reliable alternatives for lung function assessment in preschool children, especially due to the minimal co-operation required from the subject and the versatility of the test. These techniques will enable definitive diagnosis, assessment of severity and the therapeutic response of multiple, complex and often challenging clinical respiratory conditions to enable efficient management.

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technique in order to assess their usefulness in preschool children.

Basic spirometry

Basic spirometry requires the subject to be able to take tidal volume breaths and then perform a maximal inspiration followed by maximal expiration to obtain forced vital capacity (FVC), forced expiration volume in first second (FEV1), flow rate measurements and also flow-volume and volume-time curves3–7, which are used for the assessment of lung function. Current evidence suggests that preschool children possess the ability to successfully perform technically acceptable spirometry4,8–14. The validity of spirometry data depend on strict quality control and following standard protocols15,16.The main handicap for using routine spirometry to assess lung functions in preschool children is the age-limited ability of the child to perform the required respiratory manoeuvers to obtain reproducible data to satisfy international standards set for adults or even older children2,17,18. For an example, the majority of preschool age children will have the capacity to perform spirometry to obtain technically acceptable forced expiratory volume values for 0.5 seconds but only significantly lesser number of children has the ability to sustain forced expiration for 1 second to obtain FEV1 data19, because the lung volume is comparatively smaller and the airway size is proportionately larger allowing younger children to exhale the vital capacity even within less than one second19,20. Therefore, it is advisable to substitute FEV1 with FEV0.5 or FEV0.75 in the case of preschool children19.

An official statement by the American thoracic society and European respiratory society recommends a period of training for the child3,12,19, interactive computerized flow driven incentives such as blowing the candles, availability of real time flow volume curves to the operator and the operator should actively engage with the child and monitor the process. Following changes are acceptable in the flow-volume curves produced by preschool children compared to adults, the descending portion is more convex in healthy preschool children20,21, forced expiration could last less than 1 second2, best forced vital capacity (FVC) and FEV should be reported but it is not mandatory that the values are obtained from one tracing. The adult repeatability criteria of three acceptable curves is adjusted to two acceptable curves with FVC and FEV within 10% range of the maximum value for preschool children3,19. Therefore, current evidence suggests obtaining repeatable, technically sound spirometry results that enable better diagnosis of respiratory diseases in preschool children is possible, but the technical specifications, methodology and data interpretation should be tailored to suit the age of the

child22–25. The advantage of spirometry is the ability to detect airway obstruction and restriction. The restrictive pattern may be secondary to severe airway obstruction or a true restrictive pathology26, hence detection of restriction on spirometry warrants further assessment of lung volumes to confirm the diagnosis and differentiate between causes of restriction27–29

Interrupter technique

The interrupter technique30–33 is based on the physiological basis that following momentary occlusion of breathing at the level of the mouth, the pressure of the mouth will equal to the alveolar pressure. The pressure that is measured in the mouth following the occlusion of breathing is divided by the airflow just prior to the occlusion, to obtain the interrupter resistance (Rint)34. The occlusion is usually in response to peak expiratory flow and the closure lasts 100 ms to prevent initiation of voluntary breathing by the subject against the closure2,35. The subject only has to sit and quietly breathe through the mouthpiece, bacterial filter with the nose clip in situ. Cheek support should be provided by the operator to eliminate confounding of data by upper airway compliance2,36. Although a majority of tests were conducted during inspiration37 the significance of the difference in the interrupter resistance between inspiration and expiration measurements gradually declines with age in preschool aged children38. The popularity of the interrupter technique is mainly due to the minimal co-operation required from the subject and the versatility of test that enables it to be used in field settings2,34. It is also beneficial that reference values for interrupter resistance is available30,33,39,40. The interrupter technique is particularly important in instances, such as distinguishing asthmatic preschool children who present with vague symptoms of recurrent cough from isolated persistent cough41. Accuracy of the diagnosis is improved with combination of interrupter technique with bronchodilator responsiveness42.

Main disadvantages of the interrupter technique are that the best algorithm to calculate pressure in the mouth following occlusion is still to be proven and also this technique is incapable of assessing immediate post-exercise bronchial changes because it requires the subject to take quiet breaths during the assessment and, therefore, is unsuitable for diagnosing conditions such as exercise-induced variation of asthma2. But, overall, the interrupter technique provides an avenue of lung function testing with minimal subject co-operation and high reliability and high reproducibility.

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Forced oscillation technique

Resistance and impedance of the respiratory system is non-invasively measured with the forced oscillation technique43–46 by superimposing normal tidal volume breathing with external pressure waves47. The subject is only required to sit, with a nasal clip on and have support to the cheek and the floor of the mouth, while taking tidal volume breaths through the mouthpiece and the bacterial filter. The forced oscillation technique is an easy to perform, repeatable and a reliable test that could be used to in epidemiological studies48, in pulmonary test laboratories and even in paralyzed, sedated or ventilated patients49, which makes it highly useful in an emergency or ICU setting50,51, where it could be even used to determine optimal ventilator settings52. An assessment of 150 acutely ill asthmatic patients admitted to the emergency department, demonstrated the superiority of forced oscillation technique compared to spirometry, especially in preschool children50 (relative risk of 10.5 with a 95% confidence interval ranging from 8.0 to 13.8) . Furthermore, the same study illustrated that respiratory impedance values correlated not only with disease severity but also with FEV1 measurements. Also in an acute setting, forced oscillation technique is useful for assessment of bronchodilator response and the response to treatment53,54. Another advantage of the forced oscillation technique is that it is ideal for the assessment of airways in young children2 who are incapable of performing complicated respiratory manoeuvers required by methods such as spirometry and plethysmography53.

Availability of reference values specifically for preschool children55,56 and their correlation with normal and abnormal spirometry results is highly beneficial57, even though a respiratory impedance cut off value for diagnosing airway obstruction remains to be determined53. Forced oscillation technique is ideal for assessment of airway obstruction, airway hyper-responsiveness and bronchodilator reversibility, particularly in young children with poor compliance to spirometry2. Even though it has limited use in the assessment of restrictive airway diseases, it is interesting that this technique could be used to diagnose and assess the severity of a variety of conditions such as asthma58, cystic fibrosis59, chronic bronchitis60, obstructive sleep apnoea syndrome61,62, additionally forced oscillation technique provides a rare diagnostic tool to confirm exercise-induced asthma63–65.

Conclusion

Contrary to common misbelief, ample evidence exists that preschool children are capable of performing lung function

tests. Basic spirometry remains one of the most commonly used lung function tests. In preschool children the technical standards, analysis and interpretation of spirometry data should be tailored to the anatomical and physiological status of the child. Provided that adequate stimulation and supervision is done throughout the process, spirometry could yield high quality data for preschool children. The interrupter technique and the forced oscillation techniques are quickly gathering reputation as reliable tests of lung function in preschool children, especially due to the minimal co-operation required from the subject and the versatility of the test. In Sri Lanka, it is imperative that

further research is conducted on preschool children to establish local reference values and standards to enable clinical use of spirometry, interrupter technique and forced oscillation technique in the assessment of lung functions. These techniques will enable definitive diagnosis, assessment of the severity and the therapeutic response of multiple, complex and often challenging clinical respiratory conditions to enable efficient management.

References 1. Lanteri CJ, Sly PD. Changes in respiratory mechanics

with age. J Appl Physiol. 1993 Jan;74(1):369–78. 2. Beydon N, Davis SD, Lombardi E, Allen JL, Arets

HGM, Aurora P, et al. An Official American Thoracic Society/European Respiratory Society Statement: Pulmonary function testing in preschool children. Vol. 175, American Journal of Respiratory and Critical Care Medicine. 2007. p. 1304–45.

3. Nystad W, Samuelsen SO, Nafstad P, Edvardsen E, Stensrud T, K Jaakkola JJ. Feasibility of measuring lung function in preschool children.

4. Gaffin JM, Shotola NL, Martin TR, Phipatanakul W. Clinically useful spirometry in preschool-aged children: evaluation of the 2007 American Thoracic Society Guidelines. J Asthma. 2010 Sep;47(7):762–7.

5. Gracchi V, Boel M, van der Laag J, van der Ent CK. Spirometry in young children: should computer-animation programs be used during testing? Eur Respir J. 2003 May;21(5):872–5.

6. Eigen H, Bieler H, Grant D, Christoph K, Terrill D, Heilman DK, et al. Spirometric Pulmonary Function in Healthy Preschool Children. Am J Respir Crit Care Med. 2001 Mar;163(3):619–23.

7. Burity EF, Pereira CAC, Rizzo JA, Brito MCA, Sarinho ESC. Reference values for spirometry in preschool children. J Pediatr (Rio J). 2013 Jul;89(4):374–80.

8. Beydon N, Amsallem F, Bellet M, Le Boulé M, Le Chaussain M, Denjean A, et al. Pulmonary Function Tests in Preschool Children with Cystic Fibrosis.

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9. Kozlowska WJ, Bush A, Wade A, Aurora P, Carr SB, Castle RA, et al. Lung Function from Infancy to the Preschool Years after Clinical Diagnosis of Cystic Fibrosis.

10. Jeng M-J, Chang H-L, Tsai M-C, Tsao P-C, Yang C-F, Lee Y-S, et al. Spirometric pulmonary function parameters of healthy Chinese children aged 3-6 years in Taiwan. Pediatr Pulmonol. 2009 Jul;44(7):676–82.

11. Klug B, Bisgaard H. Lung function and short-term outcome in young asthmatic children. Vol. 14, Eur Respir J. 1999.

12. Eigen H, Bieler H, Grant D, Christoph K, Terrill D, Heilman DKK, et al. Spirometric pulmonary function in healthy preschool children. Am J Respir Crit Care Med. 2001 Mar;163(3 I):619–23.

13. D’angelo E, Carnelli V, D’angelo E, Milic-Emili J. Performance of forced expiratory manoeuvre in children. undefined. 2000;

14. Jones MH, Davis SD, Grant D, Christoph K, Kisling J, Tepper RS. Forced Expiratory Maneuvers in Very Young Children Assessment of Flow Limitation. Vol. 159, Am J Respir Crit Care Med. 1999.

15. Standardization of Spirometry, 1994 Update. American Thoracic Society. Am J Respir Crit Care Med. 1995 Sep;152(3):1107–36.

16. Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows. Eur Respir J. 1993 Mar;6 Suppl 16(Suppl 16):5–40.

17. Vilozni D, Barak A, Efrati O, Augarten A, Springer C, Yahav Y, et al. The role of computer games in measuring spirometry in healthy and “asthmatic” preschool children. Chest. 2005 Sep;128(3):1146–55.

18. Arets HG, Brackel HJ, van der Ent CK. Forced expiratory manoeuvres in children: do they meet ATS and ERS criteria for spirometry? Eur Respir J. 2001 Oct;18(4):655–60.

19. Aurora P, Stocks J, Oliver C, Saunders C, Castle R, Chaziparasidis G, et al. Quality Control for Spirometry in Preschool Children with and without Lung Disease. Am J Respir Crit Care Med. 2004 May;169(10):1152–9.

20. Zapletal A, Chalupová J. Forced expiratory parameters in healthy preschool children (3-6 years of age). Pediatr Pulmonol. 2003 Mar;35(3):200–7.

21. Vilozni D, Barker M, Jellouschek H, Heimann G, Blau H. An Interactive Computer-Animated System (SpiroGame) Facilitates Spirometry in Preschool Children. Am J Respir Crit Care Med. 2001 Dec;164(12):2200–5.

22. Crenesse D, Berlioz M, Bourrier T, Albertini M. Spirometry in children aged 3 to 5 years: Reliability of forced expiratory maneuvers. Pediatr Pulmonol.

2001 Jul;32(1):56–61. 23. Nystad W, Samuelsen SO, Nafstad P, Edvardsen E,

Stensrud T, Jaakkola JJK. Feasibility of measuring lung function in preschool children. Thorax. 2002 Dec;57(12):1021–7.

24. Kampschmidt JC, Brooks EG, Cherry DC, Guajardo JR, Wood PR. Feasibility of spirometry testing in preschool children. Pediatric Pulmonology Mar, 2016 p. 258–66.

25. França DC, Camargos PAM, Martins JA, Abreu MCS, E Araújo GHA, Parreira VF. Feasibility and reproducibility of spirometry and inductance plethysmography in healthy Brazilian preschoolers. Pediatr Pulmonol. 2013 Jul;48(7):716–24.

26. Mehrparvar AH, Sakhvidi MJZ, Mostaghaci M, Davari MH, Hashemi SH, Zare Z. Spirometry values for detecting a restrictive pattern in occupational health settings. Tanaffos. 2014;13(2):27–34.

27. Schultz K, D’Aquino LC, Soares MR, Gimenez A, Pereira CA de C. Lung volumes and airway resistance in patients with a possible restrictive pattern on spirometry. J Bras Pneumol. 2016;42(5):341–7.

28. Aaron SD, Dales RE, Cardinal P. How Accurate Is Spirometry at Predicting Restrictive Pulmonary Impairment? Chest. 1999 Mar;115(3):869–73.

29. Boros PW, Franczuk M, Wesolowski S. Value of spirometry in detecting volume restriction in interstitial lung disease patients. Spirometry in interstitial lung diseases. Respiration. 2004;71(4):374–9.

30. Merkus PJFM, Arets HGM, Joosten T, Siero A, Brouha M, Mijnsbergen JY, et al. Measurements of interrupter resistance: Reference values for children 3-13 yrs of age. Eur Respir J. 2002 Oct;20(4):907–11.

31. Nielsen KG, Bisgaard H. Discriminative capacity of bronchodilator response measured with three different lung function techniques in asthmatic and healthy children aged 2 to 5 years. Am J Respir Crit Care Med. 2001 Aug;164(4):554–9.

32. Merkus PJFM, Mijnsbergen JY, Hop WCJ, De Jongste JC. Interrupter Resistance in Preschool Children. Am J Respir Crit Care Med. 2001 May;163(6):1350–5.

33. Oswald-Mammosser M, Llerena C, Speich JP, Donato L, Lonsdorfer J. Measurements of respiratory system resistance by the interrupter technique in healthy and asthmatic children. Pediatr Pulmonol. 1997 Aug;24(2):78–85.

34. F M Merkus PJ. The interrupter technique. 35. Frey U, Stocks J, Coates A, Sly P, Bates J.

Specifications for equipment used for infant pulmonary function testing. ERS/ATS Task Force on

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Standards for Infant Respiratory Function Testing. European Respiratory Society/ American Thoracic Society. Eur Respir J. 2000 Oct;16(4):731–40.

36. Jackson AC, Milhorn HT, Norman JR. A reevaluation of the interrupter technique for airway resistance measurement. J Appl Physiol. 1974 Feb;36(2):264–8.

37. Chowienczyk PJ, Lawson CP, Lane S, Johnson R, Wilson N, Silverman M, et al. A flow interruption device for measurement of airway resistance. Eur Respir J. 1991 May;4(5):623–8.

38. Beydon N, Amsallem F, Bellet M, Boule M, Chaussain M, Denjean A, et al. Pre/postbronchodilator interrupter resistance values in healthy young children. Am J Respir Crit Care Med. 2002 May;165(10):1388–94.

39. Lombardi E, Sly PD, Concutelli G, Novembre E, Veneruso G, Frongia G, et al. Reference values of interrupter respiratory resistance in healthy preschool white children. Thorax. 2001 Sep;56(9):691–5.

40. Bridge PD, Ranganathan S, McKenzie SA. Measurement of airway resistance using the interrupter technique in preschool children in the ambulatory setting. Eur Respir J. 1999 Apr;13(4):792–6.

41. Chang AB. Isolated cough: probably not asthma. Arch Dis Child. 1999 Mar;80(3):211–3.

42. Bridge PD, Ranganathan S, McKenzie SA. Measurement of airway resistance using the interrupter technique in preschool children in the ambulatory setting. Eur Respir J. 1999 Apr;13(4):792–6.

43. Shackleton C, Czovek D, Grimwood K, Ware RS, Radics B, Hantos Z, et al. Defining ‘healthy’ in preschool-aged children for forced oscillation technique reference equations. Respirology. 2018;23(4).

44. Kato K, Tanaka H. [usefulness of the forced oscillation technique in the diagnosis of cough variant asthma with prolonged or chronic cough]. Arerugi. 2018;67(6):759–66.

45. Komarow HD, Myles IA, Uzzaman A, Metcalfe DD. Impulse oscillometry in the evaluation of diseases of the airways in children. Ann Allergy Asthma Immunol. 2011 Mar;106(3):191–9.

46. Marotta A, Klinnert MD, Price MR, Larsen GL, Liu AH. Impulse oscillometry provides an effective measure of lung dysfunction in 4-year-old children at risk for persistent asthma. J Allergy Clin Immunol. 2003 Aug;112(2):317–22.

47. Shirai T, Kurosawa H. Clinical Application of the Forced Oscillation Technique. Intern Med. 2016;55(6).

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Megherbi SE, Teculescu D, et al. Forced oscillation technique (FOT): a new tool for epidemiology of occupational lung diseases? Eur Respir J. 1995 Aug;8(8):1307–13.

49. Navajas D, Farré R. Forced oscillation assessment of respiratory mechanics in ventilated patients. Crit Care. 2001;5(1):3–9.

50. Ducharme FM, Davis GM. Measurement of Respiratory Resistance in the Emergency Department. Chest. 1997 Jun;111(6):1519–25.

51. Komarow HD, Myles IA, Uzzaman A, Metcalfe DD. Impulse oscillometry in the evaluation of diseases of the airways in children. Vol. 106, Annals of Allergy, Asthma and Immunology. NIH Public Access; 2011. p. 191–9.

52. Farré R, Mancini M, Rotger M, Ferrer M, Roca J, Navajas D. Oscillatory Resistance Measured during Noninvasive Proportional Assist Ventilation. Am J Respir Crit Care Med. 2001 Sep;164(5):790–4.

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54. Ortiz G, Menendez R. The effects of inhaled albuterol and salmeterol in 2- to 5-year-old asthmatic children as measured by impulse oscillometry. J Asthma. 2002 Sep;39(6):531–6.

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61. Badia Jr, Farré Ro, John Kimoff R, Ballester E, Hernández L, Rotger M, et al. Clinical Application of the Forced Oscillation Technique for CPAP Titration in the Sleep Apnea/Hypopnea Syndrome. Am J Respir Crit Care Med. 1999 Nov;160(5):1550–4.

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Author Guidelines The Anuradhapura Medical Journal (AMJ) is currently soliciting articles for consideration for future issues. The Journal strives to be a forum for all health professionals in North Central Province to publish original research and review articles in their area of expertise. The AMJ is a peer-reviewed, open access medical journal published by Anuradhapura Clinical Society (ACS). The AMJ publishes articles in medicine, basic science, public health and health promotion.

Types of articles

1 . O r i g i n a l r e s e a r c h p a p e r Original research papers are scientific reports of the results of original research. The text is limited to 2500 words, a maximum of 5 tables and figures, and up to 20 references. Manuscript should follow the IMRAD (Introduction, Methods, Results and Discussion) format in reporting. Structured abstract again in IMRAD format of up to 250 words is required.

2 . R e v i e w s Review papers should aim to provide the reader with a comprehensive overview of an importarrt subject in the field, and should be systematic and critical assessments of literature. All articles or data sources in review papers should be selected systematically for inclusion in the review and critically evaluated. They should be according to the PRISMA guidelines. The text should not exceed 3000 words, 30 references. Abstract of up to 250 words is required.

3 . B r i e f r e p o r t s Original data that is not sufficient for full paper, secondary analysis of previously published data and preliminary results of an ongoing research study can be reported as brief communications. They should not exceed 800 words, and contain more than two tables or illustrations, and more than 10 references. Manuscript should be reported as unstructured essay. Unstructured abstract of up to 150 words is required.

4 . C a s e r e p o r t s These are short discussions of a clinical case with unique features not previously described that make an important scientific observation. The cases reported should have merits of contributing to the current knowledge of the relevant subject area. They should be according to the CARE guidelines. They should not exceed 800 words, and contain more than 3 tables or illustrations, and more than 10 references.

5 . P e r s p e c t i v e s The AMJ welcomes manuscripts expressing opinions, presenting hypotheses, discussing controversial issues and new advances in medicine. They should not have more than 1000 words, 3 tables and illustrations, or 20 references. Narrative abstract.

6 . L e t t e r s t o t h e E d i t o r

The AMJ welcomes letters to the editors from academics expressing their opinions in medicine. They should not have more than 750 words, 3 tables and illustrations, or 10 references.

Manuscript preparation Manuscripts must be prepared in accordance with "uniform requirements for manuscripts submitted to biomedical Journal" developed by International Committee of Medical Journal Editors (ICMJE).

All authors must read the publication ethics and malpractice statement of the AMJ.

There is no article submission or processing fees whatsoever.

The manuscript should be in Microsoft WORD or saved as a .doc file. The language set to "English (U.K.) and not "English (U.S.). The manuscript should be double-spaced with 1-inch margins on all sides. Leave the right-hand margin ragged (unjustified). Number pages in numerical order beginning with the title page. The font and font size should be Times New Roman and 12 respectively. Include line numbers and do not use page breaks.

Cover letter Cover letter should be addressed to the editors, providing corresponding author's information (name, address, telephone and email) and stating the category of article the manuscript represents.

Author should make a full statement to the editor about all submissions and previous reports that might be regarded as prior or duplicate publication of the same or very similar work. Copies of such material should be included with the submitted paper to help the editor decide how to deal with the matter.

Optional: suggest minimum of two potential peer reviewers whom you deem appropriate and knowledgeable to review your manuscript; include official contact information and email addresses.

The ICMJE conflict of interest form (http://www.icmje.org/conflictsof-interest!) should be filled and submitted as an additional file. Manuscript with the following items start on a new page: title page, abstract, main text, references, tables and figures. Total number of tables and figures should be mentioned.

1. Title page The title of the article (less than 18 words), with the running head (a short heading) needs to be included. Abbreviations should not be used in the title. Authors are urged to include their full names, complete with surname and first names. Academic degrees should be included. Always include mailing address, phone and fax number, and email address of the corresponding author. The names and locations of institutions and the laboratories or names and locations of companies should be given for all authors. If several institutions are listed on a manuscript, it should be clearly indicated with which department and institution each author is affiliated by using superscript numbers that correspond to each author's affiliation. Author(s) should be identified only on the title page. Total number of tables and figures should be mentioned in the cover letter and in addition any other supplementary files uploaded are also needs to be mentioned here.

Author Contributions

Place the Author Contributions in the title page. Listing each author's contribution to the work is required for submission. Their initials in parenthesis should identify the contributing authors after each category. The categories should be used as appropriate: Study concept and design; obtaining funding; acquisition of the data; analysis of the data; drafting of the manuscript; critical revision of the manuscript; and approval of final manuscript. Authorship criteria are clearly defined in the ICMJE.

x Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; AND

x Drafting the work or revising it critically for important intellectual content; AND

x Final approval of the version to be published; AND

x Agreement to be accountable for all aspects of the work in ensuring that

questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Funding details Place the Funding details in the title page. Authors are required to disclose any financial and/or material support in the form of grants, equipment, and/or drugs; and to specify the nature of the support. If there is none, it should be stated as Financial/Material Support: None.

Conflict of interest Place the conflict of interest statement in the title page. This is in addition to the ICMJE conflict of interest form (http://www.icmje.org/ conflicts-of-interest/) that needs to be separately uploaded.

AMJ requires that authors and reviewers reveal any relationships that they believe could be construed as resulting in an actual, potential, or perceived conflict of interest with regard to the manuscript submitted for review. All new and revised submissions must include such a statement.

Conflict of interest exists when an author (or the authors institution), reviewer, or editor has financial or personal relationships that inappropriately influence (bias) his or her actions. The potential for conflict of interest can exist whether or not an individual believes that the relationship affects his or her scientific judgment. Financial relationships (such as employment, consultancies, stock ownership, honoraria, paid expert testimony) as well as personal relationships and academic competition must be declared. The authors declare conflicts of interests and sources of financial support as acknowledgment.

The authors are responsible for providing a conflict of interest statement on the title page of their submission, even if there are no conflicts to disclose. If there are none, it should be stated as Disclosures: None. If a potential conflict of interest is disclosed, notification concerning the relationship will be published along with the article.

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Acknowledgments Place the acknowledgements in the title page. Statements should specify the contributions that need acknowledging but do not justify authorship, such as general support by a departmental chairman; and acknowledgments of technical help.

Word count The number of words in the manuscript, exclusive of the abstract, acknowledgments, references, tables, figures, and figure legends should be included.

2 . A b s t r a c t All manuscripts that are reports of original data from scientific investigations (research and brief report) must be submitted with a structured abstract of no more than 250 words with the following headings: Introduction with the objective, methods (include details on design, setting, participants, interventions, and main outcomes measured), results, and (discussion) conclusions. Abbreviations should be kept to mimimum and do not cite references in the abstract.

Perspectives should include a narrative abstract outlining the purpose of the article, major findings, and recommendations. Abstracts for review articles should also specify how the literature was searched and how cited articles were chosen. Letter to editor does not require abstract.

2. Key words Immediately following the abstract (not on a separate page), includ e 46 key words that will assist indexers in cross-indexing your article and that may be published with the abstract. Key words should express the precise content of the manuscript, as they are used for indexing purposes. Use terms from the medical subject headings (MeSH) list of Index Medicus.

3 . M a i n t e x t Include the following headings and subheadings. Introduction/ background: (any relevant subheadings). Methods: study design (e.g., case control study, cohort study, qualitative, content analysis), participants (include target population, inclusion and exclusion criteria, and sample size), Measures, procedures, and analyses. Results: primary results in quantitative or qualitative form. Discussion: (any relevant subheadings), limitations, conclusion.

The methods section should include a statement indicating that the research was approved or exempted from the need for review by the responsible ethics review committee. When informed consent has been obtained it should be indicated in the manuscript as: Informed consent has been obtained. Use SI units as much as possible and generic names for pharmaceuticals.

4 . R e f e r e n c e s

Before submission of the manuscript, authors should verify the accuracy of all references and check that all references have been cited in the text. Use Arabic numbers in parenthesis for in text citation and numbered list of references at the end of manuscript. Number references consecutively in the order in which they are first mentioned in the text. Cite only the number assigned to the reference: use [ ] not ( ). The style and punctuation of the references should conform to strict ICMJE style. Please refer to ICMJE guidelines www.nlm.nih.gov/bsd/uniform_requirements.html

Journal Articles

Author Surname Initials. Title of article. Full title of the journal, abbreviated. Date of Publication; Volume Number (Issue Number): Page Numbers.

DOI: http://dx.doi.org/ Eg,

Agampodi SB. Regional differences of leptospirosis in Sri Lanka: observations from a flood-associated outbreak in 2011. PLOS Neglected Tropical Diseases 2014; 8: p. e2626. DOI: http://doi.org/10.137 1 /journal.pntd.0002626

Book Author Surname Initials. Title. Edition (if not the first). Place of publication: Publisher; Year.

Eg, Eisen HN. Immunology: An Introduction to Molecular and Cellular Principles of the Immune Response. 5th ed. New York: Harper and Row, 1974.

Chapter in a book Author. Title of the chapter. In: name of the editor, ed. Title of the book. City of publication: publisher; publishing year: pages Schantz EJ. Historical perspective on paralytic shellfish poisoning. In: Ragelis EP, ed. Seafood Toxins. Washington, DC: American Chemical Society; 1984:99-111.

Websites Author Surname Initials (if available). Title of Website [Internet]. Place of publication: Publisher; Date of First Publication [Date of last update; cited date]. Available from: URL

Preminger GM, Tiselius HG, Assimos DG, et al. Guideline for the management of ureteral calculi. American Urological Association, 2007. http://www.auanet.org/education/guidelines/ureteralcalculi (accessed on Feb 20, 2013)

5 . T a b l e s Tables should be in the manuscript document after the references. Indicate each table in the text in consecutive order as Table 1, Table 2, etc. Format each table double-spaced. Do not submit tables as photographs. Number each table consecutively in the order of its first citation in the text, and supply a brief title. Give each column a short heading. Place explanatory matter about the table in footnotes, not in the heading. Explain in footnotes all non-standard abbreviations. Identify statistical measures of variation such as standard deviation and standard error of the mean. Omit internal horizontal and vertical rules. If data are used from another published or unpublished source, obtain permission and acknowledge fully.

6 . F i g u r e s Figures should be uploaded separately. Cite each figure in the text in consecutive order as Figure 1, Figure 2, etc. Include a separate figure legend in the manuscript text. Make sure you use uniform lettering and sizing of your original artwork. Save text in illustrations as "graphics" or enclose the font. Only use the following fonts in your illustrations: Arial, Helvetica, Times, Symbol. Number the illustrations according to their sequence in the text. Use a logical naming convention for your artwork files. Produce images near to the desired size of the printed version. Regardless of the application used, when your electronic artwork is finalized, please "save as" or convert the images to one of the following formats, TIFF, JPEG or BMP. Always use a minimum of 300 dpi.

Patient images (medical photographs) It is the responsibility of the authors to obtain informed written consent for publication of any material (e.g. images, records etc.). Evidence of which should be available anytime for submission, on request by the chief editor. This is especially relevant for patient photographs in case reports.

The process of obtaining consent from the patient should be ideally by a person outside the team caring for the patient. Explicitly declare the areas of the body or face that would be photographed, how they should be shown and what the images would be used for.

Submission Preparation Checklist Cover letter ICMJE conflicts of interest statement Manuscript Figures Any supplementary files

Co-editors Anuradhapura Medical Journal

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Cover Story: Chalky Percher Diplacodes trivialis

Image © Lahiru Pathiraja Captured in Anuradhapura 2018

Chalky Percher Diplacodes trivialis distributed, India to Japan, Indonesia, several regions of Australia, West Pacific and Fiji. It is distributed throughout the island and inhabit in ponds, marshes, canals and lakes. Usually adult dragonflies feed on mosquitoes, fleas, flies and butterflies. Dragonflies’ nymph feeds on mosquito larvae. Dragonflies are valuable biological control of the mosquito populations. Buddhika Wijerathne.

AnuradhapuraMedicalJournal

2017Volume11

Issue1

MemberSince2014JM09912

AnuradhapuraMedicalJournalisavailableonlineat:https://amj.sljol.info/ThisJournalisprintedonacidfreepaperPrintedby:

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